bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of the K101E Substitution in HIV-1 Reverse Transcriptase in Resistance to Rilpivirine and Other Nonnucleoside Reverse Transcriptase Inhibitors
Authors: Xu Hong-Tao , Colby-Germinario Susan P. , Huang Wei , Oliveira Maureen , Han Yingshan , Quan Yudong , Petropoulos Christos J. , Wainberg Mark A.
Published: September 2013

Resistance to the recently approved nonnucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine (RPV) commonly involves substitutions at positions E138K and K101E in HIV-1 reverse transcriptase (RT), together with an M184I substitution that is associated with resistance to coutilized emtricitabine (FTC). Previous biochemical and virological studies have shown that compensatory interactions between substitutions E138K and M184I can restore enzyme processivity and the viral replication capacity. Structural modeling studies have also shown that disruption of the salt bridge between K101 and E138 can affect RPV binding. The current study was designed to investigate the impact of K101E, alone or in combination with E138K and/or M184I, on drug susceptibility, viral replication capacity, and enzyme function. We show here that K101E can be selected in cell culture by the NNRTIs etravirine (ETR), efavirenz (EFV), and dapivirine (DPV) as well as by RPV. Recombinant RT enzymes and viruses containing K101E, but not E138K, were highly resistant to nevirapine (NVP) and delavirdine (DLV) as well as ETR and RPV, but not EFV. The addition of K101E to E138K slightly enhanced ETR and RPV resistance compared to that obtained with E138K alone but restored susceptibility to NVP and DLV. The K101E substitution can compensate for deficits in viral replication capacity and enzyme processivity associated with M184I, while M184I can compensate for the diminished efficiency of DNA polymerization associated with K101E. The coexistence of K101E and E138K does not impair either viral replication or enzyme fitness. We conclude that K101E can play a significant role in resistance to RPV.
Shedding of Tumor Necrosis Factor Receptor 1 Induced by Protein A Decreases Tumor Necrosis Factor Alpha Availability and Inflammation during Systemic Staphylococcus aureus Infection
Authors: Giai Constanza , Gonzalez Cintia , Ledo Camila , Garofalo Ailin , Di Genaro María Silvia , Sordelli Daniel O. , Gomez Marisa I.
Published: September 2013

Staphylococcus aureusinfections are an important public health concern due to their increasing incidence and high rates of mortality. The success ofS. aureusas a pathogen is highly related to its enormous capacity to evade the host immune response. The critical role of tumor necrosis factor alpha (TNF-α) in the initial host defense against systemic staphylococcal infection has been demonstrated in experimental models and may partially explain the lack of significant benefits observed in clinical trials attempting to neutralize this cytokine in septic patients.S. aureusprotein A plays a key role in regulating inflammation through its ability to bind and signal through the TNF-α receptor 1 (TNFR1). In this study, we demonstrate thatS. aureus, via protein A-mediated signaling, induces early shedding of TNFR1, which precedes the secretion of TNF-αin vitroandin vivo. The results obtained using a protein A-deficient mutant andtnfr1−/−mice strongly suggest that the increased levels of soluble TNFR1 present during experimentalS. aureusinfection may neutralize circulating TNF-α and impair the host inflammatory response. Early shedding of TNFR1 induced by protein A may constitute a novel mechanism by whichS. aureussubverts the host immune response.
A Regulatory Checkpoint during Flagellar Biogenesis in Campylobacter jejuni Initiates Signal Transduction To Activate Transcription of Flagellar Genes
Authors: Boll Joseph M. , Hendrixson David R.
Published: September 2013

Many polarly flagellated bacteria require similar two-component regulatory systems (TCSs) and σ
54
to activate transcription of genes essential for flagellar motility. Herein, we discovered that in addition to the flagellar type III secretion system (T3SS), the
Campylobacter jejuni
flagellar MS ring and rotor are required to activate the FlgSR TCS. Mutants lacking the FliF MS ring and FliG C ring rotor proteins were as defective as T3SS mutants in FlgSR- and σ
54
-dependent flagellar gene expression. Also, FliF and FliG required each other for stability, which is mediated by atypical extensions to the proteins. A FliF mutant that presumably does not interact with the T3SS protein FlhA did not support flagellar gene transcription, suggesting that FliF-T3SS interactions are essential to generate a signal sensed by the cytoplasmic FlgS histidine kinase. Furthermore, the flagellar T3SS was required for FlgS to immunoprecipitate with FliF and FliG. We propose a model whereby the flagellar T3SS facilitates FliF and FliG multimerization into the MS ring and rotor. As a result, these flagellar structures form a cytoplasmic complex that interacts with and is sensed by FlgS. The synthesis of these structures appears to be a regulatory checkpoint in flagellar biogenesis that the FlgS kinase monitors to initiate signal transduction that activates σ
54
and expression of genes required for the next stage of flagellation. Given that other polar flagellates have flagellar transcriptional hierarchies that are organized similarly as in
C. jejuni
, this regulatory checkpoint may exist in a broad range of bacteria to influence similar TCSs and flagellar gene transcription.

