bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conceptual Metaphors and Mathematical Practice: On Cognitive Studies of Historical Developments in Mathematics
Authors: Schlimm Dirk 
Published: April 2013

AbstractThis article looks at recent work in cognitive science on mathematical cognition from the perspective of history and philosophy of mathematical practice. The discussion is focused on the work of Lakoff and Núñez, because this is the first comprehensive account of mathematical cognition that also addresses advanced mathematics and its history. Building on a distinction between mathematics as it is presented in textbooks and as it presents itself to the researcher, it is argued that the focus of cognitive analyses of historical developments of mathematics has been primarily on the former, even if they claim to be about the latter.
Comparison of MICs of Fluconazole and Flucytosine When Dissolved in Dimethyl Sulfoxide or Water
Authors: Fothergill Annette W. , Sanders Carmita , Wiederhold Nathan P. 
Published: April 2013

ABSTRACT

A total of 145 clinical strains of
Candida
species were tested by the Clinical and Laboratory Standards Institute M27-A3 methodology to determine if replacing water with dimethyl sulfoxide as the solvent for fluconazole and flucytosine impacted the
in vitro
potency. No significant differences in MIC values were observed with either antifungal between the two solvents against any
Candida
species, and the essential agreement for each agent between the two solvents was greater than 99%.
Evaluation of the βLACTA Test, a Novel Commercial Chromogenic Test for Rapid Detection of Ceftazidime-Nonsusceptible Pseudomonas aeruginosa Isolates
Authors: Laurent Terry , Huang Te-Din , Bogaerts Pierre , Glupczynski Youri 
Published: April 2013

ABSTRACT

A novel commercial chromogenic technique, the βLACTA test (Bio-Rad, Marnes-la-Coquette, France), was evaluated to detect nonsusceptibility to ceftazidime in
Pseudomonas aeruginosa
isolates. Easily implemented in the routine microbiology laboratory, this rapid test was sensitive (95%) and specific (87%) and presented negative and positive predictive values of 99% and 100%, respectively.
Intra-Abdominal Infections Due to Comamonas kerstersii
Authors: Almuzara Marisa N. , Cittadini Rosana , Vera Ocampo Cecilia , Bakai Romina , Traglia German , Ramirez Maria S. , del Castillo Marcelo , Vay Carlos A. 
Published: April 2013

ABSTRACTHerein, we report four cases ofComamonas kerstersiiintra-abdominal infections representing the first report of human infections caused by thisComamonasspecies. In addition, our work demonstrates the association ofC. kerstersiiwith peritonitis secondary to appendix rupture.
Kaposi's Sarcoma-Associated Herpesvirus (KSHV) Latency-Associated Nuclear Antigen Regulates the KSHV Epigenome by Association with the Histone Demethylase KDM3A
Authors: Kim Kevin Y. , Huerta Steve B. , Izumiya Chie , Wang Don-Hong , Martinez Anthony , Shevchenko Bogdan , Kung Hsing-Jien , Campbell Mel , Izumiya Yoshihiro 
Published: April 2013

ABSTRACT
Kaposi's sarcoma-associated herpesvirus (KSHV) latent genomes are tethered to host histones to form a minichromosome also known as an “episome.” Histones, which are core components of chromatin, are heavily modified by various histone-targeting enzymes. Posttranslational modifications of histones significantly influence accessibility of transcriptional factors and thus have profound effects on gene expression. Recent studies showed that epigenetic marks on the KSHV episome are well organized, exemplified by the absence of histone H3 lysine 9 (H3K9) methylation, a heterochromatic histone mark, from immediate early and latent gene promoters in naturally infected cells. The present study revealed a mechanistic insight into KSHV epigenome regulation via a complex consisting of LANA and the H3K9me1/2 histone demethylase JMJD1A/KDM3A. This complex was isolated from HeLa cell nuclear extracts stably expressing LANA and was verified by coimmunoprecipitation analyses and with purified proteins. LANA recruitment sites on the KSHV genome inversely correlated with H3K9me2 histone marks in naturally infected cells, and methylation of H3K9 significantly inhibited LANA binding to the histone H3 tail. Chromatin immunoprecipitation coupled with KSHV tiling arrays identified the recruitment sites of the complex, while depletion of LANA expression or overexpression of a KDM3A binding-deficient mutant decreased KDM3A recruitment to the KSHV genome. Finally, ablation of KDM3A expression from latently KSHV-infected cells significantly inhibited KSHV gene expression, leading to decreased KSHV replication during reactivation. Taken together, our results suggest that LANA may play a role in regulation of epigenetic marks on the KSHV genome, which is in part through association with the histone demethylase KDM3A.
Novel
cis
-Acting Element within the Capsid-Coding Region Enhances Flavivirus Viral-RNA Replication by Regulating Genome Cyclization
Authors: Liu Zhong-Yu , Li Xiao-Feng , Jiang Tao , Deng Yong-Qiang , Zhao Hui , Wang Hong-Jiang , Ye Qing , Zhu Shun-Ya , Qiu Yang , Zhou Xi , Qin E-De , Qin Cheng-Feng 
Published: April 2013

