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20860278

Do viscid secretions have a role in nasal polyp formation?

pared histologic findings on light microscopy of viscid secretions found in association with nasal polyps with those found in patients with chronic sinusitis without polyposis (CSWP). The differences might further understanding of nasal polyp pathogenesis.

20860277

Bacteremia during adenoidectomy: a comparison of suction diathermy adenoid ablation and adenoid curettage.

Transient bacteremia is induced by adenoidectomy when the integrity of the nasopharyngeal membrane is broken. The aim of this study was to determine the incidence of bacteremia in patients undergoing adenoidectomy, to identify the causative organisms, and pare the incidences of bacteremia between the two techniques suction diathermy and curettage.

20860279

Bone marrow stem cell transplantation to olfactory epithelium.

We sought to develop a new therapeutic strategy for degeneration of olfactory receptor neurons (ORNs).

20860280

Age-specific size of the upper airway structures in children during development.

The purpose of this study was to establish the largest magnetic resonance imaging study so far, by including 292 cases in a prospective fashion, to investigate the normative values of the upper airway and surrounding tissues during development.

20860281

Rationale for targeting pepsin in the treatment of reflux disease.

We undertook to (1) obtain unequivocal evidence to confirm or rebut our initial observations that pepsin is taken up by hypopharyngeal epithelial cells by receptor-mediated endocytosis, (2) investigate whether uptake of pepsin at pH 7, in nonacidic refluxate, is of pathological significance, and 3) test our hypothesis that inactive but stable pepsin (<pH 8) taken up by hypopharyngeal epithelial cells causes damage by ing reactivated inside the cell.

20860282

How does the absence or presence of subglottal medialization affect glottal airflow?

Our previous work has shown that the symmetric, smooth, convergent shape of the subglottis reduces turbulent airflow at the glottal entrance. Medialization thyroplasty may alter the glottal shape and is very likely to introduce some degree of glottal asymmetry, which could result in increased turbulence and a reduction in voice quality. This study reports the effects of medializing and not medializing the subglottis in silicone models of human cadaveric larynges.

20860283

In vitro and in vivo effects of D-allose: up-regulation of thioredoxin-interacting protein in head and neck cancer cells.

This study was aimed to investigate the relationship between the antiproliferative effects of D-allose and the up-regulation of thioredoxin-interacting protein (TXNIP) in head and neck cancer cells.

20860298

[Application of hair analysis of selected psychoactive substances for medico-legal purposes. Part I. Segmental hair analysis in cases of fatal opioids and amphetamines poisoning].

The present experimental investigations were inspired by the necessity of standardizing the procedures and analytical methods employed in hair analysis aiming at a retrospective evaluation of ingestion of various xenobiotics. Thus, in keeping with the principal premises, the main objective of the study was development of unique, novel chemico-toxicological procedures for analyzing hair content of psychoactive substances in two basic groups of substances of abuse: opioids (morphine, 6-monoacetylmorphine, codeine) and amphetamines (amphetamine, methamphetamine, MDA, MDMA, MDEA) by HPLC-APCI-MS-MS, followed by verification of the thus worked out procedures in medico-legal practice through opinionating in selected group of patients deceased due to fatal psychoactive substance poisoning (cause of death determination). Determinations of opioids and amphetamines in the hair biological matrix were performed using high performance liquid chromatography - atmospheric pressure chemical ionization - tandem mass spectrometry (HPLC-APCI-MS-MS). In the group of fatal poisonings by ,,Polish heroine", hair segmental analysis confirmed the abuse profile of the opiate or mixed (opiate-amphetamine) type, which to some measure is characteristic of Polish drug addiction, indicating the presence of these xenobiotics in the investigating hair samples in the premortem period.

20860299

[Analysis of taxus baccata alkaloids in biological samples with the use of chromatographic methods].

The aim of the experiment was to develop a method of the identification of taxines (taxine B and isotaxine B) from Taxus leaves and its application to the analysis of biological samples collected from the deceased girl. The object of the investigation was the analysis of taxines in post-mortem samples collected from a 15-year-old girl, who consumed leaves of Taxus baccata mit suicide. She died after several hours of hospitalization. Taxus alkaloids, especially taxine B and isotaxine B, are mercially available. Due to this fact, the authors worked out a preliminary method of isolating taxines from Taxus leaves and their extraction using thin layer chromatography (TLC) and solid-phase extraction (SPE). Identification of the presence of taxine B and isotaxine B in the extract from Taxus leaves was performed by high performance liquid chromatography coupled to tandem mass spectrometry with electrospray ionization (HPLC-ESI-MS-MS). The developed method was applied to determination of taxine B and isotaxine B in the biological samples collected from the girl's body. The samples were prepared using solid-phase extraction (SPE) and analyzed by HPLC-ESI-MS-MS. The results demonstrated that all the samples contained taxine B and isotaxine B. The results of toxicological investigations were confirmed by macroscopic and microscopic histological examinations.

20860300

[Population genetics of 11 STR loci in the Upper Silesia population].

The report present the results of population studies of 11 STR loci: D16S5539, D7S820, D13S317, CSF1PO, TPOX, TH01, F13A01, FESFPS, VWA, F13B, LPL originating from samples examined in Laboratory of Biological traces, Chair and Department of Forensic Medicine, Silesian Medical University. The examinations were performed in the group of 455 non-consanguinated adults, men and women, from Upper Silesia. The purpose of the investigation was to study the distribution of allele frequencies of 11 short tandem repeat representative sample of the Upper Silesia (Poland) population, to show genetic balance in agreement with Hardy-Weinberg's law for the studied population and pare homogeneity of the usefulness of 11 STR genetic markers for paternity testing and forensic identification purposes. Genomic DNA was isolated from blood samples and swabs from oral cavity by The Blood DNA Prep Plus kit (A&A Biotechnology) and EZ1 DNA tissue Kit for the use on the BioRobot EZ1. All reactions were carried out according to the manufacturer's mendations (Silver Stain Detection, Promega). POR amplification was performed following the instructions of the GenePrint STR System kit using a GeneAmp PCR System 2700 Thermal Cykler. PCR products and Promega Ladders were separated by vertical electrophoresis on 6% denaturing polyacrilamide gel (Amresco), electrophoresis and visualized by silver staining (Promega Corporation). Allele frequencies, the values of heterozygosity (Ht), polymorphism information content (PIC), power of discrimination(PD), power of exclusion (PE), paternity index (PI), and matching probability (PM) were calculated using FatRec by Dudek's program and TFPGA of Miller. The concordance with HWE was evaluated using the chi-square test. pared statistic parameters, which make an ponent of research work and opinionating, show that 11 STR loci constitutes a very useful tool for individual identification in crime research and in putative paternity research.

20860301

[Application of the QIAamp DNA Investigator Kit and Prepfiler Forensic DNA Extraction Kit in genomic DNA extraction from skeletal remains].

The report presents an application of the QIAamp DNA Investigator Kit and PrepFiler Forensic DNA Extraction Kit in genomic DNA extraction from post-mortem highly degraded skeletal remains. The analysis included 25 bone samples collected on autopsy. DNA extraction was performed in accordance with the QIAamp DNA Investigator Kit and PrepFiler Forensic DNA Extraction Kit manufacturer's isolation protocols. Amplification was performed on a Biometra termocycler using the AmpFISTR Identifiler PCR Amplification Kit according to the manufacturer's protocol. Typing of PCR products was carried out on an ABI Prism 377 DNA sequencer. The mended parameters for GeneScan analysis and Genotyper software were followed. The authors demonstrated that the QIAamp DNA Investigator Kit was more effective, convenient and statistically significantly better method which may be employed in DNA extraction from bone specimens.

20860302

[Do contusions cause skin dysfunction?].

Basing on the acquaintance with anatomy and physiology of the skin, the authors show that the emphasis placed on the functional aspect of human health, introduced by the Penal Code of 6 June 1997, should change the way contusions are subsumed under provisions of the aforementioned code.

20860304

[Mental state and the criminal responsibility--legal regulations and medical criteria in Poland and other countries].

In contemporary civilized legal systems, sanity is a prerequisite for criminal responsibility of the perpetrator. Thus, insanity resulting from certain psychiatric and psychological disorders is a circumstance excluding the guilt. General assumptions of insanity criteria are close and similar in legal systems of the majority of countries; however, certain essential differences appear in details of their interpretation and acceptance. These differences in particular appear among systems of continental European states as opposed to these, in which the judiciary system is derived from the English law. The paper presents and discusses in detail the legal and medical considerations of insanity defense in Poland, as well as outlines the legal foundations of this issue in other countries of Europe, North America and Australia.

20860306

[Reconstruction of an air-gun injury track in the neck region--a case report].

The authors present a case of an air-gun injury of the neck region with a foreign body left in situ. The DICOM files obtained during clinical CT examination puted tomography angiography) gave the opportunity for three-dimensional reconstructions of the location of the pellet, neighboring blood vessels and the bullet track--essential for a successful analysis of a possible version according to the testimonies related to the critical event.

20860303

[Common paths of psychiatry and forensic medicine--history and evolution of insanity defense concept from antiquity to modern times].

Forensic psychiatry and psychology were in their beginnings inseparably associated with the forensic medicine, constituting one of its related branches of knowledge. Progress and development of these disciplines, education and the practical application for the purposes of the law were a contribution of a several generations of forensic pathologists in the 19th and 20th centuries. One of the major issues mon interest was opinionating on the sanity of offenders. However, the problem of criminal responsibility of the mentally ill perpetrators dates back to much earlier times and has its roots in the distant beginnings of human civilization. In this paper, the history and evolution of the insanity concept (as a circumstance excluding the guilt of the offender) were presented, from the oldest theories to ideas underlying modern codifications.

20860305

[A rare D19S433*7 variant in the paternity case with mutation].

During a routine paternity casework performed with an automated genotyping using the AmpFISTR Identifiler kit, a lack of paternal allele segregation in D21S11 and off-ladder allele in D19S433 locus was observed. This raised suspicion of mutation because the other systems showed transmission of putative father's alleles to the child. To achieve the mended value of paternity index (PI), the range of analysis was extended by additional autosomal loci (Penta D and Penta E) and haplotype of the chromosome Y. No further exclusions were observed. Additionally, a new PowerPlex ESI 17 kit was used. parison, the mon for both the multiplex kits confirmed the presence of the mutation in D21S11 locus. In locus D19S433, a rare variant D19S433*7 allele was evidenced in the putative father and the child. This variant allele was included in size range of allelic ladder in the PowerPlex ESI 17 kit, but not in AmpFfSTR Identifiler kit. The variant D19S433*7 allele was not reported in the Polish population before. ThlSTRe PowerPlex ESI 17 genotyping kit has two advantages, i.e. introduction of 6 loci not included in the Identifiler kit, and extended ranges of allelic ladders. It seems that a careful scrutiny of fluorescent signals following electrophoretic separation is essential to detect rare variant alleles and to avoid misinterpretation of the results.

20860307

[Postmortem CT examination in a case of alleged drowning--a case report].

The authors present an analysis of postmortem CT examination in a case of drowning in fresh water of a young male. Both the results of conventional forensic autopsy and radiologic examination have pared. The analysis is illustrated by two-dimensional and three-dimensional reconstructions based on the DICOM files obtained during postmortem CT examination.

20860313

Clinical manifestation of central nervous system tumor.

