bluuebunny/crossref_metadata_2025 huggingface dataset:
Receptor activity‐modifying protein‐dependent impairment of calcitonin receptor splice variant Δ(1–47)hCT(a) function
Authors: Qi T , Dong M , Watkins HA , Wootten D , Miller LJ , Hay DL
Published: September 2012

Background and Purpose

Alternative splicing expands proteome diversity to GPCRs. Distinct receptor variants have been identified for a secretin family GPCR, the calcitonin receptor (CTR). The possible functional contributions of these receptor variants are further altered by their potential interactions with receptor activity‐modifying proteins (RAMPs). One variant of the human CTR lacks the first 47 residues at its N terminus [Δ(1–47)hCT(a)]. However, very little is known about the pharmacology of this variant or its ability to interact with RAMPs to form amylin receptors.

Experimental Approach

Δ(1–47)hCT(a) was characterized both with and without RAMPs in Cos7 and/or HEK293S cells. The receptor expression (ELISA assays) and function (cAMP and pERK1/2 assays) for up to six agonists and two antagonists were determined.

Key Results

Despite lacking 47 residues at the N terminus, Δ(1–47)hCT(a) was still able to express at the cell surface, but displayed a generalized reduction in peptide potency. Δ(1–47)hCT(a) retained its ability to interact with RAMP1 and formed a functional amylin receptor; this also appeared to be the case with RAMP3. On the other hand, its interaction with RAMP2 and resultant amylin receptor was reduced to a greater extent.

Conclusions and Implications

Δ(1–47)hCT(a) acts as a functional receptor at the cell surface. It exhibits altered receptor function, depending on whether it associates with a RAMP and which RAMP it interacts with. Therefore, the presence of this variant in tissues will potentially contribute to altered peptide binding and signalling, depending on the RAMP distribution in tissues.
Hox gene expression in the harvestman Phalangium opilio reveals divergent patterning of the chelicerate opisthosoma
Authors: Sharma Prashant P. , Schwager Evelyn E. , Extavour Cassandra G. , Giribet Gonzalo
Published: September 2012

Among chelicerates, Hox gene expression has only been investigated in representatives of two arachnid orders to date: Acari (mites and ticks) and Araneae (spiders). Limited data are available for the “primitive” arachnid orders, such as Scorpiones (scorpions) and Opiliones (harvestmen). Here, we present the first data on Hox gene expression in the harvestman Phalangium opilio. Ten Hox genes of this species were obtained from a de novo assembled developmental transcriptome using the Illumina GAII platform. All 10 genes are expressed in characteristic Hox‐like expression patterns, and the expression of the anterior and central Hox genes is similar to those of other chelicerates. However, intriguingly, the three posteriormost genes—Ultrabithorax, abdominal‐A, and Abdominal‐B—share an identical anterior expression boundary in the second opisthosomal segment, and their expression domains extend through the opisthosoma to the posterior growth zone. The overlap in expression domains of the posterior Hox genes is correlated with the absence of opisthosomal organs posterior to the tubular tracheae, which occur on the second opisthosomal segment. Together with the staggered profile of posterior Hox genes in spiders, these data suggest the involvement of abdominal‐A and Abdominal‐B in the evolution of heteronomous patterning of the chelicerate opisthosoma, providing a mechanism that helps explain the morphological diversity of chelicerates.
Low‐frequency repetitive transcranial magnetic stimulation for the treatment of refractory partial epilepsy: A controlled clinical study
Authors: Sun Wei , Mao Wei , Meng Xianghong , Wang Dequan , Qiao Liang , Tao Wei , Li Liping , Jia Xiaoying , Han Chunyu , Fu Mengmeng , Tong Xiaoyan , Wu Xun , Wang Yuping
Published: September 2012

Purpose:  This study was designed to evaluate the therapeutic effect of low‐frequency repetitive transcranial magnetic stimulation (rTMS) on patients with refractory partial epilepsy.

Methods:  Sixty‐four patients with refractory focal epilepsy were screened and 60 patients were randomly divided into two groups by stimulation intensity: 90% (group 1) or 20% (group 2) of resting motor threshold (rMT). Seizure frequency and interictal EEG epileptic discharges were compared between the baseline and follow‐up periods.

Key Findings:  Seizures significantly decreased following 2‐weeks high intensity (90% rMT) rTMS treatment compared with baseline level (p < 0.05). rTMS also decreased interictal epilepsy discharges and improved the scales of Symptom Checklist‐90 significantly (p < 0.05). Seizures and spikes in the follow‐up period in the patients who received low intensity (20% rMT) rTMS did not show any difference compared with baseline data (p > 0.05, respectively).