IMPORTANCE
Despite the presence of numerous two-component regulatory systems (TCSs) in bacteria, direct signals sensed by TCSs to activate signal transduction are known for only a minority. Polar flagellates, including
Pseudomonas
,
Vibrio
,
Helicobacter
, and
Campylobacter
species, require a similar TCS and σ
54
for flagellar gene transcription, but the activating signals for these TCSs are unknown. We explored signals that activate the
Campylobacter jejuni
FlgSR TCS to initiate σ
54
-dependent flagellar gene transcription. Our discoveries suggest that the FlgS histidine kinase monitors the formation of the flagellar type III secretion system and the surrounding MS and C rings. The synthesis of these structures creates a regulatory checkpoint in flagellar biogenesis that is sensed by FlgS to ensure proper transcription of the next set of genes for subsequent steps in flagellation. Given the conservation of flagellar-associated TCSs and transcriptional cascades in polar flagellates, this regulatory checkpoint in flagellar biogenesis likely impacts flagellation in a broad range of bacteria.
What a Difference a Dalton Makes: Bacterial Virulence Factors Modulate Eukaryotic Host Cell Signaling Systems via Deamidation
Authors: Washington Erica J. , Banfield Mark J. , Dangl Jeffery L.
Published: September 2013

Pathogenic bacteria commonly deploy enzymes to promote virulence. These enzymes can modulate the functions of host cell targets. While the actions of some enzymes can be very obvious (e.g., digesting plant cell walls), others have more subtle activities. Depending on the lifestyle of the bacteria, these subtle modifications can be crucially important for pathogenesis. In particular, if bacteria rely on a living host, subtle mechanisms to alter host cellular function are likely to dominate. Several bacterial virulence factors have evolved to use enzymatic deamidation as a subtle posttranslational mechanism to modify the functions of host protein targets. Deamidation is the irreversible conversion of the amino acids glutamine and asparagine to glutamic acid and aspartic acid, respectively. Interestingly, all currently characterized bacterial deamidases affect the function of the target protein by modifying a single glutamine residue in the sequence. Deamidation of target host proteins can disrupt host signaling and downstream processes by either activating or inactivating the target. Despite the subtlety of this modification, it has been shown to cause dramatic, context-dependent effects on host cells. Several crystal structures of bacterial deamidases have been solved. All are members of the papain-like superfamily and display a cysteine-based catalytic triad. However, these proteins form distinct structural subfamilies and feature combinations of modular domains of various functions. Based on the diverse pathogens that use deamidation as a mechanism to promote virulence and the recent identification of multiple deamidases, it is clear that this enzymatic activity is emerging as an important and widespread feature in bacterial pathogenesis.
Rapid recovery of membrane cofactor protein (MCP;CD46) associated atypical haemolytic uraemic syndrome with plasma exchange
Authors: Reid Victoria Louise , Mullan Adam , Erwig Lars-Peter
Published: September 2013

Atypical haemolytic uraemic syndrome (aHUS), unlike typical HUS is due to complement dysregulation. At least one abnormality of the complement system can be identified in 70% of patients. aHUS is associated with a poor prognosis with 25% mortality and 50% progress to end-stage renal disease. Genetic abnormalities in the complement system, proteins includingCFH,CFI,CFB,C3,CFHR1/3andMCP(CD46) lead to uncontrolled complement activation in aHUS. We presented the second reported case of aHUS associated with a heterozygous c.191G > T mutation in exon 2 ofMCPwho responded rapidly to plasma exchange.
150 minutes of vigorous physical activity per week predicts survival and successful ageing: a population-based 11-year longitudinal study of 12 201 older Australian men
Authors: Almeida Osvaldo P , Khan Karim M , Hankey Graeme J , Yeap Bu B , Golledge Jonathan , Flicker Leon
Published: September 2013

Background

Physical activity has been associated with improved survival, but it is unclear whether this increase in longevity is accompanied by preserved mental and physical functioning, also known as healthy ageing. We designed this study to determine whether physical activity is associated with healthy ageing in later life.

Methods

We recruited a community-representative sample of 12 201 men aged 65–83 years and followed them for 10–13 years. We assessed physical activity at the beginning and the end of the follow-up period. Participants who reported 150 min or more of vigorous physical activity per week were considered physically active. We monitored survival during the follow-up period and, at study exit, assessed the mood, cognition and functional status of survivors. Healthy ageing was defined as being alive at the end of follow-up and having a Patient Health Questionnaire score <10, Telephone Interview for Cognitive Status score >27, and no major difficulty in any instrumental or basic activity of daily living. Cox regression and general linear models were used to estimate HR of death and risk ratio (RR) of healthy ageing. Analyses were adjusted for age, education, marital status, smoking, body mass index and history of hypertension, diabetes, coronary heart disease and stroke.

Results

Two thousand and fifty-eight (16.9%) participants were physically active at study entry. Active men had lower HR of death over 10–13 years than physically inactive men (HR=0.74, 95% CI=0.68 to 0.81). Among survivors, completion of the follow-up assessment was higher in the physically active than inactive group (risk ratio, RR=1.18, 95% CI=1.08 to 1.30). Physically active men had greater chance of fulfilling criteria for healthy ageing than inactive men (RR=1.35, 95% CI=1.19 to 1.53). Men who were physically active at the baseline and follow-up assessments had the highest chance of healthy ageing compared with inactive men (RR=1.59, 95% CI=1.36 to 1.86).

Conclusions

Sustained physical activity is associated with improved survival and healthy ageing in older men. Vigorous physical activity seems to promote healthy ageing and should be encouraged when safe and feasible.
Elevated plasma GLP-1 levels and enhanced expression of cardiac GLP-1 receptors as markers of left ventricular systolic dysfunction: a cross-sectional study
Authors: Hattori Arihiro , Kawamura Itta , Yamada Yoshihisa , Kanamori Hiromitsu , Aoyama Takuma , Ushikoshi Hiroaki , Kawasaki Masanori , Nishigaki Kazuhiko , Tamemura Genzou , Minatoguchi Shinya
Published: September 2013

Objective

We aimed to elucidate usefulness of plasma glucagon-like peptide-1 (GLP-1) levels for the assessment of left ventricular (LV) dysfunction by examining the relationship among plasma GLP-1 levels, expression of cardiac GLP-1 receptors and LV function in patients with impaired and preserved LV function.

