bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cyclic Di-GMP Receptor PlzA Controls Virulence Gene Expression through RpoS in Borrelia burgdorferi
Authors: He Ming , Zhang Jun-Jie , Ye Meiping , Lou Yongliang , Yang X. Frank 
Published: November 2013

ABSTRACT

As an obligate pathogen, the Lyme disease spirochete
Borrelia burgdorferi
has a streamlined genome that encodes only two two-component signal transduction systems, Hk1-Rrp1 and Hk2-Rrp2 (in addition to CheA-CheY systems). The output of Hk1-Rrp1 is the production of the second messenger cyclic di-GMP (c-di-GMP), which is indispensable for
B. burgdorferi
to survive in the tick vector. The output of Hk2-Rrp2 is the transcriptional activation of the global regulator RpoS, which is essential for the pathogen to accomplish its tick-mouse transmission and to establish mammalian infection. Although evidence indicates that these two systems communicate with each other, how they are connected is not fully understood. In this study, we showed that the c-di-GMP-binding protein PlzA, a downstream effector of Rrp1, positively modulates the production of RpoS, a global regulator and downstream target of Rrp2. Thus, PlzA functions as a connector that links Hk1-Rrp1 with Hk2-Rrp2. We further showed that PlzA regulates
rpoS
expression through modulation of another regulator, BosR, at both the transcriptional and the posttranscriptional levels. In addition, PlzA was also capable of regulating
rpoS
expression independently of Rrp1, suggesting that besides being a c-di-GMP-binding protein, PlzA has other functions. Along with the previous finding of PlzA controlling motility, these studies demonstrate that PlzA is a multifunctional protein. These findings further reinforce the notion that
B. burgdorferi
utilizes its limited signaling systems and regulators to govern multiple cellular processes during its complex enzootic cycle between ticks and mammals.
Fungal Morphogenetic Pathways Are Required for the Hallmark Inflammatory Response during Candida albicans Vaginitis
Authors: Peters Brian M. , Palmer Glen E. , Nash Andrea K. , Lilly Elizabeth A. , Fidel Paul L. , Noverr Mairi C. 
Published: November 2013

ABSTRACT

Vulvovaginal candidiasis, caused primarily by
Candida albicans
, presents significant health issues for women of childbearing age. As a polymorphic fungus, the ability of
C. albicans
to switch between yeast and hyphal morphologies is considered its central virulence attribute. Armed with new criteria for defining vaginitis immunopathology, the purpose of this study was to determine whether the yeast-to-hypha transition is required for the hallmark inflammatory responses previously characterized during murine vaginitis. Kinetic analyses of vaginal infection with
C. albicans
in C57BL/6 mice demonstrated that fungal burdens remained constant throughout the observation period, while polymorphonuclear leukocyte (PMN), S100A8, and interleukin-1β levels obtained from vaginal lavage fluid increased by day 3 onward. Lactate dehydrogenase activity was also positively correlated with increased effectors of innate immunity. Additionally, immunodepletion of neutrophils in infected mice confirmed a nonprotective role for PMNs during vaginitis. Determination of the importance of fungal morphogenesis during vaginitis was addressed with a two-pronged approach. Intravaginal inoculation of mice with
C. albicans
strains deleted for key transcriptional regulators (
bcr1
Δ/Δ,
efg1
Δ/Δ,
cph1
Δ/Δ, and
efg1
Δ/Δ
cph1
Δ/Δ) controlling the yeast-to-hypha switch revealed a crucial role for morphogenetic signaling through the Efg1 and, to a lesser extent, the Bcr1 pathways in contributing to vaginitis immunopathology. Furthermore, overexpression of transcription factors
NRG1
and
UME6
, to maintain yeast and hyphal morphologies, respectively, confirmed the importance of morphogenesis in generating innate immune responses
in vivo
. These results highlight the yeast-to-hypha switch and the associated morphogenetic response as important virulence components for the immunopathogenesis of
Candida
vaginitis, with implications for transition from benign colonization to symptomatic infection.
Sentinel lymph nodes with isolated tumour cells and micrometastases in breast cancer: clinical relevance and prognostic significance
Authors: Ahmed Syed Salahuddin , Thike Aye Aye , Iqbal Jabed , Yong Wei Sean , Tan Benita , Madhukumar Preetha , Ong Kong Wee , Ho Gay Hui , Wong Chow Yin , Tan Puay Hoon 
Published: November 2013