Tumors of the brain and spinal cord (central nervous system, CNS) are rare pared with other sites and other diseases that can affect the length of an individual's life. However, about 20,000 new cases of primary CNS tumors are diagnosed in the United States each year, not an insignificant number. The CNS is "locked" inside a rigid and nonexpandable calvarium (except in newborns and young children); therefore, any new growths (primary or secondary) can only grow at the expense of the structures already inside the skull or spinal column. The symptoms and signs or clinical manifestations of CNS tumors depend on the location and the growth rate of these tumors. Symptoms include general nonlocalizing and focal symptoms and signs. General signs, which reflect the increase in intracranial pressure, include drowsiness, confusion, headache, nausea, vomiting, sixth nerve palsy, papilledema, generalized seizures, and cognitive impairment. Focal signs and symptoms reflect the effect of the tumor on specific structures. Special imaging techniques (such puted tomography, magnetic resonance imaging, and positron emission tomography) are essential for the localization of the lesion and for image-guided brain biopsies. The handling of these tiny biopsies often presents significant diagnostic challenges, especially at the time of frozen section examination.

20860314

Practical molecular diagnostics in neuropathology: making a tough job a little easier.

Neuropathology is a challenging field, in large part because of the consequential decisions that must be made with small biopsy material. This is especially true concerning the mon primary brain tumor, the infiltrative glioma. Fortunately, abundant research has identified specific molecular alterations that are characteristic of gliomas, according to diagnostic class and tumor grade. Such alterations include 1p19q codeletion, EGFR amplification, p16 deletion, and IDH1/2 mutations. Using specific cases as examples, this review illustrates how molecular testing is of great help in avoiding misdiagnoses and enhancing the quality of information provided to clinicians.

20860315

Astrocytic neoplasms of the central nervous system and orbit: a morphologic perspective.

Astrocytic neoplasms constitute a highly diverse category of neoplasms in the central nervous system and the orbit that span from almost benign to highly malignant neoplasms. Most tumors in the former category are potentially cured by surgery alone, while the latter group of tumors do not respond to any form of current treatment. The most critical advance in our understanding of the pathology of these tumors has divided this group into circumscribed (or solid) and infiltrating (or diffuse) categories. These two categories differ from one another in virtually every aspect and their distinction has e the principle role of the pathologist in guiding appropriate management. There is increasing insight into the biology of these neoplasms but the fundamental role of the pathologist still remains the correct morphological recognition. This short review highlights the most pertinent features of neoplasms considered within this diverse family.

20860316

Infectious lesions mimicking central nervous system neoplasms.

Infections of the central nervous system (CNS) presenting as space-occupying lesions are not mon, particularly in developing countries. Most often, infective organisms gain entry into the CNS through the hematogenous route, seed the parenchyma, and cause tissue destruction. Subsequently, some form mass lesions in a manner similar to neoplastic growths. monality in pathogenesis and pathology between infective agents and neoplastic cells underlies the similarities in their presentations. Although neoplasms are mon considerations in the presence of enhancing lesions with perilesional edema and mass effect on neuroimaging, nonneoplastic conditions-in particular, infectious lesions--can have similar imaging characteristics. The widening spectrum of opportunistic and newly recognized pathogens has added to the difficulties. Biopsy diagnosis is mandatory for neoplasms, both for confirmation of diagnosis as well as grading, but most infectious lesions are managed conservatively if the diagnosis is established by noninvasive means. This review discusses some of mon infectious lesions that mimic CNS neoplasms, with emphasis on pyogenic, tuberculous, and fungal lesions as well as parasitic and viral infections that present as intracranial space-occupying lesions. The data of infective lesions that mimicked intracranial neoplasms, from our institute, over the last 5 years, are also presented. Awareness of the pathogenetic basis of tissue injury and host response, resulting in the spectrum of clinical and imaging patterns as well as a high index of clinical suspicion, are essential for accurate diagnosis, to ensure appropriate management.

20860317

Oligodendroglial tumors: diagnostic and molecular pathology.

Oligodendroglial tumors, which pass pure oligodendroglioma and mixed oligoastrocytoma, represent the second mon glioma in adults after glioblastoma. They remain controversial neoplasms in the realm of surgical neuropathology. The early recognition of their more favorable prognosis and responsiveness to treatment pared with diffusely infiltrating astrocytomas has influenced the pathologic diagnostic interpretation, and resulted in a pervasive interobserver variability. The more recent finding of an increased frequency of 1p/19q deletion in these tumors by cytogenetic analysis, and the association of this molecular abnormality with a better prognosis has greatly impacted the field of neuro-oncology. In this review, we focus on important histopathologic aspects in the evaluation of oligodendroglial tumors, key differential diagnoses, and highlight particular clinical and molecular characteristics, as well as current diagnostic and conceptual controversies.

20860319

Building a case with hard facts.

Skill mix and staffing e under the spotlight in the final part of a Nursing Standard series in which RCN fellows consider nursing challenges.

20860321

Leadership challenge.

Nursing Standard's Power to Care campaign aims to boost the authority and status of ward sisters and charge nurses. Here we examine how nurses in Milton Keynes are pursuing its goals.

20860324

Implementation of the Mental Health Act 2007.

This article aims to contribute to an understanding of the Mental Health Act 2007, which came into force in November 2008. The article explains the link between the Mental Health Act, the Mental Health Act Code of Practice and mental health case law. It describes the guiding principles outlined in the Code of Practice, identifies the nine major changes to the Mental Health Act 1983 and discusses the role of the nurse in the care and treatment of people subject to the Mental Health Act 2007.

20860332

Appalachian women: health beliefs, self-care, and basic conditioning factors.

The purposes of this study were to: (a) describe the health beliefs and self-care of Appalachian women; and (b) describe the relationships among health beliefs, self-care, and the basic conditioning factors of Appalachian women. Orem's SCDNT was used as the theory for this study. This study used qualitative and quantitative methodologies. The study participants included 129 Appalachian women. Health beliefs and self-care were described. Significant correlations were found ponents of the basic conditioning factors and definition of health beliefs and self-care. The es from this research study support that Appalachian women do participate in self-care in promoting their health.

20860331

Strategies for providing cultural competent health care for Hmong Americans.

In the early 1980's the United States gave the Hmong preferred refugee status and a large number immigrated to the U.S. The Hmong refugees brought with them their language, social structure and customs, religious beliefs and rituals as well as their health care beliefs and practices. They were uprooted from munity and social supports and now live where the culture, language and socioeconomics are vastly different. Despite having learned a great deal about the Hmong culture over the last three decades, providing petent health care for this unique group continues to be a challenge. The purpose of this paper is to enumerate the barriers to providing health care to Hmong Americans and share strategies to respect Hmong culture when providing quality health care. Emphasis is placed on building relationships based on trust and mutual respect. Cultural exchange is encouraged as well as the need for basic cultural awareness.

20860323

Role of the ward sister: tensions, pressures and opportunities.

This article investigates the factors that have shaped the role and work experiences of ward sisters and charge nurses. The article considers how ward sisters make sense of the tensions between their clinical and managerial responsibilities and the contradictions inherent in different aspects of their role. It offers suggestions on how these tensions might be alleviated.

20860333

Native Hawaiian attitudes of culturally sensitive healthcare provider traits and behaviors.

Provision of petent healthcare has been an area of increasing focus in research due to increased mobility of individuals and Increased ethnic and cultural diversity within the populations being served. A descriptive, exploratory design was used to investigate attitudes and perceptions of 61 Native Hawaiian adults regarding care provided to them and to identify areas for further study. Three major themes were identified: (1) Participants expected to be provided with family centered, holistic, respectful, and accepting health care; (2) petent care was described as direct, open, and munication expressed with concern; and (3) Uncaring behaviors were expressed as a lack concern or acceptance which appeared to negatively impact provider ability to form relationships with individuals and their families.

20860334

Paradise Lost: how older adult Taiwanese immigrants make decisions about their living arrangements.

Understanding the process of making living arrangement decisions among older adult immigrants is essential to developing and optimizing health promotion strategies. The purpose of this study was to discover how older adult Taiwanese immigrants made decisions about their living arrangements. Fourteen Taiwanese older adult immigrants were recruited from a large Northeastern metropolitan city in the United States. A grounded theory approach was used for data collection and analysis. The process by which participants make decisions about living arrangements is best described with the metaphor of Paradise Lost. The process had three phases: Seeking Paradise, Loosing Paradise and Reconsidering Paradise.

20860320

Beware of the dog.

An anomaly in the Dangerous Dogs Act means that nurses who visit people in their own homes have little redress if they are bitten.

20860335

Aging in America: quality of life among older Vietnamese women immigrants.

The purpose of this ethnographic research was to describe factors related to and elicit the meaning of "quality of life" in a group of older Vietnamese women immigrants. Thirty-three women who emigrated from Vietnam to the United States after 1978 participated in audiotaped interviews. Ethnographic content analysis was used to identify themes and categories. Major theme ofresiliency and security were identified. The elements of health, functional status and social support were consistent with quality of life concepts described by Flanagan; and, George and Bearon while leisure and recreation was not present.

20860325

Learning how to undertake a systematic review: Part 2.

This article, the second in a two-part series, continues to describe the stages involved in conducting a systematic review. The article discusses how to select and appraise studies for inclusion in the review, and how to extract, synthesise and present the findings. A summary of the key points for writing the results and discussion sections of a report of a systematic review is also presented.

20860336

Overcoming cultural barriers to diabetes control: a qualitative study of southwestern New Mexico Hispanics.

This qualitative study examined the impact of cultural barriers on self-management of diabetes among Hispanic participants in LA VIDA (Lifestyle and Values Impact Diabetes Awareness), a diabetes intervention program in southwestern New Mexico. As part of the LA VIDA program evaluation, in depth interviews were conducted with 50 Hispanics who had participated in one or more activities, including diabetes education classes, grocery store tours, and support groups, and who had interacted with promotores (community health workers). LA VIDA participants reported that a sense of empowerment and increased self-efficacy enabled them to e cultural barriers related to the traditional Hispanic diet, lack of social support, and denial about having diabetes.

20860347

Solid-state (127)I NMR and GIPAW DFT study of metal iodides and their hydrates: structure, symmetry, and higher-order quadrupole-induced effects.

Central-transition (127)I solid-state nuclear magnetic resonance (SSNMR) spectra are presented for several anhydrous group 2 metal iodides (MgI(2), CaI(2), SrI(2), and BaI(2)), hydrates (BaI(2)·2H(2)O and SrI(2)·6H(2)O), and CdI(2) (4H polytype). Variable offset cumulative spectrum data acquisition coupled with echo pulse sequences and an 'ultrahigh' applied field of 21.1 T were usually suitable to acquire high-quality spectra. Spectral analysis revealed iodine-127 nuclear quadrupole coupling constants (C(Q)((127)I)) ranging in magnitude from 43.5 (CaI(2)) to 214 MHz (one site in SrI(2)). For very large C(Q), analytical second-order perturbation theory could not be used to reliably extract chemical shifts and a treatment which includes quadrupolar effects exactly was required (Bain, A. D. Mol. Phys. 2003, 101, 3163). Differences between second-order and exact modeling allowed us to observe 'higher-order' quadrupole-induced effects for the first time. This finding will have implications for the interpretation of SSNMR spectra of quadrupolar nuclei with large quadrupole moments. In favorable situations (i.e., C(Q)((127)I) < 120 MHz), measurements were also performed at 11.75 T which bined with the 21.1 T data allowed us to measure iodine chemical shift (CS) tensor spans in the range from 60 (BaI(2)·2H(2)O) to 300 ppm (one site in BaI(2)). These measurements represent the plete characterizations (i.e., electric field gradient and CS tensors as well as their relative orientation) of noncubic iodide sites using (127)I SSNMR. In select cases, the SSNMR data are supported with (127)I NQR measurements. We also summarize a variety of trends in the halogen SSNMR parameters for group 2 metal halides. Gauge-including projector-augmented wave putations are employed plement the experimental observations, to predict potential structures for the two hydrates, and to highlight the sensitivity of C(Q)((127)I) to minute structural changes, which has potential applications in NMR crystallography.

20860348

Tuning the intramolecular charge transfer emission from deep blue to green in ambipolar systems based on dibenzothiophene S,S-dioxide by manipulation of conjugation and strength of the electron donor units.

