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Dreamwatch
Dreamwatch was a British magazine covering science fiction and fantasy films, books and television programmes.
Published monthly by Gary Leigh (July 1983 to January 2001) and then Titan Magazines (2001 to 2007), it was a leading genre entertainment magazine, competing with SFX and Cinescape in the genre magazine market.
Overview
The publication began life in the early 1980s as an amateur fanzine dedicated to the popular science-fiction television series Doctor Who, and was published under the title Doctor Who Bulletin. In this form, it became well known for taking a generally critical tone towards the later seasons of the programme, particularly the work of producer John Nathan-Turner, who was subjected to several personal attacks in its pages. However, it became popular with some fans due to its frequent reporting of news concerning the show before it was released through official sources, and as an alternative viewpoint to the officially sanctioned Doctor Who Magazine or Celestial Toyroom, the newsletter of the Doctor Who Appreciation Society. There were, however, occasional embarrassing errors, such as the printing of an obituary for actor Kevin Stoney in 1986, who was still alive and after the article's appearance would happily sign copies for fans at conventions. The fanzine also gained a reputation for being sometimes too willing to report rumour as fact.
In 1989, the fanzine expanded to cover other genre films and television series as well as Doctor Who, and the title was changed to DreamWatch Bulletin so that the popular abbreviation DWB would remain intact. In 1994, it was turned into a fully professional newsstand magazine: the title was shortened to simply Dreamwatch, and the numbering of the magazine was restarted from issue 1.
The original fanzine was founded and edited by Gary Levy, who later changed his name to Gary Leigh. He edited the first hundred issues, before handing over editorial reins first to David Gibbs (issues 101-110) and then to Anthony Brown (111-130), after which the professional version was launched (with numbering beginning again at issue 1, and with Anthony Clark and then Paul Simpson as editors until issue 71). Leigh returned as editor with issue 72, aided by co-editor Simon J. Gerard who worked on the title on a day-to-day basis. Leigh retained ownership of the title until 2001, when he sold the magazine to Titan Magazines, part of the Titan Entertainment Group owned by Nick Landau. Gerard moved across to Titan with Dreamwatch and took the role of Contributing Editor.
Brian J. Robb became Editor/Managing Editor in June 2001 (issue 81) and continued through to September 2003 (issue 108) which marked DWBs 20th continuous year of publication. Former Deputy Editor David Bassom served as Editor from issue 109 to 123, and launched the stand-alone US edition with the help of Deputy Editor Matthew Chapman. Robb became Editor/Managing Editor of Dreamwatch once more from January 2005 (issue 124) until October 2006 (issue 145). Former deputy editor Richard Matthews then became editor for a few issues (until issue 148) before the editorship returned to Robb until issue 150, which was the last print edition, published on 25 January 2007 (issue 280 if counted from the debut issue in July 1983).
At the end of January 2007, the magazine became a web-only publication entitled Total Sci-Fi, offering SF news and features and Dreamwatch/DWB archive at www.totalscifionline.com. The website was edited by Matt McAllister, and counted many former Dreamwatch writers among its contributors. It was placed on indefinite hiatus in 2011.
Category:1983 establishments in the United Kingdom
Category:2007 disestablishments in the United Kingdom
Category:British monthly magazines
Category:British online magazines
Category:British speculative fiction magazines
Category:Defunct British science fiction magazines
Category:Doctor Who magazines
Category:Magazines established in 1983
Category:Magazines disestablished in 2007
Category:Online magazines with defunct print editions
Category:Science fiction fanzines
Category:Titan Magazines titles | {
"pile_set_name": "Wikipedia (en)"
} |
World Bank’s Young Professionals Program 2018
About World Bank’s Young Professionals Program
World Bank’s Young Professionals Program 2018 is an opportunity for young professionals to start their career and join World Bank.Every year 40 young fellows are selected by the means of World Bank’s Young Professionals Program. World Bank’s Young Professionals Program 2018 is open for candidates below 32 years with a Master’s Degree & 3 years of development-related work experience or a PhD. On this page, the complete information about the World Bank’s Young Professionals Program is given and the candidates need to scroll down below to get the complete details.
The candidates selected for World Bank’s Young Professionals Program 2018 will get the salary of international standards along with training, financial support, insurance and various other benefits. The applications for World Bank’s Young Professionals Program 2018 has started from 14 June 2017 which are available until 28 July 2017. The candidates should know that the application form can be filled only through online mode.
World Bank's Young Professional Programme Dates 2018
Events
Dates
YPP Application process begins
14 June 2017
YPP Application process ends
28 July 2017
Review of applications
June to September 2017
Technical review of second round candidates
October 2017
Updating candidates about Interview
November to December 2017
YPP Interviews
December 2017 to January 2018
Result announcement
February 2018
New YP cohorts start
September 2018
Subscribe for Regular Updates of World Bank’s Young Professionals Program
World Bank’s Young Professionals Program Eligibility Criteria
Nationality: The scholarship will be provided to the applicants belonging to the member countries of World Bank.
Age: The applicant should be born on or after 1 October 1985 i.e. should be younger than 32 years.
Academic Qualification: The applicant should possess a PhD or Master’s Degree along with relevant work experience.
Specialisation: The candidate should possess specialisation in field relevant to WBG Technical/Operations such as economics, finance, education, public health, social sciences, engineering, urban planning, agriculture, natural resources, and others
Experience: The applicant should have 3 years of development-related professional work experience or continued academic study till doctoral level.
Language: Fluency in English is must and fluency in WBG’s working languages: Arabic, Chinese, French, Portuguese, Russian, and Spanish will be a plus point.
World Bank’s Young Professionals Program Reward
otal 40 candidates will be selected from all the applications received. The fellows selected for World Bank’s Young Professionals Program will get the following benefits:
Professional Experience: As part of their two-year program and keeping in mind the business needs of their hiring units and the interest of Young Professionals, they are expected to undertake a “Stretch/Exposure Assignment” where they will gain valuable on-the-job experience.
Training: A very well designed curriculum will enable the candidates to develop a WBG mind set and quickly inculcate qualities like collaboration, leadership, integrative thinking, and innovation skills while strengthening a culture of continuous learning.
Salary: The fellows selected for the program will get internationally competitive salary on the basis of their education and experience.
Insurance: The candidates can select from Health, Life, Accident and other insurance programs depending upon their preference.
Pension Plan: After separation from World Bank, the candidate will be eligible for either a lump sum or pension depending on his/her eligibility.
Other benefits: The candidates will get other benefits such as relocation benefits, mobility premium, financial assistance and tax allowance.
World Bank’s Young Professionals Program Application form and Process
The application process for the World Bank YPP scholarship has started and the candidates can apply through online mode by following the link available on this page below. The Young Professional application for the scholarship needs to be made through online only.
Required Documents: The following documents are to be uploaded in order to complete the submission of the application form:
An updated Curriculum Vitae: The applicant should upload recent and up to date Curriculum Vitae in order to complete the application process.
Transcripts: Transcripts of educational certificates are mandatory to be uploaded while making the application.
Summary of Thesis: Applicants are required to submit a summary of the thesis submitted by them during their Masters or PhD.
Essay: Applicants are required to write an essay and submit it while completing the application process. The details of the essay are as follow:
Topic: The applicants need to write about their own contribution and the potential role of World Bank in resolving some of the challenges for the topic in not more than 1,000 words. They should focus on their area of expertise to describe your proposal.
Format: The essay needs to be submitted in doc, .docx, or .pdf format.
Size: Maximum 5 MB.
Topic for the World Bank's Young Profession Programme 2018
As mentioned above that the candidates have to submit the essay of fewer than 1,000 words about their own contribution and the potential role of World Bank in resolving some of the challenges in the topic. The topic for this year would be:
World Bank’s Young Professionals Program Selection Process
Selection Criteria: The selection of the candidate will be done on the basis of the following criteria:
Client Orientation
Professional Experience
Team Leadership
Interview: Interview will be a full day event and will be divided into 2 basic sections and the candidates invited to interviews will be asked to come to the WBG from 8:00 AM to 5:30 PM. The interviews will be conducted in two sections:
Personal Interview: A 1.5 hours personal interview with an expert panel having 3 members of the expert panel on the same field as of the candidate.
Assessment Center: The group assessment centre is done with four other candidates. It consists of a series of individual and group exercises related to an international development case study that is given to the candidates at the start of the AC. | {
"pile_set_name": "Pile-CC"
} |
Expanded (CAG)n, (CGG)n and (GAA)n trinucleotide repeat microsatellites, and mutant purine synthesis and pigmentation genes cause schizophrenia and autism.
Unstable (CAG)n trinucleotide repeat microsatellites are hypothesized to cause schizophrenia. The (CAG)n microsatellite of dominant spinal cerebellar ataxia type 1 (SCA1) is a candidate schizophrenia gene. Autism results from expansions of (CGG)n and (GAA)n trinucleotide repeat stretches at fragile X syndrome (FRAXA), and the recessive Friedreich's ataxia (FA). Dominant ataxia genes may cause schizophrenia and recessive ataxia genes may cause autism. Syndromes with autism show purine synthesis defects (PSDs) and/or pigmentation defects (PDs). Autism is caused by very lengthy expansions of (CAG)n, (CGG)n and (GAA)n repeats, while schizophrenia results from much smaller (CAG)n and (CGG)n repeat expansions. | {
"pile_set_name": "PubMed Abstracts"
} |
Åke Hodell
Åke Hodell (April 30, 1919 – July 29, 2000, Stockholm, Sweden) was a Swedish fighter pilot, poet, author, text-sound composer, and artist. Daughter Laila Hodell (author) He was the son of author Björn Hodell and brother of actor Ulla Hodell.
Hodell was trained as a fighter pilot, but after a crash during practice July 17, 1941, he had to spend the next few years in hospital. This became a turning point and he became a dedicated antimilitarist. Lying in hospital he got to know author Gunnar Ekelöf and Hodell made his debut with Flyende Pilot in 1953. That same spring, Hodell and Ekelöf travelled to Rome. In his books, Hodell experimented with what he calls elektronismer, while he on stage and in radio in the early 60s worked with text-sound composition. During this period he was also active at Pistolteatern in Stockholm. He also created the book publisher Kerberos.
One of his visual artworks, the piece "220 Volt Buddha", was used as the album cover of Swedish heavy metal band At the Gates' 1993 album With Fear I Kiss the Burning Darkness.
Discography
Verbal Brainwash and Other Works (2000, Fylkingen)
See also
Musique concrète
Sound poetry
References
Category:Swedish Air Force personnel
Category:Sound artists
Category:1919 births
Category:2000 deaths
Category:Swedish artists
Category:Swedish male writers | {
"pile_set_name": "Wikipedia (en)"
} |
Taimuraz Salkazanov is coming off a bronze medal in this year’s World Championships. He competes at 79 kilograms, which is a stacked division at the World level of wrestling, despite being a non-Olympic weight. Along with Kyle Dake, Jabrayil Hasanov, and Gadzhi Nabiev, Salkazanov proved he was among the cream of the crop. We took some time in this interview to get to know the Slovakian wrestler.
Salkazanov had tough competition to go through at Worlds this year. He won matches against Ayoub Barraj of Tunisia, Gombodorj Dorjvanchig of Mongolia, and Jitender Jitender of India before falling to Jabrayil Hasanov, who would go on to win the silver medal. He defeated Kazakhstan’s Galymzhan Usserbayev to clinch the bronze medal, his first on the senior World Championship level.
Salkazanov and his wrestling talent is a family trait. He says, “I have been wrestling for ten years. My father’s brother was my first coach. I have a family of wrestlers, therefore, it was already clear that I would wrestle.” It is no doubt that wrestling is in his blood. After Taimuraz Salkazanov won gold at U23 in 2018 over a future World champion in David Baev, it was very clear he had legitimate talent.
Taimuraz Salkazanov And The Olympics
Salkazanov is not letting his success he’s had at Worlds get to his head. “The first task is qualification for the Olympic Games.”
That is every wrestlers dream, the Olympics. The 2020 Tokoyo Games are right around the corner. “The main task of a wrestler is the Olympic Games,” says Salkazanov. “Same goes for me. I want to be Olympic unit champions.”
The Slovakian medalist is happy to be seen on such a world stage. “It is very nice to hear congratulations. The coach, parents, relatives, friends, all worry about me and always get sick. I would like to please them more often.” Winning a medal at the World Championships is a good way to qualm their stomachs.
Salkazanov Outside The Sport and the Future
Wrestling does not leave much time for much else. Salkazanov devotes his time mainly to the sport. “Almost all my time, I devote to sports. In my free time I recover. Sometimes I play the guitar.”
As for his future, Salkazanov has his mind on the present. He’s not concerned about the future. His mind is here and now. “I have not thought about what I will do after the sport. It’s too early to think about it.”
Follow Taymuraz Salkazanov on Instagram to keep up with his wrestling journey to the Olympics.
Watch Taymuraz Salkazanov defeat Galymzhan Usserbayev to win bronze at the 2019 Wrestling World Championships
Be sure to subscribe to Fight Club to stay loaded with the latest content from The Fight Library. | {
"pile_set_name": "OpenWebText2"
} |
Q:
jquery autocomplete ghost image
I have an input that is autocomplete. When I enter a value into the input I get a list and at the bottom of the list it tells me how many records it found, matching my criteria. After I select a value from the list, the list will disappear and fill the control, but it leaves an image of the selected value under the control.
Why does this happen and how do I fix it?
This is my code that returns the results:
function FillClinicsByName() {
if ($('#txtClinicName').val() == '') {
$('#txtClinicName').autocomplete({
source: function (request, response) {
$.ajax({
async: false,
delay: 250,
url: "WebService1.asmx/ClinicName",
data: "{'Name':'" + request.term.replace(/'/g, "\&apos") + "'}",
dataType: "json",
type: "POST",
contentType: "application/json; charset=utf-8",
dataFilter: function (data) { return data; },
success: function (data) {
response($.map(data.d, function (item) {
return {
label: item.split('|')[0],
val: item.split('|')[1]
} // end of return
})) // end of response
} // end of success
}); // end of ajax
}, // end of source
select: function (e, i) {
$('#hdfldClinic').val(i.item.val);
},
change: function (event, ui) {
if (!ui.item) {
$(event.target).val('');
}
},
minLength:1
}); // end of autocomplete
} // nothing in the text box
}
I am using jquery-1.10.2.js and bootstrap 3 and vs2015
A:
If I had to guess you aren't including the CSS for a jQuery UI theme. A quick fix is to add this class to your CSS:
.ui-helper-hidden-accessible {
display: none;
}
This stuff is added to the page to help screen readers for accessibility. The best thing to do is to copy jQuery's class definition at least since setting it display none will make screen readers ignore it. The CSS is as follows:
.ui-helper-hidden-accessible {
border: 0;
clip: rect(0 0 0 0);
height: 1px;
margin: -1px;
overflow: hidden;
padding: 0;
position: absolute;
width: 1px;
}
I believe you can also programmatically turn this stuff off but I am not 100% sure on how to do it and do not think it is apart of their API.
| {
"pile_set_name": "StackExchange"
} |
Q:
How can I inherit a schema but maintain separate collections using mongoose.js and node.js
I have a schema that I need to maintain as an exact copy of another schema, but keep these documents in separate collections.
var someSchema = mongoose.Schema({
"foo": {"type": String, "required": true, "index": true},
"bar": {"type": String, "required": true, "index": true},
});
The goal I'm after is a simple way to inherit the exact same schema to another model/collection without having to remember to update the second schema every time I make changes to the first.
i.e.
var someOtherSchema = mongoose.Schema( < some magic here >);
A:
Wrap it in an object and reuse the object:
var schemaObj = {
"foo": {"type": String, "required": true, "index": true},
"bar": {"type": String, "required": true, "index": true},
}
var someSchema = new mongoose.Schema(schemaObj, { collection: 'some' });
var someOtherSchema = new mongoose.Schema(schemaObj, { collection: 'someOther' });
var someModel = mongoose.model('SomeModel', someSchema);
var someOtherModel = mongoose.model('someOtherModel', someOtherSchema);
| {
"pile_set_name": "StackExchange"
} |
Online commenting cliché: "You realize that X = Y, right?" - dhruvtv
Of late, I find this clichéd phrase "You realize that X = Y (or some non-obvious statement which might not even be correct), right?" appear in online comments a lot. I find it very toxic.<p>Example on HN:<p>https://www.hnsearch.com/search#request/all&q=%22you+realize%22+%22%2C+right%3F%22&start=0<p>https://www.hnsearch.com/search#request/all&q=%22you+do+realize%22+%22%2C+right%3F%22&start=0<p>"No, you presumptuous commenter, I don't realize that. If I did, I wouldn't have said it in the first place. You realize <i>that</i>, right? Why don't you just say X = Y and leave it at that?"<p>I know it's supposed to be clever, but the novelty has worn off and now it's just very annoying.
======
anigbrowl
It's not great, but if one just says 'X = Y' and leaves it at that, then that
often leads to complaints that one is being dismissive and glib. Some people
really dislike being told they're wrong, even when citations and supplementary
material is supplied for the argument. 'You realize..' can be snarky, but
often it's an attempt to soften the blow.
------
innocentpixel
You realize that repeating something clever wears off the novelty and
ultimately becomes just very annoying?
------
AznHisoka
You realize that's because people can't help but be egostistical, right?
------
digipaper
You DO realise this is used IRL too?
| {
"pile_set_name": "HackerNews"
} |
A Taste of Trickery.
In addition to your name in the credits and a personalized letter of thanks, you will receive the Electronic Edition: pdf versions of the cards and rules for the game, including token sheets. This will let you appreciate the game in full and possibly print your own set.
A Prototype Electronic Edition of the game will be given to you immediately upon the funding of the project, and the Standard Electronic Edition will be sent along as soon as it is done. You will also automatically receive electronic updates of the game any time we make an updated edition changing any rules, art, etc.
All levels more expensive than this include this level's benefits, and more! (though their benefits are otherwise separate)
Less | {
"pile_set_name": "OpenWebText2"
} |
/* gzread.c -- zlib functions for reading gzip files
* Copyright (C) 2004, 2005, 2010 Mark Adler
* For conditions of distribution and use, see copyright notice in zlib.h
*/
#include "gzguts.h"
/* Local functions */
local int gz_load OF((gz_statep, unsigned char *, unsigned, unsigned *));
local int gz_avail OF((gz_statep));
local int gz_next4 OF((gz_statep, unsigned long *));
local int gz_head OF((gz_statep));
local int gz_decomp OF((gz_statep));
local int gz_make OF((gz_statep));
local int gz_skip OF((gz_statep, z_off64_t));
/* Use read() to load a buffer -- return -1 on error, otherwise 0. Read from
state->fd, and update state->eof, state->err, and state->msg as appropriate.
This function needs to loop on read(), since read() is not guaranteed to
read the number of bytes requested, depending on the type of descriptor. */
local int gz_load(state, buf, len, have)
gz_statep state;
unsigned char *buf;
unsigned len;
unsigned *have;
{
int ret;
*have = 0;
do {
ret = read(state->fd, buf + *have, len - *have);
if (ret <= 0)
break;
*have += ret;
} while (*have < len);
if (ret < 0) {
gz_error(state, Z_ERRNO, zstrerror());
return -1;
}
if (ret == 0)
state->eof = 1;
return 0;
}
/* Load up input buffer and set eof flag if last data loaded -- return -1 on
error, 0 otherwise. Note that the eof flag is set when the end of the input
file is reached, even though there may be unused data in the buffer. Once
that data has been used, no more attempts will be made to read the file.
gz_avail() assumes that strm->avail_in == 0. */
local int gz_avail(state)
gz_statep state;
{
z_streamp strm = &(state->strm);
if (state->err != Z_OK)
return -1;
if (state->eof == 0) {
if (gz_load(state, state->in, state->size,
(unsigned *)&(strm->avail_in)) == -1)
return -1;
strm->next_in = state->in;
}
return 0;
}
/* Get next byte from input, or -1 if end or error. */
#define NEXT() ((strm->avail_in == 0 && gz_avail(state) == -1) ? -1 : \
(strm->avail_in == 0 ? -1 : \
(strm->avail_in--, *(strm->next_in)++)))
/* Get a four-byte little-endian integer and return 0 on success and the value
in *ret. Otherwise -1 is returned and *ret is not modified. */
local int gz_next4(state, ret)
gz_statep state;
unsigned long *ret;
{
int ch;
unsigned long val;
z_streamp strm = &(state->strm);
val = NEXT();
val += (unsigned)NEXT() << 8;
val += (unsigned long)NEXT() << 16;
ch = NEXT();
if (ch == -1)
return -1;
val += (unsigned long)ch << 24;
*ret = val;
return 0;
}
/* Look for gzip header, set up for inflate or copy. state->have must be zero.
If this is the first time in, allocate required memory. state->how will be
left unchanged if there is no more input data available, will be set to COPY
if there is no gzip header and direct copying will be performed, or it will
be set to GZIP for decompression, and the gzip header will be skipped so
that the next available input data is the raw deflate stream. If direct
copying, then leftover input data from the input buffer will be copied to
the output buffer. In that case, all further file reads will be directly to
either the output buffer or a user buffer. If decompressing, the inflate
state and the check value will be initialized. gz_head() will return 0 on
success or -1 on failure. Failures may include read errors or gzip header
errors. */
local int gz_head(state)
gz_statep state;
{
z_streamp strm = &(state->strm);
int flags;
unsigned len;
/* allocate read buffers and inflate memory */
if (state->size == 0) {
/* allocate buffers */
state->in = malloc(state->want);
state->out = malloc(state->want << 1);
if (state->in == NULL || state->out == NULL) {
if (state->out != NULL)
free(state->out);
if (state->in != NULL)
free(state->in);
gz_error(state, Z_MEM_ERROR, "out of memory");
return -1;
}
state->size = state->want;
/* allocate inflate memory */
state->strm.zalloc = Z_NULL;
state->strm.zfree = Z_NULL;
state->strm.opaque = Z_NULL;
state->strm.avail_in = 0;
state->strm.next_in = Z_NULL;
if (inflateInit2(&(state->strm), -15) != Z_OK) { /* raw inflate */
free(state->out);
free(state->in);
state->size = 0;
gz_error(state, Z_MEM_ERROR, "out of memory");
return -1;
}
}
/* get some data in the input buffer */
if (strm->avail_in == 0) {
if (gz_avail(state) == -1)
return -1;
if (strm->avail_in == 0)
return 0;
}
/* look for the gzip magic header bytes 31 and 139 */
if (strm->next_in[0] == 31) {
strm->avail_in--;
strm->next_in++;
if (strm->avail_in == 0 && gz_avail(state) == -1)
return -1;
if (strm->avail_in && strm->next_in[0] == 139) {
/* we have a gzip header, woo hoo! */
strm->avail_in--;
strm->next_in++;
/* skip rest of header */
if (NEXT() != 8) { /* compression method */
gz_error(state, Z_DATA_ERROR, "unknown compression method");
return -1;
}
flags = NEXT();
if (flags & 0xe0) { /* reserved flag bits */
gz_error(state, Z_DATA_ERROR, "unknown header flags set");
return -1;
}
NEXT(); /* modification time */
NEXT();
NEXT();
NEXT();
NEXT(); /* extra flags */
NEXT(); /* operating system */
if (flags & 4) { /* extra field */
len = (unsigned)NEXT();
len += (unsigned)NEXT() << 8;
while (len--)
if (NEXT() < 0)
break;
}
if (flags & 8) /* file name */
while (NEXT() > 0)
;
if (flags & 16) /* comment */
while (NEXT() > 0)
;
if (flags & 2) { /* header crc */
NEXT();
NEXT();
}
/* an unexpected end of file is not checked for here -- it will be
noticed on the first request for uncompressed data */
/* set up for decompression */
inflateReset(strm);
strm->adler = crc32(0L, Z_NULL, 0);
state->how = GZIP;
state->direct = 0;
return 0;
}
else {
/* not a gzip file -- save first byte (31) and fall to raw i/o */
state->out[0] = 31;
state->have = 1;
}
}
/* doing raw i/o, save start of raw data for seeking, copy any leftover
input to output -- this assumes that the output buffer is larger than
the input buffer, which also assures space for gzungetc() */
state->raw = state->pos;
state->next = state->out;
if (strm->avail_in) {
memcpy(state->next + state->have, strm->next_in, strm->avail_in);
state->have += strm->avail_in;
strm->avail_in = 0;
}
state->how = COPY;
state->direct = 1;
return 0;
}
/* Decompress from input to the provided next_out and avail_out in the state.
If the end of the compressed data is reached, then verify the gzip trailer
check value and length (modulo 2^32). state->have and state->next are set
to point to the just decompressed data, and the crc is updated. If the
trailer is verified, state->how is reset to LOOK to look for the next gzip
stream or raw data, once state->have is depleted. Returns 0 on success, -1
on failure. Failures may include invalid compressed data or a failed gzip
trailer verification. */
local int gz_decomp(state)
gz_statep state;
{
int ret;
unsigned had;
unsigned long crc, len;
z_streamp strm = &(state->strm);
/* fill output buffer up to end of deflate stream */
had = strm->avail_out;
do {
/* get more input for inflate() */
if (strm->avail_in == 0 && gz_avail(state) == -1)
return -1;
if (strm->avail_in == 0) {
gz_error(state, Z_DATA_ERROR, "unexpected end of file");
return -1;
}
/* decompress and handle errors */
ret = inflate(strm, Z_NO_FLUSH);
if (ret == Z_STREAM_ERROR || ret == Z_NEED_DICT) {
gz_error(state, Z_STREAM_ERROR,
"internal error: inflate stream corrupt");
return -1;
}
if (ret == Z_MEM_ERROR) {
gz_error(state, Z_MEM_ERROR, "out of memory");
return -1;
}
if (ret == Z_DATA_ERROR) { /* deflate stream invalid */
gz_error(state, Z_DATA_ERROR,
strm->msg == NULL ? "compressed data error" : strm->msg);
return -1;
}
} while (strm->avail_out && ret != Z_STREAM_END);
/* update available output and crc check value */
state->have = had - strm->avail_out;
state->next = strm->next_out - state->have;
strm->adler = crc32(strm->adler, state->next, state->have);
/* check gzip trailer if at end of deflate stream */
if (ret == Z_STREAM_END) {
if (gz_next4(state, &crc) == -1 || gz_next4(state, &len) == -1) {
gz_error(state, Z_DATA_ERROR, "unexpected end of file");
return -1;
}
if (crc != strm->adler) {
gz_error(state, Z_DATA_ERROR, "incorrect data check");
return -1;
}
if (len != (strm->total_out & 0xffffffffL)) {
gz_error(state, Z_DATA_ERROR, "incorrect length check");
return -1;
}
state->how = LOOK; /* ready for next stream, once have is 0 (leave
state->direct unchanged to remember how) */
}
/* good decompression */
return 0;
}
/* Make data and put in the output buffer. Assumes that state->have == 0.
Data is either copied from the input file or decompressed from the input
file depending on state->how. If state->how is LOOK, then a gzip header is
looked for (and skipped if found) to determine wither to copy or decompress.
Returns -1 on error, otherwise 0. gz_make() will leave state->have as COPY
or GZIP unless the end of the input file has been reached and all data has
been processed. */
local int gz_make(state)
gz_statep state;
{
z_streamp strm = &(state->strm);
if (state->how == LOOK) { /* look for gzip header */
if (gz_head(state) == -1)
return -1;
if (state->have) /* got some data from gz_head() */
return 0;
}
if (state->how == COPY) { /* straight copy */
if (gz_load(state, state->out, state->size << 1, &(state->have)) == -1)
return -1;
state->next = state->out;
}
else if (state->how == GZIP) { /* decompress */
strm->avail_out = state->size << 1;
strm->next_out = state->out;
if (gz_decomp(state) == -1)
return -1;
}
return 0;
}
/* Skip len uncompressed bytes of output. Return -1 on error, 0 on success. */
local int gz_skip(state, len)
gz_statep state;
z_off64_t len;
{
unsigned n;
/* skip over len bytes or reach end-of-file, whichever comes first */
while (len)
/* skip over whatever is in output buffer */
if (state->have) {
n = GT_OFF(state->have) || (z_off64_t)state->have > len ?
(unsigned)len : state->have;
state->have -= n;
state->next += n;
state->pos += n;
len -= n;
}
/* output buffer empty -- return if we're at the end of the input */
else if (state->eof && state->strm.avail_in == 0)
break;
/* need more data to skip -- load up output buffer */
else {
/* get more output, looking for header if required */
if (gz_make(state) == -1)
return -1;
}
return 0;
}
/* -- see zlib.h -- */
int ZEXPORT gzread(file, buf, len)
gzFile file;
voidp buf;
unsigned len;
{
unsigned got, n;
gz_statep state;
z_streamp strm;
/* get internal structure */
if (file == NULL)
return -1;
state = (gz_statep)file;
strm = &(state->strm);
/* check that we're reading and that there's no error */
if (state->mode != GZ_READ || state->err != Z_OK)
return -1;
/* since an int is returned, make sure len fits in one, otherwise return
with an error (this avoids the flaw in the interface) */
if ((int)len < 0) {
gz_error(state, Z_BUF_ERROR, "requested length does not fit in int");
return -1;
}
/* if len is zero, avoid unnecessary operations */
if (len == 0)
return 0;
/* process a skip request */
if (state->seek) {
state->seek = 0;
if (gz_skip(state, state->skip) == -1)
return -1;
}
/* get len bytes to buf, or less than len if at the end */
got = 0;
do {
/* first just try copying data from the output buffer */
if (state->have) {
n = state->have > len ? len : state->have;
memcpy(buf, state->next, n);
state->next += n;
state->have -= n;
}
/* output buffer empty -- return if we're at the end of the input */
else if (state->eof && strm->avail_in == 0)
break;
/* need output data -- for small len or new stream load up our output
buffer */
else if (state->how == LOOK || len < (state->size << 1)) {
/* get more output, looking for header if required */
if (gz_make(state) == -1)
return -1;
continue; /* no progress yet -- go back to memcpy() above */
/* the copy above assures that we will leave with space in the
output buffer, allowing at least one gzungetc() to succeed */
}
/* large len -- read directly into user buffer */
else if (state->how == COPY) { /* read directly */
if (gz_load(state, buf, len, &n) == -1)
return -1;
}
/* large len -- decompress directly into user buffer */
else { /* state->how == GZIP */
strm->avail_out = len;
strm->next_out = buf;
if (gz_decomp(state) == -1)
return -1;
n = state->have;
state->have = 0;
}
/* update progress */
len -= n;
buf = (char *)buf + n;
got += n;
state->pos += n;
} while (len);
/* return number of bytes read into user buffer (will fit in int) */
return (int)got;
}
/* -- see zlib.h -- */
int ZEXPORT gzgetc(file)
gzFile file;
{
int ret;
unsigned char buf[1];
gz_statep state;
/* get internal structure */
if (file == NULL)
return -1;
state = (gz_statep)file;
/* check that we're reading and that there's no error */
if (state->mode != GZ_READ || state->err != Z_OK)
return -1;
/* try output buffer (no need to check for skip request) */
if (state->have) {
state->have--;
state->pos++;
return *(state->next)++;
}
/* nothing there -- try gzread() */
ret = gzread(file, buf, 1);
return ret < 1 ? -1 : buf[0];
}
/* -- see zlib.h -- */
int ZEXPORT gzungetc(c, file)
int c;
gzFile file;
{
gz_statep state;
/* get internal structure */
if (file == NULL)
return -1;
state = (gz_statep)file;
/* check that we're reading and that there's no error */
if (state->mode != GZ_READ || state->err != Z_OK)
return -1;
/* process a skip request */
if (state->seek) {
state->seek = 0;
if (gz_skip(state, state->skip) == -1)
return -1;
}
/* can't push EOF */
if (c < 0)
return -1;
/* if output buffer empty, put byte at end (allows more pushing) */
if (state->have == 0) {
state->have = 1;
state->next = state->out + (state->size << 1) - 1;
state->next[0] = c;
state->pos--;
return c;
}
/* if no room, give up (must have already done a gzungetc()) */
if (state->have == (state->size << 1)) {
gz_error(state, Z_BUF_ERROR, "out of room to push characters");
return -1;
}
/* slide output data if needed and insert byte before existing data */
if (state->next == state->out) {
unsigned char *src = state->out + state->have;
unsigned char *dest = state->out + (state->size << 1);
while (src > state->out)
*--dest = *--src;
state->next = dest;
}
state->have++;
state->next--;
state->next[0] = c;
state->pos--;
return c;
}
/* -- see zlib.h -- */
char * ZEXPORT gzgets(file, buf, len)
gzFile file;
char *buf;
int len;
{
unsigned left, n;
char *str;
unsigned char *eol;
gz_statep state;
/* check parameters and get internal structure */
if (file == NULL || buf == NULL || len < 1)
return NULL;
state = (gz_statep)file;
/* check that we're reading and that there's no error */
if (state->mode != GZ_READ || state->err != Z_OK)
return NULL;
/* process a skip request */
if (state->seek) {
state->seek = 0;
if (gz_skip(state, state->skip) == -1)
return NULL;
}
/* copy output bytes up to new line or len - 1, whichever comes first --
append a terminating zero to the string (we don't check for a zero in
the contents, let the user worry about that) */
str = buf;
left = (unsigned)len - 1;
if (left) do {
/* assure that something is in the output buffer */
if (state->have == 0) {
if (gz_make(state) == -1)
return NULL; /* error */
if (state->have == 0) { /* end of file */
if (buf == str) /* got bupkus */
return NULL;
break; /* got something -- return it */
}
}
/* look for end-of-line in current output buffer */
n = state->have > left ? left : state->have;
eol = memchr(state->next, '\n', n);
if (eol != NULL)
n = (unsigned)(eol - state->next) + 1;
/* copy through end-of-line, or remainder if not found */
memcpy(buf, state->next, n);
state->have -= n;
state->next += n;
state->pos += n;
left -= n;
buf += n;
} while (left && eol == NULL);
/* found end-of-line or out of space -- terminate string and return it */
buf[0] = 0;
return str;
}
/* -- see zlib.h -- */
int ZEXPORT gzdirect(file)
gzFile file;
{
gz_statep state;
/* get internal structure */
if (file == NULL)
return 0;
state = (gz_statep)file;
/* check that we're reading */
if (state->mode != GZ_READ)
return 0;
/* if the state is not known, but we can find out, then do so (this is
mainly for right after a gzopen() or gzdopen()) */
if (state->how == LOOK && state->have == 0)
(void)gz_head(state);
/* return 1 if reading direct, 0 if decompressing a gzip stream */
return state->direct;
}
/* -- see zlib.h -- */
int ZEXPORT gzclose_r(file)
gzFile file;
{
int ret;
gz_statep state;
/* get internal structure */
if (file == NULL)
return Z_STREAM_ERROR;
state = (gz_statep)file;
/* check that we're reading */
if (state->mode != GZ_READ)
return Z_STREAM_ERROR;
/* free memory and close file */
if (state->size) {
inflateEnd(&(state->strm));
free(state->out);
free(state->in);
}
gz_error(state, Z_OK, NULL);
free(state->path);
ret = close(state->fd);
free(state);
return ret ? Z_ERRNO : Z_OK;
}
| {
"pile_set_name": "Github"
} |
Regulation of sugar utilization by Saccharomyces cerevisiae.
There are several kinds of regulation that enable microbes to cope with rapidly changing supplies of nutrients. This is exemplified by sugar metabolism in Saccharomyces cerevisiae. Some readily reversible controls affect the activity of enzymes, either by allosteric activation and deactivation, which often occur within seconds, or by covalent modification, within minutes. Other controls regulate the amount of enzyme present in the cells, either by irreversible proteolytic inactivation of the enzyme, or by influencing enzymic synthesis. The nomenclature of these processes is often confused. | {
"pile_set_name": "PubMed Abstracts"
} |
Montoya 'would accept Inter'
By Football Italia staff
Barcelona full-back Martin Montoya’s agent confirmed “Inter would be a welcome destination.”
The 24-year-old right-back is reconsidering his future at Camp Nou after Dani Alves surprisingly renewed his contract.
“Next week we will have a meeting with Barcelona and hear what they have to say,” agent Juan de Dios Carrasco told fcinternews.
“Obviously, Martin would like to play more consistently. Before saying one way or the other, I want to first talk to the club, but as I repeat he wants to be a starting player. We’ll know much more on the situation next week.
“Inter would certainly be a welcome destination, especially if he’d be used as a regular starter. We are talking about a great club.”
The Nerazzurri could ask for a loan with option to buy at the end of the season, as Montoya’s price-tag is €10m.
Watch Serie A live in the UK on Premier Sports for just £9.99 per month including live LaLiga, Eredivisie, Scottish Cup Football and more. Visit: https://www.premiersports.com/subscribenow | {
"pile_set_name": "OpenWebText2"
} |
High Incidence of Bell's Palsy After Mastoidectomy: A Longitudinal Follow-up Study.
The objective of this study was to compare the prevalence of Bell's palsy in participants who underwent mastoidectomy (to treat chronic otitis media) and nonmastoidectomy participants (control). Using the national cohort study from the Korean Health Insurance Review and Assessment Service, mastoidectomy patients (2,045) and control participants (8,180) were matched 1:4 for age, sex, income, and region of residence. The prevalence of Bell's palsy in both the groups was measured from 0 to 10 years postoperation. In a sample of 1,025,340 Korean individuals, 7,070 were diagnosed or treated with Bell's palsy between 2002 and 2013; the annual incidence of Bell's palsy was 0.057%. The overall prevalence of Bell's palsy was three times higher in the mastoidectomy group (1.27%) than control group (0.49%) (p < 0.001). The prevalence of Bell's palsy was different between the two groups in postoperative 0 year: 0.78% for the mastoidectomy group versus 0.01% for the control group (p < 0.001). Although we could not verify the laterality, the prevalence of Bell's palsy was increased in chronic otitis media patients treated with mastoidectomy patients compared with controls, especially within a year after surgery. | {
"pile_set_name": "PubMed Abstracts"
} |
Lumbar facet joint infection associated with epidural and paraspinal abscess.
A case of lumbar facet joint infection associated with abscesses of the paraspinal muscles and the epidural space is presented. The infection did not respond to intravenous antibiotic therapy and resolved only after incision and drainage of the epidural space, involved facet joint, and paraspinal musculature. Magnetic resonance imaging, which showed a widened facet joint, epidural abscess, and paraspinal involvement, aided in diagnosis and preoperative planning. This condition is rare, and this report outlines some clinical characteristics of the infection and the usefulness of magnetic resonance imaging in visualizing the extent of the infection. | {
"pile_set_name": "PubMed Abstracts"
} |
If we’re lucky, every few months a poster is released that makes you step back from your computer and stare. A poster so gorgeous, fans and non-fans a like will bask in its beauty. Some previous examples are Olly Moss’s Star Wars posters, Ken Taylor’s Halloween poster, Tyler Stout’s Akira, Aaron Horkey’s There Will be Blood and now, you can add Tom Whalen‘s The Wizard of Oz to the list.
Whalen has long been a favorite, both here on /Film and in galleries across the country. Working consistently for Mondo and Gallery 1988 has helped the Pennsylvania-based artist develop quite a following and, as fantastic as his work always is, this poster – made for Mondo – takes the cake. It’s epic, evocative and sure to be incredibly difficult to obtain.
Check out the full image after the jump along with another new Whalen poster from, for the Looney Tunes short Knighty Knight Bugs, as well as two comic-themed posters for The Black Beetle by Francesco Francavilla.
First up, here are Tom Whalen’s latest two posters, for The Wizard of Oz and Knighty Knight Bugs.
Knighty Knight Bugs is an 18″x24″ screen print in an edition of 275. It’ll cost $40. The Wizard of Oz is 24″x36″ screen print in an edition of 350. It’ll cost $60. Both will be available Thursday June 6 at a random time by following @MondoNews.
Next up, comic artist Francesco Francavilla has taken his Dark Horse comic property The Black Beetle and, with the help of Mondo, turned it into a poster. Here is the regular and variant courtesy of Comics Alliance.
The variant will be available exclusively at HeroesCon in North Carolina in a $75 edition for 110. The regular will be on sale in the coming weeks @MondoNews, its an edition of 225 and will cost $55. Both are 24″X36″. | {
"pile_set_name": "Pile-CC"
} |
Meet Suprema Wolski: The Strongwoman
Meet Suprema Wolski: The Strongwoman
We’ve talked a bit about the setting of Sideshow. Let’s take a look at the characters.
When Abby and her brother attend the Athletic Show at McClure’s Amusements, the “astonishingly pretty” referee happens to catch her eye. She has no idea the role that this reserved and troubled young woman would play in her future, but she does know that her presence is hard to ignore.
Vulcana (1875-1946) – An early performer Suprema would have admired and one of my inspirations for Suprema’s character.
Beverly Agnes Wolski did not have a great relationship with her parents growing up. Luckily, she had her Uncle Boleslaw and Aunt Ida, who took her from the struggling farm she called home and taught her to get along as part of the carnival world. She started off fortune telling with her aunt, but quickly moved on to a sideshow act as a strongwoman, taking the name Suprema. She took to the act easily, using the performance (and training for it – there is no gaff to Suprema’s routine) as a means of reclaiming the strength and assertiveness she wasn’t allowed in her childhood.
Despite her weaknesses for soda and comics (especially romance comics, but don’t tell) and her commanding stage presence, Suprema is often cold and reserved in person. She has suffered loss in her life and is afraid to get close to others, so she is far more likely to lash out than be vulnerable. When Abby is able to be vulnerable around her, she unexpectedly finds herself softening and allowing this new and intriguing person into her world.
Sideshow is available now for pre-order from Interlude Press. Be sure to reserve your copy today. | {
"pile_set_name": "Pile-CC"
} |
The Worst Mistake People Make in Political Arguments - danielrm26
http://danielmiessler.com/blog/the-worst-mistake-people-make-in-political-arguments
======
CWuestefeld
Good advice across the board, not just for political discussion.
This is just explaining the logical fallacy of "fundamental atribution error"
(<http://en.wikipedia.org/wiki/Fundamental_attribution_error> ). More
popularly, this has been paraphrased as "never attribute to malice what can be
explained by stupidity".
Personally, I find this logical fallacy infuriating because it just doesn't
matter. Whether someone is being evil or is just wrong is irrelevant. The only
thing that matters is the end result. If someone is being charitable because
he thinks it'll make him rich in the long run, that's still good. If someone
is accidentally causing harm, we want him to stop regardless of his
intentions. And that's all that matters at the bottom line.
~~~
danielrm26
I agree that the outcome is more important, but I think the difference between
Sean Hannity and Ted Bundy should be acknowleged. They may both produce evil,
but the one who thinks he is doing good should be handled differently.
| {
"pile_set_name": "HackerNews"
} |
NOW OPEN!
A PASSION FOR BREAD AND WINE
Our goal is to provide delicious, healthful, and affordable food and drink options for the residents, businesses, and visitors of the Conejo Valley.
The team has deep roots in artisanal food and wine, and we love to showcase local farmers, winemakers, and brewers. We believe that there is magic that comes from using your hands to combine flour, water, and salt - taste our naturally leavened breads and you will see what we mean.
Our passion to connect individuals through a great food that is prepared simply, is what made Decker Kitchen a reality. | {
"pile_set_name": "Pile-CC"
} |
##
# WARNING: Metasploit no longer maintains or accepts meterpreter scripts.
# If you'd like to improve this script, please try to port it as a post
# module instead. Thank you.
##
#Meterpreter script for running WMIC commands on Windows 2003, Windows Vista
# and Windows XP and Windows 2008 targets.
#Provided by Carlos Perez at carlos_perez[at]darkoperator[dot]com
################## Variable Declarations ##################
session = client
wininfo = client.sys.config.sysinfo
# Setting Arguments
@@exec_opts = Rex::Parser::Arguments.new(
"-h" => [ false,"Help menu." ],
"-c" => [ true,"Command to execute. The command must be enclosed in double quotes."],
"-f" => [ true,"File where to saved output of command."],
"-s" => [ true,"Text file with list of commands, one per line."]
)
#Setting Argument variables
commands = []
script = []
outfile = nil
################## Function Declarations ##################
# Function for running a list of WMIC commands stored in a array, returs string
def wmicexec(session,wmiccmds= nil)
tmpout = ''
session.response_timeout=120
begin
tmp = session.sys.config.getenv('TEMP')
wmicfl = tmp + "\\"+ sprintf("%.5d",rand(100000))
wmiccmds.each do |wmi|
print_status "running command wmic #{wmi}"
print_line wmicfl
r = session.sys.process.execute("cmd.exe /c %SYSTEMROOT%\\system32\\wbem\\wmic.exe /append:#{wmicfl} #{wmi}", nil, {'Hidden' => true})
sleep(2)
#Making sure that wmic finishes before executing next wmic command
prog2check = "wmic.exe"
found = 0
while found == 0
session.sys.process.get_processes().each do |x|
found =1
if prog2check == (x['name'].downcase)
sleep(0.5)
found = 0
end
end
end
r.close
end
# Read the output file of the wmic commands
wmioutfile = session.fs.file.new(wmicfl, "rb")
until wmioutfile.eof?
tmpout << wmioutfile.read
end
wmioutfile.close
rescue ::Exception => e
print_status("Error running WMIC commands: #{e.class} #{e}")
end
# We delete the file with the wmic command output.
c = session.sys.process.execute("cmd.exe /c del #{wmicfl}", nil, {'Hidden' => true})
c.close
tmpout
end
# Function for writing results of other functions to a file
def filewrt(file2wrt, data2wrt)
output = ::File.open(file2wrt, "a")
data2wrt.each_line do |d|
output.puts(d)
end
output.close
end
#check for proper Meterpreter Platform
def unsupported
print_error("This version of Meterpreter is not supported with this Script!")
raise Rex::Script::Completed
end
def usage
print_line("Windows WMIC Command Execution Meterpreter Script ")
print_line @@exec_opts.usage
print_line("USAGE:")
print_line("run wmic -c \"WMIC Command Argument\"\n")
print_line("NOTE:")
print_line("Not all arguments for WMIC can be used, the /append: option is used by the script")
print_line("for output retrieval. Arguments must be encased in double quotes and special characters escaped\n")
print_line("Example:")
print_line("run wmic -c \"useraccount where (name = \\\'Administrator\\\') get name, sid\"\n")
raise Rex::Script::Completed
end
################## Main ##################
@@exec_opts.parse(args) { |opt, idx, val|
case opt
when "-c"
commands.concat(val.split("/"))
when "-s"
script = val
if not ::File.exist?(script)
raise "Command List File does not exists!"
else
::File.open(script, "r").each_line do |line|
next if line.strip.length < 1
next if line[0,1] == "#"
commands << line.chomp
end
end
when "-f"
outfile = val
when "-h"
usage
else
print_error "Unknown option: #{opt}"
usage
end
}
if args.length == 0
usage
end
unsupported if client.platform != 'windows'
if outfile == nil
print_status wmicexec(session,commands)
else
print_status("Saving output of WMIC to #{outfile}")
filewrt(outfile, wmicexec(session,commands))
end
| {
"pile_set_name": "Github"
} |
1
100
40
16 4
19 6
9 21
4 8
2 11
10 15
12 14
5 18
31 11
5 23
28 27
2 9
17 33
35 3
27 9
14 10
26 16
2 11
30 25
2 32
31 15
31 6
33 14
10 21
16 25
13 33
8 29
21 11
13 19
26 5
11 33
32 7
29 17
20 23
1 33
16 31
13 15
24 25
22 13
26 8
| {
"pile_set_name": "Github"
} |
Brush Burning Banned
The Department of Environmental Conservation reminds New Yorkers that with warming temperatures and dry conditions, residential brush burning in towns with less than 20,000 residents is prohibited through May 14th. With the lack of snow cover over much of the State and unseasonably warm temperatures forecasted, experts believe conditions for wild fires will be heightened in the coming weeks. Since being enacted in 2009, the DEC says the ban has been extremely effective in reducing the number of wildfires. | {
"pile_set_name": "Pile-CC"
} |
Psychosocial Factors in Children and Youth With Special Health Care Needs and Their Families.
Children and youth with special health care needs (CYSHCN) and their families may experience a variety of internal (ie, emotional and behavioral) and external (ie, interpersonal, financial, housing, and educational) psychosocial factors that can influence their health and wellness. Many CYSHCN and their families are resilient and thrive. Medical home teams can partner with CYSHCN and their families to screen for, evaluate, and promote psychosocial health to increase protective factors and ameliorate risk factors. Medical home teams can promote protective psychosocial factors as part of coordinated, comprehensive chronic care for CYSHCN and their families. A team-based care approach may entail collaboration across the care spectrum, including youth, families, behavioral health providers, specialists, child care providers, schools, social services, and other community agencies. The purpose of this clinical report is to raise awareness of the impact of psychosocial factors on the health and wellness of CYSHCN and their families. This clinical report provides guidance for pediatric providers to facilitate and coordinate care that can have a positive influence on the overall health, wellness, and quality of life of CYSHCN and their families. | {
"pile_set_name": "PubMed Abstracts"
} |
Seasonal and sex-linked variations in hepatic and extrahepatic biotransformation activities in striped mullet (Mullus barbatus).
Microsomal cytochrome P450 content, NADPH-cytochrome c reductase, and phase I (ethoxycoumarin and ethoxyresorufin O-dealkylases) and phase II (glutathione S-transferase and UDP-glucuronyltransferase) activities were studied in the liver and intestine of the striped mullet (Mullus barbatus) for 8 months (before and during sexual maturation). Biotransformation activities were much lower in extrahepatic tissues than the corresponding activities in the liver. Intestinal and hepatic biotransformation activities presented similar seasonal fluctuations: Phase I activity increased from October to February (during water cooling) and generally decreased before spawning; Phase II activity was not greatly different. Moreover, NADPH-cytochrome c reductase, ethoxyresorufin O-dealkylase, and glutathione S-transferase activities were measured in the kidney during the sexual maturation period. Renal phase I and phase II activities showed very little fluctuation during the 5 months studied. Cytochrome P450 and ethoxycoumarin and ethoxyresorufin O-dealkylases exhibited sex-linked differences during sexual maturation, whatever the tissue: in the liver the values are higher in male fish, whereas in the intestine and kidney they are lower. | {
"pile_set_name": "PubMed Abstracts"
} |
College football public-school head coaches cash in big with bonuses to end regular season
Steve Berkowitz | USA TODAY
With conference championships decided and bowl bids handed out, college football head coaches at Bowl Subdivision public schools have picked up nearly $9.5 million in bonuses this season.
This past week alone, they totaled more than $2.5 million — and that's just part of the overall incentive payout schools will make to assistant coaches, strength coaches, athletics directors and a range of team staffers.
For the first time, USA TODAY Sports has been tracking on a weekly basis the amounts public-school football head coaches are scheduled to be getting and for what achievements.
Below are details of amounts achieved since the end of the regular season. The information is based on contracts USA TODAY Sports obtained from the schools through open-records requests, and shows the coaches' employers during the season. Since then, Lane Kiffin has moved from Florida Atlantic to Mississippi, Mike Norvell from Memphis to Florida State and Eli Drinkwitz has agreed to move from Appalachian State to Missouri.
Overall, Oregon's Mario Cristobal has racked up the greatest total at $1.175 million. But LSU's Ed Orgeron has $1.05 million and could pick up more from coaching honors and if the Tigers advance in the College Football Playoff. For some perspective on that: 39 FBS public-school head coaches were making less than $1 million in basic annual compensation from their respective schools this season.
More: Bonus earned by football coaches in FBS in regular season
COACHES SALARIES REPORT: Six surprising numbers from the database
UNTOUCHABLE: Gus Malzahn’s massive buyout at Auburn has big implications
DATABASE: How much each college football coach makes
Appalachian State: Eli Drinkwitz
$50,000: Win Sun Belt championship
***
Boise State: Bryan Harsin
$100,000: Win Mountain West championship
***
Central Michigan: Jim McElwain
$25,000: MAC coach of the year
***
Cincinnati: Luke Fickell
$50,000: Team among top 25 of final College Football Playoff ranking
***
Clemson: Dabo Swinney
$150,000: Win ACC championship
$150,000: Team plays in College Football Playoff semifinals (increases total for bowl play to $200,000 so far)
***
Florida: Dan Mullen
$100,000: Team plays in New Year's Six non-semifinal (increases total for bowl play to $200,000)
***
Florida Atlantic: Lane Kiffin
$10,000: Win Conference USA championship
***
Georgia: Kirby Smart
$100,000: Team plays in New Year's Six non-semifinal (increases total for bowl play to $175,000)
***
Hawaii: Nick Rolovich
$20,000: Mountain West coach of the year
***
Louisiana-Lafayette: Billy Napier
$25,000: Sun Belt coach of the year
***
Louisiana State: Ed Orgeron
$200,000: Win SEC championship
$225,000: Team plays in College Football Playoff semifinals (increases total for bowl play to $250,000 so far)
***
Louisville: Scott Satterfield
$50,000: ACC coach of the year
***
Memphis: Mike Norvell
$140,000: Team plays in New Year's Six non-semifinal (increases total for bowl play to $175,000)
$20,000: Team among No. 25 through No. 11 in final College Football Playoff rankings
***
Miami (Ohio): Chuck Martin
$44,428: Win MAC championship
***
Minnesota: P.J. Fleck
$50,000: Big Ten coach of the year by coaches
***
Ohio State: Ryan Day
$50,000: Big Ten coach of the year by media
$100,000: Win Big Ten championship
$250,000: Team plays in College Football Playoff semifinals
***
Oklahoma: Lincoln Riley
$50,000: Win Big 12 championship
$50,000: Team among top 5 in final CFP ranking
$125,000: Team plays in College Football Playoff semifinals (increases total for bowl play to $150,000 so far)
***
Oregon: Mario Cristobal
$150,000: Win Pac-12 championship
$25,000: Team plays in New Year's Six non-semifinal (increases total for bowl play to $175,000)
***
Penn State: James Franklin
$100,000: Team plays in New Year's Six non-semifinal (increases total for bowl play to $300,000)
***
Utah: Kyle Whittingham
$85,000: Team among top 25 of final College Football Playoff ranking (increases total for rankings to $100,000)
***
Western Michigan: Tim Lester | {
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The possibilities for creating, using, and completing adjective quizzes are endless. You can use quizzes to get better at adjective spelling skills, or you can increase your knowledge of adjective grammar rules.
Another helpful (and fun!) use of an adjective quiz is to test your knowledge of the meanings of certain adjectives. Some quizzes will focus on just one of these areas, and some will include a little of each area. Use our printable quiz sheet to help you practice your adjectives or as a template to give you ideas for creating your own quizzes. The answers to the questions are given in the corresponding section below.
Adjective Spelling Quiz
If you are concerned about spelling abilities when it comes to spelling adjectives, try out our spelling quiz and then use it as a template for creating more quizzes. For each question create three different spellings of each adjective, one that's correct and two others that are close in spelling to make it a litlle trickier. For example, the quiz provides three spellings - say, "fancyest," "fanciest," or "fancest"- and you have to circle which one is correct.
Students can check their answers using YourDictionary - our online dictionaries make it easy to look up words and learn their correct spelling.
Check out the printable Adjective Quiz for some sample questions on adjective spelling.
Adjective Grammar Quiz
A quiz is an excellent way to test whether the adjective is being used correctly in a sentence. For example, the quiz can test if you know if the adjective is modifying the correct word or if it is placed too far away from the noun it is modifying.
Our printable Adjective Quiz offers several questions that will help with the grammatical understanding of adjectives. You will be able to check you knowledge of the adjective being used correctly in the sentence. Other options to include in a grammar quiz are filling in the blanks with an appropriate adjective or circling all the adjectives in a paragraph.
Adjective Definition Quiz
Another way to use quizzes related to adjectives is to take some that test your knowledge of the meanings of adjectives. Many people use common adjectives in their daily lives, but when asked the actual definition of the adjective, they are stumped.
It can be difficult to pin down exactly what an adjective means unless you study definitions and make an effort to learn the real meanings of adjectives. By making quizzes for yourself or your students that force the quiz-taker to learn the definitions of tricky adjectives, you or the student can quickly boost vocabulary knowledge. For a start on developing your own quiz, check out the printable quiz provided.
