bluuebunny/crossref_metadata_2025_split huggingface dataset:
Making a Non-Parametric Density Estimator More Attractive, and More Accurate, by Data Perturbation
Authors: Doosti Hassan , Hall Peter 
Published: May 2015

Summary
Motivated by both the shortcomings of high order density estimators, and the increasingly large data sets in many areas of modern science, we introduce new high order, non-parametric density estimators that are guaranteed to be positive and do not have highly oscillatory tails. Our approach is based on data perturbation, e.g. by tilting or data sharpening. It leads to new estimators that are more accurate than conventional kernel techniques that use positive kernels, but which nevertheless enjoy the positivity property, and are far less ‘wiggly’ than high order kernel estimators. We investigate performance by theoretical analysis and in a numerical study.
Pleistocene aeolianites at Cape Spencer, South Australia; record of a vanished inner neritic cool‐water carbonate factory
Authors: James Noel P. , Bone Yvonne 
Published: May 2015

AbstractAeolianites are integral components of many modern and ancient carbonate depositional systems. Southern Australia contains some of the most impressive and extensive late Cenozoic aeolianites in the modern world. Pleistocene aeolianites on Yorke Peninsula are sculpted into imposing seacliffs up to 60 m high and comprise two distinct imposing complexes of the Late Pleistocene Bridgewater Formation. The lower aeolianite complex, which forms the bulk of the cliffs, is a series of stacked palaeodunes and intervening palaeosols. The diagenetic low Mg‐calcite sediment particles are mostly bivalves, echinoids, bryozoans and small benthic foraminifera. This association is similar to sediments forming offshore today on the adjacent shelf in a warm‐temperate ocean. By contrast, the upper aeolianite complex is a series of mineralogically metastable biofragmental carbonates in a succession of stacked lenticular palaeodunes with impressive interbedded calcretes and palaeosols. Bivalves, geniculate coralline algae and benthic foraminifera, together with sparse peloids and ooids, dominate sediment grains. Fragments of large benthic foraminifera including Marginopora vertebralis, a photosymbiont‐bearing protist, are particularly conspicuous. Palaeocean temperatures are interpreted as having been sub‐tropical, somewhat warmer than offshore carbonate factories in the region today. The older aeolianite complex is tentatively correlated with Marine Isotope Stage 11, whereas the upper complex is equivalent to Marine Isotope Stage 5e. Marine Isotope Stage 5e deposits exposed elsewhere in southern Australia (Glanville Formation) are distinctive with a subtropical biota, including Marginopora vertebralis. Thus, in this example, palaeodune sediment faithfully records the nature of the adjacent inner neritic carbonate factory. By inference, aeolianites are potential repositories of information about the nature of long‐vanished marine systems that have been removed due to erosion, tectonic obliteration or are inaccessible in the subsurface. Such information includes not only the nature of marine environments themselves but also palaeoceanography.
Ethylene suppresses tomato (Solanum lycopersicum) fruit set through modification of gibberellin metabolism
Authors: Shinozaki Yoshihito , Hao Shuhei , Kojima Mikiko , Sakakibara Hitoshi , Ozeki‐Iida Yuko , Zheng Yi , Fei Zhangjun , Zhong Silin , Giovannoni James J. , Rose Jocelyn K.C. , Okabe Yoshihiro , Heta Yumi , Ezura Hiroshi , Ariizumi Tohru 
Published: May 2015