The efficient synthesis and photophysical properties of a series of ambipolar donor-acceptor-donor systems is described where the acceptor is dibenzothiophene S,S-dioxide and the donor is fluorene, carbazole, or arylamine. The systems exhibit intramolecular charge transfer (ICT) states (of variable ICT character strengths) leading to fluorescence emission ranging from deep blue to green with moderate to high photoluminescence quantum yields. The emission properties can be effectively tuned by systematically changing the position of substitution on both donor and acceptor units (which affects the extent of conjugation) and the redox potentials of the donor units. The results are supported by cyclic voltammetric data and TD-DFT calculations.

20860349

Re-engineering erythropoietin as an IgG fusion protein that penetrates the blood-brain barrier in the mouse.

Erythropoietin (EPO) is a potent neuroprotective agent that could be developed for the treatment of multiple brain disorders. However, EPO does not cross the blood-brain barrier (BBB). A brain-penetrating form of EPO, specific for the mouse, was engineered by fusion of the 166 amino acid EPO to the carboxyl terminus of the heavy chain of a chimeric monoclonal antibody (mAb) against the mouse transferrin receptor (TfR), and this new fusion protein is designated cTfRMAb-EPO. The fusion protein was expressed in stably transfected Chinese hamster ovary cells and purified by protein G chromatography. The fusion protein was homogeneous on SDS-PAGE and Western blotting, and bound the mouse EPO receptor (EPOR) with high affinity, ED50 = 0.33 ± 0.04 nM. The cTfRMAb-EPO fusion protein was radiolabeled by tritiation and injected intravenously (iv) into adult mice for measurements of the plasma pharmacokinetics and brain uptake. The (3)H-fusion protein was rapidly cleared from the blood with a clearance rate of 5.9 ± 0.3 mL/min/kg, which is 14-fold faster than the clearance of EPO in the mouse. The cTfRMAb-EPO fusion protein penetrated the BBB in vivo, as shown by the capillary depletion method. The brain uptake of the cTfRMAb-EPO fusion protein was 2.0 ± 0.1% injected dose/g of brain following iv administration. The high level of brain uptake of the fusion protein enables pharmacologic increases in exogenous EPO in the mouse brain following the systemic injection of the cTfRMAb-EPO fusion protein. In conclusion, EPO has been re-engineered as an IgG fusion protein that binds dual receptors: the mouse TfR, to enable penetration of the BBB, and the mouse EPOR, to produce neuroprotection in brain behind the intact BBB.

20860350

Electronic structure and (1)H NMR chemical shifts in host-guest complexes of cucurbit[6]uril and sym-tetramethyl cucurbit[6]uril with imidazole derivatives.

Binding patterns and (1)H NMR chemical shifts in plexes of protonated N-(4-hydroxylphenyl)imidazole (g1), N-(4-aminophenyl)imidazole (g2), 2-phenylimidazole (g3) guests with cucurbit[6]uril (CB[6]), and sym-substituted tetramethyl cucurbit[6]uril (TMeCB[6]) in the gas phase as well as in water have been investigated using the density functional theory. It has been shown that the plexes of g1 and g2 with CB[6] or TMeCB[6] exhibit selective encapsulation of the phenyl moiety with its substituents binding to portal oxygens on the lower rim of the host and imidazole protons facilitate C-H···O interactions externally with upper rim ureido oxygens. On the other hand, the lowest-energy plex encapsulates the imidazole ring within the host, engendering N-H···O interactions with portal oxygens on the upper rim of the host with the phenyl ring residing outside the cavity owing to an absence of para-substituent and show qualitatively different host-guest binding patterns. Calculated (1)H NMR spectra of plexes in water reveal shielding of phenyl ring protons within the host cavity which exhibit signals at 0.2-0.5 ppm, whereas the protons of the imidazole ring participating in hydrogen bonded interactions exhibit deshielding, and the corresponding (1)H NMR signals are downshifted by 1.1-1.5 ppm in the pared to those in the unbound guest. (1)H NMR chemical shifts of plexes thus obtained are in consonant with δ(H) patterns observed in experiments reported in the literature.

20860345

Cone beam CT--anatomic assessment and legal issues: the new standards of care.

Until the recent introduction of cone puted tomography scanners, standard 2-D imaging provided a moderate contribution to overall treatment planning when considering the diagnostic potential, costs of study and risks to the patient. Cone puted tomography-dedicated maxillofacial imaging scanners provide broader imaging tools for anatomic assessment and have e widely available. This article discusses the uses and benefits of 3-D imaging, as well as the impact on the standard of care. Many phases of patient care involve imaging to assist with diagnosis, treatment planning, risk assessment and treatment. Techniques employing X-rays, visible light, ultrasound, lasers and magnetic fields have been used in medicine and dentistry to create images. All forms of imaging require a coupled system of emitters and sensors. For example, a cephalometric image is produced using an X-ray emitter and film sensor. Imaging systems can be categorized in many different ways based upon emitter or output type (examples; film-based, digital, 2-D and 3-D images). The resultant images can be used to evaluate the anatomy of interest, including surface and subsurface. The ultimate quest of all forms of imaging is to reveal the anatomic truth; that is, to portray the anatomy as it exists in nature. Thoughtful clinical application of image acquisition requires matching the uses and limitations of the available imaging choices to achieve the desired diagnostic information (imaging goal) while keeping the risks and costs to the patient as low as possible. Imaging data must provide a benefit at an acceptable cost and risk. Two-dimensional representation of 3-D anatomies creates images that have poor spatial accuracy, are static in space and time, and contain information voids. These 2-D measurements have propagated legacy databases of inaccurate morphometric measurements. Current development in imaging technology for dentistry includes digital imaging and improved sensor technology. Multidimensional anatomical reconstruction can be performed through software applications. The ultimate reward of technological imaging advancements is the 3-D representations (digital volume) of anatomy as it exists in nature (anatomic truth). Analysis of the accurate digital volume can provide clinically relevant spatial information or data. Visualization and analysis of 3-D information can benefit a dental practice by providing data that will improve diagnosis, risk assessment, treatment e and treatment efficiency, and reduce plications. This article discusses the uses and benefits of 3-D imaging (cone beam CT, CBCT) for diagnosis, treatment planning and the legal issues affecting the standard of care, as well as offering risk management tips and use guidance.

20860351

Selective binding of antiinfluenza drugs and their analogues to 'open' and 'closed' conformations of H5N1 neuraminidase.

It was suggested that the open conformation of the 150-loop of H5N1 avian influenza neuraminidase is intrinsically lower in energy than the closed conformation and that oseltamivir (tamiflu) favors binding to the closed conformation through a relatively slow conformational change [Russell, R. J. Nature 2006, 443, 45-49]. In the present work, a putational study is performed to investigate the binding mechanism of five ligands to H5N1 neuraminidase (H5N1 NA) with the 150-loop in both open and closed conformations through molecular docking, molecular dynamics simulations, and MM/PBSA free energy calculation. Our result shows that the electrostatic interactions between polar groups on the 150-loop and the charged groups of the ligands play a key role on the binding selectivity. In particular, ligands having a small positively charged group favor binding to the closed conformation of H5N1 NA, while those having a large positively charged group generally prefer binding to the open conformation. Our analysis suggests that it may be possible to design new inhibitors with large basic groups that are selective for the open conformation and thereby have stronger binding affinity to H5N1 neuraminidase.

20860352

Analysis of measured and calculated Raman spectra of indole, 3-methylindole, and tryptophan on the basis of observed and predicted isotope shifts.

The aromatic amino acid tryptophan plays an important role in protein electron-transfer and in enzyme catalysis. Tryptophan is also used as a probe of its local protein environment and of dynamic changes in this environment. Raman spectroscopy of tryptophan has been an important tool to monitor tryptophan, its radicals, and its protein environment. The proper interpretation of the Raman spectra requires not only the correct assignment of Raman bands to vibrational normal modes but also the correct identification of the Raman bands in the spectrum. A significant amount of experimental putational work has been devoted to this problem, but inconsistencies still persist. In this work, the Raman spectra of indole, 3-methylindole (3MI), tryptophan, and several of their isotopomers have been measured to determine the isotope shifts of the Raman bands. Density functional theory calculations with the B3LYP functional and the 6-311+G(d,p) basis set have been performed on indole, 3MI, 3-ethylindole (3EI), and several of their isotopomers to predict isotope shifts of the vibrational normal modes. Comparison of the observed and predicted isotope shifts results in a consistent assignment of Raman bands to vibrational normal modes that can be used for both assignment and identification of the Raman bands. For correct assignments, it is important to determine force field scaling factors for each molecule separately, and scaling factors of 0.9824, 0.9843, and 0.9857 are determined for indole, 3MI, and 3EI, respectively. It is also important to use more than one parameter to assign vibrational normal modes to Raman bands, for example, the inclusion of isotope shifts other than those obtained from H/D-exchange. Finally, the results indicate that the Fermi doublet of indole may consist of just two fundamentals, whereas one fundamental and bination band are identified for the Fermi resonance that gives rise to the doublet in 3MI and tryptophan.

20860353

A combined experimental and computational thermodynamic study of difluoronitrobenzene isomers.

This work reports the experimental putational thermochemical study performed on three difluorinated nitrobenzene isomers: 2,4-difluoronitrobenzene (2,4-DFNB), 2,5-difluoronitrobenzene (2,5-DFNB), and 3,4-difluoronitrobenzene (3,4-DFNB). The standard (p° = 0.1 MPa) molar enthalpies of formation in the liquid phase of pounds were derived from the standard molar energies bustion, in oxygen, at T = 298.15 K, measured by rotating bustion calorimetry. A static method was used to perform the vapor pressure study of the pounds allowing the construction of the phase diagrams and determination of the respective triple point coordinates, as well as the standard molar enthalpies of vaporization, sublimation, and fusion for two of the isomers (2,4-DFNB and 3,4-DFNB). For 2,5-difluoronitrobenzene, only liquid vapor pressures were measured enabling the determination of the standard molar enthalpies of vaporization. Combining the thermodynamic parameters of pounds studied, the following standard (p° = 0.1 MPa) molar enthalpies of formation in the gaseous phase, at T = 298.15 K, were derived: Δ(f)H(m)° (2,4-DFNB, g) = -(296.3 ± 1.8) kJ · mol⁻¹, Δ(f)H(m)° (2,5-DFNB, g) = -(288.2 ± 2.1) kJ · mol⁻¹, and Δ(f)H(m)° (3,4-DFNB, g) = -(302.4 ± 2.1) kJ · mol⁻¹. Using the empirical scheme developed by Cox, several approaches were evaluated in order to identify the best method for estimating the standard molar gas phase enthalpies of formation of pounds. The estimated values pared to the ones obtained experimentally, and the approach providing the parison with experiment was used to estimate the thermodynamic behavior of the other difluorinated nitrobenzene isomers not included in this study. Additionally, the enthalpies of formation of pounds along with the enthalpies of formation of the other isomers not studied experimentally, i.e., 2,3-DFNB, 2,6-DFNB, and 3,5-DFNB, were estimated using posite G3MP2B3 approach together with adequate gas-phase working reactions. Furthermore, we also used putational approach to calculate the gas-phase basicities, proton and electron affinities, and, finally, adiabatic ionization enthalpies.

20860354

Miniaturized high-resolution time-of-flight mass spectrometer MULTUM-S II with an infinite flight path.