Answers:
1. sorry; 2. angry; 3. lively; 4. high; 5. nervous
How to Make an Adjective Quiz
Making quizzes can often be easier than taking them, since there are so many options when it comes to designing and constructing an adjective quiz. By testing your vocabulary or quizzing your understanding of the spelling and grammar of adjectives, you will learn more about adjectives and grow as a writer and public speaker.
As you become more familiar with adjectives, their uses, and meanings, you will become a more precise speaker and will develop your ability to effectively describe things for other people. Your adjective vocabulary will increase exponentially.
YourDictionary has created a sample Adjective Quiz with questions that cover all three types of adjective quizzes - spelling, grammar and definitions. For more ideas, consider starting with one or more of YourDictionary's adjective worksheets. These can help you construct your adjective quiz and give you ideas for more questions.
Post a comment.
Adjective Quiz
By YourDictionary
The possibilities for creating, using, and completing adjective quizzes are endless. You can use quizzes to get better at adjective spelling skills, or you can increase your knowledge of adjective grammar rules.
Another helpful (and fun!) use of an adjective quiz is to test your knowledge of the meanings of certain adjectives. Some quizzes will focus on just one of these areas, and some will include a little of each area. Use our printable quiz sheet to help you practice your adjectives or as a template to give you ideas for creating your own quizzes. The answers to the questions are given in the corresponding section below. | {
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Worried about squirrels getting into your bird feeder??
What the hell is that line made of??
Worried about squirrels getting into your bird feeder?? What the hell is that line made of??
Worried about squirrels getting into your bird feeder??
Worried about squirrels getting into your bird feeder?? | {
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Beverly Wilshire Dental stands as the trusted and innovative leading centre for dentistry. Beverly Wilshire brand continues to be synonymous with medical beauty because of our highly skilled specialists, world class technologies, facilities and service. We help make dental visits easy with our innovative services and commitment to your smile.
Dr Yoganjali Dorairaj - General Dentistry, BDS (AIMST)
Dr Yoganjali obtained her Bachelor of Dental Surgery (B.D.S.) from Aimst University, Kedah. After graduation, Dr Yoganjali had served in the Ministry of Health and completed all the specialities postings before joining private sector. She refined her knowledge and skills by actively attending conferences and practical trainings.
A member of the Malaysian Dental Association, Dr Yoganjali found great passion in dentistry as she enjoys the diversity in this field and the hands-on nature of a dentist. Also an art lover, she gets the both worlds being in dentistry where science meets art. Dr Yoganjali believes a great smile is everyone’s asset and should not be neglected. She strongly believes in practicing at the forefront of the evolving field of dentistry by keeping abreast with latest research and technology to provide better service to her patients.
Graduated in 1997 from University of Western Australia in Perth, Dr Khairil Aznan joined Ministry of Health as a dental officer for nearly two years. He then joined University Kebangsaan Malaysia as a training lecturer and in 2001, he was offered a full scholarship to specialize in Orthodontics. He obtained Masters of Medical Science (Orthodontics) from University of Sheffield in 2003. He completed his Membership in Orthodontics from Royal College of Surgeons of Edinburgh in 2004. Currently, he is a Consultant in Orthodontics and Senior Lecturer in Department of Orthodontics, Faculty of Dentistry, University Kebangsaan Malaysia.
Dr Khairil Aznan believes that everyone deserves to have a great smile with well aligned teeth regardless of age. Besides aligning teeth using conventional metal & ceramic braces for aesthetics/ cosmetic/ oral health, Dr Khairil Aznan also uses the latest low friction Self Ligating Braces. He also uses clear aligners in patients who prefer to have their teeth aligned without having braces. Other than that, he is also involves in Dentofacial-Orthopaedic and uses Functional Appliances to correct jaw problems in growing children. His special interest is in Complex Orthodontics cases such as Orthognathic treatment (braces & jaw surgery).
Dr Khairil Aznan is a board member of the National Specialist Register (Orthodontics). He is also a member of Malaysian Association of Orthodontics & Academy of Medicine, Malaysia. He enjoys travelling with family and outdoor activities such as riding superbike, trekking & snorkeling.
Having 27 years’ experience under his belt, Datuk Dr Mohd Noor Awang graduated from University of Malaya Dental School in Bachelor of Dental Surgery (BDS) in 1979 and obtained his postgraduate degree Master Science (MSc) in Oral & Maxillofacial Surgery from University of London in 1983.
He began his career as an academician & clinician in the field of Oral & Maxillofacial Surgery at University of Malaya Dental School since 1981 and was appointed as an Associate Professor in Oral & Maxillofacial Surgery and Deputy Dean in 1990. He has published numerous papers, books, monogram and new surgical techniques in Oral & Maxillofacial Surgery both local & international publications.
In 1992 he venture into private healthcare practice and was appointed as Senior Consultant Oral & Maxillofacial Surgeon. Throughout his career he has made major contributions in raising public awareness on dental health through public talks, forums and being a regular guest speaker for radio talk shows & TVs such as ‘Good Morning Malaysia’. He is also a columnist on oral health for national newspaper Berita Harian. In view of his continuous public interests and long serving of national interests especially in promoting good healthcare he was conferred ‘Darjah Kebesaran Panglima Mahkota Wilayah (Wilayah Persekutuan)’ by The Royal Highness Yang Di Agong.
Verified clinics are dental practices that have been checked by our team to be up-to-date and current . Verification is done personally clinic by clinic . This is an effort from our part to make sure the information on our pages are accurate to serve you better. | {
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Distribution of C22-, C24- and C26-alpha-unit-containing mycolic acid homologues in mycobacteria.
There are three mycolic acid homologues with C22-, C24- and C26-alpha-units in Mycobacterium. In order to reveal the composition and distribution of these homologues in each subclass and molecular species of mycolic acids and to compare them with the composition of constitutive non-polar fatty acids (free and bound forms), we have separated non-polar fatty acids and each subclass of mycolic acids from 21 mycobacterial species by thin-layer chromatography, and analyzed non-polar fatty acid methyl esters by gas chromatography (GC) and the cleavage products of methyl mycolate by pyrolysis GC. We further performed mass chromatographic analysis of trimethylsilyl (TMS) ether derivatives of mycolic acid methyl esters by monitoring [B-29]+ ions (loss of CHO from the alpha-branched-chain structure of mycolic acids) of m/z 426, 454 and 482 which are attributed to C22-, C24- and C26-alpha-units of TMS ether derivatives of methyl mycolates, respectively, (Kaneda, K. et al, J. Clin. Microbiol. 24: 1060-1070, 1986). By pyrolysis GC, C22:0, C24:0 and C26:0 fatty acid methyl esters generated by the C2-C3 cleavage of C22-, C24- and C26-alpha-unit-containing mycolic acid methyl esters, respectively, were detected. Their proportion was almost the same among subclasses of mycolic acids in every Mycobacterium and also similar to the proportion of constitutive non-polar C22:0, C24:0 and C26:0 fatty acids. By mass chromatography, the composition and distribution of C22- and C24-alpha-unit-containing homologues were revealed to be similar between alpha- and alpha'-mycolic acids in every Mycobacterium.(ABSTRACT TRUNCATED AT 250 WORDS) | {
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[Elderly residents in homes for the aged: adjustment in the light of Callista Roy].
This study aimed to evaluate the adaptation of elderly individuals voluntarily reside in Institution for the Aged (LTCF) in the city of Fortaleza-CE, based on the theoretical model of Roy. Descriptive study, in a IPLI involving thirteen elderly residents. Data collect was through interviews in the months of October and December 2011 and organized by thematic content analysis. The following themes has emerged: I Physical subdivided into body sensation and body image; Staff and I, subdivided into self-consistency and auto ideal be moral-ethical-spiritual. Thus, the option to live in ILPI not effectively changed the lives of elderly people. They managed to adapt to the local and coexist well with internal and external stimuli. | {
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Just four short months ago, I wrote an article about Star Trek Technologies and how close we are to achieving each one. I think I can speak for most trekkies when I say that the day things like tricorders, replicators, cloaking devices and universal translators all be come realities is going to be very exciting.
As it turns out, Microsoft has just developed what many people are calling the first generation universal translator. Before now, the closest thing we really had to that was a Phraselator, which is a device used by the military. It is simply a one-way translator that plays pre-recorded messages (I know, lame). And of course, there are iPhone apps like Word Lens, which translates text into English in real time, and Google Translate, but those don’t really count in my opinion.
Just last week, Microsoft unveiled their Translator Hub which is a system that translates speech from one language to another, but get this, it spits it back out in a voice that sounds similar to your own (tone of voice, speed, etc.). It will be free to use, and it comes with 26 pre-installed languages. You can click over to Technology Review to listen to a few audio clips of this technology in action. According to Star Trek, the universal translator was invented right before the year 2151, so I suppose we are ahead of schedule. I can’t help but think that James T. Kirk would be proud. Now if we could just get a handle on a modern day replicator, that would be great since I’d like to replicate myself another caramel macchiato right now. | {
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As part of the launch of the new Bentley GT3R, Simon Stock shot a short film depicting “95 years of Bentley Motorsport Heritage”, with one of the original Bentley Blowers, the Speed 8, and the GT3 race car taking centre stage, before revealing the GT3R. Stills were also shot, and we did some retouching and colour grading to help produce the beautiful images below. The film can be seen here. | {
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Chisum House
The Chisum House is a historic house at 1320 South Cumberland Street in Little Rock, Arkansas. It is a two-story frame structure, with a hip roof and an exterior sheathed in clapboards and decorative cut shingles. The roof is capped by a pair of finials, and there is a three-story square tower angled at one corner, topped by a bellcast roof and finial. The design is varied in the Queen Anne style, with multiple sizes and configurations of windows and porches, the latter featuring turned woodwork. Built in 1894, it is one of the city's relatively few Queen Anne Victorians. It was built for Jason Sowell, one of the city's leading families, in what was then its most exclusive neighborhood.
The house was listed on the National Register of Historic Places in 1975.
See also
National Register of Historic Places listings in Little Rock, Arkansas
References
Category:Houses on the National Register of Historic Places in Arkansas
Category:Queen Anne architecture in Arkansas
Category:Houses completed in 1894
Category:Houses in Little Rock, Arkansas
Category:National Register of Historic Places in Little Rock, Arkansas
Category:Historic district contributing properties in Arkansas | {
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3
Let c(p) be the third derivative of -p**6/120 + p**4/24 + 8*p**3/3 + 77*p**2. Find the first derivative of c(m) wrt m.
-3*m**2 + 1
Let h(b) = -20*b**2 - 5*b - 165. Let a(u) = 40*u**2 + 13*u + 329. Let p(m) = -2*a(m) - 5*h(m). Differentiate p(r) wrt r.
40*r - 1
Let x(c) be the third derivative of -383*c**5/60 + 29*c**4/8 - c**3/6 - 393*c**2. Find the second derivative of x(y) wrt y.
-766
Suppose 5*d = 6*v - 4*v + 87, 0 = -5*d + 5*v + 90. What is the second derivative of 2*a**3 - 60 + 116 - 56 - d*a wrt a?
12*a
Let n(q) be the first derivative of -9*q**6/10 + 29*q**2/2 - 22*q - 14. Let o(u) be the first derivative of n(u). Differentiate o(r) wrt r.
-108*r**3
Let n(f) be the second derivative of 11/12*f**4 + 0*f**2 + 0*f**3 + 12*f + 0 - 13/20*f**5. What is the third derivative of n(d) wrt d?
-78
Let z(f) = -f**3 - f. Let s(d) = -3*d**3 - 53*d**2 - 4*d - 43. Let k(c) = s(c) - 4*z(c). Find the first derivative of k(p) wrt p.
3*p**2 - 106*p
Let m(q) be the third derivative of -29*q**7/210 - q**6/60 - 19*q**5/15 + q**4/12 + 131*q**2 + 2*q. Find the third derivative of m(t) wrt t.
-696*t - 12
Let a(m) = -65*m**3 + 5*m + 99. Let o(b) = -126 - 39*b**3 + 32*b**3 - 23 + 104*b**3 - 8*b. Let p(j) = 8*a(j) + 5*o(j). What is the derivative of p(l) wrt l?
-105*l**2
Suppose 5*u = -2*m + 50 + 33, -3*u + 2*m + 37 = 0. Find the first derivative of -b**4 - u*b + 7*b + 8*b - 18 wrt b.
-4*b**3
Let o = -4 + 4. Suppose -4 = -n - o*n. Find the second derivative of -2*f**2 - 2*f + f**2 - 2*f**n + f**2 wrt f.
-24*f**2
Let q(b) = 61*b**6 - 9*b**3 + 165*b**2. Let c(m) = -31*m**6 + 4*m**3 - 83*m**2. Let w(y) = -9*c(y) - 4*q(y). Find the third derivative of w(r) wrt r.
4200*r**3
Let f(a) = -371*a**4 - 47*a**2 + 2*a + 2. Let b(r) = 5931*r**4 + 753*r**2 - 33*r - 33. Let p(j) = -2*b(j) - 33*f(j). Find the third derivative of p(i) wrt i.
9144*i
Let h(y) = y**2. Let a(p) = 17*p**4 + 4*p**2 + 3*p - 13 + 13 + p**2. Let i(r) = -a(r) + 5*h(r). What is the second derivative of i(z) wrt z?
-204*z**2
Let s(a) = -69*a**2 - 32*a - 5. Let t(f) = -208*f**2 - 94*f - 14. Let w(c) = 8*s(c) - 3*t(c). What is the second derivative of w(z) wrt z?
144
Let x(w) = 33*w + 135. Let u(o) = 38*o + 134. Let j(p) = 4*u(p) - 3*x(p). What is the derivative of j(h) wrt h?
53
Let g = -2 - -6. Find the first derivative of 3*l**4 + 9*l**g + 8 + 3*l**4 - l**4 wrt l.
56*l**3
Let f(r) be the second derivative of 20*r**7/21 - 169*r**4/12 + 95*r. Find the third derivative of f(a) wrt a.
2400*a**2
Let s be 201/15 - (-6)/(-15). Suppose -d - s = -17. What is the second derivative of -51*g**2 + d*g + 41*g**2 + 8*g wrt g?
-20
Let v(k) = -k**2 + 9*k - 7. Let g be v(8). Let t(w) = 12*w**2 - w + 1. Let h be t(g). Find the first derivative of p**3 - h - 8*p**3 - 5*p**3 wrt p.
-36*p**2
Let h(a) = 57*a - 60. Let z(c) = c - 1. Let i(s) = h(s) - 3*z(s). What is the derivative of i(o) wrt o?
54
Let a(i) = i**3 - 16*i**2 + 14*i + 17. Let t be (-9)/15 - 156/(-10). Let r be a(t). What is the third derivative of 4*y**r - 65*y**4 + 65*y**4 - 8*y**6 wrt y?
-960*y**3
Let b(o) = -2*o**3 + o**2 - o - 1. Let y(i) = -72*i**4 + 4*i**3 - 2*i**2 + 2*i - 317. Let c(n) = -2*b(n) - y(n). Find the first derivative of c(p) wrt p.
288*p**3
Let q(i) = 493*i**4 - 11*i**2 + 141*i. Let c(h) = -99*h**4 + 2*h**2 - 28*h. Let r(p) = 11*c(p) + 2*q(p). What is the second derivative of r(k) wrt k?
-1236*k**2
Let y(s) be the third derivative of s**7/70 + 4*s**5/15 + 139*s**4/12 - s**3/3 - 763*s**2. What is the second derivative of y(x) wrt x?
36*x**2 + 32
What is the third derivative of 8*l + 43*l**5 + 221*l**2 + 2*l**3 - 2 - 217*l**2 + 2 wrt l?
2580*l**2 + 12
Let h(j) be the third derivative of 2*j**6/3 - 11*j**5/10 + 38*j**2 - 2*j. Find the third derivative of h(k) wrt k.
480
Find the third derivative of 1255 + 1255 + 249*u**6 + 279*u**6 - 175*u**2 - 2510 wrt u.
63360*u**3
Find the second derivative of 33*p + 11*p**5 + 0*p - 54*p**5 wrt p.
-860*p**3
Let z(t) be the second derivative of -161*t**5/10 - 113*t**3/6 + t**2/2 + 387*t. What is the second derivative of z(b) wrt b?
-1932*b
Let z(u) = 18*u**2 - u + 56. Let o(a) = 90*a**2 - 5*a + 281. Let s(f) = 2*o(f) - 11*z(f). Find the first derivative of s(g) wrt g.
-36*g + 1
Let l be (1 + 0)*(5 - -2). Let y be (12/14)/((-42)/(-196)). Find the first derivative of -3 - 4*k**y + 5 - 3 - l wrt k.
-16*k**3
Let f(q) be the first derivative of q**7/3 - 5*q**3/2 - 2*q + 2. Let w(v) be the first derivative of f(v). Find the second derivative of w(p) wrt p.
280*p**3
Suppose 0 = -4*i - i + 50. Let t = i + -7. What is the third derivative of t*x**2 - 16*x - 8*x**3 + 16*x wrt x?
-48
Let y(v) = -78*v**2 + 3*v - 10. Let b(q) = -2*q**2. Let r(u) = 6*b(u) + y(u). Find the second derivative of r(c) wrt c.
-180
Let y(f) = -219*f**3 - 17*f + 13. Let c(b) = -216*b**3 - 16*b + 12. Let i(n) = 7*c(n) - 6*y(n). What is the second derivative of i(u) wrt u?
-1188*u
What is the derivative of 137 + 145 - 10*u**2 - 301 + 11*u**3 wrt u?
33*u**2 - 20*u
Let c(g) be the third derivative of -1/210*g**7 + 0*g + 0*g**4 - 10/3*g**3 + 14*g**2 + 0*g**5 + 0*g**6 + 0. Find the first derivative of c(q) wrt q.
-4*q**3
Let x(c) be the second derivative of -13*c + 0*c**3 + 0 + 11/15*c**6 - 19/12*c**4 + 0*c**2 + 0*c**5. What is the third derivative of x(b) wrt b?
528*b
Let d(j) be the third derivative of -47*j**7/105 - 59*j**5/60 + 131*j**2. Find the third derivative of d(a) wrt a.
-2256*a
Let p(l) be the third derivative of 202*l**7/105 - 58*l**5/15 + 465*l**2. Find the third derivative of p(f) wrt f.
9696*f
Let n(g) = -g**3 + 11*g**2 - 8*g + 1. Let o be n(10). What is the first derivative of -1 - 17*y**2 + o*y**2 - 11 wrt y?
8*y
Let n = 1 + -3. Let m be n - (-8 - -1 - 1). What is the second derivative of -4*x**2 - 2*x + 4 + m - 10 wrt x?
-8
Let q = 3 + -9. Let j(c) = -3*c**2 + 5*c + 4. Let t(k) = 3*k**2 - 6*k - 4. Let x(b) = q*j(b) - 5*t(b). Differentiate x(g) with respect to g.
6*g
Let i(d) = 7*d + 0*d - 4*d - 15*d**2 + 8*d. Let n(x) = 29*x**2 - 21*x. Let g(p) = 13*i(p) + 6*n(p). What is the second derivative of g(m) wrt m?
-42
What is the third derivative of -14*h**2 + 78*h**2 - 114*h**4 + 8*h**4 wrt h?
-2544*h
Let o(m) = -72*m**2 + 10*m - 2. Let k(q) = -69*q**2 + 11*q - 3. Let z(f) = -2*k(f) + 3*o(f). What is the second derivative of z(t) wrt t?
-156
Find the second derivative of -2*c**2 + 2179 + 170*c**2 - 44*c - 2179 wrt c.
336
Let l(b) be the second derivative of b**7/280 - b**5/60 - b**4/12 + 8*b. Let o(y) be the third derivative of l(y). Find the first derivative of o(x) wrt x.
18*x
Let j(z) = -36*z**3 + 2*z - 2*z - 9 + 20*z**2. Let m(u) = -9*u**3 + 5*u**2 - 2. Let a(g) = 2*j(g) - 9*m(g). Find the third derivative of a(x) wrt x.
54
Let z = 47 + 2. Find the second derivative of -z*h**3 - 3*h**4 + 49*h**3 - 14*h wrt h.
-36*h**2
Suppose 4*b = -2*n + n, -5*n + 5*b + 50 = 0. What is the second derivative of -n*a**3 - 17*a - 12*a + 20*a wrt a?
-48*a
Let p(u) be the second derivative of 3 + 0*u**4 - 4*u - 1/10*u**5 + 5/3*u**3 - 21/2*u**2. What is the derivative of p(x) wrt x?
-6*x**2 + 10
Let l be (-1 - 4)*20/(-25). Find the third derivative of 0*v**l - 8*v**2 + v**2 + 0*v**2 - 18*v**4 wrt v.
-432*v
Let s(k) = -231*k**4 - 21*k**3 + 678*k**2 + 21. Let c(v) = -2*v**4 - v**3 + v**2 + 1. Let h(y) = 21*c(y) - s(y). Find the third derivative of h(u) wrt u.
4536*u
Let u(s) = -3*s**3 + s**2 - 4*s - 2. Let f be u(-2). Differentiate -7 + f*y**4 - 26 - 7 wrt y.
136*y**3
Let m(g) = -2*g**5 + 10*g**3 + g**2 + 318*g + 9. Let b(x) = x**5 - 6*x**3 - 159*x - 5. Let o(t) = 5*b(t) + 3*m(t). Find the second derivative of o(r) wrt r.
-20*r**3 + 6
Let w(k) be the second derivative of 26*k**6/5 - 505*k**2/2 - 140*k. What is the derivative of w(x) wrt x?
624*x**3
Let d(m) be the second derivative of m**6/6 - 31*m**5/20 - 118*m**3/3 - m**2/2 + 73*m. Find the second derivative of d(y) wrt y.
60*y**2 - 186*y
Let s(i) = -3*i + 7. Let d be s(-9). What is the derivative of d - 13*v + 0 - 15*v - 9*v wrt v?
-37
Let p be (3 + 4 + -2)*-7. Let h(l) = -95*l**3 + 60. Let s(v) = -8*v**3 + 5. Let i(m) = p*s(m) + 3*h(m). What is the first derivative of i(q) wrt q?
-15*q**2
Let h(v) be the first derivative of 2*v**4/3 + 7*v**2/2 + 14*v + 13. Let y(t) be the first derivative of h(t). Different | {
"pile_set_name": "DM Mathematics"
} |
Ustadgah
Ustadgah is a Hindustani music school located in New Delhi. It was started by noted Sufi singer, Zila Khan. The school also helps talented students from underprivileged background to hone their singing skills.
History
The school was conceptualised in 2008 to impart Hindustani music training to students. And it started functioning from March 2010.
References
External links
Official site
Category:Music schools in India
Category:New Delhi | {
"pile_set_name": "Wikipedia (en)"
} |
Clinical pharmacokinetics of morphine.
Morphine (M) is recommended by the World Health Organization as the treatment of choice for moderate-to-severe cancer pain. Development of sensitive radioimmunoassays (RIA) and high-performance liquid chromatography in the past 20 years has allowed study of the pharmacokinetics of M, which remain incompletely understood. Data derived by RIA must be interpreted with caution due to cross-reactivity with anti-sera by metabolites, impairing assay specificity. The pharmacokinetics of M have been determined for various clinical situations, but there is large interpatient variability for most parameters. M is readily absorbed from all routes of administration, except transdermal, and it can be injected spinally. Peak plasma levels are achieved within 15-20 min of intramuscular and subcutaneous administration, and within 30-90 min after oral. Peak levels after oral administration are much lower than after parenteral routes, since oral M undergoes extensive first-pass metabolism in the liver. With repeated administration, the oral-parenteral relative potency ratio is 1:3 M can be administered epidurally or intrathecally and has also been given intracerebroventricularly. Epidural M enters the subarachnoid space, but is also absorbed into the systemic circulation. Only 5% of a dose crosses the dura. M administered in the lumbar region is quickly redistributed in the cerebrospinal fluid in a rostral direction, explaining the high incidence of systemic side effects following spinal administration. After absorption, M is rapidly and widely distributed and crosses the blood-brain barrier. With therapeutic doses, plasma protein binding is only 20-35%, and the volume of distribution is 1-6 L/kg. The primary site of M metabolism is the liver, and the dose should be reduced in patients with liver disease. Glucuronidation is the main metabolic pathway, but the principal metabolite, morphine-3-glucuronide (M3G), is inactive. Morphine-6-glucuronide (M6G) is produced in smaller amounts than M3G, but is pharmacologically active and many times more potent than M. The ratio of M6G to M in plasma, after a dose of M, is approximately 10:1, and the ratio does not change with increasing doses or prolonged treatment. Normorphine (NM) is also active, and is formed to a greater extent after oral administration; it is not, however, usually found in plasma. NM may be neurotoxic. M and its metabolites are excreted by the kidney, but urinary free M accounts for less than 10% of an administered dose. In patients with renal insufficiency, the metabolites accumulate, though M itself is still excreted.(ABSTRACT TRUNCATED AT 400 WORDS) | {
"pile_set_name": "PubMed Abstracts"
} |
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If you own a 1999 green Honda civic You're gonna have a bad time | {
"pile_set_name": "OpenWebText2"
} |
Introduction
============
Oral cavity cancer is among the leading 10 most commonly diagnosed cancers. Squamous cell carcinoma of the tongue is one of the most common tumors in head and neck cancers ([@b1-mmr-05-04-1116]). During the past several decades, great progress has been made in surgery, radiation therapy and chemotherapy, yet the 5-year survival rate of oral cancer has remained approximately 50% ([@b2-mmr-05-04-1116]). In addition, these patients are at high risk for tumor recurrence and second primary tumors after regular treatment. Furthermore, the molecular mechanisms underlying the pathogenesis of oral cancer remain elusive.
Cancer stem cells (CSCs) were first discovered in 1997 in acute myeloid leukemia, and have recently been found in several tumor types, including lung, breast, brain, liver, pancreas and colon cancers ([@b3-mmr-05-04-1116],[@b4-mmr-05-04-1116]). This unique subpopulation of cancer cells possesses the ability to self-renew, proliferate and differentiate through developmental signaling pathways in aberrant ways ([@b4-mmr-05-04-1116]). CSCs have also been reported to be involved in tumor metastasis and recurrence. Accumulating data indicate that tongue squamous cell carcinoma harbors tumor-initiating cells or CSCs ([@b5-mmr-05-04-1116]--[@b7-mmr-05-04-1116]). Certain CSC-related genes, such as bone morphogenetic protein-4 (BMP-4), octamer-binding transcription factor 4 (Oct4), the homeobox protein Nanog, CD133 and B-cell-specific Moloney murine leukemia virus insertion site 1 (Bmi-1), have been identified and characterized in tongue squamous cell carcinoma ([@b5-mmr-05-04-1116],[@b7-mmr-05-04-1116]--[@b10-mmr-05-04-1116]).
Aldehyde dehydrogenase (ALDH) enzymes play a critical role in the metabolism of many molecules, and in the detoxification of external and internal substances, such as alcohol and toxins. Studies have shown that ALDH is a CSC marker in certain solid tumors, including colon, breast and lung cancers ([@b11-mmr-05-04-1116]--[@b13-mmr-05-04-1116]). In addition, the 19 ALDH family members may function differently, depending on the type of tissue and tumors ([@b14-mmr-05-04-1116]). In this study, we observed that the Tca8113 tongue squamous cell carcinoma cell line harbored 1.3% of ALDH^+^ cells, which displayed CSC characteristics. The ALDH^+^ subpopulation possessed an elevated capacity to proliferate, differentiate and self-renew in comparison to their ALDH^−^ counterparts. Our data suggest that ALDH activity is a CSC marker for tongue squamous cell carcinoma; therefore, targeting ALDH may be a potential therapeutic strategy.
Materials and methods
=====================
Cell line and reagents
----------------------
The Tca8113 human tongue squamous cell carcinoma cell line was provided by the State Key Laboratory of Oral Diseases of Sichuan University, China. Tca8113 cells were cultured in RPMI-1640 (Life Technologies Inc.) and supplemented with 10% fetal calf serum (Gibco) at 37°C in a humidified atmosphere containing 5% CO~2~. Epidermal growth factors and basic fibroblast growth factors were purchased from PeproTech.
Aldefluor assay and flow cytometry
----------------------------------
The Aldefluor kit (Stem Cell Technologies) was utilized to profile and isolate cells with high and low ALDH activity as previously described ([@b15-mmr-05-04-1116]). Cells were incubated in Aldefluor assay buffer containing the ALDH substrate, BODIPY-aminoacetaldehyde (BAAA), at 37°C for 45 min. Cells that were able to catalyze BAAA to its fluorescent product, BODIPY-aminoacetate (BAA), were considered ALDH^+^ cells. The enzymatic activity of ALDH was blocked by a specific inhibitor, DEAB. Sorting gates for fluorescence-activated cell sorting (FACS) were drawn relative to baseline fluorescence, which was determined by DEAB-treated samples. After incubation, cells were resuspended in fresh assay buffer. ALDH^+^ and ALDH^−^ cells were sorted by a BD Aria (BD Biosciences).
Proliferation assay
-------------------
Sorted ALDH^+^, ALDH^−^ cells and their parental cells were seeded in 96-well plates with a density of 1,000 cells/ml. Cell proliferation was detected after culturing for 1, 3, 5 and 7 days using the Cell Counting kit-8 (Dojindo) according to the manufacturer's instructions. Data are shown as the means ± SD.
Differentiation assay
---------------------
Unsorted and sorted single cells were cultured in regular medium. ALDH activity was measured when the cells became 85% confluent.
Tumorsphere formation assay
---------------------------
Sorted ALDH^+^ and ALDH^−^ single cells were cultured in serum-free medium in 6-well plates at a density of 20,000 cells/ml. Tumorspheres were detected and images were captured using a Zeiss inverted microscope.
Suppression subtractive hybridization (SSH)
-------------------------------------------
Total RNA from sorted ALDH^+^ and ALDH^−^ cells was extracted with TRIzol (Invitrogen) according to the manufacturer's instructions. Double-stranded cDNA was generated using PCR-Select cDNA Subtraction kit (Clontech). cDNAs were digested with *Rsa*I (New England Biolabs). The tester cDNA (ALDH^+^ cells) was subdivided into two portions and each was ligated to a different double-stranded adaptor (1 and 2). Enrichment of differentially expressed transcripts was achieved in two successive rounds of PCR amplifications that employed different adapters (1 and 2), and sequential subtractive hybridization of the tester to an excess of driver cDNA (ALDH^−^ cells). Purified cDNA was ligated into the pGEM-T easy vector system (Promega) and DH5α-competent cells were transformed. Selected clones were grown in LB medium with 1 μg/ml ampicillin. For sequencing, the plasmids were extracted and sequenced using BigDye Terminator Cycle Sequencing Ready Reaction kit (Applied Biosystems) with M13 primers on an ABI-PRISM 3100 (Applied Biosystems) automated gene analyzer.
Statistical methods
-------------------
Two-way ANOVA was performed to determine the significant differences in cell growth between sorted and unsorted cells *in vitro*.
Results
=======
Identification of ALDH^+^ subpopulation in Tca8113 tongue squamous cell carcinoma cells
---------------------------------------------------------------------------------------
The enzymatic activity of ALDH has been demonstrated to be a CSC marker in several cancer cell lines and patient tumor samples ([@b4-mmr-05-04-1116]). To examine whether human tongue squamous cell carcinoma contains a subpopulation with high ALDH activity, Aldefluor assays were performed to identify ALDH^+^ cells in the Tca8113 cell line. In the presence of the ALDH-specific inhibitor DEAB, ALDH^+^ cells were barely observed. Notably, \~1.3% of Tca8113 cells displayed very bright fluorescence in the absence of DEAB ([Fig. 1](#f1-mmr-05-04-1116){ref-type="fig"}). This result indicates that the Tca8113 human tongue squamous cell carcinoma cell line contains a subset of cells with high ALDH enzymatic activity. Our data are consistent with a previous report that the Tca8113 cell line harbors \~1% of CD133^+^ cells, which is another well-studied CSC marker ([@b7-mmr-05-04-1116]).
Enhanced proliferation of ALDH^+^ tongue squamous cell carcinoma cells
----------------------------------------------------------------------
CSCs possess an increased capacity for proliferation, differentiation and tumorigenicity. We hypothesized that ALDH^+^ cells in the Tca8113 cell line are CSCs. To test this hypothesis, we compared the proliferation rate of sorted ALDH^+^, ALDH^−^ cells and parental Tca8113 cells using Cell Counting Kit-8. After a 5-day culture, ALDH^+^ cells proliferated significantly faster than their ALDH^−^ counterparts, whereas the unsorted cells exhibited a similar proliferation rate as that of the ALDH^−^ cells ([Fig. 2](#f2-mmr-05-04-1116){ref-type="fig"}). This result indicates that ALDH^+^ cells in the Tca8113 cell line have enhanced capacity to proliferate relative to ALDH^−^ cells *in vitro*.
ALDH^+^ tongue squamous cell carcinoma cells form tumorspheres
--------------------------------------------------------------
Similar to normal stem cells, CSCs are able to self-renew through asymmetric cell divisions. Tumorsphere formation assays are widely used to evaluate self-renewal and differentiation at the single-cell level *in vitro*. Separated ALDH^+^ and ALDH^−^ single cells were maintained in serum-free medium, in which non-CSCs cannot survive. On day 5, ALDH^+^ cells started to aggregate with each other. Clear tumorspheres were observed on day 10, while most single cells were already dead ([Fig. 3B and C](#f3-mmr-05-04-1116){ref-type="fig"}). By contrast, tumorspheres were barely found in the plates seeded with ALDH^−^ cells ([Fig. 3E and F](#f3-mmr-05-04-1116){ref-type="fig"}).
Differentiation of ALDH^+^ tongue squamous cell carcinoma cells
---------------------------------------------------------------
One critical characteristic of CSCs is the ability to differentiate and form all types of tumor cells. To evaluate the differentiation capacity of ALDH^+^ cells, the percentage of ALDH^+^ cells was continuously measured during the culture of isolated ALDH^+^ cells in regular medium. We observed that the percentage of ALDH^+^ cells gradually reduced to the level of parental Tca8113 cells, whereas the amount of ALDH^−^ counterparts increased ([Fig. 4](#f4-mmr-05-04-1116){ref-type="fig"}). Taken together, these data demonstrate that ALDH^+^ cells self-renew, differentiate and generate ALDH^−^ subpopulations *in vitro*.
ALDH^+^ tongue squamous cell carcinoma cells express CSC-related genes
----------------------------------------------------------------------
Previous studies have reported that certain signaling pathways, such as Notch, Wnt and Hedgehog pathways, play critical roles in regulating CSCs for self-renewal, differentiation and proliferation ([@b4-mmr-05-04-1116],[@b12-mmr-05-04-1116]). Therefore, we compared gene expression profiles between ALDH^+^ and ALDH^−^ fractions using the suppression subtraction hybridization assay. Based on sequencing and bioinformatics analyses, 62 genes were found to be differentially expressed in the two fractions isolated from Tca8113 cells, among which 9 genes are involved in CSC biology ([Table I](#tI-mmr-05-04-1116){ref-type="table"}). For example, the Notch2 signaling pathway is known to be essential for the growth of tumor neurospheres and xenografts ([@b16-mmr-05-04-1116]). In summary, there were 28 upregulated and 34 downregulated genes in the ALDH^+^ subpopulation relative to the ALDH^−^ fraction. Our results provide insight into understanding the molecular mechanisms of CSCs in tongue squamous cell carcinoma.
Discussion
==========
Cancer is a complex disease that results from dozens of genetic and epigenetic mutations. Although it is known that cancer cells are heterogeneous, the mechanism by which cancer cells become heterogeneous during the mulitstep process of tumorigenesis is largely unknown. The potential role of CSCs in this process has been the source of great interest in cancer biology and translational cancer research since the first identification of CSCs in leukemia by John Dick in 1997 ([@b3-mmr-05-04-1116]), and in solid tumors by Michael Clarke in 2003 ([@b17-mmr-05-04-1116]). The CSC model states that only a small subpopulation of cancer cells functions as cancer-initiating cells with unlimited proliferation potential, whereas the majority of cancer cells are differentiated cells with limited proliferation capacity. Thereby, the CSC hypothesis provides a rational explanation for the recurrence of tumors after chemotherapy or radiation therapy, and drug resistance. Targeting CSCs may be the key for complete inhibition or killing of cancer cells. Thus, identification and characterization of CSCs in different types of cancers can help our understanding of cancer biology and anticancer drug development.
Identification of CSC markers is the first step in CSC research. Many molecules have been used to identify a subpopulation of cancer cell lines or tumor samples which possess CSC properties. For example, in breast cancer both CD44 high/CD24 low and ALDH are CSC markers. CD133 is also a promising CSC marker for brain tumors and colon cancers ([@b4-mmr-05-04-1116]). The ALDH superfamily of NAD(P)^+^-dependent multifunctional enzymes catalyze the oxidation of various aldehydes to their corresponding carboxylic acids. ALDH isozymes are widely distributed in tissues and organs. ALDH was first demonstrated to be highly enriched in hematopoietic stem cells. Stem cells isolated using Aldefluor assays have been utilized in regenerative medicine, such as bone marrow transplantation ([@b14-mmr-05-04-1116]). Recently, ALDH activity has been reported to be a CSC marker in certain solid tumors, including breast, lung, liver, pancreas, prostate and colon cancers. In this study, Aldefluor assays were applied to enrich a subset of cells with CSC characteristics from the Tca8113 tongue squamous cell carcinoma cell line. To determine the functional differences between sorted ALDH^+^ and ALDH^−^ fractions, we compared their proliferation and found that ALDH^+^ Tca8113 cells proliferated faster than ALDH^−^ cells *in vitro*.
Self-renewal and differentiation are essential properties of CSCs. Our *in vitro* differentiation assays showed that ALDH^+^ cells were able to differentiate into ALDH^−^ cells, and to maintain undifferentiated ALDH^+^ parts. By contrast, ALDH^−^ cells did not generate ALDH^+^ cells under the same conditions. Non-adherent sphere formation assays have been accepted to evaluate putative CSC activity. This assay predicts that a CSC can be serially passaged for many cycles and generates a tumorsphere resembling the primary sphere. Our sphere formation and differentiation results demonstrated that ALDH^+^ cells could self-renew and differentiate to ALDH^−^ cells. We also observed that a small portion of sorted ALDH^−^ cells survived in serum-free medium and formed spheres, which may be caused by the contamination during FACS sorting procedure. Together, these data confirmed that ALDH activity is valuable in identifying tongue squamous cell carcinoma stem cells. Kang *et al* ([@b7-mmr-05-04-1116]) recently reported that CD133 may be a potential tumor-initiating marker for the Tca183 cell line. They carried out similar experiments and showed that CD133^+^ cells possessed a higher ability of proliferation, differentiation and sphere formation than CD133^−^ cells. It will be interesting to test whether these two markers identify the same subpopulation of Tca183 cells.
In this study, we not only showed that ALDH activity can serve as a marker to identify CSCs in tongue squamous cell carcinoma, but we also compared the gene expression patterns between isolated fractions using the suppression subtractive hybridization assay. It was interesting to find that CD44 was one of the 28 overexpressed genes in the ALDH^+^ fraction, indicating that ALDH^+^ cells may overlap with the CD44^+^ subpopulation. Notch2 is another upregulated gene in ALDH^+^ cells. It has been demonstrated that knockdown of Notch2 sensitizes glioma stem cells to radiation and impairs xenograft tumor formation ([@b16-mmr-05-04-1116]). Further analysis of these differentially expressed genes in CSCs is required to identify new therapeutic targets of tongue squamous cell carcinoma.
This study was supported by grants from the ChongQing Science and Technology Commission Project (no. 2008-2-232). The authors thank Medjaden Bioscience Limited for assisting in the preparation of this manuscript.
{#f1-mmr-05-04-1116}
{#f2-mmr-05-04-1116}
{#f3-mmr-05-04-1116}
{#f4-mmr-05-04-1116}
######
Differentially expressed cancer stem cell-related genes.
Gene name Accession no. Identified E-value Gene ID Gene symbol Chromosome location
----------------------------------------------------------------------------------------------- ---------------- --------------- ----------- ------------- ------------- ---------------------
Homo sapiens inositol 1,4,5-triphosphate receptor, type 1 (ITPR1), RefSeqGene on chromosome 3 NG_016144.1 253/254 (99%) 1.00E-127 269954693 ITPR1 3p26-p25
Homo sapiens notch 2 (NOTCH2), RefSeqGene on chromosome 1 NG_008163.1 512/514 (99%) 0 4853 NOTCH2 1p13-p11
Homo sapiens nuclear receptor corepressor 1 (NCOR1), transcript variant 3, mRNA NM_001190440.1 213/214 (99%) 1.00E-106 9611 NCOR1 17p11.2
Homo sapiens retinoblastoma 1 (RB1), mRNA NM_000321.2 269/270 (99%) 1.00E-137 5925 RB1 13q14.2
Homo sapiens CREB binding protein (CREBBP), RefSeqGene on chromosome NG_009873.1 197/198 (99%) 1.00E-96 1387 CREBBP 16p13.3
Homo sapiens SMAD family member 1 (SMAD1), transcript variant 2, mRNA NM_001003688.1 262/263 (99%) 1.00E-133 4086 SMAD1 7p15
Homo sapiens Niemann-Pick disease, type C1 (NPC1), RefSeqGene on chromosome 18 NG_012795.1 174/175 (99%) 3.00E-83 4864 NPC1 18q11-q12
Homo sapiens epidermal growth factor receptor (EGFR), RefSeqGene on chromosome 7 NG_007726.1 207/208 (99%) 3.00E-102 1956 EGFR 7p12
Homo sapiens septin 9 (SEPT9), transcript variant 4, mRNA NM_001113495.1 379/380 (99%) 0 10801 SEPT9 SEPT9 17q25
| {
"pile_set_name": "PubMed Central"
} |
IN THE COURT OF APPEALS OF THE STATE OF IDAHO
Docket No. 41503
STATE OF IDAHO, ) 2014 Unpublished Opinion No. 675
)
Plaintiff-Respondent, ) Filed: August 18, 2014
)
v. ) Stephen W. Kenyon, Clerk
)
JAIME TAYLOR REYES, ) THIS IS AN UNPUBLISHED
) OPINION AND SHALL NOT
Defendant-Appellant. ) BE CITED AS AUTHORITY
)
Appeal from the District Court of the Fourth Judicial District, State of Idaho, Ada
County. Hon. Deborah A. Bail, District Judge.
Judgment of conviction and concurrent unified sentences of seven years, with a
minimum period of confinement of one year, for grand theft and burglary,
affirmed; order denying I.C.R. 35 motion for reduction of sentence, affirmed.
Sara B. Thomas, State Appellate Public Defender; Shawn F. Wilkerson, Deputy
Appellate Public Defender, Boise, for appellant.
Hon. Lawrence G. Wasden, Attorney General; Kenneth K. Jorgensen, Deputy
Attorney General, Boise, for respondent.
________________________________________________
Before LANSING, Judge; GRATTON, Judge;
and MELANSON, Judge
PER CURIAM
Jaime Taylor Reyes pled guilty to grand theft, Idaho Code §§ 18-2403(1), 18-2407(1)(b),
18-2409 and burglary, I.C. § 18-1401. The district court sentenced Reyes to concurrent unified
terms of seven years, with a minimum period of confinement of one year. Reyes filed an Idaho
Criminal Rule 35 motion, which the district court denied. Reyes appeals asserting that the
district court abused its discretion by imposing excessive sentences and by denying his Rule 35
motion.
Sentencing is a matter for the trial court’s discretion. Both our standard of review and the
factors to be considered in evaluating the reasonableness of the sentence are well established.
1
See State v. Hernandez, 121 Idaho 114, 117-18, 822 P.2d 1011, 1014-15 (Ct. App. 1991); State
v. Lopez, 106 Idaho 447, 449-51, 680 P.2d 869, 871-73 (Ct. App. 1984); State v. Toohill, 103
Idaho 565, 568, 650 P.2d 707, 710 (Ct. App. 1982). When reviewing the length of a sentence,
we consider the defendant’s entire sentence. State v. Oliver, 144 Idaho 722, 726, 170 P.3d 387,
391 (2007). Applying these standards, and having reviewed the record in this case, we cannot
say that the district court abused its discretion.
Next, we review whether the district court erred in denying Reyes’ Rule 35 motion. A
motion for reduction of sentence under I.C.R. 35 is essentially a plea for leniency, addressed to
the sound discretion of the court. State v. Knighton, 143 Idaho 318, 319, 144 P.3d 23, 24 (2006);
State v. Allbee, 115 Idaho 845, 846, 771 P.2d 66, 67 (Ct. App. 1989). In presenting a Rule 35
motion, the defendant must show that the sentence is excessive in light of new or additional
information subsequently provided to the district court in support of the motion. State v.
Huffman, 144 Idaho 201, 203, 159 P.3d 838, 840 (2007). In conducting our review of the grant
or denial of a Rule 35 motion, we consider the entire record and apply the same criteria used for
determining the reasonableness of the original sentence. State v. Forde, 113 Idaho 21, 22, 740
P.2d 63, 64 (Ct. App. 1987); Lopez, 106 Idaho at 449-51, 680 P.2d at 871-73. Upon review of
the record, we conclude no abuse of discretion has been shown.
Therefore, Reyes’ judgment of conviction and sentence, and the district court’s order
denying Reyes’ Rule 35 motion, are affirmed.
2
| {
"pile_set_name": "FreeLaw"
} |
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HEADACHE FROM COMPUTER USE? MORE REDDIT SHOULD HELP | {
"pile_set_name": "OpenWebText2"
} |
Q:
Creating new record fails to save relationship_id
An organization has many members, and a relationship has been created between both models. A member of an organization is allowed to create additional members for that specific organization. This works fine. A system admin can go to the profile of any organization and then click 'create new member' to create a new member that organization. However, currently for the admin the organization_id does not save with the newly created member, thereby causing errors. Does anyone have an idea why the organization_id does not save?
Members controller:
def new
if current_user.admin?
if params[:organization_id].nil?
flash[:danger] = "Please select an organization first"
redirect_to organizations_path
else
@organization = Organization.find(params[:organization_id])
@member = @organization.members.build
end
else
@member = current_organization.members.build
end
end
def create
if current_user.admin?
@member = Member.new(new_params)
else
@member = current_organization.members.build(new_params)
end
if @member.save
@member.send_activation_email
flash[:success] = "A confirmation email will be sent to the new user."
redirect_to member_url(@member)
else
render 'new'
end
end
private
def new_params
params.require(:member).permit(:email,
:username,
:password,
:password_confirmation)
end
Members new view:
<%= form_for(@member) do |f| %>
<%= render 'shared/error_messages', object: f.object %>
<% if current_user.admin? %>
<%= f.text_field :organization_id, placeholder: 'Organization id', autocomplete: 'off', class: 'form-control', disabled: "disabled" %>
<% end %>
<%= f.email_field :email, placeholder: 'Email', autocomplete: 'off', class: 'form-control' %>
<%= f.text_field :username, maxlength: 15, placeholder: 'Username', autocomplete: 'off', class: 'form-control' %>
<%= f.password_field :password, placeholder: 'Password', autocomplete: 'off', class: 'form-control' %>
<%= f.password_field :password_confirmation, placeholder: 'Confirm password', autocomplete: 'off', class: 'form-control' %>
<%= f.submit "Sign up", class: "formbutton btn btn-default" %>
<% end %>
The organization profile view contains the following link to the member new view:
<%= link_to image_tag("add.png", title: "add member", height: '15'), new_member_path(organization_id: @organization.id) %>
Part of the members model:
belongs_to :organization
default_scope -> { includes(:organization).order('organizations.org_name , username') }
attr_accessor :remember_token, :activation_token, :reset_token
before_save :downcase_email, :downcase_username
before_create :create_activation_digest
#validates :organization_id, presence: true # Commented this out because of a joined form that doesn't work with this validation.
VALID_EMAIL_REGEX = /\A[\w+\-.]+@[a-z\d\-]+(\.[a-z\d\-]+)*\.[a-z]+\z/i
validates :email, presence: true,
length: { maximum: 255 },
format: { with: VALID_EMAIL_REGEX },
uniqueness: { case_sensitive: false }
VALID_USERNAME_REGEX = /\A[a-zA-Z0-9_-]+\z/i
validates :username, presence: true,
length: { in: 6..15 },
format: { with: VALID_USERNAME_REGEX },
uniqueness: { case_sensitive: false }
A:
The problem turned out to be disabled: "disabled" in the form. A disabled field does not get send on submit. Changing it to readonly: "readonly" solved it. See: What's the difference between disabled="disabled" and readonly="readonly" for HTML form input fields?
| {
"pile_set_name": "StackExchange"
} |
from dataclasses import dataclass
import enum
from typing import Optional
@dataclass
class Keys:
public_view_key: bytes
secret_view_key: bytes
public_spend_key: bytes
secret_spend_key: Optional[bytes]
addr: str
@enum.unique
class SigType(enum.IntEnum):
REAL = 1
FAKE = 2
@enum.unique
class Type(enum.IntEnum):
SCALAR = 1
DERIVATION = 2
AMOUNT_KEY = 3
ALPHA = 4
@enum.unique
class InsType(enum.IntEnum):
INS_NONE = 0x00
INS_RESET = 0x02
INS_LOCK_DISPLAY = 0x04
INS_GET_KEY = 0x20
INS_DISPLAY_ADDRESS = 0x21
INS_PUT_KEY = 0x22
INS_GET_CHACHA8_PREKEY = 0x24
INS_VERIFY_KEY = 0x26
INS_MANAGE_SEEDWORDS = 0x28
INS_SECRET_KEY_TO_PUBLIC_KEY = 0x30
INS_GEN_KEY_DERIVATION = 0x32
INS_DERIVATION_TO_SCALAR = 0x34
INS_DERIVE_PUBLIC_KEY = 0x36
INS_DERIVE_SECRET_KEY = 0x38
INS_GEN_KEY_IMAGE = 0x3A
INS_SECRET_KEY_ADD = 0x3C
INS_GENERATE_KEYPAIR = 0x40
INS_SECRET_SCAL_MUL_KEY = 0x42
INS_SECRET_SCAL_MUL_BASE = 0x44
INS_DERIVE_SUBADDRESS_PUBLIC_KEY = 0x46
INS_GET_SUBADDRESS = 0x48
INS_GET_SUBADDRESS_SPEND_PUBLIC_KEY = 0x4A
INS_GET_SUBADDRESS_SECRET_KEY = 0x4C
INS_OPEN_TX = 0x70
INS_SET_SIGNATURE_MODE = 0x72
INS_GET_ADDITIONAL_KEY = 0x74
INS_STEALTH = 0x76
INS_GEN_COMMITMENT_MASK = 0x77
INS_BLIND = 0x78
INS_UNBLIND = 0x7A
INS_GEN_TXOUT_KEYS = 0x7B
INS_PREFIX_HASH = 0x7D
INS_VALIDATE = 0x7C
INS_MLSAG = 0x7E
INS_CLOSE_TX = 0x80
INS_GET_TX_PROOF = 0xA0
INS_GEN_SIGNATURE = 0xA2
INS_GEN_RING_SIGNATURE = 0xA4
INS_GET_RESPONSE = 0xc0
def __repr__(self):
return f"{self.name}[{hex(self.value)}]"
| {
"pile_set_name": "Github"
} |
Chryseobacterium flavum sp. nov., isolated from polluted soil.
A Gram-negative, non-motile, rod-shaped bacterial strain, designated CW-E 2(T), was isolated from a polluted soil sample collected from Jiangsu Province, China. A taxonomic study of the isolate, including phylogenetic analysis based on 16S rRNA gene sequences and phenotypic characteristics, was carried out. The predominant menaquinone was MK-6 and the major fatty acids were i-C(15 : 0), i-C(17 : 0) 3-OH, i-C(17 : 1) omega 9c and summed feature 4. The G+C content of the DNA was 37.2 mol%. Based on phenotypic and genotypic characteristics, strain CW-E 2(T) represents a novel species of the genus Chryseobacterium for which the name Chryseobacterium flavum sp. nov. is proposed. The type strain is CW-E 2(T) (=KCTC 12877(T)=CCTCC AB 206147(T)). | {
"pile_set_name": "PubMed Abstracts"
} |
Q:
.Net Core 2.0 - Azure Active Directory - NGinX reverse Proxy - HTTPS
I have a .NET Core 2.0 website, running on Linux, listening on port 5000, behind an NGinX reverse proxy, which is listening on port 80 and 442. NGinX is configured to redirect HTTP traffic to HTTPS, and handle all communication over HTTPS. The NGinx Reverse Proxy and Asp.Net Core app are within their own docker containers, on a shared network.
This setup is currently working as described.
However, I would now like to Authenticate my users against our Azure Active Directory. I have run into a problem and don't know where to go from here.
First, let me show you how I have most of this configured, and then I'll explain my error.
NGinx (nginx.conf)
worker_processes 2;
events { worker_connections 1024; }
http {
sendfile on;
upstream docker-dotnet {
server mycomp_prod:5000;
}
server {
listen 80;
server_name sales.mycompany.com;
return 301 https://$host$request_uri;
}
server {
listen 443 ssl;
server_name sales.mycompany.com;
ssl_certificate /etc/nginx/ssl/combined.crt;
ssl_certificate_key /etc/nginx/ssl/salesmycompany.key;
location / {
proxy_pass http://docker-dotnet;
proxy_redirect off;
proxy_set_header Host $host;
proxy_set_header X-Real-IP $remote_addr;
proxy_set_header X-Forwarded-For $proxy_add_x_forwarded_for;
proxy_set_header X-Forwarded-Host $server_name;
}
}
}
Dotnet:Startup.cs ConfigureServices()
services.AddAuthentication(sharedOptions =>
{
sharedOptions.DefaultScheme = CookieAuthenticationDefaults.AuthenticationScheme;
sharedOptions.DefaultChallengeScheme = OpenIdConnectDefaults.AuthenticationScheme;
})
.AddAzureAd(options => Configuration.Bind("AzureAd", options))
.AddCookie();
Dotnet:Startup.cs Configure()
app.UseForwardedHeaders(new ForwardedHeadersOptions
{
ForwardedHeaders = ForwardedHeaders.XForwardedFor | ForwardedHeaders.XForwardedProto
});
app.UseAuthentication();
Dotnet: appsettings.json
{
"AzureAd": {
"Instance": "https://login.microsoftonline.com/",
"Domain": "mycompany.com",
"TenantId": "my-tenant-id",
"ClientId": "my-client-id",
"CallbackPath": "/signin-oidc"
},
In My Azure Active Directory Tentant
I have configured 2 "Reply URLs"
https://sales.mycompany.com/signin-oidc
https://sales.mycompany.com
Now for the error / My Question
When I hit the site, I sign in. Afterward signing in, and choosing whether or not to "Stay signed in", I'm taken to a page with an error.
You can see in the error, that the Reply Address that is attempting to be redirected to, is HTTP, not HTTPS. I think this is coming from the line in appsettings.json that says:
"CallbackPath": "/signin-oidc"
And since my .NET Core Site (via Kestrel on port 5000) is not on HTTPS, it's trying to load http://example.com/signin-oidc, instead of HTTPS. Remember that my .NET Core Site is behind an NGinX reverse Proxy, which is configured to handle traffic on 443.