Design

Prospective study.

Setting

Number of participating center: 1, Gifu, Japan.

Participants

Number of patients enrolled: 102 patients who underwent elective cardiac catheterisation for coronary artery disease, cardiomyopathy and valvular heart disease, and 6 patients who underwent cardiac biopsy.

Results

The plasma GLP-1 level was significantly increased in patients with impaired LV function (5.7±1.9 pmol/L) as compared with those with preserved LV function (2.7±1.6 pmol/L). Plasma GLP-1 and plasma brain natriuretic peptide (BNP) levels were inversely correlated with the LV ejection fraction(EF), respectively. Plasma GLP-1 level positively correlated with plasma BNP level. Multivariate logistic regression analysis revealed that plasma GLP-1 level was an independent determinant of the impaired LV function, whereas plasma BNP level was not. Intensity of immunostaining for GLP-1 receptor protein was significantly enhanced in patients with impaired LV function compared with those with preserved LV function.

Conclusions

The plasma GLP-1 level was increased in patients with impaired systolic LV function and inversely correlated with the LVEF. The expressions of GLP-1 receptors were enhanced in hearts with impaired LV function. These may suggest that endogenous GLP-1-GLP-1 receptor system serves as a compensatory mechanism for systolic LV dysfunction.

Trial registration

UMIN-CTR, ID=UMIN000009361, registration number: R000011000.
Building a safer foundation: the Lessons Learnt patient safety training programme
Authors: Ahmed Maria , Arora Sonal , Tiew Stephenie , Hayden Jacky , Sevdalis Nick , Vincent Charles , Baker Paul
Published: September 2013

Objectives

To develop, implement and evaluate a novel patient safety training programme for junior doctors across a Foundation School—‘Lessons Learnt: Building a Safer Foundation’.

Design, setting and participants

Prospective preintervention /postintervention study across 16 Foundation Programmes in North West England, UK. 1169 participants including all Foundation Programme Directors, Administrators, Foundation trainees and senior faculty.

Interventions

Half-day stakeholder engagement event and faculty development through recruitment and training of local senior doctors. Foundation trainee-led monthly 60-min sessions integrated into compulsory Foundation teaching from January to July 2011 comprising case-based discussion and analysis of patient safety incidents encountered in practice, facilitated by trained faculty.

Main outcome measures

Participants’ satisfaction and Foundation trainees’ patient safety knowledge, skills, attitudes and behavioural change.

Results

Participants reported high levels of satisfaction with ‘Lessons Learnt’. There was a significant improvement in trainees’ objective patient safety knowledge scores (Meanpreintervention=51.1%, SD=17.3%; Meanpostintervention=57.6%, SD=20.1%, p<0.001); subjective knowledge ratings and patient safety skills. Trainees’ perceived control and behavioural intentions regarding safety improved significantly postintervention. Feelings and personal beliefs about safety did not shift significantly. Trainees reported significantly more patient safety incidents in the 6 months following introduction of ‘Lessons Learnt’ (Meanpreintervention=0.67, SD=1.11; Meanpostintervention=1.18, SD=1.46, p<0.001). 32 quality improvement projects were initiated by trainees, spanning the development of novel clinical protocols; implementation of user-informed teaching and improved rota design

Conclusions

Patient safety training can be implemented and sustained to deliver significant improvements in patient safety knowledge, skills and behaviours of junior doctors—with potential for wider positive organisational impact. Medical education commissioners and providers could adopt and build upon the ‘Lessons Learnt’ approach as a springboard to promote medical engagement in quality and safety improvement.
Pyogenic liver abscess
Authors: Webb Gwilym James , Chapman Thomas Patrick , Cadman Philip John , Gorard David Angelo
Published: September 2013

Pyogenic liver abscess has a variable clinical presentation. Its management requires input from several disciplines and is often coordinated by a gastroenterologist. This review examines demographics, clinical presentation, aetiology, diagnosis and prognosis; a suggested management approach, including antibiotic selection, radiological intervention and indications for surgery, is offered from a physician's perspective.
Cloud point extraction of Pd(II), Au(III), and Ag(I) prior to their determination by graphite furnace atomic absorption spectrometry
Authors: Mortada Wael I. , Z. Ali Al-Ahmad , Hassanien Mohamed M.
Published: September 2013

A simple and rapid cloud point extraction methodology has been developed for the separation and preconcentration of palladium (Pd2+), gold (Au3+), and silver (Ag+) ions. The metal ions in the initial aqueous solution were complexed with 4-allylthiosemicarbazide, and Triton X-114 was added as surfactant. Dilution of the surfactant-rich phase with acidified metanol was performed after phase separation, and the metal ions were determined by graphite furnace atomic absorption spectrometry. The main factors affecting the cloud point extraction procedure, such as pH, concentration of the ligand, amount of Triton X-114, equilibrium temperature, and incubation time, were investigated and optimized. Under the optimum experimental, the calibration graphs were linear upto 100 μg L−1 for Pd2+ and Au3+ and up to 80 μg L−1 for Ag+. The enrichment factors were 48, 53, and 51 for Pd2+, Au3+, and Ag+, respectively. The limits of detection, based on three times the standard deviation of the blank signal by seven replicate measurements, were 0.15, 0.07, and 0.04 μg L−1 for Pd2+, Au3+, and Ag+, respectively. The accuracy of the results was verified by analyzing spiked real samples (water, blood, and urine) as well as by comparison the results of geological samples with those obtained by ICP−MS after solvent extraction using ammonium pyrrolidinedithiocarbamate in methyl isobutyl ketone. The proposed method has been applied for the determination of the metal ions in real samples with satisfactory results.
How do shellfisheries influence genetic connectivity in metapopulations? A modeling study examining the role of lower size limits in oyster fisheries
Authors: Munroe Daphne M. , Hofmann Eileen E. , Powell Eric N. , Klinck John M.
Published: September 2013

