bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mouse Hepatitis Virus Stem-Loop 4 Functions as a Spacer Element Required To Drive Subgenomic RNA Synthesis
Authors: Yang Dong , Liu Pinghua , Giedroc David P. , Leibowitz Julian 
Published: June 2011

ABSTRACT

The 5′ 140 nucleotides of the mouse hepatitis virus (MHV) 5′ untranslated region (5′UTR) are predicted to contain three secondary structures, stem-loop 1 (SL1), SL2, and SL4. SL1 and SL2 are required for subgenomic RNA synthesis. The current study focuses on SL4, which contains two base-paired regions, SL4a and SL4b. A series of reverse genetic experiments show that SL4a is not required to be base paired. Neither the structure, the sequence, nor the putative 8-amino-acid open reading frame (ORF) in SL4b is required for viral replication. Viruses containing separate deletions of SL4a and SL4b are viable. However, deletion of SL4 is lethal, and genomes carrying this deletion are defective in directing subgenomic RNA synthesis. Deletion of
131
ACA
133
just 3′ to SL4 has a profound impact on viral replication. Viruses carrying the
131
ACA
133
deletion were heterogeneous in plaque size. We isolated three viruses with second-site mutations in the 5′UTR which compensated for decreased plaque sizes, delayed growth kinetics, and lower titers associated with the
131
ACA
133
deletion. The second-site mutations are predicted to change either the spacing between SL1 and SL2 or that between SL2 and SL4 or to destabilize the proximal portion of SL4a in our model. A mutant constructed by replacing SL4 with a shorter sequence-unrelated stem-loop was viable. These results suggest that the proposed SL4 in the MHV 5′UTR functions in part as a spacer element that orients SL1, SL2, and the transcriptional regulatory sequence (TRS), and this spacer function may play an important role in directing subgenomic RNA synthesis.
Engineered Single Human CD4 Domains as Potent HIV-1 Inhibitors and Components of Vaccine Immunogens
Authors: Chen Weizao , Feng Yang , Gong Rui , Zhu Zhongyu , Wang Yanping , Zhao Qi , Dimitrov Dimiter S. 
Published: June 2011

ABSTRACT
Soluble forms of the HIV-1 receptor CD4 (sCD4) have been extensively characterized for more than 2 decades as promising inhibitors and components of vaccine immunogens. However, they were mostly based on the first two CD4 domains (D1D2), and numerous attempts to develop functional, high-affinity, stable soluble one-domain sCD4 (D1) have not been successful because of the strong interactions between the two domains. We have hypothesized that combining the power of structure-based design with sequential panning of large D1 mutant libraries against different HIV-1 envelope glycoproteins (Envs) and screening for soluble mutants could not only help solve the fundamental stability problem of isolated D1, but may also allow improvement of D1 affinity while preserving its cross-reactivity. By using this strategy, we identified two stable monomeric D1 mutants, mD1.1 and mD1.2, which were significantly more soluble and bound Env gp120s more strongly (50-fold) than D1D2, neutralized a panel of HIV-1 primary isolates from different clades more potently than D1D2, induced conformational changes in gp120, and sensitized HIV-1 for neutralization by CD4-induced antibodies. mD1.1 and mD1.2 exhibited much lower binding to human blood cell lines than D1D2; moreover, they preserved a β-strand secondary structure and stability against thermally induced unfolding, trypsin digestion, and degradation by human serum. Because of their superior properties, mD1.1 and mD1.2 could be potentially useful as candidate therapeutics, components of vaccine immunogens, and research reagents for exploration of HIV-1 entry and immune responses. Our approach could be applied to other cases where soluble isolated protein domains are needed.
Alcohol involvement in aggression between intimate partners in New Zealand: a national cross-sectional study
Authors: Connor Jennie L , Kypri Kypros , Bell Melanie L , Cousins Kimberly 
Published: June 2011