Thank you,
A:
I saw this and was able to get it working: https://github.com/aspnet/Security/issues/1702
var fordwardedHeaderOptions = new ForwardedHeadersOptions
{
ForwardedHeaders = ForwardedHeaders.XForwardedFor | ForwardedHeaders.XForwardedProto
};
fordwardedHeaderOptions.KnownNetworks.Clear();
fordwardedHeaderOptions.KnownProxies.Clear();
app.UseForwardedHeaders(fordwardedHeaderOptions);
| {
"pile_set_name": "StackExchange"
} |
Q:
Mixed content error in loading a view from an HttpResponse() in ajax
Before all, I precise that there is no trailing http in the code and my nginx server has no apparent configuration error. I find this issue very strange:
I got a main view with different tabs, each one being served by CBV. For example I call the content of the company tab with this HTML code:
<li class="">
<a href="{% url "staffpanel:companies:company_detail" company.pk %}" id='companyTab' data-toggle="tab">{% trans "Company" %}</a>
</li>
and it naturally calls this view which is loaded in the tab content <div id="tabContent"></div> with this code:
class CompanyDetail(StaffPanelMixin, DetailView):
model = Company
template_name = "staffpanel/companies/_company.html"
and the following js:
$('a[data-toggle="tab"]').on('show.bs.tab', function (event){
var tab = $(event.target).attr("id");
var action = $(event.target).attr("href");
$.get(action, null, function( data ) {
$("#tabContent").html( data );
});
return false;
});
On each tab I can open a form into a modal block. This form calls an update CBV that let users edit the object displayed in the tab. The update view validation is as following:
class CompanyUpdate(StaffPanelMixin, UpdateView):
template_name = "staffpanel/companies/_company_form.html"
model = Company
form_class = CompanyUpdateForm
def get_success_url(self):
return reverse("staffpanel:companies:company_detail",
args=(self.object.pk,))
For now, every thing is fine. If the form is not valid, data are correctly returned in the form contained into the modal block, displaying as expected the form with message errors. Thanks to this code:
$(document).on('submit', '#companyForm', function () {
var form = $('#companyForm');
var actionUrl = form.prop('action');
var modal = $('#genericModal');
ajaxform(new FormData(form[0]), modal, actionUrl);
return false;
});
function ajaxform(formData, modal, actionUrl) {
$.ajax({
url: actionUrl,
type: 'POST',
data: formData,
processData: false,
contentType: false,
success: function (data) {
if (($(".has-error", data).length != 0) || ($(".alert", data).length !=0 )) {
$(".modal-content").html( data )
}
else {
modal.modal('hide');
$("#tabContent").html( data );
}
}
});
}
The issue comes with the success message. While it works fine in case of invalid form it failed to load the success url and raises a mixed content error and look for the view with the wrong protocol. I'm using SSL and it calls the detail view with HTTP instead of HTTPS.
I must precise that the update view does its job correctly as the data are updated. It's really a problem of returning the detail CBV.
Is it a bug? Am I doing wrong with js (surely)? Why can js load detail CBV in a case (loading tabs) and not after an update (as this is strictly the same view that is called)? Why does the url protocol change by the way?
NB: I tried to set SECURE_PROXY_SSL_HEADER and SECURE_SSL_REDIRECT in django settings with no success. (I fell in a loop of infinite redirection).
A:
It appears that I wasn't able to load directly the page without having this painful mixed content issue (change of HTTPS in HTTP due to HttpResponse()).
So my solution was to return a JsonResponse containing the success_url and then I was able to load from js the tab.
I overwritten the form_valid in my update view as following:
def form_valid(self, form);
super().form_valid(form)
return JsonResponse({'succes_url': self.get_success_url()})
and in my ajax call, I had to replace this line:
$("#tabContent").html( data );
with this one:
$("#tabContent").load( data['success_url'] );
and that's it.
Hope this helps !
| {
"pile_set_name": "StackExchange"
} |
Eyoh
Eyoh is a surname. Notable people with the surname include:
Effiong Eyoh (born 1996), Nigerian footballer
Ndumbe Eyoh (1949–2006), Cameroonian theatre director, critic and playwright | {
"pile_set_name": "Wikipedia (en)"
} |
Shannon Sullivan, the woman who led a grassroots effort to recall Spokane Mayor Jim West, is launching a new campaign to recall Spokane County Prosecutor Steve Tucker.
During an interview Thursday morning, Sullivan said she has a weight on her heart to keep public officials accountable, that the recall of Tucker is neither a mud-slinging campaign against the prosecutor nor is it an attack on Tucker personally, but is rather about the facts of his tenure as prosecutor and his performance as the county's top legal officer.
Sullivan claims, in a four-page statement of charges, that Tucker has committed acts of malfeasance, misfeasance and violations of his oath of office as prosecutor. She asserts that Tucker had a duty to investigate and prosecute a number of crimes committed in Spokane County but on numerous occasions failed to do so.
She alleges that Ron Wright, a former police officer, claimed to have learned through an "undisclosed source" that at a political rally Tucker "said he would not prosecute police officers." That statement was supported by another claim by Wright that, during a conversation with Spokane city councilman Bob Apple, Apple remembered that Tucker had made similar comments at a labor rally several years earlier.
At that labor rally, Tucker, according to Apple, stated "he would not prosecute public employees."
In 2006, Tucker said he would not file any charges against Daniel Ross, a former Spokane firefighter who admitted having sex and taking explicit pictures of a 16-year-old girl who he had met online while inside a Spokane fire station. Tucker never filed charges against Ross and subsequently a claim filed by the teen against the city was dismissed. A case in federal court was tossed out because Tucker never filed any charges against Ross.
"This case was a blatant miscarriage of justice, which was manipulated by the prosecutor in collusion with other high-level city officials to protect the city and the city employed perpetrator," Sullivan alleges.
A few weeks after the Ross incident on March 20, Otto Zehm died in the wake of a confrontation with Spokane police officers at a North Division Zip Trip convenience store. At the time, both city and police officials denied any wrongdoing on the part of Spokane police officers, claiming that Zehm had lunged at officers which precipitated the aggressiveness of their response toward him. Tucker never prosecuted anyone in the case.
In the Zehm case, Sullivan alleges that Zehm's death was a "well-planned and blatant cover-up by public officials of a police-involved homicide." She alleges that Tucker was well aware of what she calls the "criminal circumstances" of the cover-up by Assistant City Attorney Rocky Treppidi and City Attorney Howard Delaney, along with members of the police department's command staff and yet Tucker took no action to prosecute Thompson.
Three years after Zehm's death, the US Attorney's Office filed charges against Spokane Police Officer Karl Thompson on grounds of use of excessive force and violation of civil rights in the Zehm case. Thompson went to trial in Yakima earlier this year, was found guilty on both counts, and is scheduled to be sentenced in January 2012.
Sullivan said Thursday morning that she will be handing her charges for recall over to Spokane County Auditor Vicky Dalton Friday. Dalton says the charges will be submitted to the Attorney General so he can write the synopsis within 15 days, then the Supreme Court will decide whether or not it will be put on the ballot within 15 days as well.
Given there is no appeal from Tucker, Sullivan has 180 days to gather more than 42,000 signatures. The recall election would be between 45-60 days after that.
Tucker is reportedly out of the area, won't be back until next Tuesday and was unavailable for comment on Sullivan's recall initiative.
Sullivan last led a single-woman effort to recall Spokane Mayor Jim West in 2005. Sullivan waged her battle to get West recalled in the wake of reports by The Spokesman-Review that, while mayor he alleged he used his position to further the careers of young men he met online.
A former state lawmaker, West voted against a number of gay-friendly bills while serving in Olympia during his nearly three decades in public office.
From challenges in superior court to an appearance before the state's high court, Sullivan continued to fight for the recall. Her efforts resulted in the December 2005 recall vote where Spokane voters overwhelming supported a measure to recall Mayor Jim West.
65-percent of voters who participated in the recall supported the recall, leading to his ouster. He was the first mayor in Spokane history to be recalled before his term expired.
West died in July 2006 from complications from cancer surgery seven months after he was forced out of office. | {
"pile_set_name": "Pile-CC"
} |
Introduction {#s1}
============
Exosomes are 40--100 nm vesicles that are released by many eukaryotic cells. These vesicles are formed through invagination of the membrane into the multivesicular endosome (MVE) and can be released from the cell upon fusion of the MVE with the plasma membrane [@pntd.0002185-Thery1]. Although exosomes were once believed to be just packed with inert debris, current research suggests that along with other released vesicles, exosomes actually have an important part to play in different forms of long distance cell-cell communications [@pntd.0002185-Nieuwland1].
Studies on exosomes derived from macrophages or dendritic cells (DCs) infected with bacteria shows that these exosomes are generally pro-inflammatory to naive macrophages, induce maturation of DCs and activate both CD4+ and CD8+ T cells [@pntd.0002185-ONeill1], [@pntd.0002185-Schorey1]. In addition, bacterial antigens such as glycopeptidolipids (GPLs) and immunogenic proteins have been found to be present on these exosomes and to be responsible for the pro-inflammatory nature of these exosomes [@pntd.0002185-Bhatnagar1], [@pntd.0002185-Giri1]. Therefore, exosomes introduce a novel class of communication among immune cells for antigen presentation and immune activation.
In contrast to bacterial pathogens, the biology of exosomes released from macrophages infected with immunomodulatory parasites such as *Leishmania* has not been previously studied. *Leishmania* parasites toggle between the extracellular motile and flagellated promastigotes, dwelling in the Phlebotomine sandfly and the roundshape nonmotile amastigotes residing in the phagolysosome of the mammalian macrophage [@pntd.0002185-Reithinger1]. These parasites have the ability to successfully parasitize macrophages thanks to their mechanisms for efficient inhibition of the signaling and microbicidal functions of their host. The hallmarks of these modulations are activation of protein tyrosine phosphatases (PTPs), inhibition of proinflammatory transcription factors NF-κB, AP-1 and STAT-1 as well as other critical signaling molecules such as JAK-2, IRAK-1 and MAP Kinases. Together, modulation of these molecules and pathways results in deactivation of macrophage microbicidal functions such as production of nitric oxide (NO) or proinflammatory cytokines such as TNF and IL-12. In addition to inhibition of macrophage functions, *Leishmania* infection renders the macrophage unresponsive to external stimulations such as LPS or IFN-γ (Reviewed in [@pntd.0002185-Shio1]). Moreover, we recently showed that GP63, the major surface protease of *Leishmania*, is able to gain access to the macrophage cytoplasm and directly cleave many intracellular targets, leading to inactivation of the macrophage [@pntd.0002185-Gomez1]--[@pntd.0002185-Jaramillo1]. Considering the modulatory nature of these parasites, studying the exosomes released from *Leishmania*-infected macrophages is of great interest. Importantly, it can shed light on how protein sorting to exosomes is altered following *Leishmania* infection and how it could affect targeting and functions of exosomes on other immune cells.
Different classes of proteins are now recurrently observed to be sorted into exosomes, such as proteins involved in adhesion (tetraspanins and integrins), vesicular trafficking (Alix, Tsg101), molecular chaperones (HSP 70, HSP 90), metabolic enzymes, and also cytoskeletal proteins [@pntd.0002185-Thery1]. Nevertheless, the content of exosomes is highly dependent on the cell type, its developmental status, as well as external stimulations [@pntd.0002185-Palmisano1], [@pntd.0002185-Carayon1]. The combined function of those proteins on the recipient cell is still a subject of study. Still, exosomes have also been shown to carry molecules with known function in cell-cell interactions, such as MHC I or II, co-stimulatory molecules (e.g. CD80), and cytokines (e.g. TNF-α, TGF-β). The specific combination of surface molecules on exosomes could allow for specific targeting of the cytokines to distinct recipient cells. Additionally, infection with intracellular pathogens such as viruses or *Mycobacterium* species has shown to alter exosome content [@pntd.0002185-ONeill1], [@pntd.0002185-Schorey1], [@pntd.0002185-Meckes1]. However, besides looking at specific markers or cytokines, alterations in the total proteome of macrophage exosomes after stimulation or infection have not been studied. Studying the proteome of exosomes is critical for understanding their biology, target selection and possible effects on recipient cells. Here we report the first comparative proteomic analysis of macrophage exosomes after LPS stimulation or infection with *Leishmania mexicana*. We show that the contents of macrophage exosomes go through dynamic changes following LPS stimulation or *Leishmania* infection. Furthermore, we show how these exosomes induce signaling and modulate expression of immune-related genes in naive macrophages.
Materials and Methods {#s2}
=====================
Cell and parasite culture {#s2a}
-------------------------
J774A.1 murine macrophages were cultured in RPMI1640 medium (Wisent) supplemented with 10% heat-inactivated fetal bovine serum (FBS), streptomycin (100 µg/ml), penicillin (100 U/ml), and 2 mM L-glutamine at 37°C and 5% CO~2~. *L. mexicana* parasites were cultured in Schneider\'s Drosophila Medium (SDM) supplemented with 10% FBS at 25°C.
Exosome collection and purification {#s2b}
-----------------------------------
Macrophages were stimulated with 100 ng/ml of LPS (Sigma), infected with stationary *L. mexicana* parasites at 1∶20 ratio or left untreated for 6 h. Macrophages were then washed with PBS and cultured for 24 h in RPMI medium supplemented with exosome-free FBS. Exosome-free FBS was acquired by overnight ultracentrifugation of FBS at 100,000 g for exosome collection. Culture supernatant was then collected and centrifugated at 4,000 g for 20 min to clear floating cells and debris. Supernatant was then passed through a 0.45 µm filter (Pall) to clear debris. Exosomes were pelleted by 1 h centrifugation at 100,000 g. Pelleted exosomes were resuspended, passed through a 0.22 µm filter (Pall) and washed in 20 mM HEPES pH 7.5. Washed exosomes were then resuspended in sterile HEPES 20 mM and kept at −80°C until use. In order to acquire ultrapure exosomes for mass spectrometry, following pelleting, resuspended exosomes were rapidly mixed with a cocktail of protease inhibitors (Roche) and washed in HEPES. Exosomes were then overlayed on a 0--2M gradient of sucrose and centrifugated for 12--16 h at 100,000 g. Fractions corresponding to 1.13--1.19M of sucrose were collected, passed through a 0.22 µm filter and pelleted at 100,000 g for 1 h. Exosomes were then resuspended in HEPES buffer and kept at −80°C until use. Purified exosomes were quantified using MicroBCA protein dosing assay (Thermo).
Transmission electron microscopy {#s2c}
--------------------------------
Exosomes were put on Fomvar Carbon grids (Mecalab, QC, Canada), fixed in 1% glutaraldehyde and stained with 1% uranyl acetate. Samples were visualized using FEI Technai-12 120 KV transmission electron microscope and AMT XR80C CCD Camera.
Pseudomigration and protein digestion with trypsin {#s2d}
--------------------------------------------------
Proteins (5 µg) were loaded on an SDS-PAGE polyacrylamide gel containing 10% sucrose and run for 1 cm into the resolving gel. In-gel digestion was performed as described previously [@pntd.0002185-Havlis1]. The gel lane was excised into 3 bands and each band was cut into 1 mm^3^ pieces. Gel pieces were first washed with water for 5 min and then dehydrated with acetonitrile (ACN). Proteins were reduced by adding the reduction buffer (10 mM DTT, 100 mM ammonium bicarbonate) for 30 min at 40°C, and then alkylated by adding the alkylation buffer (55 mM iodoacetamide, 100 mM ammonium bicarbonate) for 20 min at 40°C. Gel pieces were dehydrated and washed at 40°C by adding ACN for 5 min before discarding all the reagents. Gel pieces were dried for 5 min at 40°C and then re-hydrated at 4°C for 40 min with the trypsin solution (6 ng/µl of sequencing grade trypsin (Promega), 25 mM ammonium bicarbonate). The concentration of trypsin was kept low to reduce signal suppression effects and background originating from autolysis products when performing LC-MS/MS analysis. Protein digestion was performed at 58°C for 1 h and stopped with 15 µl of 1% formic acid/2% ACN. Supernatant was transferred into a 96-well plate and peptides extraction was performed with two 30 min extraction steps at room temperature using the extraction buffer (1% formic acid/50% ACN). All peptide extracts were pooled into the 96-well plate and then completely dried in vacuum centrifuge. The plate was sealed and stored at −20°C until LC-MS/MS analysis.
LC-MS/MS {#s2e}
--------
Prior to LC-MS/MS, protein digests were re-solubilized under agitation for 15 min in 10 µl of 0.2% formic acid. Desalting/cleanup of the digests was performed by using C~18~ ZipTip pipette tips (Millipore, Billerica, MA). Eluates were dried down in vacuum centrifuge and then re-solubilized under agitation for 15 min in 10 µL of 2% ACN/1% formic acid. The LC column was a C18 reversed phase column packed with a high-pressure packing cell. A 75 µm i.d. Self-Pack PicoFrit fused silica capillary column (New Objective, Woburn, MA) of 15 cm long was packed with the C18 Jupiter 5 µm 300 Å reverse-phase material (Phenomenex, Torrance, CA). The column was installed on the Easy-nLC II system (Proxeon Biosystems, Odense, Denmark) and coupled to the LTQ Orbitrap Velos (ThermoFisher Scientific, Bremen, Germany) equipped with a Proxeon nanoelectrospray ion source. The buffers used for chromatography were 0.2% formic acid (buffer A) and 100% ACN/0.2% formic acid (buffer B). During the first 12 min, 5 µl of sample was loaded on column at a flow rate of 600 nl/min and, subsequently, the gradient went from 2--55% buffer B in 100 min at a flow rate of 250 nl/min followed by a rapid increase to 90% buffer B and then came back at 2% buffer B for 10 min at a flowrate of 600 nl/min. LC-MS/MS data acquisition was accomplished using a eleven scan event cycle comprised of a full scan MS for scan event 1 acquired in the Orbitrap. The mass resolution for MS was set to 60,000 (at m/z 400) and used to trigger the ten additional MS/MS events acquired in parallel in the linear ion trap for the top ten most intense ions. Mass over charge ratio range was from 380 to 2000 for MS scanning with a target value of 1,000,000 charges and from ∼1/3 of parent m/z ratio to 2000 for MS/MS scanning with a target value of 10,000 charges. The data dependent scan events used a maximum ion fill time of 100 ms and 1 microscan. Target ions already selected for MS/MS were dynamically excluded for 25 s. Nanospray and S-lens voltages were set to 0.9--1.8 kV and 50 V, respectively. Capillary temperature was set to 225°C. MS/MS conditions were: normalized collision energy, 35 V; activation q, 0.25; activation time, 10 ms.
Protein identification {#s2f}
----------------------
Protein database searching was performed with Mascot 2.2 (Matrix Science) against NCBI *Mus musculus* and *Leishmania* protein databases. The mass tolerances for precursor and fragment ions were set to 10 ppm and 0.6 Da, respectively. Trypsin was used as the enzyme allowing for up to 2 missed cleavages. Carbamidomethyl and oxidation of methionine were allowed as variable modifications.
Bioinformatic analyses of the proteomic data {#s2g}
--------------------------------------------
Duplicates of separately analyzed sets of MS/MS data were used for calculation of the Exponentially modified protein abundance index (emPAI) values using emPAICalc web server (<http://empai.iab.keio.ac.jp/>) [@pntd.0002185-Shinoda1]. Mascot output files were uploaded to emPAICalc server and hits with minimum 3 peptides and minimum score of 20 were chosen as true hits for further analyses. Gene Ontology (GO) annotations of identified proteins were extracted using STRAP software [@pntd.0002185-Bhatia1]. Protein-protein interaction networks of the identified proteins were created using STRING database with default parameters and visualized using Cytoscape software 2.8 [@pntd.0002185-Szklarczyk1], [@pntd.0002185-Smoot1].
*In vitro* stimulation and infection {#s2h}
------------------------------------
J774 macrophages were left un-treated, stimulated with 3--5 µg/ml of exosomes, 100 ng/ml of LPS or infected with stationary *L. mexicana* parasites at the ratio of 1∶20. Following the mentioned time-courses, cells were washed with PBS (3 times for the infected cells) and then lysed with appropriate lysing reagent as described below.
Western blotting {#s2i}
----------------
Following *in vitro* stimulation, cells were lysed in a Western blotting lysis buffer. Proteins were dosed by Bradford reagent (Biorad) and run on SDS-PAGE according to standard methods. Proteins were blotted to Hy-bond nylon members (Amersham) and were detected by antibodies against actin, tubulin, PGK1, PABP, ERK, phospho-ERK, JNK, phospho-JNK, p38 and phospho p38 (all from Cell Signaling), or anti-phosphotyrosine clone 4G10 (Millipore). Anti-mouse or anti-rabbit and anti-rat antibodies conjugated to horse-radish peroxidise (HRP) (Amersham) were used as secondary antibodies. Membranes were then visualized by ECL Western blotting detection system (Amersham).
Electrophoretic Mobility Shift Assay (EMSA) {#s2j}
-------------------------------------------
EMSA was performed as described previously [@pntd.0002185-Hassani1]. Briefly, nuclear proteins were extracted using an isotonic and then a hypotonic buffer. Extracted nuclear proteins were incubated with radiolabelled consensus sequences of NF-κB (5′-AGTTGAGGGGACTTTCCCAGGC-3′), AP-1(5′-AGCTCGCGTGACTCAGCTG-3′) and SP-1 (5′-ATTCGATCGGGGCGGGGCGAGC-3′) (Santa Cruz, CA, USA) as non-specific control. Samples were run on a native 4% acrylamide gel. Following electrophoresis, gels were dried and autoradiography was performed using Kodak film.
Densitometry {#s2k}
------------
Densitometry was performed using ImageJ software (NIH). Mean grey values of bands (ratio of phospho-proteins against their respective total proteins in case of MAP Kinases) were acquired and then normalized against the non-treated sample.
Quantitative real-time PCR (qRT-PCR) {#s2l}
------------------------------------
J774 macrophages were left untreated, infected with stationary *L. mexicana* parasites at 1∶20 ratio, stimulated with 100 ng/ml of LPS or 5 µg/ml of exosomes for 8 h. Following stimulation, cells were washed with PBS, (3 times for infected cells) and were lysed in Tryzol reagent (Invitrogen) according to the manufacturer\'s instructions for RNA extraction. Extracted RNA was then cleaned-up using Qiagen clean-up columns. Clearance of possible genomic DNA contamination was performed using DNase I (Promega) according to manufacturer\'s protocol. 1 µg of total RNA was used for cDNA preparation using reverse transcriptase enzyme Superscript III (Invitrogen) and random oligo-hexamers (Invitrogen). Samples were then treated with *Escherichia coli* RNase H (Invitrogen) for clearance of RNA-DNA helices. qRT-PCR was performed using Qiagen SABioscience RT^2^ profiler arrays in a Strategene mx3000 thermocycler according to SABiosciences protocol. Results were analyzed by ΔΔCt method using the Qiagen qRT-PCR data analysis web interface.
Results {#s3}
=======
Purification of exosomes from LPS-stimulated and *Leishmania*-infected macrophages {#s3a}
----------------------------------------------------------------------------------
To collect exosomes from *Leishmania*-infected macrophages, we infected J774 macrophages with stationary *L. mexicana* parasites for 6 h to confidently saturate all macrophages with parasites. We washed away non-internalized parasites by PBS and incubated the macrophages in exosome-free medium for 24 h (LEISHX). Similarly, we stimulated the macrophages with 100 ng/ml of LPS as a strong stimulant for 6 h, to compare its effect with the immunomodulatory properties of *Leishmania* (LPSX). As a negative control, we incubated non-treated macrophages in exosome-free media for 24 h (NILX).
Following incubations, we collected the conditioned medium and extracted the exosomes via multiple centrifugation and filtration processes as detailed in the [materials and methods](#s2){ref-type="sec"} section. Exosomes settle at the density of 1.13 to 1.19 g/ml as can be seen in [Figure 1A](#pntd-0002185-g001){ref-type="fig"} that shows a silver staining of fractions following sucrose density gradient centrifugation of exosomes. We further verified presence and purity of exosomes by western blotting against actin, known to be enriched in exosomes ([Figure 1B](#pntd-0002185-g001){ref-type="fig"}). We did not observe any differences in density of exosomes after density gradient centrifugation of NILX, LPSX and LEISHX samples (data not shown). We recovered consistently but non-significantly less exosomes from LPS macrophages but observed no difference amongst LEISHX and NILX in terms of protein amount. Reduction in exosome release following LPS stimulation has been previously described to occur in DCs [@pntd.0002185-Thery2]. It is important to mention that our purification steps, especially involving filtration and density gradient centrifugation, would minimize contamination of our samples with other types of secreted vesicles. Nevertheless, transmission electron microscopy (TEM) of all samples showed only vesicles of 40--100 nm in size and morphology described for exosomes. We did not observe any vesicles of larger size suggesting that there was negligible if any contamination with larger secreted vesicles such as membrane vesicles [@pntd.0002185-Simpson1]. No differences were observed among the samples suggesting that morphology and size of exosomes remain unaltered following LPS stimulation or *Leishmania* infection (representative TEM image shown in [figure 1C](#pntd-0002185-g001){ref-type="fig"}).
{#pntd-0002185-g001}
Comparative proteomic analysis of exosomes reveals major modulations following infection or LPS stimulation {#s3b}
-----------------------------------------------------------------------------------------------------------
We performed mass spectrometry (LC-MS/MS) to analyze the content of the purified exosomes. Due to multiple washing steps in the purification, very few hits of contaminated serum proteins were found and were removed from the protein list. Detailed spectrum and peptide report as well as Pearson Coefficients comparing sample replicates against other samples are available in Supplemental [File S1](#pntd.0002185.s001){ref-type="supplementary-material"}. Because peptide counts are not a reliable quantitative measure for sample comparison, we analyzed our proteomic data using the exponentially modified protein abundance index (emPAI) [@pntd.0002185-Ishihama1]. This method, calculates a ratio of observed to observable peptides, based on factors such as the conditions of the mass spectrometry analyses, protein biochemical properties and previously published empirical data. emPAI values are proposed to be linearly correlated to protein concentration and to give a more accurate estimate of protein abundance compared to simple peptide or spectral count [@pntd.0002185-Shinoda1], [@pntd.0002185-Ishihama1]. Only proteins with minimum 3 peptides and peptide score higher than 20 were considered as true hits. Also some proteins had to be removed because their relevant information was absent in the emPAI database. With these criteria, we ended up with a total of 248 proteins, which we used as the primary list for the rest of our analyses. The selected proteins and their calculated emPAI values are listed in supplemental [files S1](#pntd.0002185.s001){ref-type="supplementary-material"} and [S2](#pntd.0002185.s002){ref-type="supplementary-material"} respectively. We found 137 proteins in NILX, 173 proteins in LPSX and 200 proteins in LEISHX ([Figure 2](#pntd-0002185-g002){ref-type="fig"}). We compared the list of the identified proteins against previously published exosome data at Exocarta database ([www.exocarta.org](http://www.exocarta.org), [@pntd.0002185-Mathivanan1]) and found that the majority of the hits had been previously observed to be present in at least one group of exosomes (Supplemental [File S1](#pntd.0002185.s001){ref-type="supplementary-material"}).
{#pntd-0002185-g002}
Since it had been previously reported that proteins from bacterial pathogens such as *Mycobacterium* can enter the macrophage exosomes, we also looked for *Leishmania* proteins in our MS/MS data. Interestingly, we observed positive hits for *Leishmania* surface metalloprotease GP63 in LEISHX exosomes and as expected not in NILX or LPSX (Supplemental [File S3](#pntd.0002185.s003){ref-type="supplementary-material"}). To our knowledge, this is the first report of a protein from a eukaryotic parasite entering macrophage exosomes.
Interestingly, we observed that a high percentage of discovered proteins are shared among the 3 samples. 78% of proteins found in NILX, 62% of those found in LPSX and only 53% of proteins found in LEISHX were common among the 3 samples (107 proteins). While LEISHX had the highest number of unique proteins (44, 22%), LPSX and LEISHX had the highest percentage of shared proteins in between pairs (37, ∼20%). Therefore, we decided to compare the levels of abundance of the shared proteins among the samples.
We compared the levels of abundance of the common 107 proteins by calculating their LEISHX/NILX and LPSX/NILX emPAI ratios (Supplemental [File S2](#pntd.0002185.s002){ref-type="supplementary-material"}). Log~10~ of these ratios are plotted in [Figure 3A and B](#pntd-0002185-g003){ref-type="fig"}, sorted from highest to lowest ratio for LEISHX/NILX and LPSX/NILX, respectively. The plots clearly show that although these proteins are shared among exosomes of naive, LPS-stimulated and *Leishmania*-infected exosomes, their abundance is greatly altered following these stimulations. In fact, very few proteins appear to have equal abundance, and a significant percentage have been altered more than 2 or 3 fold (Log~10~\>0.3, [Figure 3C](#pntd-0002185-g003){ref-type="fig"}). Interestingly, it appears that increase or decrease in abundance follows a similar trend in LPSX and LEISHX samples, whereby proteins increased in LEISHX are also increased in LPSX and vice-versa (Correlation coefficient = 0.72). This trend can also be observed when plotting the frequency distributions of LEISHX/NILX and LPSX/NILX emPAI ratios ([Figure 3C](#pntd-0002185-g003){ref-type="fig"}). However, not all proteins follow the trend. In fact, ∼30% of proteins show opposite and divergent modulations between LPSX and LEISHX.
{#pntd-0002185-g003}
We next compared modulation of proteins between LEISHX and LPSX themselves and also included the 37 proteins common between them to the 107 common proteins ([Figure 4A](#pntd-0002185-g004){ref-type="fig"}). About half of the identified proteins have higher abundance in LEISHX, while about 35% have higher abundance in LPSX. However, frequency distribution of the emPAI ratios shows that the majority of the modulations lie within 2-fold difference (−0.3\>Log~10~\<0.3) ([Figure 4B](#pntd-0002185-g004){ref-type="fig"}). Together these results show that *Leishmania* infection and LPS stimulation induce a similar trend of modulations in protein abundance in macrophage exosomes; although significant differences exist amongst the two types of stimulations.
{#pntd-0002185-g004}
Gene Ontology and Network Analysis suggest modulation of specific protein groups {#s3c}
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Various groups of proteins are sorted into exosomes. Having seen the modulations in protein abundance, as well as in the presence/absence of proteins among samples ([Figures 2](#pntd-0002185-g002){ref-type="fig"}--[4](#pntd-0002185-g004){ref-type="fig"}), we used Gene Ontology (GO) classification of proteins to look at the cellular localization, function and biological processes of groups that were up- or down-regulated. For simplicity, we merged the proteins unique to one sample with the proteins up-regulated in the same sample. We chose proteins with 1.5 fold or more difference in their emPAI value (−0.15\>Log~10~\<0.15) as the ones that are modulated between two samples. It is worthy to mention that since we chose proteins with minimum of 3 peptides as our starting criteria for inclusion into analyses, and we used emPAI analyses for correction of MS error, we are confident that 1.5 fold differences can have a real biological meaning. These cut-off lines resulted in labelling of 130 and 103 proteins as up-regulated in LEISHX and LPSX respectively. 51 and 60 proteins were also described as down-regulated in LEISHX and LPSX respectively. Finally, comparing LEISHX and LPSX resulted in 108 proteins higher in LEISHX compared to LPSX and 56 in the opposite. Between 20--25% of proteins in each comparison group were labelled as unchanged.
Comparative graphs of number of GO terms associated with each group of proteins show modulations in proteins associated with multiple functions, processes and cellular localizations in both LEISHX and LPSX ([Figure 5](#pntd-0002185-g005){ref-type="fig"}). The comparative GO graphs of molecular function are presented in Supplemental [File S4](#pntd.0002185.s004){ref-type="supplementary-material"}. Since more proteins are up-regulated than down-regulated in LEISHX and LPSX, it is not surprising that there appears to be generally more increases in GO terms associated with these samples. Although LPSX and LEISHX show similar patterns in up and down regulations compared to NILX ([Figure 5A and B](#pntd-0002185-g005){ref-type="fig"}), direct comparison of LPSX and LEISHX reveals many differences in their associated GO terms. This shows that despite similarity, distinct functional groups and cellular processes are enriched in each set of exosomes.
{#pntd-0002185-g005}
Finally, to assess at the functional differences among the three samples at the protein level, we created exosome protein-protein interaction (PPI) networks using the STRING database for PPIs. [Figure 6A](#pntd-0002185-g006){ref-type="fig"} shows the PPI network of the proteins identified in LEISHX (PPI networks of NILX and LPSX can be seen in Supplemental [File S5](#pntd.0002185.s005){ref-type="supplementary-material"}). Looking closely at the PPI network, different functional groups of proteins known to be enriched in exosomes can be observed as interaction groups. For instance, circle I includes proteins associated with the plasma membrane and cell binding such as Integrin-β1 and β2 (Itgb1, Itgb2), CD63 and ICAM1, circle II includes chaperones such as members of the T-complex proteins, circle III includes proteins important in vesicular trafficking such as TSG101 and Alix (Pcdc6ip) and circle IV includes metabolic enzymes such as enolase, phosphoglycerate kinase (PGK1), lactate dehydrogenase (Ldha) and hexokinase (HK3). Other proteins usually present in exosomes such as signaling proteins, annexins and proteins involved in translation can also be observed in the PPI network. It can also be seen that actin (actb) is one of the proteins that connects these interaction groups with each other.
{#pntd-0002185-g006}
Since proteins associated with the plasma membrane generated the largest interaction group, we decided to compare those proteins among NILX, LPSX and LEISHX samples. [Figures 6B and C](#pntd-0002185-g006){ref-type="fig"} show the proteins in the PPI network bearing the Cellular Component GO term, *plasma membrane* in LPSX and LEISHX respectively. Interestingly, many modulations occur with proteins involved in cell-cell contact. Levels of surface receptors or co-receptors such as Fc-γ-receptor 1 (Fcgr1), TLR2, CD40 and CD14 seem to increase with both stimulations. Integrins seem to be modulated with Integrin-β1 and Integrin-α4 decreasing and Integrin-β5 increasing, while Integrin-β4 remains unchanged. On the other hand, CD9 and CD44, two proteins important in cell-cell interaction and usually seen in exosomes, only increased in LPSX and not in LEISHX, while LEISHX shows an increase in PTPN6 (SHP-1), a PTP that we have shown to be modulated and activated after *Leishmania* infection [@pntd.0002185-Gomez1], [@pntd.0002185-Forget1]. Together, our PPI network analysis of exosomes allows us to closely monitor the alterations in exosome surface that could play a role in exosome targeting and effector functions on recipient cells.
Verification of the proteomic data {#s3d}
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We verified a number of the alterations in protein content in exosomes observed in our MS/MS results by western blotting. Firstly, we were able to confirm presence of GP63 in LEISHX ([Figure 7A](#pntd-0002185-g007){ref-type="fig"}). Then, we looked at tubulin and PGK1, both of which that had shown higher emPAI values in both LPSX and LEISHX compared to NILX and we were able to observe their increase by western blotting as well ([Figure 7B](#pntd-0002185-g007){ref-type="fig"}). In fact, we did not detect PGK1 in NILX by MS/MS that is probably due to its low abundance in these exosomes. Lastly, we looked at polyadenylated binding protein (PABP). Although emPAI values from MS/MS data showed reduction of in PABP in LPSX and LEISHX, we detected equal levels of this protein by western blotting. This reiterates the fact that results from MS/MS analyses should always be taken with caution.
{#pntd-0002185-g007}
LPS and *Leishmania*-induced exosomes trigger activatory signaling in naive macrophages {#s3e}
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Although the effect of exosomes on recipient cell function has been previously studied, the signaling pathways triggered leading to those functions have not been explored. To look at signaling pathways induced via exosome stimulation, we stimulated naive J774 macrophages with 3 µg/ml of pelleted and washed NILX, LPSX, LEISHX exosomes for 1 h and looked at patterns of general tyrosine phosphorylation, as well as phosphorylation of MAP Kinases ERK, JNK and P38. [Figure 8A](#pntd-0002185-g008){ref-type="fig"} shows that stimulation with LPSX and LEISHX induces early Tyr phosphorylation of multiple proteins within as short as 15 min and increasing up to 1 h. Expectedly, stimulation with NILX does not induce a strong tyrosine phosphorylation compared to LPSX and LEISHX. Comparison of LPSX and LEISHX-stimulated cells identified both similar and unique Tyr phosphorylation patterns. We also looked at phosphorylation of MAP Kinases in naive macrophages within 1 h of stimulation with exosomes ([Figure 8B](#pntd-0002185-g008){ref-type="fig"}). All 3 groups of exosomes appeared to induce phosphorylation of MAP Kinases, except for JNK which was not induced as strongly by LEISHX. Densitometric quantification of 3 separate experiments also supports weaker phosphorylation of JNK in response to LEISHX stimulation compared to other exosomes.
{#pntd-0002185-g008}
Looking more downstream of protein phosphorylation, we studied activation of prominent pro-inflammatory transcription factors (TFs) NF-κB and AP-1 by exosomes. We stimulated naive macrophages with 3 µg/ml of exosomes for 1 h and performed EMSAs on extracted nuclear proteins ([Figure 9](#pntd-0002185-g009){ref-type="fig"}). We observed that all 3 exosomes induce nuclear translocation of NF-κB and AP-1, although translocation of NF-κB is slightly less induced in response to LEISHX stimulation ([Figure 9A](#pntd-0002185-g009){ref-type="fig"}). Infection with *L. mexicana* itself results in degradation of AP-1 and alteration of NF-κB as we had previously reported [@pntd.0002185-Hassani1], [@pntd.0002185-Gregory1]. We did not detect translocation of STAT-1 following exosome stimulation (data not shown). Overall, we saw that macrophage exosomes are capable of stimulating signaling molecules in naive macrophages, possibly resulting in distinct responses.
{#pntd-0002185-g009}
Quantitative real-time PCR (qRT-PCR) reveals the downstream effects of exosome stimulation {#s3f}
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The observed distinct activation patterns of signaling molecules and transcription factors by exosomes can lead to modulation of expression of many genes and different activation states in the recipient cell. To further scrutinize exosome-induced modulation of gene expression, we prepared cDNA from J774 macrophages stimulated with exosomes for 8 h and performed qRT-PCR using Qiagen SABiosciences RT^2^ Profiler arrays. Using these arrays, we measured modulation of expression of 90 immune related genes in exosome-stimulated macrophages. LPS (100 ng/ml) and *L. mexicana* infection were used as controls. The genes found to be at least 2-fold up-regulated or down-regulated after exosome stimulation are listed in [Tables 1](#pntd-0002185-t001){ref-type="table"} and [2](#pntd-0002185-t002){ref-type="table"} (for complete data see Supplemental [File S6](#pntd.0002185.s006){ref-type="supplementary-material"}). All 3 groups of exosomes appeared to be more stimulatory than inhibitory, as they induced more gene up-regulation than down-regulation. Especially, we observed up-regulation of pro-inflammatory cytokines such as IL-6 and IL-1 as well as certain interleukin receptors and TLRs. This is concurrent with our observations on activation of signaling molecules by exosomes. [Figure 10](#pntd-0002185-g010){ref-type="fig"} shows up-regulations and down-regulations that are shared following stimulation of macrophages with NILX, LPSX and LEISHX exosomes. The 10 genes that are induced by all 3 groups constitute ∼40--60% of the genes upregulated by each ([Figure 10A](#pntd-0002185-g010){ref-type="fig"}). Interestingly, more than 80% of genes induced by NILX are induced by LEISHX as well, while this percentage for LPSX is only 50%. Additionally, LPSX induces the most unique set of genes compared to the other 2 groups. The same is true for the downregulated genes by LPSX ([Figure 10B](#pntd-0002185-g010){ref-type="fig"}). This shows that NILX and LEISHX modulate gene expression more similarly compared to LPSX. Therefore, it suggests that exosomes from *Leishmania*-infected macrophages resemble more those of untreated macrophages than LPS-stimulated and activated macrophages. Infection with *L. mexicana* did not result in a stimulatory in terms of induction of immune-related genes and macrophage activation, in comparison to LPS and exosomes (Supplemental [File S6](#pntd.0002185.s006){ref-type="supplementary-material"}). This is not surprising since *Leishmania* strongly modulates the pro-inflammatory transcription factors to avoid macrophage activation and establish its infection ([Figure 9](#pntd-0002185-g009){ref-type="fig"} and [@pntd.0002185-Contreras1], [@pntd.0002185-Gregory1]). Concurrently, the exosomes released from the infected macrophages also did not possess strong pro-inflammatory properties compared to naive exosomes.
{#pntd-0002185-g010}
10.1371/journal.pntd.0002185.t001
###### List of genes upregulated by at least one set of macrophage exosomes.
{#pntd-0002185-t001-1}
\# Name Description NILX LPSX LEISHX
-------- ----------- ------------------------------------------------- ----------- ----------- ------------
**1** Adora2a Adenosine A2a receptor **9.56** −1 **23.86**
**2** Camp Cathelicidin antimicrobial peptide **2.36** **3.45** **2.24**
**3** Casp4 Caspase 4, apoptosis-related cysteine peptidase **5.86** **3.2** **4.55**
**4** Ccl2 Chemokine (C-C motif) ligand 2 **4.52** 1.36 **4.68**
**5** Cd14 CD14 antigen 1.67 −1.11 **2.06**
**6** Chuk Conserved helix-loop-helix ubiquitous kinase **2.7** **2.38** **3.63**
**7** Clec7a C-type lectin domain family 7, member a **14.95** 1.38 1.35
**8** Cybb Cytochrome b-245, beta polypeptide 1.77 1.61 **2.62**
**9** Dmbt1 Deleted in malignant brain tumors 1 1.04 **2.82** 1.28
**10** Hmox1 Heme oxygenase (decycling) 1 **3.24** 1.65 **4.02**
**11** Ifnb1 Interferon beta 1, fibroblast **10.94** **17.01** **7.95**
**12** Il1a Interleukin 1 alpha **155.1** 1.79 **358.71**
**13** Il1b Interleukin 1 beta **149.8** **3.13** **920.75**
**14** Il1f5 Interleukin 1 family, member 5 (delta) −1.04 **7.51** 1.59
**15** Il1f8 Interleukin 1 family, member 8 **4.68** **2.33** 1.02
**16** Il1f9 Interleukin 1 family, member 9 **13.28** **5.71** **13.66**
**17** Il1r1 Interleukin 1 receptor, type I **3.74** 1.98 **4.2**
**18** Il1rapl2 Interleukin 1 receptor accessory protein-like 2 **4.19** **2.24** 1.37
**19** Il1rl2 Interleukin 1 receptor-like 2 1.23 1.62 **7.42**
**20** Il1rn Interleukin 1 receptor antagonist **3.26** −1.07 **4.47**
**21** Il6 Interleukin 6 **7.82** **7.33** **48.06**
**22** Irak2 Interleukin-1 receptor-associated kinase 2 **2.64** **2.12** **3.65**
**23** Irf1 Interferon regulatory factor 1 1.41 **3.12** 1.21
**24** Mapk8 Mitogen-activated protein kinase 8 1.11 **10.4** 1.44
**25** Myd88 Myeloid differentiation response gene 88 −1.39 **3.94** 1.86
**26** Nfkb2 NF-kappa B, p49/p100 **2.59** −1 1.7
**27** Nfkbia NF-kappa B inhibitor, alpha **2.96** 1.91 **4.02**
**28** Nos2 Nitric oxide synthase 2, inducible 1.81 1.61 **6.95**
**29** Proc Protein C **2.19** **12.07** 1.06
**30** Ptafr Platelet-activating factor receptor **2.98** −1.15 **3.01**
**31** Serpina1a Serine peptidase inhibitor, clade A, member 1a **2.04** 1.96 **2.02**
**32** Serpine1 Serine peptidase inhibitor, clade E, member 1 **3.51** −1.02 **3.56**
**33** Tlr1 Toll-like receptor 1 1.36 **2.37** **2.29**
**34** Tlr2 Toll-like receptor 2 1.71 1.4 **2.53**
**35** Tlr4 Toll-like receptor 4 −1.32 **3.03** 1.25
**36** Tlr6 Toll-like receptor 6 **2.44** **2.22** **9.2**
**37** Tnf Tumor necrosis factor **2.21** 1.61 **2.41**
**38** Traf6 Tnf receptor-associated factor 6 1.45 **2.65** 1.55
**39** Trem1 Triggering recepter of myeloid cells 1 **2.71** **2.69** **2.32**
Fold regulation against non-treated samples, calculated using ΔΔCt method, normalized against a panel of 3 house-keeping genes.
Results are average of 2 replicates. Numbers in bold are indicative of at least 2-fold upregulation.
Genes that are at least 2-fold up-regulated by one of the exosomes are listed.
10.1371/journal.pntd.0002185.t002
###### List of genes down-regulated by at least one set of macrophage exosomes.
{#pntd-0002185-t002-2}
\# Name Description NILX LPSX LEISHX
-------- --------- -------------------------------------------- ----------- ------------ ------------
**1** C8a Complement component 8, alpha polypeptide −1.3 1.62 **−3.12**
**2** Cxcr4 Chemokine (C-X-C motif) receptor 4 **−7.96** **−89.37** **−9.98**
**3** Ikbkb Inhibitor of kappaB kinase beta −1.02 **−92.84** −1.02
**4** Il1f10 Interleukin 1 family, member 10 **−2.36** −1.35 −1.96
**5** Il1r2 Interleukin 1 receptor, type II **−20.8** **−9.89** **−10.33**
**6** Irak1 Interleukin-1 receptor-associated kinase 1 **−2.15** **−2.07** −1.85
**7** Lalba Lactalbumin, alpha **−2** **−3.15** −1.64
**8** Ltf Lactotransferrin 1.49 **−4.65** −1.07
**9** Mif Macrophage migration inhibitory factor −1.88 **−2.72** −1.52
**10** Pglyrp1 Peptidoglycan recognition protein 1 **−2.45** 1.52 −1.5
**11** Pglyrp3 Peptidoglycan recognition protein 3 **−4.75** **−2.83** **−2.88**
**12** Prg2 Proteoglycan 2, bone marrow 1.01 **−2.61** **−3.68**
**13** Sftpd Surfactant associated protein D 1.43 **−3.38** **−4.17**
**14** Tollip Toll interacting protein 1.17 1.18 **−2.28**
Fold regulation against non-treated samples, calculated using ΔΔCt method, normalized against a panel of 3 house-keeping genes.
Results are average of 2 replicates. Numbers in bold are indicative of at least 2-fold upregulation.
Genes that are at least 2-fold down-regulated by one of the exosomes are listed.
Overall, we compared the modulations that occur in macrophage exosome protein content, as well as their effector function on recipient cells, following *L. mexicana* infection and LPS stimulation. These data provide a better understanding of biology of exosomes and host-parasite interactions of *Leishmania*.
Discussion {#s4}
==========
Studies on different functions of secreted vesicles, especially exosomes have now established them as yet another route for cell-cell communication, especially among immune cells [@pntd.0002185-Thery1]. Furthermore, it is now clear that sophisticated mechanisms are involved in exosome formation and exosomal protein sorting [@pntd.0002185-Nickel1], [@pntd.0002185-Baietti1]. Importantly, different extracellular stimulations or infectious agents such as viruses, intracellular bacteria or protozoa have been shown to alter exosome release from their host cells [@pntd.0002185-Meckes1], [@pntd.0002185-Bhatnagar2]. However, modulations in the protein content of exosomes following these stimulations, especially infection, had not been previously studied. Here we report the first comparative proteomic analysis of naive macrophage exosomes against exosomes produced following stimulation with LPS or infection with *L. mexicana*. We interestingly observed that around 50--80% of proteins are shared among NILX, LPSX and LEISHX exosomes and this includes proteins that are usually reported to be sorted into exosomes, such as proteins involved in cell-cell communication, folding, vesicular trafficking and signaling. Combining the unique hits and also nuances in the levels of the shared proteins, we were able to look closely at the alterations in the sorting of functional groups of proteins into exosomes following these stimulations (See [Figures 5](#pntd-0002185-g005){ref-type="fig"} and [6](#pntd-0002185-g006){ref-type="fig"}).
We used emPAI values for our proteomic comparisons, which is a method regularly applied to assist in quantitative analysis of label-free mass spectrometric data [@pntd.0002185-Adav1]--[@pntd.0002185-Monteiro1]. This method allowed us to better quantify the differences among NILX, LPSX and LEISHX and observe many alterations in the levels of common proteins ([Figures 3](#pntd-0002185-g003){ref-type="fig"}--[6](#pntd-0002185-g006){ref-type="fig"}).
Choi *et al.* recently created the PPI network of proteins in exosomes derived from human colorectal cancer cells. They suggested that interacting proteins form complexes and functional modules in exosomes; and that PPIs can be involved in exosomal protein sorting [@pntd.0002185-Choi1]. We observed similar functional groups as those of Choi *et al.* and we were able to see how changes in the status of the macrophage can alter the composition and also abundance of these functional groups. Unfortunately, to date the underlying reasons for presence or absence of many of these proteins in exosomes are unclear. Therefore, our study can help connect the dots between the status of the macrophage, the contents of the released exosomes and their effector functions. For instance, using PPI networks of exosomes we saw that increases in chaperones occurred in both LPS and LEISHX, although increases in metabolic enzymes was more evident in LEISHX ([Figure 6](#pntd-0002185-g006){ref-type="fig"}). Plasma membrane associated proteins showed most differences among the three sample groups, which can suggest that most alterations in exosome content could most importantly affect its targeting of recipient cells [@pntd.0002185-Rana1].
We were able to show that *Leishmania* GP63 is sorted into exosomes of infected macrophages via both MS/MS analysis and western blotting. GP63 is a key and highly abundant virulence factor of *Leishmania* promastigotes and our lab has previously shown that this enzyme is able to gain access to the macrophage cytoplasm and nucleus very early following *Leishmania* infection [@pntd.0002185-Gomez1], [@pntd.0002185-Contreras1] to alter many signaling molecules of the macrophage. It is therefore possible that presence of only GP63 and not other *Leishmania* proteins in the macrophage exosomes is due to its direct entrance through the cytosol and not through the communication of the phagolysosome with the MVE. Another possibility is that GP63 is a contamination from the parasites and not macrophage exosomes. We believe this to be very improbable because *firstly*, the unphagocytosed parasites were taken out by multiple washes before the exosomes-collection media was put on the macrophages; *secondly*, we did not detect any other proteins that are enriched in *Leishmania* exosomes or exoproteome; and *thirdly*, the collected exosomes were washed multiple times during the purification process to avoid contamination with any CM content.
Previous studies on exosomes released from infected cells with viruses and bacteria such as Herpes Simplex virus, Epstein-Barr virus and *Mycobacterium* sp. also showed that proteins from intracellular pathogens could be sorted into exosomes [@pntd.0002185-Giri1], [@pntd.0002185-Meckes1]. In addition, it was proposed that the pro-inflammatory properties of exosomes released from bacterially infected macrophages are due to presence of these molecules and their triggering of pattern recognition receptors (PRRs) on the recipient cells [@pntd.0002185-ONeill1]. However, we did not detect any *Leishmania* proteins other than GP63 to be sorted into exosomes by MS/MS or western blotting of common immunogenic *Leishmania* proteins such as LACK [@pntd.0002185-Kelly1] (data not shown). GP63 is not naturally immunogenic, but is rather an immunomodulatory protein (see [@pntd.0002185-Shio1], [@pntd.0002185-Yao1] for reviews). Therefore, this could in part explain the absence of strong pro-inflammatory properties in LEISHX compared to NILX exosomes. The reasons for absence of other *Leishmania* proteins in macrophage exosomes could be the possible modulation of the interactions between the phagolysosome and the MVE.
We observed that the macrophage exosomes were able to induce phosphorylation of signaling proteins and translocation of activatory TFs into the nucleus. It was intriguing to observe a reduction in JNK phosphorylation following stimulation with LEISHX but not other exosomes. We speculate that this could be due to transfer of activated PTPs from the infected to the naive macrophage. As we have shown previously, *Leishmania* infection results in activation of a number of macrophage PTPs in a cleavage-dependent manner [@pntd.0002185-Gomez1], [@pntd.0002185-Hassani1]. In addition, our proteomic results show that exosomes contain PTPs, especially SHP-1 levels were shown to be increased in LEISHX ([Figure 6C](#pntd-0002185-g006){ref-type="fig"}). Therefore, these transferred and active PTPs could possibly be involved in dephosphorylation of JNK. Similar mechanisms might also participate in reduction of NF-κB nuclear translocations.
To see how the activation of the signaling molecules is translated into function, we measured regulation of expression of immune-related genes by NILX, LPSX and LEISHX exosomes. Interestingly, all exosomes showed a relatively stimulatory behaviour and induced the expression of cytokines such as IL-6, members of the IL-1 family as well as certain receptors such as Interleukin receptors and TLRs ([Table 1](#pntd-0002185-t001){ref-type="table"} and [Figure 10](#pntd-0002185-g010){ref-type="fig"}). Exosome-induced production of cytokines such as IL-6, IL-1 and TNF by macrophages and monocytes has been reported elsewhere as well [@pntd.0002185-Southcombe1], [@pntd.0002185-Atay1]. Nevertheless, we did not detect secretion of TNF or NO by the exosome-stimulated macrophages (Data not shown). This shows that production and release of these critical immune modulators could be regulated at multiple levels. Exosomes might provide one of the necessary signals for this purpose. The relatively weak immuno-stimulatory properties of LPSX exosomes compared to macrophages infected with bacteria in other studies (reviewed in [@pntd.0002185-Schorey1]) could be because we stimulated the macrophages with only LPS rather than living bacteria. Although it has been reported for bacterial antigens to be sorted into exosomes, this might not occur as much with LPS. Thus, LPSX exosomes might not be as immuno-stimulatory as exosomes derived from bacterially infected macrophages. Still, it was interesting to observe that the members of the LPS downstream signaling pathway, namely TLR4, MyD88 and TRAF6 to be up-regulated by LPSX, maybe priming macrophages for more sensitive detection of LPS in the environment.
The fact that we observed a pro-inflammatory behavior for NILX exosomes poses a question on its physiological relevance. However, one should bear in mind that there are fundamental shortcomings in the *in vitro* exosome function studies. First, there is limited knowledge on the physiological concentration and half-life of exosomes *in vivo*; thus most studies looking at exosomes *in vitro* usually have to use arbitrary concentrations. Additionally, the concerted effect of exosomes from various sources together with other factors such as cytokines and growth factors might lead to different outcomes from what observed *in vitro*.
Gene-expression regulation patterns of NILX and LEISHX looked alike ([Figure 10A](#pntd-0002185-g010){ref-type="fig"}). This is in contrary to the exosomes released by bacterially infected macrophages, where they have been shown to have strong pro-inflammatory properties, compared to naive exosomes [@pntd.0002185-ONeill1]--[@pntd.0002185-Bhatnagar1], [@pntd.0002185-Bhatnagar2]. However, *Leishmania*-induced exosomes do not show this behavior and appear to be more similar to naive exosomes, especially compared with LPS-induced exosomes. This is despite the fact that the macrophage is infected with an intracellular pathogen and its exosome content is altered. Therefore, *Leishmania* alters exosome production by the macrophage in a fashion that matches its other immune evasion virulence mechanisms.
One of the genes upregulated by NILX and very strongly by LEISHX is the Adenosine receptor 2a (Adora2a). Extracellular adenosine (usually generated during stress and inflammation via dephosphorylation of extracellular ATP) has been suggested to be a modulator of the innate immune response [@pntd.0002185-Kumar1]. Especially, binding of adenosine to Adora2a in macrophages results in an inhibitory response consisting of increased IL-10 and reduced TNF release [@pntd.0002185-Hasko1]. Interestingly, a recent study also showed that *Leishmania amazonensis* utilizes this receptor to antagonize inflammation and spread infection [@pntd.0002185-Figueiredo1]. Thus, LEISHX upregulates Adora2a in bystander macrophages that could potentially be the next in line to be infected and more readily inhibited.
To conclude, we observed that LPS stimulation and *Leishmania* infection induce modulation of exosomal sorting into macrophages, especially with plasma membrane associated proteins. These modulations in turn altered effector functions and targeting of released exosomes. We were able to see that these modulations result in activation of signaling proteins and differential regulation of expression of immune-related genes. Our study also suggests that *Leishmania* could modulate the host\'s exosome machinery in its benefit; a virulence mechanism which needs to be further explored, especially by looking at antigen presentation by *Leishmania*-induced exosomes. Together our results give a better understanding of exosome biology in the innate immune system, connecting it to *Leishmania* host-parasite interactions.
Supporting Information {#s5}
======================
######
**Spectrum and peptide information for the mass spectrometry data.**
(XLS)
######
Click here for additional data file.
######
**Calculated comparative emPAI values.**
(XLS)
######
Click here for additional data file.
######
**Spectrum and peptide information for the Mass spectrometry data, analyzed with the** ***Leishmania*** **database.**
(XLS)
######
Click here for additional data file.
######
**Other GO comparisons (Continued from** [**Figure 5**](#pntd-0002185-g005){ref-type="fig"} **).** **A--C.** Pair-wise comparisons of GO terms associated with Molecular Function among NILX, LPSX and LEISHX are shown.
(PDF)
######
Click here for additional data file.
######
**High resolution PPI networks of NILX, LPSX and LEISHX exosomal proteins.**
(PDF)
######
Click here for additional data file.
######
**Complete qRT-PCR data.**
(XLS)
######
Click here for additional data file.