AimWe performed a retrospective review to determine the prognostic significance of isolated tumour cells (ITCs) and micrometastases to the sentinel lymph nodes of patients with breast cancer.MethodsA total of 1044 patients with a diagnosis of invasive carcinoma of the breast who underwent surgical treatment including the sentinel lymph node biopsy procedure from July 2004 to October 2009 were included in the study.ResultsIn 710 (68%) patients, no metastasis was seen to the sentinel lymph nodes. ITCs were detected in 22 (2.1%) patients, micrometastasis in 52 (5.0%) and macrometastases in 260 (24.9%). With a median follow-up of 28.8 months, disease recurrence was seen in 38 (3.6%) patients and 15 (1.5%) patients died of disease. No disease recurrence or deaths were recorded in women with ITCs in sentinel lymph nodes. In the micrometastasis group, 2 patients suffered disease recurrence and both died of disease.ConclusionsWe conclude that ITCs in the sentinel lymph nodes did not adversely impact disease free and overall survivals. Although only 2 recurrences with subsequent death occurred in the micrometastasis group, it may suggest a propensity for presence of micrometastases to augur a worse outcome, and justifies continued segregation of ITCs from micrometastasis.
Male hypercalciuric stone formers with low renal calcium reabsorption
Authors: Walker Valerie , Cook Paul , Griffin Damian G 
Published: November 2013

AimsHypercalciuria is a common poorly understood abnormality among stone formers. We aimed to identify hypercalciuric male stone formers with a primary defect in renal calcium reabsorption and to look for associated risk factors.MethodsA retrospective cross-sectional database study of 623 male idiopathic calcium stone formers with normal plasma ultrafilterable calcium levels attending the Southampton stone clinic. Filtered calcium was estimated from plasma ultrafilterable calcium (60% of total plasma calcium) and 24 h creatinine clearance. Reabsorbed calcium was the difference between filtered and excreted calcium.Results276 men had hypercalciuria (urine calcium >7.50 mmol/24 h); 347 had normocalciuria. Hypercalciuric men filtered more calcium than normocalciuric men: median values 247 and 227 mmol/24 h, but the ranges overlapped (175–371 and 153–316 mmol/24 h). However, across the entire filtration range, hypercalciuric men reabsorbed less of the filtered calcium. Among the hypercalciuric men, we noticed differences between those with high and low filtration. We therefore compared data for hypercalciuric men in the highest and lowest filtration quintiles (n=55). Men with high filtration were younger at their first stone episode and had significantly higher plasma ultrafilterable calcium and calcium reabsorption, urinary calcium, oxalate, urate and creatinine excretion and creatinine clearance. 35% with high filtration and 40% with low filtration had recurrent stones; 27% and 20%, respectively, had an affected first-degree relative.ConclusionsHypercalciuric men reabsorbed proportionately less filtered calcium than normocalciuric men. Among hypercalciuric men, the risks for stones were higher in those with a high than a low filtered calcium load and presentation was earlier.
Contracts for First-Class Classes
Authors: Strickland T. Stephen , Dimoulas Christos , Takikawa Asumu , Felleisen Matthias 
Published: November 2013