SummaryFruit set in angiosperms marks the transition from flowering to fruit production and a commitment to seed dispersal. Studies with Solanum lycopersicum (tomato) fruit have shown that pollination and subsequent fertilization induce the biosynthesis of several hormones, including auxin and gibberellins (GAs), which stimulate fruit set. Circumstantial evidence suggests that the gaseous hormone ethylene may also influence fruit set, but this has yet to be substantiated with molecular or mechanistic data. Here, we examined fruit set at the biochemical and genetic levels, using hormone and inhibitor treatments, and mutants that affect auxin or ethylene signaling. The expression of system–1 ethylene biosynthetic genes and the production of ethylene decreased during pollination‐dependent fruit set in wild‐type tomato and during pollination‐independent fruit set in the auxin hypersensitive mutant iaa9–3. Blocking ethylene perception in emasculated flowers, using either the ethylene‐insensitive Sletr1–1 mutation or 1–methylcyclopropene (1–MCP), resulted in elongated parthenocarpic fruit and increased cell expansion, whereas simultaneous treatment with the GA biosynthesis inhibitor paclobutrazol (PAC) inhibited parthenocarpy. Additionally, the application of the ethylene precursor 1–aminocyclopropane‐1‐carboxylic acid (ACC) to pollinated ovaries reduced fruit set. Furthermore, Sletr1–1 parthenocarpic fruits did not exhibit increased auxin accumulation, but rather had elevated levels of bioactive GAs, most likely reflecting an increase in transcripts encoding the GA‐biosynthetic enzyme SlGA20ox3, as well as a reduction in the levels of transcripts encoding the GA‐inactivating enzymes SlGA2ox4 and SlGA2ox5. Taken together, our results suggest that ethylene plays a role in tomato fruit set by suppressing GA metabolism.
A Multistate Investigation of Antibiotic‐ResistantSalmonella entericaSerotype I 4,[5],12:i:‐ Infections as Part of an International Outbreak Associated with Frozen Feeder Rodents
Authors: Cartwright E. J. , Nguyen T. , Melluso C. , Ayers T. , Lane C. , Hodges A. , Li X. , Quammen J. , Yendell S. J. , Adams J. , Mitchell J. , Rickert R. , Klos R. , Williams I. T. , Barton Behravesh C. , Wright J. 
Published: May 2015

SummaryWhile most humanSalmonellainfections result from exposure to contaminated foods, an estimated 11% of allSalmonellainfections are attributed to animal exposures, including both direct animal handling and indirect exposures such as cleaning cages and handling contaminated pet food. This report describes the epidemiologic, environmental and laboratory investigations conducted in the United States as part of the response to an international outbreak of tetracycline‐resistantSalmonella entericaserotype I 4,[5],12:i:‐ infections with over 500 illnesses occurring from 2008 to 2010. This investigation found that illness due to the outbreak strain was significantly associated with exposure to pet reptiles and frozen feeder rodents used as food for pet reptiles.Salmonellaisolates indistinguishable from the outbreak strain were isolated from a frozen feeder mice‐fed reptile owned by a case patient, as well as from frozen feeder mice and environmental samples collected from a rodent producing facility (Company A). An international voluntary recall of all Company A produced frozen feeder animals sold between May 2009 and July 2010 occurred. Only 13% of cases in our investigation were aware of the association betweenSalmonellainfection and mice or rats. Consumers, the pet industry, healthcare providers and veterinarians need to be aware of the potential health risk posed by feeder rodents, whether live or frozen. Frozen feeder rodent producers, suppliers and distributors should follow the animal food labelling requirements as described in 21CFR§501.5, and all packages of frozen feeder rodents should include safe handling instructions. Persons should wash their hands thoroughly with soap and water after handling live or frozen feeder rodents, as well as reptiles or anything in the area where the animals live. Continued opportunities exist for public health officials, the pet industry, veterinarians and consumers to work together to prevent salmonellosis associated with pet food, pets and other animals.
Identification of Gram-Negative Bacteria and Genetic Resistance Determinants from Positive Blood Culture Broths by Use of the Verigene Gram-Negative Blood Culture Multiplex Microarray-Based Molecular Assay
Authors: Ledeboer Nathan A. , Lopansri Bert K. , Dhiman Neelam , Cavagnolo Robert , Carroll Karen C. , Granato Paul , Thomson Richard , Butler-Wu Susan M. , Berger Heather , Samuel Linoj , Pancholi Preeti , Swyers Lettie , Hansen Glen T. , Tran Nam K. , Polage Christopher R. , Thomson Kenneth S. , Hanson Nancy D. , Winegar Richard , Buchan Blake W. 
Published: May 2015