Fisheries can potentially alter evolutionary processes such as genetic connectivity and lead to genotypic changes in stocks. Using an individual-based metapopulation genetics model, we examined the possible influence of oyster (Crassostrea virginica) fisheries on genetic connectivity. We simulated a range of realistic fishing pressures, with and without a minimum size limit (limit = 63.5 mm), over a range of fishing scenarios including single-area and stock-wide fisheries. Movement of a neutral marker gene provided an indicator of gene transfer between populations. Simulations showed that fishing may alter genetic connectivity. Increasing fishing pressure tended to decrease potential for fished populations to export genes in fisheries with and without size limits. On average, when instantaneous fishing mortality, location, and time period are held constant, fishing unrestricted by size results in a 3.5% lower allele export. Depression of the spawning potential ratio by unrestricted fishing relative to size-limited fishing argues for more conservative fishing mortality targets for unrestricted fisheries. These results demonstrate the importance of considering the influence of fisheries on source–sink dynamics in future management of marine populations.
Cannibals by night? In situ video monitoring reveals diel shifts in inter- and intra-specific predation on the American lobster
Authors: Oppenheim Noah G. , Wahle Richard A.
Published: September 2013

We conducted tethering experiments in the field to evaluate day–night differences in the identity and frequency of predators encountered by the American lobster (Homarus americanus) in coastal Maine, USA. Separate daytime and nighttime deployments were conducted using tethered lobsters under infrared-illuminated video surveillance. Supplemental tethering trials without video surveillance provided further quantitative information on diel and size-specific predation patterns. We found crabs to be the most common predators during the day, whereas lobsters prevailed at night. Contrary to expectations, we measured higher predation rates at night than during the day, suggesting that nocturnal interactions with conspecifics may play a more important role in lobster population regulation than previously thought when lobster population densities are high and large predatory fish are rare. As large predatory groundfish have been depleted in the Gulf of Maine, lobster populations have reached historic highs, making density-dependent feedbacks such as cannibalism more likely.
Fine-scale catch data reveal clusters of large predators in the pelagic realm
Authors: Capello M. , Bach P. , Romanov E.
Published: September 2013

The management and conservation of large pelagic fish commonly rely on fisheries data and thus crucially depend on our understanding of the fish response to the fishing gear. Stock assessment of both tropical and temperate tuna strongly leans on the catch statistics derived from pelagic longline fisheries. However, the role of the spatial distribution of catches of tuna and bycatch species over the gear, which can affect the estimated tuna abundance, is still neglected. In this study, we analyzed data obtained from 147 instrumented pelagic longline sets equipped with hook timers and temperature depth recorders to characterize the distribution of hooking contacts and success at a fine temporal and spatial scale. Scientific surveys were carried out in the Central–South Pacific Ocean (French Polynesia), targeting tropical (Thunnus albacares, Thunnus obesus) and temperate (Thunnus alalunga) tuna. Data analysis based on spatial point processes and stochastic modeling demonstrate the presence of spatio-temporal clusters for both hooking contacts and hooking success. The comparative analysis of the observed spatio-temporal patterns for different oceanographic zones revealed the persistent structure of the clusters, suggesting that they are neither related to local environmental conditions nor to the spatial distribution of prey species.
Diel vertical migration of adult burbot: a dynamic trade-off among feeding opportunity, predation avoidance, and bioenergetic gain
Authors: Harrison P.M. , Gutowsky L.F.G. , Martins E.G. , Patterson D.A. , Leake A. , Cooke S.J. , Power M.
Published: September 2013

Diel vertical migration (DVM) of pelagic organisms is typically attributed to bioenergetic gain, foraging opportunity, predator avoidance, and multifactor hypotheses. While a number of benthic species perform nightly migrations into shallower waters, the function of these DVMs has largely been ignored in benthic fishes. We used depth and temperature sensing telemetry to investigate DVM function in burbot (Lota lota), a freshwater benthic piscivore. We modeled the influence of season, diel period, and body size on the depth, vertical activity, migration probability, and thermal experience of 47 adult burbot over 2 years in a reservoir in British Columbia, Canada. Burbot were found to occupy significantly shallower water at night than during the day. Our results, which showed elevated nightly activity and a seasonal size-structured depth distribution during DVMs, suggest these migrations likely provide a feeding opportunity “window” for this nocturnal predator, constrained by predation or cannibalism threats to smaller individuals. The observed thermal experience patterns suggest DVM may also provide a seasonal bioenergetic advantage. Our detection of within-individual plasticity in migration strategy is indicative of a partial migration. Taken together, our results suggest a multifactor DVM hypothesis: a dynamic trade-off among bioenergetic advantage, foraging opportunity, and predation threat.
CASIMIR CHARGE AND AN EXPLANATION FOR C VIOLATION
Authors: GAO LI , PENG GUANG-XIONG
Published: September 2013

In this paper, the concept of Casimir charge is introduced, which is defined to be the characteristic quantity that describes an elementary particle. From the viewpoint of Casimir charge, the definition of charge conjugation is analyzed. As a result we find that the definition is not self-consistent, perhaps this is responsible for C violation.
UNIMODULAR CONSTRAINT ON GLOBAL SCALE INVARIANCE
Authors: SINGH NAVEEN K.
Published: September 2013