ObjectivesTo examine the role of alcohol at the time of aggressive incidents between intimate partners in the general population by gender, by estimating (1) prevalence and severity of aggression, and drinking at the time, (2) associations of drinking at the time of the aggression with reported severity, anger and fear, and (3) association of usual drinking patterns with partner aggression.DesignA national survey of 18–70-year-olds using an electoral roll sample obtained self-reported alcohol consumption, partner's alcohol consumption and details of the most severe partner aggression by the respondent and towards the respondent in the past 2 years. The mean scores for associated severity, anger and fear were analysed by gender and alcohol involvement. Multinomial models estimated associations of drinking patterns with aggression to and from the respondent.ResultsThe response rate was 49% (n=1925). Men and women reported similar prevalence of victimisation and perpetration of aggression (11–15%). Alcohol was involved in more than 25% of incidents, and reported more by women than by men, particularly male-only drinking when the respondent was the victim. Women reported greater severity, anger and fear with victimisation than men, and drinking was associated with greater reported severity. Heavy episodic drinking by respondents was associated with a threefold increase in victimisation and doubling of perpetration of aggression involving alcohol. Heavy episodic drinking by either partner was also associated with drinking being involved in reported aggression.ConclusionsThe experience of intimate-partner aggression in a cross-section of households differs by gender and the involvement of alcohol, and ‘counts’ of aggressive acts in a population-based survey do not reflect the reality of gender differences. Heavy episodic drinking patterns are associated with more aggression involving alcohol within relationships, and alcohol involvement is associated with increased severity.
AXIOMATIZATIONS AND FACTORIZATIONS OF SUGENO UTILITY FUNCTIONS
Authors: COUCEIRO MIGUEL , WALDHAUSER TAMÁS 
Published: June 2011

In this paper we consider a multicriteria aggregation model where local utility functions of different sorts are aggregated using Sugeno integrals, and which we refer to as Sugeno utility functions. We propose a general approach to study such functions via the notion of pseudo-Sugeno integral (or, equivalently, pseudo-polynomial function), which naturally generalizes that of Sugeno integral, and provide several axiomatizations for this class of functions.Moreover, we address and solve the problem of factorizing a Sugeno utility function as a composition q(φ1(x1),…,φn(xn)) of a Sugeno integral q with local utility functions φi, if such a factorization exists.
VHL Gene Mutations and Their Effects on Hypoxia Inducible Factor HIFα: Identification of Potential Driver and Passenger Mutations
Authors: Rechsteiner Markus P. , von Teichman Adriana , Nowicka Anna , Sulser Tullio , Schraml Peter , Moch Holger 
Published: June 2011

Abstract
Mutations of the von Hippel-Lindau (VHL) gene are frequent in clear cell renal cell carcinomas (ccRCC). Nonsense and frameshift mutations abrogate the function of the VHL protein (pVHL), whereas missense mutations can have different effects. To identify those missense mutations with functional consequences, we sequenced VHL in 256 sporadic ccRCC and identified 187 different VHL mutations of which 65 were missense mutations. Location and destabilizing effects of VHL missense mutations were determined in silico. The majority of the thermodynamically destabilizing missense mutations were located in exon 1 in the core of pVHL, whereas protein surface mutations in exon 3 affected the interaction domains of elongin B and C. Their impact on pVHL's functionality was further investigated in vitro by stably reintroducing VHL missense mutations into a VHL null cell line and by monitoring the green fluorescent protein (GFP) signals after the transfection of a hypoxia inducible factor (HIF)α-GFP expression vector. pVHL's functionality ranged from no effect to complete HIF stabilization. Interestingly, Asn78Ser, Asp121Tyr, and Val130Phe selectively influenced HIF1α and HIF2α degradation. In summary, we obtained three different groups of missense mutations: one with severe destabilization of pVHL; a second without destabilizing effects on pVHL but relevance for the interaction with HIFα, elongin B, and elongin C; and a third with pVHL functions comparable with wild type. We therefore conclude that the specific impact of missense mutations may help to distinguish between driver and passenger mutations and may explain responses of ccRCC patients to HIF-targeted therapies. Cancer Res; 71(16); 5500–11. ©2011 AACR.
Matrix Metalloproteinase (MMP)-3 Activates MMP-9 Mediated Vascular Smooth Muscle Cell Migration and Neointima Formation in Mice
Authors: Johnson Jason L. , Dwivedi Amrita , Somerville Michelle , George Sarah J. , Newby Andrew C. 
Published: July 2011

Objective—
Several matrix metalloproteinases (MMPs) have been implicated in extracellular matrix destruction and other actions that lead to plaque rupture and myocardial infarction. Conversely, other MMPs have been shown to promote vascular smooth muscle cell (VSMC)–driven neointima formation, which contributes to restenosis, fibrous cap formation, and plaque stability. MMP-3 knockout reduced VSMC accumulation in mouse atherosclerotic plaques, implicating MMP-3 in neointima formation. We therefore investigated the effect of MMP-3 knockout on neointima formation after carotid ligation in vivo and VSMC migration in vitro.