Significance:  Low‐frequency high intensity rTMS (90% rMT) delivered into the epileptogenic zone had a significant antiepileptic effect on patients with refractory partial seizures. rTMS treatment can also reduce the interictal epileptic discharge frequency and improve the psychological condition of these patients.
War, the Presidency, and Legislative Voting Behavior
Authors: Howell William G. , Rogowski Jon C.
Published: September 2012

An extraordinary body of scholarship suggests that war, perhaps more than any other contributor, is responsible for the emergence of a distinctly modern presidency. Central to this argument is a belief that members of Congress predictably and reliably line up behind the president during times of war. Few scholars, however, have actually subjected this argument to quantitative investigation. This article does so. Estimating ideal points for members of Congress at the start and end of the most significant wars in the past century, we find consistent—albeit not uniform—evidence of a wartime effect. The outbreaks of both world wars and the post‐9/11 era—though not the Korean or Vietnam wars—coincided with discernible changes in member voting behavior that better reflected the ideological leanings of the presidents then in office. In the aftermath of all these wars, meanwhile, members shifted away from the sitting president’s ideological orientation. These findings are not confined to any single subset of policies, are robust to a wide variety of modeling specifications, and run contrary to scholarship that emphasizes ideological consistency in members’ voting behavior.
Unmarked Racializing Discourse, Facework, and Identity in Talk about Immigrants in Italy
Authors: Pagliai Valentina
Published: September 2012

Drawing from research on racial formation processes in discourse concerning immigrants to Italy, this article argues that when racializing discourses are introduced as unmarked in a conversation, the coparticipant is put in a position of having to readily agree or openly disagree—with the second option endangering face. Racializing discourses introduced as unmarked thus tend to obtain acquiescence from the coparticipant. At the same time, they work at constructing shared identities around racist and racializing stances, where the unmarking becomes indexical of such shared identities. Instead of seeing racism as a stable belief in the mind of the individual, my analysis suggests that we should consider it as something the person does in interaction. The requirements of conversational rules of engagement, the needs of face, the relationship among the interactants, as well as their moral view, influence the participants' response to racializing discourses in interaction, and whether they might coconstruct or oppose them. [racialization, markedness theory, facework, racism, immigration, Italy]
Facilitation by tussock‐forming species on seedling establishment collapses in an extreme drought year in a post‐mined Sphagnum peatland
Authors: Koyama Asuka , Tsuyuzaki Shiro
Published: September 2012

Questions

Does the facilitation of herbaceous species seedling establishment by tussock‐forming species collapse in an extreme drought year? Do different germination phenologies, between the seedling species, influence the variation in facilitation?

Location

A post‐mined Sphagnum peatland at Sarobetsu mire, Hokkaido, northern Japan.

Methods

The effects of tussock‐forming species, as potential facilitators, on seedling emergence and survival of five perennial herbs were examined during a 4‐yr seedling monitoring, which included an extreme drought. The general effects of tussocks on each seedling species during annual variations were simultaneously assessed using hierarchical Bayesian analysis. To examine the stress limiting seedling establishment, which was ameliorated by the tussocks, micro‐environments (i.e. light, temperature, water content and erosion) altered by morphological traits of the tussocks with litter cover were compared to those in open areas.

Results

In general, tussocks facilitated seedling establishment of all species through a positive effect on emergence and no effect on survival; however, the facilitative effect declined for several species in an extreme drought year. Peat erosion was the limiting stress on seedling establishment in normal years, however, peat water content also limited seedling establishment in a drought year. During the drought year, the positive effect of tussocks on seedling emergence for species that germinated before or during the drought was weakened for one species, and a negative effect on seedling survival emerged in another species. In contrast, species that germinated after the drought did not exhibit annual variation in the effects of tussocks on seedling emergence and survival.

Conclusions

Our results illustrate that collapse of facilitation arises under extremely severe conditions through addition of infrequently occurring stress (drought) on frequently occurring stress (peat erosion). Variation in seedling emergence and survival of the five study species in response to severe drought suggests that species‐specific traits must be considered when assessing how facilitation varies temporally. Further, these findings suggest that facilitation in temporally varying environments can drive plant community composition and dynamics.
Evaluation of flooded areas with satellite imagery using an objective hydrologic criterion
Authors: Varni Marcelo R. , Entraigas Ilda , Migueltorena Valeria , Comas Rocío
Published: September 2012

A method for computing flooded areas in relation to precedent climatic conditions in a plain area is evaluated. The studied area includes the most important production area for cattle breeding in Argentina; therefore, waterlogging periods create significant economic losses. In order to conduct this study, Landsat images that represent different hydrological conditions were used. The method is based on the frequency analysis of rainfall records of the 30, 60 and 120 days prior each image, thus obtaining a seasonally weighted mean frequency. In order to minimize biases of individual images, the images were combined linearly so as to obtain composed images with the desired antecedent precipitation frequency. Then, the flooded areas were associated with the frequency of the antecedent rainfall. Therefore, frequencies equal to or higher than 50% are associated with semi‐permanent or permanent lentic waterbodies. Consequently, lower frequencies are associated with waterlogged areas reaching 35% of flooded area for a 20% precipitation frequency.
Rage Against the Machine: The Case for System‐Level Emotions
Authors: Solak Nevin , Jost John T. , Sümer Nebi , Clore Gerald L.
Published: September 2012

Although psychologists have generally conceptualized emotions in light of individual‐ and group‐ level approaches, in the current paper we propose that there are also system‐level emotional events, including both system‐based emotions (experienced as a direct or indirect consequence of system‐level characteristics) and system‐targeted emotions (reflecting evaluations that support or oppose the overarching social system). We begin by discussing how emotions are embedded in the social system and what system‐level functions they serve. We draw on system justification theory to understand the reciprocal relations between emotional life and ideologies that justify or challenge social systems. We then focus on three empirical propositions concerning the dynamics of system‐level emotions: (I) System‐based emotions reflect one’s subjective as well as objective standing in the social order; (II) System‐based emotions reflect one’s subjective appraisal of the social order; and (III) System‐level emotions affect action tendencies and behaviors, including behaviors that promote system stability versus change. The investigation of system‐level emotions promises to deepen our scientific understanding of the motivational dynamics of social stability and social change and to uncover the affective dimension of system justification processes. Extending the social psychological analysis of emotions to include contextual features at the level of social systems builds a much‐needed bridge between emotion research in psychology and sociology.
Spinal arachnoiditis as a consequence of aneurysm‐related subarachnoid haemorrhage
Authors: van Heerden Jolandi , McAuliffe William
Published: September 2012