A new miniature multiturn time-of-flight (TOF) analyzer "MULTUM-S II" has been designed and constructed. This instrument consists of an electron ionization source, the multiturn TOF ion optics, a detector, vacuum system, and electronic circuits. The multiturn TOF analyzer consists of four electrostatic toroidal sectors and two additional electric toroidal sectors for the purpose of ion injection/ejection. The size and weight of the system is less than 50 cm × 57 cm × 30 cm and 35 kg (including vacuum pumps and electronic circuits). The multiturn TOF analyzer is capable of high mass resolution because of its infinite flight path utilizing perfect space and time focused closed flight orbit. To evaluate the resolution in MULTUM-S II, separation of pyridine (¹²C₅H₅N) and the ponent of benzene (¹³C¹²C₅H₆) was performed at a mass resolution of about 20,000. Another performance characteristic of the MULTUM-S II was demonstrated by the separation of the greenhouse gas doublet CO₂ and N₂O (Δm = 0.0113 Da). While the mass difference is a mere 0.01 Da, the instrument could easily separate the two peaks at a calculated mass resolution of 31,600. The MULTUM-S II offers high mass resolution mass spectrometry in a miniaturized/portable enclosure.

20860355

Metallacarboranes: toward promising hydrogen storage metal organic frameworks.

Using first principles calculations, we show the high hydrogen storage capacity of metallacarboranes, where the transition metal (TM) atoms can bind up to 5 H(2)-molecules. The average binding energy of ∼0.3 eV/H favorably lies within the reversible adsorption range. Among the first row TM atoms, Sc and Ti are found to be the optimum in maximizing the H(2) storage (∼8 wt %) on the metallacarborane cluster. Being an integral part of the cage, TMs do not suffer from the aggregation problem, which has been the biggest hurdle for the success of TM-decorated graphitic materials for hydrogen storage. Furthermore, the presence of carbon atom in the cages permits linking the metallacarboranes to form metal organic frameworks, which are thus able to adsorb hydrogen via Kubas interaction, in addition to van der Waals physisorption.

20860356

Photocatalytic formation of I-I bonds using DNA which enables detection of single nucleotide polymorphisms.

By decreasing the HOMO energy gap between the base-pairs to increase the charge conductivity of DNA, the positive charge photochemically generated in DNA can be made to migrate along the π-way of DNA over long distances to form a long-lived charge-separated state. By fine-tuning the kinetics of the charge-transfer reactions, we designed a functionalized DNA system in which absorbed photon energy is converted into chemical energy to form I-I covalent bonds, where more than 100 I(2) molecules were produced per functionalized DNA. Utilizing the fact that charge-transfer kinetics through DNA is sensitive to the presence of a single mismatch that causes the perturbation of the π-stacks, single nucleotide polymorphisms (SNPs) in genomic sequences were detected by measuring the photon energy conversion efficiency in DNA by a conventional starch iodine method.

20860357

The structure of formaldehyde-inhibited xanthine oxidase determined by 35 GHz 2H ENDOR spectroscopy.

The formaldehyde-inhibited Mo(V) state of xanthine oxidase (I) has been studied for four decades, yet it has not proven possible to distinguish unequivocally among the several structures proposed for this form. The uniquely large isotropic hyperfine coupling for (13)C from CH(2)O led to the intriguing suggestion of a direct Mo-C bond for the active site of I. This suggestion was supported by the recent crystal structures of glycol- and glycerol-inhibited forms of aldehyde oxidoreductase, a member of the xanthine oxidase family. (1)H and (2)H ENDOR spectra of I(C(1,2)H(2)O) in H(2)O/D(2)O buffer now have unambiguously revealed that the active-site structure of I contains a CH(2)O adduct of Mo(V) in the form of a four-membered ring with S and O linking the C to Mo and have ruled out a direct Mo-C bond. Density functional putations are consistent with this conclusion. We interpret the large (13)C coupling as resulting from a "transannular hyperfine interaction".

20860358

Stimuli-responsive smart gels realized via modular protein design.

Smart gels have a variety of applications, including tissue engineering and controlled drug delivery. Here we present a modular, bottom-up approach that permits the creation of protein-based smart gels with encoded morphology, functionality, and responsiveness to external stimuli. The properties of these gels are encoded by the proteins from which they are synthesized. In particular, the strength and density of the network of intermolecular cross-links are specified by the interactions of the gels' constituent protein modules with their cognate peptide ligands. Thus, these gels exhibit stimuli-responsive assembly and disassembly, dissolving (or gelling) under conditions that weaken (or strengthen) the protein-peptide interaction. We further demonstrate that such gels can encapsulate and release both proteins and small molecules and that their rheological properties are well suited for biomedical applications.

20860359

Nickel-catalyzed stereoselective glycosylation with C(2)-N-substituted benzylidene D-glucosamine and galactosamine trichloroacetimidates for the formation of 1,2-cis-2-amino glycosides. Applications to the synthesis of heparin disaccharides, GPI anchor pseudodisaccharides, and α-GalNAc.

The 1,2-cis-2-amino glycosides are ponents found within a variety of biologically important oligosaccharides and glycopeptides. Although there are remarkable advances in the synthesis of 1,2-cis-2-amino glycosides, disadvantages of the current state-of-the-art methods include limited substrate scope, low yields, long reaction times, and anomeric mixtures. We have developed a novel method for the synthesis of 1,2-cis-2-amino glycosides via nickel-catalyzed α-selective glycosylation with C(2)-N-substituted benzylidene D-glucosamine and galactosamine trichloroacetimidates. These glycosyl donors are capable of coupling to a wide variety of alcohols to provide glycoconjugates in high yields with excellent levels of α-selectivity. Additionally, only a substoichiometric amount of nickel (5-10 mol %) is required for the reaction to occur at 25 °C. The current nickel method relies on the nature of the plex to control the α-selectivity. The reactive sites of the nucleophiles or the nature of the protecting groups have little effect on the α-selectivity. This methodology has also been successfully applied to both disaccharide donors and acceptors to provide the corresponding oligosaccharides in high yields and α-selectivity. The efficacy of the nickel procedure has been further applied toward the preparation of heparin disaccharides, GPI anchor pseudodisaccharides, and α-GluNAc/GalNAc. Mechanistic studies suggest that the presence of the substituted benzylidene functionality at the C(2)-amino position of glycosyl donors is crucial for the high α-selectivity observed in the coupling products. Additionally, the α-orientation of the C(1)-trichloroacetimidate group on glycosyl donors is necessary for the coupling process to occur.

20860360

Ratiometric and intensity-based zinc sensors built on rhodol and rhodamine platforms.

A xanthene-forming condensation reaction yields rhodol and rhodamine dyes carrying a zinc-binding ligand that includes the aniline-type nitrogen donor of the fluorophores. Upon zinc coordination in neutral aqueous solution, rhodol RF3 behaves as a ratiometric sensor, and rhodamine RA1 acts as a turn-off intensity-based indicator. Both pounds bind the divalent zinc cation with micromolar affinity.

20860361

A coordination cage with an adaptable cavity size.

A hexanuclear coordination cage can increase the size of its cavity from nearly zero to more than 500 Å(3), which allows the encapsulation of two coronene molecules.

20860362

Highly fluorescent platinum(II) organometallic complexes of perylene and perylene monoimide, with Pt σ-bonded directly to the perylene core.

3-Bromoperylene (BrPer) or N-(2,5-di-tert-butylphenyl)-9-bromo-perylene-3,4-dicarboximide (BrPMI) react with [Pt(PEt(3))(4)] to yield trans-[PtR(PEt(3))(2)Br] (R = Per, 1a; R = PMI, 1b). Neutral and cationic plexes containing a Pt(PEt(3))X group have been prepared from 1a,b by substitution of the Br ligand by a variety of other ligands (NCS, CN, NO(3), CN(t)Bu, PyMe). The X-ray structures of trans-[PtR(PEt(3))(2)X] (R = Per, X = NCS (2a); R = PMI, X = NO(3) (4b); R = Per, X = CN(t)Bu (5a)) show that the perylenyl fragment remains nearly planar and is arranged almost orthogonal to the coordination plane: The three molecules appear as individual entities in the solid state, with no π-π stacking of perylenyl rings. Each plex exhibits fluorescence associated to the perylene or PMI fragments with emission quantum yields, in solution at room temperature, in the range 0.30-0.80 and emission lifetimes ∼4 ns, but with significantly different emission maxima, by influence of the X ligands on Pt. The similarity of the overall luminescence spectra of these plexes with the perylene or PMI strongly suggests a perylene-dominated intraligand π-π*emissive state, metal-perturbed by interaction of the platinum fragment mostly via polarization of the Ar-Pt bond.

20860363

Three-dimensional metal-organic frameworks based on tetrahedral and square-planar building blocks: hydrogen sorption and dye uptake studies.

Two three-dimensional metal-organic frameworks (MOFs) with tetraphenylmethane-derived tetracarboxylate linkers and copper paddle-wheel secondary building units were synthesized and characterized by single-crystal X-ray crystallographic studies. The two MOFs show a similar 4,4-connectivity but very different homocrossing and interpenetrating PtS network topologies and exhibit permanent porosity as probed by gas adsorption and dye inclusion experiments.

20860364

(Ag2TeS3)2·A2S6 (A = Rb, Cs): layers of silver thiotellurite intergrown with alkali-metal polysulfides.

The pounds RbAg(2)TeS(6) and CsAg(2)TeS(6) crystallize in the noncentrosymmetric space group P6(3)cm, with a = 19.15 Å, c = 14.64 Å, and V = 4648 Å(3) and a = 19.41 Å, c = 14.84 Å, and V = 4839 Å(3), respectively. The structures posed of neutral [Ag(2)TeS(3)] layers alternating with charge-balanced salt layers containing polysulfide chains of [S(6)](2-) and alkali-metal ions. RbAg(2)TeS(6) and CsAg(2)TeS(6) are air- and water-stable, wide-band-gap semiconductors (E(g) ∼ 2.0 eV) exhibiting nonlinear-optical second-harmonic generation.

20860365

Synthesis of quaternary carbon stereogenic centers through enantioselective Cu-catalyzed allylic substitutions with vinylaluminum reagents.

Catalytic enantioselective allylic substitution (EAS) reactions, which involve the use of alkyl- or aryl-substituted vinylaluminum reagents and afford 1,4-dienes containing a quaternary carbon stereogenic center at their C-3 site, are disclosed. The C-C bond-forming transformations are promoted by 0.5-2.5 mol % of sulfonate bearing chiral bidentate N-heterocyclic carbene plexes, furnishing the desired products efficiently (66-97% yield of isolated products) and in high site (>98% S(N)2')- and enantioselectivity [up to 99:1 enantiomer ratio (er)]. To the best of our knowledge, the present report puts forward the first cases of allylic substitution reactions that result in the generation of all-carbon quaternary stereogenic centers through the addition of a vinyl unit. The aryl- and vinyl-substituted vinylaluminum reagents, which cannot be prepared in high efficiency through direct reaction with diisobutylaluminum hydride, are accessed through a recently introduced Ni-catalyzed reaction of the corresponding terminal alkynes with the same inexpensive metal-hydride agent. Sequential Ni-catalyzed hydrometalations and Cu-catalyzed C-C bond-forming reactions allow for efficient and selective synthesis of a range of enantiomerically enriched EAS products, which cannot be accessed by previously disclosed strategies (due to inefficient vinylmetal synthesis or low reactivity and/or selectivity with Si-substituted derivatives). The utility of the protocols developed is demonstrated through a concise enantioselective synthesis of natural product bakuchiol.

20860366

New anthracenedione derivatives with improved biological activity by virtue of stable drug-DNA adduct formation.

Mitoxantrone is an anticancer agent that acts as a topoisomerase II poison, however, it can also be activated by formaldehyde to form DNA adducts. Pixantrone, a 2-aza-anthracenedione with terminal primary amino groups in its side chains, forms formaldehyde-mediated adducts with DNA more efficiently than mitoxantrone. Molecular modeling studies indicated that extension of the "linker" region of anthracenedione side arms would allow the terminal primary amino greater flexibility and thus access to the guanine residues on the opposite DNA strand. New derivatives based on the pixantrone and mitoxantrone backbones were synthesized, and these incorporated primary amino groups as well as extended side chains. The stability of DNA adducts increased with increasing side chain length of the derivatives. A mitoxantrone derivative bearing extended side chains (7) formed the most stable adducts with ∼100-fold enhanced pared to mitoxantrone. This finding is of great interest because long-lived drug-DNA adducts are expected to perturb DNA-dependent functions at all stages of the cell cycle.