ABSTRACT

Bloodstream infection is a serious condition associated with significant morbidity and mortality. The outcome of these infections can be positively affected by the early implementation of effective antibiotic therapy based on the identification of the infecting organism and genetic markers associated with antibiotic resistance. In this study, we evaluated the microarray-based Verigene Gram-negative blood culture (BC-GN) assay in the identification of 8 genus or species targets and 6 genetic resistance determinants in positive blood culture broths. A total of 1,847 blood cultures containing Gram-negative organisms were tested using the BC-GN assay. This comprised 729 prospective fresh, 781 prospective or retrospective frozen, and 337 simulated cultures representing 7 types of aerobic culture media. The results were compared to those with standard bacterial culture and biochemical identification with nucleic acid sequence confirmation of the resistance determinants. Among monomicrobial cultures, the positive percent agreement (PPA) of the BC-GN assay with the reference method was as follows;
Escherichia coli
, 100%;
Klebsiella pneumoniae
, 92.9%;
Klebsiella oxytoca
, 95.5%;
Enterobacter
spp., 99.3%;
Pseudomonas aeruginosa
, 98.9%;
Proteus
spp., 100%;
Acinetobacter
spp., 98.4%; and
Citrobacter
spp., 100%. All organism identification targets demonstrated >99.5% negative percent agreement (NPA) with the reference method. Of note, 25/26 cultures containing
K. pneumoniae
that were reported as not detected by the BC-GN assay were subsequently identified as
Klebsiella variicola
. The PPA for identification of resistance determinants was as follows;
bla
CTX-M
, 98.9%;
bla
KPC
, 100%;
bla
NDM
, 96.2%;
bla
OXA
, 94.3%;
bla
VIM
, 100%; and
bla
IMP
, 100%. All resistance determinant targets demonstrated >99.9% NPA. Among polymicrobial specimens, the BC-GN assay correctly identified at least one organism in 95.4% of the broths and correctly identified all organisms present in 54.5% of the broths. The sample-to-result processing and automated reading of the detection microarray results enables results within 2 h of culture positivity.
Fatal West Nile Virus Encephalitis in a Heart Transplant Recipient
Authors: Gomez Adam J. , Waggoner Jesse J. , Itoh Megumi , Hollander Seth A. , Gutierrez Kathleen M. , Budvytiene Indre , Banaei Niaz , Pinsky Benjamin A. 
Published: May 2015

ABSTRACT
The diagnosis of encephalitis is particularly challenging in immunocompromised patients. We report here a case of fatal West Nile virus encephalitis confounded by the presence of budding yeast in the cerebrospinal fluid (CSF) from a patient who had undergone heart transplantation for dilated cardiomyopathy 11 months prior to presentation of neurologic symptoms.
Hepatitis C Virus Core Mutations Associated with False-Negative Serological Results for Genotype 3a Core Antigen
Authors: Nguyen Linh Thuy , Dunford Linda , Freitas Ines , Holder Paul , Nguyen Lan Anh , O'Gorman Joanne , Connell Jeff , Carr Michael , Hall William , De Gascun Cillian 
Published: May 2015

ABSTRACT

Genetic characterization of the genotype 3a (GT3a) hepatitis C virus (HCV)
core
region from HCV core antigen (HCVcAg)-negative/RNA-positive cases and HCVcAg-positive/RNA-positive controls identified significant associations between the substitutions A48T and T49A/P and failure to detect HCVcAg (
P
< 0.05). Polymorphisms at residues 48 and 49 in the core protein are present across all major epidemic and endemic GTs. These findings have implications for HCV diagnosis, particularly in low-income regions in which GT3a HCV is endemic.
Rectal Carriage of Extended-Spectrum-Beta-Lactamase-Producing Enterobacteriaceae in Hospitalized Patients: Selective Preenrichment Increases Yield of Screening
Authors: Kluytmans-van den Bergh M. F. Q. , Verhulst C. , Willemsen L. E. , Verkade E. , Bonten M. J. M. , Kluytmans J. A. J. W. 
Published: May 2015

ABSTRACT

This study evaluated the added value of selective preenrichment for the detection of rectal carriage of extended-spectrum-beta-lactamase-producing
Enterobacteriaceae
(ESBL-E). ESBL-E rectal carriage was identified in 4.8% of hospitalized patients, and 25.9% of ESBL-E rectal carriers were identified with selective preenrichment only.
FUSE Binding Protein 1 Facilitates Persistent Hepatitis C Virus Replication in Hepatoma Cells by Regulating Tumor Suppressor p53
Authors: Dixit Updesh , Pandey Ashutosh K. , Liu Zhihe , Kumar Sushil , Neiditch Matthew B. , Klein Kenneth M. , Pandey Virendra N. 
Published: May 2015