We study a model with global scale invariance within the framework of unimodular gravity. The global scale invariant gravitational action which follows the unimodular general coordinate transformations is considered without invoking any scalar field. This is generalization of conformal theory described [P. D. Mannheim and D. Kazanas, Astrophys. J. 342, 635 (1989)]. The possible solutions for the gravitational potential under static linear field approximation are discussed. The new modified solution has additional corrections to the Schwarzschild solution which describe the galactic rotational curve. A comparative study of unimodular theory with conformal theory is also presented. Furthermore, the cosmological solution is studied and it is shown that the unimodular constraint preserve the de Sitter solution explaining the dark energy of the universe.
与公民互动: 中国新移民在新加坡
Authors: 游俊豪
Published: September 2013

本文焦点投射在中国新移民在新加坡的社会语境和政策层面。新加坡提供了一个鲜明的案例，显示目前中国新移民的融入遭遇体制性和结构性的问题。在汇流到新加坡的各种离散华人脉络当中，新移民被给予当代中国国别性的标志，使得他们区别于在地的主流社会。来自各种各样的背景，新移民个别透过向下、平行、向上等方向同在地社会互动，在多元文化和多元族群的语境当中，面对英语广度使用和高度价值所形成的界线，也面对体制的管治。为了妥善处理国民的诉求，新加坡政府致力优化公民可以享有的资源和空间，拉开公民跟包括中国新移民在内的外籍人士的距离。晚近移民政策的频繁修订，反映新加坡政府在重层结构里分别管治移民的数量、身份、空间。这些对人口流动的重新界定，无非是要彰显主流社会的固定性，让它成为国民与公民可以接受的社会规范。
新加坡独立前崛起的华商文化资本积累
Authors: 龙坚
Published: September 2013

本论文应用布迪厄 (Pierre Bourdieu) 资本理论，从场域与资本相互关联的视角来探讨新加坡独立前崛起的华商文化资本的动态积累特征。本文认为：在新加坡这个独特的社会场域中，华商必然要面对本土华族文化圈、本土多元文化圈、以及西方文化、中国文化的相互碰撞和交叠。实践表明：在其所处的年代和场域里，这些华商尽管拥有较低层次的文化资本、社会资本和经济资本，但并不对外在的决定性结构作出机械反应，不管这种结构是经济的、政治的、社会的或文化的。文化习性、传统风俗和信仰等都已渗透到他们个体或集体的反应之中，并调节着外在结构的影响。这些华商保有了自身所携带的传统伦理道德规范与价值体系的同时，在所处社会场域中有机地进行文化调适，从而形成了颇具比较优势的文化资本特色；此外，个体行动者是否能在场域中获得最佳的竞争优势，重要的不是其倚赖哪一种资本，而是恰当把握各种资本的配置。
告别/记录的吊诡: 论黎紫书的 （长篇） 小说实验
Authors: 朱崇科
Published: September 2013

黎紫书的长篇小说 《告别的年代》 整体来看是一部佳作，它几乎涵容了黎紫书所擅长的所有叙事技艺和主题，以相当繁复的手法再现了杜丽安故事，也隐喻了华人世代进入后 “五一三” 时空时的务实化、世俗化，乃至堕落化的可能危机与境界，呈现出告别/记录的吊诡。但在小说技艺繁复的同时，其后设装置亦有搅局之嫌，并未真正摆脱台湾场域的影响的焦虑，实现对自我的真正超越和经典化书写。
A Lesson in Resource Management
Authors: Neville-Neil George
Published: September 2013

Dear KV, I’ve been reworking a device driver for a high-end, high-performance networking card and I have a resource allocation problem. The devices I’m working with have several network ports, but these are not always in use; in fact, many of our customers use only one of the four available ports. It would greatly simplify the logic in my driver if I could allocate the resources for all the ports -- no matter how many there are -- when the device driver is first loaded into the system, instead of dealing with allocation whenever an administrator brings up an interface. I should point out that this device has a good deal of complexity and the resource allocation isn’t as simple as a quick malloc of memory and pointer jiggling -- a lot of moving parts are inside this thing.
Genome-wide analysis of the p53 gene regulatory network in the developing mouse kidney
Authors: Li Yuwen , Liu Jiao , McLaughlin Nathan , Bachvarov Dimcho , Saifudeen Zubaida , El-Dahr Samir S.
Published: September 2013

Despite mounting evidence that p53 senses and responds to physiological cues in vivo, existing knowledge regarding p53 function and target genes is largely derived from studies in cancer or stressed cells. Herein we utilize p53 transcriptome and ChIP-Seq (chromatin immunoprecipitation-high throughput sequencing) analyses to identify p53 regulated pathways in the embryonic kidney, an organ that develops via mesenchymal-epithelial interactions. This integrated approach allowed identification of novel genes that are possible direct p53 targets during kidney development. We find the p53-regulated transcriptome in the embryonic kidney is largely composed of genes regulating developmental, morphogenesis, and metabolic pathways. Surprisingly, genes in cell cycle and apoptosis pathways account for <5% of differentially expressed transcripts. Of 7,893 p53-occupied genomic regions (peaks), the vast majority contain consensus p53 binding sites. Interestingly, 78% of p53 peaks in the developing kidney lie within proximal promoters of annotated genes compared with 7% in a representative cancer cell line; 25% of the differentially expressed p53-bound genes are present in nephron progenitors and nascent nephrons, including key transcriptional regulators, components of Fgf, Wnt, Bmp, and Notch pathways, and ciliogenesis genes. The results indicate widespread p53 binding to the genome in vivo and context-dependent differences in the p53 regulon between cancer, stress, and development. To our knowledge, this is the first comprehensive analysis of the p53 transcriptome and cistrome in a developing mammalian organ, substantiating the role of p53 as a bona fide developmental regulator. We conclude p53 targets transcriptional networks regulating nephrogenesis and cellular metabolism during kidney development.
Tryptophan-Kynurenine Metabolism and Insulin Resistance in Hepatitis C Patients
Authors: Oxenkrug G. F. , Turski W. A. , Zgrajka W. , Weinstock J. V. , Summergrad P.
Published: September 2013