Mass spectrometry analyses were performed in the Mass Spectrometry platform of the Institut de Recherche Clinique de Montréal (IRCM). The authors are thankful to Mr. Saman Amirpour Amraii and Dr. Hamed Shateri Najafabadi for their help with the computational analyses and their insightful comments. The authors would also like to thank Dr. José Theodoro for their aid with the ultracentrifugation equipment, as well as Dr. Russell Jones, Dr. Connie Krawczyk and Dr. Joachim Madrenas for their aid with the qRT-PCR equipment. Electron microscopy was performed at the McGill Facility for Electron Microscopy Research (FEMR).
[^1]: The authors have declared that no competing interests exist.
[^2]: Conceived and designed the experiments: KH MO. Performed the experiments: KH. Analyzed the data: KH MO. Wrote the paper: KH MO.
| {
"pile_set_name": "PubMed Central"
} |
36 Millionen Euro an Großspenden : CDU und CSU erhalten die meisten Parteispenden
Die CDU und CSU erhalten den größten Anteil an Spenden. Foto: Federico Gambarini
Berlin Von wem erhalten Parteien eigentlich ihr Geld? Bei Spenden über 50.000 Euro lässt sich das auf der Homepage des Bundestags einsehen. Die Union erhält das meiste Spendengeld.
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Weiterleiten Drucken Von Marc Latsch
Wenn Unternehmen Geld an Parteien spenden, sorgt das stets für Diskussionen. Eine Gabe für die Demokratie nennen es die Spender gern. Kritiker vermuten den Versuch einer politischen Einflussnahme. In den vergangenen 17 Jahren sind rund 67 Millionen Euro Großspenden an deutsche Parteien geflossen. Ein Großteil davon an die Unionsparteien. Das ist das Ergebnis einer Auswertung unserer Redaktion.
Seit Juli 2002 müssen alle Parteispenden über 50 000 Euro unverzüglich beim Bundestagspräsidenten angezeigt werden. Sie werden anschließend auf der Homepage des Bundestags veröffentlicht. Und bieten bei genauerem Hinsehen so manche Erkenntnis.
Der Gesamtbetrag der Spenden ist von Jahr zu Jahr großen Schwankungen unterworfen. Wurden 2005 fast neun Millionen an Großspenden angezeigt, waren es 2012 nur knapp eineinhalb Millionen. Vor allem vor Bundestagswahlen geht die Spendenbereitschaft nach oben. Und doch lässt sich eine eher sinkende Tendenz ablesen. Vier der fünf höchsten Gesamtbeträge stammen aus den Jahren 2002 bis 2009. Nur das Wahljahr 2017 ist die Ausnahme. Für Verfassungsrechtler Hans Herbert von Arnim ist das keine Überraschung. "Man kann das ja auch daran sehen, dass verschiedene Unternehmen gar nicht mehr spenden", sagt er, zum Beispiel Daimler und Allianz.
Unternehmen steigen auf „Sponsoring um“
Keine Großspenden heißt aber nicht keine Unterstützung, auch das macht von Arnim deutlich. Viele Unternehmen steigen dafür auf "Sponsoring" um, mieten Stände auf Parteitagen und ringen dort um Einfluss. Oder bleiben mit ihren Einzelspenden unter der 50 000-Euro-Grenze, bei der der Spender sofort veröffentlicht werden muss. "Diese Grenze ist zu hoch. Auch mit geringeren Beträgen kann man Einfluss geltend machen", sagt von Arnim.
Die mit Abstand meisten Großspenden gehen an die CDU. Knapp 26 der 67 Millionen Euro erhielten die Christdemokraten. Es folgen FDP mit 11,4 und CSU mit 10,6 Millionen Euro. Weit mehr als zwei Drittel aller zwischen 2002 und 2019 deklarierten Großspenden entfallen auf diese drei Parteien. SPD (6,8 Millionen) und Grüne (2,7 Millionen) folgen mit deutlichem Abstand. Linke (175 000 Euro) und AfD (100 000 Euro) zeigten in diesem Zeitraum jeweils nur eine einzige Großspende an. "CDU, CSU und FDP gelten als besonders wirtschaftsnah. Sie erhalten daher einen besonders großen Teil der Spenden", sagt von Arnim.
Regelmäßige Großspenden
Es gibt Großspender, die treten nur ein einziges Mal auf. Und es gibt jene, auf die sich die Parteien Jahr für Jahr verlassen können. Bestes Beispiel hierfür ist der Verband der Bayerischen Metall- und Elektroindustrie. Der spendet, nicht nur, aber mit besonderer Vorliebe für die CSU. 7,2 Millionen Euro kamen so in 17 Jahren zusammen. Mehr als zwei Drittel aller CSU-Großspenden. Auch bei anderen Parteien gibt es derartige Beispiele. So traf das Daimler-Spendenaus vor allem die SPD. Zuvor erhielt sie knapp ein Drittel ihrer Großspenden von dort. | {
"pile_set_name": "OpenWebText2"
} |
Q:
alertDialog disclaimer shows on every run
I want to add an disclaimer to my app which pops up at the first start of the app. If the User declines, the app closes. If the user opens the app again the disclaimer should pop up again until the user accepts it. Once accepted it should hide and don't pop up anymore.
My problem: If I accepted the disclaimer it closes and everything is fine.
But when I launch the app it pops up again.
@Override
protected void onCreate(Bundle savedInstanceState) {
super.onCreate(savedInstanceState);
setContentView(R.layout.activity_main);
final SharedPreferences pref = getSharedPreferences("Preferences", MODE_PRIVATE);
String lver = pref.getString("Version", "");
String ver = this.getString(R.string.version);
if(ver != lver)
{
AlertDialog.Builder builder = new AlertDialog.Builder(this);
builder.setTitle("Disclaimer")
.setMessage(this.getString(R.string.disclaimer))
.setCancelable(false)
.setIcon(R.drawable.caution)
.setPositiveButton("Accept", new DialogInterface.OnClickListener() {
SharedPreferences.Editor edit = pref.edit();
public void onClick (DialogInterface dialog, int id) {
boolean accepted = true;
dialog.cancel();
if(accepted == true)
{
edit.putString("Version", this.getString(R.string.version));
edit.commit();}
}
private String getString(int version) {
// I had to create this method, cause i got an error the line above this.getstring(R.string.version)
return null;
}
})
.setNegativeButton("Decline", new DialogInterface.OnClickListener() {
public void onClick(DialogInterface dialog, int id) {
MainActivity.this.finish();
}
});
AlertDialog disc = builder.create();
disc.show();
} }
I found a quite similar question, but I couldn't solve my problem with it.
I would be really happy about an answer and if possible a good explanation in the code. Cause I wanna learn more/why it solved my problem and don't want to copy & insert a code and be happy that it works.
A:
Your problem is the if condition ver != lver, because you should check Strings for equality with equals.
if(ver.equals(lver))
Because this problem has been discussed many of times here is a link which should explain it well.
Furthermore change this part (I commentated in code)
// this doesn't belong here. get it in onClick of the positive Button
final SharedPreferences pref = getSharedPreferences("Preferences", MODE_PRIVATE);
builder.setTitle("Disclaimer")
.setMessage(this.getString(R.string.disclaimer))
.setCancelable(false)
.setIcon(R.drawable.caution)
.setPositiveButton("Accept", new DialogInterface.OnClickListener() {
SharedPreferences.Editor edit = pref.edit(); // the same as with the pef object
public void onClick (DialogInterface dialog, int id) {
boolean accepted = true; // no need for this because the if clause will always be true
dialog.cancel(); // cancel the dialog IF the job here is done
if(accepted == true)
{
edit.putString("Version", this.getString(R.string.version)); // delete the this pointer
edit.commit();}
}
// no need for this method
private String getString(int version) {
// I had to create this method, cause i got an error the line above this.getstring(R.string.version)
return null;
}
});
.setNegativeButton("Decline", new DialogInterface.OnClickListener() {
public void onClick(DialogInterface dialog, int id) {
MainActivity.this.finish();
}
});
to this
builder.setTitle("Disclaimer")
.setMessage(this.getString(R.string.disclaimer))
.setCancelable(false)
.setIcon(R.drawable.caution)
.setPositiveButton("Accept", new DialogInterface.OnClickListener() {
public void onClick (DialogInterface dialog, int id) {
SharedPreferences pref = getSharedPreferences("Preferences", MODE_PRIVATE);
SharedPreferences.Editor edit = pref.edit();
edit.putString("Version", getString(R.string.version));
edit.commit();
dialog.cancel();
}
});
.setNegativeButton("Decline", new DialogInterface.OnClickListener() {
public void onClick(DialogInterface dialog, int id) {
MainActivity.this.finish();
}
});
Now it should be fine
| {
"pile_set_name": "StackExchange"
} |
//
// Encog(tm) Core v3.3 - .Net Version (unit test)
// http://www.heatonresearch.com/encog/
//
// Copyright 2008-2014 Heaton Research, Inc.
//
// Licensed under the Apache License, Version 2.0 (the "License");
// you may not use this file except in compliance with the License.
// You may obtain a copy of the License at
//
// http://www.apache.org/licenses/LICENSE-2.0
//
// Unless required by applicable law or agreed to in writing, software
// distributed under the License is distributed on an "AS IS" BASIS,
// WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
// See the License for the specific language governing permissions and
// limitations under the License.
//
// For more information on Heaton Research copyrights, licenses
// and trademarks visit:
// http://www.heatonresearch.com/copyright
//
using System;
using System.Text;
using System.Collections.Generic;
using System.Linq;
using Microsoft.VisualStudio.TestTools.UnitTesting;
using System.IO;
using Encog.Util;
using Encog.Util.File;
using Encog.Util.CSV;
namespace Encog.App.Analyst
{
[TestClass]
public class TestAnalystRegression
{
public TempDir TEMP_DIR = new TempDir();
[TestMethod]
public void TestRegression()
{
FileInfo rawFile = TEMP_DIR.CreateFile("simple.csv");
FileInfo egaFile = TEMP_DIR.CreateFile("simple.ega");
FileInfo outputFile = TEMP_DIR.CreateFile("simple_output.csv");
FileUtil.CopyResource("Encog.Resources.simple.csv", rawFile);
FileUtil.CopyResource("Encog.Resources.simple-r.ega", egaFile);
EncogAnalyst analyst = new EncogAnalyst();
analyst.Load(egaFile);
analyst.ExecuteTask("task-full");
ReadCSV csv = new ReadCSV(outputFile.ToString(), true, CSVFormat.English);
while (csv.Next())
{
double diff = Math.Abs(csv.GetDouble(2) - csv.GetDouble(4));
Assert.IsTrue(diff < 1.5);
}
Assert.AreEqual(4, analyst.Script.Fields.Length);
Assert.AreEqual(3, analyst.Script.Fields[3].ClassMembers.Count);
csv.Close();
}
}
}
| {
"pile_set_name": "Github"
} |
/* $Id: tif_dir.c,v 1.113 2012-06-14 20:32:53 fwarmerdam Exp $ */
/*
* Copyright (c) 1988-1997 Sam Leffler
* Copyright (c) 1991-1997 Silicon Graphics, Inc.
*
* Permission to use, copy, modify, distribute, and sell this software and
* its documentation for any purpose is hereby granted without fee, provided
* that (i) the above copyright notices and this permission notice appear in
* all copies of the software and related documentation, and (ii) the names of
* Sam Leffler and Silicon Graphics may not be used in any advertising or
* publicity relating to the software without the specific, prior written
* permission of Sam Leffler and Silicon Graphics.
*
* THE SOFTWARE IS PROVIDED "AS-IS" AND WITHOUT WARRANTY OF ANY KIND,
* EXPRESS, IMPLIED OR OTHERWISE, INCLUDING WITHOUT LIMITATION, ANY
* WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE.
*
* IN NO EVENT SHALL SAM LEFFLER OR SILICON GRAPHICS BE LIABLE FOR
* ANY SPECIAL, INCIDENTAL, INDIRECT OR CONSEQUENTIAL DAMAGES OF ANY KIND,
* OR ANY DAMAGES WHATSOEVER RESULTING FROM LOSS OF USE, DATA OR PROFITS,
* WHETHER OR NOT ADVISED OF THE POSSIBILITY OF DAMAGE, AND ON ANY THEORY OF
* LIABILITY, ARISING OUT OF OR IN CONNECTION WITH THE USE OR PERFORMANCE
* OF THIS SOFTWARE.
*/
/*
* TIFF Library.
*
* Directory Tag Get & Set Routines.
* (and also some miscellaneous stuff)
*/
#include "tiffiop.h"
/*
* These are used in the backwards compatibility code...
*/
#define DATATYPE_VOID 0 /* !untyped data */
#define DATATYPE_INT 1 /* !signed integer data */
#define DATATYPE_UINT 2 /* !unsigned integer data */
#define DATATYPE_IEEEFP 3 /* !IEEE floating point data */
static void
setByteArray(void** vpp, void* vp, size_t nmemb, size_t elem_size)
{
if (*vpp)
_TIFFfree(*vpp), *vpp = 0;
if (vp) {
tmsize_t bytes = (tmsize_t)(nmemb * elem_size);
if (elem_size && bytes / elem_size == nmemb)
*vpp = (void*) _TIFFmalloc(bytes);
if (*vpp)
_TIFFmemcpy(*vpp, vp, bytes);
}
}
void _TIFFsetByteArray(void** vpp, void* vp, uint32 n)
{ setByteArray(vpp, vp, n, 1); }
void _TIFFsetString(char** cpp, char* cp)
{ setByteArray((void**) cpp, (void*) cp, strlen(cp)+1, 1); }
void _TIFFsetNString(char** cpp, char* cp, uint32 n)
{ setByteArray((void**) cpp, (void*) cp, n, 1); }
void _TIFFsetShortArray(uint16** wpp, uint16* wp, uint32 n)
{ setByteArray((void**) wpp, (void*) wp, n, sizeof (uint16)); }
void _TIFFsetLongArray(uint32** lpp, uint32* lp, uint32 n)
{ setByteArray((void**) lpp, (void*) lp, n, sizeof (uint32)); }
void _TIFFsetLong8Array(uint64** lpp, uint64* lp, uint32 n)
{ setByteArray((void**) lpp, (void*) lp, n, sizeof (uint64)); }
void _TIFFsetFloatArray(float** fpp, float* fp, uint32 n)
{ setByteArray((void**) fpp, (void*) fp, n, sizeof (float)); }
void _TIFFsetDoubleArray(double** dpp, double* dp, uint32 n)
{ setByteArray((void**) dpp, (void*) dp, n, sizeof (double)); }
static void
setDoubleArrayOneValue(double** vpp, double value, size_t nmemb)
{
if (*vpp)
_TIFFfree(*vpp);
*vpp = _TIFFmalloc(nmemb*sizeof(double));
if (*vpp)
{
while (nmemb--)
((double*)*vpp)[nmemb] = value;
}
}
/*
* Install extra samples information.
*/
static int
setExtraSamples(TIFFDirectory* td, va_list ap, uint32* v)
{
/* XXX: Unassociated alpha data == 999 is a known Corel Draw bug, see below */
#define EXTRASAMPLE_COREL_UNASSALPHA 999
uint16* va;
uint32 i;
*v = (uint16) va_arg(ap, uint16_vap);
if ((uint16) *v > td->td_samplesperpixel)
return 0;
va = va_arg(ap, uint16*);
if (*v > 0 && va == NULL) /* typically missing param */
return 0;
for (i = 0; i < *v; i++) {
if (va[i] > EXTRASAMPLE_UNASSALPHA) {
/*
* XXX: Corel Draw is known to produce incorrect
* ExtraSamples tags which must be patched here if we
* want to be able to open some of the damaged TIFF
* files:
*/
if (va[i] == EXTRASAMPLE_COREL_UNASSALPHA)
va[i] = EXTRASAMPLE_UNASSALPHA;
else
return 0;
}
}
td->td_extrasamples = (uint16) *v;
_TIFFsetShortArray(&td->td_sampleinfo, va, td->td_extrasamples);
return 1;
#undef EXTRASAMPLE_COREL_UNASSALPHA
}
/*
* Confirm we have "samplesperpixel" ink names separated by \0. Returns
* zero if the ink names are not as expected.
*/
static uint32
checkInkNamesString(TIFF* tif, uint32 slen, const char* s)
{
TIFFDirectory* td = &tif->tif_dir;
uint16 i = td->td_samplesperpixel;
if (slen > 0) {
const char* ep = s+slen;
const char* cp = s;
for (; i > 0; i--) {
for (; cp < ep && *cp != '\0'; cp++) {}
if (cp >= ep)
goto bad;
cp++; /* skip \0 */
}
return ((uint32)(cp-s));
}
bad:
TIFFErrorExt(tif->tif_clientdata, "TIFFSetField",
"%s: Invalid InkNames value; expecting %d names, found %d",
tif->tif_name,
td->td_samplesperpixel,
td->td_samplesperpixel-i);
return (0);
}
static int
_TIFFVSetField(TIFF* tif, uint32 tag, va_list ap)
{
static const char module[] = "_TIFFVSetField";
TIFFDirectory* td = &tif->tif_dir;
int status = 1;
uint32 v32, i, v;
char* s;
const TIFFField *fip = TIFFFindField(tif, tag, TIFF_ANY);
uint32 standard_tag = tag;
/*
* We want to force the custom code to be used for custom
* fields even if the tag happens to match a well known
* one - important for reinterpreted handling of standard
* tag values in custom directories (ie. EXIF)
*/
if (fip->field_bit == FIELD_CUSTOM) {
standard_tag = 0;
}
switch (standard_tag) {
case TIFFTAG_SUBFILETYPE:
td->td_subfiletype = (uint32) va_arg(ap, uint32);
break;
case TIFFTAG_IMAGEWIDTH:
td->td_imagewidth = (uint32) va_arg(ap, uint32);
break;
case TIFFTAG_IMAGELENGTH:
td->td_imagelength = (uint32) va_arg(ap, uint32);
break;
case TIFFTAG_BITSPERSAMPLE:
td->td_bitspersample = (uint16) va_arg(ap, uint16_vap);
/*
* If the data require post-decoding processing to byte-swap
* samples, set it up here. Note that since tags are required
* to be ordered, compression code can override this behaviour
* in the setup method if it wants to roll the post decoding
* work in with its normal work.
*/
if (tif->tif_flags & TIFF_SWAB) {
if (td->td_bitspersample == 8)
tif->tif_postdecode = _TIFFNoPostDecode;
else if (td->td_bitspersample == 16)
tif->tif_postdecode = _TIFFSwab16BitData;
else if (td->td_bitspersample == 24)
tif->tif_postdecode = _TIFFSwab24BitData;
else if (td->td_bitspersample == 32)
tif->tif_postdecode = _TIFFSwab32BitData;
else if (td->td_bitspersample == 64)
tif->tif_postdecode = _TIFFSwab64BitData;
else if (td->td_bitspersample == 128) /* two 64's */
tif->tif_postdecode = _TIFFSwab64BitData;
}
break;
case TIFFTAG_COMPRESSION:
v = (uint16) va_arg(ap, uint16_vap);
/*
* If we're changing the compression scheme, the notify the
* previous module so that it can cleanup any state it's
* setup.
*/
if (TIFFFieldSet(tif, FIELD_COMPRESSION)) {
if ((uint32)td->td_compression == v)
break;
(*tif->tif_cleanup)(tif);
tif->tif_flags &= ~TIFF_CODERSETUP;
}
/*
* Setup new compression routine state.
*/
if( (status = TIFFSetCompressionScheme(tif, v)) != 0 )
td->td_compression = (uint16) v;
else
status = 0;
break;
case TIFFTAG_PHOTOMETRIC:
td->td_photometric = (uint16) va_arg(ap, uint16_vap);
break;
case TIFFTAG_THRESHHOLDING:
td->td_threshholding = (uint16) va_arg(ap, uint16_vap);
break;
case TIFFTAG_FILLORDER:
v = (uint16) va_arg(ap, uint16_vap);
if (v != FILLORDER_LSB2MSB && v != FILLORDER_MSB2LSB)
goto badvalue;
td->td_fillorder = (uint16) v;
break;
case TIFFTAG_ORIENTATION:
v = (uint16) va_arg(ap, uint16_vap);
if (v < ORIENTATION_TOPLEFT || ORIENTATION_LEFTBOT < v)
goto badvalue;
else
td->td_orientation = (uint16) v;
break;
case TIFFTAG_SAMPLESPERPIXEL:
v = (uint16) va_arg(ap, uint16_vap);
if (v == 0)
goto badvalue;
td->td_samplesperpixel = (uint16) v;
break;
case TIFFTAG_ROWSPERSTRIP:
v32 = (uint32) va_arg(ap, uint32);
if (v32 == 0)
goto badvalue32;
td->td_rowsperstrip = v32;
if (!TIFFFieldSet(tif, FIELD_TILEDIMENSIONS)) {
td->td_tilelength = v32;
td->td_tilewidth = td->td_imagewidth;
}
break;
case TIFFTAG_MINSAMPLEVALUE:
td->td_minsamplevalue = (uint16) va_arg(ap, uint16_vap);
break;
case TIFFTAG_MAXSAMPLEVALUE:
td->td_maxsamplevalue = (uint16) va_arg(ap, uint16_vap);
break;
case TIFFTAG_SMINSAMPLEVALUE:
if (tif->tif_flags & TIFF_PERSAMPLE)
_TIFFsetDoubleArray(&td->td_sminsamplevalue, va_arg(ap, double*), td->td_samplesperpixel);
else
setDoubleArrayOneValue(&td->td_sminsamplevalue, va_arg(ap, double), td->td_samplesperpixel);
break;
case TIFFTAG_SMAXSAMPLEVALUE:
if (tif->tif_flags & TIFF_PERSAMPLE)
_TIFFsetDoubleArray(&td->td_smaxsamplevalue, va_arg(ap, double*), td->td_samplesperpixel);
else
setDoubleArrayOneValue(&td->td_smaxsamplevalue, va_arg(ap, double), td->td_samplesperpixel);
break;
case TIFFTAG_XRESOLUTION:
td->td_xresolution = (float) va_arg(ap, double);
break;
case TIFFTAG_YRESOLUTION:
td->td_yresolution = (float) va_arg(ap, double);
break;
case TIFFTAG_PLANARCONFIG:
v = (uint16) va_arg(ap, uint16_vap);
if (v != PLANARCONFIG_CONTIG && v != PLANARCONFIG_SEPARATE)
goto badvalue;
td->td_planarconfig = (uint16) v;
break;
case TIFFTAG_XPOSITION:
td->td_xposition = (float) va_arg(ap, double);
break;
case TIFFTAG_YPOSITION:
td->td_yposition = (float) va_arg(ap, double);
break;
case TIFFTAG_RESOLUTIONUNIT:
v = (uint16) va_arg(ap, uint16_vap);
if (v < RESUNIT_NONE || RESUNIT_CENTIMETER < v)
goto badvalue;
td->td_resolutionunit = (uint16) v;
break;
case TIFFTAG_PAGENUMBER:
td->td_pagenumber[0] = (uint16) va_arg(ap, uint16_vap);
td->td_pagenumber[1] = (uint16) va_arg(ap, uint16_vap);
break;
case TIFFTAG_HALFTONEHINTS:
td->td_halftonehints[0] = (uint16) va_arg(ap, uint16_vap);
td->td_halftonehints[1] = (uint16) va_arg(ap, uint16_vap);
break;
case TIFFTAG_COLORMAP:
v32 = (uint32)(1L<<td->td_bitspersample);
_TIFFsetShortArray(&td->td_colormap[0], va_arg(ap, uint16*), v32);
_TIFFsetShortArray(&td->td_colormap[1], va_arg(ap, uint16*), v32);
_TIFFsetShortArray(&td->td_colormap[2], va_arg(ap, uint16*), v32);
break;
case TIFFTAG_EXTRASAMPLES:
if (!setExtraSamples(td, ap, &v))
goto badvalue;
break;
case TIFFTAG_MATTEING:
td->td_extrasamples = (((uint16) va_arg(ap, uint16_vap)) != 0);
if (td->td_extrasamples) {
uint16 sv = EXTRASAMPLE_ASSOCALPHA;
_TIFFsetShortArray(&td->td_sampleinfo, &sv, 1);
}
break;
case TIFFTAG_TILEWIDTH:
v32 = (uint32) va_arg(ap, uint32);
if (v32 % 16) {
if (tif->tif_mode != O_RDONLY)
goto badvalue32;
TIFFWarningExt(tif->tif_clientdata, tif->tif_name,
"Nonstandard tile width %d, convert file", v32);
}
td->td_tilewidth = v32;
tif->tif_flags |= TIFF_ISTILED;
break;
case TIFFTAG_TILELENGTH:
v32 = (uint32) va_arg(ap, uint32);
if (v32 % 16) {
if (tif->tif_mode != O_RDONLY)
goto badvalue32;
TIFFWarningExt(tif->tif_clientdata, tif->tif_name,
"Nonstandard tile length %d, convert file", v32);
}
td->td_tilelength = v32;
tif->tif_flags |= TIFF_ISTILED;
break;
case TIFFTAG_TILEDEPTH:
v32 = (uint32) va_arg(ap, uint32);
if (v32 == 0)
goto badvalue32;
td->td_tiledepth = v32;
break;
case TIFFTAG_DATATYPE:
v = (uint16) va_arg(ap, uint16_vap);
switch (v) {
case DATATYPE_VOID: v = SAMPLEFORMAT_VOID; break;
case DATATYPE_INT: v = SAMPLEFORMAT_INT; break;
case DATATYPE_UINT: v = SAMPLEFORMAT_UINT; break;
case DATATYPE_IEEEFP: v = SAMPLEFORMAT_IEEEFP;break;
default: goto badvalue;
}
td->td_sampleformat = (uint16) v;
break;
case TIFFTAG_SAMPLEFORMAT:
v = (uint16) va_arg(ap, uint16_vap);
if (v < SAMPLEFORMAT_UINT || SAMPLEFORMAT_COMPLEXIEEEFP < v)
goto badvalue;
td->td_sampleformat = (uint16) v;
/* Try to fix up the SWAB function for complex data. */
if( td->td_sampleformat == SAMPLEFORMAT_COMPLEXINT
&& td->td_bitspersample == 32
&& tif->tif_postdecode == _TIFFSwab32BitData )
tif->tif_postdecode = _TIFFSwab16BitData;
else if( (td->td_sampleformat == SAMPLEFORMAT_COMPLEXINT
|| td->td_sampleformat == SAMPLEFORMAT_COMPLEXIEEEFP)
&& td->td_bitspersample == 64
&& tif->tif_postdecode == _TIFFSwab64BitData )
tif->tif_postdecode = _TIFFSwab32BitData;
break;
case TIFFTAG_IMAGEDEPTH:
td->td_imagedepth = (uint32) va_arg(ap, uint32);
break;
case TIFFTAG_SUBIFD:
if ((tif->tif_flags & TIFF_INSUBIFD) == 0) {
td->td_nsubifd = (uint16) va_arg(ap, uint16_vap);
_TIFFsetLong8Array(&td->td_subifd, (uint64*) va_arg(ap, uint64*),
(long) td->td_nsubifd);
} else {
TIFFErrorExt(tif->tif_clientdata, module,
"%s: Sorry, cannot nest SubIFDs",
tif->tif_name);
status = 0;
}
break;
case TIFFTAG_YCBCRPOSITIONING:
td->td_ycbcrpositioning = (uint16) va_arg(ap, uint16_vap);
break;
case TIFFTAG_YCBCRSUBSAMPLING:
td->td_ycbcrsubsampling[0] = (uint16) va_arg(ap, uint16_vap);
td->td_ycbcrsubsampling[1] = (uint16) va_arg(ap, uint16_vap);
break;
case TIFFTAG_TRANSFERFUNCTION:
v = (td->td_samplesperpixel - td->td_extrasamples) > 1 ? 3 : 1;
for (i = 0; i < v; i++)
_TIFFsetShortArray(&td->td_transferfunction[i],
va_arg(ap, uint16*), 1L<<td->td_bitspersample);
break;
case TIFFTAG_REFERENCEBLACKWHITE:
/* XXX should check for null range */
_TIFFsetFloatArray(&td->td_refblackwhite, va_arg(ap, float*), 6);
break;
case TIFFTAG_INKNAMES:
v = (uint16) va_arg(ap, uint16_vap);
s = va_arg(ap, char*);
v = checkInkNamesString(tif, v, s);
status = v > 0;
if( v > 0 ) {
_TIFFsetNString(&td->td_inknames, s, v);
td->td_inknameslen = v;
}
break;
case TIFFTAG_PERSAMPLE:
v = (uint16) va_arg(ap, uint16_vap);
if( v == PERSAMPLE_MULTI )
tif->tif_flags |= TIFF_PERSAMPLE;
else
tif->tif_flags &= ~TIFF_PERSAMPLE;
break;
default: {
TIFFTagValue *tv;
int tv_size, iCustom;
/*
* This can happen if multiple images are open with different
* codecs which have private tags. The global tag information
* table may then have tags that are valid for one file but not
* the other. If the client tries to set a tag that is not valid
* for the image's codec then we'll arrive here. This
* happens, for example, when tiffcp is used to convert between
* compression schemes and codec-specific tags are blindly copied.
*/
if(fip == NULL || fip->field_bit != FIELD_CUSTOM) {
TIFFErrorExt(tif->tif_clientdata, module,
"%s: Invalid %stag \"%s\" (not supported by codec)",
tif->tif_name, isPseudoTag(tag) ? "pseudo-" : "",
fip ? fip->field_name : "Unknown");
status = 0;
break;
}
/*
* Find the existing entry for this custom value.
*/
tv = NULL;
for (iCustom = 0; iCustom < td->td_customValueCount; iCustom++) {
if (td->td_customValues[iCustom].info->field_tag == tag) {
tv = td->td_customValues + iCustom;
if (tv->value != NULL) {
_TIFFfree(tv->value);
tv->value = NULL;
}
break;
}
}
/*
* Grow the custom list if the entry was not found.
*/
if(tv == NULL) {
TIFFTagValue *new_customValues;
td->td_customValueCount++;
new_customValues = (TIFFTagValue *)
_TIFFrealloc(td->td_customValues,
sizeof(TIFFTagValue) * td->td_customValueCount);
if (!new_customValues) {
TIFFErrorExt(tif->tif_clientdata, module,
"%s: Failed to allocate space for list of custom values",
tif->tif_name);
status = 0;
goto end;
}
td->td_customValues = new_customValues;
tv = td->td_customValues + (td->td_customValueCount - 1);
tv->info = fip;
tv->value = NULL;
tv->count = 0;
}
/*
* Set custom value ... save a copy of the custom tag value.
*/
tv_size = _TIFFDataSize(fip->field_type);
if (tv_size == 0) {
status = 0;
TIFFErrorExt(tif->tif_clientdata, module,
"%s: Bad field type %d for \"%s\"",
tif->tif_name, fip->field_type,
fip->field_name);
goto end;
}
if (fip->field_type == TIFF_ASCII)
{
uint32 ma;
char* mb;
if (fip->field_passcount)
{
assert(fip->field_writecount==TIFF_VARIABLE2);
ma=(uint32)va_arg(ap,uint32);
mb=(char*)va_arg(ap,char*);
}
else
{
mb=(char*)va_arg(ap,char*);
ma=(uint32)(strlen(mb)+1);
}
tv->count=ma;
setByteArray(&tv->value,mb,ma,1);
}
else
{
if (fip->field_passcount) {
if (fip->field_writecount == TIFF_VARIABLE2)
tv->count = (uint32) va_arg(ap, uint32);
else
tv->count = (int) va_arg(ap, int);
} else if (fip->field_writecount == TIFF_VARIABLE
|| fip->field_writecount == TIFF_VARIABLE2)
tv->count = 1;
else if (fip->field_writecount == TIFF_SPP)
tv->count = td->td_samplesperpixel;
else
tv->count = fip->field_writecount;
if (tv->count == 0) {
status = 0;
TIFFErrorExt(tif->tif_clientdata, module,
"%s: Null count for \"%s\" (type "
"%d, writecount %d, passcount %d)",
tif->tif_name,
fip->field_name,
fip->field_type,
fip->field_writecount,
fip->field_passcount);
goto end;
}
tv->value = _TIFFCheckMalloc(tif, tv->count, tv_size,
"custom tag binary object");
if (!tv->value) {
status = 0;
goto end;
}
if (fip->field_tag == TIFFTAG_DOTRANGE
&& strcmp(fip->field_name,"DotRange") == 0) {
/* TODO: This is an evil exception and should not have been
handled this way ... likely best if we move it into
the directory structure with an explicit field in
libtiff 4.1 and assign it a FIELD_ value */
uint16 v[2];
v[0] = (uint16)va_arg(ap, int);
v[1] = (uint16)va_arg(ap, int);
_TIFFmemcpy(tv->value, &v, 4);
}
else if (fip->field_passcount
|| fip->field_writecount == TIFF_VARIABLE
|| fip->field_writecount == TIFF_VARIABLE2
|| fip->field_writecount == TIFF_SPP
|| tv->count > 1) {
_TIFFmemcpy(tv->value, va_arg(ap, void *),
tv->count * tv_size);
} else {
char *val = (char *)tv->value;
assert( tv->count == 1 );
switch (fip->field_type) {
case TIFF_BYTE:
case TIFF_UNDEFINED:
{
uint8 v = (uint8)va_arg(ap, int);
_TIFFmemcpy(val, &v, tv_size);
}
break;
case TIFF_SBYTE:
{
int8 v = (int8)va_arg(ap, int);
_TIFFmemcpy(val, &v, tv_size);
}
break;
case TIFF_SHORT:
{
uint16 v = (uint16)va_arg(ap, int);
_TIFFmemcpy(val, &v, tv_size);
}
break;
case TIFF_SSHORT:
{
int16 v = (int16)va_arg(ap, int);
_TIFFmemcpy(val, &v, tv_size);
}
break;
case TIFF_LONG:
case TIFF_IFD:
{
uint32 v = va_arg(ap, uint32);
_TIFFmemcpy(val, &v, tv_size);
}
break;
case TIFF_SLONG:
{
int32 v = va_arg(ap, int32);
_TIFFmemcpy(val, &v, tv_size);
}
break;
case TIFF_LONG8:
case TIFF_IFD8:
{
uint64 v = va_arg(ap, uint64);
_TIFFmemcpy(val, &v, tv_size);
}
break;
case TIFF_SLONG8:
{
int64 v = va_arg(ap, int64);
_TIFFmemcpy(val, &v, tv_size);
}
break;
case TIFF_RATIONAL:
case TIFF_SRATIONAL:
case TIFF_FLOAT:
{
float v = (float)va_arg(ap, double);
_TIFFmemcpy(val, &v, tv_size);
}
break;
case TIFF_DOUBLE:
{
double v = va_arg(ap, double);
_TIFFmemcpy(val, &v, tv_size);
}
break;
default:
_TIFFmemset(val, 0, tv_size);
status = 0;
break;
}
}
}
}
}
if (status) {
const TIFFField* fip=TIFFFieldWithTag(tif,tag);
if (fip)
TIFFSetFieldBit(tif, fip->field_bit);
tif->tif_flags |= TIFF_DIRTYDIRECT;
}
end:
va_end(ap);
return (status);
badvalue:
{
const TIFFField* fip=TIFFFieldWithTag(tif,tag);
TIFFErrorExt(tif->tif_clientdata, module,
"%s: Bad value %u for \"%s\" tag",
tif->tif_name, v,
fip ? fip->field_name : "Unknown");
va_end(ap);
}
return (0);
badvalue32:
{
const TIFFField* fip=TIFFFieldWithTag(tif,tag);
TIFFErrorExt(tif->tif_clientdata, module,
"%s: Bad value %u for \"%s\" tag",
tif->tif_name, v32,
fip ? fip->field_name : "Unknown");
va_end(ap);
}
return (0);
}
/*
* Return 1/0 according to whether or not
* it is permissible to set the tag's value.
* Note that we allow ImageLength to be changed
* so that we can append and extend to images.
* Any other tag may not be altered once writing
* has commenced, unless its value has no effect
* on the format of the data that is written.
*/
static int
OkToChangeTag(TIFF* tif, uint32 tag)
{
const TIFFField* fip = TIFFFindField(tif, tag, TIFF_ANY);
if (!fip) { /* unknown tag */
TIFFErrorExt(tif->tif_clientdata, "TIFFSetField", "%s: Unknown %stag %u",
tif->tif_name, isPseudoTag(tag) ? "pseudo-" : "", tag);
return (0);
}
if (tag != TIFFTAG_IMAGELENGTH && (tif->tif_flags & TIFF_BEENWRITING) &&
!fip->field_oktochange) {
/*
* Consult info table to see if tag can be changed
* after we've started writing. We only allow changes
* to those tags that don't/shouldn't affect the
* compression and/or format of the data.
*/
TIFFErrorExt(tif->tif_clientdata, "TIFFSetField",
"%s: Cannot modify tag \"%s\" while writing",
tif->tif_name, fip->field_name);
return (0);
}
return (1);
}
/*
* Record the value of a field in the
* internal directory structure. The
* field will be written to the file
* when/if the directory structure is
* updated.
*/
int
TIFFSetField(TIFF* tif, uint32 tag, ...)
{
va_list ap;
int status;
va_start(ap, tag);
status = TIFFVSetField(tif, tag, ap);
va_end(ap);
return (status);
}
/*
* Clear the contents of the field in the internal structure.
*/
int
TIFFUnsetField(TIFF* tif, uint32 tag)
{
const TIFFField *fip = TIFFFieldWithTag(tif, tag);
TIFFDirectory* td = &tif->tif_dir;
if( !fip )
return 0;
if( fip->field_bit != FIELD_CUSTOM )
TIFFClrFieldBit(tif, fip->field_bit);
else
{
TIFFTagValue *tv = NULL;
int i;
for (i = 0; i < td->td_customValueCount; i++) {
tv = td->td_customValues + i;
if( tv->info->field_tag == tag )
break;
}
if( i < td->td_customValueCount )
{
_TIFFfree(tv->value);
for( ; i < td->td_customValueCount-1; i++) {
td->td_customValues[i] = td->td_customValues[i+1];
}
td->td_customValueCount--;
}
}
tif->tif_flags |= TIFF_DIRTYDIRECT;
return (1);
}
/*
* Like TIFFSetField, but taking a varargs
* parameter list. This routine is useful
* for building higher-level interfaces on
* top of the library.
*/
int
TIFFVSetField(TIFF* tif, uint32 tag, va_list ap)
{
return OkToChangeTag(tif, tag) ?
(*tif->tif_tagmethods.vsetfield)(tif, tag, ap) : 0;
}
static int
_TIFFVGetField(TIFF* tif, uint32 tag, va_list ap)
{
TIFFDirectory* td = &tif->tif_dir;
int ret_val = 1;
uint32 standard_tag = tag;
const TIFFField* fip = TIFFFindField(tif, tag, TIFF_ANY);
/*
* We want to force the custom code to be used for custom
* fields even if the tag happens to match a well known
* one - important for reinterpreted handling of standard
* tag values in custom directories (ie. EXIF)
*/
if (fip->field_bit == FIELD_CUSTOM) {
standard_tag = 0;
}
switch (standard_tag) {
case TIFFTAG_SUBFILETYPE:
*va_arg(ap, uint32*) = td->td_subfiletype;
break;
case TIFFTAG_IMAGEWIDTH:
*va_arg(ap, uint32*) = td->td_imagewidth;
break;
case TIFFTAG_IMAGELENGTH:
*va_arg(ap, uint32*) = td->td_imagelength;
break;
case TIFFTAG_BITSPERSAMPLE:
*va_arg(ap, uint16*) = td->td_bitspersample;
break;
case TIFFTAG_COMPRESSION:
*va_arg(ap, uint16*) = td->td_compression;
break;
case TIFFTAG_PHOTOMETRIC:
*va_arg(ap, uint16*) = td->td_photometric;
break;
case TIFFTAG_THRESHHOLDING:
*va_arg(ap, uint16*) = td->td_threshholding;
break;
case TIFFTAG_FILLORDER:
*va_arg(ap, uint16*) = td->td_fillorder;
break;
case TIFFTAG_ORIENTATION:
*va_arg(ap, uint16*) = td->td_orientation;
break;
case TIFFTAG_SAMPLESPERPIXEL:
*va_arg(ap, uint16*) = td->td_samplesperpixel;
break;
case TIFFTAG_ROWSPERSTRIP:
*va_arg(ap, uint32*) = td->td_rowsperstrip;
break;
case TIFFTAG_MINSAMPLEVALUE:
*va_arg(ap, uint16*) = td->td_minsamplevalue;
break;
case TIFFTAG_MAXSAMPLEVALUE:
*va_arg(ap, uint16*) = td->td_maxsamplevalue;
break;
case TIFFTAG_SMINSAMPLEVALUE:
if (tif->tif_flags & TIFF_PERSAMPLE)
*va_arg(ap, double**) = td->td_sminsamplevalue;
else
{
/* libtiff historially treats this as a single value. */
uint16 i;
double v = td->td_sminsamplevalue[0];
for (i=1; i < td->td_samplesperpixel; ++i)
if( td->td_sminsamplevalue[i] < v )
v = td->td_sminsamplevalue[i];
*va_arg(ap, double*) = v;
}
break;
case TIFFTAG_SMAXSAMPLEVALUE:
if (tif->tif_flags & TIFF_PERSAMPLE)
*va_arg(ap, double**) = td->td_smaxsamplevalue;
else
{
/* libtiff historially treats this as a single value. */
uint16 i;
double v = td->td_smaxsamplevalue[0];
for (i=1; i < td->td_samplesperpixel; ++i)
if( td->td_smaxsamplevalue[i] > v )
v = td->td_smaxsamplevalue[i];
*va_arg(ap, double*) = v;
}
break;
case TIFFTAG_XRESOLUTION:
*va_arg(ap, float*) = td->td_xresolution;
break;
case TIFFTAG_YRESOLUTION:
*va_arg(ap, float*) = td->td_yresolution;
break;
case TIFFTAG_PLANARCONFIG:
*va_arg(ap, uint16*) = td->td_planarconfig;
break;
case TIFFTAG_XPOSITION:
*va_arg(ap, float*) = td->td_xposition;
break;
case TIFFTAG_YPOSITION:
*va_arg(ap, float*) = td->td_yposition;
break;
case TIFFTAG_RESOLUTIONUNIT:
*va_arg(ap, uint16*) = td->td_resolutionunit;
break;
case TIFFTAG_PAGENUMBER:
*va_arg(ap, uint16*) = td->td_pagenumber[0];
*va_arg(ap, uint16*) = td->td_pagenumber[1];
break;
case TIFFTAG_HALFTONEHINTS:
*va_arg(ap, uint16*) = td->td_halftonehints[0];
*va_arg(ap, uint16*) = td->td_halftonehints[1];
break;
case TIFFTAG_COLORMAP:
*va_arg(ap, uint16**) = td->td_colormap[0];
*va_arg(ap, uint16**) = td->td_colormap[1];
*va_arg(ap, uint16**) = td->td_colormap[2];
break;
case TIFFTAG_STRIPOFFSETS:
case TIFFTAG_TILEOFFSETS:
_TIFFFillStriles( tif );
*va_arg(ap, uint64**) = td->td_stripoffset;
break;
case TIFFTAG_STRIPBYTECOUNTS:
case TIFFTAG_TILEBYTECOUNTS:
_TIFFFillStriles( tif );
*va_arg(ap, uint64**) = td->td_stripbytecount;
break;
case TIFFTAG_MATTEING:
*va_arg(ap, uint16*) =
(td->td_extrasamples == 1 &&
td->td_sampleinfo[0] == EXTRASAMPLE_ASSOCALPHA);
break;
case TIFFTAG_EXTRASAMPLES:
*va_arg(ap, uint16*) = td->td_extrasamples;
*va_arg(ap, uint16**) = td->td_sampleinfo;
break;
case TIFFTAG_TILEWIDTH:
*va_arg(ap, uint32*) = td->td_tilewidth;
break;
case TIFFTAG_TILELENGTH:
*va_arg(ap, uint32*) = td->td_tilelength;
break;
case TIFFTAG_TILEDEPTH:
*va_arg(ap, uint32*) = td->td_tiledepth;
break;
case TIFFTAG_DATATYPE:
switch (td->td_sampleformat) {
case SAMPLEFORMAT_UINT:
*va_arg(ap, uint16*) = DATATYPE_UINT;
break;
case SAMPLEFORMAT_INT:
*va_arg(ap, uint16*) = DATATYPE_INT;
break;
case SAMPLEFORMAT_IEEEFP:
*va_arg(ap, uint16*) = DATATYPE_IEEEFP;
break;
case SAMPLEFORMAT_VOID:
*va_arg(ap, uint16*) = DATATYPE_VOID;
break;
}
break;
case TIFFTAG_SAMPLEFORMAT:
*va_arg(ap, uint16*) = td->td_sampleformat;
break;
case TIFFTAG_IMAGEDEPTH:
*va_arg(ap, uint32*) = td->td_imagedepth;
break;
case TIFFTAG_SUBIFD:
*va_arg(ap, uint16*) = td->td_nsubifd;
*va_arg(ap, uint64**) = td->td_subifd;
break;
case TIFFTAG_YCBCRPOSITIONING:
*va_arg(ap, uint16*) = td->td_ycbcrpositioning;
break;
case TIFFTAG_YCBCRSUBSAMPLING:
*va_arg(ap, uint16*) = td->td_ycbcrsubsampling[0];
*va_arg(ap, uint16*) = td->td_ycbcrsubsampling[1];
break;
case TIFFTAG_TRANSFERFUNCTION:
*va_arg(ap, uint16**) = td->td_transferfunction[0];
if (td->td_samplesperpixel - td->td_extrasamples > 1) {
*va_arg(ap, uint16**) = td->td_transferfunction[1];
*va_arg(ap, uint16**) = td->td_transferfunction[2];
}
break;
case TIFFTAG_REFERENCEBLACKWHITE:
*va_arg(ap, float**) = td->td_refblackwhite;
break;
case TIFFTAG_INKNAMES:
*va_arg(ap, char**) = td->td_inknames;
break;
default:
{
int i;
/*
* This can happen if multiple images are open
* with different codecs which have private
* tags. The global tag information table may
* then have tags that are valid for one file
* but not the other. If the client tries to
* get a tag that is not valid for the image's
* codec then we'll arrive here.
*/
if( fip == NULL || fip->field_bit != FIELD_CUSTOM )
{
TIFFErrorExt(tif->tif_clientdata, "_TIFFVGetField",
"%s: Invalid %stag \"%s\" "
"(not supported by codec)",
tif->tif_name,
isPseudoTag(tag) ? "pseudo-" : "",
fip ? fip->field_name : "Unknown");
ret_val = 0;
break;
}
/*
* Do we have a custom value?
*/
ret_val = 0;
for (i = 0; i < td->td_customValueCount; i++) {
TIFFTagValue *tv = td->td_customValues + i;
if (tv->info->field_tag != tag)
continue;
if (fip->field_passcount) {
if (fip->field_readcount == TIFF_VARIABLE2)
*va_arg(ap, uint32*) = (uint32)tv->count;
else /* Assume TIFF_VARIABLE */
*va_arg(ap, uint16*) = (uint16)tv->count;
*va_arg(ap, void **) = tv->value;
ret_val = 1;
} else if (fip->field_tag == TIFFTAG_DOTRANGE
&& strcmp(fip->field_name,"DotRange") == 0) {
/* TODO: This is an evil exception and should not have been
handled this way ... likely best if we move it into
the directory structure with an explicit field in
libtiff 4.1 and assign it a FIELD_ value */
*va_arg(ap, uint16*) = ((uint16 *)tv->value)[0];
*va_arg(ap, uint16*) = ((uint16 *)tv->value)[1];
ret_val = 1;
} else {
if (fip->field_type == TIFF_ASCII
|| fip->field_readcount == TIFF_VARIABLE
|| fip->field_readcount == TIFF_VARIABLE2
|| fip->field_readcount == TIFF_SPP
|| tv->count > 1) {
*va_arg(ap, void **) = tv->value;
ret_val = 1;
} else {
char *val = (char *)tv->value;
assert( tv->count == 1 );
switch (fip->field_type) {
case TIFF_BYTE:
case TIFF_UNDEFINED:
*va_arg(ap, uint8*) =
*(uint8 *)val;
ret_val = 1;
break;
case TIFF_SBYTE:
*va_arg(ap, int8*) =
*(int8 *)val;
ret_val = 1;
break;
case TIFF_SHORT:
*va_arg(ap, uint16*) =
*(uint16 *)val;
ret_val = 1;
break;
case TIFF_SSHORT:
*va_arg(ap, int16*) =
*(int16 *)val;
ret_val = 1;
break;
case TIFF_LONG:
case TIFF_IFD:
*va_arg(ap, uint32*) =
*(uint32 *)val;
ret_val = 1;
break;
case TIFF_SLONG:
*va_arg(ap, int32*) =
*(int32 *)val;
ret_val = 1;
break;
case TIFF_LONG8:
case TIFF_IFD8:
*va_arg(ap, uint64*) =
*(uint64 *)val;
ret_val = 1;
break;
case TIFF_SLONG8:
*va_arg(ap, int64*) =
*(int64 *)val;
ret_val = 1;
break;
case TIFF_RATIONAL:
case TIFF_SRATIONAL:
case TIFF_FLOAT:
*va_arg(ap, float*) =
*(float *)val;
ret_val = 1;
break;
case TIFF_DOUBLE:
*va_arg(ap, double*) =
*(double *)val;
ret_val = 1;
break;
default:
ret_val = 0;
break;
}
}
}
break;
}
}
}
return(ret_val);
}
/*
* Return the value of a field in the
* internal directory structure.
*/
int
TIFFGetField(TIFF* tif, uint32 tag, ...)
{
int status;
va_list ap;
va_start(ap, tag);
status = TIFFVGetField(tif, tag, ap);
va_end(ap);
return (status);
}
/*
* Like TIFFGetField, but taking a varargs
* parameter list. This routine is useful
* for building higher-level interfaces on
* top of the library.
*/
int
TIFFVGetField(TIFF* tif, uint32 tag, va_list ap)
{
const TIFFField* fip = TIFFFindField(tif, tag, TIFF_ANY);
return (fip && (isPseudoTag(tag) || TIFFFieldSet(tif, fip->field_bit)) ?
(*tif->tif_tagmethods.vgetfield)(tif, tag, ap) : 0);
}
#define CleanupField(member) { \
if (td->member) { \
_TIFFfree(td->member); \
td->member = 0; \
} \
}
/*
* Release storage associated with a directory.
*/
void
TIFFFreeDirectory(TIFF* tif)
{
TIFFDirectory *td = &tif->tif_dir;
int i;
_TIFFmemset(td->td_fieldsset, 0, FIELD_SETLONGS);
CleanupField(td_sminsamplevalue);
CleanupField(td_smaxsamplevalue);
CleanupField(td_colormap[0]);
CleanupField(td_colormap[1]);
CleanupField(td_colormap[2]);
CleanupField(td_sampleinfo);
CleanupField(td_subifd);
CleanupField(td_inknames);
CleanupField(td_refblackwhite);
CleanupField(td_transferfunction[0]);
CleanupField(td_transferfunction[1]);
CleanupField(td_transferfunction[2]);
CleanupField(td_stripoffset);
CleanupField(td_stripbytecount);
TIFFClrFieldBit(tif, FIELD_YCBCRSUBSAMPLING);
TIFFClrFieldBit(tif, FIELD_YCBCRPOSITIONING);
/* Cleanup custom tag values */
for( i = 0; i < td->td_customValueCount; i++ ) {
if (td->td_customValues[i].value)
_TIFFfree(td->td_customValues[i].value);
}
td->td_customValueCount = 0;
CleanupField(td_customValues);
#if defined(DEFER_STRILE_LOAD)
_TIFFmemset( &(td->td_stripoffset_entry), 0, sizeof(TIFFDirEntry));
_TIFFmemset( &(td->td_stripbytecount_entry), 0, sizeof(TIFFDirEntry));
#endif
}
#undef CleanupField
/*
* Client Tag extension support (from Niles Ritter).
*/
static TIFFExtendProc _TIFFextender = (TIFFExtendProc) NULL;
TIFFExtendProc
TIFFSetTagExtender(TIFFExtendProc extender)
{
TIFFExtendProc prev = _TIFFextender;
_TIFFextender = extender;
return (prev);
}
/*
* Setup for a new directory. Should we automatically call
* TIFFWriteDirectory() if the current one is dirty?
*
* The newly created directory will not exist on the file till
* TIFFWriteDirectory(), TIFFFlush() or TIFFClose() is called.
*/
int
TIFFCreateDirectory(TIFF* tif)
{
TIFFDefaultDirectory(tif);
tif->tif_diroff = 0;
tif->tif_nextdiroff = 0;
tif->tif_curoff = 0;
tif->tif_row = (uint32) -1;
tif->tif_curstrip = (uint32) -1;
return 0;
}
int
TIFFCreateCustomDirectory(TIFF* tif, const TIFFFieldArray* infoarray)
{
TIFFDefaultDirectory(tif);
/*
* Reset the field definitions to match the application provided list.
* Hopefully TIFFDefaultDirectory() won't have done anything irreversable
* based on it's assumption this is an image directory.
*/
_TIFFSetupFields(tif, infoarray);
tif->tif_diroff = 0;
tif->tif_nextdiroff = 0;
tif->tif_curoff = 0;
tif->tif_row = (uint32) -1;
tif->tif_curstrip = (uint32) -1;
return 0;
}
int
TIFFCreateEXIFDirectory(TIFF* tif)
{
const TIFFFieldArray* exifFieldArray;
exifFieldArray = _TIFFGetExifFields();
return TIFFCreateCustomDirectory(tif, exifFieldArray);
}
/*
* Setup a default directory structure.
*/
int
TIFFDefaultDirectory(TIFF* tif)
{
register TIFFDirectory* td = &tif->tif_dir;
const TIFFFieldArray* tiffFieldArray;
tiffFieldArray = _TIFFGetFields();
_TIFFSetupFields(tif, tiffFieldArray);
_TIFFmemset(td, 0, sizeof (*td));
td->td_fillorder = FILLORDER_MSB2LSB;
td->td_bitspersample = 1;
td->td_threshholding = THRESHHOLD_BILEVEL;
td->td_orientation = ORIENTATION_TOPLEFT;
td->td_samplesperpixel = 1;
td->td_rowsperstrip = (uint32) -1;
td->td_tilewidth = 0;
td->td_tilelength = 0;
td->td_tiledepth = 1;
td->td_stripbytecountsorted = 1; /* Our own arrays always sorted. */
td->td_resolutionunit = RESUNIT_INCH;
td->td_sampleformat = SAMPLEFORMAT_UINT;
td->td_imagedepth = 1;
td->td_ycbcrsubsampling[0] = 2;
td->td_ycbcrsubsampling[1] = 2;
td->td_ycbcrpositioning = YCBCRPOSITION_CENTERED;
tif->tif_postdecode = _TIFFNoPostDecode;
tif->tif_foundfield = NULL;
tif->tif_tagmethods.vsetfield = _TIFFVSetField;
tif->tif_tagmethods.vgetfield = _TIFFVGetField;
tif->tif_tagmethods.printdir = NULL;
/*
* Give client code a chance to install their own
* tag extensions & methods, prior to compression overloads.
*/
if (_TIFFextender)
(*_TIFFextender)(tif);
(void) TIFFSetField(tif, TIFFTAG_COMPRESSION, COMPRESSION_NONE);
/*
* NB: The directory is marked dirty as a result of setting
* up the default compression scheme. However, this really
* isn't correct -- we want TIFF_DIRTYDIRECT to be set only
* if the user does something. We could just do the setup
* by hand, but it seems better to use the normal mechanism
* (i.e. TIFFSetField).
*/
tif->tif_flags &= ~TIFF_DIRTYDIRECT;
/*
* As per http://bugzilla.remotesensing.org/show_bug.cgi?id=19
* we clear the ISTILED flag when setting up a new directory.
* Should we also be clearing stuff like INSUBIFD?