First-class classes enable programmers to abstract over patterns in the class hierarchy and to experiment with new forms of object-oriented programming such as mixins and traits. This increase in expressive power calls for tools to control the complexity of the software architecture. A contract system is one possible tool that has seen much use in object-oriented programming languages, but existing contract systems cannot cope with first-class classes. On the one hand, the typical contract language deals only with plain values such as numbers, while classes are higher-order values. On the other hand, contract specifications are usually contained within class definitions, while classes as values call for a separate contract language.
This article presents the design and implementation of a contract system for first-class classes as well as a two-pronged evaluation. The first one states and proves a “blame correctness” theorem for a model of our language. The theorem shows that when the contract system assigns blame to a component for a contract violation, the component is indeed responsible for providing the nonconforming value. The second part, consisting of benchmarks and case studies, demonstrates the need for the rich contract language and validates that our implementation approach is performant with respect to time.
A Collagen-Remodeling Gene Signature Regulated by TGF-β Signaling Is Associated with Metastasis and Poor Survival in Serous Ovarian Cancer
Authors: Cheon Dong-Joo , Tong Yunguang , Sim Myung-Shin , Dering Judy , Berel Dror , Cui Xiaojiang , Lester Jenny , Beach Jessica A. , Tighiouart Mourad , Walts Ann E. , Karlan Beth Y. , Orsulic Sandra 
Published: November 2013

AbstractPurpose: To elucidate molecular pathways contributing to metastatic cancer progression and poor clinical outcome in serous ovarian cancer.Experimental Design: Poor survival signatures from three different serous ovarian cancer datasets were compared and a common set of genes was identified. The predictive value of this gene signature was validated in independent datasets. The expression of the signature genes was evaluated in primary, metastatic, and/or recurrent cancers using quantitative PCR and in situ hybridization. Alterations in gene expression by TGF-β1 and functional consequences of loss of COL11A1 were evaluated using pharmacologic and knockdown approaches, respectively.Results: We identified and validated a 10-gene signature (AEBP1, COL11A1, COL5A1, COL6A2, LOX, POSTN, SNAI2, THBS2, TIMP3, and VCAN) that is associated with poor overall survival (OS) in patients with high-grade serous ovarian cancer. The signature genes encode extracellular matrix proteins involved in collagen remodeling. Expression of the signature genes is regulated by TGF-β1 signaling and is enriched in metastases in comparison with primary ovarian tumors. We demonstrate that levels of COL11A1, one of the signature genes, continuously increase during ovarian cancer disease progression, with the highest expression in recurrent metastases. Knockdown of COL11A1 decreases in vitro cell migration, invasion, and tumor progression in mice.Conclusion: Our findings suggest that collagen-remodeling genes regulated by TGF-β1 signaling promote metastasis and contribute to poor OS in patients with serous ovarian cancer. Our 10-gene signature has both predictive value and biologic relevance and thus may be useful as a therapeutic target. Clin Cancer Res; 20(3); 711–23. ©2013 AACR.
Cyclone Wind Field Asymmetries during Extratropical Transition in the Western North Pacific
Authors: Loridan T. , Scherer E. , Dixon M. , Bellone E. , Khare S. 
Published: November 2013

AbstractRisk-assessment systems for wind hazards (e.g., hurricanes or typhoons) often rely on simple parametric wind field formulations. They are built using extensive observations of tropical cyclones and make assumptions about wind field asymmetry. In this framework, maximum winds are always simulated to the right of the cyclone, but analysis of the Climate Forecast System Reanalysis database for the western North Pacific Ocean suggests that wind fields from cyclones undergoing extratropical transition around Japan often present features that cannot be adequately simulated under these assumptions. These “left-hand-side contribution” (LHSC) wind fields exhibit strong winds on both sides of the moving cyclone with the maximum magnitude often located to the left. Classification of cyclones in terms of their most frequent patterns reveals that 67% of cases that make a transition around Japan are dominantly LHSC. They are more likely in autumn and have more intense maximum winds. The results from this study show the need for a new approach to the modeling of transitioning wind fields in the context of risk-assessment systems.
Parameter Study of Tropical Cyclones in Rotating Radiative–Convective Equilibrium with Column Physics and Resolution of a 25-km GCM
Authors: Zhou Wenyu , Held Isaac M. , Garner Stephen T. 
Published: November 2013