Only a few case reports currently exist regarding symptomatic spinal arachnoiditis following aneurysm‐related subarachnoid haemorrhage. We present three patients who developed symptomatic spinal arachnoiditis following spontaneous aneurysm rupture. Following initial aneurysm and subarachnoid haemorrhage management (including ventriculo‐peritoneal shunt placement), all three patients developed gradually worsening neurological abnormalities, and subsequent imaging demonstrated spinal arachnoiditis. Despite spinal decompression, all three patients experienced progressively worsening neurological decline.
Analysis of the impact of chest wall constraints on eligibility for a randomized trial of stereotactic body radiotherapy of peripheral stage I non‐small cell lung cancer
Authors: Siva Shankar , Shaw Mark , Chesson Brent , Gill Suki , Ball David
Published: September 2012

Introduction

Chest wall toxicities are recognized complications of stereotactic radiotherapy (SBRT) in non‐small cell lung cancer. To minimize toxicity, the Trans‐Tasman Radiation Oncology Group (TROG) 09.02 ‘CHISEL’ study protocol excluded patients with tumours within 1 cm of the chest wall. The purpose of this study is to evaluate the implication of chest wall proximity constraints on patient eligibility, toxicity and potential accrual.

Methods

Exclusion zones of 1 cm beyond the mediastinum and 2 cm beyond the bifurcation of the lobar bronchi were incorporated into the CHISEL credentialing CT dataset. Volumes of lung within which tumours varying from 1 cm to 5 cm in diameter may occupy and remain eligible for the CHISEL study were calculated. These volumes were compared to a hypothetical model in which the 1 cm chest wall proximity restriction was removed.

Results

The percentage of lung area in which a tumour mass can occupy and be suitable for CHISEL in the left and right lung were 54% and 60% respectively. Removing the constraint increased the percentage of available lung to 83% and 87% respectively. Considering a 2 cm spherical tumour, only 21% and 31% of tumours in the left and right lung would be eligible with the chest wall constraint, whilst 39% and 50% respectively would be eligible without the constraint.

Conclusions

The exclusion of tumours less than 1 cm to chest wall significantly reduces the proportion of patients eligible for the CHISEL protocol. A review of the literature pertaining to chest wall toxicity after stereotactic radiotherapy supports a change in chest wall exclusion criteria for the CHISEL study.
Assessment and improvement of radiation oncology trainee contouring ability utilizing consensus‐based penalty metrics
Authors: Hallock Abhirami , Bauman Glenn , Read Nancy , D'Souza David , Perera Francisco , Aivas Inge , Best Lara , Cao Jeffrey , Louie Alexander V. , Wiebe Ericka , Sexton Tracy , Gaede Stewart , Battista Jerry , Rodrigues George
Published: September 2012

Introduction

The objective of this study was to develop and assess the feasibility of utilizing consensus‐based penalty metrics for the purpose of critical structure and organ at risk (OAR) contouring quality assurance and improvement.

Methods

A Delphi study was conducted to obtain consensus on contouring penalty metrics to assess trainee‐generated OAR contours. Voxel‐based penalty metric equations were used to score regions of discordance between trainee and expert contour sets. The utility of these penalty metric scores for objective feedback on contouring quality was assessed by using cases prepared for weekly radiation oncology radiation oncology trainee treatment planning rounds.

Results

In two Delphi rounds, six radiation oncology specialists reached agreement on clinical importance/impact and organ radiosensitivity as the two primary criteria for the creation of the Critical Structure Inter‐comparison of Segmentation (CriSIS) penalty functions. Linear/quadratic penalty scoring functions (for over‐ and under‐contouring) with one of four levels of severity (none, low, moderate and high) were assigned for each of 20 OARs in order to generate a CriSIS score when new OAR contours are compared with reference/expert standards. Six cases (central nervous system, head and neck, gastrointestinal, genitourinary, gynaecological and thoracic) then were used to validate 18 OAR metrics through comparison of trainee and expert contour sets using the consensus derived CriSIS functions. For 14 OARs, there was an improvement in CriSIS score post‐educational intervention.

Conclusions

The use of consensus‐based contouring penalty metrics to provide quantitative information for contouring improvement is feasible.
Agency Costs, Mispricing, and Ownership Structure
Authors: Chernenko Sergey , Foley C. Fritz , Greenwood Robin
Published: September 2012

Standard theories of ownership assume insiders ultimately bear all agency costs and therefore act to minimize conflicts of interest. However, overvalued equity can offset these costs and induce listings associated with higher agency costs. We explore this possibility by examining a sample of public listings of Japanese subsidiaries. Subsidiaries in which the parent sells a larger stake and subsidiaries with greater scope for expropriation by the parent firm are more overpriced at listing, and minority shareholders fare poorly after listing as mispricing corrects. Parent firms often repurchase subsidiaries at large discounts to valuations at the time of listing and experience positive abnormal returns when repurchases are announced.
The Effects of Succession Choice Surrounding CEO Turnover Announcements: Evidence from Marathon Successions
Authors: Intintoli Vincent J.
Published: September 2012