*/
tif->tif_flags &= ~TIFF_ISTILED;
return (1);
}
static int
TIFFAdvanceDirectory(TIFF* tif, uint64* nextdir, uint64* off)
{
static const char module[] = "TIFFAdvanceDirectory";
if (isMapped(tif))
{
uint64 poff=*nextdir;
if (!(tif->tif_flags&TIFF_BIGTIFF))
{
tmsize_t poffa,poffb,poffc,poffd;
uint16 dircount;
uint32 nextdir32;
poffa=(tmsize_t)poff;
poffb=poffa+sizeof(uint16);
if (((uint64)poffa!=poff)||(poffb<poffa)||(poffb<(tmsize_t)sizeof(uint16))||(poffb>tif->tif_size))
{
TIFFErrorExt(tif->tif_clientdata,module,"Error fetching directory count");
return(0);
}
_TIFFmemcpy(&dircount,tif->tif_base+poffa,sizeof(uint16));
if (tif->tif_flags&TIFF_SWAB)
TIFFSwabShort(&dircount);
poffc=poffb+dircount*12;
poffd=poffc+sizeof(uint32);
if ((poffc<poffb)||(poffc<dircount*12)||(poffd<poffc)||(poffd<(tmsize_t)sizeof(uint32))||(poffd>tif->tif_size))
{
TIFFErrorExt(tif->tif_clientdata,module,"Error fetching directory link");
return(0);
}
if (off!=NULL)
*off=(uint64)poffc;
_TIFFmemcpy(&nextdir32,tif->tif_base+poffc,sizeof(uint32));
if (tif->tif_flags&TIFF_SWAB)
TIFFSwabLong(&nextdir32);
*nextdir=nextdir32;
}
else
{
tmsize_t poffa,poffb,poffc,poffd;
uint64 dircount64;
uint16 dircount16;
poffa=(tmsize_t)poff;
poffb=poffa+sizeof(uint64);
if (((uint64)poffa!=poff)||(poffb<poffa)||(poffb<(tmsize_t)sizeof(uint64))||(poffb>tif->tif_size))
{
TIFFErrorExt(tif->tif_clientdata,module,"Error fetching directory count");
return(0);
}
_TIFFmemcpy(&dircount64,tif->tif_base+poffa,sizeof(uint64));
if (tif->tif_flags&TIFF_SWAB)
TIFFSwabLong8(&dircount64);
if (dircount64>0xFFFF)
{
TIFFErrorExt(tif->tif_clientdata,module,"Sanity check on directory count failed");
return(0);
}
dircount16=(uint16)dircount64;
poffc=poffb+dircount16*20;
poffd=poffc+sizeof(uint64);
if ((poffc<poffb)||(poffc<dircount16*20)||(poffd<poffc)||(poffd<(tmsize_t)sizeof(uint64))||(poffd>tif->tif_size))
{
TIFFErrorExt(tif->tif_clientdata,module,"Error fetching directory link");
return(0);
}
if (off!=NULL)
*off=(uint64)poffc;
_TIFFmemcpy(nextdir,tif->tif_base+poffc,sizeof(uint64));
if (tif->tif_flags&TIFF_SWAB)
TIFFSwabLong8(nextdir);
}
return(1);
}
else
{
if (!(tif->tif_flags&TIFF_BIGTIFF))
{
uint16 dircount;
uint32 nextdir32;
if (!SeekOK(tif, *nextdir) ||
!ReadOK(tif, &dircount, sizeof (uint16))) {
TIFFErrorExt(tif->tif_clientdata, module, "%s: Error fetching directory count",
tif->tif_name);
return (0);
}
if (tif->tif_flags & TIFF_SWAB)
TIFFSwabShort(&dircount);
if (off != NULL)
*off = TIFFSeekFile(tif,
dircount*12, SEEK_CUR);
else
(void) TIFFSeekFile(tif,
dircount*12, SEEK_CUR);
if (!ReadOK(tif, &nextdir32, sizeof (uint32))) {
TIFFErrorExt(tif->tif_clientdata, module, "%s: Error fetching directory link",
tif->tif_name);
return (0);
}
if (tif->tif_flags & TIFF_SWAB)
TIFFSwabLong(&nextdir32);
*nextdir=nextdir32;
}
else
{
uint64 dircount64;
uint16 dircount16;
if (!SeekOK(tif, *nextdir) ||
!ReadOK(tif, &dircount64, sizeof (uint64))) {
TIFFErrorExt(tif->tif_clientdata, module, "%s: Error fetching directory count",
tif->tif_name);
return (0);
}
if (tif->tif_flags & TIFF_SWAB)
TIFFSwabLong8(&dircount64);
if (dircount64>0xFFFF)
{
TIFFErrorExt(tif->tif_clientdata, module, "Error fetching directory count");
return(0);
}
dircount16 = (uint16)dircount64;
if (off != NULL)
*off = TIFFSeekFile(tif,
dircount16*20, SEEK_CUR);
else
(void) TIFFSeekFile(tif,
dircount16*20, SEEK_CUR);
if (!ReadOK(tif, nextdir, sizeof (uint64))) {
TIFFErrorExt(tif->tif_clientdata, module, "%s: Error fetching directory link",
tif->tif_name);
return (0);
}
if (tif->tif_flags & TIFF_SWAB)
TIFFSwabLong8(nextdir);
}
return (1);
}
}
/*
* Count the number of directories in a file.
*/
uint16
TIFFNumberOfDirectories(TIFF* tif)
{
uint64 nextdir;
uint16 n;
if (!(tif->tif_flags&TIFF_BIGTIFF))
nextdir = tif->tif_header.classic.tiff_diroff;
else
nextdir = tif->tif_header.big.tiff_diroff;
n = 0;
while (nextdir != 0 && TIFFAdvanceDirectory(tif, &nextdir, NULL))
n++;
return (n);
}
/*
* Set the n-th directory as the current directory.
* NB: Directories are numbered starting at 0.
*/
int
TIFFSetDirectory(TIFF* tif, uint16 dirn)
{
uint64 nextdir;
uint16 n;
if (!(tif->tif_flags&TIFF_BIGTIFF))
nextdir = tif->tif_header.classic.tiff_diroff;
else
nextdir = tif->tif_header.big.tiff_diroff;
for (n = dirn; n > 0 && nextdir != 0; n--)
if (!TIFFAdvanceDirectory(tif, &nextdir, NULL))
return (0);
tif->tif_nextdiroff = nextdir;
/*
* Set curdir to the actual directory index. The
* -1 is because TIFFReadDirectory will increment
* tif_curdir after successfully reading the directory.
*/
tif->tif_curdir = (dirn - n) - 1;
/*
* Reset tif_dirnumber counter and start new list of seen directories.
* We need this to prevent IFD loops.
*/
tif->tif_dirnumber = 0;
return (TIFFReadDirectory(tif));
}
/*
* Set the current directory to be the directory
* located at the specified file offset. This interface
* is used mainly to access directories linked with
* the SubIFD tag (e.g. thumbnail images).
*/
int
TIFFSetSubDirectory(TIFF* tif, uint64 diroff)
{
tif->tif_nextdiroff = diroff;
/*
* Reset tif_dirnumber counter and start new list of seen directories.
* We need this to prevent IFD loops.
*/
tif->tif_dirnumber = 0;
return (TIFFReadDirectory(tif));
}
/*
* Return file offset of the current directory.
*/
uint64
TIFFCurrentDirOffset(TIFF* tif)
{
return (tif->tif_diroff);
}
/*
* Return an indication of whether or not we are
* at the last directory in the file.
*/
int
TIFFLastDirectory(TIFF* tif)
{
return (tif->tif_nextdiroff == 0);
}
/*
* Unlink the specified directory from the directory chain.
*/
int
TIFFUnlinkDirectory(TIFF* tif, uint16 dirn)
{
static const char module[] = "TIFFUnlinkDirectory";
uint64 nextdir;
uint64 off;
uint16 n;
if (tif->tif_mode == O_RDONLY) {
TIFFErrorExt(tif->tif_clientdata, module,
"Can not unlink directory in read-only file");
return (0);
}
/*
* Go to the directory before the one we want
* to unlink and nab the offset of the link
* field we'll need to patch.
*/
if (!(tif->tif_flags&TIFF_BIGTIFF))
{
nextdir = tif->tif_header.classic.tiff_diroff;
off = 4;
}
else
{
nextdir = tif->tif_header.big.tiff_diroff;
off = 8;
}
for (n = dirn-1; n > 0; n--) {
if (nextdir == 0) {
TIFFErrorExt(tif->tif_clientdata, module, "Directory %d does not exist", dirn);
return (0);
}
if (!TIFFAdvanceDirectory(tif, &nextdir, &off))
return (0);
}
/*
* Advance to the directory to be unlinked and fetch
* the offset of the directory that follows.
*/
if (!TIFFAdvanceDirectory(tif, &nextdir, NULL))
return (0);
/*
* Go back and patch the link field of the preceding
* directory to point to the offset of the directory
* that follows.
*/
(void) TIFFSeekFile(tif, off, SEEK_SET);
if (!(tif->tif_flags&TIFF_BIGTIFF))
{
uint32 nextdir32;
nextdir32=(uint32)nextdir;
assert((uint64)nextdir32==nextdir);
if (tif->tif_flags & TIFF_SWAB)
TIFFSwabLong(&nextdir32);
if (!WriteOK(tif, &nextdir32, sizeof (uint32))) {
TIFFErrorExt(tif->tif_clientdata, module, "Error writing directory link");
return (0);
}
}
else
{
if (tif->tif_flags & TIFF_SWAB)
TIFFSwabLong8(&nextdir);
if (!WriteOK(tif, &nextdir, sizeof (uint64))) {
TIFFErrorExt(tif->tif_clientdata, module, "Error writing directory link");
return (0);
}
}
/*
* Leave directory state setup safely. We don't have
* facilities for doing inserting and removing directories,
* so it's safest to just invalidate everything. This
* means that the caller can only append to the directory
* chain.
*/
(*tif->tif_cleanup)(tif);
if ((tif->tif_flags & TIFF_MYBUFFER) && tif->tif_rawdata) {
_TIFFfree(tif->tif_rawdata);
tif->tif_rawdata = NULL;
tif->tif_rawcc = 0;
tif->tif_rawdataoff = 0;
tif->tif_rawdataloaded = 0;
}
tif->tif_flags &= ~(TIFF_BEENWRITING|TIFF_BUFFERSETUP|TIFF_POSTENCODE|TIFF_BUF4WRITE);
TIFFFreeDirectory(tif);
TIFFDefaultDirectory(tif);
tif->tif_diroff = 0; /* force link on next write */
tif->tif_nextdiroff = 0; /* next write must be at end */
tif->tif_curoff = 0;
tif->tif_row = (uint32) -1;
tif->tif_curstrip = (uint32) -1;
return (1);
}
/* vim: set ts=8 sts=8 sw=8 noet: */
/*
* Local Variables:
* mode: c
* c-basic-offset: 8
* fill-column: 78
* End:
*/
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235 B.R. 272 (1999)
In re NextWAVE PERSONAL COMMUNICATIONS, INC., et al., Debtors.
NextWave Personal Communications, Inc., Plaintiff,
v.
Federal Communications Commission, Defendant.
Bankruptcy No. 98 B 21529(ASH). Adversary No. 98-5178A.
United States Bankruptcy Court, S.D. New York.
February 16, 1999.
Andrews & Kurth L.L.P, By Deborah L. Schrier-Rape, Dallas, TX, for plaintiff/debtor.
*273 Mary Jo White, United States Attorney for the Southern District of New York, By Daniel S. Alter, New York City, for defendant.
DECISION ON PARTIAL SUMMARY JUDGMENT MOTION
ADLAI S. HARDIN, Jr., Bankruptcy Judge.
Nextwave Personal Communications, Inc. ("Nextwave" or "debtor") commenced this adversary proceeding to set aside its aggregate $4.7 billion of transfers and obligations to the Federal Communications Commission ("FCC") incurred in its acquisition of 63 broadband Personal Communication Services licenses ("C Block licenses") as a constructive fraudulent conveyance under 11 U.S.C. § 544(b). The FCC has moved for partial summary judgment under Bankruptcy Rule 7056(b) to determine the effective date of Nextwave's $4.74 billion of transfers and obligations for purposes of Section 544(b). As set out below, I find that the effective date of the debtor's $4.74 billion of transfers and obligations under Bankruptcy Code Section 544 is January 3, 1997.
Jurisdiction
This Court has jurisdiction over this matter pursuant to 28 U.S.C. §§ 1334(a) and 157(a) and the standing order of reference of Acting Chief Judge Robert J. Ward dated July 10, 1984. This adversary proceeding is a core proceeding under 28 U.S.C. § 157(b)(2)(H).
Undisputed Facts
The following facts are undisputed by the parties. The FCC conducted an auction of C Block licenses from December 18, 1995 to May 6, 1996, and a reauction of C Block licenses from July 3 to July 16, 1996. The debtor participated in the bidding in both of these auctions and was declared the high bidder on May 8, 1996 for 56 C Block licenses and on July 23, 1996 for an additional 7 reauctioned C Block licenses, for a total of 63 C Block licenses.
As part of the FCC's auction process, bidders were required to deposit "qualifying amounts" in order to participate in the auction. The debtor deposited qualifying amounts of $79,225,000 on December 1, 1995 and $6,984,244 on June 13, 1996. After the debtor was declared the winning bidder on May 6, 1996 as to the 56 C Block licenses, it deposited an additional $130,834,333 on May 10, 1996 and further deposit of $20.138.825 on July 23, 1996 when it was declared the winning bidder for the 7 C Block licenses. The debtor's deposits at the close of the bidding process totalled $237,182,402, or approximately 5% of the $4.7 billion it bid for all 63 C Block Licenses.
Following the close of the auction process, FCC regulations required the debtor to submit applications for approval of the issuance of the 63 C Block licenses. The debtor submitted applications as to the 56 and 7 C block licenses on May 22 and July 17, 1996, respectively. While these applications were pending, two rival bidders, Antigone Communications L.P. and PCS Devco, Inc., petitioned the FCC to deny the debtor's applications on various grounds. The FCC investigated the matter and found that certain elements of Nexwave's capital structure exceeded statutory foreign ownership benchmarks. In response, the debtor filed a restructuring plan with the FCC on December 30, 1996 to bring its capital structure into compliance with FCC regulations. On January 3, 1997, the FCC conditionally granted licenses for all 63 C Block licenses, subject to the debtor's implementation of its proposed capital restructuring plan.
Following the FCC's January 3, 1997 license grant, the debtor was required to deposit an additional 5% of the total $4.74 billion bid price, or a further $237 million. The debtor deposited this additional amount on January 9, 1997, raising its total deposits to $474 million. On February 19, 1997 the debtor signed notes dated January 3, 1997 in the aggregate principal *274 amount of $4.27 billion (the "Notes") for the balance of the $4.74 billion it bid at auction.
Discussion
The parties dispute the date on which the debtor incurred its $4.74 billion obligation to the FCC. That date is relevant for purposes of the debtor's avoidance claim under Bankruptcy Code Section 544(b), which provides in pertinent part:
The trustee may avoid any transfer of an interest of the debtor in property or any obligation incurred by the debtor that is voidable under applicable law ...
11 U.S.C. § 544(b) (emphasis added). Because the FCC has moved only for a determination of that date, this decision is limited to a finding of fact and conclusion of law as to that date and does not address any remaining factual or legal issues regarding the debtor's Section 544 claim.
The FCC argues that the debtor incurred its obligations when "the hammer fell" at the C Block auctions on May 8 and July 23, 1996. The debtor argues that it did not incur the obligations at issue in this proceeding until at least January 3, 1997,[1] the date on which the FCC conditionally granted the licenses and the effective date of the Notes.
The resolution of this motion must follow from identifying precisely which obligation the debtor seeks to avoid. Stripped to its essential proposition, the debtor's Section 544 claim is that it did not receive reasonably equivalent value in the C Block licenses it was granted in return for its $4.74 billion obligations. To measure the reasonable equivalence in value of the C Block licenses and the obligations incurred therefor, one must ask (i) when did the debtor receive the licenses and (ii) when did it become obligated to pay for them. These questions are determined by the rules governing the auction itself. See In re Wilson Freight Co., 30 B.R. 971, 975 (Bankr.S.D.N.Y.1983) (announced terms of auction binding upon participants). Those rules are found in the FCC regulations governing the auction process at 47 C.F.R. §§ 1.2101-1.2111, entitled "Subpart Q, Competitive Bidding Process."
With regard to question (i), both sides agree that the winning bidder neither received nor became entitled to receive the C Block licenses upon being declared the winning bidder under the FCC regulations. The winning bidder must apply to the FCC, complete the regulatory approval process and perhaps (as in this debtor's case) overcome objections. The winning bidder has no legal right to receive or utilize the licenses bid upon unless and until its application is approved by the FCC. All the debtor received on May 8 and July 23, 1996 when it was declared high bidder was the exclusive right to apply for the 63 licenses. As stated by the FCC's counsel at a hearing in this Court on January 28, 1999 (Tr. at 15):
THE COURT: Wait a second. You're asking for words, namely, "reasonably equivalent value" and that raises a question of value for what? And equivalent to what?
MS. SCHWARTZ: To what they got.
THE COURT: What did they get?
MS. SCHWARTZ: What they got was the right to apply for these licenses that were essential to their business. And without those licenses, they would have no business.
Thus, the debtor did not become entitled to receive the 63 C Block licenses until at the earliest the January 3, 1996 decision of the FCC granting the debtor's applications.
Under FCC regulations, once bidding has ended the FCC must notify the high bidder and declare bidding closed. 47 C.F.R. § 1.2107(a). Within five days of the notification, the winning bidder who is *275 a "qualified designated entity" (as is the debtor) must bring its total deposits up to 10% of its bid as a downpayment. 47 C.F.R. § 1.2107(b). Significantly, once the downpayment is tendered, the FCC holds the downpayment:
until the high bidder has been awarded the license and has paid the remaining balance due on the license, in which case it will not be returned, or until the winning bidder is found unqualified to be a licensee or has defaulted, in which case it will be returned, less applicable penalties.
Id. In other words, one of three events must occur after the winning bidder tenders the downpayment but before award of the license: either the winning bidder pays the balance of the bid, in which case the downpayment is applied toward the license, or the winning bidder defaults, or the winning bidder is disqualified. Significantly, if the winning bidder defaults or is disqualified, although penalties may be assessed under Section 1.2104, the downpayment must be returned net of any penalties[2].
Nor is the obligation on the full amount of the bid fixed upon tender of the downpayment. A winning bidder who timely submits its downpayment must also submit a "long-form" application for license approval in its respective areas of service. 47 C.F.R. § 1.2107(c). If the bidder fails to timely submit its application, it is deemed to have defaulted and is subject to Section 1.2104 penalties. Id. The bidder's default subjects it to applicable penalties to be subtracted from the downpayment, but does not leave the bidder liable on the full amount of the bid.
These provisions make it clear that the debtor was not legally bound on the full amount of its winning bid upon being declared the high bidder. At the "fall of the hammer" the debtor did incur a potential liability in the event that it either defaulted or was disqualified (neither of which occurred in this case), but under the FCC regulations that potential liability was quite different from the amount of the winning bid.
The potential default liability incurred at the fall of the hammer consisted of penalties calculated on the basis of the difference between the winning bid and the winning bid at any subsequent reauction if any, plus applicable percentage penalties. See 47 C.F.R. § 1.2104. Nothing in this calculation explicitly or implicitly binds the winning bidder to the full amount of its bid. Indeed, the express requirement that the downpayment be refunded less any penalties in the event of default or disqualification negates any implied liability for the full amount of the bid. The penalty obligations upon default or disqualification are entirely separate from and mutually exclusive of the obligations the bidder would incur upon granting of the license and tender of the balance of the bid. Whether the debtor might have been liable for any of these penalty amounts is not at issue.
Having determined that the debtor's liability for the full amount of the obligation did not attach upon its being declared the high bidder, nor upon tender of the downpayment or even submission of the license approval application, the issue remains as to when the full liability did attach.
The auction rules provide that the grant of a license is expressly conditioned upon payment of the balance of the obligation. Section 1.2109(a) provides:
Unless otherwise specified in these rules, auction winners are required to pay the balance of their winning bids in a lump sum within five (5) business days following award of the license. Grant of the license will be conditioned on full and timely payment of the winning bid. *276 47 C.F.R. § 1.2109(a) (emphasis supplied). If the bidder fails to satisfy Section 1.2109(a), the license application is deemed dismissed, the bidder is liable for Section 1.2104 penalties against the downpayment, and the FCC may either reauction the license or offer it to the next highest bidder. 47 C.F.R. § 1.2109(b). Similarly, any bidder who is found unqualified, defaults in timely remitting the balance of the bid or is disqualified becomes liable for Section 1.2104 penalties, after which the FCC may conduct a new auction. Id. Taking these sections together, had the debtor failed to tender the balance or otherwise defaulted, it would have been liable only for the Section 1.2104 penalties against its downpayment. Thus the earliest date at which the debtor could have been liable for the full amount of its bid obligations is the date it complied with Section 1.2109(a) by paying the balance of its cash obligations and issuing the Notes. The debtor complied with Section 1.2109(a) effective at the earliest on January 3, 1996 by tendering the balance of its bids in cash and the Notes. It thereby became liable for the full amount of its bid obligations by reason of its Notes.
To summarize, under the FCC regulations it is clear that the debtor incurred a contingent liability for default by entering into the bidding process and by being declared the high bidder. However the contingent default obligations that the debtor might have incurred by participating in the bidding process (which were never actually incurred by the debtor) were quite different from the debtor's obligations for the full amount of its bids, which only became fixed upon its tender in cash and the Notes of the balance due on the C Block licenses granted on January 3, 1997. That obligation, not the contingent penalty obligations, is the subject of the debtor's Section 544 avoidance action.
It is apparent that the FCC's position on this motion is incongruent both with its own regulations and with the debtor's claim in this adversary proceeding. The constructive fraudulent conveyance claim asserts that the aggregate consideration given by the debtor effective January 3, 1997 for the 63 licenses (i.e., the cash transfers totalling $474 million and the Notes totalling $4.26 billion) was not reasonably equivalent to the value of the licenses granted on January 3, 1997. In arguing that May 8 and July 23, 1996 are the debtor's liability dates for valuation purposes, the FCC focuses not on the actual $4.7 billion purchase price which became effective January 3, 1997, but on the debtor's contingent exposure to default penalties which were never incurred and never could be incurred if the licenses were granted. Moreover, the property to be valued the licenses was not granted in May and June 1996, but on January 3, 1997.
For the foregoing reasons, I find as a matter of fact and law that the date upon which the debtor incurred its obligations to the FCC for purposes of Bankruptcy Code Section 544(b) is January 3, 1997.[3]
* * *
Counsel for the Nextwave and the FCC are directed to confer and jointly prepare an order, agreed as to form, consistent with this decision, without prejudice to the FCC's right to appeal.
NOTES
[1] While it did not actually execute its Notes for the balance of its bid until February 19, 1997, the debtor does not contest using the effective date of the Notes, January 3, 1997. (Debtor's Memorandum at 8, note 2).
[2] It appears that one party in the bidding process, BDCPS, Inc., in fact failed to timely submit its downpayment, thereby defaulting, and was assessed a penalty in accordance with Section 1.2104, but there is no indication that the full amount of its high bid was assessed. (Exhibit J to debtor's Memorandum in Opposition).
[3] The January 3, 1997 date is based upon the date of the FCC's decision granting the licenses and constitutes the earliest effective date of the debtor's obligations for purposes of this adversary proceeding under Section 544. This ruling is without prejudice to the right of either party to argue that a later date should be determinative if the difference is material.
| {
"pile_set_name": "FreeLaw"
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What do you think of the plans, General Twobabies? AHH!! I'M A TERRORIST!! (brody from homeland but-not-really reveals he has a bomb vest strapped on himself) oh my You will pay for your war crimes!! General Twobabies begins gnawing on his finger. The general is teething on your finger. Awww Ow.
Part of the General Twobabies series. | {
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Roman Catholic Diocese of Mottola
The Diocese of Mottola or Diocese of Motula (Latin: Dioecesis Motulensis) was a Roman Catholic diocese located in the town of Mottola in the province of Taranto in the region of Apulia in southeast Italy. In 1818, it was suppressed to the Diocese of Castellaneta.
Since 1968, the diocese has periodically been a titular see.
Territory
The diocese included the villages of Mottola, Palagiano, Massafra and Palagianello.
The episcopal see was the town of Mottola, where the church of Santa Maria Assunta, also dedicated to Saint Thomas Becket, patron of the city, served as a cathedral.
History
The Diocese of Mottola was erected in Norman times, after they conquered the city in 1023. The first bishop historically documented is John, mentioned in the diploma of 1081 in which Riccardo Siniscalco, Lord of Mottola and Castellaneta, donated some churches of Mottola and Massafra at the abbey of Cava, "assensum Ioannis Mutulensis episcopi," that is, "with the consent of John, the bishop of Mottola."
The next Bishop of Mottola was Amuro, who in December 1100 confirmed for Abbot Orso of Santa Maria di Banzi his possession of the church of San Matteo in the territory of Castellaneta. In the diploma Amuro he signs as Mutulensis atque Castellanitensis ecclesie presul, bishop of the church of Mottola and Castellaneta, suggesting that at the time the two dioceses were united with one bishop. However, the union must have been short-lived, because in 1110 the Diocese of Mottola was again autonomous. In that year Bishop Valcauso, who confirmed to the Abbot of Cava the possession of the monasteries of Sant'Angelo and of San Vito di Casalrotto, of some churches, lands and other goods.
Since its foundation, the Diocese was part of the ecclesiastical province of the Archdiocese of Taranto.
The Diocese of Mottola had several notable bishops: Bishop Angelo Pascali (1537-1550) participated in the Council of Trent; Scipione Rebiba (1551-1556), later Archbishop of Pisa and Cardinal Ludovico della Quadra (1664-1695), completed the construction Of the Rosary Chapel; in 1600 Bishop Silvestro Tufo established the diocesan seminary, and Michele Palmieri (1798-1804) was the last bishop of Mottola.
Fourteen years after the death of Palmieri, a period in which the seat remained vacant, with the agreement (6 February 1818) between Pope Pius VII and Ferdinand I of Bourbon King of Naples, the diocese was suppressed and its territories were united to the diocese of Castellaneta . This act was effected on June 27, 1818, with De utiliori of Pius VII.
Mottola has been a titular bishopric of the Catholic Church since 1968. Angelo De Donatis, was named titular bishop of Mottola in September 2015 and then titular archbishop of Mottola in May 2017. He ceased to hold the title upon being made a cardinal. Gianfranco Gallone, newly appointed Apostolic Nuncio to Zambia and Malawi, has been the titular archbishop of Mottola since being consecrated a bishop on 19 March 2019.
Ordinaries
Diocese of Mottola
Erected: 1023
Latin Name: Motulensis
Metropolitan: Archdiocese of Taranto
Ciliberto de Fumis (Appointed 1040 – )
...
Nicola de Genupia (17 Mar 1468 – 1471 Died)
...
Pietro Guercio (de Quercius) (13 Aug 1512 – 1524 Died)
Guido Guidone (10 Feb 1525 – 1528 Died)
Vito Ferrato (7 Aug 1528 – 1537 Died)
Angelo Pasquali, O.P. (6 Mar 1537 – 1550 Died)
Scipione Rebiba (12 Oct 1551 – 13 Apr 1556 Appointed, Archbishop of Pisa)
Cesare Gesualdo (13 Mar 1560 – 1566 Died)
Giovanni Ludovico da Campania (5 Jul 1566 – 1579 Died)
Jaime Miguel Miguélez (3 Aug 1579 – 1599 Died)
Silvestro Tufo, C.R. (29 Nov 1599 – Oct 1600 Died)
Benedetto Rossi, C.R. (3 Dec 1601 – 1622 Died)
Francesco Saluzzo (2 May 1622 – 1627 Resigned)
Serafino Rinaldo (de Nuceria), O.P. (14 Apr 1627 – 27 Apr 1627 Died)
Tommaso d'Ancora (Tommaso Ariconi), C.R. (9 Sep 1630 – 8 Jan 1635 Confirmed, Archbishop of Trani)
Giovanni Battista Falesi, O.P. (15 Jan 1638 – 1648 Died)
Tommaso d'Aquino, C.R. (24 Aug 1648 – 1651 Died)
Giovanni Camponeschi, O.F.M. (22 Jun 1654 – 1657 Died)
Gennaro De Andrea (8 Aug 1661 – 1664 Died)
Ludovico della Quadra (21 Jul 1664 – 15 Jan 1695 Resigned)
Francesco della Marra (2 Apr 1696 – Aug 1696 Died)
Michele Maria Dentice (27 Mar 1697 – Oct 1698 Died)
...
Pier Paolo Mastrilli (26 Nov 1703 – 7 Apr 1713 Died)
Biagio Antonio Copeti (15 May 1719 – May 1727 Died)
Antonio Bianchi di Gennaro, O.F.M. (24 Apr 1728 Confirmed – Aug 1729 Died)
Giovanni Antonio Chiaiese (12 Feb 1731 – Aug 1732 Died)
Nicola Paolo Pandolfelli (20 Jan 1734 – 19 Apr 1766 Died)
Stefano (Ildefonso) Ortiz Cortes, O.S.B. (2 Jun 1766 – Mar 1791 Died)
Agostino Andriani (18 Jun 1792 – 1795 Died)
Michele Palmieri (29 Jan 1798 – 29 Oct 1804 Appointed, Bishop of Troia)
1818: Suppressed to the Diocese of Castellaneta
Titular See
Bernard Joseph McLaughlin (28 December 1968 – 5 January 2015)
Angelo De Donatis (14 September 2015 – 28 June 2018)
Gianfranco Gallone (2 February 2019 - present)
References
Category:Former Roman Catholic dioceses in Italy | {
"pile_set_name": "Wikipedia (en)"
} |
543 U.S. 998
AZUBUKOv.BERKSHIRE MUTUAL INSURANCE CO. ET AL.
No. 03-11045.
Supreme Court of United States.
November 29, 2004.
1
C. A. 11th Cir. Motion of petitioner for reconsideration of order denying leave to proceed in forma pauperis [ante, p. 803] denied.
| {
"pile_set_name": "FreeLaw"
} |
Monster Munchies
Monster Munchies is a cookery show which is broadcast on the British television channel Good Food. It is hosted by Matt Dawson.
Format
Teams made up of local cooks from the location where the episode is filmed, make mega dishes within a 24-hour time limit, sourcing large quantities of ingredients and firing up industrial-sized ovens. Five local judges will cast their eye over the enormous creations, and hundreds of local people will eat the dishes when they’re completed. The winning team get a large gold wooden spoon.
Series 2
Series 2 began airing in November 2011.
References
Category:UKTV television programmes
Category:2010s British television series
Category:2011 British television series debuts
Category:2011 British television series endings
Category:British cooking television programmes | {
"pile_set_name": "Wikipedia (en)"
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Reconstruction of lower lip with myomucosal advancement flap.
In this article, a new surgical procedure that can be used for reconstruction of lower lip defects of any size is described. In this prospective study, the surgical procedure was applied in 16 patients. In this procedure, the mucosa and the orbicularis oris muscle of the lower lip are repaired with a composite flap, and the skin defect is closed using local skin flaps. The patients were assessed in terms of complications, mouth opening, sphincter function of the mouth, and sensation in the lower lip. The aesthetic results obtained in all patients were satisfactory. Sufficient oral sphincter function was achieved in all patients. Reconstruction of lower lip defects using the procedure described here can be performed in patients with lower lip defects of any size as long as the mucosal and skin repair lines are not superimposed. This procedure yielded good sphincter function and aesthetic results. | {
"pile_set_name": "PubMed Abstracts"
} |
John Stanley "Stan" Hansen II[1] (born August 29, 1949)[1] is an American actor, author and retired professional wrestler. Hansen is renowned for his stiff wrestling style, which he attributes to his poor eyesight.[5][11] He is also known for his gimmick as a loud, violent cowboy who wanted to fight everybody,[8][9] which he further emphasized by appearing in interviews with a cowboy hat, leather vest and bullrope while often chewing on tobacco.[10][12] Considered to be among the most successful and popular gaijins in professional wrestling history, Hansen became more well known and revered in Japan than in his native United States.[8][9] Despite this, Hansen still found championship success in both countries.
Hansen competed in the American Wrestling Association (AWA) from 1985 to 1986. He won the World Heavyweight Championship on December 29, 1985, from Rick Martel.[4] On June 29, 1986, he no-showed a title defense against the number one contender Nick Bockwinkel due to disagreements with management, forcing the AWA to default the title to Bockwinkel.[5] Rumors suggest that Hansen was actually in the building that evening and had been informed by AWA promoter Verne Gagne of the pending loss to Bockwinkel. Hansen allegedly called All Japan Pro Wrestling president Giant Baba to ask if losing the championship was acceptable, but Baba had already lined up challengers for Hansen and did not permit Hansen to drop the championship. In the end, Hansen refused to drop the title to Bockwinkel and was stripped of the championship; Bockwinkel was given one of the tag team belts, which was then billed as the AWA World Heavyweight Championship due to Hansen still possessing the true title belt. Hansen immediately returned to Japan and defended the AWA World Heavyweight Championship, despite being stripped of it.[4][13] The AWA threatened legal action if Hansen continued to carry the belt and refer to himself as the organization's champion, so Hansen responded by running over the belt with his truck and mailing it back with the mud tracks still on it.[4][5][13] This chain of events was reviewed in an interview with Hansen at an NWA Legends convention, in which he expressed regret over the way he handled the situation and ultimately complimented Gagne.[13]
Hansen first came to New Japan Pro Wrestling (NJPW) in May 1980 doing one off shows where usually teamed and fought Bob Backlund. From November 21 to December 13, 1980, Hansen did a tour for New Japan Pro Wrestling, where he competed in the first MSG league (later renamed the G1 Tag League). He teamed with Hulk Hogan, but they failed to win. He returned that April to wrestle Antonio Inoki in an unsuccessful match. He returned for several more one off shows until leaving the promotion in early 1981.[16]
Hansen returned at NJPW's Super Fight in Tokyo Dome event in 1990, where he had an infamous interpromotional match against Vader. The match for the IWGP Heavyweight Championship saw Big Van Vader (representing New Japan, while Hansen represented All Japan) get struck in the eye during the entrances by Hansen's Bullrope. Both men were known to use a stiff style of wrestling, resulting in a nasty exchange where each man threw legitimate punches. The match ended in a draw, and Hansen never returned to New Japan.[17]
In addition to championship matches, Hansen also competed in other high-profile matches. At the NJPW Super Fight in Tokyo Dome show on February 2, 1990, Hansen competed in another notable match as he represented AJPW against NJPW representative Big Van Vader. This particular match became renowned for its stiffness, as Hansen and Vader repeatedly exchanged blows until Hansen unintentionally poked Vader's right eye with his thumb, which caused the eye to pop out of its socket.[4][5] After removing his mask, pushing the eye back into its socket and holding it in place with his eyelid, Vader continued wrestling Hansen until the match was rendered a no contest. As a result of the injury, Vader required a metal plate to be surgically placed under his eye.[5] On April 13, 1990, the World Wrestling Federation and AJPW held a supershow called Wrestling Summit at the Tokyo Dome in Tokyo, in which Hansen lost to Hulk Hogan in the main event.[18] Hansen won his first Triple Crown Heavyweight Championship by defeating Terry Gordy on June 8, 1990, and wrestled a rematch in NJPW against Vader on June 12.[19]
In late 1990, Hansen began appearing in World Championship Wrestling (WCW), feuding with Lex Luger over the NWA United States Heavyweight Championship. On October 27 at Halloween Havoc, Hansen defeated Luger to win the title, ending Luger's record-setting reign at 523 days.[4][20] On December 16 at Starrcade, Hansen re-lost the title to Luger in a bullrope match. During this period, Hansen continued working tours for All Japan, teaming with Dan Spivey to finish second in the World's Strongest Tag Determination League in November and December. Hansen wrestled another rematch with Vader at the WrestleWar pay-per-view in February 1991. On April 18, Hansen and Spivey won the AJPW World Tag Team Championship from Terry Gordy and Steve Williams, and teamed occasionally upon their return to WCW. In June, Hansen left WCW and returned full-time to All Japan after a disagreement over an idea to group him with The Desperados, a trio of bumbling cowboys looking for Hansen through a series of vignettes.[13] His last WCW match occurred on June 23 in Atlanta.[21] As a result of his departure, The Desperados' angle was dropped and the trio was quickly dissolved.[13]
Upon his return to AJPW, Hansen began a major feud with Mitsuharu Misawa, during which time they traded the Triple Crown Championship between one another.[4] Following Giant Baba's death, Misawa became the new booker and quickly began de-emphasizing Hansen and other foreign talent, in favor of new native recruits such as Takao Omori and Yoshihiro Takayama.
Soon after retiring, Hansen successfully underwent surgery on his back and knees, the latter of which were both replaced.[22] After recovering, he became the commissioner of AJPW's Pacific Wrestling Federation championship governing body, which saw him appear during Triple Crown and World Tag Team Championship matches to issue proclamations of the matches.[13] In July 2007, Hansen voluntarily resigned from the position, with Hiroshi Hase replacing him.[13]
1Hansen won the championship after Ted Turner purchased Mid-Atlantic Championship Wrestling from Jim Crockett, Jr. and renamed the promotion World Championship Wrestling. Hansen's reign was also prior to the championship being renamed the WCW United States Heavyweight Championship. | {
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1. Field of the Invention
The present invention is related to document retrieval and categorization, as well as information searches, and more specifically to a computer-performed method, computer system and computer program product for document tagging and retrieval using per-subject dictionaries that include subject-determining-power scores for entries.
2. Description of Related Art
Information storage and retrieval in computer systems is an ever-evolving technology as collections of data become progressively larger and more complex. So-called “big data” involves collection of large amounts of data that may be essentially unfiltered and uncategorized. While businesses, government and other entities would like to capitalize on information that can be gleaned from such large collections of data, techniques to efficiently retrieve a manageable amount of information in response to a query are needed.
Retrieval of information from present-day databases and other more loosely-coupled information sources such as the Internet is typically performed by either crawler-based indexing, in which software engines obtain indexing information from stored documents, or from human-built directories that categorize the stored documents. However, once the data source becomes sufficiently large, the size of the response to a query also grows.
Therefore, it would be desirable to provide a method, computer system and computer program that can more efficiently handle categorization of documents and retrieval of documents in response to queries. | {
"pile_set_name": "USPTO Backgrounds"
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77 F.3d 469
NOTICE: Fourth Circuit Local Rule 36(c) states that citation of unpublished dispositions is disfavored except for establishing res judicata, estoppel, or the law of the case and requires service of copies of cited unpublished dispositions of the Fourth Circuit.Fred MEADE, Petitioner,v.DIRECTOR, OFFICE OF WORKERS' COMPENSATION PROGRAMS, UNITEDSTATES DEPARTMENT OF LABOR; Island Creek CoalCompany, Respondents.
No. 94-2585.
United States Court of Appeals, Fourth Circuit.
Submitted Jan. 26, 1996.Decided Feb. 16, 1996.
On Petition for Review of an Order of the Benefits Review Board. (93-1526-BLA)
Fred Meade, Petitioner Pro Se. Christian P. Barber, J. Matthew McCracken, UNITED STATES DEPARTMENT OF LABOR, Washington, D.C.; Douglas Allan Smoot, JACKSON & KELLY, Charleston, West Virginia, for Respondents.
Ben.Rev.Bd.
AFFIRMED.
Before NIEMEYER and HAMILTON, Circuit Judges, and BUTZNER, Senior Circuit Judge.
PER CURIAM:
1
Appellant seeks review of the Benefits Review Board's decision and order affirming the administrative law judge's denial of black lung benefits pursuant to 30 U.S.C.A. §§ 901-945 (West 1986 & Supp.1993). Our review of the record discloses that the Board's decision is based upon substantial evidence and is without reversible error. Accordingly, we affirm on the reasoning of the Board. Meade v. Director, Office of Workers' Compensation Programs, No. 93-1526-BLA (B.R.B. Nov. 25, 1994). We dispense with oral argument because the facts and legal contentions are adequately presented in the materials before the court and argument would not aid the decisional process.
AFFIRMED
| {
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This invention relates to the field of dielectric optical waveguides and optical telecommunications.
Optical waveguides guide optical signals to propagate along a preferred path or paths. Accordingly, they can be used to carry optical signal information between different locations and thus they form the basis of optical telecommunication networks. The most prevalent type of optical waveguide is an optical fiber based on index guiding. Such fibers include a core region extending along a waveguide axis and a cladding region surrounding the core about the waveguide axis and having a refractive index less than that of the core region. Because of the index-contrast, optical rays propagating substantially along the waveguide axis in the higher-index core can undergo total internal reflection (TIR) from the core-cladding interface. As a result, the optical fiber guides one or more modes of electromagnetic (EM) radiation to propagate in the core along the waveguide axis. The number of such guided modes increases with core diameter. Notably, the index-guiding mechanism precludes the presence of any cladding modes lying below the lowest-frequency guided mode. Almost all index-guided optical fibers in use commercially are silica-based in which one or both of the core and cladding are doped with impurities to produce the index contrast and generate the core-cladding interface. For example, commonly used silica optical fibers have indices of about 1.45 and index contrasts of up to about 2–3% for wavelengths in the range of 1.5 microns.
Signals traveling down an optical fiber slowly attenuate, necessitating periodic amplification and/or regeneration, typically every 50–100 km. Such amplifiers are costly, and are especially inconvenient in submarine cables where space, power sources, and maintenance are problematic. Losses for silica-based optical fibers have been driven down to about 0.2 dB/km, at which point they become limited by the Rayleigh scattering processes. Rayleigh scattering results from microscopic interactions of the light with the medium at a molecular scale and is proportional to ω4ρ, where ω is the light frequency and ρ is the material density, along with some other constants of the material.
In addition to loss, signals propagating along an optical fiber may also undergo nonlinear interactions. In an ideal linear material, light does not interact with itself-this is what allows a fiber to carry multiple communications channels simultaneously in separate wavelengths (wavelength-division multiplexing, or WDM), without interactions or crosstalk. Any real optical medium (even vacuum), however, possesses some nonlinear properties. Although the nonlinearities of silica and other common materials are weak, they become significant when light is propagated over long distances (hundreds or thousands of kilometers) or with high powers. Such nonlinear properties have many undesirable effects including: self/cross phase modulation (SPM/XPM), which can cause increased pulse broadening and limit bitrates; and afour-wave mixing (FWM) and stimulated Raman/Brillouin scattering (SRS/SBS), which induce crosstalk between different wavelength channels and can limit the number of achievable channels for WDM. Such nonlinearities are a physical property of the material in the waveguide and typically scale with the density of the waveguide core.
Typically, optical fibers used for long-distance communications have a core small enough to support only one fundamental mode in a desired frequency range, and therefore called “single-mode” fibers. Single mode operation is necessary to limit signal degradation caused by modal dispersion, which occurs when a signal can couple to multiple guided modes having different speeds. Nonetheless, the name “single-mode” fiber is something of a misnomer. Actually, single-mode fibers support two optical modes, consisting of the two orthogonal polarizations of light in the fiber. The existence and similarity of these two modes is the source of a problem known as polarization-mode dispersion (PMD). An ideal fiber would possess perfect rotational symmetry about its axis, in which case the two modes would behave identically (they are “degenerate”) and cause no difficulties. In practice, however, real fibers have some acircularity when they are manufactured, and in addition there are environmental stresses that break the symmetry. This has two effects, both of which occur in a random and unpredictable fashion along the fiber: first, the polarization of light rotates as it propagates down the fiber; and second, the two polarizations travel at different speeds. Thus, any transmitted signal will consist of randomly varying polarizations which travel at randomly varying speeds, resulting in PMD: pulses spread out over time, and will eventually overlap unless bit rate and/or distance is limited. There are also other deleterious effects, such as polarization-dependent loss. Although there are other guided modes that have full circular symmetry, and thus are truly “singlet” modes, such modes are not the fundamental modes and are only possible with a core large enough to support multiple modes. In conventional optical fibers, however, the PMD effects associated with the fundamental mode of a small core supporting only a “single-mode” are far preferable to the effects of modal dispersion in a larger core multi-mode fiber.
Another problem with directing optical signals along an optical waveguide is the presence of chromatic or group-velocity dispersion in that waveguide. Such dispersion is a measure of the degree to which different frequencies of the guided radiation propagate at different speeds (i.e., group velocities) along the waveguide axis. Because any optical pulse includes a range of frequencies, dispersion causes an optical pulse to spread in time as its different frequency components travel at different speeds. With such spreading, neighboring pulses or “bits” in an optical signal may begin to overlap and thereby degrade signal detection. Thus, absent compensation, dispersion over an optical transmission length places an upper limit on the bit-rate or bandwidth of an optical signal.
Chromatic dispersion includes two contributions: material dispersion and waveguide dispersion. Material dispersion comes from the frequency-dependence of the refractive index of the material constituents of the optical waveguide. Waveguide dispersion comes from frequency-dependent changes in the spatial distribution of a guided mode. As the spatial distribution of a guided modes changes, it sample different regions of the waveguide, and therefore “sees” a change in the average index of the waveguide that effectively changes its group velocity. In conventional silica optical fibers, material dispersion and waveguide dispersion cancel each other out at approximately 1310 nm producing a point of zero dispersion. Silica optical fibers have also been modified to move the zero dispersion point to around 1550 nm, which corresponds to a minimum in material absorption for silica.
Unfortunately, while operating at zero dispersion minimizes pulse spreading, it also enhances nonlinear interactions in the optical fiber such as four wave mixing (FWM) because different frequencies remain phase-matched over large distances. This is particularly problematic in wavelength-division multiplexing (WDM) systems where multiple signals are carried at different wavelengths in a common optical fiber. In such WDM systems, FWM introduces cross talk between the different wavelength channels as described above. To address this problem, WDM systems transmit signals through optical fibers that introduce a sufficient dispersion to minimize cross-phase modulation, and thereafter transmits the signals through a “dispersion compensating fiber” (DCF), to cancel the original dispersion and minimize pulse spreading in the compensated signal. Unfortunately, aggregate interactions between the dispersion and other nonlinear processes such as self-phase modulation can complicate dispersion compensation.
Another type of waveguide fiber, one that is not based on TIR index-guiding, is a Bragg fiber, which includes multiple dielectric layers surrounding a core about a waveguide axis. The multiple layers form a cylindrical mirror that confines light to the core over a range of frequencies. The multiple layers form what is known as a photonic crystal, and the Bragg fiber is an example of a photonic crystal fiber. Some researchers have commented that Bragg fibers are not feasible for long distance optical transmission (see N. J. Doran and K. J. Blow, J. of Lightwave Tech., LT-1:588, 1983). | {
"pile_set_name": "USPTO Backgrounds"
} |
Q:
wget, self-signed certs and a custom HTTPS server
For various reasons I have created a simple HTTP server, and added SSL support via OpenSSL. I'm using self-signed certificates. IE, Firefox and Chrome happily load content as long as I add the CA to the trusted root CAs.
However, wget (even when using the --no-check-certificate flag) reports:
OpenSSL: error:14094410:SSL routines:SSL3_READ_BYTES:sslv3 alert handshake failure
If I run the OpenSSL client against my server using:
openssl s_client -connect dnvista:82 -debug
I get back:
verify error:num=19:self signed certificate in certificate chain
verify return:0
and then
5852:error:14094410:SSL routines:SSL3_READ_BYTES:sslv3 alert handshake failure:.\ssl\s3_pkt.c:1060:SSL alert number 40
5852:error:140790E5:SSL routines:SSL23_WRITE:ssl handshake failure:.\ssl\s23_lib.c:188:
Do wget and the OpenSSL client simply not work with self-signed certificates?
UPDATE:
For anyone that comes along later, adding this code helped with the OpenSSL client and Firefox:
EC_KEY *ecdh = EC_KEY_new_by_curve_name(NID_X9_62_prime256v1);
SSL_CTX_set_tmp_ecdh(ctx, ecdh);
EC_KEY_free(ecdh);
A:
I checked the man page of wget, and --no-check-certificate only seems to affect the server certificate. You need to specify your self-signed certificate as a valid CA certificate locally.
To do this, specify the certificate as --ca-certificate=... in wget and -CAfile in the s_client case.
A:
You can also install trusted root CA certificates into OpenSSL in one of a number of ways:
Put your CA certificate in /etc/pki/tls/certs or equivalent directory, then create a link based on the certificate hash. See http://gagravarr.org/writing/openssl-certs/others.shtml#ca-openssl for details.
Append your CA certificate to /etc/pki/tls/certs/ca-bundle.crt, /etc/pki/tls/cert.pem, or equivalent CA bundle.
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1. Introduction {#sec1-foods-08-00030}
===============
The use of honey has a long history. The sweet food made by bees obtaining nectar from flowers is called flower honey. When bees obtain the sweet secretions of aphids or other insects, the product is called honeydew \[[@B1-foods-08-00030]\]. Honey is usually maintained in a liquid state. The other is called crystallized honey; many factors such as chemical composition, a degree of supersaturation, viscosity, a fructose/glucose ratio, moisture and dextrine content, water activity, micro-crystals and nucleation seeds presence, age, storage temperature and thermal history all influence its properties \[[@B2-foods-08-00030]\].
Fermentation is a problem for honey. The liquid mixture contains water, fructose and acid, so yeast could develop when the water content reaches a certain level \[[@B3-foods-08-00030]\]. The higher the water content, the greater the occurrence of fermentation and spoilage. The water content in called moisture content (MC) in the food industry. Rockland \[[@B4-foods-08-00030]\] determined that the amount of the free water is really a response to the development of yeast, and not MC. The amount of free water could be described as water activity (Aw). The Aw for honey ranges from 0.5\~0.65 \[[@B5-foods-08-00030],[@B6-foods-08-00030],[@B7-foods-08-00030],[@B8-foods-08-00030],[@B9-foods-08-00030],[@B10-foods-08-00030],[@B11-foods-08-00030]\]. The limiting Aw for yeast in honey is about 0.61\~0.62 \[[@B12-foods-08-00030]\] according to Beuchat et al. \[[@B12-foods-08-00030]\] and 0.60 \[[@B8-foods-08-00030],[@B10-foods-08-00030],[@B13-foods-08-00030],[@B14-foods-08-00030]\] according to Beckh et al. \[[@B13-foods-08-00030]\], Gletier et al. \[[@B8-foods-08-00030]\], Ruegg and Blanc \[[@B14-foods-08-00030]\], and Zamora and Chirife \[[@B10-foods-08-00030]\].
The official method for MC measurement is refractometric measurement. It is inexpensive and easy to use. However, it cannot be directly used for crystallized honey.
With a promising methods for measuring Aw, the MC of honey can then be calculated using a previously established empirical equation. Some experiments have been performed to determine the Aw and MC data of honey, subsequently establishing the relationship between Aw and MC by regression analysis. Several models have been proposed \[[@B5-foods-08-00030],[@B6-foods-08-00030],[@B7-foods-08-00030],[@B9-foods-08-00030],[@B11-foods-08-00030],[@B13-foods-08-00030],[@B14-foods-08-00030],[@B15-foods-08-00030],[@B16-foods-08-00030],[@B17-foods-08-00030],[@B18-foods-08-00030],[@B19-foods-08-00030]\].
The factors affecting the Aw of honey included the type (flower or honey dew), state (liquid or crystallized), climatic and botanical origins, and induced fine granulation \[[@B5-foods-08-00030],[@B6-foods-08-00030],[@B10-foods-08-00030],[@B19-foods-08-00030]\].
Glitter et al. \[[@B8-foods-08-00030]\] compared two types of honey: flower and honeydew, in liquid or crystallized state. At the same MC, Aw was higher for crystallized than for liquid honey. At the same Aw in liquid state, MC was higher for honeydew than for flower honey; there was no difference between the two types in the crystallized state. However, only correlation coefficients (r) between Aw and MC were reported in this study. No statistical methods were reported for comparison.
Cavia et al. \[[@B6-foods-08-00030]\] compared three groups of honey from different climatic regions and harvest years. The *t*-test, used to assess differences between groups, revealed no significant difference among the groups. The author then pooled the three groups of datasets and proposed an empirical equation. In comparing this equation with that in the literature, the intercepts and slopes of these equations differed. The authors mention these differences related to the measurement of Aw and MC.
Chirife et al. \[[@B7-foods-08-00030]\] established a linear equation for Aw and MC from 36 liquid Argentinian honey samples and compared this equation with that from Beck et al. \[[@B13-foods-08-00030]\]. The slope and intercept differed, and the results were attributed to the lack of accuracy of measurement techniques and the inference of different botanical sources and geographical collection sites. Abramovic et al. \[[@B5-foods-08-00030]\] investigated the correlation between Aw and MC for flower and honeydew honey in Slovenia. At the same MC, Aw was higher for honeydew than for flower honeys. The two datasets were pooled and a linear equation for Aw and MC was established. Comparing regression parameters with five other empirical equations in the literature, the difference found was attributed to the sugar composition and measurement of Aw. Zamora et al. \[[@B11-foods-08-00030]\] examined the data from Beckh et al. \[[@B13-foods-08-00030]\] in fluid, partially crystalline and crystalline honey and found no significant differences by F-test. However, the determination of coefficient $R^{2}$ was only 0.53 for the pooled data. Zamora et al. \[[@B11-foods-08-00030]\] found no significant difference in the relationship between Aw and MC for honey by botanical source or collection site. Comparing four regression equations in the literature, the authors found that the slope for the three datasets was similar \[[@B11-foods-08-00030]\]. Perez et al. \[[@B8-foods-08-00030]\] reviewed 10 datasets for Aw and MC in flower honey and proposed a weighted average regression equation by using meta-analysis.
Recently, modern regression analysis was proposed to analyze treatment \[[@B20-foods-08-00030],[@B21-foods-08-00030],[@B22-foods-08-00030]\]. If the influencing factor for the treatment has several levels of qualitative categories, the significance of these treatments can be tested by categorical testing with regression analysis \[[@B20-foods-08-00030],[@B21-foods-08-00030],[@B22-foods-08-00030]\].
The objectives of this study were to: (1) determine the Aw/MC relationships for floral honey between 10 and 30 °C; and (2) evaluate the factors affecting the sorption isotherms of honey with previously published data by using regression analysis.
2. Materials and Methods {#sec2-foods-08-00030}
========================
2.1. Materials {#sec2dot1-foods-08-00030}
--------------
The floral honey used for this study was Longyuan honey collected at the Chunglaun Township, Nantou, Taiwan. The initial moisture content of the sample was 17.16% on a w.b.
The desired moisture content for storage and processing ranges from 17% to 22% w.b. The samples were rewetted by adding the amount of the water necessary to reach the desired moisture content. The sample preparation was performed according to the study by Shen and Chen \[[@B23-foods-08-00030]\]. All samples were sealed in glass vessels and stored at 5 °C for three weeks to ensure uniform moisture content. The moisture content of the honey was measured by using the ATAGO DR-A1 ABBE Refractometer (Atago Inc., Bellevue, WA, USA). The total number of sample in this study was 27. There were nine moisture contents, and three replicates of each moisture content.
2.2. RH Meter {#sec2dot2-foods-08-00030}
-------------
The THT-V2 humidity transmitter (Shinyei technology, Kobe, Japan) was used to determine the water activity of the floral honey. These RH sensors were calibrated with several saturated salt solutions, and the accuracy of the RH meter was within 0.7% RH after calibration. All measured RH values were transformed into actual values by using previously established calibration equations to enhance its accuracy.
2.3. Aw Method {#sec2dot3-foods-08-00030}
--------------
The set-up for the Aw method is shown in [Figure 1](#foods-08-00030-f001){ref-type="fig"}. Samples at known moisture contents were placed in a glass vessel, sealed with a rubber stopper to ensure airtight conditions, and then placed in a temperature-controlled chamber that was maintained at 5 °C. The volume of the vessel was 250 mL. When the temperature and the RH within the container were stabilized, the vapor pressure of the samples and the interstitial air in the vessel reached the equilibrium state. The RH and temperature values were determined. To ensure the equilibrium state, each temperature level was maintained for 12 h, then adjusted to next temperature level. All Aw values were measured at five temperatures (10, 15, 20, 25 and 30 °C). After finishing the experiments, the samples were taken from each vessel to determine the moisture content using the ATAGO DR-A1 ABBE Refractometer.
This technique has been used to determinate sorption isotherm for autoclaved aerated concrete \[[@B24-foods-08-00030]\], sweet potato slices \[[@B25-foods-08-00030]\], pea seeds \[[@B26-foods-08-00030]\] and Oolong tea \[[@B27-foods-08-00030]\].