20860367

Dynamics of biocatalytic microengines mediated by variable friction control.

We describe the motion of self-propelled hybrid microengines containing catalase enzyme covalently bound to the cavity of rolled-up microtubes. The high efficiency of these hybrid microengines allows them to move at a very low concentration of peroxide fuel. The dynamics of the catalytic engines is mediated by the generation of front-side bubbles, which increase the drag force and make them turn. The specific modification of the inner layer of microtubes with biomolecules can lead to other configurations to generate motion from different chemical fuels.

20860368

Magnetic properties of segregated layers containing M(II)3(μ3-OH)2 (M = Co or Ni) diamond chains bridged by cis,cis,cis-1,2,4,5-cyclohexanetetracarboxylate.

We report the hydrothermal synthesis, X-ray crystal structures, and thermal, optical, and magnetic properties of two isostructural layered coordination polymers, [M(II)(5)(OH)(2)(chtc)(2)(H(2)O)(10)]·2H(2)O where M = Co (1Co) or Ni (2Ni) and chtc = cis,cis,cis-1,2,4,5-cyclohexanetetracarboxylate. The structures consist of segregated layers where each layer is formed of M(3)(OH)(2) diamond chains, involving edge- and corner-sharing octahedra, bridged by M(chtc)(2). In the space created by the chains and the bridges exists channels, which house the coordinated and noncoordinated water molecules, all hydrogen bonded to form a dodecamer, with a central cyclohexane chair shape ring. Interestingly, the water molecules of 2Ni are more difficult to remove than those of 1Co, but pyrolysis of the latter takes place at higher temperature. The magnetic properties are characterized by Néel transition to pensated antiferromagnets at 5.8 K (1Co) and 3.0 K (2Ni). The moments are easily reversed in an applied field of 150 Oe (1Co) and 300 Oe (2Ni) to a ferrimagnet with one pensated moment followed by a nonlinear increase to a saturation corresponding to a ferrimagnet with three pensated moments. Further, point charge calculations to estimate the weak bonding energies between the various types of interaction are reported.

20860369

The use of polarizable [AuX2(CN)2]- (X = Br, I) building blocks toward the formation of birefringent coordination polymers.

The [(n)Bu(4)N][AuX(2)(CN)(2)] (X = Br, I) salts were synthesized and structurally characterized. Both feature square-planar [AuX(2)(CN)(2)](-) anions, with trans cyano and halo ligands, which aggregate via halogen-halogen interactions. The aggregation of [AuX(2)(CN)(2)](-) units results in the parallel alignment of all of the Br-Au-Br moieties in the anions along the [110] and [110] directions. Two crystal habits of [(n)Bu(4)N][AuBr(2)(CN)(2)] were grown: with (110) and (001) as the primary faces. The birefringence in the (110) plane was found to be Δn = 0.051(4) and was <0.03 in the (001) plane. Using the [AuBr(2)(CN)(2)](-) unit, [M(phen)(2)][AuBr(2)(CN)(2)](2) (M = Fe, Ni), [Ni(terpy)(2)][AuBr(2)(CN)(2)](2), [Fe(terpy)(2)][AuBr(2)(CN)(2)][ClO(4)], and [Cu(phen)(2)(NO(3))][AuBr(2)(CN)(2)] (phen = 1,10-phenanthroline, terpy = 2,2';6',2''-terpyridine) were synthesized and structurally characterized: they formed ionic structures with coordinatively saturated metal cations and structurally aligning Br···Br interactions between the [AuBr(2)(CN)(2)](-) anions. A plex, Cu(terpy)[AuBr(2)(CN)(2)](2), was prepared, as well as the coordination polymer, [Ni(en)(2)(AuBr(2)(CN)(2))][AuBr(2)(CN)(2)]·MeOH (en = ethylenediamine). The structure consists of layers of chains of Ni(en)(2)(AuBr(2)(CN)(2))(+) units and chains of unbound [AuBr(2)(CN)(2)](-) units formed via Br···Br interactions; a Δn = 0.131(3) was measured. The Δn values were related to the supramolecular structures in terms of the relative intermolecular alignment of Br-Au-Br and NC-Au-CN bonds. These measurements both demonstrate the utility of the Au-Br bonds in enhancing birefringence and show that the contribution of the M-CN units to the overall birefringence of cyanometallate coordinations polymers is non-negligible.

20860371

Effects of organic and conventional growth systems on the content of flavonoids in onions and phenolic acids in carrots and potatoes.

The demand for organic food products is steadily increasing partly due to the expected health benefits of organic food consumption. Polyphenols, such as flavonoids and phenolic acids, are a group of secondary plant metabolites with presumably beneficial health effects, and contents in plants are affected by, for example, plant nutrient availability, climate, pathogen infection, and pest attack. In the current study, onions, carrots, and potatoes were cultivated in two-year field trials in three different geographical prising one conventional and two organic agricultural systems. The contents of flavonoids and phenolic acids in plants were analyzed by pressurized liquid extraction and high-performance liquid chromatography-ultraviolet quantification. In onions and carrots, no statistically significant differences between growth systems were found for any of the analyzed polyphenols. On the basis of the present study carried out under well-controlled conditions, it cannot be concluded that organically grown onions, carrots, and potatoes generally have higher contents of health-promoting secondary metabolites parison with the conventionally cultivated ones.

20860370

Discovery of 1-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9-(quinolin-3-yl)benzo[h][1,6]naphthyridin-2(1H)-one as a highly potent, selective mammalian target of rapamycin (mTOR) inhibitor for the treatment of cancer.

The mTOR protein is a master regulator of cell growth and proliferation, and inhibitors of its kinase activity have the potential to e new class of anticancer drugs. Starting from quinoline 1, which was identified in a biochemical mTOR assay, we developed a tricyclic benzonaphthyridinone inhibitor 37 (Torin1), which inhibited phosphorylation of mTORC1 and mTORC2 substrates in cells at concentrations of 2 and 10 nM, respectively. Moreover, Torin1 exhibits 1000-fold selectivity for mTOR over PI3K (EC(50) = 1800 nM) and exhibits 100-fold binding selectivity relative to 450 other protein kinases. Torin1 was efficacious at a dose of 20 mg/kg in a U87MG xenograft model and demonstrated good pharmacodynamic inhibition of downstream effectors of mTOR in tumor and peripheral tissues. These results demonstrate that Torin1 is a useful probe of mTOR-dependent phenomena and that benzonaphthridinones represent a promising scaffold for the further development of mTOR-specific inhibitors with the potential for clinical utility.

20860372

Facile access to tetravalent cerium compounds: one-electron oxidation using iodine(III) reagents.

Readily accessible and easy-to-use phenyliodine(III) dichloride, PhICl(2), has been established as an innovative and superior reagent for the one-electron oxidation of prising amide, amidinate, and cyclopentadienyl derivatives. Its use allowed the successful synthesis and structural characterization of the first members of three new classes of chloro-functionalized pounds, including the long sought-after Cp(3)CeCl.

20860373

High resolution measurement of methyl 13C(m)-13C and 1H(m)-13C(m) residual dipolar couplings in large proteins.

NMR methodology is developed for high-resolution, accurate measurements of methyl (1)H(m)-(13)C(m) ((1)D(CH)) and (13)C(m)-(13)C ((1)D(CC)) residual dipolar couplings (RDCs) in ILV-methyl-protonated high-molecular-weight proteins. Both types of RDCs are measured in a three-dimensional (3D) mode that allows dispersion of correlations to the third ((13)C(β/γ)) dimension, alleviating the problem of overlap of methyl resonances in plex and methyl-abundant protein structures. The methodology is applied to selectively ILV-protonated 82-kDa monomeric enzyme malate synthase G (MSG) that contains 273 ILV methyl groups with substantial overlap of methyl resonances in 2D methyl (1)H-(13)C correlation maps. A good agreement is observed between the measured RDCs of both types and those calculated from the crystallographic coordinates of MSG for the residues with low-amplitude internal dynamics. Although the measurement of (1)D(CH) RDCs from the acquisition dimension of NMR spectra imposes certain limitations on the accuracy of obtained (1)D(CH) values, (1)D(CH) couplings can be approximately corrected for cross-correlated relaxation effects. The ratios of (1)D(CH) and (1)D(CC) couplings ((1)D(CH)/(1)D(CC)) are independent of methyl axis dynamics and the details of residual alignment [Ottiger, M.; Bax, A. J. Am. Chem. Soc. 1999, 121, 4690.]. The (1)D(CH)/(1)D(CC) ratios obtained in MSG can therefore validate the employed correction scheme.

20860374

Synthesis of graphene aerogel with high electrical conductivity.

We report the synthesis of ultra-low-density three-dimensional macroassemblies of graphene sheets that exhibit high electrical conductivities and large internal surface areas. These materials are prepared as monolithic solids from suspensions of single-layer graphene oxide in which organic sol-gel chemistry is used to cross-link the individual sheets. The resulting gels are supercritically dried and then thermally reduced to yield graphene aerogels with densities approaching 10 mg/cm(3). In contrast to methods that utilize physical cross-links between GO, this approach provides covalent carbon bonding between the graphene sheets. These graphene aerogels exhibit an improvement in bulk electrical conductivity of more than 2 orders of magnitude (∼1 × 10(2) pared to graphene assemblies with physical cross-links alone (∼5 × 10(-1) S/m). The graphene aerogels also possess large surface areas (584 m(2)/g) and pore volumes (2.96 cm(3)/g), making these materials viable candidates for use in energy storage, catalysis, and sensing applications.

20860376

Long-term simulation of human exposure to atmospheric perfluorooctanoic acid (PFOA) and perfluorooctanoate (PFO) in the Osaka urban area, Japan.

A publicly available atmospheric transport model, the Weather Research and Forecasting Chemistry Model ( ), was used to simulate atmospheric perfluorooctanoic acid (PFOA) and perfluorooctanoate (PFO) emitted from a point source in the Osaka urban area (also known as Keihanshin), Japan. The time period of the simulation was from 1983 to 2008. The modeled air concentrations were highly correlated (r = 0.91) with the observed air concentrations. Intake levels by inhalation of simulated air concentrations and through the gastrointestinal tract as estimated by the food duplicate method were input to a pharmacokinetic model of the human body to simulate serum concentrations of PFOA and PFO (PFO(A)). For validation of the atmospheric model, simulated values pared with those observed in serum samples. The simulated values generally agreed with those observed in serum samples from residents of the Keihanshin area (r = 0.93). It was confirmed that the atmospheric model was generally capable of projecting features of atmospheric PFO(A) as well as serum concentrations of PFO(A) in this case. The results indicated a dominant contribution of the ponent to serum PFO(A) in humans near the point source in the Keihanshin area. In 2008, that contribution was about 70%.

20860377

Amino acids at water-vapor interfaces: surface activity and orientational ordering.

The surface activity and orientational ordering of amino acids at water-vapor interfaces were studied with molecular dynamics simulations bination with thermodynamic integration and umbrella sampling. Asparagine, representing amino acids with polar side chains, displays no surface activity. Tryptophan, in contrast, with its hydrophobic indole ring as side chain unveils a free energy minimum at the water-vapor interface, which lies 6 kJ/mol under the hydration free energy. To study the orientational ordering of tryptophan along the interface, the order parameter was calculated. At the free energy minimum and at the Gibbs dividing surface, the order parameter reveals a parallel alignment of the indole ring with the water surface exposing the π-system to electrophiles in the hydrophobic phase and indicating polarization dependent spectroscopy. In the vicinity of this position a perpendicular orientation is obtained. The surface excess, calculated from the potential of mean force along the interface, is in excellent agreement with experimental measurements.