Methods and Results—

Twenty-eight days after left carotid ligation, MMP-3 knockout significantly reduced neointima formation (75%,
P
<0.01) compared with wild-type (WT) littermates, and also reduced remodeling of ligated and contralateral carotid arteries. Gelatin zymography illustrated that MMP-3 knockout abolished MMP-9 activation in ligated carotids and scratch-wounded VSMC cultures. MMP-3 knockout also attenuated VSMC migration into a scratch wound by 59% compared with WT cells. Addition of exogenous MMP-3 or activated MMP-9 restored migration of MMP-3 knockouts to that of WT VSMCs, but exogenous MMP-3 had no effect on migration in MMP-9 knockout VSMCs. MMP-9 knockout or knockdown with small interfering RNA significantly retarded VSMC migration to the same extent as MMP-3 knockout.

Conclusion—
These results indicate for the first time that MMP-3 mediated activation of MMP-9 is required for efficient neointima formation after carotid ligation in vivo and for VSMC migration in vitro, whereas MMP-12 plays a redundant role. These findings add to the understanding of MMP action in plaque stability and restenosis.
Vitamin D Deficiency Is Associated With Subclinical Carotid Atherosclerosis
Authors: Carrelli Angela L. , Walker Marcella D. , Lowe Hyesoo , McMahon Don J. , Rundek Tatjana , Sacco Ralph L. , Silverberg Shonni J. 
Published: July 2011

Background and Purpose—
The purpose of this study was to assess the association of vitamin D deficiency and indices of mineral metabolism with subclinical carotid markers that predict cardiovascular events.

Methods—
Two hundred three community-dwelling adults (Northern Manhattan Study; age, 68±11; age range, 50 to 93 years) had serum measurements (calcium, phosphorus, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, parathyroid hormone) and carotid ultrasound (plaque presence, number, maximal carotid plaque thickness, intima-media thickness).

Results—

Adjusting for cardiovascular risk factors, plaque number was associated with phosphorus levels (β=0.39 per 1-mg/dL increase;
P
=0.02) and calcium–phosphorus product (β=0.36 per 10-U increase;
P
=0.03). In those with plaque (N=116 [57%]), the association of plaque number with phosphorus and calcium–phosphorus product persisted. In addition, 25-hydroxyvitamin D was inversely associated with both intima-media thickness (β=−0.01 per 10-ng/mL increase;
P
=0.05) and maximal carotid plaque thickness (β=−0.10 per 10-ng/mL increase;
P
=0.03). In a model containing traditional cardiac risk factors and indices of mineral metabolism, 25-hydroxyvitamin D accounted for 13% of the variance in both intima-media thickness and maximal carotid plaque thickness. Calcium, parathyroid hormone, and 1,25-dihydroxyvitamin D levels were not associated with carotid measures.

Conclusions—
After adjusting for cardiovascular risk factors and renal function, serum phosphorus and calcium–phosphorus product were associated with a greater burden of subclinical carotid atherosclerosis. Low 25-hydroxyvitamin D levels were associated with increased intima-media thickness and maximal carotid plaque thickness in those with plaque, and 25-hydroxyvitamin D contributed in a robust manner to the variance in both. These results confirm and extend data on the association of low vitamin D levels with subclinical carotid atherosclerosis. The precise nature of this association and the optimum levels of vitamin D for vascular health remain to be elucidated.
Blood–Brain Barrier Permeability Abnormalities in Vascular Cognitive Impairment
Authors: Taheri Saeid , Gasparovic Charles , Huisa Branko N. , Adair John C. , Edmonds Elaine , Prestopnik Jillian , Grossetete Mark , Shah N. Jon , Wills John , Qualls Clifford , Rosenberg Gary A. 
Published: July 2011

Background and Purpose—
Disruption of the blood–brain barrier has been proposed to be important in vascular cognitive impairment. Increased cerebrospinal fluid albumin and contrast-enhanced MRI provide supporting evidence, but quantification of the blood–brain barrier permeability in patients with vascular cognitive impairment is lacking. Therefore, we acquired dynamic contrast-enhanced MRI to quantify blood–brain barrier permeability in vascular cognitive impairment.