2.4. Literature Survey {#sec2dot4-foods-08-00030}
----------------------
The six datasets from five countries used to evaluate the factors affecting the regression parameters between Aw and MC are in [Table 1](#foods-08-00030-t001){ref-type="table"}. The published models used, along with the data from the literature and seven other published models, are displayed in [Table 2](#foods-08-00030-t002){ref-type="table"}.
2.5. Categorical Tests {#sec2dot5-foods-08-00030}
----------------------
If the influencing factor has several levels of qualitative categories, the significance of the qualitative treatment could be tested by *t*-test or F-test.
### 2.5.1. Testing the Slope for Two Treatments {#sec2dot5dot1-foods-08-00030}
To evaluate the effect of categorical variables such as type or state of honey, an indicator variable is used. The equation for the regression line relating two types of datasets that differ in both intercept and slope are as follows:$$y = b_{o} + b_{1}X_{1} + b_{2}Z_{1} + b_{3}X_{1}Z_{1} + \varepsilon$$ $$Z_{1} = 0,if~the~data~is~from~f{{actor}~A},$$ $$~~Z_{1} = 1,if~the~data~is~from~f{{actor}~B}$$ $${For}~{factor}~A:~y = b_{o} + b_{1}X_{1} + \varepsilon$$ $${For}~{factor}~A:~y = \left( {b_{o} + b_{2}} \right) + \left( {b_{1} + b_{3}} \right)X_{1} + \varepsilon$$ $$H_{0}:b_{2} = b_{3} = 0$$ $$H_{1}:b_{2} \neq 0,b_{3} \neq 0$$
To test the hypothesis that two regression lines have the same slope or intercept, we could use the *t*-test.
### 2.5.2. Testing the Slope for Three Treatments {#sec2dot5dot2-foods-08-00030}
For three treatments, the regression equations relating datasets that differ in both intercept and slope are as follows:$$~y = b_{o} + b_{1}X_{1} + b_{2}Z_{1} + b_{3}Z_{2} + b_{4}X_{1}Z_{1} + b_{5}X_{1}Z_{2} + \varepsilon$$ $$Z_{1} = Z_{2} = 0,if~the~observation~is~from~A,$$ $$Z_{1} = 1~and~Z_{2} = 0,if~the~observation~is~from~B,$$ $$Z_{1} = 0~and~Z_{2} = 1,if~the~observationis~from~C,$$ $${For}~{factor}~A:~y = b_{o} + b_{1}X_{1} + \varepsilon$$ $${For}~{factor}~B:~y = \left( {b_{o} + b_{2}} \right) + \left( {b_{1} + b_{4}} \right)X_{1} + \varepsilon$$ $${For}~{factor}~C:~y = \left( {b_{o} + b_{3}} \right) + \left( {b_{1} + b_{5}} \right)X_{1} + \varepsilon$$ $$H_{0}:b_{4} = b_{5} = 0$$ $$H_{1}:b_{4} \neq 0,b_{5} \neq 0$$
### 2.5.3. Two Indicator Variables {#sec2dot5dot3-foods-08-00030}
If the qualitative variables have two qualitative factors (e.g., flower and honeydew, crystallized and liquefied), the regression line can be expressed as follows:$$y = b_{o} + b_{1}X_{1} + b_{2}Z_{1} + b_{3}Z_{2} + b_{4}X_{1} + b_{5}X_{1}Z_{2} + \varepsilon$$ $$a:~{liquefied},~{flower}:~Z_{1} = 0,Z_{2} = 0$$ $$y = b_{o} + b_{1}X_{1} + ~\varepsilon$$ $$b:~{crystallized},~{flower}:~Z_{1} = 0,Z_{2} = 1$$ $$y = \left( {b_{o} + b_{3}} \right) + \left( {b_{o} + b_{5}} \right)X_{1} + \varepsilon$$ $$c:~{liquefied},~{honeydew}:~Z_{1} = 1,Z_{2} = 0$$ $$y = \left( {b_{o} + b_{2}} \right) + \left( {b_{o} + b_{4}} \right)X_{1} + \varepsilon$$ $$d:~{crystallized},~{honeydew}:~Z_{1} = 1,Z_{2} = 1$$ $$y = \left( {b_{o} + b_{2} + b_{3}} \right) + \left( {b_{1} + b_{4} + b_{5}} \right)X_{1} + \varepsilon$$
3. Results {#sec3-foods-08-00030}
==========
3.1. Water Activity of Honey {#sec3dot1-foods-08-00030}
----------------------------
The Aw/MC data at five temperatures are shown in [Figure 2](#foods-08-00030-f002){ref-type="fig"}. Temperature significantly affected the Aw/MC data.
The results of the estimated parameters and comparison statistics for the linear equation at different temperature are in [Table 3](#foods-08-00030-t003){ref-type="table"}. The effect of temperature on parameters A and B is shown in [Figure 3](#foods-08-00030-f003){ref-type="fig"} and [Figure 4](#foods-08-00030-f004){ref-type="fig"}.
The empirical regression equations between parameters and temperature were established. The equation for A and B was expressed as:$${A~ = ~ - 0.06999~ - ~0.0019264{Temp}~ + ~3.000030~ \times 10^{- 4}}{{Temp}^{2},R^{2} = 0.991}$$ $${B~ = ~0.03516~ - ~0.0010345{Temp}~ + ~1.4149~ \times 10^{- 5}}{{Temp}^{2},R^{2} = 0.990}$$
Three forms of the linear equation that incorporated the temperature term were proposed as follows:$${{Aw}~ = ~ - 0.06999~ - ~0.0019264{Temp}~ + ~3.000030~ \times 10^{- 4}{Temp}^{2}~ + ~0.3516}{\left. - 0.0010345{Temp}~ + ~1.4149 \times 10^{- 5}{Temp}^{2} \right){MC}}$$
3.2. Comparison with Published Data {#sec3dot2-foods-08-00030}
-----------------------------------
The Aw/MC linear equation of floral honey at 25 °C in this study was compared with published data ([Figure 5](#foods-08-00030-f005){ref-type="fig"}). At MC \< 20.5%, the Aw values of this study were lower than other data. However, when MC \> 20.5%, the Aw values of this study were higher than those of Gleiter et al. \[[@B8-foods-08-00030]\]. The reason for this could be that the Aw/MC data were affected by honey type (flower or honeydew), harvesting year, geographical collection site, botanical source and other factors. Further study was executed to study the factors influencing the Aw/MC data.
3.3. Effect of Honey Type on Aw {#sec3dot3-foods-08-00030}
-------------------------------
Two types of honey (flower and honeydew) \[[@B5-foods-08-00030]\] were used to evaluate the factors affecting the relationship between Aw and MC by Equation (1). The data distribution and predicted lines are in [Figure 6](#foods-08-00030-f006){ref-type="fig"}.
The results of the linear regression are as follows: $$\begin{array}{cllll}
{{Aw} =} & {0.20801 +} & {0.019985{MC} -} & {0.00189Z +} & {0.00108Z \cdot {MC}} \\
& \left( 11.45 \right) & \left( 17.29 \right) & \left( - 0.074 \right) & \left( 0.66 \right) \\
\end{array}$$ $$R^{2}~ = ~0.823$$ where *Z* is the categorized variable, *Z* = 0 is flower honey and *Z* = 1 is honeydew honey. The numbers in parentheses below the estimated values of parameters are *t*-test values for the estimated value. The *t* and *p* values for Z·MC were 0.665 and 0.112, respectively. Type had no significant effect on the Aw and MC relationship.
The adequate equation was as follows: $$\begin{array}{clll}
{{Aw} =} & {0.19964 +} & {0.020579{MC} +} & {0.014766Z} \\
& \left( 15.49 \right) & \left( 25.06 \right) & \left( 9.18 \right) \\
\end{array}$$
For flower honey,
For honeydew honey,
From Equation (17)--(19), we found no significant difference in the slope of the linear equation for flower and honeydew honey. However, the intercept significantly differed with two types of honey.
3.4. Effect of the Type and State of Honey on the Aw and MC Relationship {#sec3dot4-foods-08-00030}
------------------------------------------------------------------------
The datasets for Glitter et al. \[[@B8-foods-08-00030]\] included different honey types (flower and honeydew) and states (liquid and crystallized). Two indicator variables were analyzed by Equation (8).
The regression equation was as follows:$$\begin{array}{clllll}
{{Aw} =} & {0.30845 +} & {0.016905{MC} +} & {0.018156Z_{1} +} & {0.034193Z_{2} -} & {0.00391Z_{2} \cdot {MC}} \\
& \left( 24.12 \right) & \left( 21.83 \right) & \left( 14.76 \right) & \left( 2.71 \right) & \left( - 3.93 \right) \\
\end{array}$$ $$R^{2}~ = ~0.831$$
For crystallized flower honey, $Z_{1}$ = 0, $Z_{2}$ = 0,
For liquid flower honey, $Z_{1}$ = 0, $~Z_{2}$ = 1.0
For crystallized honeydew honey,$~Z_{1} = 1.0,~~Z_{2} = 0$
For liquid honeydew honey, $Z_{1} = 1.0,~~Z_{2} = 1.0$
The results indicated a significant difference in the intercept. With the same crystallized state, flower and honeydew honey had a similar slope, 0.016905. With the same liquid state, the slope was 0.012995. That is, the state not the type of honey significantly affects the slope parameter of the Aw linear equation. The prediction lines of two states and two types of honey are in [Figure 7](#foods-08-00030-f007){ref-type="fig"}.
3.5. Comparison of the Correlation between Aw and MC with Two Datasets {#sec3dot5-foods-08-00030}
----------------------------------------------------------------------
Several datasets for Aw and MC for honey were used to evaluate factors affecting correlation between the Aw and MC.
### 3.5.1. Argentinian \[[@B7-foods-08-00030]\] and Slovenian Honeys \[[@B5-foods-08-00030]\] {#sec3dot5dot1-foods-08-00030}
The datasets from different countries with the liquid state are in [Figure 8](#foods-08-00030-f008){ref-type="fig"}.
Two datasets for Slovenia honey were pooled and evaluated by Equation (4). The regression equation was as follows:$$\begin{array}{cllll}
{{Aw} =} & {0.22826 +} & {0.019149{MC} +} & {0.0412Z -} & {0.00147Z \cdot {MC}} \\
& \left( 15.64 \right) & \left( 20.39 \right) & \left( 1.449 \right) & \left( - 0.901 \right) \\
\end{array}$$
The *t*-test value for *Z*·MC was −0.901 and not significant. The adequate linear equation was as follows:$$\begin{array}{clll}
{{Aw} =} & {0.23581 +} & {0.018662{MC} +} & {0.015256Z} \\
& \left( 19.75 \right) & \left( 24.30 \right) & \left( 5.66 \right) \\
\end{array}$$
### 3.5.2. German and Slovenian Honeys {#sec3dot5dot2-foods-08-00030}
The datasets for Aw and MC for the two countries had the same slope, but a different intercept.
The datasets from Germany (pooled flower and honeydew, liquid state) \[[@B8-foods-08-00030]\] and Slovenia (liquid state) honey \[[@B5-foods-08-00030]\] are in [Figure 9](#foods-08-00030-f009){ref-type="fig"} and were used for assessing the influencing factors.
The linear equation was as follows:$$\begin{array}{cllll}
{{Aw} =} & {0.22826 +} & {0.019149{MC} +} & {0.095601Z -} & {0.00302Z \cdot {MC}} \\
& \left( 14.40 \right) & \left( 18.76 \right) & \left( 4.88 \right) & \left( - 1.080 \right) \\
\end{array}$$
The *t*-test value for $Z \cdot$MC was insignificant. The adequate equation is as follows:$$\begin{array}{clll}
{{Aw} =} & {0.31305 +} & {0.013680{MC} +} & {0.026313Z} \\
& \left( 28.94 \right) & \left( 19.74 \right) & \left( 15.31 \right) \\
\end{array}$$
The type (flower or honeydew) did not significantly affect the slope.
### 3.5.3. Mixed-Source and Slovenian Honeys {#sec3dot5dot3-foods-08-00030}
The datasets from different types and states \[[@B13-foods-08-00030]\] and Slovenian honey (pooled liquid states: flower and honeydew) \[[@B5-foods-08-00030]\] are evaluate in [Figure 10](#foods-08-00030-f010){ref-type="fig"}.
The linear regression was as follows: $$\begin{array}{cllll}
{{Aw} =} & {0.22826 +} & {0.019149M +} & {0.11401Z -} & {0.00507Z \cdot {MC}} \\
& \left( 13.31 \right) & \left( 13.43 \right) & \left( 4.0513 \right) & \left( - 2.96 \right) \\
\end{array}$$
The *Z*$\cdot$MC had a *t*-test value of -2.96 and *p* = 0.00336, showing a significant effect. Both datasets had different slopes and intercepts.
Chirife et al. \[[@B7-foods-08-00030]\] compared the correlation for Argentina fluid honey and mixed honey from different countries \[[@B13-foods-08-00030]\] and found that the intercept and slopes of both differed. These results could be explained by the source of the honey. The Argentinian honey was liquid, the mixed honey included liquid, crystallized and partially crystallized states.
### 3.5.4. Spanish and Slovenian Honeys {#sec3dot5dot4-foods-08-00030}
The datasets from Spain (flower honey, unknown state) \[[@B6-foods-08-00030]\] and Slovenia (pooled data of liquid states, flower and honeydew) \[[@B5-foods-08-00030]\] are in [Figure 11](#foods-08-00030-f011){ref-type="fig"}. The regression equation was as follows:$$\begin{array}{cllll}
{{Aw} =} & {0.22826 +} & {0.019149{MC} +} & {0.094645Z -} & {0.00273Z \cdot {MC}} \\
& \left( 13.41 \right) & \left( 17.48 \right) & \left( 5.03 \right) & \left( - 2.30 \right) \\
\end{array}$$
The *t*-test value for *Z*$\cdot$MC was −2.30, with *p* = 0.022, so datasets for the two countries had different slopes and intercepts.
### 3.5.5. German (Crystallized State) and Slovenian (Liquid State) Honeys {#sec3dot5dot5-foods-08-00030}
The datasets from Gleiter et al. \[[@B8-foods-08-00030]\] and Abramovic et al. \[[@B5-foods-08-00030]\] for honey in different states are assessed ([Figure 12](#foods-08-00030-f012){ref-type="fig"}).
The regression equation was as follows:$$\begin{array}{cllll}
{{Aw} =} & {0.22826 +} & {0.019149{MC} +} & {0.14899Z -} & {0.00719Z \cdot {MC}} \\
& \left( 12.01 \right) & \left( 15.66 \right) & \left( 6.46 \right) & \left( - 5.34 \right) \\
\end{array}$$
The linear equations for the two datasets had different slopes and intercepts.
### 3.5.6. Comparing the Correlation between Aw and MC with Three Datasets {#sec3dot5dot6-foods-08-00030}
**a. Case 1**
Three datasets were used: German liquid flower ($Z_{1}$ = 0, $Z_{2} = 0$) and honeydew ($Z_{1}$ = 1,$~Z_{2} = 0$) honey \[[@B8-foods-08-00030]\] and Argentinian liquid honey ($Z_{1}$ = 0,$~Z_{2} = 1$) \[[@B7-foods-08-00030]\].
The linear equation was as follows:$$\begin{array}{cllll}
{{Aw} =} & {0.31565 +} & {0.014452{MC} +} & {0.009275Z_{1} +} & {0.02677Z_{2}} \\
& \left( 39.61 \right) & \left( 30.26 \right) & \left( 4.87 \right) & \left( 20.06 \right) \\
\end{array}$$
The slope of the three datasets was identical, and the intercepts significantly differed.
**b. Case 2**
Three datasets, Slovenian \[[@B5-foods-08-00030]\] liquid honeydew ($Z_{1}$ = 0,$~Z_{2} = 0$) and flower honey ($Z_{1}~$= 1,$~Z_{2} = 0$) and Argentinian liquid honey \[[@B7-foods-08-00030]\], were used.
The linear equation was as follows:$$\begin{array}{cllll}
{{Aw} =} & {0.21471 +} & {0.019558{MC} +} & {0.020636Z_{1} +} & {0.014421Z_{2}} \\
& \left( 21.62 \right) & \left( 31.07 \right) & \left( 9.15 \right) & \left( 9.54 \right) \\
\end{array}$$
The slope of the three datasets was identical and the intercepts significantly differed.
Zamora et al. \[[@B10-foods-08-00030]\] compared regression equations for Aw and MC for honey from different countries and found no significant difference based on botanical source or geographical collection site. Our study confirms these results.
**c. Case 3**
Three datasets, German crystallized flower and honeydew honey ($Z_{1}$ = 0,$~Z_{2} = 0$) \[[@B8-foods-08-00030]\], Argentinian liquid honey ($Z_{1~}$= 1,$~Z_{2} = 0$) \[[@B7-foods-08-00030]\] and Slovenian liquid honeydew and flower honey ($Z_{1}$ = 0,$~Z_{2} = 1$) \[[@B5-foods-08-00030]\], were used. The linear equation was as follows:$$\begin{array}{cllllll}
{{Aw} =} & {0.31724 +} & {0.01136{MC} -} & {0.14899Z_{1} -} & {0.10886Z_{2} +} & {0.007789Z_{1} \cdot {MC} +} & {0.006316Z_{2} \cdot {MC}} \\
& \left( 29.95 \right) & \left( 14.77 \right) & \left( - 6.70 \right) & \left( - 3.38 \right) & \left( 5.53 \right) & \left( 3.42 \right) \\
\end{array}$$
The slopes and intercepts of the three datasets significantly differed.
### 3.5.7. Outlier Detection {#sec3dot5dot7-foods-08-00030}
The intercept and slope of the equation for the dataset of flower honey from La Palma Island, Spain, significantly differed from those in other datasets \[[@B9-foods-08-00030]\]. Outlier data (17.2233, 0.6084) was found by the Cook's distance test \[[@B21-foods-08-00030]\]. The original linear equation proposed by the authors was as follows:$${Aw}~ = ~0.35732~ + ~0.01349{MC},~R^{2}~ = ~0.63$$
After deleting this data, the new equation was as follows:$${Aw}~ = ~0.32842~ + ~0.01495{MC},~~R^{2}~ = ~0.93$$
The comparison between Equations (32) and (33) is shown in [Figure 13](#foods-08-00030-f013){ref-type="fig"}.
After deleting this data point, the slope, intercept and coefficient of determination changed obviously.
If we compare all data from Sanjuan et al. \[[@B9-foods-08-00030]\] with the datasets for Argentinian honey \[[@B7-foods-08-00030]\], the linear equation was as follows:$$\begin{array}{cllll}
{{Aw} =} & {0.26838 +} & {0.017675{MC} -} & {11.4662Z +} & {48.35758Z \cdot {MC}} \\
& \left( 0.48 \right) & \left( 0.59 \right) & \left( - 3.22 \right) & \left( 8.15 \right) \\
\end{array}$$
The intercept and slope for the two datasets differed significantly.
If the outlier was deleted from the datasets of Sanjuan et al. \[[@B9-foods-08-00030]\], the equation for evaluating the two datasets was as follows:$$\begin{array}{clll}
{{Aw} =} & {0.27478 +} & {0.017310{MC} +} & {0.013714Z} \\
& \left( 25.40 \right) & \left( 28.19 \right) & \left( 7.31 \right) \\
\end{array}$$
The slope of the two datasets was identical. From the results of Equations (37) and (38), the outlier significantly affected the comparison results for the two datasets. With modern regression analysis, more useful information on correlation between Aw and MC could be found. The results indicated the importance of finding the correct equation with modern regression.
4. Discussion {#sec4-foods-08-00030}
=============
Based on the study of the datasets of Gleiter et al. \[[@B8-foods-08-00030]\], the intercept parameters differed significantly. The slope parameter could be classified into two categories: liquid and crystallized. Thus, the slope for the linear equation was affected only by the state of the honey. The type of honey, flower and honeydew, and other factors did not affect the slope but did affect the intercept.
Chirife et al. \[[@B7-foods-08-00030]\] found that Aw in honey was determined mainly by the concentrations of fructose and glucose that are most abundant in honey. The authors developed an Aw equation from the effect of the osmotic concertation on the osmotic coefficient, which was as follows: where Φ is the osmotic coefficient, m is molality and v is the number of moles of kinetic units.
By Taylor's expansion, and assuming 0.018mv \<\< 1, the new relationship is as follows:
For very concentrated and small intervals of sugar solutions, Equation (40) was rewritten as follows:$${Aw}~ = ~A~ - ~B~\left( s \right)~ = ~b_{0} + b_{1}{MC}$$where (s) is the solid concentration in water, and A and B are constants.
In this study, we found the slope to be affected only by the state of the honey (liquid or crystallized). The other factors, such as type (flower or honeydew), geographical collection sites and botanical source did not significantly affect the slope, but did affect the intercept of the Aw equation.
Perez et al. \[[@B18-foods-08-00030]\] selected 10 datasets of flower honey to study the relationship between Aw and MC and found similar but not identical the slopes and intercepts of these linear regressions. The authors attributed the finding to sampling error, accuracy of the Aw measurement, and variation in sugar composition. The slopes for 10 datasets ranged from 0.0149 to 0.0197. However, the state of honey was not mentioned in this research. We found a slope of 0.016905 for crystallized honey and 0.012995 for liquid honey for the datasets of Gleiter et al. \[[@B8-foods-08-00030]\]. The wide slope range for the 10 datasets from the study of Perez et al. \[[@B18-foods-08-00030]\] may be explained by the effects due to the state of honey. The slope for the linear equation for Slovenia honey \[[@B5-foods-08-00030]\] and five other datasets ranged from 0.014 to 0.0196. The difference in parameters was attributed to sugar composition and the Aw determination methods by the authors. The significant difference between the two maximum and minimum slope values, 0.014 and 0.0196, could be explained by the state of the honey.
The study by Cavia et al. \[[@B6-foods-08-00030]\] included three groups of samples. The *G*~1~ and *G*~2~ datasets were obtained in 1996 and 1998 from a continental climate, and the *G*~3~ datasets was obtained in 1998 from an oceanic climate. The slopes for the Aw model were 0.02149 and 0.02362 for *G*~1~ and *G*~2~ and 0.01476 for *G*~3~. The significant difference between the three slopes could be explained by the effect of climate on the state of the honey. The crystallized state enhanced by the continental climate may be due to the difference in slope values.
The MC of honey is considered to be the criterion for the honey industry. The MC is usually determined by the refractometric technique. The method is simple and inexpensive. However, the MC could be affected by weather conditions, original moisture content of the nectar, and environmental temperature and humidity after harvesting. The storage materials and sealed technique also affect MC. The MC of the crystallized state cannot be directly measured by refractometer.
The Aw is measured by some commercial equipment. The criterion of Aw \< 0.6 may be used as a safety standard to prevent the development of osmotolerant yeasts. Recently, the performance of electronic hygrometers has been improved. They have been used to determine the Aw of tea leaves and other materials \[[@B23-foods-08-00030],[@B24-foods-08-00030]\].
In this study, we found an effect of factors on slope for the correlation between Aw and MC. The state of honey, crystallized and liquid, had a significant effect on the slope value. However, other factors, such as harvesting year, botanic source and collection sites did not affect the slope but did affect the intercept. Therefore, no universal linear equation for Aw and MC could be established. The Aw value may be used as the criterion for the honey industry and directly determined by an electronic hygrometer. Then the MC of honey could be calculated by the specific linear equation between Aw and MC. The effect of the temperature needs to be considered.
In the traditional MC and AW determination method, honey must be liquefied previously, so that all crystals are totally melted, such that all measurements can be done with liquid honey. By the Aw method used in this study, the Aw values of crystallized honey could be determined directly in the crystalline state.
In this study, the moisture content of liquid honey was measured by using a refractometer. There are two official procedures Association Official Analytical Chemists (AOAC) and European Honey Commission (EHC) \[[@B28-foods-08-00030],[@B29-foods-08-00030]\] for determining the moisture content. A comparison between the official method and the refractometer has been reported \[[@B30-foods-08-00030]\]. The comparison between the official method and the refractometer of floral honey used in this study will be further studied.
5. Conclusions {#sec5-foods-08-00030}
==============
Conclusions were drawn from the results of this study.
The Aw/MC data at five temperatures were determined, and temperature significantly affected the Aw/MC data. The linear equation could be used to express the relationship between Aw and MC of Honeys. The empirical regression equations between parameters and temperature were established. The intercept and slope of the linear equation could be expressed as the polynomial equations.
The slope of the correlation between Aw and MC was affected by the state of honey (liquid and crystallized). The intercept was significantly affected by honey type (flower or honeydew), harvesting year, geographical collection site and botanical source. The outliers in the dataset significantly affected the comparison results. Modern regression analysis can provide useful information for the correlation between Aw and MC. No universal linear equation for Aw and MC could be established. The Aw value may be used as the criterion for honey industry, and then the MC of honeys can be calculated by the specific linear equation between Aw and MC.
The author would like to thank the Ministry of Science and Technology of the Republic of China for financially supporting this research under Contract No. MOST-104-2313-B-005-031.
This research received no external funding.
The author declare no conflict of interest.
{#foods-08-00030-f001}
{#foods-08-00030-f002}
{#foods-08-00030-f003}
{#foods-08-00030-f004}
![Comparison of Aw/MC equation at 25 °C with models from literature: \[[@B5-foods-08-00030],[@B7-foods-08-00030],[@B8-foods-08-00030],[@B9-foods-08-00030],[@B10-foods-08-00030],[@B12-foods-08-00030],[@B18-foods-08-00030]\].](foods-08-00030-g005){#foods-08-00030-f005}
![The relationship between water activity (Aw) and moisture content (MC) of flower and honeydew honey in Slovenia \[[@B5-foods-08-00030]\].](foods-08-00030-g006){#foods-08-00030-f006}
![The prediction equations between water activity and moisture content including different type (flower and honeydew) and state (liquid and crystallized) of honey \[[@B8-foods-08-00030]\].](foods-08-00030-g007){#foods-08-00030-f007}
![The relationship between water activity and moisture content of flower and honeydew honey from Argentinian \[[@B7-foods-08-00030]\] and Slovenia \[[@B5-foods-08-00030]\].](foods-08-00030-g008){#foods-08-00030-f008}
![The relationship between water activity and moisture content for datasets for honey from Germany (pooled of the flower and honeydew, liquid state) \[[@B8-foods-08-00030]\] and Slovenia (liquid state) \[[@B5-foods-08-00030]\].](foods-08-00030-g009){#foods-08-00030-f009}
![The relationship between water activity and moisture content for datasets for honey of different types and states \[[@B13-foods-08-00030]\] and Slovenia (pooled data of liquid states: flower and honeydew) \[[@B5-foods-08-00030]\].](foods-08-00030-g010){#foods-08-00030-f010}
![The relationship between water activity and moisture content for datasets for honey from Spain (flower honeys, unknown state) \[[@B6-foods-08-00030]\] and Slovenia (pooled data of liquid states, flower and honeydew) \[[@B5-foods-08-00030]\].](foods-08-00030-g011){#foods-08-00030-f011}
![The relationship between water activity and moisture content for datasets for honey from Germany \[[@B8-foods-08-00030]\] and Slovenia \[[@B5-foods-08-00030]\].](foods-08-00030-g012){#foods-08-00030-f012}
![The comparison between two equations with and without outliers in the datasets of Sanjuan et al. \[[@B9-foods-08-00030]\].](foods-08-00030-g013){#foods-08-00030-f013}
foods-08-00030-t001_Table 1
######
Selected studies on the relationship between water activity and moisture content in honey.
----------------------------------------------------------------------------------------------------------------------------------------------------------------
Types Geographical Original of Honeys Aw Determination Method Sample Size Moisture Range (%) Reference
--------------------- --------------------------------- ------------------------- ------------- -------------------- -------------------------------------------
Honeydew and flower Slovenia Cx-2T\ 150 13.4-18.6 Abramovic et al. \[[@B5-foods-08-00030]\]
Chill-mirror\
Aw system
Flower Spain\ Cx-2T\ 90 14.2-21.5 Cavia et al. \[[@B6-foods-08-00030]\]
(liquid and crystallized) Chill-mirror\
Aw meter
Flower Argentine Aqual series 3\ 35 13.8-20.8 Chirife et al. \[[@B7-foods-08-00030]\]
Model TE dew-point\
Aw meter
Honeydew and flower Germany Navasian Aw meter 166 14.2-22.7 Gleiter et al. \[[@B8-foods-08-00030]\]
Flower Spain Aqual series 3\ 13 16.5\~19.4 Sanjuan et al. \[[@B9-foods-08-00030]\]
Model TE dew-point\
Aw meter
Flower Argentine\ Aqual series 3\ 36 15.8\~27.1 Zamora et al. \[[@B11-foods-08-00030]\]
(liquid and crystallized) Model TE dew-point\
Aw meter
----------------------------------------------------------------------------------------------------------------------------------------------------------------
foods-08-00030-t002_Table 2
######
Published equations of water activity and moisture content of honey.
Study Equations $\mathbf{\mathbf{R}^{2}~\left( r \right)}$ Reference
--------------------------------------- -------------------------- -------------------------------------------- --------------------------------------------
I. Datasets used in this study.
1\. Aw = 0.23 + 0.019MC (0.843) Abramovic et al. \[[@B5-foods-08-00030]\]
2\. Aw = 0.2674 + 0.01955MC (0.709) Cavia et al. \[[@B6-foods-08-00030]\]
3\. Aw = 0.262 + 0.0179MC 0.969 Chirife et al. \[[@B7-foods-08-00030]\]
4\. Aw = 0.35732 + 0.01349MC 0.654 Sanjuan et al. \[[@B9-foods-08-00030]\]
5\. Aw = 0.305 + 0.0155MC 0.969 Zamora et al. \[[@B11-foods-08-00030]\]
II\. Datasets not used in this study.
1\. Aw = 0.13 + 0.025MC (0.8230) Alcala and Gomez \[[@B15-foods-08-00030]\]
2\. Aw = 0.342 + 0.014MC (0.723) Beckh et al. \[[@B13-foods-08-00030]\]
3\. Aw = 0.25643 + 0.01965MC (0.813) Estupinan et al. \[[@B16-foods-08-00030]\]
4\. Aw = 0.38242 + 0.01211MC (0.765) Millan et al. \[[@B17-foods-08-00030]\]
5\. Aw = 0.2686 + 0.01756MC Meta-analysis Perez et al. \[[@B18-foods-08-00030]\]
6\. Aw = 0.0.271 + 0.0177MC (0.901) Ruegg and Blanc \[[@B14-foods-08-00030]\]
7\. Aw = 0.248 + 0.0175MC (0.973) Salamanca et al. \[[@B19-foods-08-00030]\]
foods-08-00030-t003_Table 3
######
Estimated values of parameters in the linear equation.
----------------------------------------------------------------------------------------------------------------------------------------------------
Temperature °C Parameters $\mathbf{{Coefficients}~{of}~{Determination}~\mathbf{R}^{2}}$ Standard of Deviations of Estimated Values\
s
---------------- ------------ --------------------------------------------------------------- --------------------------------------------- --------
10 0.09520 0.026172 0.908 0.3195
15 0.14395 0.023511 0.936 0.2611
20 0.20243 0.020089 0.987 0.2165
25 0.22204 0.018839 0.968 0.1710
30 0.23771 0.017768 0.958 0.1536
----------------------------------------------------------------------------------------------------------------------------------------------------
| {
"pile_set_name": "PubMed Central"
} |
Contains a cycle of 11 folk-song settings for mixed choir with chamber ensemble (or chamber orchestra). Titles featured are: The Bold Grenadier, The Keel Row, The Willow Tree, The Sprig of Thyme, Down By The Sally Gardens, The Cuckoo, I Know Where I'm Going, Willow Song, O Can Ye Sow Cushions, The Miller of Dee and Afton Water. | {
"pile_set_name": "Pile-CC"
} |
City of Mesa Cemetery
The City of Mesa Cemetery is a historic cemetery located at 1212 N. Center Street in the city of Mesa, Arizona. It is the final resting place of various notable early citizens of Mesa. Among those who are interred in the cemetery are early pioneers, mayors, businessman, criminals and veterans of the United States Armed Forces.
History
The first known inhabitants of the area were the Hohokam, a Native-American tribe. The Hohokam were the builders of the original canal system in this area and the area of Maricopa in general. The canals were the largest and most sophisticated in the prehistoric Western Hemisphere. It is unknown what happened to the Hohokam and their destiny. With the disappearance of the Hohokam, the area was then settled by the members of the Apache tribe.
In 1877, Daniel Webster Jones, a Mormon pioneer, left St. George, Utah to led an expedition in Arizona with the intention of founding a Mormon settlement. Jones' settlement was initially known as Jonesville.
Pioneers Francis Martin Pomeroy, Charles Crismon, George Warren Sirrine and Charles I. Robson arrived from Utah and founded the First Mesa Company. This company dug irrigation canals, but not in Jonesville. Instead the canal were dug on top of a mesa nearby, thus the namesake of the current town. In 1880 the Second Mesa Company settled to the west of the First Mesa Company.
On July 17, 1878, Mesa City was registered as a townsite and in 1883, the first cemetery in Mesa was established. In 1891, the citizens of Mesa decided to purchase land along Center Street north of Brown Road to officially establish acuity cemetery after a smallpox epidemic that claimed the lives of 44 residents. In this land they established what is now the City of Mesa Cemetery. The cemetery is operated by the City of Mesa Parks, Recreation and Community Facilities Department.
The cemetery is divided into the following five interment sections:
The Garden Section
The Original Section
The Rolling Meadows Section
The Heritage Garden Section, established in 1998
The North View Area, established in 2013.
There are also "infant sections". The infant grave sites are located within the North View and Heritage Garden sections. The cemetery has a "Memorial Acres", which is an expansion section containing an additional 1,059 grave sites.:
The cemetery has a special section in the "Historical Area" where the unknowns who perished during the Great Depression era are buried. There is a memorial on the grounds dedicated to their memory. The area reflects on a bleak period of American history when even permanent memorials were a luxury. There is also a Commonwealth war interment of 23 military personnel who perished in the Second World War.
Notable interments
Among the many notable citizens of the city who are interred in the cemetery are the following:
Dr. Lucius C. Alston (1892–1958) - Dr. Alston was the first African-American doctor to serve Mesa. His house is listed in the National Register of Historic Places, reference number 12000240.
Oscar Virgil Crismon (1909-1985) - Crismon served as Mayor of Mesa from 1950-1952.
George Nicholas Goodman (1885–1959) - Goodman served as Mayor of Mesa during the following years: 1938–1942, 1946–1948 and 1952–1956.
Pedro Warner Guerrero (1896–1995) - Guererro was the founder of the Guerrero-Lindsey Sign Company. In 1946, with R.G. Scarborough and Ann Encke, he founded the Rosarita Mexican Foods Company. Rosita has become a nationwide known brand. Mesa's Pedro Guerrero Rotary Park is named for him.
William Johnson LeBaron (1856–1929) - LeBaron served as Mayor of Mesa from 1888 to 1896.
Collins Rowes Hakes (1837–1916) and Mabel Ana Morse Hakes (1840-1909) - Collins Rowes Hakes, together with Riley Morse and Orlando and Orin Merrill, was the first to discover gold in the Goldfield area by the Superstition Mountains. His wife was president of the Mesa Ward Relief Society for five years and counselor and then president of the Maricopa Stake Relief Society, and was the Mesa representative to the Woman's Suffrage Convention in Chicago in 1893.
Waylon Jennings (1937–2002) - Jennings was an American singer, songwriter, musician, and actor. Jennings gave up his seat on the ill-fated flight that crashed and killed Buddy Holly, J. P. Richardson, Ritchie Valens, and pilot Roger Peterson. In 2001, he was inducted into the Country Music Hall of Fame.
Daniel Webster Jones (1830-1915) – Jones was commissioned by Brigham Young to start a Mormon settlement in the Salt River Valley of Arizona. The settlement was originally called Jonesville and later renamed Lehi. Lehi was eventually incorporated into Mesa.
John L. Lee a.k.a. "Powder River Jack" (1874-1946) - Lee was a cowboy who was known for setting cowboy poems to music. He was an entertainer in Buffalo Bill Cody's Wild West Show. "Across the Great Divide", "The Cody Stampede" and "The Song of the San Marcos" are among the many songs which he wrote. His wife, Kitty Lee, (1868-1955) is buried alongside him.
Ramon Garcia Mendoza (1914–1999) - R.G. Mendoza was the first Hispanic police chief in Mesa. His house is listed in the Mesa Historic Property Register. He was the son of Ramon Somoza Mendoza.
Ramon Somoza Mendoza (1876–1951) - Mendoza was the first Hispanic police officer in Meza. The Mendoza Elementary School in Mesa was named in his honor. His son Ramon G. Mendoza, who led the department from 1969 to 1978, was Mesas' first Hispanic police chief.
Ernesto Arturo Miranda (1941–1976) - Miranda was a laborer whose conviction on kidnapping, rape, and armed robbery charges based on his confession under police interrogation was set aside in the landmark U.S. Supreme Court case (Miranda v. Arizona), which ruled that criminal suspects must be informed of their right against self-incrimination and their right to consult with an attorney before being questioned by police. This warning is known as the Miranda Rights.
Ralph Fleetwood Palmer (1875–1954) - Dr. Palmer served as the Mayor of Mesa from 1910-1912.
Orley Seymour Stapley (1872–1942 - Stapley served in the Arizona State Senate from 1914 to 1915. He established a chain of hardware stores throughout the state. Stapley Junior High School in Mesa was named in his honor.
Also interred are the four founding fathers of Mesa:
Charles Crismon (1805–1890)
Francis Martin Pomeroy (1822–1882)
Charles Innes Robson (1837–1894)
George Warren Sirrine (1818–1902). His house, the "Sirrine house", is listed in the National Register of Historic Places, reference number 95001082.
Graves
National Register of Historic Places
The following houses of the interred are listed in the National Register of Historic Places or listed as historical by the Mesa Historical Society:
The Sirrine House - Built in 1896 (NRHP) Historic Significance: Architecture/Engineering, Architect, builder, or engineer: Sirrine, Joel E., Architectural Style: Queen Anne, Area of Significance: Architecture, Period of Significance: 1900-1924, 1875-1899.
The Dr. Lucius Charles Alston House - Built in 1920 (NRHP). The Dr. Lucius Charles Alston House is associated with the history of the development of the African American community in Mesa. The house served as Dr. Alston's office while practicing medicine in Mesa.
The Ramon Garcia Mendoza House - Built in 1944 and is located at 126 N. Pomeroy Lane. Ramon Garcia Mendoza was the first Hispanic Chief of Police in Mesa. He became a police officer in a time when segregation was still practiced in the city. Mendoza was appointed police chief in 1969 and served until his retirement in 1978. It is listed in the Mesa Historic Property Register.
See also
Mesa, Arizona
Adamsville A.O.U.W. Cemetery
Home Mission Cemetery
Glendale Memorial Park Cemetery
Pioneer and Military Memorial Park
Goodyear Farms Historic Cemetery
Double Butte Cemetery
Greenwood/Memory Lawn Mortuary & Cemetery
St. Francis Catholic Cemetery
Historic Pinal Cemetery
List of historic properties in Mesa, Arizona
National Register of Historic Places listings in Maricopa County, Arizona
References
Further reading
Mesa (Images of America: Arizona), by Lisa A. Anderson and Alice C. Jung. Arcadia Publishing.
Category:Cemeteries in Arizona
Category:Buildings and structures in Mesa, Arizona
Category:Commonwealth War Graves Commission cemeteries in the United States | {
"pile_set_name": "Wikipedia (en)"
} |
# -*- coding: UTF-8 -*-
from __future__ import absolute_import, with_statement
import pytest
from mock import Mock, patch
import parse
from behave.matchers import Match, Matcher, ParseMatcher, RegexMatcher, \
SimplifiedRegexMatcher, CucumberRegexMatcher
from behave import matchers, runner
class DummyMatcher(Matcher):
desired_result = None
def check_match(self, step):
return DummyMatcher.desired_result
class TestMatcher(object):
# pylint: disable=invalid-name, no-self-use
def setUp(self):
DummyMatcher.desired_result = None
def test_returns_none_if_check_match_returns_none(self):
matcher = DummyMatcher(None, None)
assert matcher.match('just a random step') is None
def test_returns_match_object_if_check_match_returns_arguments(self):
arguments = ['some', 'random', 'objects']
func = lambda x: -x
DummyMatcher.desired_result = arguments
matcher = DummyMatcher(func, None)
match = matcher.match('just a random step')
assert isinstance(match, Match)
assert match.func is func
assert match.arguments == arguments
class TestParseMatcher(object):
# pylint: disable=invalid-name, no-self-use
def setUp(self):
self.recorded_args = None
def record_args(self, *args, **kwargs):
self.recorded_args = (args, kwargs)
def test_returns_none_if_parser_does_not_match(self):
# pylint: disable=redefined-outer-name
# REASON: parse
matcher = ParseMatcher(None, 'a string')
with patch.object(matcher.parser, 'parse') as parse:
parse.return_value = None
assert matcher.match('just a random step') is None
def test_returns_arguments_based_on_matches(self):
func = lambda x: -x
matcher = ParseMatcher(func, 'foo')
results = parse.Result([1, 2, 3], {'foo': 'bar', 'baz': -45.3},
{
0: (13, 14),
1: (16, 17),
2: (22, 23),
'foo': (32, 35),
'baz': (39, 44),
})
expected = [
(13, 14, '1', 1, None),
(16, 17, '2', 2, None),
(22, 23, '3', 3, None),
(32, 35, 'bar', 'bar', 'foo'),
(39, 44, '-45.3', -45.3, 'baz'),
]
with patch.object(matcher.parser, 'parse') as p:
p.return_value = results
m = matcher.match('some numbers 1, 2 and 3 and the bar is -45.3')
assert m.func is func
args = m.arguments
have = [(a.start, a.end, a.original, a.value, a.name) for a in args]
assert have == expected
def test_named_arguments(self):
text = "has a {string}, an {integer:d} and a {decimal:f}"
matcher = ParseMatcher(self.record_args, text)
context = runner.Context(Mock())
m = matcher.match("has a foo, an 11 and a 3.14159")
m.run(context)
assert self.recorded_args, ((context,) == {
'string': 'foo',
'integer': 11,
'decimal': 3.14159
})
def test_positional_arguments(self):
text = "has a {}, an {:d} and a {:f}"
matcher = ParseMatcher(self.record_args, text)
context = runner.Context(Mock())
m = matcher.match("has a foo, an 11 and a 3.14159")
m.run(context)
assert self.recorded_args == ((context, 'foo', 11, 3.14159), {})
class TestRegexMatcher(object):
# pylint: disable=invalid-name, no-self-use
MATCHER_CLASS = RegexMatcher
def test_returns_none_if_regex_does_not_match(self):
RegexMatcher = self.MATCHER_CLASS
matcher = RegexMatcher(None, 'a string')
regex = Mock()
regex.match.return_value = None
matcher.regex = regex
assert matcher.match('just a random step') is None
def test_returns_arguments_based_on_groups(self):
RegexMatcher = self.MATCHER_CLASS
func = lambda x: -x
matcher = RegexMatcher(func, 'foo')
regex = Mock()
regex.groupindex = {'foo': 4, 'baz': 5}
match = Mock()
match.groups.return_value = ('1', '2', '3', 'bar', '-45.3')
positions = {
1: (13, 14),
2: (16, 17),
3: (22, 23),
4: (32, 35),
5: (39, 44),
}
match.start.side_effect = lambda idx: positions[idx][0]
match.end.side_effect = lambda idx: positions[idx][1]
regex.match.return_value = match
matcher.regex = regex
expected = [
(13, 14, '1', '1', None),
(16, 17, '2', '2', None),
(22, 23, '3', '3', None),
(32, 35, 'bar', 'bar', 'foo'),
(39, 44, '-45.3', '-45.3', 'baz'),
]
m = matcher.match('some numbers 1, 2 and 3 and the bar is -45.3')
assert m.func is func
args = m.arguments
have = [(a.start, a.end, a.original, a.value, a.name) for a in args]
assert have == expected
class TestSimplifiedRegexMatcher(TestRegexMatcher):
MATCHER_CLASS = SimplifiedRegexMatcher
def test_steps_with_same_prefix_are_not_ordering_sensitive(self):
# -- RELATED-TO: issue #280
# pylint: disable=unused-argument
def step_func1(context): pass # pylint: disable=multiple-statements
def step_func2(context): pass # pylint: disable=multiple-statements
# pylint: enable=unused-argument
matcher1 = SimplifiedRegexMatcher(step_func1, "I do something")
matcher2 = SimplifiedRegexMatcher(step_func2, "I do something more")
# -- CHECK: ORDERING SENSITIVITY
matched1 = matcher1.match(matcher2.pattern)
matched2 = matcher2.match(matcher1.pattern)
assert matched1 is None
assert matched2 is None
# -- CHECK: Can match itself (if step text is simple)
matched1 = matcher1.match(matcher1.pattern)
matched2 = matcher2.match(matcher2.pattern)
assert isinstance(matched1, Match)
assert isinstance(matched2, Match)
def test_step_should_not_use_regex_begin_marker(self):
with pytest.raises(AssertionError):
SimplifiedRegexMatcher(None, "^I do something")
def test_step_should_not_use_regex_end_marker(self):
with pytest.raises(AssertionError):
SimplifiedRegexMatcher(None, "I do something$")
def test_step_should_not_use_regex_begin_and_end_marker(self):
with pytest.raises(AssertionError):
SimplifiedRegexMatcher(None, "^I do something$")
class TestCucumberRegexMatcher(TestRegexMatcher):
MATCHER_CLASS = CucumberRegexMatcher
def test_steps_with_same_prefix_are_not_ordering_sensitive(self):
# -- RELATED-TO: issue #280
# pylint: disable=unused-argument
def step_func1(context): pass # pylint: disable=multiple-statements
def step_func2(context): pass # pylint: disable=multiple-statements
# pylint: enable=unused-argument
matcher1 = CucumberRegexMatcher(step_func1, "^I do something$")
matcher2 = CucumberRegexMatcher(step_func2, "^I do something more$")
# -- CHECK: ORDERING SENSITIVITY
matched1 = matcher1.match(matcher2.pattern[1:-1])
matched2 = matcher2.match(matcher1.pattern[1:-1])
assert matched1 is None
assert matched2 is None
# -- CHECK: Can match itself (if step text is simple)
matched1 = matcher1.match(matcher1.pattern[1:-1])
matched2 = matcher2.match(matcher2.pattern[1:-1])
assert isinstance(matched1, Match)
assert isinstance(matched2, Match)
def test_step_should_use_regex_begin_marker(self):
CucumberRegexMatcher(None, "^I do something")
def test_step_should_use_regex_end_marker(self):
CucumberRegexMatcher(None, "I do something$")
def test_step_should_use_regex_begin_and_end_marker(self):
CucumberRegexMatcher(None, "^I do something$")
def test_step_matcher_current_matcher():
current_matcher = matchers.current_matcher
for name, klass in list(matchers.matcher_mapping.items()):
matchers.use_step_matcher(name)
matcher = matchers.get_matcher(lambda x: -x, 'foo')
assert isinstance(matcher, klass)
matchers.current_matcher = current_matcher
| {
"pile_set_name": "Github"
} |
http://www.risklab.ch/ | {
"pile_set_name": "Enron Emails"
} |
Introduction {#Sec1}
============
The last two decades have seen a rising trend in the immunocompromised patients (Richardson [@CR48]; Krcmery [@CR25]; Warnock and Richardson [@CR66]; Ribes et al. [@CR47]), who are at a heightened risk for "opportunistic" fungal infections (mycoses). The fungal infections can affect any part of the body and cause superficial mycoses (affecting only the outermost layers of the skin and hair), cutaneous mycoses (extending deeper into the layers of the skin, hair, and nail), subcutaneous mycoses (involve the dermis, subcutaneous tissues, muscle, and fascia), or systemic mycoses (dissemination in the body). The fungal diseases (listed in Table [12.1](#Tab1){ref-type="table"}) are classified according to the three important phyla of the fungal taxonomy -- Ascomycetes, Basidiomycetes, and Zygomycetes. These diseases turn out to be severe if disseminated, which is common in the immunosuppressed. Candidiasis is one of the highly frequent fungal infections in 90% of untreated, advanced HIV cases suffering from oropharyngeal candidiasis according to World Health Organization (WHO) 2010 statistics. Another study reported overall mortality rate of approximately 80% for zygomycosis (Ribes et al. [@CR47]) and 80--90% in invasive aspergillosis of high-risk leukemia patients and allogeneic bone marrow transplant patients (Chamilos and Kontoyiannis [@CR4]).Table 12.1Fungal diseases associated with immunocompromised patientsDiseaseCausal fungal agentSymptomsTreatmentAscomycetesCandidiasis*Candida albicans*, *C.tropicalis*Localized infection of the skin or mucosal membranes like the vagina: itching, burning, soreness, irritation, and a whitish dischargeClotrimazole, nystatin, amphotericin B, fluconazole, caspofunginsAspergillosis*Aspergillus fumigatus* (causes more than 95% of cases), *A. flavus*Fungus balls in lungs, coughing up blood; fever, chest pain, difficulty breathing; aspergillosis of the ear canal causes itching and occasionally pain and fluid drainingAmphotericin B, voriconazole, caspofunginHistoplasmosis*Histoplasma capsulatum*, *H.duboisii* (causes disease restricted to Africa and Madagascar)Acute respiratory infection leads to respiratory symptoms, malaise, fever, chest pains, dry cough, flu-like illness, fever, cough, headacheFluconazole, itraconazole, amphotericin BCoccidioidomycosis*Coccidioides immitis*Only 40% cases symptomatic, flu-like symptoms, fever, cough, headache, rash, myalgias, chest pain, fatigue, arthralgiaFluconazole, amphotericin B, voriconazole, posaconazoleBlastomycosis*Blastomyces dermatitidis*Fever, chills, myalgia, arthralgia, pleuritic chest pain, cough, difficulty breathing can become disseminated to mostly skin, bones, and genitourinary tractAmphotericin B, itraconazole, voriconazolePenicilliosis*Penicillium marneffei*Fever, weight loss, anemia, pneumonitis, skin lesions, pharyngeal, and palatal lesionsAmphotericin B, itraconazoleBasidiomycetesCryptococcosis*Cryptococcus neoformans*, *C.grubii*Headache, fever, visual loss, osteolytic bony lesions, meningitis, calcification in lungsFluconazole, amphotericin BZygomycetesZygomycosis*Rhizopus oryzae, R.rhizopodiformis, Rhizomucor pusillus, Absidia corymbifera, Apophysomyces elegans, Mucor circinelloides*Facial pain, headache, nausea, fever, blood or pus draining from nose, lethargy, impaired vision, bulging eyes, convulsions, ulcers in roof of mouth, may become disseminatedAmphotericin B, posaconazole
The existing fungal treatments require parallel approaches involving surgical intervention and antifungal therapy (Ribes et al. [@CR47]*).* Surgical intervention has shown improving survival rates for many patients, but surgery is not the only solution in treating fungal diseases. The currently available antifungal drugs comprise polyenes, macrolides, azole drugs, and echinocandins (Mukherjee et al. [@CR34]*).* Among them, the polyene amphotericin B is the first-line drug of choice for invasive mycoses (Ribes et al. [@CR47]). These drugs have drawbacks such as nephrotoxicity and hepatotoxicity as exhibited by liposomal amphotericin B, narrow spectrum of activity as shown by fluconazole, and itraconazole causes problems with absorption (Pauw and Picazo [@CR44]). Moreover, the fungi are acquiring resistance recurrently against novel antifungal agents (Rogers [@CR49]) either due to defects in drug import and efflux of drugs, variations in intracellular drug processing, alterations in the enzymes of a target-specific biosynthetic pathway, or its competitive inhibition (Chamilos and Kontoyiannis [@CR4]; Bhanderi et al. [@CR3]).
The existing treatments are not effective due to varied susceptibility of fungi toward the drugs; hence, newer safe and effective therapeutic interventions are desired. There have been reports of the use of gene therapy, antisense oligonucleotides, ribozymes, DNAzymes, and RNAi therapy. RNAi scores several benefits over other techniques, for instance, its effective delivery into various organs at low concentrations, thereby increasing safety, its cost-effectiveness as compared to protein/enzymes, and its non-immunogenicity bypassing the interferon pathway (Ruddon [@CR51]). Subsequently, it was marked the "Breakthrough of the Year" in 2002 by *Science magazine*. One of the recent developments in this field has been the FDA approval of siRNA (short interfering RNA) drug DGFi in 2008, developed by Quark Pharmaceuticals, Inc., for use in kidney transplantation. Another siRNA-based therapy, Sirna-027 originally developed by Sirna Therapeutics for the treatment of acute macular degeneration, is moving forward into phase II clinical trials. Hence, the vital relevance of innovative treatments like the siRNA therapy can be envisaged for antifungal infections. RNAi application has also been identified in functional genomics and therapeutics, viz., cancer, neurodegenerative diseases, and multiple sclerosis besides fungal infection. This chapter presents the prospects of RNAi technology in fungal infection.
RNA Interference in Fungi {#Sec2}
=========================
Gene cosuppression (RNAi-type phenomenon), which is more commonly known as "quelling" in fungi, was first discovered in the filamentous fungus *Neurospora crassa* by Romano and Macino ([@CR50]). The significant aspect of RNAi was established in 1998 when Fire and Mello found out that dsRNA is 10--100 times more effective in triggering silencing as compared to ssRNA in *Caenorhabditis elegans* (Fire et al. [@CR9]*)* for which they shared the Nobel Prize in Medicine and Physiology in 2006.
RNAi naturally occurring "sequence-specific gene silencing" phenomenon and evolutionarily highly conserved mechanism are well developed in eukaryotic organisms, which is induced by double-stranded small noncoding RNA (dsRNA). These RNA-mediated gene silencing pathways have been comparatively thoroughly known and established in plant and animal system and are widely investigated in a variety of fungi, few of them are reported on opportunistic pathogenic fungi in human. The RNAi machinery in fungi shares similar mechanistic principles with other organisms where RNAi has been discovered which consists of dsRNA precursors, Dicer enzyme, RISC (RNA-induced silencing complex), and the target mRNA. The dsRNA is processed into short interfering RNA (siRNA) by two steps -- the initiator step and the effector step. In the *initiator step*, the dsRNA is cleaved by the enzyme Dicer of the RNase III family (Jinek and Doudna [@CR19]) into specific lengths of 21--25 nucleotides. In the *effector step*, the siRNA must segregate into "competent" single strands (the guide strands) which are guided through a ribonucleotide protein complex called the RISC (Siomi and Siomi [@CR56]), a member of the Argonaute family of proteins (Song et al. [@CR58], [@CR59]; Leuschner et al. [@CR26]; Fulci and Macino [@CR10]). Both Dicer and RISC complex require ATP for energy. The Argonaute has a N-terminal domain, PAZ domain, a middle domain, and a PIWI domain. It is the "guide strand" which is incorporated into RISC; the non-incorporated strand known as the "passenger strand" is also crucial for proper target mRNA cleavage. Until the passenger strand is not cleaved at ten nucleotides from the 5′ phosphate of the guide strand, target mRNA cleavage is severely impaired (Leuschner et al. [@CR26]). The cleaved target mRNA is utilized by RNA-dependent RNA polymerase (RdRp) generating more dsRNA that is further recognized and cleaved by Dicer to increase the number of siRNA molecules (Schepers [@CR52]). Genes responsible for RNAi have been discovered in fungi such as *qde-1* (*quelling deficient-1*) which was the first RNAi gene discovered in *N. crassa* which encodes a cellular RdRp. Simultaneously, *qde-2* was cloned and found out to encode Argonaute protein. Further, partially redundant Dicer proteins DCL-1 (Dicer-like-1) and DCL-2 have been characterized from *N. crassa* by reverse genetics (Li et al. [@CR27]).