ABSTRACT

cis
-Acting elements in the viral genome RNA (vRNA) are essential for the translation, replication, and/or encapsidation of RNA viruses. In this study, a novel conserved
cis
-acting element was identified in the capsid-coding region of mosquito-borne flavivirus. The
d
ownstream of 5′
c
yclization
s
equence (5′CS)
p
seudo
k
not (DCS-PK) element has a three-stem pseudoknot structure, as demonstrated by structure prediction and biochemical analysis. Using dengue virus as a model, we show that DCS-PK enhances vRNA replication and that its function depends on its secondary structure and specific primary sequence. Mutagenesis revealed that the highly conserved stem 1 and loop 2, which are involved in potential loop-helix interactions, are crucial for DCS-PK function. A predicted loop 1-stem 3 base triple interaction is important for the structural stability and function of DCS-PK. Moreover, the function of DCS-PK depends on its position relative to the 5′CS, and the presence of DCS-PK facilitates the formation of 5′-3′ RNA complexes. Taken together, our results reveal that the
cis
-acting element DCS-PK enhances vRNA replication by regulating genome cyclization, and DCS-PK might interplay with other
cis
-acting elements to form a functional vRNA cyclization domain, thus playing critical roles during the flavivirus life cycle and evolution.
A Vicilin-Like Seed Storage Protein, PAP85, Is Involved in Tobacco Mosaic Virus Replication
Authors: Chen Cheng-En , Yeh Kuo-Chen , Wu Shu-Hsing , Wang Hsiang-Iu , Yeh Hsin-Hung 
Published: April 2013

ABSTRACT

One striking feature of viruses with RNA genomes is the modification of the host membrane structure during early infection. This process requires both virus- and host-encoded proteins; however, the host factors involved and their role in this process remain largely unknown. On infection with
Tobacco mosaic virus
(TMV), a positive-strand RNA virus, the filamentous and tubular endoplasmic reticulum (ER) converts to aggregations at the early stage and returns to filamentous at the late infectious stage, termed the ER transition. Also, membrane- or vesicle-packaged viral replication complexes (VRCs) are induced early during infection. We used microarray assays to screen the
Arabidopsis thaliana
gene(s) responding to infection with TMV in the initial infection stage and identified an
Arabidopsis
gene,
PAP85
(annotated as a vicilin-like seed storage protein), with upregulated expression during 0.5 to 6 h of TMV infection. TMV accumulation was reduced in
pap85
-RNA interference (RNAi)
Arabidopsis
and restored to wild-type levels when PAP85 was overexpressed in
pap85
-RNAi
Arabidopsis
. We did not observe the ER transition in TMV-infected
PAP85
-knockdown
Arabidopsis
protoplasts. In addition, TMV accumulation was reduced in
PAP85
-knockdown protoplasts. VRC accumulation was reduced, but not significantly (
P
= 0.06), in
PAP85
-knockdown protoplasts. Coexpression of PAP85 and the TMV main replicase (P126), but not their expression alone in
Arabidopsis
protoplasts, could induce ER aggregations.
A Herpes Simplex Virus Scaffold Peptide That Binds the Portal Vertex Inhibits Early Steps in Viral Replication
Authors: Yang Kui , Wills Elizabeth , Baines Joel D. 
Published: April 2013