This study examines marathon successions, which I define as top executive searches that are extended past the formal departure notice of the incumbent chief executive officer (CEO). Marathons should be used when search costs are high and when little time passes from when the incumbent steps down to when they leave the firm. Consistent with these predictions, marathons primarily follow surprise departures and forced turnovers. Marathons are also likely for firms operating in heterogeneous industries that face early tenure incumbent departures. These findings shed light on an increasingly prevalent form of succession and provide insight into the rationale and implications behind the announcement.
High-Throughput Sequencing Reveals the Incomplete, Short-Term Recovery of Infant Gut Microbiota following Parenteral Antibiotic Treatment with Ampicillin and Gentamicin
Authors: Fouhy Fiona , Guinane Caitriona M. , Hussey Seamus , Wall Rebecca , Ryan C. Anthony , Dempsey Eugene M. , Murphy Brendan , Ross R. Paul , Fitzgerald Gerald F. , Stanton Catherine , Cotter Paul D.
Published: September 2012

The infant gut microbiota undergoes dramatic changes during the first 2 years of life. The acquisition and development of this population can be influenced by numerous factors, and antibiotic treatment has been suggested as one of the most significant. Despite this, however, there have been relatively few studies which have investigated the short-term recovery of the infant gut microbiota following antibiotic treatment. The aim of this study was to use high-throughput sequencing (employing both 16S rRNA and
rpoB
-specific primers) and quantitative PCR to compare the gut microbiota of nine infants who underwent parenteral antibiotic treatment with ampicillin and gentamicin (within 48 h of birth), 4 and 8 weeks after the conclusion of treatment, relative to that of nine matched healthy controls. The investigation revealed that the gut microbiota of the antibiotic-treated infants had significantly higher proportions of
Proteobacteria
(
P
= 0.0049) and significantly lower proportions of
Actinobacteria
(
P
= 0.00001) (and the associated genus
Bifidobacterium
[
P
= 0.0132]) as well as the genus
Lactobacillus
(
P
= 0.0182) than the untreated controls 4 weeks after the cessation of treatment. By week 8, the
Proteobacteria
levels remained significantly higher in the treated infants (
P
= 0.0049), but the
Actinobacteria
,
Bifidobacterium
, and
Lactobacillus
levels had recovered and were similar to those in the control samples. Despite this recovery of total
Bifidobacterium
numbers,
rpoB
-targeted pyrosequencing revealed that the number of different
Bifidobacterium
species present in the antibiotic-treated infants was reduced. It is thus apparent that the combined use of ampicillin and gentamicin in early life can have significant effects on the evolution of the infant gut microbiota, the long-term health implications of which remain unknown.
In VitroActivities of Nine Antifungal Drugs against 81 Phialophora and Cyphellophora Isolates
Authors: Feng Peiying , Najafzadeh M. Javad , Sun Jiufeng , Ahmed Sarah , Xi Liyan , de Hoog G. Sybren , Lai Wei , Lu Chun , Klaassen Corné H. , Meis Jacques F.
Published: September 2012

Cyphellophora guyanensis(n= 15), otherCyphellophoraspecies (n= 11),Phialophora europaea(n= 43), and otherPhialophoraspecies (n= 12) were testedin vitroagainst nine antifungal drugs. The MIC90s across all of the strains (n= 81) were, in increasing order, as follows: posaconazole, 0.063 μg/ml; itraconazole, 0.5 μg/ml; voriconazole, 1 μg/ml; micafungin, 1 μg/ml; terbinafine, 2 μg/ml; isavuconazole, 4 μg/ml; caspofungin, 4 μg/ml; fluconazole, 8 μg/ml; amphotericin B, 16 μg/ml.
Prevention and Treatment of Virulent Bacterial Biofilms with an Enzymatic Nitric Oxide-Releasing Dressing
Authors: Sulemankhil Imran , Ganopolsky Jorge Gabriel , Dieni Christopher Anthony , Dan Andrei Florin , Jones Mitchell Lawrence , Prakash Satya
Published: September 2012

The use of percutaneous medical devices often results in nosocomial infections. Attachment of microorganisms to the surfaces of these medical devices triggers biofilm formation, which presents significant complications to the health of a patient and may lead to septicemia, thromboembolism, or endocarditis if not correctly treated. Although several antimicrobials are commonly used for prevention of biofilm formation, they have limited efficacy against formed biofilms. In this study, we report the use of an enzymatic, gaseous nitric oxide (gNO)-releasing dressing for the prevention and treatment of
Acinetobacter baumannii
, methicillin-resistant
Staphylococcus aureus
, and
Pseudomonas aeruginosa
biofilms. Results show that the bactericidal activity against biofilms of the test strains was dependent on time and rate of gNO release from the dressing. Following 6 h of treatment, gNO-releasing dressings significantly inhibited the growth of test strains relative to vehicle control dressings, demonstrating eradication of bacterial concentrations of up to 10
5
CFU/cm
2
. Complete cell death was observed for both prevention of biofilm formation and treatment of 24-h-grown biofilms after 6 h of treatment with the gNO-releasing dressings. Further, gNO-releasing dressings were more efficient against formed biofilms than other antimicrobial agents currently used. These results demonstrate that the gNO-releasing dressing can produce sufficient levels of gNO over a therapeutically relevant duration for maximal bactericidal effects against virulent bacterial strains known to cause nosocomial infections.
Red Man Syndrome Adverse Reaction following Intravenous Infusion of Cefepime
Authors: Panos George , Watson Dionysios C. , Sargianou Maria , Kampiotis Dionysios , Chra Paraskevi
Published: September 2012

