bluuebunny/crossref_metadata_2025_split huggingface dataset:
Memory B Cell Responses to Vibrio cholerae O1 Lipopolysaccharide Are Associated with Protection against Infection from Household Contacts of Patients with Cholera in Bangladesh
Authors: Patel Sweta M. , Rahman Mohammad Arif , Mohasin M. , Riyadh M. Asrafuzzaman , Leung Daniel T. , Alam Mohammad Murshid , Chowdhury Fahima , Khan Ashraful I. , Weil Ana A. , Aktar Amena , Nazim Mohammad , LaRocque Regina C. , Ryan Edward T. , Calderwood Stephen B. , Qadri Firdausi , Harris Jason B. 
Published: April 2012

ABSTRACT

Vibrio cholerae
O1 causes cholera, a dehydrating diarrheal disease. We have previously shown that
V. cholerae
-specific memory B cell responses develop after cholera infection, and we hypothesize that these mediate long-term protective immunity against cholera. We prospectively followed household contacts of cholera patients to determine whether the presence of circulating
V. cholerae
O1 antigen-specific memory B cells on enrollment was associated with protection against
V. cholerae
infection over a 30-day period. Two hundred thirty-six household contacts of 122 index patients with cholera were enrolled. The presence of lipopolysaccharide (LPS)-specific IgG memory B cells in peripheral blood on study entry was associated with a 68% decrease in the risk of infection in household contacts (
P
= 0.032). No protection was associated with cholera toxin B subunit (CtxB)-specific memory B cells or IgA memory B cells specific to LPS. These results suggest that LPS-specific IgG memory B cells may be important in protection against infection with
V. cholerae
O1.
Identification and Diagnostic Utility of Leishmania infantum Proteins Found in Urine Samples from Patients with Visceral Leishmaniasis
Authors: Abeijon Claudia , Kashino Suely S. , Silva Fernando O. , Costa Dorcas L. , Fujiwara Ricardo T. , Costa Carlos H. N. , Campos-Neto Antonio 
Published: April 2012

ABSTRACT

Despite the clear need to control visceral leishmaniasis (VL), the existing diagnostic tests have serious shortcomings. Here, we introduce an innovative approach to directly identify
Leishmania infantum
antigens produced
in vivo
in humans with VL. We combined reverse-phase high-performance liquid chromatography (RP-HPLC) with mass spectrometry and categorized three distinct
L. infantum
proteins presumably produced in bone marrow/spleen/liver and excreted in the urine of patients with VL. The genes coding for these proteins (
L. infantum
iron superoxide dismutase, NCBI accession number
XP_001467866.1
;
L. infantum
tryparedoxin, NCBI accession number
XP_001466642.1
; and
L. infantum
nuclear transport factor 2, NCBI accession number
XP_001463738.1
) were cloned, and the recombinant molecules were produced in
Escherichia coli
. Antibodies to these proteins were produced in rabbits and chickens and were used to develop a capture enzyme-linked immunosorbent assay (ELISA) designed to detect these
L. infantum
antigens in the urine of VL patients. Specificity of the antibodies was confirmed by a Western blot analysis using both recombinant proteins and whole parasite extract. Importantly, a urinary antigen detection assay assembled with pairs of antibodies specific for each of these antigens identified 17 of 19 patients with VL. These results indicate that an improved antigen detection assay based on
L. infantum
proteins present in the urine of patients with VL may represent an important new strategy for the development of a specific and accurate diagnostic test that has the potential to both distinguish active VL from asymptomatic infection and serve as an important tool to monitor therapy efficacy.
TP-RT Domain Interactions of Duck Hepatitis B Virus Reverse Transcriptase in
cis
and in
trans
during Protein-Primed Initiation of DNA Synthesis
In Vitro
Authors: Boregowda Rajeev K. , Adams Christina , Hu Jianming 
Published: April 2012