ABSTRACT

Previous experiments identified a 12-amino-acid (aa) peptide that was sufficient to interact with the herpes simplex virus 1 (HSV-1) portal protein and was necessary to incorporate the portal into capsids. In the present study, cells were treated at various times postinfection with peptides consisting of a portion of the
Drosophila
antennapedia protein, previously shown to enter cells efficiently, fused to either wild-type HSV-1 scaffold peptide (YPYYPGEARGAP) or a control peptide that contained changes at positions 4 and 5. These 4-tyrosine and 5-proline residues are highly conserved in herpesvirus scaffold proteins and were previously shown to be critical for the portal interaction. Treatment early in infection with subtoxic levels of wild-type peptide reduced viral infectivity by over 1,000-fold, while the mutant peptide had little effect on viral yields. In cells infected for 3 h in the presence of wild-type peptide, capsids were observed to transit to the nuclear rim normally, as viewed by fluorescence microscopy. However, observation by electron microscopy in thin sections revealed an aberrant and significant increase of DNA-containing capsids compared to infected cells treated with the mutant peptide. Early treatment with peptide also prevented formation of viral DNA replication compartments. These data suggest that the antiviral peptide stabilizes capsids early in infection, causing retention of DNA within them, and that this activity correlates with peptide binding to the portal protein. The data are consistent with the hypothesis that the portal vertex is the conduit through which DNA is ejected to initiate infection.
Sulfamoylbenzamide Derivatives Inhibit the Assembly of Hepatitis B Virus Nucleocapsids
Authors: Campagna Matthew R. , Liu Fei , Mao Richeng , Mills Courtney , Cai Dawei , Guo Fang , Zhao Xuesen , Ye Hong , Cuconati Andrea , Guo Haitao , Chang Jinhong , Xu Xiaodong , Block Timothy M. , Guo Ju-Tao 
Published: April 2013

ABSTRACT
Chronic hepatitis B virus (HBV) infection, a serious public health problem leading to cirrhosis and hepatocellular carcinoma, is currently treated with either pegylated alpha interferon (pegIFN-α) or one of the five nucleos(t)ide analogue viral DNA polymerase inhibitors. However, neither pegIFN-α nor nucleos(t)ide analogues are capable of reliably curing the viral infection. In order to develop novel antiviral drugs against HBV, we established a cell-based screening assay by using an immortalized mouse hepatocyte-derived stable cell line supporting a high level of HBV replication in a tetracycline-inducible manner. Screening of a library consisting of 26,900 small molecules led to the discovery of a series of sulfamoylbenzamide (SBA) derivatives that significantly reduced the amount of cytoplasmic HBV DNA. Structure-activity relationship studies have thus far identified a group of fluorine-substituted SBAs with submicromolar antiviral activity against HBV in human hepatoma cells. Mechanistic analyses reveal that the compounds dose dependently inhibit the formation of pregenomic RNA (pgRNA)-containing nucleocapsids of HBV but not other animal hepadnaviruses, such as woodchuck hepatitis virus (WHV) and duck hepatitis B virus (DHBV). Moreover, heterologous genetic complementation studies of capsid protein, DNA polymerase, and pgRNA between HBV and WHV suggest that HBV capsid protein confers sensitivity to the SBAs. In summary, SBAs represent a novel chemical entity with superior activity and a unique antiviral mechanism and are thus warranted for further development as novel antiviral therapeutics for the treatment of chronic hepatitis B.
Replication and Immunogenicity of Swine, Equine, and Avian H3 Subtype Influenza Viruses in Mice and Ferrets
Authors: Baz Mariana , Paskel Myeisha , Matsuoka Yumiko , Zengel James , Cheng Xing , Jin Hong , Subbarao Kanta 
Published: April 2013

ABSTRACT
Since it is difficult to predict which influenza virus subtype will cause an influenza pandemic, it is important to prepare influenza virus vaccines against different subtypes and evaluate the safety and immunogenicity of candidate vaccines in preclinical and clinical studies prior to a pandemic. In addition to infecting humans, H3 influenza viruses commonly infect pigs, horses, and avian species. We selected 11 swine, equine, and avian H3 influenza viruses and evaluated their kinetics of replication and ability to induce a broadly cross-reactive antibody response in mice and ferrets. The swine and equine viruses replicated well in the upper respiratory tract of mice. With the exception of one avian virus that replicated poorly in the lower respiratory tract, all of the viruses replicated in mouse lungs. In ferrets, all of the viruses replicated well in the upper respiratory tract, but the equine viruses replicated poorly in the lungs. Extrapulmonary spread was not observed in either mice or ferrets. No single virus elicited antibodies that cross-reacted with viruses from all three animal sources. Avian and equine H3 viruses elicited broadly cross-reactive antibodies against heterologous viruses isolated from the same or other species, but the swine viruses did not. We selected an equine and an avian H3 influenza virus for further development as vaccines.
Patient expectations of minor injury care: a cross-sectional survey
Authors: Whiteley Jack , Goodacre Steve 
Published: April 2013