We report the first case of cefepime-induced “red-man syndrome,” which appeared 30 min following drug infusion and was confirmed with a rechallenge test. This syndrome is classically associated with vancomycin infusion and is the result of non-IgE mediated mast cell degranulation. While this adverse effect can be easily managed with drug withdrawal and antihistamine administration, it is unknown whether it can be prevented with slower cefepime infusion and preinfusion antihistamines, as is the case with vancomycin.
Structure-Activity Relationships among the Kanamycin Aminoglycosides: Role of Ring I Hydroxyl and Amino Groups
Authors: Salian Sumantha , Matt Tanja , Akbergenov Rashid , Harish Shinde , Meyer Martin , Duscha Stefan , Shcherbakov Dmitri , Bernet Bruno B. , Vasella Andrea , Westhof Eric , Böttger Erik C.
Published: September 2012

The kanamycins form an important subgroup of the 4,6-disubstituted 2-deoxystreptamine aminoglycoside antibiotics, comprising kanamycin A, kanamycin B, tobramycin, and dibekacin. These compounds interfere with protein synthesis by targeting the ribosomal decoding A site, and they differ in the numbers and locations of amino and hydroxy groups of the glucopyranosyl moiety (ring I). We synthesized kanamycin analogues characterized by subtle variations of the 2′ and 6′ substituents of ring I. The functional activities of the kanamycins and the synthesized analogues were investigated (i) in cell-free translation assays on wild-type and mutant bacterial ribosomes to study drug-target interaction, (ii) in MIC assays to assess antibacterial activity, and (iii) in rabbit reticulocyte translation assays to determine activity on eukaryotic ribosomes. Position 2′ forms an intramolecular H bond with O5 of ring II, helping the relative orientations of the two rings with respect to each other. This bond becomes critical for drug activity when a 6′-OH substituent is present.
T-2307 Causes Collapse of Mitochondrial Membrane Potential in Yeast
Authors: Shibata Tatsuya , Takahashi Toshinari , Yamada Eio , Kimura Akiko , Nishikawa Hiroshi , Hayakawa Hiroyoshi , Nomura Nobuhiko , Mitsuyama Junichi
Published: September 2012

T-2307, an arylamidine compound, has been previously reported to have broad-spectrum
in vitro
and
in vivo
antifungal activities against clinically significant pathogens, including
Candida
species,
Cryptococcus neoformans
, and
Aspergillus
species, and is now undergoing clinical trials. Here we investigated the mechanism of action of T-2307 using yeast cells and mitochondria isolated from yeast and rat liver. Nonfermentative growth of
Candida albicans
and
Saccharomyces cerevisiae
in glycerol medium, in which yeasts relied on mitochondrial respiratory function, was inhibited at 0.001 to 0.002 μg/ml (0.002 to 0.004 μM) of T-2307. However, fermentative growth in dextrose medium was not inhibited by T-2307. Microscopic examination using Mitotracker fluorescent dye, a cell-permeant mitochondrion-specific probe, demonstrated that T-2307 impaired the mitochondrial function of
C. albicans
and
S. cerevisiae
at concentrations near the MIC in glycerol medium. T-2307 collapsed the mitochondrial membrane potential in mitochondria isolated from
S. cerevisiae
at 20 μM. On the other hand, in isolated rat liver mitochondria, T-2307 did not have any effect on the mitochondrial membrane potential at 10 mM. Moreover, T-2307 had little inhibitory and stimulatory effect on mitochondrial respiration in rat liver mitochondria. In conclusion, T-2307 selectively disrupted yeast mitochondrial function, and it was also demonstrated that the fungal mitochondrion is an attractive antifungal target.
Construction and Evaluation of a Novel Recombinant T Cell Epitope-Based Vaccine against Coccidioidomycosis
Authors: Hurtgen Brady J. , Hung Chiung-Yu , Ostroff Gary R. , Levitz Stuart M. , Cole Garry T.
Published: September 2012

Clinical and animal studies of coccidioidomycosis have demonstrated that activated CD4+T lymphocytes are essential for protection against this fungal respiratory disease. We previously reported a vaccine againstCoccidioidesinfection which contained three recombinant CD4+T cell-reactive proteins and induced a robust, protective immune response in mice. Due to the anticipated high cost of production and clinical assessment of this multivalent vaccine, we generated a single protein which contained immunodominant T cell epitopes of the three polypeptides. Epitopes were initially identified by computational prediction of their ability to bind promiscuously to human major histocompatibility complex class II (MHC II) molecules. Cellular immunoassays confirmed the immunogenicity of the synthesized epitope peptides, whilein vitrobinding assays revealed a range of peptide affinity for MHC II. A DNA construct was synthesized for bacterial expression of a recombinant protein vaccine which contained five epitopes with the highest affinity for human MHC II, each fused with leader and spacer peptides proposed to optimize epitope processing and presentation to T cell receptors. Recall assays of immune T lymphocytes obtained from human MHC II-expressing HLA-DR4 transgenic mice confirmed that 4 of the 5 epitope peptides were processed. Mice immunized with the epitope-based vaccine admixed with a synthetic oligodeoxynucleotide adjuvant or loaded into yeast glucan particles and then challenged intranasally withCoccidioidesshowed early lung infiltration of activated T helper-1 (Th1), Th2, and Th17 cells, elevated gamma interferon (IFN-γ) and interleukin (IL)-17 production, significant reduction of fungal burden, and prolongation of survival compared to nonvaccinated mice. This is the first report of an epitope-based vaccine against coccidioidomycosis.
CsrRS and Environmental pH Regulate Group B Streptococcus Adherence to Human Epithelial Cells and Extracellular Matrix
Authors: Park Su Eun , Jiang Shengmei , Wessels Michael R.
Published: September 2012