ABSTRACT

The hepadnavirus reverse transcriptase (RT) has the unique ability to initiate viral DNA synthesis using RT itself as a protein primer. Protein priming requires complex interactions between the N-terminal TP (terminal protein) domain, where the primer (a specific Y residue) resides, and the central RT domain, which harbors the polymerase active site. While it normally utilizes the
cis
-linked TP to prime DNA synthesis (
cis
-priming), we found that the duck hepatitis B virus (DHBV) RT domain, in the context of the full-length RT protein or a mini-RT construct containing only truncated TP and RT domains, could additionally use a separate TP or RT domain in
trans
as a primer (
trans
-priming).
trans
interaction could also be demonstrated by the inhibitory effect (
trans
-inhibition) on
cis
-priming by TP and RT domain sequences provided in
trans
. Protein priming was further shown to induce RT conformational changes that resulted in TP-RT domain dissociation, altered priming site selection, and a gain of sensitivity to a pyrophosphate analog inhibitor.
trans
-priming,
trans
-inhibition, and
trans
-complementation, which requires separate TP and RT domains to reconstitute a functional RT protein, were employed to define the sequences in the TP and RT domains that could mediate physical or functional inter- and intradomain interactions. These results provide new insights into TP-RT domain interactions and conformational dynamics during protein priming and suggest novel means to inhibit protein priming by targeting these interactions and the associated conformational transitions.
Profound Amplification of Pathogenic Murine Polytropic Retrovirus Release from Coinfected Cells
Authors: Rosenke Kyle , Lavignon Marc , Malik Frank , Kolokithas Angelo , Hendrick Duncan , Virtaneva Kimmo , Peterson Karin , Evans Leonard H. 
Published: April 2012

ABSTRACT

Previous studies indicate that mice infected with mixtures of mouse retroviruses (murine leukemia viruses [MuLVs]) exhibit dramatically altered pathology compared to mice infected with individual viruses of the mixture. Coinoculation of the ecotropic virus Friend MuLV (F-MuLV) with Fr98, a polytropic MuLV, induced a rapidly fatal neurological disease that was not observed in infections with either virus alone. The polytropic virus load in coinoculated mice was markedly enhanced, while the ecotropic F-MuLV load was unchanged. Furthermore, pseudotyping of the polytropic MuLV genome within ecotropic virions was nearly complete in coinoculated mice. In an effort to better understand these phenomena, we examined mixed retrovirus infections by utilizing
in vitro
cell lines. Similar to
in vivo
mixed infections, the polytropic MuLV genome was extensively pseudotyped within ecotropic virions; polytropic virus release was profoundly elevated in coinfected cells, and the ecotropic virus release was unchanged. A reduced level of polytropic SU protein on the surfaces of coinfected cells was observed and correlated with a reduced level of nonpseudotyped polytropic virion release. Marked amplification and pseudotyping of the polytropic MuLV were also observed in mixed Fr98–F-MuLV infections of cell lines derived from the central nervous system (CNS), the target for Fr98 pathogenesis. Additional experiments indicated that pseudotyping contributed to the elevated polytropic virus titer by increasing the efficiency of packaging and release of the polytropic genomes within ecotropic virions. Mixed infections are the rule rather than the exception in retroviral infection, and the ability to examine them
in vitro
should facilitate a more thorough understanding of retroviral interactions in general.
Initial HIV-1 Antigen-Specific CD8
+
T Cells in Acute HIV-1 Infection Inhibit Transmitted/Founder Virus Replication
Authors: Freel Stephanie A. , Picking Ralph A. , Ferrari Guido , Ding Haitao , Ochsenbauer Christina , Kappes John C. , Kirchherr Jennifer L. , Soderberg Kelly A. , Weinhold Kent J. , Cunningham Coleen K. , Denny Thomas N. , Crump John A. , Cohen Myron S. , McMichael Andrew J. , Haynes Barton F. , Tomaras Georgia D. 
Published: April 2012