Method—
We studied 60 patients with suspected vascular cognitive impairment. They had neurological and neuropsychological testing, permeability measurements with dynamic contrast-enhanced MRI, and lumbar puncture to measure albumin index. Patients were separated clinically into subcortical ischemic vascular disease (SIVD), multiple and lacunar infarcts, and leukoaraiosis. Twenty volunteers were controls for the dynamic contrast-enhanced MRI studies, and control cerebrospinal fluid was obtained from 20 individuals undergoing spinal anesthesia for nonneurological problems.

Results—

Thirty-six patients were classified as SIVD, 8 as multiple and lacunar infarcts, and 9 as leukoaraiosis. The albumin index was significantly increased in the SIVD group compared with 20 control subjects. Permeabilities for the patients with vascular cognitive impairment measured by dynamic contrast-enhanced MRI were significantly increased over control subjects (
P
<0.05). Patient age did not correlate with either the blood–brain barrier permeability or albumin index. Highest albumin index values were seen in the SIVD group (
P
<0.05) and were significantly increased over multiple and lacunar infarcts. K
i
values were elevated over control subjects in SIVD but were similar to multiple and lacunar infarcts.

Conclusions—
There was abnormal permeability in white matter in patients with SIVD as shown by dynamic contrast-enhanced MRI and albumin index. Future studies will be needed to determine the relationship of blood–brain barrier damage and development of white matter hyperintensities.
On Changing El Niño: A View from Time-Varying Annual Cycle, Interannual Variability, and Mean State
Authors: Qian Cheng , Wu Zhaohua , Fu Congbin , Wang Dongxiao 
Published: July 2011

Abstract
This study investigates changes in the frequency of ENSO, especially the prolonged 1990–95 El Niño event, in the context of secular changes in the annual cycle, ENSO interannual variability, and background mean state of the tropical eastern Pacific sea surface temperature (SST). The ensemble empirical mode decomposition (EEMD) method is applied to isolate those components from the Niño-3 SST index for the period 1880–2008. It is shown that the annual cycle [referred to as a refined modulated annual cycle (MAC)] has strong interannual modulation and secular change in both amplitude and phase: a clear transition from increasing to decreasing amplitude around 1947/48, with both linear trends before and after this turning point statistically significant and the amplitude decreasing by 14% since then, and a significant phase delay trend for the period 1881–1938, but hardly any thereafter. A clear transition from significant deceasing to increasing by about 30% in the amplitude of the ENSO interannual variability around 1937 is also found. When El Niño events are represented as the collective interannual variability, their frequency is found to be almost equivalent to that of La Niña events after 1976. A method for conducting synthetic experiments based on time series analysis further reveals that the apparent prolonged 1990–95 El Niño event was not caused solely by ENSO interannual variability. Rather, the 1991/92 warm period is attributable to an interannual variation superimposed by change in the background mean state; the 1993 warm period is attributable to change in the mean state; and the 1994/95 warm period is attributable to a residual annual cycle, which cannot be fully excluded by a 30-yr mean annual cycle approach. The impact that changing base periods has on the classification of ENSO events and possible solutions is also discussed.
Investigation of Ensemble Variance as a Measure of True Forecast Variance
Authors: Kolczynski Walter C. , Stauffer David R. , Haupt Sue Ellen , Altman Naomi S. , Deng Aijun 
Published: July 2011