Streptococcus agalactiae
(group B
Streptococcus
or GBS) is a common colonizer of the gastrointestinal and genital tracts and an important cause of invasive infections in newborn infants and in adults with predisposing chronic conditions or advanced age. Attachment to epithelial surfaces at mucosal sites is a critical step in the successful colonization of a human host, and regulation of this process is likely to play an important role in both commensalism and dissemination to cause invasive disease. We found that inactivation of the CsrRS (or CovRS) two-component system increased GBS adherence to epithelial cells derived from human vaginal, cervical, and respiratory epithelium, as well as increasing adherence to extracellular matrix proteins and increasing biofilm formation on polystyrene. Neutral (as opposed to acidic) pH enhanced GBS binding to vaginal epithelial cells and to fibrinogen and fibronectin, effects that were partially dependent on CsrRS. The regulatory effects of CsrRS and environmental pH on bacterial adherence correlated with their effects on the expression of multiple surface adhesins, as assessed by quantitative reverse transcription-PCR. We conclude that GBS adherence to epithelial and abiotic surfaces is regulated by the CsrRS two-component system and by environmental pH through their regulatory effects on the expression of bacterial surface adhesins. Dynamic regulation of GBS adherence enhances the organism's adaptability to survival in multiple niches in the human host.
First reported detection of a low pathogenicity avian influenza virus subtype H9 infection in domestic fowl in England
Authors: Parker C. D. , Reid S. M. , Ball A. , Cox W. J. , Essen S. C. , Hanna A. , Mahmood S. , Slomka M. J. , Irvine R. M. , Brown I. H.
Published: September 2012

In December 2010, infection with a H9N1 low pathogenicity avian influenza (LPAI) virus was detected in a broiler breeder flock in East Anglia. Disease suspicion was based on acute drops in egg production in two of four sheds on the premises, poor egg shell quality and evidence of diarrhoea. H9N1 LPAI virus infection was confirmed by real‐time reverse transcription PCR. Sequencing revealed high nucleotide identity of 93.6 per cent and 97.9 per cent with contemporary North American H9 and Eurasian N1 genes, respectively. Attempted virus isolation in embryonated specific pathogen free (SPF) fowls' eggs was unsuccessful. Epidemiological investigations were conducted to identify the source of infection and any onward spread. These concluded that infection was restricted to the affected premises, and no contacts or movements of poultry, people or fomites could be attributed as the source of infection. However, the infection followed a period of extremely cold weather and snow which impacted on the biosecurity protocols on site, and also led to increased wild bird activity locally, including waterfowl and game birds around the farm buildings. Analysis of the N1 gene sequence suggested direct introduction from wild birds. Although H9 infection in poultry is not notifiable, H9N2 LPAI viruses have been associated with production and mortality episodes in poultry in many parts of Asia and the Middle East. In the present H9N1 outbreak, clinical signs were relatively mild in the poultry with no mortality, transient impact on egg production and no indication of zoonotic spread. However, this first reported detection of H9 LPAI virus in chickens in England was also the first H9 UK poultry case for 40 years, and vindicates the need for continued vigilance and surveillance of avian influenza viruses in poultry populations.
Structural requirements of salicylaldehyde benzoylhydrazones and their Cu(II) complexes for anticancer activity
Authors: Tan Shiow Jin , Sk Mahasin Alam , Lee Peter Peng Foo , Yan Yaw Kai , Lim Kok Hwa
Published: September 2012

Salicylaldehyde benzoylhydrazone (H2sb) has a variety of biological activities including anticancer activity. The Cu(II) complexes of H2sbs possess enhanced anticancer activity as compared with their free ligands. A quantitative structure–activity relationship (QSAR) analysis was performed on a series of H2sb ligands and their corresponding Cu(II) complexes to capture the structural requirements that are responsible for the bioactivity. The predictive QSAR models were developed using statistical techniques such as multiple linear regression (MLR) and principal component regression analysis (PCRA). We used different combinations of various descriptors such as a physicochemical descriptor, electrotopological state atom (ETSA) indices, and descriptors derived from density functional theory (DFT) calculations. The DFT-derived descriptors used for QSAR analysis are HOMO and LUMO energies, atomic charges, chemical potential, and hardness. Our developed models showed the importance of the lipophilicity index (ClogP), ETSA indices, and atomic charges for anticancer activities of the H2sb analogs and their Cu(II) complexes. In addition, our MLR models revealed that, while the global lipophilicity index and hardness are important for anticancer activity of H2sb ligands, chemical potential and HOMO energy are important for the anticancer activity of Cu(II) complexes.
BLOCK-DIAGONALIZATION OF OPERATORS WITH GAPS, WITH APPLICATIONS TO DIRAC OPERATORS
Authors: CUENIN JEAN-CLAUDE
Published: September 2012