Background and objectiveLittle is known about the expectations of patients attending the emergency department (ED) with minor injuries. Failure to address expectations may lead to dissatisfaction and poor compliance. We aimed to describe patient expectations of minor injury care and explore the association between unmet expectations and patient satisfaction.MethodsWe undertook a cross-sectional questionnaire survey of 300 patients attending the ED with minor injuries on weekdays between 9:00 and 17:00. Participants completed a questionnaire asking which tests and treatments they expected, which they consequently received, whether explanations were given for tests and treatments, and how they rated satisfaction with care.ResultsThe most frequently expected interventions were x-ray, analgesia and bandage/strapping. In each case the proportion expecting intervention was significantly higher than the proportion receiving intervention: x-ray (58% vs 47%, p<0.001); analgesia (40% vs 20%, p<0.001); bandage/strapping (39% vs 22%, p<0.001). There were no significant differences between the proportions expecting and receiving other interventions. At least one unmet expectation was reported by 208/300 patients (69%) but an explanation was received in 151/208 cases (73%). Conversely, 106 (35%) received an unexpected intervention, of whom 79/106 (74%) received an explanation. Patients with unmet expectations tended to rate the satisfaction lower, but the difference was not statistically significant (p=0.187).ConclusionsPatients often expect interventions for minor injuries that they do not receive, but in most cases an explanation was given. We were unable to demonstrate an association between unmet expectations and reduced satisfaction with care.
Career choices for emergency medicine: national surveys of graduates of 1993–2009 from all UK medical schools
Authors: Svirko Elena , Lambert Trevor , Brand Lois , Goldacre Michael J 
Published: April 2013

BackgroundIn the UK, recruitment of adequate numbers of doctors to emergency medicine (EM) has been problematic. With this as background, we analysed data about career choice for, and progression in, EM in a large multi-purpose study of doctors’ careers.MethodsQuestionnaire surveys of medical graduates of 1993, 1996, 1999, 2000, 2002, 2005, 2008 and 2009 from all UK medical schools.ResultsEM was specified as a first choice of career by 4.2% of graduates in postgraduate year 1, 4.8% in year 3, and 3.8% in year 5. Graduates who chose EM were much less likely to be certain about their choice than those who chose other specialties. Of those who specified EM as their first choice of career in year 1, only 26% still had it as their first choice in year 5. Of those who gave EM as their first career choice in year 5, only 27% had given EM as their first choice in year 1. Switches to EM were made, notably, by doctors who previously favoured surgical specialties, hospital physician-led specialties and anaesthetics.ConclusionsEarly career choices for EM are less predictive of career destinations than choices for other specialties, and, compared with many other specialties, doctors who pursue it may turn to it relatively late. Training policies on transferable competencies should enable clinical trainees in other related specialties to bank some of their skills if they transfer to EM, rather than necessarily having to start core training in year 1 of EM specialty training.
THERMODYNAMIC QUANTITIES AT HIGH PRESSURES IN THE i AND θ PHASES OF SOLID NITROGEN DEDUCED BY RAMAN FREQUENCY SHIFTS FOR THE INTERNAL MODES IN LITERATURE
Authors: YURTSEVEN H. , SARITAŞ S. 
Published: April 2013

The pressure dependence of the Raman frequencies of the internal modes is analyzed (T = 300 K ) for the phases i and θ of solid nitrogen using the experimental data from the literature. Through the mode Grüneisen parameter, the isothermal compressibility κT, thermal expansion αp and the specific heat Cp–Cv are calculated as a function of pressure using the Raman data in these phases. We obtain that the αp varies linearly with the (1/υ)(∂υ/∂P)T and also that the Cp–Cv varies linearly with the αp for N 2. Our results show that by means of the analysis given here, the αp, κT and Cp–Cv can be predicted from the Raman frequency shifts for the i and θ phases of solid nitrogen.
DOG1 Regulates Growth and IGFBP5 in Gastrointestinal Stromal Tumors
Authors: Simon Susanne , Grabellus Florian , Ferrera Loretta , Galietta Luis , Schwindenhammer Benjamin , Mühlenberg Thomas , Taeger Georg , Eilers Grant , Treckmann Juergen , Breitenbuecher Frank , Schuler Martin , Taguchi Takahiro , Fletcher Jonathan A. , Bauer Sebastian 
Published: April 2013