Chronic hepatitis C virus (HCV) infection is associated with 50% incidence of insulin resistance (IR) that is fourfold higher than that in non-HCV population. IR impairs the outcome of antiviral treatment. The molecular mechanisms of IR in HCV are not entirely clear. Experimental and clinical data suggested that hepatitis C virus per se is diabetogenic. However, presence of HCV alone does not affect IR. It was proposed that IR is mediated by proinflammatory cytokines, mainly by TNF-alpha. TNF-alpha potentiates interferon-gamma-induced transcriptional activation of indoleamine 2,3-dioxygenase, the rate-limiting enzyme of tryptophan- (TRP-) kynurenine (KYN) metabolism. Upregulation of TRP-KYN metabolism was reported in HCV patients. KYN and some of its derivatives affect insulin signaling pathways. We hypothesized that upregulation of TRP-KYN metabolism might contribute to the development of IR in HCV. To check this suggestion, we evaluated serum concentrations of TRP and KYN and HOMA-IR and HOMA-beta in 60 chronic HCV patients considered for the treatment with IFN-alpha. KYN and TRP concentrations correlated with HOMA-IR and HOMA-beta scores. Our data suggest the involvement of KYN and its metabolites in the development of IR in HCV patients. TRP-KYN metabolism might be a new target for prevention and treatment of IR in HCV patients.
Effects of Severe Hypoxia on Bone Marrow Mesenchymal Stem Cells Differentiation Potential
Authors: Cicione Claudia , Muiños-López Emma , Hermida-Gómez Tamara , Fuentes-Boquete Isaac , Díaz-Prado Silvia , Blanco Francisco J.
Published: September 2013

Background. The interests in mesenchymal stem cells (MSCs) and their application in cell therapy have resulted in a better understanding of the basic biology of these cells. Recently hypoxia has been indicated as crucial for complete chondrogenesis. We aimed at analyzing bone marrow MSCs (BM-MSCs) differentiation capacity under normoxic and severe hypoxic culture conditions.Methods. MSCs were characterized by flow cytometry and differentiated towards adipocytes, osteoblasts, and chondrocytes under normoxic or severe hypoxic conditions. The differentiations were confirmed comparing each treated point with a control point made of cells grown in DMEM and fetal bovine serum (FBS).Results. BM-MSCs from the donors displayed only few phenotypical differences in surface antigens expressions. Analyzing marker genes expression levels of the treated cells compared to their control point for each lineage showed a good differentiation in normoxic conditions and the absence of this differentiation capacity in severe hypoxic cultures.Conclusions. In our experimental conditions, severe hypoxia affects thein vitrodifferentiation potential of BM-MSCs. Adipogenic, osteogenic, and chondrogenic differentiations are absent in severe hypoxic conditions. Our work underlines that severe hypoxia slows cell differentiation by means of molecular mechanisms since a decrease in the expression of adipocyte-, osteoblast-, and chondrocyte-specific genes was observed.
Postmortem Computed Tomography Imaging in the Investigation of Nontraumatic Death in Infants and Children
Authors: Noda Yukihiro , Yoshimura Ken , Tsuji Shoji , Ohashi Atsushi , Kawasaki Hirohide , Kaneko Kazunari , Ikeda Shigeki , Kurokawa Hiroaki , Tanigawa Noboru
Published: September 2013

Objective. To determine the accuracy of postmortem computed tomography (PMCT) for the assessment of causes in nontraumatic deaths in children.Study Design. We enrolled cases of nontraumatic deaths of infants and children who underwent PMCT at a single center. The presumed cause of death determined by PMCT was prospectively compared with the clinical and pathological diagnoses of deaths.Results. Thirty-eight cases were enrolled for analysis. Among them, seven cases also underwent conventional medical autopsy. PMCT revealed an identifiable cause of death in accordance with the clinical diagnosis of death in 16 cases of the 38 cases (the concordance rate was 42%) and in accordance with the autopsy cause of death in four of the seven autopsy cases (the concordance rate was 57%). Among eight cases with unknown cause of death by clinical diagnosis, four cases (50%) were identified with cardiac tamponade as a cause of death (one case) and intracranial hemorrhage suggesting abuse (3 cases).Conclusions. PMCT seems to be a promising technique that might serve as a substitute for conventional medical autopsy and give us the complementary information to clinical diagnoses particularly in cases of child abuse. Larger multicenter trials are worthwhile to validate the general feasibility of PMCT.
Possible Implication of FcγReceptor-Mediated Trogocytosis in Susceptibility to Systemic Autoimmune Disease
Authors: Masuda Sakiko , Iwasaki Sari , Tomaru Utano , Baba Tomohisa , Katsumata Kazuaki , Ishizu Akihiro
Published: September 2013