We present new results on the block-diagonalization of operators with spectral gaps, based on a method of Langer and Tretter, and apply them to Dirac operators on three-dimensional Euclidean space with unbounded potentials. For the Coulomb potential, we achieve an exact diagonalization up to nuclear charge Z = 124 (which covers all chemical elements) and prove the convergence of an approximate block-diagonalization up to Z = 62, thus considerably improving the upper bounds Z = 93 and Z = 51, respectively, established by Siedentop and Stockmeyer.
Analyst Conflicts and Research Quality
Authors: Agrawal Anup , Chen Mark A.
Published: September 2012

This paper examines whether the quality of stock analysts' forecasts is related to conflicts of interest from their employers' investment banking (IB) and brokerage businesses. We consider four aspects of forecast quality: accuracy, bias, and revision frequency of quarterly earnings per share (EPS) forecasts and relative optimism in long-term earnings growth (LTG) forecasts. Using a unique dataset that contains the annual revenue breakdown of analysts' employers among IB, brokerage, and other businesses, we uncover two main findings. First, accuracy and bias in quarterly EPS forecasts appear to be unrelated to conflict magnitudes after controlling for forecast age, firm resources, and analyst characteristics. Second, relative optimism in LTG forecasts and the revision frequency of quarterly EPS forecasts are positively related to the importance of brokerage business to analysts' employers. Additional tests suggest that the frequency of quarterly forecast revisions is positively related to analysts' trade generation incentives. Our findings suggest that reputation concerns keep analysts honest with respect to short-term earnings forecasts but not LTG forecasts. In addition, conflicts from brokerage appear to play a more important role in shaping analysts' forecasting behavior than has been previously recognized.
Fine-mapping diabetes-related traits, including insulin resistance, in heterogeneous stock rats
Authors: Woods Leah C. Solberg , Holl Katie L. , Oreper Daniel , Xie Yuying , Tsaih Shirng-Wern , Valdar William
Published: September 2012

Type 2 diabetes (T2D) is a disease of relative insulin deficiency resulting from both insulin resistance and beta cell failure. We have previously used heterogeneous stock (HS) rats to fine-map a locus for glucose tolerance. We show here that glucose intolerance in the founder strains of the HS colony is mediated by different mechanisms: insulin resistance in WKY and an insulin secretion defect in ACI, and we demonstrate a high degree of variability for measures of insulin resistance and insulin secretion in HS rats. As such, our goal was to use HS rats to fine-map several diabetes-related traits within a region on rat chromosome 1. We measured blood glucose and plasma insulin levels after a glucose tolerance test in 782 male HS rats. Using 97 SSLP markers, we genotyped a 68 Mb region on rat chromosome 1 previously implicated in glucose and insulin regulation. We used linkage disequilibrium mapping by mixed model regression with inferred descent to identify a region from 198.85 to 205.9 that contains one or more quantitative trait loci (QTL) for fasting insulin and a measure of insulin resistance, the quantitative insulin sensitivity check index. This region also encompasses loci identified for fasting glucose and Insulin_AUC (area under the curve). A separate <3 Mb QTL was identified for body weight. Using a novel penalized regression method we then estimated effects of alternative haplotype pairings under each locus. These studies highlight the utility of HS rats for fine-mapping genetic loci involved in the underlying causes of T2D.
Intravitreal Devices for the Treatment of Vitreous Inflammation
Authors: Christoforidis John B. , Chang Susie , Jiang Angela , Wang Jillian , Cebulla Colleen M.
Published: September 2012

The eye is a well-suited organ for local delivery of therapeutics to treat vitreous inflammation as well as other pathologic conditions that induce visual loss. Several conditions are particularly challenging to treat and often require chronic courses of therapy. The use of implantable intravitreal devices for drug delivery is an emerging field in the treatment of vitreous inflammation as well as other ophthalmologic diseases. There are unique challenges in the design of these devices which include implants, polymers, and micro- and nanoparticles. This paper reviews current and investigational drug delivery systems for treating vitreous inflammation as well as other pathologic conditions that induce visual loss. The use of nonbiodegradable devices such as polyvinyl alcohol-ethylene vinyl acetate polymers and polysulfone capillary fibers, and biodegradable devices such as polylactic acid, polyglycolic acid, and polylactic-co-glycolic acid, polycaprolactones, and polyanhydrides are reviewed. Clinically used implantable devices for therapeutic agents including ganciclovir, fluocinolone acetonide, triamcinolone acetonide, and dexamethasone are described. Finally, recently developed investigational particulate drug delivery systems in the form of liposomes, microspheres, and nanoparticles are examined.
In SituChemical Oxidation of UltrasmallMoOxNanoparticles in Suspensions
Authors: Lee Yun-Ju , Barrera Diego , Luo Kaiyuan , Hsu Julia W. P.
Published: September 2012