ABSTRACT

CD8-mediated virus inhibition can be detected in HIV-1-positive subjects who naturally control virus replication. Characterizing the inhibitory function of CD8
+
T cells during acute HIV-1 infection (AHI) can elucidate the nature of the CD8
+
responses that can be rapidly elicited and that contribute to virus control. We examined the timing and HIV-1 antigen specificity of antiviral CD8
+
T cells during AHI. Autologous and heterologous CD8
+
T cell antiviral functions were assessed longitudinally during AHI in five donors from the CHAVI 001 cohort using a CD8
+
T cell-mediated virus inhibition assay (CD8 VIA) and transmitted/founder (T/F) viruses. Potent CD8
+
antiviral responses against heterologous T/F viruses appeared during AHI at the first time point sampled in each of the 5 donors (Fiebig stages 1/2 to 5). Inhibition of an autologous T/F virus was durable to 48 weeks; however, inhibition of heterologous responses declined concurrent with the resolution of viremia. HIV-1 viruses from 6 months postinfection were more resistant to CD8
+
-mediated virus inhibition than cognate T/F viruses, demonstrating that the virus escapes early from CD8
+
T cell-mediated inhibition of virus replication. CD8
+
T cell antigen-specific subsets mediated inhibition of T/F virus replication via soluble components, and these soluble responses were stimulated by peptide pools that include epitopes that were shown to drive HIV-1 escape during AHI. These data provide insights into the mechanisms of CD8-mediated virus inhibition and suggest that functional analyses will be important for determining whether similar antigen-specific virus inhibition can be induced by T cell-directed vaccine strategies.
Identification of the Galactose Binding Domain of the Adeno-Associated Virus Serotype 9 Capsid
Authors: Bell Christie L. , Gurda Brittney L. , Van Vliet Kim , Agbandje-McKenna Mavis , Wilson James M. 
Published: April 2012

ABSTRACT

Adeno-associated virus serotype 9 (AAV9) vectors show promise for gene therapy of a variety of diseases due to their ability to transduce multiple tissues, including heart, skeletal muscle, and the alveolar epithelium of the lung. In addition, AAV9 is unique compared to other AAV serotypes in that it is capable of surpassing the blood-brain barrier and transducing neurons in the brain and spinal cord. It has recently been shown that AAV9 uses galactose as a receptor to transduce many different cell types
in vitro
, as well as cells of the mouse airway
in vivo
. In this study, we sought to identify the specific amino acids of the AAV9 capsid necessary for binding to galactose. By site-directed mutagenesis and cell binding assays, plus computational ligand docking studies, we discovered five amino acids, including N470, D271, N272, Y446, and W503, which are required for galactose binding that form a pocket at the base of the protrusions around the icosahedral 3-fold axes of symmetry. The importance of these amino acids for tissue tropism was also confirmed by
in vivo
studies in the mouse lung. Identifying the interactions necessary for AAV9 binding to galactose may lead to advances in vector engineering.
Net Clinical Benefit of Warfarin in Patients With Atrial Fibrillation
Authors: Friberg Leif , Rosenqvist Mårten , Lip Gregory Y.H. 
Published: April 2012

Background—
Known risk factors for bleeding during anticoagulant treatment are largely the same as those predicting thromboembolic events in patients with atrial fibrillation (AF). Our objective was to investigate how to maximize the likelihood of avoiding both stroke and bleeding.

Methods and Results—

All 182 678 subjects with atrial fibrillation in the Swedish Hospital Discharge Register were studied for an average of 1.5 years (260 000 patient-years at risk). Patients were stratified according to risk scores with the use of historic
International Classification of Disease
diagnostic codes in the register. Information about medication was obtained from the Swedish Drug Registry. Our primary end point was net benefit defined as number of avoided ischemic strokes with anticoagulation minus the number of excess intracranial bleedings with a weight of 1.5 to compensate for the generally more severe outcome with intracranial bleedings. The adjusted net clinical benefit favored anticoagulation for almost all atrial fibrillation patients. The exceptions were patients at very low risk of ischemic stroke with a CHA
2
DS
2
-VASc score of 0 and moderately elevated bleeding risk (−1.7%/y). The results were broadly similar with CHADS
2
, except for patients with very low embolic risk; the CHA
2
DS
2
-VASc was able to identify those patients (n=6205, 3.9% of all patients) who had no net clinical benefit or even some disadvantage from anticoagulant treatment.