Abstract
Rotating radiative–convective equilibrium is studied by extracting the column physics of a mesoscale-resolution global atmospheric model that simulates realistic hurricane frequency statistics and then coupling it to rotating hydrostatic dynamics in doubly periodic domains. The parameter study helps in understanding the tropical cyclones simulated in the global model and also provides a reference point for analogous studies with cloud-resolving models.
The authors first examine the sensitivity of the equilibrium achieved in a large square domain (2 × 104 km on a side) to sea surface temperature, ambient rotation rate, and surface drag coefficient. In such a large domain, multiple tropical cyclones exist simultaneously. The size and intensity of these tropical cyclones are investigated.
The variation of rotating radiative–convective equilibrium with domain size is also studied. As domain size increases, the equilibrium evolves through four regimes: a single tropical depression, an intermittent tropical cyclone with widely varying intensity, a single sustained storm, and finally multiple storms. As SST increases or ambient rotation rate f decreases, the sustained storm regime shifts toward larger domain size. The storm’s natural extent in large domains can be understood from this regime behavior.
The radius of maximum surface wind, although only marginally resolved, increases with SST and increases with f for small f when the domain is large enough. These parameter dependencies can be modified or even reversed if the domain is smaller than the storm’s natural extent.
Performance of Hot Plate for Measuring Solid Precipitation in Complex Terrain during the 2010 Vancouver Winter Olympics
Authors: Boudala Faisal S. , Rasmussen Roy , Isaac George A. , Scott Bill 
Published: November 2013

Abstract
Solid precipitation intensity, snow density, wind speed, and temperature were collected from November 2009 to February 2010 at a naturally sheltered station located at an altitude of 1640 m MSL on Whistler Mountain in British Colombia, Canada. The snowfall was measured using the instruments OTT Pluvio; the Yankee Environmental Systems, Inc., hot plate (HP); and the Vaisala FD12P (optical weather sensor). The snow amount and density were also measured manually daily. The observed wind speeds were in the range 0–4.5 m s−1 with a mean value of 0.5 m s−1. Based on this study, the HP overestimated the snow amount by about a factor of 2 as compared to the Pluvio measurements. Further data analysis using the raw output HP data suggests that this was because of false precipitations produced, particularly by the downslope flows in the complex terrain when the wind speeds were relatively stronger. This false precipitation varied from −0.9 to 1.3 mm h−1 with two peaks at 0.1 and 0.3 mm h−1 depending on wind speed—the larger peak being at higher wind speeds. Since the observed wind speeds were relatively calm, setting the correction factor to 0.15 mm h−1 gave reasonable values as compared to the Pluvio data. The difference between the corrected HP and Pluvio accumulation data varied from 16% to 3% depending on wind speed. The observed snow density in January 2010 varied from 0.04 to 0.32 g cm−3 with a mean value of 0.08 g cm−3. The snow amount measured using the corrected HP data agreed well with the manually measured values with a correlation coefficient of 0.93.
Weather, Climate, and the Economy: Explaining Risk Perceptions of Global Warming, 2001–10*
Authors: Shao Wanyun , Keim Barry D. , Garand James C. , Hamilton Lawrence C. 
Published: November 2013

Abstract
Two series of national survey datasets (2001–10), supplemented with monthly temperature and precipitation data and unemployment data, are used to examine how weather and climate, economic performance, and individuals’ sociodemographic backgrounds and political orientations affect public perceptions of global warming. Consistent with previous studies, political orientations play a key role in determining public perceptions of global warming. Democrats and liberals are more likely than Republicans and conservatives to see global warming as an immediate and serious problem. Sociodemographic characteristics are also shown to be significant factors, with young people, women, and racial minorities likely to show higher concern about global warming than their counterparts. Moreover, individuals with lower income and higher levels of education tend to be more concerned about global warming. Net of these factors, summer temperature trends over the past 10 years, among other weather and climate measures, are shown to have consistently positive effects on public perceptions of global warming. This suggests that individuals who have experienced increasing summer heat are most likely to perceive immediate impacts and severity of global warming. Surprisingly, macroeconomic conditions—represented by the unemployment rate at the county level—do not appear to influence public perceptions of global warming.
Controllability for nonlinear evolution equations with monotone operators
Authors: Kang Yong Han , Jeong Jin-Mun , Rho Hyun-Hee 
Published: November 2013

Abstract
In this paper, we investigate the approximate controllability for nonlinear evolution equations with monotone operators and nonlinear controllers according to monotone operator theory. We also give the regularity for the nonlinear equation. Finally, an example, to which our main result can be applied, is given.