20860375

Photocleavable peptide-conjugated magnetic beads for protein kinase assays by MALDI-TOF MS.

Peptides were immobilized onto superparamagnetic beads via photocleavable linkers. This enabled simple, rapid, and label-free protein kinase assays via MALDI-TOF MS detection of substrate peptide phosphorylation. Abltide, a model substrate for the Abl protein tyrosine kinase model, was coupled onto amine-terminated beads, incubated with ATP and binant c-Abl kinase, and released and further detected to determine phosphorylation. Abltide phosphorylation was found to depend significantly on the length position of linkers to the bead surface. Inserting a diblock spacer of poly(glycine) and poly(ethylene glycol) segments markedly enhanced phosphorylation. To validate the assay, the activity of two small-molecule kinase inhibitors, imatinib and dasatinib, which target the oncogenic mutant tyrosine kinase Bcr-Abl to treat chronic myeloid leukemia (CML), was tested. Examining inhibition of the purified c-Abl or Bcr-Abl in K562 CML cell extracts, IC(50) values were determined to be consistent with the literature. This simple, label-free, MALDI-based protein kinase assay can be readily adapted to allow multiplexed assays of multiple peptide substrates and/or analysis of alternative post-translational modifications as a tool for drug discovery and clinical testing.

20860378

Proteome analysis of multiple compartments in a mouse model of chemical-induced asthma.

Occupational asthma is the principal cause of work-related respiratory disease in the industrial world. Toluene-2,4-diisocyanate (TDI) is one of the mon respiratory sensitizers leading to occupational asthma. Using a mouse model of chemical-induced asthma, we explored proteome changes in partments of mice sensitized and challenged with TDI or acetone-olive oil (AOO; vehicle). Airway reactivity to methacholine and a bronchoalveolar lavage (BAL) cell count was assessed in treated and control mice, 1 day after challenge. Subsequently, two-dimensional differential gel electrophoresis (2D-DIGE) was performed on auricular lymph nodes, BAL, and paring TDI-treated and vehicle-treated control mice. The differentially expressed proteins were identified by mass spectrometry and pathway analysis was performed. TDI-treated mice exhibit increased airway reactivity (2.6-fold increase) and a neutrophilic inflammation in the BAL pared to control mice. 2D-DIGE showed 53, 210, and 40 differentially expressed proteins in the auricular lymph nodes, BAL, and serum of TDI-treated versus vehicle-treated mice, respectively. Several of the identified proteins could be linked with inflammation, neutrophil chemotaxis, and/or oxidative stress. Physiologic and immunologic readouts of the asthmatic phenotype, such as inflammation, were confirmed in partments by several of the differentially expressed proteins via 2D-DIGE puterized pathway analysis.

20860379

Atomistic simulation of water percolation and proton hopping in Nafion fuel cell membrane.

We have performed a detailed analysis of water clustering and percolation in hydrated Nafion configurations generated by classical molecular dynamics simulations. Our results show that at low hydration levels H(2)O molecules are isolated and a continuous hydrogen-bonded network forms as the hydration level is increased. Our quantitative analysis has established a hydration level (λ) between 5 and 6 H(2)O/SO(3)(-) as the percolation threshold of Nafion. We have also examined the effect of such a network on proton transport by studying the structural diffusion of protons using the quantum hopping molecular dynamics method. The mean residence time of the proton on a water molecule decreases by 2 orders of magnitude when the λ value is increased from 5 to 15. The proton diffusion coefficient in Nafion at a λ value of 15 is about 1.1 × 10(-5) cm(2)/s in agreement with experiment. The results provide quantitative atomic-level evidence of water network percolation in Nafion and its effect on proton conductivity.

20860380

Dynamic hybrid life cycle assessment of energy and carbon of multicrystalline silicon photovoltaic systems.

This paper advances the life cycle assessment (LCA) of photovoltaic systems by expanding the boundary of the included processes using hybrid LCA and accounting for the technology-driven dynamics of embodied energy and carbon emissions. Hybrid LCA is an extended method bines bottom-up process-sum and top-down economic input-output (EIO) methods. In 2007, the embodied energy was 4354 MJ/m(2) and the energy payback time (EPBT) was 2.2 years for a multicrystalline silicon PV system under 1700 kWh/m(2)/yr of solar radiation. These results are higher than those of process-sum LCA by approximately 60%, indicating that processes excluded in process-sum LCA, such as transportation, are significant. Even though PV is a low-carbon technology, the difference between hybrid and process-sum results for 10% penetration of PV in the U.S. electrical grid is 0.13% of total current grid emissions. Extending LCA from the process-sum to hybrid analysis makes a significant difference. Dynamics are characterized through a retrospective analysis and future outlook for PV manufacturing from 2001 to 2011. During this decade, the embodied carbon fell substantially, from 60 g CO(2)/kWh in 2001 to 21 g/kWh in 2011, indicating that technological progress is realizing reductions in embodied environmental impacts as well as lower module price.

20860381

Novel pyridylmethylamines as highly selective 5-HT(1A) superagonists.

To further improve the maximal serotonergic efficacy and better understand the configurational requirements for 5-HT(1A) binding and activation, we generated and biologically investigated structural variants of the lead structure befiradol. For a bioisosteric replacement of the 3-chloro-4-fluoro moiety, a focused library of pounds by solution phase parallel synthesis was developed. Target binding of pound collection was investigated, and their affinities for 5-HT(2), α(1), and α(2)-adrenergic as well as D(1)-D(4) dopamine receptors pared. For particularly interesting pounds, intrinsic activities at 5-HT(1A) were examined in vitro employing a GTPγS assay. The investigation guided us to highly selective 5HT(1A) superagonists. The benzothiophene-3-carboxamide 8bt revealed almost exclusive 5HT(1A) recognition with a K(i) value of 2.7 nM and a maximal efficacy of 124%. To get insights into the bioactive conformation of pound collection, we synthesized conformationally constrained bicyclic scaffolds when SAR data indicated a chair-type geometry and an equatorially dispositioned aminomethyl substituent for the 4,4-disubstituted piperidine moiety.

20860383

The thermosalient phenomenon. "Jumping crystals" and crystal chemistry of the anticholinergic agent oxitropium bromide.

The anticholinergic agent oxitropium bromide possesses rich crystal chemistry, most remarkably exhibiting a strong thermosalient effect ("jumping crystal" effect), a mechanical property with potential applications in organic-based actuators. The thermosalient effect, manifested in forceful jumps of up to several centimeters, was investigated by bination of structural, microscopic, spectroscopic, and thermoanalytical techniques, providing data on which to base a proposed mechanism for the phenomenon. Direct observation of the effect in a single crystal and structure determination of both phases revealed that the jumping of the crystals is a macroscopic manifestation of a highly anisotropic change in the cell volume. The cell distortion is panied by a conformational change of the oxitropium cation, which triggers increased separation between the ion pairs in the lattice at nearly identical separation between the cation and the anion within each ion pair. At the molecular level, the cation acts as a molecular posed of two rigid parts (epoxy-aza-tricyclic-nonyl portion and phenyl ring) that are bridged by a flexible ester linkage. The structure of the rigid, inert aza-tricyclic portion remains practically unaffected by the temperature, suggesting a mechanism in which the large, thermally accumulated strain is transferred over the ester bridge to the phenyl ring, which rotates to trigger the phase transition. Mechanistic details of the higher temperature solid-state phenomena are also presented. The high-temperature phase can also be obtained by grinding or UV irradiation of the room-temperature phase. In addition, if it is irradiated with UV light in the presence of KBr, the high-temperature phase undergoes intramolecular photochemical rearrangement. Heating the high-temperature phase to slightly below the melting temperature results in an additional solid-state reaction that results in the conversion of the salt to a mixture of pounds.

20860382

Crystals in which some metal atoms are more equal than others: inequalities from crystal packing and their spectroscopic/magnetic consequences.

Crystal structures of the pounds CrCrFe(dpa)(4)Cl(2) (1), CrCrMn(dpa)(4)Cl(2) (2), and MoMoMn(dpa)(4)Cl(2) (3) (dpa = 2,2'-dipyridylamide) show disorder in the metal atom positions such that the linear M(A)[quadruple bond]M(A)···M(B) array for a given molecule in the crystal is oriented in one of two opposing directions. Despite the fact that the direct coordination sphere of the metals in the two crystallographically independent orientations is identical, subtle differences in some metal-ligand bond distances are observed in 1 and 3 due to differences in the orientation of a solvent molecule of crystallization. The Fe(II) and Mn(II) ions serve as sensitive local spectroscopic probes that have been interrogated by Mössbauer spectroscopy and high-field EPR spectroscopy, respectively. The subtle differences in the two independent Fe and Mn sites in 1 and 3 unexpectedly give rise to unusually large differences in the measured Fe quadrupole splitting (ΔE(Q)) in 1 and Mn zero-field splitting (D) in 3. Variable-temperature/single-crystal EPR spectroscopy has allowed us to determine that the temperature-dependent D tensors in 3 are oriented along the metal-metal axis and that they show significantly different dynamic behavior with temperature. The differences in ΔE(Q) and D are reproduced by density functional calculations on truncated models for 1 and 3 that lack the quadruply bonded M(A)[quadruple bond]M(A) groups, though the magnitude of the calculated effect is not as large as that observed experimentally. We suggest that the large observed differences in ΔE(Q) and D for the individual sites could be due to the influence of the strong diamagnetic anisotropy of the quadruply bonded M[quadruple bond]M unit.

20860384

Boronic acid porphyrin receptor for ginsenoside sensing.

Ginsenoside detection was pursued through the design of a porphyrin receptor containing two boronic acid units. This receptor was found to undergo different degrees of fluorescence quenching with five ginsenoside guests and an acylated derivative. The trends in the 1:1 binding constants, as well as ESI-HRMS analysis, support a binding mode in which the ginsenoside sugar units are bound to the boronic acid groups, while the steroid core and porphyrin ring participate in hydrophobic interactions.

20860385

High-pressure dielectric investigations of nanocolloidal Aerosil-nematic liquid crystal composites.

We report the effect of applied pressure on the dielectric properties posites of a nematic liquid crystal with hydrophilic Aerosil particles. The study, which is the first of its kind on the nanocolloidal Aerosil systems, also has the novelty that a weakly polar nematogen is used as the host material. In conjunction with differential scanning calorimetric data, these measurements show that not only T(N-Iso), the nematic-isotropic transition at room pressure, but several other parameters exhibit a nonmonotonic variation with increasing Aerosil concentration. The dependence of the relaxation frequency of the mode connected with the reorientations of the molecules around their short axis is probed along isobaric as well as isothermal paths, and the determined activation parameters are discussed in terms of the chemical structure of the host molecule. The temperature dependence of the relaxation frequency at atmospheric pressure, exhibiting non-Arrhenius behavior, has been analyzed using the Vogel-Fulcher-Tamann expression, yielding information regarding the influence of the Aerosil concentration on the fragility strength as well as the glass transition temperature. The calorimetric data is also discussed in terms of the concept of a crossover from the random-dilution to the random-field limits.

20860386

Length scales and dynamics in the reorientational relaxation of tracers in molecular and polymeric glass formers via electron spin resonance spectroscopy.

It is widely accepted that a temperature region exists above the glass transition temperature, playing a fundamental role in the physics of polymers and glass formers. In this region, several dynamic crossovers have been experimentally and numerically revealed in the past years and the onset of glassy behavior is generally located, because of cooperative and heterogeneous features exhibited by the dynamics. In this Article, the rotational dynamics of two different stiff molecular spin probes dissolved in poly(propylene glycol) has been investigated by electron spin resonance spectroscopy in a wide temperature range. Decoupling phenomena between macroscopic and microscopic transport properties have been observed in the crossover region. parison with previous studies carried out with the same tracers dissolved in different polymers and glass formers strongly supports the idea that the observed crossover signals the onset of spatial correlations of dynamics on the length scale probed by the tracers.