Leukocytes can “gnaw away” the plasma membrane of other cells. This phenomenon, called trogocytosis, occurs subsequent to cell-to-cell adhesion. Currently, two mechanisms of trogocytosis, adhesion molecule-mediated trogocytosis and Fcγreceptor-(FcγR-) mediated trogocytosis, have been identified. In our earlier study, we established anin vitromodel of FcγR-mediated trogocytosis, namely, CD8 translocation model from T cells to neutrophils. By using this model, we demonstrated that the molecules transferred to neutrophils via FcγR-mediated trogocytosis were taken into the cytoplasm immediately. This result suggests that the chance of molecules transferred via FcγR-mediated trogocytosis to play a role on the cell surface could be time-limited. Thus, we consider the physiological role of FcγR-mediated trogocytosis as a means to remove antibodies (Abs) that bind with self-molecules rather than to extract molecules from other cells. This concept means that FcγR-mediated trogocytosis can be a defense mechanism to Ab-mediated autoimmune response. Moreover, the activity of FcγR-mediated trogocytosis was revealed to be parallel to the endocytotic activity of neutrophils, which was critically related to the susceptibility to systemic autoimmune diseases. The collective findings suggest that FcγR-mediated trogocytosis could physiologically play a role in removal of Abs bound to self-antigens and prevent autoimmune diseases.
Emergence in Western African Countries of MDR-TB, Focus on Côte d’Ivoire
Authors: Ekaza Euloge , N’Guessan Raymond Kouassi , Kacou-N’Douba Adèle , Aka N’Guetta , Kouakou Jacquemin , Le Vacon Françoise , Altare Fréderic , Potel Gilles , de-La-Cochetiere Marie-France
Published: September 2013

Tuberculosis (TB) is responsible for a high mortality rate (2.5%) worldwide, mainly in developing countries with a high prevalence of human immunodeficiency virus (HIV). The emergence of multiresistant strains of TB poses an extreme risk for TB outbreaks and highlights the need for global TB control strategies. Among Western African countries, Côte d’Ivoire (CI) represents a specific example of a country with great potential to prevent TB. Specifically, CI has a promising healthcare system for monitoring diseases, including vaccination programs. However, military and political conflict in CI favors the spread of infectious diseases, TB being among the most devastating. Compilation of the studies identifying common causes of TB would be extremely beneficial for the development of treatment and prevention strategies. Therefore, the purpose of this comprehensive review is to evaluate the epidemiology of TB in CI, describe the factors involved in pathogenesis, and suggest simple and applicable prevention strategies.
A Method for Fast Generating the VIE-MoM Matrix with the SWG Functions
Authors: Chen Shu-Wen , Zhou Hou-Xing , Li Wei-Dong , Hua Guang , Hong Wei
Published: September 2013

A method for fast generating the VIE-MoM matrix with the SWG functions is proposed. This method makes the integrals representing the shared data independent of any quadratures and hence can ensure both the efficiency and accuracy. In the VIE-MoM, the time cost of filling the VIE-MoM matrix is prominent especially for an electrically large object. With the proposed method, the time cost of filling the VIE-MoM matrix can be reduced by about 85% compared with the traditional basis-basis matching method. Numerical examples are provided to demonstrate the efficiency and accuracy of the proposed method.
Charged-Hadron Pseudorapidity Distributions in p-p and Pb-Pb Collisions at LHC Energies
Authors: Li Bao-Chun , Wang Ya-Zhou
Published: September 2013

Pseudorapidity distributions of charged hadrons produced in p-p and Pb-Pb collisions at LHC energies were measured by the CMS and ALICE Collaborations, respectively. An improved Tsallis distribution in the two-cylinder model is used to describe the pseudorapidity spectra. We consider the rapidity shift at the longitudinal direction in the geometrical picture of the collisions. The calculated results are in agreement with the experimental data. The gap between the projectile cylinder and the target cylinder increases with the centralities. The rapidity shifts in the cylinders also increase with the centralities.
Medicolegal Considerations with Intravenous Tissue Plasminogen Activator in Stroke: A Systematic Review
Authors: Bhatt Archit , Safdar Adnan , Chaudhari Dhara , Clark Diane , Pollak Amber , Majid Arshad , Kassab Mounzer
Published: September 2013

Background.Intravenous tPA (tissue plasminogen activator) therapy remains underutilized in patients with Acute Ischemic Stroke (AIS). Anecdotal data indicates that physicians are increasingly liable for administering and for failure to administer tPA.Methods.An extensive search of Medline, Embase, Westlaw, LexisNexis Legal, and Google Scholar databases was performed. Case studies that involved malpractice litigation in ischemic stroke and thrombolytic therapy were analyzed systematically.Results.We identified 789 ischemic stroke litigation cases, of which 46 cases were related to intravenous tPA and stroke litigation. Case descriptions of 40 cases were available. Data for verdicts were available for 38 patients. The most frequent plaintiff claim was related to failure to administer intravenous tPA (38, 95%). Only 2 (5.0%) claim involved complications of treatment with tPA. Hospitals were defendants in majority of the 36 cases. Physicians were involved in 33 cases. While ED physicians were involved in 25 (60.52%) cases, neurologists were involved in 8 (20.0%) cases. There were 26 (65%) defendant-favored and 12 (30%) plaintiff-favored verdicts.Conclusion.Physicians and hospitals are at an increased risk of litigation in patients with AIS when in IV-tPA is being considered for treatment. While majority of the cases litigated were cases where tPA was not administered, only about 1 in 20 cases was litigated when complications occurred.
Condensation Energy for a Two-Gap Superconducting State in Nanoparticles
Authors: Kruchinin Sergei P. , Kawabe Hiroyuki , Nagao Hidemi , Nakazawa Yasuhiro
Published: September 2013