Abstract
The uncertainty in meteorological predictions is of interest for applications ranging from economic to recreational to public safety. One common method to estimate uncertainty is by using meteorological ensembles. These ensembles provide an easily quantifiable measure of the uncertainty in the forecast in the form of the ensemble variance. However, ensemble variance may not accurately reflect the actual uncertainty, so any measure of uncertainty derived from the ensemble should be calibrated to provide a more reliable estimate of the actual uncertainty in the forecast. A previous study introduced the linear variance calibration (LVC) as a simple method to determine the ensemble variance to error variance relationship and demonstrated this technique on real ensemble data. The LVC parameters, the slopes, and y intercepts, however, are generally different from the ideal values.
This current study uses a stochastic model to examine the LVC in a controlled setting. The stochastic model is capable of simulating underdispersive and overdispersive ensembles as well as perfectly reliable ensembles. Because the underlying relationship is specified, LVC results can be compared to theoretical values of the slope and y intercept. Results indicate that all types of ensembles produce calibration slopes that are smaller than their theoretical values for ensemble sizes less than several hundred members, with corresponding y intercepts greater than their theoretical values. This indicates that all ensembles, even otherwise perfect ensembles, should be calibrated if the ensemble size is less than several hundred.
In addition, it is shown that an adjustment factor can be computed for inadequate ensemble size. This adjustment factor is independent of the stochastic model and is applicable to any linear regression of error variance on ensemble variance. When applied to experiments using the stochastic model, the adjustment produces LVC parameters near their theoretical values for all ensemble sizes. Although the adjustment is unnecessary when applying LVC, it allows for a more accurate assessment of the reliability of ensembles, and a fair comparison of the reliability for differently sized ensembles.
Multiscale Processes Leading to Supercells in the Landfalling Outer Rainbands of Hurricane Katrina (2005)
Authors: Green Benjamin W. , Zhang Fuqing , Markowski Paul 
Published: July 2011

AbstractShallow supercells are frequently observed within the outer rainbands—both onshore and offshore—of landfalling tropical cyclones (TCs). Such supercells can produce tornadoes along the coast even when the center of the parent TC is hundreds of kilometers from land, as was the case with Hurricane Katrina (2005). A convection-permitting simulation with 1.5-km grid spacing in the innermost domain is used in conjunction with radar, radiosonde, and surface observations to investigate the multiscale conditions conducive to supercells in the landfalling outer rainbands of Katrina. Several hours before the eye of the TC made landfall, a baroclinic zone developed along the coast; this front strongly influenced the horizontal distributions of cell-relative helicity and CAPE such that the largest values of these parameters were located over land and water, respectively. An example of a tornadic supercell in the outer rainbands of Katrina is examined. This cell intensified just before landfall and spawned a tornado along the coast, demonstrating the ability of baroclinic boundaries to enhance low-level horizontal vorticity and subsequently intensify updraft rotation within passing cells. Farther inland, the tornadic cell weakened rapidly, suggesting the presence of a narrow coastal zone in which both shear and buoyancy are favorable for tornadogenesis.
Stigmatization of ‘psychiatric label’ by medical and non-medical students
Authors: Totic Sanja , Stojiljković Dragan , Pavlovic Zorana , Zaric Nenad , Zarkovic Boris , Malic Ljubica , Mihaljevic Marina , Jašović-Gašić Miroslava , Marić Nadja P. 
Published: July 2011

Backround: Stigmatization of psychiatric patients is present both in the general population and among healthcare professionals. Aim: To determine the attitudes and behaviour of medical students towards a person who goes to a psychiatrist, before and after psychiatric rotation, and to compare those attitudes between medical and non-medical students. Methods: The study included 525 medical students (second and sixth year of studies) and 154 students of law. The study instrument was a three-part self-reported questionnaire (socio-demographic data, Rosenberg Self-Esteem Scale and a vignette depicting a young, mentally healthy person). The experimental intervention consisted of ascribing a ‘psychiatric label’ to only one set of vignettes. All the vignettes (with or without the ‘psychiatric label’) were followed by 14 statements addressing the acceptance of a person described by vignette, as judged by social distance (four-point Likert scale). Results: Higher tendency to stigmatize was found in medical students in the final year, after psychiatric rotation ( Z U = −3.12, p = .002), particularly in a closer relationship ( Z U = −2.67, p = .007) between a student and a hypothetical person who goes to a psychiatrist. The non-medical students had a similar tendency to stigmatize as medical students before psychiatric rotation ( Z U = −0.03, p = .975). Neither gender, nor the size of student’s place of origin or average academic mark was associated with the tendency to stigmatize in our sample. However, student’s elf-esteem was lower in those with a tendency to stigmatize more in a distant relationship (ρ = −0.157, p = .005). Conclusions: Psychiatric education can either reinforce stigmatization or reduce it. Therefore, detailed analyses of educational domains that reinforce stigma will be the starting point for anti-stigma action.