20860387

Toward a prediction of the redox properties of electroactive SAMs: a free energy calculation by molecular simulation.

We report free energy calculations of FcC(6)S-/C(4)S-Au and FcC(6)S-/C(12)S-Au binary self-assembled monolayers (SAMs) formed by one ferrocenylhexanethiolate chain and alkylthiolate chains. We demonstrate that the free energy perturbation methods are able to reproduce the positive shift of the redox potential when the coadsorbed butanethiolate C(4)S chains are replaced by dodecanethiolate C(12)S chains. The different contributions to the Ewald summation involved in the perturbation process are thoroughly described. plete the study by a microscopic description of the binary SAMs before and after oxidation. The molecular dynamics (MD) simulations evidence that the formation of the ion-pair between the ferricinium and a single perchlorate anion of the supporting electrolyte is more favored in FcC(6)S-/C(12)S-Au SAM.

20860388

Simulations of a protein crystal with a high resolution X-ray structure: evaluation of force fields and water models.

We use classical molecular dynamics and binations of force fields and water models to simulate a protein crystal observed by room-temperature X-ray diffraction. The high resolution of the diffraction data (0.96 Å) and the simplicity of the crystallization solution (nearly pure water) make it possible to attribute any inconsistencies between the crystal structure and our simulations to artifacts of the models rather than inadequate representation of the crystal environment or uncertainty in the experiment. All simulations were extended for 100 ns of production dynamics, permitting some long-time scale artifacts of each model to emerge. The most noticeable effect of these artifacts is a model-dependent drift in the unit cell dimensions, which can e as large as 5% in certain force fields; the underlying cause is the replacement of native crystallographic contacts with non-native ones, which can occur with heterogeneity (loss of crystallographic symmetry) in simulations with some force fields. We find that the AMBER FF99SB force field maintains a lattice structure nearest that seen in the X-ray data, and produces the most realistic atomic fluctuations parison to crystallographic B-factors) of all the models tested. We find that the choice of water model has a minor effect parison to the choice of protein model. We also identify a number of artifacts that occur throughout all of the simulations: excessive formation of hydrogen bonds or salt bridges between polar groups and loss of hydrophobic interactions. This study is intended as a foundation for future work that will identify individual parameters in each molecular model that can be modified to improve their representations of protein structure and thermodynamics.

20860389

Cationic alkylaluminum-complexed zirconocene hydrides as participants in olefin polymerization catalysis.

The plexed zirconocene trihydride cation [(SBI)Zr(μ-H)(3)(Al(i)Bu(2))(2)](+), which is obtained by reaction of (SBI)ZrCl(2) with [Ph(3)C][B(C(6)F(5))(4)] and excess HAl(i)Bu(2) in toluene solution, catalyzes the formation of isotactic polypropene when exposed to propene at -30 °C. This cation remains the sole observable species in catalyst systems free of pounds. In the presence of AlMe(3), however, exposure to propene causes the trihydride cation to pletely converted, under concurrent consumption of all hydride species by propene hydroalumination, to the doubly Me-bridged cation [(SBI)Zr(μ-Me)(2)AlMe(2)](+). The latter then es the resting state for further propene polymerization, which produces, by chain transfer to Al, mainly AlMe(2)-capped isotactic polypropene.

20860390

Characterization of plant exudates by principal-component and cluster analyses with nuclear magnetic resonance variables.

ponent and cluster analyses have been applied to nuclear magnetic resonance data for exudates derived from both conifers and angiosperms in order to classify these materials on the basis of molecular structure. The method succeeds in distinguishing resins produced by the conifer families Araucariaceae, Cupressaceae, and Pinaceae from each other and from resins produced by the angiosperm family Fabaceae. Other exudate types, including gums, gum resins, and kinos, also are distinguished from each other and from the resins.

20860391

Isolation and characterization of diastereomers of discorhabdins H and K and assignment of absolute configuration to discorhabdins D, N, Q, S, T, and U.

Investigations of four different sponge populations of Latrunculia species collected in New Zealand waters has led to the characterization of a new diastereomer of discorhabdin H, named discorhabdin H2, confirmation of the structure of discorhabdin K ((+)-7), and presentation of a new diastereomer, discorhabdin K2 ((-)-8). In each case the structures were established by extensive NMR and MS studies and the absolute configurations interrogated by electronic circular dichroism (ECD). Absolute configurations were assigned to the known metabolites discorhabdins H, D, 2-hydroxy-D, N, and Q parison of ECD spectra with those recorded for discorhabdin alkaloids of defined absolute configuration, while the configurations of discorhabdins S, T, and U were assigned by semisynthesis from (+)-(6S,8S)-discorhabdin B.

20860392

Chemical interactions of surface-active agents with growing resorcinol-formaldehyde gels.

The influence of cationic, anionic, and nonionic surfactants (S) on the characteristics of carbon xerogels was analyzed. The polymerization of resorcinol (R) and formaldehyde (F) was developed in an aqueous solution of S without any additional catalyst. The gels obtained were dried in air to obtain organic xerogels and then carbonized to carbon xerogels. The prepared samples were characterized by FTIR, TG, SEM, and N(2) and CO(2) adsorption. The formation of RF-S copolymers was observed for cationic and nonionic surfactants, but this was not observed for anionic S, probably because of repulsive electrostatic interactions between the two organic phases. Nevertheless, anionic S leads to a greater morphological transformation with the formation of nonporous needle particles associated with the higher pH induced by this S. Carbon xerogels are microporous materials with interesting molecular sieve behavior. The posites undergo greater shrinkage than do the pure RF xerogel; consequently, a narrower microporosity is obtained.

20860393

Palladium-catalyzed amination of unprotected halo-7-azaindoles.

Simple and efficient procedures for the Pd-catalyzed cross-coupling of primary and secondary amines with halo-7-azaindoles(pyrrolo[2,3-b]pyridine) are presented. Previously, no general method was available to ensure the highly selective reaction of the heteroaryl halide in the presence of the unprotected azaindole N-H. Using palladium precatalysts recently reported by our group, such reactions are easily plished under mild conditions that can be applied to cross-coupling reactions with a wide array of aliphatic and aromatic amines.

20860394

A five-step synthesis of (S)-macrostomine from (S)-nicotine.

A concise synthesis of (S)-macrostomine has been plished in five steps from natural nicotine in 19% overall yield via a pyridyne Diels-Alder cycloaddition reaction as the key step. A Kumada cross-coupling reaction on a 1-chloroisoquinoline intermediate provided the natural product.

20860395

Cleavage and reorganization of Zr-C/Si-C bonds leading to Zr/Si-N organometallic and heterocyclic compounds.

The t-BuCN-stabilized plexes 2 are generated in situ in high yields from the Si-tethered diynes, Cp(2)Zr(II) species, and 2 equiv of t-BuCN via a coordination-induced Zr-C/Si-C bond cleavage and reorganization. Complexes 2 have been demonstrated to be synthetically very useful. A variety of novel Zr/Si pounds and Si/N pounds, such as azasilacyclopentadienes, azasilacyclohexadienes, and allenylazazirconacycles, are obtained in high yields plexes 2 are treated with ketones, carbodiimides, alkynes, elemental sulfur (S(8)), acid chlorides, or nitriles. In this chemistry, t-BuCN behaves as both an initiator and a brake/release handle to initiate and control the reaction process.

20860396

Supramolecular chirality in organogels: a detailed spectroscopic, morphological, and rheological investigation of gels (and xerogels) derived from alkyl pyrenyl urethanes.

This Article addresses the formation of chiral supramolecular structures in the organogels derived from chiral organogelator 1R (or 2R), and its mixtures with its enantiomer (1S) and achiral analogue 3 by extensive circular dichroism (CD) spectroscopic measurements. Morphological analysis by atomic force microscopy (AFM) and scanning electron microscopy (SEM) plemented by the measurements of their bulk properties by thermal stability and rheological studies. Specific molecular recognition events (1/3 vs 2/3) and solvent effects (isooctane vs dodecane) were found to be critical in the formation of chiral aggregates. Theoretical studies were also carried out to understand the interactions responsible for the formation of the superstructures.

20860398

How micropatterns and air pressure affect splashing on surfaces.

We experimentally investigate the splashing mechanism of a millimeter-sized ethanol drop impinging on a structured solid posed of micropillars, through side-view and top-view high-speed imaging. By increasing the impact velocity, we can tune the impact e from a gentle deposition to a violent splash, at which tiny droplets are emitted as the liquid sheet spreads laterally. We measure the splashing threshold for different micropatterns and find that the arrangement of the pillars significantly affects the splashing e. In particular, directional splashing in the direction in which air flows through the pattern is possible. Our top-view observations of impact dynamics reveal that entrapped air is responsible for the splashing. Indeed, by lowering the pressure of the surrounding air we show that we can suppress the splashing in the explored parameter regime.

20860397

Cellular response of polyvalent oligonucleotide-gold nanoparticle conjugates.

Nanoparticles are finding utility in myriad biotechnological applications, including gene regulation, intracellular imaging, and medical diagnostics. Thus, evaluating the patibility of these nanomaterials is imperative. Here we use genome-wide expression profiling to study the biological response of HeLa cells to gold nanoparticles functionalized with nucleic acids. Our study finds that the biological response to gold nanoparticles stabilized by weakly bound surface ligands is significant (cells recognize and react to the presence of the particles), yet when these same nanoparticles are stably functionalized with covalently attached nucleic acids, the cell shows no measurable response. This finding is important for researchers studying and using nanomaterials in biological settings, as it demonstrates how slight changes in surface chemistry and particle stability can lead to significant differences in cellular responses.

20860399

Computer simulation of argon adsorption on graphite surface from subcritical to supercritical conditions: the behavior of differential and integral molar enthalpies of adsorption.

We investigate in detail puter simulation of argon adsorption on a graphite surface over a very wide range of temperature, from below the triple point to well above the critical point. Adsorption over such a wide temperature range has not been reported previously in the form of adsorption isotherms and enthalpy change during adsorption. The adsorption isotherms can be classified broadly into four categories: below the triple point, the isotherms show stepwise character (a strict layering mechanism) with 2D condensation; type II (according to the IUPAC classification) is followed by isotherms at temperatures above the triple point and below the critical point and a sharp spike is seen for isotherms in the neighborhood of the critical point; and finally the typical behavior of a maximum is observed for isotherms above the critical point. For the isosteric heat, the heat curve (plotted against loading) remains finite for subcritical conditions but is infinite (singularity) at the maximum in excess loading for supercritical adsorption. For the latter case, a better representation of the energy change is the use of the integral molecular enthalpy because this does not exhibit a singularity as in the case of isosteric heat. pare the differential and integral molecular enthalpies for the subcritical and supercritical adsorptions.

20860400

Reactive dynamics in micelles: auramine O in solution and adsorbed on regular micelles.

The role of confinement in the suppression of the excited-state reaction of the dye molecule auramine O in nanoscale water droplets is investigated by contrasting the behavior of the dye in solution and on regular and reverse micelles. Auramine O photophysics are studied in bulk water, at the interface between regular micelles and bulk water, and in the aerosol OT (AOT)-stabilized aqueous nanodroplet. It is shown that the reaction of auramine O in bulk water is to a first approximation determined by aqueous solvation dynamics rather than solvent viscosity. This is in contrast to the result in more viscous and slowly relaxing solvents, where the solvent viscosity controls the rate. This result suggests the possibility of multiple reaction pathways on the excited-state surface. The reaction rate at the regular micelle-water interface is slower than in bulk water but significantly faster than in nanoconfined water, indicating a distinct effect of confinement on the reaction rate. It is suggested that the degree of perturbation of the water structure at the interface is the factor controlling the rate of the reaction. Specifically, the water structure is strongly perturbed at the AOT-confined water interface, suppressing the ability of fast collective solvent reorientation to promote the auramine O excited-state reaction. This effect is less marked at the interface between the micelle and bulk water. The contrast between these results indicates a route whereby confinement modifies ultrafast reaction dynamics in micelles.