Recent technology and experiments have fabricated high-quality superconducting MgB2 nanoparticles.
We investigate properties of two-gap superconductivity in nanosized systems by using a
two-sublevel model. In the present work, we analyze the results obtained for superconducting granules
in the case of multiband superconductivity. We discuss the finite size effect in multiband
superconductors. A definition of the critical level spacing of two-gap superconductivity is also presented,
and we discuss the condensation energy and the parity gap of two-gap superconductivity
in relation to the size dependence of those properties with two bulk gaps and the effective pair
scattering process between two sublevels.
Antioxidant, Antiproliferative, and Antiangiogenesis Effects of Polyphenol-Rich Seaweed (Sargassum muticum)
Authors: Namvar Farideh , Mohamad Rosfarizan , Baharara Javad , Zafar-Balanejad Saeedeh , Fargahi Fahimeh , Rahman Heshu Sulaiman
Published: September 2013

In the present study, we evaluated the effect of brown seaweedsSargassum muticummethanolic extract (SMME), against MCF-7 and MDA-MB-231 breast cancer cell lines proliferation. This algae extract was also evaluated for reducing activity and total polyphenol content. The MTT assay results indicated that the extracts were cytotoxic against breast cancer cell lines in a dose-dependent manner, with IC50of 22 μg/ml for MCF-7 and 55 μg/ml for MDA-MB-231 cell lines. The percentages of apoptotic MCF-7-treated cells increased from 13% to 67% by increasing the concentration of the SMME. The antiproliferative efficacy of this algal extract was positively correlated with the total polyphenol contents, suggesting a causal link related to extract content of phenolic acids. Cell cycle analysis showed a significant increase in the accumulation of SMME-treated cells at sub-G1 phase, indicating the induction of apoptosis by SMME. Further apoptosis induction was confirmed by Hoechst 33342 and AO/PI staining. Also SMME implanted in vivo into fertilized chicken eggs induced dose-related antiangiogenic activity in the chorioallantoic membrane (CAM). Our results imply a new insight on the novel function ofSargassum muticumpolyphenol-rich seaweed in cancer research by induction of apoptosis, antioxidant, and antiangiogenesis effects.
Effects of Deer Settling Stimulus and Deer Density on Regeneration in a Harvested Southern New England Forest
Authors: Barrett Kevin J. , Schmitz Oswald J.
Published: September 2013

Elevated deer densities have led to reports of forest regeneration failure and ecological damage. However, there is growing evidence that the biophysical conditions of a forest that make it attractive to deer may be a contributing factor in determining browsing levels. Thus, an understanding of settling stimulus—how attractive an area is to deer in terms of food-independent habitat requirements—is potentially important to manage deer browsing impacts. We tested the settling stimulus hypothesis by evaluating the degree to which thermal settling stimulus and deer density are related to spatial variation in browsing intensity across different forest harvesting strategies over the course of a year. We determined if deer were impacting plant communities and if they resulted in changes in plant cover. We quantified the thermal environment around each harvest and tested to see if it influenced deer density and browsing impact. We found that deer had an impact on the landscape but did not alter plant cover or diminish forest regeneration capacity. Deer density and browse impact had a relationship with thermal settling stimulus for summer and fall months, and deer density had a relationship with browse impact in the winter on woody plants. We conclude that thermal settling stimulus is an important predictor for deer density and browsing impact.
4D Clinical Imaging for Dynamic CAD
Authors: Lauren Mark , McIntyre Frederick
Published: September 2013

A basic 4D imaging system to capture the jaw motion has been developed that produces high resolution 3D surface data. Fluorescent microspheres are brushed onto the areas of the upper and the lower arches to be imaged, producing a high-contrast random optical pattern. A hand-held imaging device operated at about 10 cm from the mouth captures time-based perspective images of the fluorescent areas. Each set of images, containing both upper and the lower arch data, is converted to a 3d point mesh using photogrammetry, thereby providing an instantaneous relative jaw position. Eight 3d positions per second are captured. Using one of the 3d frames as a reference, incremental transforms are derived to express the free body motion of the mandible. Conventional 3d models of the dentition are directly registered to the reference frame, allowing them to be animated using the derived transforms.
Autism in Preschoolers: Does Individual Clinician’s First Visit Diagnosis Agree with Final Comprehensive Diagnosis?
Authors: Westman Andersson Gunilla , Miniscalco Carmela , Gillberg Christopher
Published: September 2013

Comprehensive clinical diagnosis based on all available information is considered the “gold standard” in autism spectrum disorders (ASD). We examined agreement across independent assessments (clinical judgment) of 34 young children (age 24–46 months) with suspected ASD, assessed by a multidisciplinary team, and final comprehensive clinical diagnosis. Agreement across settings and between each clinician’s assessment and final diagnosis was moderate. The poorest fit was found at assessment in connection with psychological evaluation and the best with preschool observation and parent interview. Some individual clinicians had good and others had poor fit with final diagnosis. Disagreement across assessments was pronounced for girls. The findings suggest that multidisciplinary assessments remain important and that comprehensive clinical diagnosis should still be regarded as the gold standard in ASD.
Giant Fibroelastoma of the Aortic Valve
Authors: di Summa Michele , Iezzi Federica
Published: September 2013

Fibroelastomas account for less than 10% of all cardiac tumours, representing the most common valvular and the second most common cardiac benign tumour, following myxomas. Fibroelastomas are histologically benign; they can result in life-threatening complications such as stroke, acute valvular dysfunction, embolism, ventricular fibrillation, and sudden death. Surgical resection should be offered to all patients who have symptoms and to asymptomatic patients who have pedunculated lesions or tumors larger than 1 cm in diameter. Valve-sparing excision produces good long-term results in most instances. We report our surgical experience of a giant fibroelastoma in the aortic valve.