ABSTRACT

Hepatitis C virus (HCV) is a leading cause of chronic hepatitis C (CHC), liver cirrhosis, and hepatocellular carcinoma (HCC). Immunohistochemistry of archived HCC tumors showed abundant FBP1 expression in HCC tumors with the CHC background. Oncomine data analysis of normal versus HCC tumors with the CHC background indicated a 4-fold increase in FBP1 expression with a concomitant 2.5-fold decrease in the expression of p53. We found that FBP1 promotes HCV replication by inhibiting p53 and regulating BCCIP and TCTP, which are positive and negative regulators of p53, respectively. The severe inhibition of HCV replication in FBP1-knockdown Huh7.5 cells was restored to a normal level by downregulation of either p53 or BCCIP. Although p53 in Huh7.5 cells is transcriptionally inactive as a result of Y220C mutation, we found that the activation and DNA binding ability of Y220C p53 were strongly suppressed by FBP1 but significantly activated upon knockdown of FBP1. Transient expression of FBP1 in FBP1 knockdown cells fully restored the control phenotype in which the DNA binding ability of p53 was strongly suppressed. Using electrophoretic mobility shift assay (EMSA) and isothermal titration calorimetry (ITC), we found no significant difference in
in vitro
target DNA binding affinity of recombinant wild-type p53 and its Y220C mutant p53. However, in the presence of recombinant FBP1, the DNA binding ability of p53 is strongly inhibited. We confirmed that FBP1 downregulates BCCIP, p21, and p53 and upregulates TCTP under radiation-induced stress. Since FBP1 is overexpressed in most HCC tumors with an HCV background, it may have a role in promoting persistent virus infection and tumorigenesis.

IMPORTANCE
It is our novel finding that FUSE binding protein 1 (FBP1) strongly inhibits the function of tumor suppressor p53 and is an essential host cell factor required for HCV replication. Oncomine data analysis of a large number of samples has revealed that overexpression of FBP1 in most HCC tumors with chronic hepatitis C is significantly linked with the decreased expression level of p53. The most significant finding is that FBP1 not only physically interacts with p53 and interferes with its binding to the target DNA but also functions as a negative regulator of p53 under cellular stress. FBP1 is barely detectable in normal differentiated cells; its overexpression in HCC tumors with the CHC background suggests that FBP1 has an important role in promoting HCV infection and HCC tumors by suppressing p53.
Prolonged Antiretroviral Therapy Preserves HIV-1-Specific CD8 T Cells with Stem Cell-Like Properties
Authors: Vigano Selena , Negron Jordi , Ouyang Zhengyu , Rosenberg Eric S. , Walker Bruce D. , Lichterfeld Mathias , Yu Xu G. 
Published: May 2015

ABSTRACT

HIV-1-specific CD8 T cells can influence HIV-1 disease progression during untreated HIV-1 infection, but the functional and phenotypic properties of HIV-1-specific CD8 T cells in individuals treated with suppressive antiretroviral therapy remain less well understood. Here we show that a subgroup of HIV-1-specific CD8 T cells with stem cell-like properties, termed T memory stem cells (T
SCM
cells), is enriched in patients receiving suppressive antiretroviral therapy compared with their levels in untreated progressors or controllers. In addition, a prolonged duration of antiretroviral therapy was associated with a progressive increase in the relative proportions of these stem cell-like HIV-1-specific CD8 T cells. Interestingly, the proportions of HIV-1-specific CD8 T
SCM
cells and total HIV-1-specific CD8 T
SCM
cells were associated with the CD4 T cell counts during treatment with antiretroviral therapy but not with CD4 T cell counts, viral loads, or immune activation parameters in untreated patients, including controllers. HIV-1-specific CD8 T
SCM
cells had increased abilities to secrete interleukin-2 in response to viral antigen, while secretion of gamma interferon (IFN-γ) was more limited in comparison to alternative HIV-1-specific CD8 T cell subsets; however, only proportions of IFN-γ-secreting HIV-1-specific CD8 T
SCM
cells were associated with CD4 T cell counts during antiretroviral therapy. Together, these data suggest that HIV-1-specific CD8 T
SCM
cells represent a long-lasting component of the cellular immune response to HIV-1 that persists in an antigen-independent fashion during antiretroviral therapy but seems unable to survive and expand under conditions of ongoing viral replication during untreated infection.