20860401

Metallic nanoshells with semiconductor cores: optical characteristics modified by core medium properties.

It is well-known that the geometry of a nanoshell controls the resonance frequencies of its plasmon modes; however, the properties of the core material also strongly influence its optical properties. Here we report the synthesis of Au nanoshells with semiconductor cores of cuprous oxide and examine their optical characteristics. This material system allows us to systematically examine the role of core material on nanoshell optical paring Cu(2)O core nanoshells (ε(c) ∼ 7) to lower core dielectric constant SiO(2) core nanoshells (ε(c) = 2) and higher dielectric constant mixed valency iron oxide nanoshells (ε(c) = 12). Increasing the core dielectric constant increases nanoparticle absorption efficiency, reduces plasmon line width, and modifies plasmon energies. Modifying the core medium provides an additional means of tailoring both the near- and far-field optical properties in this unique nanoparticle system.

20860402

Self-assembled enzyme capsules in ionic liquid [BMIM][BF4] as templating nanoreactors for hollow silica nanocontainers.

Most of the self-assembly studies have hitherto explored the aqueous media as fluid phase for self-assembly of amphiphilic biomacromolecules, wherein architectural modification of biomolecules is generally a prerequisite for self-assembly of modified biomolecules. We demonstrate for the first time that ionic liquids can act as nonaqueous designer solvents to self-assemble amphiphilic biomacromolecules without requiring their prior modification. To this end, we show that enzyme (phytase) molecules self-assembled in the presence of an appropriate ionic liquid, resulting in the formation of enzyme capsules. Phytase capsules synthesized using this approach were further used as templating nanoreactors for the synthesis of enzyme-containing hollow silica nanocontainers. In situ immobilized phytase enzyme in the silica nanocontainers, when subjected to enzyme-reusability application, establishes them as excellent reusable biocatalysts.

20860403

Efficient Pd-catalyzed amination reactions for heterocycle functionalization.

The Pd-catalyzed amination of unprotected benzo-fused heterocycles is reported, which allows for greater flexibility and efficiency in the modification of this important class of molecules. The generality of these simple and efficient procedures is demonstrated through the synthesis of a wide variety of structural types.

20860404

Stereocontrol of 5,5-spiroketals in the synthesis of cephalosporolide H epimers.

A blueprint for controlling the stereochemistry of oxygenated 5,5-spiroketals using chelation effects is provided. Chelation specifically of zinc salts (other protic and Lewis acids were less effective) between the spiroketal oxygen and an appropriately positioned alcohol group overrides normal biases in the preparation of 5,5-spiroketals, as illustrated by the stereocontrolled synthesis of epimeric cephalosporolide H isomers. This study provides new and valuable information for prescribing the chirality of the stereogenic core of 5,5-spiroketals.

20860405

Calculated nuclear magnetic resonance parameters for multiproton-exchange and nonbonded-hydrogen rotation processes in cyclic water clusters.

In this work we report, for the first time, calculations of nuclear magnetic resonance parameters for the processes of multiproton-exchange and nonbonded-proton rotations in small, cyclic water clusters. The simultaneous proton exchange induces a large decrease in the oxygen shielding constants in both clusters, with a mean value of -52.6 ppm for the water trimer and -50.1 ppm for the water tetramer. The (1(h))J(OH) coupling constant between an oxygen nucleus and exchanging proton decreases (in absolute value) along the path, changes sign, finally reaching a value of 5-7 Hz. The changes in the NMR parameters induced by the nonbonded proton rotations are smaller. The calculated dependencies of the intermolecular spin-spin coupling constants upon rotation reveal that the largest changes are expected for the couplings transmitted through the hydrogen bond between the rotating and neighboring molecule which acts as a proton donor. The symmetry-adapted perturbation theory (SAPT) interaction energy calculations for each dimer forming the water trimer have allowed us to relate a strength of interactions within pairs of water molecules with coupling constant values. The predicted maximal values of the interaction-energy terms (energetically unfavorable orientations of the constituent dimers) along paths correlate with the extremal values of the spin-spin coupling constants, which mostly correspond to the maximal couplings along pathways.

20860406

Complex surface concentration gradients by stenciled "electro click chemistry".

Complex one- or two-dimensional concentration gradients of alkynated molecules are produced on azidized conducting polymer substrates by stenciled "electro click chemistry". The latter describes the local electrochemical generation of catalytically active Cu(I) required plete a "click reaction" between alkynes and azides at room temperature. A stencil on the counter electrode defines the shape and multiplicity of the gradient(s) on the conducting polymer substrate, while the specific reaction conditions control gradient steepness and the maximum concentration deposited. Biologically active ligands including cell binding peptides are patterned in gradients by this method without losing their biological function or the conductivity of the polymer.

20860407

Dioxin-like activity in Japanese indoor dusts evaluated by means of in vitro bioassay and instrumental analysis: brominated dibenzofurans are an important contributor.

In our previous study, we demonstrated that dioxin-like activity in sulfuric-acid-treated extracts of Japanese indoor dust was higher than the activity in contaminated sediments. In the current study, we used high-performance liquid chromatography (HPLC) fractionation bination with the dioxin-responsive chemical-activated luciferase gene expression (DR-CALUX) assay and gas chromatography-high-resolution mass spectrometry (GC-HRMS) to quantitatively evaluate pounds in indoor dusts. Selected four sulfuric-acid-treated extracts of indoor dusts were fractionated into seven fractions by means of HPLC with a nitrophenylpropylsilica column, and the activity in the first fraction of each extract was much higher than the activities in the other fractions. Therefore, each of the first fractions was further fractionated into 90 fractions by HPLC with an octadecylsilica column, and all the fractions were analyzed by means of the DR-CALUX assay. On the basis of elution characteristics, the pounds in the fractions showing high activity were determined to be polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), coplanar polychlorinated biphenyls (Co-PCBs), and polychlorinated naphthalenes (PCNs), or supposed to be polybrominated dibenzo-p-dioxins and dibenzofurans (PBDD/Fs). pounds in the 33 dusts extracts were quantified by means of GC-HRMS, and their median-based contributions of the theoretical CALUX-TEQs [2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-tetraCDD) equivalent] chemically calculated for PBDFs, PCDDs, PCDFs, non-ortho Co-PCBs, PCNs, and mono-ortho Co-PCBs to the experimental values (38-1400 pg/g, median 160 pg/g) were 17%, 14%, 8.8%, 0.98%, 0.10%, and 0.019%, respectively. Our results indicate that PBDFs, which are not internationally regulated dioxins, were important contributors to dioxin-like activity in Japanese dust and that further analysis of PBDFs in indoor dust is required so that the risk of exposure to pounds via dust can be assessed.

20860408

Myo1e binds anionic phospholipids with high affinity.

Myo1e is a single-headed motor protein that has been shown to play roles in clathrin-mediated endocytosis in HeLa cells and podocyte function in the kidney. The myo1e C-terminal tail domain includes a basic region that is required for localization to clathrin-coated vesicles and contains a putative pleckstrin-homology (PH) domain that has been shown to play a role in phospholipid binding in other myosin-I proteins. We used sedimentation assays, stopped-flow fluorescence, and fluorescence microscopy to determine the membrane binding affinities, kinetics, and in vivo localization of fluorescently labeled binant myo1e-tail constructs. We found that the myo1e tail binds tightly to large unilamellar vesicles (LUVs) containing physiological concentrations of the anionic phospholipids phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P(2)) or phosphatidylserine. The rate of myo1e attachment to LUVs nears the diffusion limit while the calculated rate of detachment from LUVs is slow (k(diss) ≤ 0.4 s(-1)). Mutation of conserved residues in the myo1e PH domain has little effect on lipid binding in vitro or membrane localization in vivo. Soluble inositol phosphate headgroups, such as inositol 1,4,5-trisphosphate, pete with PtdIns(4,5)P(2) for binding, but the apparent affinity for the soluble inositol phosphate is substantially lower than that for PtdIns(4,5)P(2). These results suggest that myo1e binds lipids through nonspecific electrostatic interactions rather than a stereospecific protein-phosphoinositide interaction.

20860409

Molecular studies of model surfaces of metals from single crystals to nanoparticles under catalytic reaction conditions. Evolution from prenatal and postmortem studies of catalysts.

Molecular level studies of metal crystal and nanoparticle surfaces under catalytic reaction conditions at ambient pressures during turnover were made possible by the use of instruments developed at the University of California at Berkeley. Sum frequency generation vibrational spectroscopy (SFGVS), owing to its surface specificity and sensitivity, is able to identify the vibrational features of adsorbed monolayers of molecules. We identified reaction intermediates, different from reactants and products, under reaction conditions and for multipath reactions on metal single crystals and nanoparticles of varying size and shape. The high-pressure scanning tunneling microscope (HP-STM) revealed the dynamics of a catalytically active metallic surface by detecting the mobility of the adsorbed species during catalytic turnover. It also demonstrated the reversible and adsorbate-driven surface restructuring of platinum when exposed to molecules such as CO and ethylene. Ambient pressure X-ray photoelectron spectroscopy (AP-XPS) detected the reversible changes of position in rhodium-palladium, platinum-palladium, and other bimetallic nanoparticles as the reactant atmosphere changed from oxidizing to reducing. It was found that metal nanoparticles of less than 2 nm in size are present in higher oxidation states, which alters and enhances their catalytic activity. The catalytic nanodiode (CND) confirmed that a catalytic reaction-induced current flow exists at oxide-metal interfaces, which correlates well with the reaction turnover.

20860411

Hess-Schaad group additivity type model predicts superaromaticity.

The classical Hess-Schaad reference state and group additivity (GA) model has been adapted to evaluate the resonance energies of several polycyclic aromatic hydrocarbons (PAHs). It was found that benzene is the least stable species in this series, and hence, claims that the concept of superaromaticity is dead are overestimated.

20860410

Long-range interaction networks in the function and fidelity of poliovirus RNA-dependent RNA polymerase studied by nuclear magnetic resonance.

The fidelity of the poliovirus RNA-dependent RNA polymerase (3D(pol)) plays a direct role in the genomic evolution and pathogenesis of the virus. A single site mutation (Gly64Ser) that is remote from the catalytic center results in a higher fidelity polymerase. NMR studies with [methyl-(13)C]methionine-labeled protein were used pare the solution structure and dynamics of wild-type and Gly64Ser 3D(pol). The chemical shifts for the Met6 resonance were significantly different between wild-type and Gly64Ser 3D(pol) when bound in plexes with RNA and incorrect, but not with correct, nucleotide, suggesting that the Gly64Ser mutation induces structural changes in the N-terminal β-strand when the enzyme is bound to incorrect but not correct nucleotide. We also observe changes in the transverse relaxation times for methionines near regions important for nucleotide and RNA binding and catalysis. Our strategy to assign the [methyl-(13)C]methionine resonances involved separately mutating each of the 17 methionines. Several substitutions produced additional resonances for both Met6 and Met187, a reporter for RNA binding, and conformational changes in the highly conserved motif B loop, even though these methionines are greater than 20 Å apart. The results for Gly64Ser and the other mutants are intriguing considering that they can result in structural and/or dynamic changes to methionines distant from the site of mutation. We propose that there is a long-distance network operating throughout 3D(pol) that coordinates ligand binding, conformational changes, and catalysis. Mutation of Gly64 results in structural and/or dynamic changes to the network that may affect polymerase fidelity.