MSC:35F25, 93C20.
PlantTFcat: an online plant transcription factor and transcriptional regulator categorization and analysis tool
Authors: Dai Xinbin , Sinharoy Senjuti , Udvardi Michael , Zhao Patrick Xuechun 
Published: November 2013

Abstract

Background
Plants regulate intrinsic gene expression through transcription factors (TFs), transcriptional regulators (TRs), chromatin regulators (CRs), and the basal transcription machinery. An understanding of plant gene regulatory mechanisms at a systems level requires the identification of these regulatory elements on a genomic scale.

Results
Here, we present PlantTFcat, a high-performance web-based analysis tool that is designed to identify and categorize plant TF/TR/CR genes from genome-scale protein and nucleic acid sequences by systematically analyzing InterProScan domain patterns in protein sequences. The comprehensive prediction logics that are included in PlantTFcat are based on relationships between gene families and conserved domains from 108 published plant TF/TR/CR families. These prediction logics effectively distinguish TF/TR/CR families with common conserved domains. Our systematic performance evaluations indicate that PlantTFcat annotates known TF/TR/CR families with high coverage and sensitivity.

Conclusions
PlantTFcat provides an analysis tool to identify and categorize plant TF/TR/CR genes on a genomic scale. PlantTFcat is freely available to the public at http://plantgrn.noble.org/PlantTFcat/.
Dynamics of malaria transmission and susceptibility to clinical malaria episodes following treatment of Plasmodium falciparum asymptomatic carriers: results of a cluster-randomized study of community-wide screening and treatment, and a parallel entomology study
Authors: Tiono Alfred B , Guelbeogo Moussa W , Sagnon N Falé , Nébié Issa , Sirima Sodiomon B , Mukhopadhyay Amitava , Hamed Kamal 
Published: November 2013

Abstract

Background
In malaria-endemic countries, large proportions of individuals infected with Plasmodium falciparum are asymptomatic and constitute a reservoir of parasites for infection of newly hatched mosquitoes.

Methods
Two studies were run in parallel in Burkina Faso to evaluate the impact of systematic identification and treatment of asymptomatic carriers of P. falciparum, detected by rapid diagnostic test, on disease transmission and susceptibility to clinical malaria episodes. A clinical study assessed the incidence of symptomatic malaria episodes with a parasite density >5,000/μL after three screening and treatment campaigns ~1 month apart before the rainy season; and an entomological study determined the effect of these campaigns on malaria transmission as measured by entomological inoculation rate.

Results
The intervention arm had lower prevalence of asymptomatic carriers of asexual parasites and lower prevalence of gametocyte carriers during campaigns 2 and 3 as compared to the control arm. During the entire follow-up period, out of 13,767 at-risk subjects, 2,516 subjects (intervention arm 1,332; control arm 1,184) had symptomatic malaria. Kaplan-Meier analysis of the incidence of first symptomatic malaria episode with a parasite density >5,000/μL showed that, in the total population, the two treatment arms were similar until Week 11–12 after campaign 3, corresponding with the beginning of the malaria transmission season, after which the probability of being free of symptomatic malaria was lower in the intervention arm (logrank p < 0.0001). Similar trends were observed in infants and children <5 years and in individuals ≥5 years of age. In infants and children <5 years old who experienced symptomatic malaria episodes, the geometric mean P. falciparum density was lower in the intervention arm than the control arm. This trend was not seen in those individuals aged ≥5 years. Over the year, monthly variation in mosquito density and entomological inoculation rate was comparable in both arms, with September peaks in both indices.

Conclusion
Community screening and targeted treatment of asymptomatic carriers of P. falciparum had no effect on the dynamics of malaria transmission, but seemed to be associated with an increase in the treated community’s susceptibility to symptomatic malaria episodes after the screening campaigns had finished. These results highlight the importance of further exploratory studies to better understand the dynamics of disease transmission in the context of malaria elimination.