So far, RNAi mechanism has not been observed in *Saccharomyces cerevisiae*, *Candida guilliermondii*, *C. lusitaniae*, *C. tropicalis*, and *Ustilago maydis* (Nakayashiki [@CR37]; Münsterkötter and Mannhaupt [@CR35])*.* In *S.cerevisiae*, it has been attributed to the absence of conserved components like Dicer-like RNases, Argonaute or PIWI-like components, and RNA-dependent RNA polymerases. However, RNAi was very recently discovered in *S. castellii*, which is closely related to *S.cerevisiae*, and also in *C. albicans*, a common human pathogen, by David P. Bartel's lab \[22\] (Drinnenberg et al. [@CR6])*.* They found out that these species with noncanonical Dicer activity have RNase III domain containing gene to generate siRNA(s). This gene is orthologous to RNase III domains of other Argonaute-containing budding yeasts and is mostly enriched in long inverted repeats and transposable elements.
siRNA Design and Computational Tools {#Sec3}
====================================
A significant facet of siRNA design involves identification and characterization of gene target which plays a key role in the survival of the organism such that suppression of the gene by inhibiting translation should limit the growth of the fungus. A particular fungal disease is often caused by more than one fungus, for instance, zygomycosis is caused by *Rhizopus*, *Absidia*, *Mucor*, and *Rhizomucor*. siRNA can be designed taking into consideration a conserved antifungal drug target present ubiquitously in the species, so that the drug discovery process becomes less intricate; but a crucial point to be taken care of is that the protein and its corresponding gene should not have similarities with the human genome, such that the human processes are not affected. For instance, cell wall is a very promising target in disease-causing fungi. The pathway for formation of cell wall is readily accessible (Moussian [@CR32]), and the KEGG database ([http://www.genome.jp/kegg/](http://www.genome.jp/kegg)) can be referred. Silencing a gene coding for a significant component of the cell wall biosynthesis pathway can delimit the formation of cell wall and hence restrain the growth of the pathogenic fungus. For instance, a study reported loss of a cell wall polysaccharide, α-(1,3) glucan synthase from the cell walls of *Histoplasma capsulatum* which led to decreased virulence and pathogenesis of the fungi (Rappleye et al. [@CR45]). Apart from the cell wall, targeting can be carried out against lipid biosynthesis pathways or at the translational or posttranslational levels. Previous studies have led to the confirmation of N-myristoyl transferase, lanosterol 14-α demethylase, and geranylgeranyl transferase I as potential drug targets against which antifungal drugs benzofurans, azoles, and azaphilones have been designed, respectively (Kawasaki et al. [@CR23]; Song et al. 2004; Singh et al. [@CR55]). Furthermore, orthologous and paralogous studies can be performed to check the presence of the target gene in other related organisms, which can highlight the evolutionary history of the gene, and information about gene conservation can acquaint us with the vital relevance of the gene.
siRNA should be a perfect complementary match to its target mRNA, and hence, it needs to be cautiously designed. Various computational tools are freely available online for designing siRNA. For instance, the Ambion's siRNA Target Finder, Eurofins MWG Operon's free online siMAX™ Design Tool, the BLOCK-iT™ RNAi Designer from Invitrogen, the SVM RNAi 3.6, and the siDESIGN Center by Dharmacon can be used for siRNA designing against fungal genes. The designing of siRNA molecule is purely dependent on suitable selection of various siRNA features, viz., sequence, motif, GC content, and thermodynamic features, etc. Moreover, various studies have documented the comparison among few siRNA design tools (Yiu et al. [@CR69]; Matveeva et al. [@CR29]). The tools mainly follow the Reynolds et al. ([@CR46]) or Tuschl et al. ([@CR62]) guidelines for rational siRNA design of usually 21 nucleotides in length. Few guidelines are described in onward section. According to these guidelines, regions within 50--100 bp of the start codon and the termination codon; intronic regions, stretches of 4 or more bases such as AAAA and CCCC; and regions with GC content less than 30% or more than 60%, single-nucleotide polymorphisms, repeats, and low complex sequences should be avoided.
General Guidelines for siRNA Designing {#Sec4}
--------------------------------------
Many guidelines to design siRNA were proposed by different groups which are mentioned below.
### MPI (Max-Planck-Institute) Rule Set {#Sec5}
Tuschl et al. ([@CR62]) have provided a set of guidelines (commonly known as the MPI principles) on how to design effective siRNA.
Initially an empirical rules (based on GC content and symmetric 3′ TT overhangs) for effective siRNA designing were established by Tuschl et al. ([@CR62]), which have been found to show significant proportion of ineffective siRNAs as described by Yiu et al. ([@CR69]) and identify the need of understanding the structural features of sequences (Yiu et al. [@CR69]). Therefore, the new rules were suggested with advancement of technology for effective designing of siRNA, (1)where select targeted region from a given cDNA sequence beginning 50--100 nt. downstream of start codon (2) afterward finds 23-nt sequence motif AA (N\<sub\>19). If no suitable sequence is found, then find for 23-nt sequence motif NA(N\<sub\>21) and convert the 3′ end of the sense siRNA to TT or search for \[N (any nucleotide base pair)A (adenine) R (adenine or guanine (purines)) (N\<sub\>17)Y(thymine or cytosine (pyrimidines)) NN\], and the GC content must be around 50% in target sequence.
### Rational siRNA Design {#Sec6}
In the designing of efficient siRNA molecule, a rational rule sets (total of eight criteria with weight values) were developed after the experiential analysis of the silencing efficiency of 180 siRNAs targeting the mRNA of two genes, by Reynolds et al. ([@CR46]) at Dharmacon, Inc.; these rules/criteria cover the different compositional properties such as sequential features of individual siRNAs. These characteristics are used by rational siRNA design algorithm to evaluate potential targeted sequences and assign scores to them (Reynolds et al. [@CR46]). The higher value or score of these sequences reflects the higher chance of success of RNAi experiment.
The tools offered by Dharmacon, Inc. deploy the eight criteria-based (rational siRNA design rules) guideline, while Maurice Ho et al. have developed the Excel-based template on similar guidelines and available at <http://boz094.ust.hk/RNAi/siRNA>.
It is clear from Fig. [12.1](#Fig1){ref-type="fig"} that different base pair shows differential stability with respect to their position (H = A, C or U).Fig. 12.1Relative stability of both ends of the siRNA (Adopted from Reynolds et al. [@CR46])
### Challenges {#Sec7}
Despite several in silico siRNA design cases being reported in fungal systems, there are challenges that need to be addressed. These include optimal siRNA designing, off targeting, and efficient delivery systems apart from the genomic architecture and levels of organizational complexity. For example, whole-genome duplication events are commonly observed in fungi (Wapinski et al. [@CR65]; Dujon et al. [@CR7]; Ibrahim et al. [@CR17]) such as in *Rhizopus oryzae*, giving rise to paralogous genes might not have 100% nucleotide sequence similarity with each other, which are actively expressed to code for an enzyme. Such constraints are often envisaged while designing effective siRNA against a fungal enzyme, as targeting only one out of many genes for a given enzyme target doesn't result in a very high efficacy for silencing (Yamada et al. [@CR68]) silenced only one out of the three α-amylase genes in *Aspergillus oryzae* and found merely 10% silencing, which is not sufficient to enter the therapeutic phase. Hence, designing common siRNA for all the genes targeting an enzyme becomes a very arduous task. Chitin synthase is a well-accepted antifungal drug target, yet it cannot be used to design siRNA(s) for *R. oryzae* because genome level analysis has revealed that 23 genes can encode chitin synthase (Ibrahim et al. [@CR17])*.* The prospects of selecting the conserved regions of an enzyme are lucrative, as a single siRNA might be effective against several fungi causing a particular disease, but the enzyme should be present exclusively in fungi. Hence, target selection is critical toward its gene nature and diversity.
### Resources and Tools {#Sec8}
There are several tools available to design the siRNA, few of them are described in Table [12.2](#Tab2){ref-type="table"}.Table 12.2List of selected siRNA design toolsS. nosiRNA designing toolWebsite1OligoWalk<http://rna.urmc.rochester.edu/cgi-bin/server_exe/oligowalk/oligowalk_form.cgi>2BLOCK-iT™ RNAi designer<https://rnaidesigner.thermofisher.com/rnaiexpress/rnaiExpress.jsp>3RNAi design tool<http://eu.idtdna.com/Scitools/Applications/RNAi/RNAi.aspx?source=menu>4siDESIGN center[http://dharmacon.gelifesciences.com/design-center/](http://dharmacon.gelifesciences.com/design-center)5siRNA at whitehead<http://sirna.wi.mit.edu>/6TROD<http://www.unige.ch/sciences/biologie/bicel/websoft/RNAi.html>7AsiDesigner<http://sysbio.kribb.re.kr:8080/AsiDesigner/menuDesigner.jsf>8GenScript's siRNA design center<http://www.genscript.com/design_center.html>9SiDirect<http://sidirect2.rnai.jp>/10Side<http://predictor.nchu.edu.tw/side/about_siDE.php>11siVirus<http://sivirus.rnai.jp>/12DSIR<http://biodev.extra.cea.fr/DSIR>13SiSearch<http://www.biolabprotocols.com/details/2985/siSearch.html>
#### siVirus {#FPar1}
It is an effective siRNA designing tool for several divergent viral genomes such as human immunodeficiency virus (HIV), *hepatitis C virus* (HCV), influenza virus, and *SARS coronavirus*, based on various siRNA designing guidelines such as Ui-Tei et al. ([@CR63]), Reynolds et al. ([@CR46]), and Amarzguioui and Prydz ([@CR1]), while the off-targeting siRNA sequences were identified using siDirect tool. Out of 35 predicted siRNAs, 31 sequences of siRNA against conserved region of HIV-1 genome have shown inhibition of viral replication, which conclusively supports the designing capacity of these tools (Naito et al. [@CR36]).
#### RNA Rule Set 1.0 {#FPar2}
It is a Java-based program to predict the efficient siRNA design. Basically siRNArules 1.0 operates with two scoring sums: one for the positive rules deduced from the set of the best siRNAs and one for the negative rules deduced from the set of the worst siRNAs. The rank is calculated by a simple sum of these two values. How these rules should be weighted to obtain the most efficient algorithm is a challenge for the open-source community (Holen [@CR14]).
#### DSIR {#FPar3}
This tool was developed by Vert et al. ([@CR64]) which uses only two parameters for designing of siRNA, i.e., position-specific thermodynamic stability and non-position-specific motif formation. Their composite score decides which siRNA is better through lasso regression technique. It also provides the options to design 19--21 bp siRNA. The effectiveness of this tool is comparable and evaluated as one of the best tools by Matveeva et al. ([@CR29]) while comparing with other tools.
RNAi Delivery {#Sec9}
=============
In silico siRNA designing is followed by its efficient delivery into an organism of choice for knockdown of the target gene. siRNA delivery strategies employed in fungi mainly comprise of soaking approach using chemically synthesized siRNA or inserting inverted repeat transgenes (IRT) into the desired plasmid using long-hairpin RNA (lhRNA). Table [12.3](#Tab3){ref-type="table"} lists some of the fungal species in which these strategies have been performed.Table 12.3Silencing by exogenous siRNAPresence of RNAi machinery in fungiGene targetedStrategyInhibitionRefs.Ascomycetes*Aspergillus nidulansODC* -- fungal ornithine decarboxylase geneSoaking methodInhibition of 10%, 26%, 33%, 33% observed with 10 nM, 15 nM, 20 nM, 25 nM siRNA, respectivelyKhatri and Rajam ([@CR24])*Aspergillus nidulans*Bristle brlAβ -- developmental regulatory geneInverted repeat of alcA (alcohol dehydrogenase) promoters flanking 498 bp brlAβ upstreamExpression was 3--4 fold less abundant on threonine than that on glucoseBarton and Prade ([@CR2])*Aspergillus oryzae*brlA and α-amylase genesHairpin RNA cassette of 556 bp brlA, 1656 bp, and 750 bp α-amylaseDecreased signal for brlA gene, reduction in α-amylase activityIbrahim et al. ([@CR17])*Aspergillus fumigatus*ALB1/PKSP -- polyketide synthase (melanin biosynthesis pathway) and FKS1 β-(1,3) glucan synthase (cell wall polysaccharide)500 bp inverted repeats of ALB1, FKS, and FKS/ALB129% of pALB1 transformants showed 5% (white colonies) or 24% (light-green colonies) reduction in ALB1 expression, 1% of pFKS1 transformants showed complete RNAi phenotypeMouyna et al. ([@CR33])*Aspergillus niger*xlnR encodes xylanases and cellulasesInverted repeat of 834 bp of *xlnR*12% transformants showed decreased activitiesOliveira et al. ([@CR42])*Aspergillus parasiticus* and *A. flavus*AflR -- transcription factor for expression of aflatoxin biosynthetic genesInverted repeat of 670 bp of *aflRaflR* IRT transformants expressed *verA* at levels below the detection limits by N.BlotMcDonald et al. ([@CR30])*VerA --* gene which is a part of aflatoxin biosynthetic pathway*Fusarium graminearum*Tri6 -- transcription factor regulating expression of trichothecene (mycotoxin) biosynthetic genesInverted repeat constructs of tri6 ORF with 602 nt in sense and 588 nt in antisense directionWheat head blight did not spread to neighboring spikeletsMcDonald et al. ([@CR30])*Fusarium verticilloides* (or *F. moniliforme*)*gus* gene-encoding beta-glucuronidaseInverted repeat of 627 bp of *gus* geneTwo transformed colonies showed a reduction of 62% and 96% in the *gus* gene expressionTinoco et al. ([@CR61])*Neurospora crassa*Albino gene *al-1* involved in carotenoid biosynthesisFull length *al-1* gene (1971 bp)24% of transformants showed albino phenotypeCogoni and Macino ([@CR5])*Magnaporthe oryzae (M. grisea)*Enhanced GFP (eGFP)Constructs with sense-sense, antisense-antisense, and sense-antisense orientation of \~700 nt of eGFP40 out of 80 IRT transformants emitted 20% fluorescence relative to original GFPKadotani et al. ([@CR21])*Schizosaccharomyces pombe*Enhanced GFP (eGFP)Inverted repeat of 760 bp of eGFPGfp mRNA reduced more than twofoldSigova et al. ([@CR54])*Histoplasma capsulatum*AGS1 or α-(1,3)-glucan synthase, cell wall polysaccharideInverted repeat of 678 bp of coding sequence of AGS1Loss of α-(1,3)-glucan synthase from cell wallsRappleye et al. ([@CR45])*Cryptococcus neoformans* (JEC21 strain)CAP59 -- capsule synthesis520 nt inverted repeats of CAP59 and ADE2\~25% reduction giving dull (CAP59suppression) and pink (ADE2 suppression) coloniesLiu et al. ([@CR28])ADE2 -- adenine biosynthesis*Bipolaris oryzae*PKS1 -- polyketide synthase gene, involved in melanin biosynthesis pathwayInverted repeats of PKS1 gene fragment (756 bp)70% of the transformants showed a melanin-deficient (white color) phenotypeMoriwaki et al. ([@CR31])*Sclerotinia sclerotiorumrgb1* encoding PP2A (type 2A phosphoprotein phosphatase) B regulatory subunitInverted repeat of 1.1 kbp of *rgb1* under the control of *A. nidulans* promoter and terminator*rgb1* suppression inhibited sclerotial maturation and caused reduced pathogenesisErental et al. ([@CR8])*Colletotrichum lagenarium*Enhanced GFP (eGFP)Construct consisted of 0.72 kb eGFP under the control of *A. nidulans* promoter and terminatorGFP fluorescence reduced to less than 20% of the parent strainNakayashiki et al. ([@CR38])Basidiomycetes*Coprinus cinereus*recA-like recombinase in meiosis -- Lim15/Dmc1Vector construct with 750 nt antisense and 650 nt sense strand23% having meiotic defects, i.e., fruiting body having white capNamekawa et al. ([@CR39])*Schizophyllum commune*Structural gene -- SC15334 nt hairpin construct of SC1580% reduction in aerial hyphae formation and attachmentJong et al. ([@CR20])Zygomycetes*Mortierella alpina*Δ12-desaturase desaturates oleic acid to linoleic acid467 nt inverted repeat of Δ12-desaturase25--88% decrease in fatty acid productionTakeno et al. ([@CR60])*Mucor circinelloidescarB* -- encodes phytoene dehydrogenase enzyme, involved in carotenoid biosynthesis pathwaypMAT647 with 2483 nt of *carB*pMAT647 and pMAT754 gave a silencing frequency of 3.16% and 3.12% with a complete albino phenotypeNicolás et al. ([@CR41])pMAT754 with complete cDNA sequence (2334 nt) of *carB*
Soaking {#Sec10}
-------
This technique employs chemically synthesized siRNA(s) which are absorbed by the organism. Briefly, it involves annealing of the siRNA strands, quantification of the siRNA duplex, and soaking of the organism with these double-stranded siRNA(s). This protocol has been followed in protozoan parasite *Entamoeba histolytica* (Solis and Guillén [@CR57]) and schistosomes (Ndegwa et al. [@CR40]). In the model filamentous fungus, *Aspergillus nidulans*, 10 nM, 15 nM, 20 nM, and 25 nM siRNA were used, and a growth inhibition of 10%, 26%, 33%, 33% was observed, respectively, along with a 50% reduction in germ tube length following treatment with 10 nM siRNA-treated samples (Khatri and Rajam [@CR24]; Amarzguioui et al. 2004). The soaking method results in transient expression making it less potent than direct microinjection (Schepers [@CR52]), and therefore its efficiency in targeting the fungal thick cell walls consistently is not much significant.
Transgenic RNAi {#Sec11}
---------------
The soaking method, transient RNAi, has limitations in terms of duration and experimental variability of the RNAi effect. The expression of inverted repeat (IR) transgenes, transgenic RNAi, has been shown to induce stable RNAi in fungi (Liu et al. [@CR28])**.** However, variability, often, has been observed in the gene silencing effect by dsRNA-producing transgenes depending on the target gene, the type of construct, site of integration, and transgene copy number. An IRT is constructed using a target gene sequence, which is incorporated in an organism-specific plasmid. The plasmid containing IRT is transformed into the organism that upon transcription forms a hairpin loop which is cleaved by endogenous Dicer to generate siRNA(s). The generated small interfering RNAs (siRNAs) cleave the endogenous mRNA(s) with the help of RISC. Considering that there are several hairpin-expressing RNA systems available for robust RNA silencing using a tissue-specific RNA pol II promoter for tissue-specific expression of dsRNA and that hairpin RNA assures efficient formation of dsRNA, it is the frequently used method for induction of RNA silencing (Paddison and Vogt [@CR43]). One type of IRTs is a long-hairpin RNA (lhRNA) which generally consists of more than 300 bp open reading frame, a spacer of approximately 250--500 oligonucleotides and an inverted repeat of the gene sequence. The IRT construct is inserted into the plasmid specific for a particular fungus and is transformed into the respective fungi either by protoplast formation or electroporation. But the transformation/cloning efficiency for long inverted repeats of a cDNA is very low, and the selection process is very time-consuming. The construction of lhRNA(s) is difficult as it involves several rounds of PCR and cloning steps, and moreover, it's necessary that vectors/plasmids should be available for each species to carry out siRNA delivery. Generally the longer size of spacer helps in the easy cloning of the inverted repeat and improves the efficiency of RNAi. Here, the use of IR constructs containing a short spacer (20--50 bp) in the middle of an inverted repeat improves the cloning efficiency (Yu et al. [@CR70]*)*. Moreover, the presence of introns as a spacer in the constructs also improves their effectiveness and enhances cloning efficiency \[48. 49\] (Wesley et al. [@CR67]*, Kalidas and Smith* [@CR22]). Nevertheless, these strategies have been successfully used to trigger silencing in various fungal systems like *Bipolaris oryzae* (Moriwaki et al. [@CR31]*)* in which an IRT was constructed consisting of sense and antisense polyketide synthase gene of 756 bp encoding for melanin production separated by a spacer of cutinase gene intron obtained from a study on *Magnaporthe oryzae* (Kadotani et al. [@CR21]), and this yielded melanin-deficient (white) phenotype in 70% transformants. Another study reported only 12% transformants of *xlnR* encoding xylanases and cellulases of *A. niger* (Oliveira et al. [@CR42]) showing decreased activities compared to the control strain. The reason was attributed to either rearrangement in silencing constructs or apparent decrease in xylanolytic activities or may be absence of "true" co-transformants.
Another prominent IRT successfully used in mammalian systems is the short-hairpin RNA (shRNA) which consists of a 19 bp siRNA sense and antisense sequence separated by a spacer of 9 nucleotides where the siRNA sequence should be 100% homologous to the target mRNA. The shRNA expression vectors available for mammalian systems require RNA polymerase III system as shown in Fig. [12.2](#Fig2){ref-type="fig"}.Fig. 12.2A schematic representation of the two delivery methods of siRNA is shown. (**a**) Soaking method which involves soaking of fungi with siRNA. (**b**) IRT consists of the sense and antisense orientation of the gene separated by a spacer. It is incorporated into plasmid and transformed into fungi*.* Endogenous Dicer cleaves the hairpin loop which is formed upon transcription of IRT and siRNA(s) is generated. (**c**) The passenger strand is cleaved, and the guide strand of siRNA enters the RISC where it cleaves the target mRNA
Validation of Gene Silencing {#Sec12}
============================
A preliminary way to investigate the knockdown of a gene and percentage of silencing in fungus is to measure the mycelial growth of fungus by either colony diameter method or mycelial dry weight method (radial growth assays). Blotting techniques, fluorescence imaging, and biochemical assays are the further confirmatory tests which are used to analyze silencing at the RNA and protein levels. A study was carried out by Kadotani et al. ([@CR21]) in the blast fungus *M. oryzae* (Holen [@CR14]) in which they investigated RNA silencing using enhanced green fluorescent protein (eGFP). Sense-sense, antisense-antisense, and sense-antisense IRT constructs of eGFP separated by a partial sequence of β-glucuronidase gene as internal spacer were employed. Significant silencing was induced only by sense-antisense IRT construct as detected by the loss of GFP fluorescence using an image analyzer. Several studies have employed Northern blot analysis for studying gene silencing in various fungi (Yamada et al. [@CR68]; Kadotani et al. [@CR21]; Hammond et al. [@CR12], [@CR13]; Hammond and Keller [@CR11]; Segers et al. [@CR53]; Janus et al. [@CR18]). The captured fluorescence images of plasmids (IRTs) containing fluorescence tags like GFP (Segers et al. [@CR53]; Janus et al. [@CR18]) assist in better understanding of protein localization, confirm the presence of plasmid in the cell, and also facilitate in differentiating the silenced from the non-silenced transformants. Real-time PCR and the reverse transcription PCR (Khatri and Rajam [@CR24]; Oliveira et al. [@CR42]; Janus et al. [@CR18]; Liu et al. [@CR28]) setup are also employed using appropriate gene-specific primers to detect and quantify the gene transcript levels. Liu et al. conducted a study (Liu et al. [@CR28]) on RNA silencing in the pathogenic fungus *Cryptococcus neoformans* where they constructed IRTs on genes related to capsule synthesis and adenine biosynthesis pathway. They observed 25% reduction in the gene expression imparting the transformants with dull and pink colonies, respectively, and silencing analyzed by employing reverse transcription PCR with gene-specific primers and PCR product stained with SYBR Green I nucleic acid gel stain for analysis of DNA-associated fluorescence. Janus et al. investigated a reporter system *DsRed* to identify silencing transformants by cosilencing *DsRed* with the protein isopenicillin N synthase (*pcbC*) involved in cephalosporin C biosynthesis in the filamentous fungus *Acremonium chrysogenum* and employed immunoblotting using a polyclonal antibody against the isopenicillin N synthase to assess the downregulation of the *pcbC* gene (Janus et al. [@CR18]). Biochemical assays can be performed as well which are specific for the enzyme/protein of interest to evaluate silencing of the target protein by specific siRNA(s). Hammond and Keller in 2005 executed the norsolorinic acid (NOR) analysis by thin-layer chromatography and observed whether the *A. nidulans aflR* IRTs can suppress NOR production (Hammond and Keller [@CR11]). Research discoveries in vitro need to be accompanied by establishment of the potentiality of siRNA as a therapeutic. The antifungal drug dosages within the therapeutic window have been tested and determined on animal models, mostly murine models (Ibrahim et al. [@CR15], [@CR16]) for fungal diseases like zygomycosis, aspergillosis, candidiasis, cryptococcosis; but no pharmacological studies have yet been conducted on animal models employing siRNA therapy for fungal infections. Thus, dedicated efforts are needed to assess siRNA therapy for mycoses in various animal models and further investigate in humans through clinical trials.
Conclusion {#Sec13}
==========
RNAi has been explored in fungi in the post-genomics era, not only to understand the RNA silencing machinery but also as a tool to treat fungal diseases which cannot be effectively managed by conventional drugs. For instance, the past few decades have seen a rise in the opportunistic invasive fungal infections (mycoses) due to significant increase in the population of immunocompromised patients. The limitations of existing antifungal therapies have provided impetus toward exploring RNAi as a therapeutic option. *N. crassa* was the organism in which the first RNAi gene was discovered which was succeeded by numerous in vitro studies to achieve improved silencing in fungi and promising RNAi as a therapeutic tool. Identification of a potential target gene is necessitated against which siRNA is designed in silico, and recent whole-genome studies in fungi have greatly expedited the novel drug discovery process. Even though RNAi-related research discoveries have made rapid progress from in vitro to in vivo and clinical trials for neurodegenerative diseases and cancer, proper pharmacokinetic parameters of safety and efficacy for RNAi still remain to be answered for mycoses. RNAi as a therapeutic approach is relatively at a nascent stage, and uninterrupted probing should prove useful to drive it as a preferred option for the treatment of mycoses in the long run.
| {
"pile_set_name": "PubMed Central"
} |
0)/(v**0/v)**(-1/27) assuming v is positive.
v**(-1621/27)
Simplify ((u**(-3/2))**(-29))**(-25) assuming u is positive.
u**(-2175/2)
Simplify (g*g**3/g)**(-36) assuming g is positive.
g**(-108)
Simplify ((g*g/((g*g/(g/(g*g/g**(-11)))*g)/g)*g)/g**(6/5))**(-8) assuming g is positive.
g**(488/5)
Simplify (j**(-29)*j)/(j*j**(-13)) assuming j is positive.
j**(-16)
Simplify ((r*r**(-1)/r)**3)**(-2/3) assuming r is positive.
r**2
Simplify (o**0/o)**(-12)*o**(1/6)/(o*(o/o**(-2/3))/o*o) assuming o is positive.
o**(19/2)
Simplify ((o**0)**13)**(-39/2) assuming o is positive.
1
Simplify ((b/(b/((b/b**(1/2))/b)))**(-39))**(2/13) assuming b is positive.
b**3
Simplify ((o**(-1/5)*o)/(o/(o**(-2/5)/o*o*o)))/(o/(o**(-2)*o))**(-22/7) assuming o is positive.
o**(234/35)
Simplify (q**5/q)**(-16) assuming q is positive.
q**(-64)
Simplify (q*q**2)/q*(q**(-3)/q)/q*(q**(-2))**14 assuming q is positive.
q**(-31)
Simplify j*j**(-14/5)*j*j/j**(-20) assuming j is positive.
j**(101/5)
Simplify t**(-1/10)*t**(3/5)/t assuming t is positive.
1/sqrt(t)
Simplify (f**(1/2)/f*f)**(-1/17)/((f**3*f)/((f/((((f/(f**(-2)/f))/f)/f)/f))/f*f)) assuming f is positive.
f**(-137/34)
Simplify (h**(-5))**(-2) assuming h is positive.
h**10
Simplify ((q**(2/11)/q)/(q**(-2)*q))/(q/(q*q**1))**(-20) assuming q is positive.
q**(-218/11)
Simplify n*n**(3/10)*n*n*n/(n**10/n)*n assuming n is positive.
n**(-37/10)
Simplify z**(3/17)*z**(-2/79)/z assuming z is positive.
z**(-1140/1343)
Simplify (h**(-1)*h**(1/3))/(h**(2/9)/(h/h**1)) assuming h is positive.
h**(-8/9)
Simplify (y*y**8)/y*y/(y**(1/5)/y)*y*y/y**(2/11)*y/(y*y**(2/9)/y) assuming y is positive.
y**(6136/495)
Simplify (d*d**(-18))**(1/21) assuming d is positive.
d**(-17/21)
Simplify y**(-14)/((y*(y/(y*y/(y/(y*y/(y**(-2/61)*y)))))/y*y)/y) assuming y is positive.
y**(-791/61)
Simplify (d**(-2))**48/(d/d**(1/3)*d**(-3/7)) assuming d is positive.
d**(-2021/21)
Simplify (l/l**(-6)*l)**(-23/5) assuming l is positive.
l**(-184/5)
Simplify n/((n**(-6/7)*n)/n)*(n*n**(-1))/n*(n/(n**(-7)/n))/n**(2/7) assuming n is positive.
n**(67/7)
Simplify ((n/((n*n**(1/3)*n)/n))/n*(n*n**7)/n)/(n**(3/4)/n**(-1/9)) assuming n is positive.
n**(173/36)
Simplify (x**7/x)**17 assuming x is positive.
x**102
Simplify ((o**(4/7)/o)/(o*o**3))/(o**1*o**(1/8)) assuming o is positive.
o**(-311/56)
Simplify (p*(((((p**(-1/4)/p)/p)/p*p)/p)/p)/p)**(-14) assuming p is positive.
p**(119/2)
Simplify i*i*i/(i*(i/((((i**(8/5)/i)/i)/i*i)/i*i))/i)*i**(-21) assuming i is positive.
i**(-97/5)
Simplify d**(7/4)*d*d**(20/7) assuming d is positive.
d**(157/28)
Simplify ((x*(x/(x**1*x))/x*x)**(-12/5))**40 assuming x is positive.
1
Simplify (b**(2/17)*b/b**(3/4))**(1/13) assuming b is positive.
b**(25/884)
Simplify (w/(w*w**(-2/3)))/w**18 assuming w is positive.
w**(-52/3)
Simplify a*a**(-12)*a*a*a**23 assuming a is positive.
a**14
Simplify ((u*u/(u*u/(u/(u/u**(1/11)))))/u**6)**(-25/4) assuming u is positive.
u**(1625/44)
Simplify (w/w**(-14))**(1/43) assuming w is positive.
w**(15/43)
Simplify ((g**0*g)**(2/165))**38 assuming g is positive.
g**(76/165)
Simplify (z*z/(z**(3/16)/z*z*z))/((z/(z/(z**(-12/17)/z*z)))/z) assuming z is positive.
z**(685/272)
Simplify (o**(-5)*(o**(-1/11)/o*o)/o)/(o**(2/3))**(2/29) assuming o is positive.
o**(-5873/957)
Simplify m*(((m**(-2/9)*m)/m)/m)/m*(m/m**7)/m*m*((m*m**(2/11))/m)/m*m*m**(-10)/m assuming m is positive.
m**(-1786/99)
Simplify (((u/u**(-1))/u)/u)**49/((u/(u/u**6))/(u*u/((u/(u*u/(u/(u**1*u*u*u))*u))/u*u))) assuming u is positive.
u
Simplify (x**(1/4))**(-15/11)*(x*x**(-1/3))**(1/12) assuming x is positive.
x**(-113/396)
Simplify ((k*k**(-2)/k)/(k**(-1/2)/k))/((k/(k**(-7)*k))/((k/k**7)/k*k)) assuming k is positive.
k**(-27/2)
Simplify (x*x**2*x)**(-49)/(x*x**(2/7)/x*x)**(2/13) assuming x is positive.
x**(-17854/91)
Simplify (v*v**38)/(v/v**(-21)) assuming v is positive.
v**17
Simplify (u/(u*u**(-3)/u*u*u*u))/((u**13*u)/u) assuming u is positive.
u**(-12)
Simplify (l**(2/7)*l*l*l)**(-10/7)*(l/l**4*l)/(((l/(l/(l*((l*l**(-6)*l)/l)/l)))/l)/l) assuming l is positive.
l**(15/49)
Simplify (b**(-2/5)/b)**(-2/21)/(b**(-1/2))**45 assuming b is positive.
b**(679/30)
Simplify (r/(r/(r/(r**(-1/3)*r))))**(-3)*(r**(2/7)/r)**(2/9) assuming r is positive.
r**(-73/63)
Simplify (s*(s/(s/(s*s**(-1/34))))/s)/(s/((s*(s/((s/s**(-2/73))/s))/s)/s)*s*s) assuming s is positive.
s**(-5105/2482)
Simplify ((j**(5/6)/j)/j)/(j**(-3/4)/j) assuming j is positive.
j**(7/12)
Simplify (d**8*d)**(1/27) assuming d is positive.
d**(1/3)
Simplify (n**(-5)/n)/n*n*n**(-7)*(n**(-5/3)/n)/(n*n*n**(2/23)*n) assuming n is positive.
n**(-1294/69)
Simplify (l/(l**(9/8)/l))/l*l*l**(-9/7)/l assuming l is positive.
l**(-79/56)
Simplify ((z**(-6)*z*z*z)/((z*z*z**(-6))/z))**(1/3) assuming z is positive.
z**(2/3)
Simplify n**(3/4)/(n/n**(9/2)) assuming n is positive.
n**(17/4)
Simplify (j*j*(j/(j/(j*j**(-36))*j))/j*j)/((j**19*j)/j) assuming j is positive.
j**(-53)
Simplify (d*(d**14/d)/d)**(1/6) assuming d is positive.
d**(13/6)
Simplify (g**0)**(-25)/(g**(3/10)/(g*g*g**(-1/8))) assuming g is positive.
g**(63/40)
Simplify (h*h**0*h)**(1/11)*h**(-1/4)/(h/(h/((h/h**(-1/2))/h))*h) assuming h is positive.
h**(-69/44)
Simplify (o**(7/4))**12 assuming o is positive.
o**21
Simplify (l**(-2/13)*l)**(-1) assuming l is positive.
l**(-11/13)
Simplify (t/(t**(2/25)/t)*t**(1/4))**(-28) assuming t is positive.
t**(-1519/25)
Simplify (x*x**32/x)**(6/37) assuming x is positive.
x**(192/37)
Simplify ((z/(z*z**5*z*z))/((z/(z/(z/z**6)))/z))/(z**(1/3)/(z*z*z**(-2/19))) assuming z is positive.
z**(32/57)
Simplify (q/(q*q**(-2/7)/q*q))**(-35)/(q/((q/(q*q**(-4))*q)/q)*q**7) assuming q is positive.
q**(-14)
Simplify (s*(s**8/s*s)/s*s)/s**(-5/3)*s**(-1/4)*s*s**(-3/5) assuming s is positive.
s**(649/60)
Simplify w**(-21)/w**(16/5) assuming w is positive.
w**(-121/5)
Simplify m/(m*m**(-15)/m*m)*m**(1/22)*m*m assuming m is positive.
m**(375/22)
Simplify u**23/u**5 assuming u is positive.
u**18
Simplify ((t**(-1/3)/t)/t**(3/4))/(t*(t**(-1)*t)/t*t*t**(-1/4)) assuming t is positive.
t**(-17/6)
Simplify ((h**(-2)/h)**45)**(-26) assuming h is positive.
h**3510
Simplify (m*m**1*m)**(18/7)/(m/m**(-2/5))**(-42) assuming m is positive.
m**(2328/35)
Simplify (b/b**11)**(-18/5) assuming b is positive.
b**36
Simplify n**(4/5)*n*n/(n/((n*n*n**2)/n))*(n*n**(-2/13)*n*n)/n**9 assuming n is positive.
n**(-88/65)
Simplify (t**0)**(-11)/(t*t**(1/6)*t*t*t**1) assuming t is positive.
t**(-25/6)
Simplify r**1*r*r*(r/r**(3/2))/r*r*r*(r/(r/(r/r**(-2/3))*r))**(-23/3) assuming r is positive.
r**(-29/18)
Simplify (r**(1/6)*(r*r/(r/r**6))/r)**(-44) assuming r is positive.
r**(-814/3)
Simplify (z*(((z*z**22)/z)/z)/z)/(z/((z**(2/49)/z)/z*z)) assuming z is positive.
z**(933/49)
Simplify l**11/(l**2/l) assuming l is positive.
l**10
Simplify ((b*b**(-2/13))/b**(3/5))**(-18) assuming b is positive.
b**(-288/65)
Simplify (t**10/t**(-15))**(-34) assuming t is positive.
t**(-850)
Simplify (v/(v**(-3/7)/v)*v/v**(3/8))**43 assuming v is positive.
v**(7353/56)
Simplify (k**0)**32*(k*k**(-1/11))/k**7 assuming k is positive.
k**(-67/11)
Simplify (r*r**(2/45))/r**(-2) assuming r is positive.
r**(137/45)
Simplify ((s**1)**(2/47))**(-50) assuming s is positive.
s**(-100/47)
Simplify (g**(1/3))**29/(g*g**(-1/3)*g)**(-34) assuming g is positive.
g**(199/3)
Simplify (d*d*d/(d/(d*d*d*d*(d*d*(d/((d/d**2)/d))/d)/d*d))*d)**(1/5) assuming d is positive.
d**(11/5)
Simplify (x*x/(x*x**(-1/2)))/x**(1/6)*x/(x*x**(-1)*x*x)*x/(x*x/x**(-1/6)) assuming x is positive.
x**(-5/6)
Simplify (((a**(3/4)/a)/a)/(a/(a/a**1)))/(a*a/a**(-2)*a*a*a*a**(-7)*a*a) assuming a is positive.
a**(-17/4)
Simplify (i**(-2/7)*i)**(-6/11)*(i**(-1/4))**(-14) assuming i is positive.
i**(479/154)
Simplify (i**(-7/3)*i)**9 assuming i is positive.
i**(-12)
Simplify ((d/(d*d*(d/(d**11/d))/d*d))/d)/(d*(d*d**(-10))/d) assuming d is positive.
d**16
Simplify b**(-8/5)*b**22 assuming b is positive.
b**(102/5)
Simplify (((d*(d*(d**2/d)/d)/d*d*d)/d*d)/(d/d**4*d))**(2/9) assuming d is positive.
d**(10/9)
Simplify (q**(4/7)*q**10)**33 assuming q is positive.
q**(2442/7)
Simplify (g/(g**21/g))**(-2/17) assuming g is positive.
g**(38/17)
Simplify r**(-25)*r*r**(-3) assuming r is positive.
r**(-27)
Simplify (a**(-4)*a/(a/(a/a**4))*a* | {
"pile_set_name": "DM Mathematics"
} |
Bayesian model averaging for ligand discovery.
High-throughput screening (HTS) is now a standard approach used in the pharmaceutical industry to identify potential drug-like lead molecules. The analysis linking biological data with molecular properties is a major goal in both academic and pharmaceutical research. This paper presents a Bayesian analysis of high-dimensional descriptor data using Markov chain Monte Carlo (MCMC) simulations for learning classification trees as a novel method for pharmacophore and ligand discovery. We use experimentally determined binding affinity data with the protein pyruvate kinase to train and assess our model averaging algorithm and then apply it to a large database of over 3.7 million molecules. We compare the results of a number of variations on the central Bayesian theme to that of two Neural Network (NN) architectures and that of Support Vector Machines (SVM). The main Bayesian algorithm, in addition to achieving high specificity and sensitivity, also lends itself naturally to classifying test sets with missing data and providing a ranking for the classified compounds. The approach has been used to select and rank potential biologically active compounds and could provide a powerful tool in compound testing. | {
"pile_set_name": "PubMed Abstracts"
} |
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For a quick assistance, please contact 9000711144, 9000511144, 9640311144 | {
"pile_set_name": "OpenWebText2"
} |
Reds express interest in Viciedo
The Reds are interested free agent Dayan Viciedo.The Chicago White Sox released Viciedo this week after designating him for assignment. Viciedo hit .231/.281/.405 with 21 home runs and 58 RBI for the Chicago White Sox in 2014. He's played first base, third base and outfield in his five-year big league career.
His best year was 2012 when he hit .255/.300/.444 with 25 home runs and 78 RBI.
Viciedo, a 25-year-old Cuban, signed with the White Sox in 2008. He has 3.1 years service time, so the club that signs him will control him for three years.
"We inquired about him," Reds general manager Walt Jocketty said. "I don't know how far it will go. We're looking at where we would play him." | {
"pile_set_name": "OpenWebText2"
} |
Q:
Code does not wait for user to finish typing in the repeat password section
I am trying to setup a signup view with using parse.com as backend but for some reason whenever i start typing in the reenter password field, as soon as i type something, it starts going through this
else if ([password compare:passwordAgain] != NSOrderedSame) {
// We have non-zero strings.
// Check for equal password strings.
textError = YES;
errorText = [errorText stringByAppendingString:passwordMismatchText];
[_reEnterPasswordField becomeFirstResponder];
NSLog(@"stops here");
}
method and sends me the error message passwordMismatchText. It goes through this message everytime i change a word whether i added or deleted it. When I use the same methods with xib the files i had no problem. But after I try to do the same thing with storyboards I am having this issue. I tried creating a user default for _doneButton.enabled == YES and put an another if around the errorText =[...] message, but did not solve the problem. I appreciate for the help.
SignUpViewController.h
#import <UIKit/UIKit.h>
@interface SignUpViewController : UIViewController<UITextFieldDelegate>
@property (weak, nonatomic) IBOutlet UIBarButtonItem *doneButton;
@property (weak, nonatomic) IBOutlet UITextField *userNameField;
@property (weak, nonatomic) IBOutlet UITextField *passwordField;
@property (weak, nonatomic) IBOutlet UITextField *reEnterPasswordField;
- (IBAction)done:(id)sender;
- (IBAction)cancel:(id)sender;
@end
SignUpViewController.m
#import "SignUpViewController.h"
#import <Parse/Parse.h>
#import "ActivityView.h"
#import "ProfileViewController.h"
@interface SignUpViewController ()
- (void)textInputChanged:(NSNotification *)note;
-(void)processFieldEntries;
- (BOOL)shouldEnableDoneButton;
@end
@implementation SignUpViewController
@synthesize doneButton = _doneButton;
@synthesize userNameField = _userNameField;
@synthesize passwordField = _passwordField;
@synthesize reEnterPasswordField = _reEnterPasswordField;
- (id)initWithNibName:(NSString *)nibNameOrNil bundle:(NSBundle *)nibBundleOrNil
{
self = [super initWithNibName:nibNameOrNil bundle:nibBundleOrNil];
if (self) {
// Custom initialization
}
return self;
}
- (void)viewDidLoad
{
[super viewDidLoad];
[[NSNotificationCenter defaultCenter ]addObserver:self selector:@selector(textInputChanged:) name: UITextFieldTextDidChangeNotification object:_userNameField];
[[NSNotificationCenter defaultCenter]addObserver:self selector:@selector(textInputChanged:) name:UITextFieldTextDidChangeNotification object:_passwordField];
[[NSNotificationCenter defaultCenter]addObserver:self selector:@selector(textInputChanged:) name:UITextFieldTextDidChangeNotification object:_reEnterPasswordField];
_doneButton.enabled = NO;
NSLog(@"nsnotification is working fine");
}
-(void)viewWillAppear:(BOOL)animated
{
[_userNameField becomeFirstResponder];
[super viewWillAppear:animated];
NSLog(@"indeed usernamefield became a first responder");
}
- (void)didReceiveMemoryWarning
{
[super didReceiveMemoryWarning];
// Dispose of any resources that can be recreated.
}
-(BOOL)textFieldShouldReturn:(UITextField *)textField
{
if (textField == _userNameField ) {
[_userNameField becomeFirstResponder];
}
if (textField == _passwordField) {
[_passwordField becomeFirstResponder];
}
if (textField == _reEnterPasswordField)
{
[_reEnterPasswordField becomeFirstResponder];
}
NSLog(@"keyboard action works fine ");
return YES;
}
-(BOOL)shouldEnableDoneButton
{
BOOL enableDoneButton = NO;
if (_userNameField.text != nil &&
_userNameField.text.length > 0 &&
_passwordField.text != nil &&
_passwordField.text.length > 0 &&
_reEnterPasswordField.text != nil &&
_reEnterPasswordField.text.length > 0)
{
[self processFieldEntries];
enableDoneButton = YES;
NSLog(@"done button enabled");
}
return enableDoneButton;
}
-(void)textInputChanged:(NSNotification *)note
{
_doneButton.enabled = [self shouldEnableDoneButton];
}
- (IBAction)done:(id)sender {
[_userNameField resignFirstResponder];
[_passwordField resignFirstResponder];
[_reEnterPasswordField resignFirstResponder];
[self processFieldEntries];
NSLog(@"do you see this");
}
- (IBAction)cancel:(id)sender
{
[self.presentingViewController dismissViewControllerAnimated:YES completion:nil];
}
-(void)processFieldEntries
{
// Check that we have a non-zero username and passwords.
// Compare password and passwordAgain for equality
// Throw up a dialog that tells them what they did wrong if they did it wrong.
NSString *username = _userNameField.text;
NSString *password = _passwordField.text;
NSString *passwordAgain = _reEnterPasswordField.text;
NSString *errorText = @"Please ";
NSString *usernameBlankText = @"enter a username";
NSString *passwordBlankText = @"enter a password";
NSString *joinText = @", and ";
NSString *passwordMismatchText = @"enter the same password twice";
BOOL textError = NO;
NSLog(@"validation begins here");
// Messaging nil will return 0, so these checks implicitly check for nil text.
if (username.length == 0 || password.length == 0 || passwordAgain.length == 0) {
textError = YES;
// Set up the keyboard for the first field missing input:
if (passwordAgain.length == 0) {
[_reEnterPasswordField becomeFirstResponder];
}
if (password.length == 0) {
[_passwordField becomeFirstResponder];
}
if (username.length == 0) {
[_userNameField becomeFirstResponder];
}
if (username.length == 0) {
errorText = [errorText stringByAppendingString:usernameBlankText];
}
if (password.length == 0 || passwordAgain.length == 0) {
if (username.length == 0) { // We need some joining text in the error:
errorText = [errorText stringByAppendingString:joinText];
}
errorText = [errorText stringByAppendingString:passwordBlankText];
}
} else if ([password compare:passwordAgain] != NSOrderedSame) {
// We have non-zero strings.
// Check for equal password strings.
textError = YES;
errorText = [errorText stringByAppendingString:passwordMismatchText];
[_reEnterPasswordField becomeFirstResponder];
NSLog(@"stops here");
}
if (textError) {
UIAlertView *alertView = [[UIAlertView alloc] initWithTitle:errorText message:nil delegate:self cancelButtonTitle:nil otherButtonTitles:@"Ok", nil];
[alertView show];
return;
}
NSLog(@"validation works just fine");
// Everything looks good; try to log in.
// Disable the done button for now.
_doneButton.enabled = NO;
ActivityView *activityCircle = [[ActivityView alloc] initWithFrame:CGRectMake(0.f, 0.f, self.view.frame.size.width, self.view.frame.size.height)];
UILabel *label = activityCircle.label;
label.text = @"Signing You Up";
label.font = [UIFont boldSystemFontOfSize:20.f];
[activityCircle.activityIndicator startAnimating];
[activityCircle layoutSubviews];
[self.view addSubview:activityCircle];
NSLog(@"activity view works just fine");
//parse registeration
// Call into an object somewhere that has code for setting up a user.
// The app delegate cares about this, but so do a lot of other objects.
// For now, do this inline.
PFUser *user = [PFUser user];
user.username = username;
user.password = password;
[user signUpInBackgroundWithBlock:^(BOOL succeeded, NSError *error) {
if (error) {
UIAlertView *alertView = [[UIAlertView alloc] initWithTitle:[[error userInfo] objectForKey:@"error"] message:nil delegate:self cancelButtonTitle:nil otherButtonTitles:@"Ok", nil];
[alertView show];
_doneButton.enabled = [self shouldEnableDoneButton];
[activityCircle.activityIndicator stopAnimating];
[activityCircle removeFromSuperview];
// Bring the keyboard back up, because they'll probably need to change something.
[_userNameField becomeFirstResponder];
return;
}
// Success!
[activityCircle.activityIndicator stopAnimating];
[activityCircle removeFromSuperview];
//add the next screen here
}];
NSLog(@"user signedup just fine");
//now pass the view from sign up to profile view
}
/*
//this one didnt work
-(void)prepareForSegue:(UIStoryboardSegue *)segue sender:(id)sender
{
ProfileViewController *myProfileView = [segue destinationViewController];
if (_doneButton.enabled == YES) {
[myProfileView performSegueWithIdentifier:@"SignUpSegue" sender:_doneButton];
}
}
*/
-(BOOL)shouldPerformSegueWithIdentifier:(NSString *)identifier sender:(id)sender
{
NSLog(@"is this method visible");
if (_doneButton.enabled == YES) {
[self performSegueWithIdentifier:@"SignUpSegue" sender:_doneButton];
}
return NO;
}
@end
this is the log files that I am getting
2013-09-06 02:49:19.938 nsnotification is working fine
2013-09-06 02:49:19.942 indeed usernamefield became a first responder
2013-09-06 02:49:47.446 validation begins here
2013-09-06 02:49:47.448 stops here
2013-09-06 02:49:47.485 done button enabled
2013-09-06 02:49:49.271 validation begins here
2013-09-06 02:49:49.273 stops here
2013-09-06 02:49:49.296 done button enabled
2013-09-06 02:49:51.257 validation begins here
2013-09-06 02:49:51.259 validation works just fine
2013-09-06 02:49:51.265 activity view works just fine
2013-09-06 02:49:51.270 user signedup just fine
2013-09-06 02:49:51.271 done button enabled
A:
You are triggering the code to run by your observation of UITextFieldTextDidChangeNotification. As this moves through your methods you eventually call processFieldEntries. Probably you shouldn't be calling processFieldEntries from shouldEnableDoneButton.
| {
"pile_set_name": "StackExchange"
} |
Rotational invariance approach for the evaluation of multiple phases in interferometry in the presence of nonsinusoidal waveforms and noise.
Incorporation of two phase-shifting devices in a holographic moiré configuration not only renders the interferometer compatible with automated measurements but also allows for simultaneous measurement of multiple phase information in the interferometer. However, simultaneous handling of multiple phase steps and subsequent simultaneous determination of multiple phase distributions requires the introduction of novel tools in phase-shifting interferometry. In this context, the aim of this paper is to propose a subspace invariance approach to address these issues. This approach takes advantage of the rotational invariance of signal subspaces spanned by two temporally displaced data sets formed from the intensity fringes recorded temporally on pixels of the CCD camera. The method first identifies the arbitrary phase steps imparted to the piezoactuator devices. The estimated phase steps are subsequently applied in the linear Vandermonde system of equations to determine the phase distributions. The method also allows for handling nonsinusoidal wavefronts. Since the phase steps are extracted at every point on the interferogram, the method is applicable to configurations that use spherical beams. The robustness of the method is investigated by adding white Gaussian noise during the simulations. | {
"pile_set_name": "PubMed Abstracts"
} |
Knicks Blogger Mike Miller Talks Knicks Offseason Moves
PostDontLie.com's Mike Miller reacts to offseason moves.
With the Knicks making a series of big moves in the offseason after their playoff exit, PostDontLie.com's Mike Miller joined me to talk about New York's most recent efforts to catch the Heat and Pacers at the top of the Eastern Conference.
Miller gives his thoughts on recent speculation about Carmelo Anthony, what role he expects for the Knicks' first round pick, Tim Hardaway Jr., to play, and new contracts for JR Smith and Pablo Prigioni. He also talks about the biggest loss from the Andrea Bargnani trade and what the loss of Chris Copeland means to the Knicks.
To hear the interview, click below, and tell us what you think in the comments section. | {
"pile_set_name": "Pile-CC"
} |
Tom Eaton
Tom Eaton (born April 8, 1982) is a prop comic. He tours nationally in the U.S. with his "trunk o' junk", the trademark of his prop comedy. Eaton has performed his comedy act in over three countries and on two continents.
Biography
Early life
Eaton was born in Orange County, California, on April 8, 1982. He is the son of Thomas Eaton Sr., a sandwich magnate from Wisconsin. He began performing in junior high school theater, playing the role of Sancho Panza in the Spiro Agnew Junior High School production of Man of La Mancha.
Career
After briefly moving to Chicago, he was tapped as a presenter for the 2002 Comedy Central Roast of Chevy Chase
In 2004, Eaton was in early talks with ESPN2 to act as the sidekick for a late night sports variety show hosted by Scottie Pippen called Just Inside the Arc. ESPN opted to fill the time slot with World Series of Poker reruns.
Eaton was awarded the Don Knotts Memorial Award by the Greater San Bernardino, California, Key Club for his contributions to their 2006 "Suds and Duds" car wash–clothing drive. He is the second recipient of this award.
Eaton tours comedy clubs nationally in the U.S. He is also the voice of Emilio the Llama in the web cartoon Two for Tacos, which was released on the web in fall 2009.
References
External links
Falling 4u The Musical Home Page
Category:American stand-up comedians
Category:1982 births
Category:Living people
Category:Prop comics
Category:21st-century American comedians | {
"pile_set_name": "Wikipedia (en)"
} |
// Copyright 2015 PingCAP, Inc.
//
// Licensed under the Apache License, Version 2.0 (the "License");
// you may not use this file except in compliance with the License.
// You may obtain a copy of the License at
//
// http://www.apache.org/licenses/LICENSE-2.0
//
// Unless required by applicable law or agreed to in writing, software
// distributed under the License is distributed on an "AS IS" BASIS,
// See the License for the specific language governing permissions and
// limitations under the License.
package mysql
type lengthAndDecimal struct {
length int
decimal int
}
// defaultLengthAndDecimal provides default Flen and Decimal for fields
// from CREATE TABLE when they are unspecified.
var defaultLengthAndDecimal = map[byte]lengthAndDecimal{
TypeBit: {1, 0},
TypeTiny: {4, 0},
TypeShort: {6, 0},
TypeInt24: {9, 0},
TypeLong: {11, 0},
TypeLonglong: {20, 0},
TypeDouble: {22, -1},
TypeFloat: {12, -1},
TypeNewDecimal: {11, 0},
TypeDuration: {10, 0},
TypeDate: {10, 0},
TypeTimestamp: {19, 0},
TypeDatetime: {19, 0},
TypeYear: {4, 0},
TypeString: {1, 0},
TypeVarchar: {5, 0},
TypeVarString: {5, 0},
TypeTinyBlob: {255, 0},
TypeBlob: {65535, 0},
TypeMediumBlob: {16777215, 0},
TypeLongBlob: {4294967295, 0},
TypeJSON: {4294967295, 0},
TypeNull: {0, 0},
TypeSet: {-1, 0},
TypeEnum: {-1, 0},
}
// IsIntegerType indicate whether tp is an integer type.
func IsIntegerType(tp byte) bool {
switch tp {
case TypeTiny, TypeShort, TypeInt24, TypeLong, TypeLonglong:
return true
}
return false
}
// GetDefaultFieldLengthAndDecimal returns the default display length (flen) and decimal length for column.
// Call this when no Flen assigned in ddl.
// or column value is calculated from an expression.
// For example: "select count(*) from t;", the column type is int64 and Flen in ResultField will be 21.
// See https://dev.mysql.com/doc/refman/5.7/en/storage-requirements.html
func GetDefaultFieldLengthAndDecimal(tp byte) (flen int, decimal int) {
val, ok := defaultLengthAndDecimal[tp]
if ok {
return val.length, val.decimal
}
return -1, -1
}
// defaultLengthAndDecimal provides default Flen and Decimal for fields
// from CAST when they are unspecified.
var defaultLengthAndDecimalForCast = map[byte]lengthAndDecimal{
TypeString: {0, -1}, // Flen & Decimal differs.
TypeDate: {10, 0},
TypeDatetime: {19, 0},
TypeNewDecimal: {11, 0},
TypeDuration: {10, 0},
TypeLonglong: {22, 0},
TypeJSON: {4194304, 0}, // Flen differs.
}
// GetDefaultFieldLengthAndDecimalForCast returns the default display length (flen) and decimal length for casted column
// when flen or decimal is not specified.
func GetDefaultFieldLengthAndDecimalForCast(tp byte) (flen int, decimal int) {
val, ok := defaultLengthAndDecimalForCast[tp]
if ok {
return val.length, val.decimal
}
return -1, -1
}
| {
"pile_set_name": "Github"
} |
Increased thymic output in HIV-negative patients after antiretroviral therapy.