Nanoparticle suspensions represent a promising route toward low cost, large area solution deposition of functional thin films for applications in energy conversion, flexible electronics, and sensors. However, parameters such size, stoichiometry, and electronic properties must be controlled to achieve best results for the target application. In this report, we demonstrate that such control can be achieved viain situchemical oxidation ofMoOxnanoparticles in suspensions. Starting from a microwave-synthesized suspension of ultrasmall (d~2 nm)MoOxnanoparticles in n-butanol, we added H2O2at room temperature to chemically oxidize the nanoparticles. We systematically varied H2O2concentration and reaction time and found that they significantly affected oxidation state and work function ofMoOxnanoparticle films. In particular, we achieved a continuous tuning ofMoOxwork function from 4.4 to 5.0 eV, corresponding to oxidation of as-synthesizedMoOxnanoparticle (20% Mo6+) to essentially pure MoO3. This was achieved without significantly modifying nanoparticle size or stability. Such precise control ofMoOxstoichiometry and work function is critical for the optimization ofMoOxnanoparticles for applications in organic optoelectronics. Moreover, the simplicity of the chemical oxidation procedure should be applicable for the development of other transition oxide nanomaterials with tunable composition and properties.
Analysis of a Pareto Mixture Distribution for Maritime Surveillance Radar
Authors: Weinberg Graham V. , Finch Daniel
Published: September 2012

The Pareto distribution has been shown to be an excellent model for X‐band high‐resolution maritime surveillance radar clutter returns. Given the success of mixture distributions in radar, it is thus of interest to consider the effect of Pareto mixture models. This paper introduces a formulation of a Pareto intensity mixture distribution and investigates coherent multilook radar detector performance using this new clutter model. Clutter parameter estimates are derived from data sets produced by the Defence Science and Technology Organisation′s Ingara maritime surveillance radar.
Myocardial Viability: What We Knew and What Is New
Authors: Shabana Adel , El-Menyar Ayman
Published: September 2012

Some patients with chronic ischemic left ventricular dysfunction have shown significant improvements of contractility with favorable long-term prognosis after revascularization. Several imaging techniques are available for the assessment of viable myocardium, based on the detection of preserved perfusion, preserved glucose metabolism, intact cell membrane and mitochondria, and presence of contractile reserve. Nuclear cardiology techniques, dobutamine echocardiography and positron emission tomography are used to assess myocardial viability. In recent years, new advances have improved methods of detecting myocardial viability. This paper summarizes the pathophysiology, methods, and impact of detection of myocardial viability, concentrating on recent advances in such methods. We reviewed the literature using search engines MIDLINE, SCOUPS, and EMBASE from 1988 to February 2012. We used key words: myocardial viability, hibernation, stunning, and ischemic cardiomyopathy. Recent studies showed that the presence of viable myocardium was associated with a greater likelihood of survival in patients with coronary artery disease and LV dysfunction, but the assessment of myocardial viability did not identify patients with survival benefit from revascularization, as compared with medical therapy alone. This topic is still debatable and needs more evidence.
Characterizations of Asymptotic Cone of the Solution Set of a Composite Convex Optimization Problem
Authors: Chen Zhe
Published: September 2012

We characterize the asymptotic cone of the solution set of a convex composite optimization problem. We then apply the obtained results to study the necessary and sufficient conditions for the nonemptiness and compactness of the solution set of the problem. Our results generalize and improve some known results in literature.
Retrospective Analysis of Metabolic Syndrome: Prevalence and Distribution in Executive Population in Urban Pakistan
Authors: Ali Niloufer Sultan , Khuwaja Ali Khan , Adnan-ur-Rahman  , Nanji Kashmira
Published: September 2012

Background. Metabolic Syndrome (MetS) is a major public health concern. Objective. The aim of this study was to estimate the frequency of MetS, its components, and factors associated with MetS amongst apparently healthy individuals in Pakistan. Methods. A retrospective cross-sectional study was conducted at the executive Clinics of Aga Khan Hospital, Pakistan. Medical records of patients aged ≥18 years visiting the clinics from July 2011 to December 2011 were consecutively reviewed. Records in which either MetS components data or 10% of overall data was missing were excluded. A total of 1329 participants’ records was included in final analysis. Data was analyzed using SPSS version 19 and multivariable logistic regression was used to identify the factors associated with MetS. Results. A total of 847 (63.7%) participants had MetS; mean age of the participants were 47.6 ± 11.6 years. About 70.4% were males and 29.6% were females. Approximately 70% of participants had BMI ≥25 kg/m2. MetS was associated with male gender (AOR = 2.1; 95% C.I: 1.6–3.2) and history of diabetes among parents (AOR = 3.0; 95% C.I: 1.6–6.0). Conclusion. This study shows that a large proportion of population has MetS and is overweight or obese. This requires urgent interventions on part of health care providers’ especially family physicians. Educating masses about life style factors can make a difference. Further researches on this issue are warranted.
Fabrication of Highly Rough Ag Nanobud Substrates and Surface‐Enhanced Raman Scattering of λ‐DNA Molecules
Authors: Deng Chuyun , Ma Wanyun , Sun Jia-Lin
Published: September 2012

Raman scattering signals can be enhanced by several orders of magnitude on surface‐enhanced Raman scattering (SERS) substrates made from noble metal nanostructures. Some SERS substrates are even able to detect single‐molecule Raman signals. A novel silver nanobud (AgNB) substrate with superior SERS activity was fabricated with a solid‐state ionics method. The AgNB substrate was formed by tightly collocated unidirectional 100 nm size silver buds, presenting a highly rough surface topography. Distinct SERS signals of single λ‐DNA molecules in water were detected on AgNB substrates. AgNB substrates were compared with disordered silver nanowire (AgNW) substrates manufactured by the same method through the SERS detection of λ‐DNA solutions. This original AgNB substrate provides a reliable approach towards trace analysis of biomacromolecules and promotes the utilization of the SERS technique in biomedical research.