Conclusions—
In almost all patients with atrial fibrillation, the risk of ischemic stroke without anticoagulant treatment is higher than the risk of intracranial bleeding with anticoagulant treatment. Analysis of the net benefit indicates that more patients may benefit from anticoagulant treatment.
Covariability of Surface Wind and Stress Responses to Sea Surface Temperature Fronts
Authors: O’Neill Larry W. , Chelton Dudley B. , Esbensen Steven K. 
Published: April 2012

Abstract
The responses of surface wind and wind stress to spatial variations of sea surface temperature (SST) are investigated using satellite observations of the surface wind from the Quick Scatterometer (QuikSCAT) and SST from the Advanced Microwave Scanning Radiometer on the Advanced Microwave Scanning Radiometer for Earth Observing System (EOS) (AMSR-E) Aqua satellite. This analysis considers the 7-yr period June 2002–May 2009 during which both instruments were operating. Attention is focused in the Kuroshio, North and South Atlantic, and Agulhas Return Current regions. Since scatterometer wind stresses are computed solely as a nonlinear function of the scatterometer-derived 10-m equivalent neutral wind speed (ENW), qualitatively similar responses of the stress and ENW to SST are expected. However, the responses are found to be more complicated on the oceanic mesoscale. First, the stress and ENW are both approximately linearly related to SST, despite a nonlinear relationship between them. Second, the stress response to SST is 2 to 5 times stronger during winter compared to summer, while the ENW response to SST exhibits relatively little seasonal variability. Finally, the stress response to SST can be strong in regions where the ENW response is weak and vice versa.
A straightforward algebraic manipulation shows that the stress perturbations are directly proportional to the ENW perturbations multiplied by a nonlinear function of the ambient large-scale ENW. This proportionality explains why both the stress and ENW depend linearly on the mesoscale SST perturbations, while the dependence of the stress perturbations on the ambient large-scale ENW explains both the seasonal pulsing and the geographic variability of the stress response to SST compared with the less variable ENW response.
Biases in the Atlantic ITCZ in Seasonal–Interannual Variations for a Coarse- and a High-Resolution Coupled Climate Model
Authors: Doi Takeshi , Vecchi Gabriel A. , Rosati Anthony J. , Delworth Thomas L. 
Published: April 2012

Abstract
Using two fully coupled ocean–atmosphere models—Climate Model version 2.1 (CM2.1), developed at the Geophysical Fluid Dynamics Laboratory, and Climate Model version 2.5 (CM2.5), a new high-resolution climate model based on CM2.1—the characteristics and sources of SST and precipitation biases associated with the Atlantic ITCZ have been investigated.
CM2.5 has an improved simulation of the annual mean and the annual cycle of the rainfall over the Sahel and northern South America, while CM2.1 shows excessive Sahel rainfall and lack of northern South America rainfall in boreal summer. This marked improvement in CM2.5 is due to not only high-resolved orography but also a significant reduction of biases in the seasonal meridional migration of the ITCZ. In particular, the seasonal northward migration of the ITCZ in boreal summer is coupled to the seasonal variation of SST and a subsurface doming of the thermocline in the northeastern tropical Atlantic, known as the Guinea Dome. Improvements in the ITCZ allow for better representation of the coupled processes that are important for an abrupt seasonally phase-locked decay of the interannual SST anomaly in the northern tropical Atlantic.
Nevertheless, the differences between CM2.5 and CM2.1 were not sufficient to reduce the warm SST biases in the eastern equatorial region and Angola–Benguela area. The weak bias of southerly winds along the southwestern African coast associated with the excessive southward migration bias of the ITCZ may be a key to improve the warm SST biases there.
Dry and Moist Idealized Experiments with a Two-Dimensional Spectral Element Model
Authors: Gaberšek Saša , Giraldo Francis X. , Doyle James D. 
Published: April 2012

Abstract
A nonhydrostatic, fully compressible spectral element (SE) model is evaluated in a series of two-dimensional idealized simulations. A dry formulation of the model is evaluated for a linear hydrostatic mountain-wave case, and a version with moisture is tested for a squall line. In the SE method, two setup parameters control the spatial resolution: the number of elements (h) and the polynomial order (p) of the basis functions. In this paper, the h−p parameter space is systematically explored, with the average horizontal resolution (Δx) varying from 0.2 to 10 km in 91 simulations.
The dry experiments are evaluated using an analytic solution. The ratio of Δx/a &lt; 0.2, where a is the mountain half-width, is sufficient to accurately resolve the mountain wave. Accuracy, computational cost, and convergence to the analytic solution are evaluated and compared to a second-order finite-difference (FD) model. The increase in computational cost by refining the spatial resolution yields a significant accuracy gain for the SE, with only a marginal improvement for the FD model.
The squall line is evaluated across the control parameter space by assessing three integrated quantities: total precipitation accumulation, maximum vertical velocity, and maximum precipitation rate. The squall line is adequately resolved with Δx &lt; 2 km and p &gt; 5. There is little variation in metrics due to the varying nodal spacing within an element at the same average Δx. When the spatial resolution is refined, the analyzed metrics no longer converge. The nonlinear nature of moist convection is responsible for this resolution dependence as a result of localized buoyancy sources, evident in the vertical velocity spectrum.
Phenomenological Description of Tropical Clouds Using CloudSat Cloud Classification
Authors: Behrangi Ali , Kubar Terry , Lambrigtsen Bjorn 
Published: April 2012