Abstract
Gastrointestinal stromal tumors (GIST) are characterized by activating mutations of KIT or platelet-derived growth factor receptor α(PDGFRA), which can be therapeutically targeted by tyrosine kinase inhibitors (TKI) such as imatinib. Despite long-lasting responses, most patients eventually progress after TKI therapy. The calcium-dependent chloride channel DOG1 (ANO1/TMEM16A), which is strongly and specifically expressed in GIST, is used as a diagnostic marker to differentiate GIST from other sarcomas. Here, we report that loss of DOG1 expression occurs together with loss of KIT expression in a subset of GIST resistant to KIT inhibitors, and we illustrate the functional role of DOG1 in tumor growth, KIT expression, and imatinib response. Although DOG1 is a crucial regulator of chloride balance in GIST cells, we found that RNAi-mediated silencing or pharmacologic inhibition of DOG1 did not alter cell growth or KIT signaling in vitro. In contrast, DOG1 silencing delayed the growth of GIST xenografts in vivo. Expression profiling of explanted tumors after DOG1 blockade revealed a strong upregulation in the expression of insulin-like growth factor-binding protein 5 (IGFBP5), a potent antiangiogenic factor implicated in tumor suppression. Similar results were obtained after selection of imatinib-resistant DOG1- and KIT-negative cells derived from parental DOG1 and KIT-positive GIST cells, where a 5,000-fold increase in IGFBP5 mRNA transcripts were documented. In summary, our findings establish the oncogenic activity of DOG1 in GIST involving modulation of IGF/IGF receptor signaling in the tumor microenvironment through the antiangiogenic factor IGFBP5. Cancer Res; 73(12); 3661–70. ©2013 AACR.
Race and Colon Cancer Survival in an Equal-Access Health Care System
Authors: Andaya Abegail A. , Enewold Lindsey , Zahm Shelia H. , Shriver Craig D. , Stojadinovic Alexander , McGlynn Katherine A. , Zhu Kangmin 
Published: April 2013

Abstract
Studies have shown that Whites have a higher colorectal cancer survival rate than Blacks. However, it is unclear whether racial disparities result from unequal access to medical care or factors other than health care access or both. This study assessed whether non-Hispanic Whites (NHW) and non-Hispanic Blacks (NHB) differ in colon cancer survival in an equal-access health care system and examined whether racial differences varied by demographic and tumor characteristics. The study included 2,537 Military Health System patients diagnosed with colon cancer between 1998 and 2007. Median follow-up time was 31.4 months. Cox models estimated HRs and 95% confidence intervals (CI) for race, overall and stratified by age at diagnosis, sex, and tumor stage. No difference in overall survival (OS) between NHWs and NHBs was observed in general. However, among patients younger than 50 years old, NHBs experienced significantly worse OS than NHWs (HR: 2.03, 95% CI: 1.30–3.19). Furthermore, stratification by sex and tumor stage showed that this racial disparity was confined to women (HR: 2.87; 95% CI: 1.35–6.11) and patients with distant stage disease (HR: 2.45; 95% CI: 1.15–5.22) in this age group. When medical care is equally available to NHWs and NHBs, similar overall colon cancer survival was observed; however, evidence of racial differences in survival was apparent for patients younger than 50 years old. This study suggests that factors other than access to care may be related to racial disparities in colon cancer survival among younger, but not older, patients. Cancer Epidemiol Biomarkers Prev; 22(6); 1030–6. ©2013 AACR.
Colorectal Cancer: Looking for Answers in the Microbiota
Authors: Jobin Christian 
Published: April 2013

Abstract
Summary: At a simplistic level, colorectal cancer arises from mutations in various proto-oncogenes and tumor suppressor genes. Aside from genetically inherited factors, environmental, lifestyle, and dietary habits have all been identified as risk agents promoting mutational events leading to the development of colorectal cancer. This “In Focus” presents evidence that the intestinal endogenous bacterial community represents a risk factor for the development of colorectal cancer. Cancer Discov; 3(4); 384–7. ©2013 AACR.