To determine the effects of antiretroviral therapy on thymic output independent of HIV infection. Thymic output was evaluated by quantifying signal joint T-cell receptor (TCR) recombination excision circles in peripheral blood lymphocytes from HIV-negative patients undergoing prophylactic antiretroviral therapy. Additionally, effects of the HIV protease inhibitor nelfinavir were assessed in vivo on TCR-induced death of murine double-positive thymocytes. Five out of seven HIV-negative patients undergoing prophylactic antiretroviral therapy exhibited a dramatic increase (1-3 log10) in recent thymic emigrants containing signal joint TCR recombination excision circles while their peripheral T cell compartments remained relatively unaffected. None of the patients developed subsequent HIV infections. Interestingly, nelfinavir did not have significant effects on TCR-induced apoptosis of murine thymocytes in vivo. Antiretroviral therapy augments thymic output independent of HIV. Furthermore, nelfinavir does not dramatically affect TCR-induced thymocyte death in mice, thus central tolerance remains intact. | {
"pile_set_name": "PubMed Abstracts"
} |
We Love RI
110% Effort
Picture Perfect
You deserve to look great and so does your house or condominium.
We are a boutique real estate company located on the East Side of Providence serving all of Rhode Island.
Hello, I’m Joshua Deaner, a Licensed Real Estate Broker on the East Side of Providence. My team and I would love to assist you with your home purchase or house sale. As experts in the Greater Providence real estate market, we can help you find the property of your choice in the most efficient and stress-free manner possible.
By providing experience, knowledge, and insight we can assist you in locating your ideal house in the Providence area. We are not satisfied until we find that hidden gem amongst all properties. Our commitment is to build a long lasting relationship with you by treating others the way we would like to be treated.
With The Rhode Guide Real Estate Co., you can buy or sell homes with confidence.
We would love to learn more about you and your real estate needs. Let’s get together to discuss over a cup of coffee (with our compliments, of course). Please give us a call @ 401-415-9777. | {
"pile_set_name": "Pile-CC"
} |
Q:
How to run Spring Shell scripts in a JUnit test
I have a Spring Shell-based application and a couple of scripts. Is there an easy way to run the scripts in a JUnit test such that a test fails, if some exception/error occurs during the execution of the script?
The purpose of the tests is to make sure that all correct scripts run without errors.
Update 1:
Here's a little helper class for running scripts in JUnit:
import org.apache.commons.io.FileUtils;
import org.springframework.shell.Bootstrap;
import org.springframework.shell.core.CommandResult;
import org.springframework.shell.core.JLineShellComponent;
import java.io.File;
import java.io.IOException;
import java.util.List;
import static org.fest.assertions.api.Assertions.*;
public class ScriptRunner {
public void runScript(final File file) throws IOException
{
final Bootstrap bootstrap = new Bootstrap();
final JLineShellComponent shell = bootstrap.getJLineShellComponent();
final List<String> lines = FileUtils.readLines(file);
for (final String line : lines) {
execVerify(line, shell);
}
}
private void execVerify(final String command, final JLineShellComponent shell) {
final CommandResult result = shell.executeCommand(command);
assertThat(result.isSuccess()).isTrue();
}
}
A:
You can create an instance of Bootstrap, get the shell out of it and then executeCommand() (including the shell command) on it.
You may be interested in what is done in Spring XD for this: https://github.com/spring-projects/spring-xd/blob/master/spring-xd-shell/src/test/java/org/springframework/xd/shell/AbstractShellIntegrationTest.java (although there are a lot of XD specific details)
| {
"pile_set_name": "StackExchange"
} |
There is plenty of speculation about how hundreds of non-combatants were killed in Mosul, all apparently by accident. US and Iraqi forces have admitted partial culpability. But there are other causative factors at work.
Locals survey the damage done by the airtstrike. (Pictures via social media, head of Mosul council, Basma Basim)
The dramatic and tragic events in Mosul on March 22, that saw hundreds of civilians killed when a whole city block was levelled by an aerial strike has dominated Iraqi news coverage over the past week.
The extremist group known as the Islamic State, which had controlled Mosul since the middle of 2014, had brought hundreds of civilians into the area, often forcing several families to live in one house, in a neighbourhood littered with bombed and burned vehicles. Other families were trapped in Mosul and simply sought shelter there. A mistaken bombing raid by the international coalition fighting the Islamic State, or IS, group in Mosul levelled a whole block and caused, quite literally, hundreds of deaths and injuries, trapping whole families beneath rubble.
The incident caused a temporary stoppage of the operation and a re-evaluation of tactics. The international coalition said that the bombs had been dropped at the behest of the Iraqi forces on the ground, who call in locations of IS fighters.
In terms of American involvement in the tragedy, Iraqi officials have confirmed that the US wants to end the fighting with a victory over the IS group as soon as possible. This has seen more US participation on the ground. There are also some French military units on the northern outskirts of Mosul.
In other battles, an exit route has been left for the extremists. This didn't happen in Mosul, trapping extremists and civilians. Senior commanders refuse to speculate as to why.
This week the New York Times reported on what they described as “the fullest acceptance of responsibility by an American commander since the March 17 airstrike”.
A senior US commander in Iraq, Stephen J. Townsend, said that a US airstrike most likely led to the collapse of the buildings. But he also said there would be an investigation to see if explosives stored by the IS group inside or nearby might not also have caused the larger damage.
The US general said that the rules governing combat in Iraq had not changed significantly but that decision-making about when and where air strikes should take place had been “decentralized”. Iraqi soldiers themselves have commented on how much faster the decision-making process has become.
Even before the incident in March, Khamis al-Khanjar, an Iraqi business mogul who has supported Sunni Muslim parties in Iraq financially, was warning that the US’ increased enthusiasm for fighting the IS group was dangerous and likely to increase the number of civilian casualties. He told Reuters that those Mosul locals who had welcomed their liberators in eastern Mosul were now extremely frightened of US airstrikes.
But local analysts believe there is more background that needs to be considered when apportioning blame for this tragedy.
For example, some analysts believe that one of the biggest mistakes made in Mosul was laying siege to the city, which has meant that the IS fighters are trapped, along with thousands of civilians.
Other fights against the IS group elsewhere in the country used a different strategy, one that made sure to leave an exit route for the extremists. This happened in Fallujah, Ramadi, Tikrit and Baiji and meant that there was no need for protracted fighting because the IS fighters could flee.
For example, in Fallujah in May and June, the plan involved federal police forces coming into the city from the north and east, accompanied by members of Shiite Muslim militias. Iraq’s counter-terrorism forces came in from the south. The west side of the city was supposed to be left open so the IS members could escape to Al Qaem, the Iraqi city on the border of Syria.
Rumour had it that some politicians were annoyed at how warmly Mosul residents greeted senior generals. A PR victory for the Iraqi army is not necessarily welcomed by the militias.
“The same thing was supposed to happen in Mosul,” says Raed al-Tamimi, an Iraqi army colonel working in Mosul. “When we were fighting in eastern Mosul we did not have as many losses because the extremists could exit into western Mosul, by crossing the river. We expected that the IS fighters would then withdraw from the west of Mosul towards the Syrian border, through Tal Afar and Biaj. But this didn’t happen.”
However al-Tamimi and other officers were reluctant to speculate as to why this didn’t happen.
When the military campaign to push the IS group out of Mosul began in October last year, Iraq’s often-controversial Shiite Muslim militias, originally all volunteers, were not supposed to take part in the operation in the large northern city. This is because Mosul, with a Sunni majority population, has been a defacto capital in Iraq for the IS group and there were concerns that the Shiite militias would take revenge on the Sunni population.
Instead the Shiite Muslim militias started fighting to the west of Mosul, saying that they wanted to push the IS group out of the town of Tal Afar, which was once home to Shiite Muslims of Turkmen ethnicity, many of whom had been forced to flee the town. They also announced that they wanted to cut off the IS group’s route to Raqqa, their base in neighbouring Syria.
In early November 2016, two of the best-known leaders of the militias, Abu Mahdi al-Mohandes of Hezbollah and Hadi al-Ameri, a Badr organization commander, announced that their forces had successfully cut off the road leading into Syria.
Worth noting, some of the leaders of the Shiite Muslim militias see Iraq and Syria as one battlefront. Some of their forces are actually fighting in Syria in support of the Syrian leader, Bashar al-Assad. This is because they are close to Iran, whose government is supporting al-Assad. And the Iranians believe that if the IS group is allowed to flee into Syria, this will increase pressure on their ally, al-Assad. In this case, it is better to keep the IS fighters divided and fighting on two fronts.
Mosul locals removing corpses from the bombed area.
“In real terms, the fronts in Iraq and Syria are connected and our fighters are ready to go to Syria, if the Iraqi government gives us permission,” Ahmed al-Assadi, a spokesperson for the Shiite militias said at a press conference on December 24 last year.
But there are certainly some Iraqi Shiite factions that are now fighting in Syria without any official Iraqi approval.
The other possible misstep made by the Iraqi military was cutting off the road between Mosul and Tal Afar. Had the IS fighters been able to withdraw to Tal Afar, this may have been a better place to meet them in battle. Tal Afar has largely been abandoned by its residents and fighting here would have avoided at least some of the civilian casualties now occurring in Mosul.
The other thing that has puzzled some observers is the fact that Iraq’s elite counter-terrorism forces, who fought so carefully on the eastern side of the city and were credited with saving many civilian lives, are taking less of a leading role in the fighting on the western side of Mosul.
Iraq’s federal police are now leading the fight against the IS group on the western side of the city. This is despite the fact that the federal police don’t have as much experience in guerrilla warfare as the counter-terrorism forces. The federal police were established as another wing of the regular military and in some parts of the country they play the same role as the police.
For example, in Baghdad and in other southern provinces, the federal police work alongside the regular police, maintaining security, supervising checkpoints and following up on criminal complaints.
The Iraqi government has yet to explain the need for this change in strategy around personnel. Some Iraqi analysts have suggested it is because the counter-terrorism troops lost many men in Mosul and are no longer capable of leading the fight. But in fact, these forces are still fighting in western Mosul and supervised by the same officers who fought in the eastern half of the city.
Rumour had it that, in fact, some politicians were annoyed that the senior generals of the counter-terrorism forces were being greeted so warmly by Mosul residents, because they managed to defeat the IS group and protect civilian lives. Victories achieved by the Iraqi army are not necessarily altogether welcomed by politicians affiliated with the militias. The counter terrorism forces bring back the Iraqi army's dginity and reputation, says one local observer. Whereas the militias like to see the raqi army as weak and present themselves as the best possible alternative.
There is also a lesser-known conflict at play. The counter-terrorism forces do not apparently like to fight alongside the Shiite Muslim militias. However the federal police coordinate better with the militias.
A past example of these tensions can be seen in the fighting around Tikrit in early 2015. While the Iraqi government and military wanted the support of air cover from the international coalition, the Shiite Muslim militias said they were opposed to it. Conflict broke out between militia head Hadi al-Ameri and Abdul Wahab al-Saedi, the commander of the counter-terrorism forces. Al-Ameri accused al-Saedi of cooperating too closely with US forces and the resulting conflict saw al-Saedi removed from his post.
The federal police and the Shiite Muslim militias fight more happily alongside one another because the police are under the control of Iraq’s Ministry of the Interior, and this has been run by Shiite Muslim politicians for the past 14 years. Accordingly, many of the staff and officers are also Shiite Muslims. On January 30 this year, Qasim al-Araji was named the new Minister of the Interior. Al-Araji is also a leading member of one of the largest militias, the Badr group.
Last Saturday, senior Sunni Muslim politician, Osama al-Nujaifi, Iraq’s vice-president, who is originally from Mosul, said in an official statement that the new strategy in Mosul, including the excessive use of cannons and rockets by pro-government forces, were causing more civilian deaths. Could it be that some pro-government forces are a little trigger happy, when it comes to calling in air strikes?
The current fighting in Mosul is likely to be the last and most significant battle against the IS group in Iraq, after three years of the country being terrorised by the extremists. The siege that has trapped the extremists in Mosul, the lack of the elite fighting forces that previously achieved so much and the new US enthusiasm for fighting the IS group, can all be partially blamed for the fact that this all-important battle is not going the way it should. Accidental or not, outcomes like those hundreds of civilian deaths don’t just have a high human cost; they will continue to bear upon the country’s future. | {
"pile_set_name": "OpenWebText2"
} |
/*###ICF### Section handled by ICF editor, don't touch! ****/
/*-Editor annotation file-*/
/* IcfEditorFile="$TOOLKIT_DIR$\config\ide\IcfEditor\cortex_v1_0.xml" */
/*-Specials-*/
define symbol __ICFEDIT_intvec_start__ = 0x08000000;
/*-Memory Regions-*/
define symbol __ICFEDIT_region_ROM_start__ = 0x08000000;
define symbol __ICFEDIT_region_ROM_end__ = 0x0807FFFF;
define symbol __ICFEDIT_region_RAM_start__ = 0x20000000;
define symbol __ICFEDIT_region_RAM_end__ = 0x2001FFFF;
/*-Sizes-*/
define symbol __ICFEDIT_size_cstack__ = 0x400;
define symbol __ICFEDIT_size_heap__ = 0x200;
/**** End of ICF editor section. ###ICF###*/
define memory mem with size = 4G;
define region ROM_region = mem:[from __ICFEDIT_region_ROM_start__ to __ICFEDIT_region_ROM_end__];
define region RAM_region = mem:[from __ICFEDIT_region_RAM_start__ to __ICFEDIT_region_RAM_end__];
define block CSTACK with alignment = 8, size = __ICFEDIT_size_cstack__ { };
define block HEAP with alignment = 8, size = __ICFEDIT_size_heap__ { };
initialize by copy { readwrite };
do not initialize { section .noinit };
place at address mem:__ICFEDIT_intvec_start__ { readonly section .intvec };
place in ROM_region { readonly };
place in RAM_region { readwrite,
block CSTACK, block HEAP }; | {
"pile_set_name": "Github"
} |
1. Field of the Invention
The present invention relates to a working device which is equipped with a tool rest suitable for working a noncircular workpiece, such as a piston of an internal combustion engine.
2. Description of the Related Art
FIG. 7 shows a piston for an internal combustion engine. The piston 10 has a main body 12 formed from an aluminum casting, and the main body 12 has a through hole 13 into which a piston pin pierces. Although a head 15 of the piston main body 12 is also formed from an aluminum casting, a groove portion 14 which receives a piston ring is made of cast iron. That is, the piston 10 is formed from dissimilar metal materials of aluminum casting and cast iron.
In the lathe turning of an outside diameter portion of this piston 10, the piston which is a workpiece is held by a work spindle and rotated and the outside diameter portion is machined by use of a cutting tool T1.
Because the piston 10 has a noncircular (oval) outside diameter profile, noncircular cutting is performed by moving the tool T1 back and forth in synchronization with the rotation of the workpiece 1.
In performing this noncircular working, it is possible to perform noncircular working by reciprocating a usual tool rest in synchronization with the rotation of the work spindle.
However, a tool rest is equipped with a large number of working tools and has a large weight and, therefore, the tool rest has also a large inertial force. Therefore, the tool rest cannot cope with high-speed reciprocal movements.
The Japanese Patent Laid-Open Publication No. 5-200601 discloses a working device for noncircular working provided with a tool rest dedicated to noncircular working.
In the noncircular workpiece shown in FIG. 7, which is formed from dissimilar metals, it is necessary to perform groove working for a ring in addition to the cutting of an outside diameter portion.
Therefore, it is preferred that a noncircular working device be equipped with multiple tools suited to different materials and the different working of the materials.
The object of the present invention is to provide a noncircular working device equipped with multiple tools suited to different materials and the different working of the materials. | {
"pile_set_name": "USPTO Backgrounds"
} |
Assessment of sources and fate of nitrate in shallow groundwater of an agricultural area by using a multi-tracer approach.
Nitrate isotopic values are often used as a tool to understand sources of contamination in order to effectively manage groundwater quality. However, recent literature describes that biogeochemical reactions may modify these values. Therefore, data interpretation is difficult and often vague. We provide a discussion on this topic and complement the study using halides as comparative tracers assessing an aquifer underneath a sub-humid to humid region in NE Mexico. Hydrogeological information and stable water isotopes indicate that active groundwater recharge occurs in the 8000km(2) study area under present-day climatic and hydrologic conditions. Nitrate isotopes and halide ratios indicate a diverse mix of nitrate sources and transformations. Nitrate sources include organic waste and wastewater, synthetic fertilizers and soil processes. Animal manure and sewage from septic tanks were the causes of groundwater nitrate pollution within orchards and vegetable agriculture. Dairy activities within a radius of 1,000 m from a sampling point significantly contributed to nitrate pollution. Leachates from septic tanks caused nitrate pollution in residential areas. Soil nitrogen and animal waste were the sources of nitrate in groundwater under shrubland and grassland. Partial denitrification processes helped to attenuate nitrate concentration underneath agricultural lands and grassland, especially during summer months. | {
"pile_set_name": "PubMed Abstracts"
} |
a family heirloom....
Today I'm linking up with my very dear friend Jana, at the Summer House. She and I have been friends since Ellis and her oldest Josh were in kindergarten. We both were early for dropping off and picking up, so we had time each day together to become friends and we have been such ever since.
Jana has a beautiful blog, (she is the one who tutors me with all things blogging and technical).
Today she is asking people to link up with their favorite family heirloom.
I see you, the artist, Tamara, and like you I am also finding my way again. I am glad that the dreams that were lost by so many women in years gone by are not forgotten and are being given new life through women today. Let's have fun together on this wild ride! | {
"pile_set_name": "Pile-CC"
} |
HMS Diligent (1806)
HMS Diligent was the French naval brig Diligent, launched in 1800, that captured in 1806. The Royal Navy took her into service under her existing name, which it later changed, first to Prudente, and then to Wolf. During her two years of active duty with the Royal Navy she captured two small privateers. Wolf was laid up in 1808 and sold in 1811.
French service and capture
Diligent was the sixth of the six-vessel class of Vigilant-class brigs, and initially (October 1799), was designated No. 6. Although Diligent was launched in 1800, completion took until September 1801.
Capture: French account
Diligent was under the command of lieutenant de vaisseau Vincent Thevenard and part of a small squadron under Commodore Jean-Marthe-Adrien l'Hermite, in Régulus, that departed from Lorient on 22 October 1805. Diligent ran into difficulties and had to return to port that same day. The squadron went on to engage in commerce raiding off the coast of Africa and then the Caribbean.
Diligent set out again a few days later with Thevenard searching for l'Hermite and his squadron at cayenne and the Antilles, but without success. After stopping at Guadeloupe to make several essential repairs, Thevenard decided to cruise the Leeward Isles. In the morning of 25 May 1806 Diligent sighted two strange vessels in the channel northwest of Puerto Rico. They followed Diligent, but by 27 May there was only one, which Thevenard thought might be the British frigate Magicienne, which was known to be in the area. Thevenard wanted to maneuver to deliver a broadside but at a council of war with his officers that day, they advised staying away. Next morning, the crew of Diligent were exhausted from having been at the sweeps for 30 hours; Diligent, being closer to the coast had suffered from inconsistent wind conditions, while the British vessel, being further from shore, had benefited from more stable conditions. With a crew unwilling to man the guns, Thevenard eventually struck to Renard, a brig, without a shot being fired.
The court martial board unanimously acquitted Thevenard for the loss of his vessel. However, it found that he had not done everything necessary to prevent his crew from becoming discouraged and unwilling to fight. It particularly reprimanded him for having mistaken a brig for a frigate for too long.
Capture: British account
On 28 May Renard, under Commander Jeremiah Coghlan, captured Diligent after a 64-hour-long chase. She was seven days out of Pointe a Petre, Guadeloupe, with dispatches for France, which she succeeded in throwing overboard while Renard was chasing her. French records report that the capture took place in the Puerto Rico channel. She had sailed from Concarneau to Cayenne, and was cruising in the Antilles prior to her capture by the English sloop "Fox". Diligente arrived at Jamaica on 3 June.
Thévenard had surrendered his ship without a shot being fired by either side. When taken on board Renard, her smallness surprised him and he requested that he might be returned to his ship to continue the fight. Coghlan laughed at this request. Thévenard then seriously asked Coghlan for a certificate stating that he had not acted in a cowardly manner. Coghlan replied "No, I cannot do that; but I will give you one that shall specify you have acted 'prudently'!"
In his discussion of the action, the author William James, in his naval history, made much of what he termed Thevenard's cowardice. He further opined that as Thevenard had continued in the French navy until 1817, he must have misrepresented what had occurred. James did not draw attention to Renard having a broadside twice the weight of Diligents broadside and argued that Thevenard should have attempted to capture Renard by boarding.
British career
Vice-Admiral Dacres had Diligent purchased and commissioned in May as HMS Diligent (or Diligente), under Commander William Sumner Hall.
On 2 October 1806, Diligente was seven leagues south of Cape Engana when she saw a sail. After a chase of some 20 hours, the winds were so calm that Hall sent his boats after the strange vessel. After another two hours the boats captured the French schooner Napoleon. Napoleon was armed with one long 9-pounder gun and had on board 14 crew and passengers. She was on the way from Samana to Santo Domingo to secure a letter of marque and a larger crew.
In October Diligent was renamed Prudente. It apparently took some time for news of the name change to diffuse fully. Lloyd's List reported that the brig Diligente detained the American schooner Polly, which was sailing from Havana to New Orleans, and sent her into Jamaica.
In September 1807 Prudent was renamed HMS Wolf. In March 1808 Lieutenant Edmund Waller replaced Hall.
On 1 May 1808, Wolf was escorting a convoy sailing from Jamaica to London when the convoy commander, Captain Sir Charles Brisbane, in , sent Waller to round up the slowest vessels. As Waller was doing so, he sighted a strange sail to the south-east, and immediately gave chase. After a chase of two hours, Wolf was able to capture the Spanish privateer schooner Braganza, Joseph Caudanio, captain, of one gun and 54 men. She was 22 days out of Carthagena and had captured the Anne, one of the vessels in the convoy. After another chase, this of four hours, Wolf succeeded in recapturing the Anne. Wolf sent the recaptured Ann, Braugh, master, into the fleet.
Fate
Lieutenant Waller's promotion to Commander was confirmed on 20 July 1808. Wolf arrived at Plymouth on 21 July. She was paid off there and laid up. She was sold in June 1811.
Notes, citations and references
Notes
Citations
References
Marshall, John (1823–1835) Royal naval biography, or, Memoirs of the services of all the flag-officers, superannuated rear-admirals, retired-captains, post-captains, and commanders, whose names appeared on the Admiralty list of sea officers at the commencement of the present year 1823, or who have since been promoted ... (London: Longman, Hurst, Rees, Orme and Brown).
Winfield, Rif & Stephen S Roberts (2015) French Warships in the Age of Sail 1786 - 1861: Design Construction, Careers and Fates. (Seaforth Publishing).
Category:1800 ships
Category:Sloops of the Royal Navy
Category:Captured ships
Category:Ships of the French Navy | {
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This is the first-ever image of a black hole. Captured by the Event Horizon Telescope, or EHT, it reveals the supermassive black hole at the center of Messier 87, a massive galaxy 55 million light-years away.
Black holes are extremely compressed cosmic objects, containing extraordinary amounts of mass within a tiny region. (This one contains 6.5 billion times the mass of the Earth’s sun.) This mass is shrouded by an event horizon, the boundary beyond which nothing—not even light—can escape from the black hole’s powerful gravitational pull.
General relativity predicts that a black hole will cast a circular shadow on the bright, superheated material around it. This image reveals the shadow.
The EHT links eight telescopes around the globe to form an Earth-sized virtual telescope with unprecedented sensitivity and resolution. This achievement was made possible, in part, by leadership and funding from the Center for Astrophysics | Harvard & Smithsonian.
Learn more at the Event Horizon Telescope project website. | {
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; RUN: opt < %s -instcombine -S | grep "sdiv i8 \%a, 9"
; PR2048
define i8 @i(i8 %a) {
%tmp1 = sdiv i8 %a, -3
%tmp2 = sdiv i8 %tmp1, -3
ret i8 %tmp2
}
| {
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Data parallelism is pretty simple. It is the concept that you have a lot of data that you want to process — perhaps a lot of pixels in an image, perhaps you have a whole lot of payroll cheques to update. Taking that data and dividing it up among multiple processors is a method of getting data parallelism. This is an area that supercomputers have excelled at for years. It is a type of problem that is pretty well understood and more emphasis has been put on data parallelism in the past than on task parallelism.
Task parallelism, on the other hand, is where you have multiple tasks that need to be done. So perhaps you have a large data set and you want to know the minimum value and you want to know the maximum and you want to know the average. This is a rather trivial example but you could have different processors each look at the same data set and compute different answers. So task parallelism is a different way of looking at things. Instead of dividing up the data and doing the same work on different processors, in task parallelism what you're doing is dividing up the task to apply.
The most common task parallelism is something called "pipelining
Tuesday, November 26, 2013
Today I tried to add new project in VS2012 IDE for development it didn't allow me to proceed as it popup an error stating this
VS2012 IDE Issue No exports were found that match the constraint contract name
At application architecture level, we come across layers and tiers terminology.I will not delve much into these terms now but would rather focus on the details of it. Yes we know presentation , business, service , data access layer and many such stacks that defines application architecture at logical level. We then built solution taking these layers pointers into consideration. Then comes what the code files where we have domain entities, utilities , classes, interface and so on..
Well, sometimes it becomes non trivial to appropiately name such source code files unders these layers.
To complete these blogs actually I need an expert advice to make this meaningful and comprehensive. I'm sure there is no such reference atleast available online. Everyone has their own theisis of explanation and fundamentals behind.
Thursday, November 14, 2013
This is rarest of the rare error that comes when we build/debug solution in Visual Studio for .net . The problem is the missing MSCORLIB dll system.core which somehow not exists in .csproj file. The developer resort this by recreating new solution or clean the folder, get the latest code from TFS and then build it. But the problem sometimes lies as-is. One can take this to next level by locating this tag . if this is not present Add this. Forgot to mention, open this file in notepad rather VS IDE.
Then you rebuild the solution once again to get your ANIMAL(I mean your solution-which may have large number of class library in it) run.
Do post your comment if run into similar problem or please let me know the best way to get away with this one.
Tuesday, November 12, 2013
Its long time in my career and sometimes we flumble with the basics, concepts and fundamentals.
Here is the list of few design patterns or terminology where we come across during day to day SDLC life cycle. I will try updating this particular post in future to include the most favourable one.
Facade: It provides simplied interface to a larger body of code-class library. In simple terms a group of class library or dll referenced in single interface and this later expose to calling events or client.
Purpose - It wraps poorly designed collections of API into or with single well designed API.
Adapter : Is also called Wrapper pattern or Decorative pattern (GOF ). The actual usuage or orgin, when one should coin this- This is to be used when we have module which is to be used but incompatible with other module. At such places we create interface out of the class and create compatible bridge to use across.
Boiler Plate Code- Is a section of code that can be included in many place with no or minimal changes.
Shotgun Debugging- To apply too many solution at a time to solve issue.Troubleshoot.
Spaghetti Code- To many branching of code, difficult to read and understand
Smoke Testing- To do high level testing to ensure system do not break. This ignores finer level of testing. Imagine a smoke pass into pipe to check leak
Regression Testing-Testing to ensure new changes do not break existing functionality. | {
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Passive gravitational sedimentation of peripheral blood increases the sensitivity of microscopic detection of malaria.
To determine if passive gravitational sedimentation of blood samples, followed by buffy coat thin smear preparation could increase the sensitivity of malaria diagnosis when compared to conventional thin smear preparation without the additional cost of centrifuges or molecular diagnostics. Blood samples were collected from 205 patients. Each patient sample was analyzed using all three methods of sample preparation. Buffy coat analysis of centrifuged blood samples greatly increased the sensitivity of malaria diagnosis when compared to standard thin smear techniques. Sensitivity between mechanically centrifuged samples and gravitationally sedimented samples showed equal improvement in sensitivity when compared to standard thin smear preparation. Passive gravitational sedimentation of red blood cells followed by buffy coat analysis dramatically improves the sensitivity of malaria diagnosis without the additional costs associated with centrifugation. | {
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Q:
Sequence of tense involving imperfect and simple past
The question arose in my mind from the sentence that opens Book 1 chapter 2 of L'Étranger by Albert Camus, together with some translations as below.
I am quoting more in French than in translations for context. Meursault, the narrator, is recalling a conversation he had with his boss a few days before.
En me réveillant, j’ai compris pourquoi mon patron avait l’air mécontent quand je lui ai demandé mes deux jours de congé : c’est aujourd’hui samedi. Je l’avais pour ainsi dire oublié, mais en me levant, cette idée m’est venue. Mon patron, tout naturellement, a pensé que j’aurais ainsi quatre jours de vacances avec mon dimanche et cela ne pouvait pas lui faire plaisir. Mais d’une part, ce n’est pas de ma faute si on a enterré maman hier au lieu d’aujourd’hui et d’autre part, j’aurais eu mon samedi et mon dimanche de toute façon. Bien entendu, cela ne m’empêche pas de comprendre tout de même mon patron.
Stuart Gilbert:
ON WAKING I understood why my employer had looked rather cross when I asked for my two days off; it’s a Saturday today.
Matthew Ward:
As I was waking up, it came to me why my boss had seemed annoyed when I asked him for two days off: Today is Saturday.
QUESTIONS
Is there an option to replace avait with avait eu without making the Camus sentence ungrammatical or changing its meaning? The result would be:
(R1) En me réveillant, j’ai compris pourquoi mon patron avait eu l’air mécontent quand je lui ai demandé mes deux jours de congé.
Is there an option to replace ai demandé with avais demandé (or eus demandé) without making the sentence ungrammatical or changing its meaning (particularly if, as per question 1, avait has become avait eu)? The result would be:
(R2) En me réveillant, j’ai compris pourquoi mon patron avait eu l’air mécontent quand je lui avais demandé (eus demandé) mes deux jours de congé.
Suppose the narrator recalled his boss's saying no. Which of the following would properly express that?
(A) En me réveillant, j’ai compris pourquoi mon patron dit non quand je lui ai demandé mes deux jours de congé.
(B) En me réveillant, j’ai compris pourquoi mon patron avait dit (eut dit) non quand je lui ai demandé mes deux jours de congé.
(C) En me réveillant, j’ai compris pourquoi mon patron avait dit (eut dit) non quand je lui avais demandé (eus demandé) mes deux jours de congé.
Please explain the answers (see Background below).
Whatever else you may do please give definite yes or no to 1 and 2 and definitely choose one (or more) of A through C for me.
BACKGROUND
Here might be an 'explanation' for the Gilbert translation. If we mark each verb instance with (grammatical tense, time of occurrence), it may go like this.
ON WAKING I understood(1, 1) why my employer had looked(2, 2) rather cross when I asked(1, 2) for my two days off; it’s a Saturday today.
The boss's had looked is both grammatically and in reality one step further into the past, hence (2, 2) as opposed to (1, 1) for the narrator's understood. The narrator's asked is grammatically even with understood but in reality contemporaneous with the boss's had looked; hence (1, 2).
This (1, 2) in the when-clause (which may be called 'doubly subordinate') may seem weird (when the 'merely subordinate' why-clause already has (2, 2)); but it is almost always done this way in English I notice. I've only seen a few exceptions, i.e. (2, 2) for 'doubly subordinate,' in Henry James. Just to be clear what I mean, a 'Henry James' sentence would go like:
ON WAKING I understood(1, 1) why my employer had looked(2, 2) rather cross when I had asked(2, 2) for my two days off; it’s a Saturday today.
By explanation for the French sentences, I have these things in mind.
Suppose the answer to question 3 is that we say (B), i.e.:
(B) En me réveillant, j’ai compris(1, 1) pourquoi mon patron avait dit (eut dit)(2, 2) non quand....
If so, why a different treatment for the Camus sentence--i.e. (1, 2) below as opposed to (2, 2) above?
En me réveillant, j’ai compris(1, 1) pourquoi mon patron avait(1, 2) l’air mécontent quand.....
Maybe grammatical aspect matters (avoir l'air having an imperfect aspect while dire has what is called a "perfective," not to be confused with a "perfect" in tense).
Maybe there is a connection to a special treatment of imperfect in indirect discourse, whereby imperfect in direct discourse remains imperfect in indirect (when most other tenses undergo a change).
Alternatively, the answer to question 3 may be (A).
If so, I would want to know what explains this exceptional treatment when, as it seems to me, French is generally more strict than English when it comes to sequence of tense.
Je te dirai quand elle sera partie.
compared with
I will tell you when she is gone.
As an aside, I am quoting two German translations. I don't know whether they are slavishly copying the French syntax or German has its own reasons to do what it does.
Uli Aumüller:
Als ich aufwachte, ist mir klargeworden, warum mein Chef verstimmt aussah, als ich ihn um zwei Tage Urlaub gebeten habe: heute ist Sonnabend.
Georg Goyert und Hans Georg Brenner:
Als ich erwachte, wurde mir klar, weshalb mein Chef so unwirsch war, als ich ihn um zwei Tage Urlaub bat: heute ist Samstag.
I have put a related question to the German board.
A:
To discuss the examples in (3), I would suggest switching from DIRE to RÉPONDRE because its present tense and its simple past have different forms minimizing confusion.
(A1) En me réveillant, j’ai compris pourquoi mon patron répond non quand je lui ai demandé mes deux jours de congé.
(A2) En me réveillant, j’ai compris pourquoi mon patron répondit non quand je lui ai demandé mes deux jours de congé.
(B) En me réveillant, j’ai compris pourquoi mon patron avait répondu non quand je lui ai demandé mes deux jours de congé.
(C) En me réveillant, j’ai compris pourquoi mon patron avait répondu non quand je lui avais demandé mes deux jours de congé.
Both (A1) and (A2) seem agrammatical. The others, (B) and (C) with the pluperfect on RÉPONDRE seem ok. Having no intuition whatsoever about the use of Subjunctive imperfective like most French speakers, I cannot comment on the other alternatives.
In (B), the time index of RÉPONDRE looks equalled to that of DEMANDER (TREP=TDEM), while in (C), it seems to be extending after (TREP≥TDEM).
Another part of your question as to do with lexical aspects of the verbs used avoir l'air is a stative verb while DIRE and RÉPONDRE are not. Someone else might be able to shed light on that part...
| {
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大好きな彼にもっと喜んでほしい♡
そんな想いから、エッチの技術を日々こっそり研究している人もいるのでは？
けれど場合によっては、女性が自分からすると「え、プロかよ？」と疑われてしまう行為もあるよう。
そこで今回は、男性が彼女にされてドン引きしたエッチのテクニックについて聞いてみました。
上に乗って「素また」
「エッチの途中、流れで彼女が俺の上にまたがる感じに……。まぁそこまではいいんですが、それから彼女が腰を前後に動かし始めて。いわゆる素またみたいな感じですよね。
彼女には悪いけどちょっと引いちゃって『風俗かよ！』ってツッコみたくなりました」（32歳／自営業）
素またといえば、風俗では定番の行為。
彼からリクエストがあった場合はいいかもしれませんが、女性のほうから勝手に始めると引かれてしまう可能性もあるようです。
もしするとしたら「こういうのって気持ちいいの？」と聞きながら、最初は慣れない感じでやってみるのが正解かも。
口で咥えて「のど輪締め」
「それまでも口でしてもらったことはあったんだけど、4回目くらいのエッチのときに、フェラからさらに深くくわえて、のどでキュって締めつけられたんです。
すごく気持ちいいんだけど『何これ何これ？プロかよ！』って感じでした。のど輪締めって技らしいですね」（27歳／公務員）
お口でするテクニックの中で、もっとも難しいともいわれる「のど輪締め」
実際にマスターしている女性はごくわずかかもしれませんが、万が一できたとしても、交際したての時期に披露するのは控えたほうがよさそうです。
エッチがマンネリ化してきたな…と思ったときに、切り札として挑戦してみるくらいがちょうどいいでしょう。
指や舌で「アナル攻め」
「元カノで、自分から俺のアナルを攻めてきた子がいました。もちろん気持ちよかったですけど『前の男に仕込まれたんだろうな』と思うと、引いたというかちょっと複雑な気持ちに」（28歳／インフラ関係）
フェラと同じくらい、アナルを指や舌で攻められて感じる男性も少なくないのだとか。
だからといって女性のほうからいきなりするのは考えもの。
「男性の気持ちいい場所を知っている＝やり慣れている」と思われてしまいかねないからです。
試すとしたら、まずは彼の性感帯を探すような流れに持っていってから「ここはどう？」と刺激してみるのがおすすめ。
最初はたどたどしさを意識して
男性が感じる方法を知り尽くしたようなやりすぎテクは、男性にドン引きされてしまう場合もあるよう。
それでも彼に気持ちよくなって欲しいなら、たとえマスターしているテクニックだとしても、最初は探りながらするような初心者っぽさを意識するといいでしょう。
「俺が育てた」感を与えることで、彼からもさらに愛しく思ってもらえるはずですよ♡
（オトナの恋カツ編集部） | {
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Monday, February 04, 2013
Cape Cod Museum of Art
In July 2012 our whole family visited the Cape Cod Museum of Art in Dennis, Massachusetts.
I was inspired to make our first visit there by a special exhibit coordinated with the New Britian Museum of American Art to make the largest exhibit of fine art by artists who painted at Provincetown, Cape Cod, which has been known as an artist colony. It was called "The Tides of Provincetown: Two Hundred Years of Cape Cod Art". Most impressive were the long descriptions with each painting that explained about the artist and the history, they were much longer than traditionally used by museums.
After snapping some photos with my iPhone I spotted the sign that said photography was banned so I don't have much that I can legally show here, to show what I have would be copyright infringement, so, they are absent.
I wound up purchasing the coffee table book to go along with the temporary exhibit because I realized there is a lot to learn and just not enough time to do it in that one visit. I was surprised at the artists who visited Provincetown and who made art while there, this display was not just about locals, it was also about famous artists who visited P-town.
If my kids learned one thing while there the trip will have been worthwhile. I personally loved the exhibit and could have spent much more time there really looking at each painting. Since the art spanned many styles of art it was a bit like viewing art along a timeline with everything from portraits, impressionism, modern, pop art, and abstract art.
Outside is a sculpture garden and an English cottage style garden which featured, of course, blue hydrangeas that are so popular on Cape Cod.
The one below, Wash-a-shore, actually is oriented incorrectly, it needs to turn 45 degrees to the right to make it vertical. I apologize but Blogger is not cooperating with me. | {
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Comparison of Self-applied Heat Therapy for Meibomian Gland Dysfunction.
To compare the effects on ocular temperature, lipid layer grade, tear film stability, and tear meniscus height after a single application of two commercially available warm compresses in mild-to-moderate dry eye and to report participant treatment preference. Forty-one subjects with mild-to-moderate dry eye symptoms were enrolled in a randomized, paired-eye, investigator-masked trial. Heat was applied simultaneously to one eye (randomized) with a portable eye mask (EyeGiene) and to the contralateral eye with a microwave-heated flaxseed eye bag (MGDRx Eye Bag). Outer and inner eyelid temperatures, tear film lipid layer grade (LLG), and noninvasive tear film breakup time (NIBUT) were measured at baseline and immediately after 10 minutes of device application. Outer and inner eyelid temperatures, LLG, and NIBUT did not differ before treatment between eyes assigned to eye mask and eye bag therapy. All measurements were significantly increased from baseline, after warming with both devices (all p < 0.05). Outer and inner eyelid temperature changes were significantly greater with the eye bag than with the eye mask (outer eyelid, +3.5 ± 1.0°C vs. +2.4 ± 0.8°C; inner eyelid, +3.5 ± 1.0°C vs. +2.5 ± 0.9°C; all p < 0.001), although there was no significant difference in LLG and NIBUT improvement between treatments (all p > 0.05). A majority of subjects (78%) preferred the application of heat with the eye bag over the eye mask. Both the EyeGiene mask and the MGDRx Eye Bag are convenient eyelid warming devices that result in clinically and statistically significant increases in NIBUT and LLG in patients with mild-to-moderate dry eye symptoms. The MGDRx Eye Bag is more effective in raising ocular temperature and is the preferred treatment method among subjects. | {
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Q:
Getting anchor element within SVG
I have an svg on my site for selecting states in the US. The format is:
<svg...>
<a xlink:href="...">
<polygon ...><title>{stateName}</title></polygon>
</a>
</svg>
After several hours of headaches trying to figure out why clicking the links caused issues with other scripts on the same site, I narrowed down the issue to the event not being passed to those functions when the target was the anchor in the svg.
So I created a separate page without those other scripts and experimented by creating the following function:
<script type="text/javascript">
(function($){
$(document).ready(function(){
$('svg a').click(function(event){
if(event.target.tagName == 'polygon'){
var target = $(this).parent();
alert('target: ' + dump(target));
}else{
alert('event: ' + dump(event.target));
}
});
});
})(jQuery);
</script>
Note: The dump() function is a custom function that outputs the contents of objects and arrays.
My first version of this code just output the event.target.tagName which was always "polygon" even though the object I'm binding the click to is the anchor. So I modified it to get the polygon's parent but that returns the svg. It's like the anchor doesn't exist.
Why is it that I cannot seem that the event for that function doesn't contain any reference to the anchor? How can I get this to behave like it would if the anchor was inside a div instead?
I tried a jQuery SVG plugin but that did nothing.
TL;DR / Clarification
The issue isn't that the anchor isn't working, clicking it will take you to the page defined in xlink:href. But any jQuery code bound to click events that are triggered when clicking these anchors within the svg either come through with the event as undefined or not containing the expected anchor object data.
How can I get the appropriate event object for these anchors?
Edit: Finally got jsfiddle to load: http://jsfiddle.net/fja4Lt0L/
Explanation of current behavior in different browsers:
FireFox: issue as described
Chrome/Safari: does nothing at all
IE: follows the link regardless of the script attached to the click event
None of those are behaviors expected of the script or intended by the coder.
A:
In SVG only graphics elements (lines, rectangles etc and text) can be the target of events. If you specify it on a container e.g. a <g> or <a> element then all their children become targets.
Just call .parentElement (if you're using raw DOM) or .parent() (if you're using jQuery) repeatedly on whatever the target is till you get an anchor element.
Here's an example or with jquery and .parent
| {
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Surgical and clinical confirmation of temporal bone CT findings in patients with otosclerosis with failed stapes surgery.
Prior descriptions of imaging after failed stapes procedures for otosclerosis predated currently available CT technology and/or failed to assess commonly used metallic implants. The purpose of this study was to correlate temporal bone CT findings with clinically and intraoperatively determined causes of surgical failure. All patients with otosclerosis undergoing stapedectomy between December 1999 and December 2010 were identified from a search of neurotology clinical records. Patients presenting because of failed stapes surgery and having temporal bone CT scans at the time of revision surgery or clinical evaluation were included. Imaging and clinical records were retrospectively evaluated by a medical student, radiology resident, and senior neuroradiologist. Stapes prosthesis complications and relevant anatomic CT findings were correlated to clinical and intraoperative findings. Twenty-two of 340 patients met inclusion criteria. Temporal bone CT findings were correlated to intraoperative findings in 17 of 22 patients and to clinical findings in 5 of 22 patients. Surgically confirmed abnormalities included 7 of 7 incus erosions, 3 of 6 piston re-sizings, 3 of 5 granulation tissues, 3 of 5 prosthesis disconnections, 3 of 4 obliterative otosclerosis, 2 of 2 oval window dislocations, and 1 labyrinthine ossificans. Clinically confirmed abnormalities included 2 cases each of superior semicircular canal dehiscence, and wrong piston size, and 1 each of piston disconnection, labyrinthine ossificans, and intravestibular footplate. CT evaluation in the setting of failed stapes surgery is challenging. Many postoperative complications such as piston migration, incus necrosis, and overt vestibular penetration are well recognized on temporal bone CT. Of particular note, superior semicircular canal dehiscence is an important contraindication to stapes surgery. | {
"pile_set_name": "PubMed Abstracts"
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Q:
I am a Junior software QA specialist, I am kind lost to understand what to do in this scenario?
Scenario:
Suppose that there is a mobile application (Hotel Booking). A particular use case does not work as expected (view booking history), as it has several defects and the business requirements need to be revised from a quality standpoint.
I would like to present to the management an analysis report that shows all types of issues (business requirements, defects, logic) for this use case and provide a possible solution for them.
What do you call this report?
Is it my job to do it as a QA specialist do it, or only business people?
Is there any supportive guide to create this report?
A:
Wonder why you want to present this to management? What is your goal here, what do you hope to achieve. Do you want to show them they have unknown quality issues?
Normaly I would expect the product to have either an issue tracker or a backlog. Just put the issues on the list, discuss it with the business owners and let them prioritize. Together consider the context, what might look like a defect to your mental model, might not be an issue for the current userbase. Consider the business effects of the change, dont just swarm a development team with trivial defects.
I have never had the need for such a report, nor would I like to create reports like that. I do like to have the right quality conversations. For this I might need metrics over time. For example number of defects in relation to the number of features develivered.
A:
You state you are junior. I wonder if you are a "team of senior + junior QAs and you are one of the juniors of the team" or you are "alone in charge of this".
If it's the first case, don't do any report, just tell your senior QAs teammates what you see and ask them for advice.
From now on for the rest of the answer I will assume that you are in this latter case and you are "in charge of all" without knowing too well what's the best way to add value to the business from your position in an organized manner.
So here's my advice:
A) Have an issue-tracker acting both as a bug-tracker and feature-request-tracker.
Making this resport you say manually is an real overkill and it will grow indefinitely until it gets unmanageable. When you have more than 500 bugs + 200 feature requests in the queue, you will not be able to manage it.
Considerations:
Every software (even small ones) needs at least a "bug tracker". There are a bunch of free ones there. I've been using "mantis bug tracker" for the last 17 years in many different companyes. It is really very ugly but it's free. https://www.mantisbt.org/ I'm not affiliated with them, there are many many others (redmine, jira (which is not free), bugzilla, etc.)
Each organization determines if the "bug tracker" also acts as a "feature-request" tracker or not. Most small companies do, as everything is simpler. This is why probably "issue-tracker" is a better name than "bug-tracker". A new feature can be seen as an "issue" and a bug as another "issue".
When you use a bug tracker as a feature tracker, you can "indicate" if something is a feature or a bug in a tag or field.
If that's a bug, you usually also specify other types of bug type (minor, major, whatever).
Usually you also specify the "project". Say your mobile application is a monolyth: you have a single project. But you can (if you want) separate "conceptually" in 2 parts: Frontend project (you set there colors, typos, button positions, responsiveness, etc...) and Backend project (you set there errors about data, backing services not responding, processes, etc.). That is arbitrary. If you are new to this, I'd advice to only use ONE project and after half a year, the "splitting" will come naturally to you.
Issues are auto-numbered. If you find 3 things that go together, open 3 issues with different number and set a mark to relate them together.
For the QA team, the bug-tracker is the "main tool" to track and document everything. It's the "always open tab" that you want in your browser.
For the dev team there are 2 approaches.
If the company uses scrum/agile/whatever method, they will work on a "backlog". If the features are kept also in the bug-tracker (ie: the issue-tracker) the backlog will most probably say "for this sprint, in order, issues #345, #22, #177, #93
If the company has 1 or 2 developers that "just do what's needed" then the simplest way is to use the "priority" flag of the issue-tracker (which typically will correlate with the bug's importance, so major bugs will most probably higher priorities than minor ones, but not necessarily). In this case, the coders just open up the issue-tracker every morning, scan the list for the "highest priority" and work on the first one. When done, the second one of highest priority, and so on. When they have resolved all the issues in "high priority" then they scan for "mid priority" and so on.
Here's an example of the Mantis I'm currenlty using, displaying the bug-levels. You can see there's the category "feature" and several levels of bugs:
B) Define black-over-white the bug levels.
If you watch the previous image, there are several names that could potentially cause confusion. Is "login not working" major or minor? Well... if noone can log in, it's clearly major. If you discover that potentially a new user registers with an email longer than 254 characters later cannot login because it exceeeds the maximum email length and that was not controlled in the registration process, but currently 100% of your users have emails shorter than 254 chars, then that is clearly a minor.
So, considerations:
It is task of the QA team to write a formal definition of those bug levels.
If you don't know where to start, I'd suggest this:
Blocker => This is now breaking business and we are loosing money right now. For example 20% of users on an ecommerce "today" can't login because of an update we did yesterday.
Crash => This is making the application to break. In a long term process (C, C++, java, etc. application running on a computer) this means the process ends with a core-dump. If we are talking about a web application this means a 5xx server error.
Major => This means that any important process cannot be completed, although we are not looing money now (otherwise it'd be a Blocker). Example: In an e-commerce the user CAN pay AND the payment is completed but after that the user is not receiving any confirmation email AND also cannot access the member's area to see his payments.
Minor => The means that any process (important or not) cannot be completed but there are workarounds that (with less comfort for the user) allow the process to be completed. For example: A list of providers in X country accessing from the country page is not working, but going to a general list, I can still get a fill list of providers and later on filter by country.
Tweak/Text/Trival => Anything that "needs" to be corrected but does not break any process. For example a typo. This is an example of thing that is "low in importance by nature" but the business managers might set as top-priority: What if you are selling white boards and in a filter visible to end-users instead of "Filter by size" it says by accident "Filter by sieze"? That must be corrected because of the bad impression to the users but still it's not blocker/crash/major/minor.
So... does not matter if you take this specific definition or you define your own. In a company I worked in, we also had sub-divisions: Is this making us loose money MORE than 2.000,00 USD per hour, or 1.999,99 USD or less? This of course depends on the company. There are tiny-projects that just make $2.000 in the full month.
So it is YOU that need to write a definition. If you can, instead of closing the definition, make a "proposal" and have managers to approve it.
C) Let the coders resolve but not close. Doubly-link the issue resolution to the commit.
Having said all this, most issue-trackers suport "workflows". When you open a new issue it is in the "new" state and when a coder starts woring on it "captures" that issue so the other coders know that is being worked on.
When the coder commits the resolution, ask them to do this:
In the git, set the commit message to "Resolves issue #456". After committing, they will get a commit hash.
In the issue-tracker, when resolving, set the resolve message to "Resolved at project-name:6a5e3f47a82c56a23b4c6ae75e84f6f75a86c72d
If that's a multi-commit case (for example the coder touched both model and controllers and views and does 3 commits, one for each semantic group, use the commit hash that "contains all"
But hey, they resolve but do never close.
If you don't have Continuous integration and automatic tests (which by the nature of your question, I assume you don't) then do not allow the coders to make the merges. Their work ends in the last commit of the issue-branc or feature-branch with a merge-request.
D) Who closes then?
You or business.
To decide, ask if this was a bug or a new issue.
D.1 - Bug
If it was a bug, then you close.
Your daily-basis task is open the issue tracker and scan for issues in "resolved" state.
Then you git clone the branch and fully-test it. If the branch passes the quality control, then it is QA that merges the issue-branch into master when approved and makes the deploy.
Of course this holds only when you don't have auotomated tests and continuous integration.
Once merged, close the bug in the issue tracker and annotate the merge hash.
D.2 - Issue
If it was a feature most probably you have some kind of "demo day" every few days or "acceptance event" by the business managers.
If you use scrum or scrum-like things at the end of the sprint you'll do a demo to the Product Owner. In that meeting, annotate the numers that have been approved by the PO.
If you don't use agile, and it's just the boss saying "do this, do that" it is worth establishing some kind of "demo to the managers" so they can "test the feature" before going to production (so the branches are not merged yet in the demo to selectively accept or reject different set of features).
In either case it is "managers" that give the "close okey" to the "resolved" state of the coder.
You always go to the demo with pre-tested branches by QA. If you don't approve the quality that's not being demoed. I mean, the demo is a "request to merge to master", not a "let's play together to test if it works".
Annotate the numbers they approve and as you previously tested the branches, you merge them into master and deploy.
E) Your report... now here it comes your real anwer
With all this in place, do not do any report. Just open in the issue-tracker a non-privileged user that just can "watch" but cannot edit. Give that user to your managers.
Meet with them, ensure this:
The managers can open the tracker,
They Can login,
They can browse to the main issue-list,
They make a very-easy-to-find bookmark,
They save their password in the broswer.
So next time it's a mater of "1-click": They'll click the bookmark with the saved credentials and they'll see the list.
THIS is your report: The list they see in the mantis, in the redmine, in the Jira or whatever.
F) Make them easy - ONLY use bug priorities and avoid textual other that the title.
How do you communicate to them?
Avoid any text oriented to the managers. All the free-texts are a conversation between coders and QA. Except for one. The title. That must be also understood by the managers.
But give the title a very very very (x 100 times) very expressive name.
Consider the difference between those two titles:
Login failing again after update
versus
Login fails with google-OAuth because the token was invalidated by the deployer script
This raises something: QA is not limited to see "what fails". It also emcompases to hack until discovering "why it fails", so the QA person needs to have a hacker-mind and really try to "break" the system with a simulation of bad intentions. The QA people need to be hacker-minded... but that would be off-topic.
So in short
If you are in a team with other senior QA, better ask them.
If you are alone and have no senior QA besides you follow this:
Install an issue tracker. Up to here not-opinion based. If you don't know what to use, I'd go for mantis, but this is opinion-based and redmine fans would kill me. Let's leave this in "have an issue-tracker".
Define bug levels written.
Set aaaaaaaaaaaaaall your currently-known issues in the issue-tracker.
If you treat bugs and features the same way, use the bug-tracker as a feature-tracker. Definitively if you manage less than 200 issues counting known-bugs and features go for this one.
Alternatively if you have a different workflow for correcting bugs with respect to feature-requests, then set the bugs in the bug-tracker and the features in another place. For example trello-lists are very easy to manage and prioritize, to create product-backlogs and sprint-backlogs easily. Or if they have the same flow but you have 500 to 1.000 pending features and 500 known bugs. Then consider if you want to separate into 2 tools.
Have users for the issue-tracker (one user for each coder, and one user (read-only) for each manager.
Ask the coders to "grab the issue" when they start working with it.
Ask the coders to never "close" the issue. Mark it as resolved instead.
You, as QA, mark it as "closed" when you have tested it before deploing and give green light to the merge deploy.
Ask the Product Owner (or the business mangers if there's no P.O.) to close the ones in the "demo" of the new features that you have already tested.
Merge all closed bugs and features.
Do a final test after-merging and pre-deploying just in case.
Deploy.
If you don't have any time-schedule, even if you don't have any agile process, I suggest to do this in cycles. If you don't have any absolute reference, do this weekly or by-weekly.
So if you choose weekly, tell your managers you need from them full-attention 2 times per week: First-time on the monday 1 or 2 horus, and any-time on the friday 1 or 2 hours.
Each monday you'll meet the managers for a pseudo-plani
Open up the issue tracker with them together.
Review the list sorted by "nature" (not priority) (blockers, majors, minors, etc).
Review what priorities were non-correlated to nature in previous weeks and see if thay still hold good. For example:
a blocker that business said "we know we loose money here but we don't care as there are more important things to do right now" (may seem silly, but can happen if you loose but not too much (say a 2% of sales) and the managers need new features to close a deal with a partner that will boost the busines half-term.
a typo or minor that for them is very important
Correct the priorities in real time if needed.
Finally review with the managers the "priority tags" of the issues recently open.
Once this is done, double-check sorting by "priority" (not nature) and agree "we will work this week first* on this, when we kill all those **then on that, when we kill all that then that. We'll work in this order until the end of the week, see how many of them we can do.
Each firady, meet the managers for a demo
Open up the issue tracker and list the closed bugs and resolved features.
For the bugs show the corrected version and say "this has been resolved, and as it was a bug I already closed it"
For the features say "so here's what we did this week, I have already tested and for me it is ready to go to production". Show the feature and ask "merge?" and get a yes/no (it can happen that a feature is ready to merge but managers want to keep it for a later release).
With all this you do not need the report you were asking for, but instead you'll add much more value as the list will be a "live list", not needing to be hand-crafted every time. The list will reflect the "real work" in "real time" if they enter to see it ad mid-week.
You have thousands of screenshots over there: https://www.google.com/search?q=mantis+screenshot&newwindow=1&client=firefox-b-d&sxsrf=ALeKk03RLE002YMYHG0etua8TAmcPaSadw:1592050273735&source=lnms&tbm=isch&sa=X&ved=2ahUKEwiR7J644f7pAhWNlxQKHc5oBZkQ_AUoAXoECAsQAw&biw=1760&bih=869
An example of "a prioritized listing" could be this one (this is a real example from the ones I manage):
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Subsets and Splits