Abstract
Two years of tropical oceanic cloud observations are analyzed using the operational CloudSat cloud classification product and Cloud–Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) lidar. Relationships are examined between cloud types, sea surface temperature (SST), and location during the CloudSat early morning and afternoon overpasses. Based on CloudSat and combined lidar–radar products, the maximum and minimum cloud fractions occur at SSTs near 303 and 299 K, respectively, corresponding to deep convective/detrained cloud populations and the transition from shallow to deep convection. For SSTs below approximately 301 K, low clouds (stratiform and stratocumulus) are dominant (cloud fraction between 0.15 and 0.37) whereas high clouds are dominant for SSTs greater than about 301 K (cloud fraction between 0.18 and 0.28). Consistent with previous studies, most tropical low clouds are associated with lower SSTs, with a strong inverse linear relationship between low cloud frequency and SST. For all cloud types except nimbostratus, stratus, and stratocumulus, a sharp increase in frequency of occurrence is observed for SSTs between 299 and 300.5 K, deduced as the onset of deeper convection. Peak fractions of high, deep convective, altostratus, and altocumulus clouds occur at SSTs close to 303 K, while cumulus clouds, which have lower tops, show a smooth cloud fractional peak about 2° cooler. Deep convective and other high cloud types decrease sharply above SSTs of 303 K, in accordance with previous work suggesting a narrow window of tropical deep convection. Finally, significant cloud frequency differences exist between CloudSat early morning and afternoon overpasses, suggesting a diurnal cycle of some cloud types, particularly stratocumulus, high, and deep convective clouds.
The Collision of Marxism and Derrida's Deconstruction in China
Authors: Xiaoping Wei 
Published: April 2012

AbstractDerrida perhaps most interests Chinese Marxist scholars through his way of separating the spirit of Marx from the ‘‘specter’’ of Marx. All those things interpreted by Derrida as ‘‘specters’’ are mainly practiced in China after 1949. Since China’s historical transition began in 1978 those ‘‘specters’’ considered by Derrida include the challenge of economic reform, and economic globalization, and could also include public ownership which has been replaced by multiple owner-ship or stock ownership, as well as allocation according to contribution which has been replaced by allocation according to contribution combined with allocation according to capital investment. The predictable result is that income equality in theory or in practice has now given way to great income difference. These phenomena are opposite to those ‘‘specters’’ of Marx, and they are the targets of the critical spirit of Marx. When Derrida name those things as ‘‘specters’’ presumably this means they could never be actualized. So when those things actually disappeared again, people would like to accept the supposition that they are only ‘‘specters’’ and could not be objectified, while what actually could be practiced is the critical spirit of Marx. It is just the paradox of the ‘‘specters’’ and the spirit of Marx in the actual situation of China that brings it about that Derrida’s deconstructive method interests some Chinese Marxist scholars, especially the younger ones. In order to understand Derrida’s appeal in China better, we need to look at the general situation of Western Marxism in China.
UNESCO, Philosophy, and Human Rights
Authors: Puglisi Giovanni 
Published: April 2012

AbstractGiovanni Puglisi presents here the theoretical and concrete context in which the Unesco Day of Philosophy took place in 2008 in Palermo, Italy. He insists on the importance for Unesco to publicly discuss issues that constitute the dialogical essence of our time, and argues that Unesco would not survive a loss of its capacity to carry out public reflection. Rights and Power, the general theme of the Palermo Day of Philosophy, appears as a very central issue for a global world, where the dynamic between formal law and social and cultural constraints need to be permanently redefined. Unesco is and must be committed to bringing together scholars, intellectuals, and other public actors of this crucial reflection.