IMPORTANCE
Memory CD8 T cells that imitate the functional properties of stem cells to maintain lifelong cellular immunity have been hypothesized for many years, but only recently have such cells, termed T memory stem cells (T
SCM
cells), been physically identified and isolated in humans, mice, and nonhuman primates. Here, we investigated whether cellular immune responses against HIV-1 include such T memory stem cells. Our data show that HIV-1-specific CD8 T memory stem cells are detectable during all stages of HIV-1 infection but occur most visibly at times of prolonged viral antigen suppression by antiretroviral combination therapy. These cells may therefore be particularly relevant for designing antiviral immune defense strategies against the residual reservoir of HIV-1-infected cells that persists despite treatment and leads to viral rebound upon treatment discontinuation.
Naturally Occurring Capsid Protein Variants of Human Papillomavirus Genotype 31 Represent a Single L1 Serotype
Authors: Bissett Sara L. , Godi Anna , Fleury Maxime J. J. , Touze Antoine , Cocuzza Clementina , Beddows Simon 
Published: May 2015

ABSTRACT
We investigated naturally occurring variation within the major (L1) and minor (L2) capsid proteins of oncogenic human papillomavirus (HPV) genotype 31 (HPV31) to determine the impact on capsid antigenicity. L1L2 pseudoviruses (PsVs) representing the three HPV31 variant lineages, variant lineages A, B, and C, exhibited comparable particle-to-infectivity ratios and morphologies. Lineage-specific L1L2 PsVs demonstrated subtle differences in susceptibility to neutralization by antibodies elicited following vaccination or preclinical L1 virus-like particle (VLP) immunization or by monoclonal antibodies; however, these differences were generally of a low magnitude. These data indicate that the diagnostic lineage-specific single nucleotide polymorphisms within the HPV31 capsid genes have a limited effect on L1 antibody-mediated neutralization and that the three HPV31 variant lineages belong to a single L1 serotype. These data contribute to our understanding of HPV L1 variant antigenicity.

IMPORTANCE
The virus coat (capsid) of the human papillomavirus contains major (L1) and minor (L2) capsid proteins. These proteins facilitate host cell attachment and viral infectivity and are the targets for antibodies which interfere with these events. In this study, we investigated the impact of naturally occurring variation within these proteins upon susceptibility to viral neutralization by antibodies induced by L1 VLP immunization. We demonstrate that HPV31 L1 and L2 variants exhibit similar susceptibility to antibody-mediated neutralization and that for the purposes of L1 VLP-based vaccines, these variant lineages represent a single serotype.
Expanding Regulatory T Cells Alleviates Chikungunya Virus-Induced Pathology in Mice
Authors: Lee Wendy W. L. , Teo Teck-Hui , Her Zhisheng , Lum Fok-Moon , Kam Yiu-Wing , Haase Doreen , Rénia Laurent , Rötzschke Olaf , Ng Lisa F. P. 
Published: May 2015

ABSTRACTChikungunya virus (CHIKV) infection is a reemerging pandemic human arboviral disease. CD4+T cells were previously shown to contribute to joint inflammation in the course of CHIKV infection in mice. The JES6-1 anti-IL-2 antibody selectively expands mouse regulatory T cells (Tregs) by forming a complex with IL-2. In this study, we show that the IL-2 JES6-1-mediated expansion of Tregs ameliorates CHIKV-induced joint pathology. It does so by inhibiting the infiltration of CD4+T cells due to the induction of anergy in CHIKV-specific CD4+effector T cells. These findings suggest that activation of Tregs could also become an alternative approach to control CHIKV-mediated disease.IMPORTANCEChikungunya virus (CHIKV) has reemerged as a pathogen of global significance. Patients infected with CHIKV suffer from incapacitating joint pain that severely affects their daily functioning. Despite the best efforts, treatment is still inadequate. While T cell-mediated immunopathology in CHIKV infections has been reported, the role of regulatory T cells (Tregs) has not been explored. The JES6-1 anti-interleukin 2 (IL-2) antibody has been demonstrated to selectively expand mouse Tregs by forming a complex with IL-2. We reveal here that IL-2 JES6-1-mediated expansion of Tregs ameliorates CHIKV-induced joint pathology in mice by neutralizing virus-specific CD4+effector T (Teff) cells. We show that this treatment abrogates the infiltration of pathogenic CD4+T cells through induction of anergy in CHIKV-specific CD4+Teff cells. This is the first evidence where the role of Tregs is demonstrated in CHIKV pathogenesis, and its expansion could control virus-mediated immunopathology.