bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human CD8+and CD4+T Cell Memory to Lymphocytic Choriomeningitis Virus Infection
Authors: Kotturi Maya F. , Swann Justine A. , Peters Bjoern , Arlehamn Cecilia Lindestam , Sidney John , Kolla Ravi V. , James Eddie A. , Akondy Rama S. , Ahmed Rafi , Kwok William W. , Buchmeier Michael J. , Sette Alessandro 
Published: September 2011

ABSTRACTAlthough cellular immunity to acute lymphocytic choriomeningitis virus (LCMV) infection has been well characterized in experimental studies in mice, the T cell response to this virus in humans is incompletely understood. Thus, we analyzed the breadths, magnitudes, and differentiation phenotypes of memory LCMV-specific CD8+and CD4+T cells in three human donors displaying a variety of disease outcomes after accidental needle stick injury or exposure to LCMV. Although only a small cohort of donors was analyzed at a single time point postinfection, several interesting observations were made. First, we were able to detect LCMV-specific CD8+and CD4+T cell responses directlyex vivoat 4 to 8 years after exposure, demonstrating the longevity of T cell memory in humans. Second, unlike in murine models of LCMV infection, we found that the breadths of memory CD8+and CD4+T cell responses were not significantly different from one another. Third, it seemed that the overall CD8+T cell response was augmented with increasing severity of disease, while the LCMV-specific CD4+T cell response magnitude was highly variable between the three different donors. Next, we found that LCMV-specific CD8+T cells in the three donors analyzed seemed to undergo an effector memory differentiation program distinct from that of CD4+T cells. Finally, the levels of expression of memory, costimulatory, and inhibitory receptors on CD8+and CD4+T cell subsets, in some instances, correlated with disease outcome. These data demonstrate for the first time LCMV-specific CD8+and CD4+T cells in infected humans and begin to provide new insights into memory T cell responses following an acute virus infection.
Expression Strategy of Densonucleosis Virus from the German Cockroach, Blattella germanica
Authors: Kapelinskaya Tatiana V. , Martynova Elena U. , Schal Coby , Mukha Dmitry V. 
Published: September 2011

ABSTRACTBlattella germanicadensovirus (BgDNV) is an autonomous parvovirus that infects the German cockroach. BgDNV possesses three mRNAs for NS proteins, two of which are splice variants of the unspliced transcript. The unspliced variant encodes open reading frame 5 (ORF5) (NS3), while NSspl1 encodes ORF3 (NS1) and ORF4 (NS2) and NSspl2 encodes the C-proximal half of NS1. BgDNV possesses three VP transcripts, one of which (VP) is unspliced, while the other two (VPspl1 and VPspl2) are generated by alternative splicing. The unspliced VP transcript contains both ORF1 and ORF2, while in VPspl1, ORF1 and ORF2 are joined in frame. The transcription of NS genes begins at an earlier stage of the virus life cycle than the transcription of VP genes. NS and VP transcripts overlap by 48 nucleotides (nt). BgDNV is characterized by two additional NS transcripts overlapping by more than 1,650 nt with VP-coding transcripts. Four different bands (97, 85, 80, and 57 kDa) corresponding to three BgDNV capsid proteins were detected on SDS-PAGE. Mass spectrometry analysis showed that the amino acid composition of the 85-kDa and 80-kDa proteins is the same. Moreover, both of these proteins are ubiquitinated. The BgDNV PLA2domain, which is critical for cellular uptake of the virus, is located in ORF2 and is present only in VP1. In contrast to all of the parvoviruses studied in this respect, VP2 has a unique N terminus that is not contained within VP1 and VP3.In siturecognition with NS1- and VP-specific antibodies revealed an uneven pattern of NS1 expression resembling a halo within the nuclear membrane.
Laparoscopic cholecystectomy under field conditions in Asiatic black bears (Ursus thibetanus) rescued from illegal bile farming in Vietnam
Authors: Pizzi R. , Cracknell J. , David S. , Laughlin D. , Broadis N. , Rouffignac M. , Duong D. V. , Girling S. , Hunt M. 
Published: September 2011

Nine adult Asiatic black bears (Ursus thibetanus) previously rescued from illegal bile farming in Vietnam were examined via abdominal ultrasound and exploratory laparoscopy for liver and gall bladder pathology. Three bears demonstrated notable gall bladder pathology, and minimally invasive cholecystectomies were performed using an open laparoscopic access approach, standard 10 to 12 mmHg carbon dioxide pneumoperitoneum and a four‐port technique. A single bear required insertion of an additional 5 mm port and use of a flexible liver retractor due to the presence of extensive adhesions between the gall bladder and quadrate and left and right medial liver lobes. The cystic duct was dissected free and this and the cystic artery were ligated by means of extracorporeal tied Meltzer knot sutures. The gall bladder was dissected free of the liver by blunt and sharp dissection, aided by 3.8 MHz monopolar radiosurgery. Bears that have had open abdominal cholecystectomies are reported as taking four to six weeks before a return to normal activity postoperatively. In contrast, these bears demonstrated rapid unremarkable healing, and were allowed unrestricted access to outside enclosures to climb trees, swim and interact normally with other bears within seven days of surgery.
SPARSE TEMPLATE-BASED VARIATIONAL IMAGE SEGMENTATION
Authors: BREITENREICHER DIRK , LELLMANN JAN , SCHNÖRR CHRISTOPH 
Published: September 2011

We introduce a variational approach to image segmentation based on sparse coverings of image domains by shape templates. The objective function combines a data term that achieves robustness by tolerating overlapping templates with a regularizer enforcing sparsity. A suitable convex relaxation leads to the variational approach that is amenable to large-scale convex programming. Our approach takes implicitly into account prior knowledge about the shape of objects and their parts, without resorting to combinatorially difficult problems of variational inference. We illustrate our approach by numerical examples and indicate how prior knowledge acquisition may be achieved by learning from examples.
Quantifying the Role of Angiogenesis in Malignant Progression of Gliomas: In Silico Modeling Integrates Imaging and Histology
Authors: Swanson Kristin R. , Rockne Russell C. , Claridge Jonathan , Chaplain Mark A. , Alvord Ellsworth C. , Anderson Alexander R.A. 
Published: September 2011

Abstract
Gliomas are uniformly fatal forms of primary brain neoplasms that vary from low- to high-grade (glioblastoma). Whereas low-grade gliomas are weakly angiogenic, glioblastomas are among the most angiogenic tumors. Thus, interactions between glioma cells and their tissue microenvironment may play an important role in aggressive tumor formation and progression. To quantitatively explore how tumor cells interact with their tissue microenvironment, we incorporated the interactions of normoxic glioma cells, hypoxic glioma cells, vascular endothelial cells, diffusible angiogenic factors, and necrosis formation into a first-generation, biologically based mathematical model for glioma growth and invasion. Model simulations quantitatively described the spectrum of in vivo dynamics of gliomas visualized with medical imaging. Furthermore, we investigated how proliferation and dispersal of glioma cells combine to induce increasing degrees of cellularity, mitoses, hypoxia-induced neoangiogenesis and necrosis, features that characterize increasing degrees of “malignancy,” and we found that changes in the net rates of proliferation (ρ) and invasion (D) are not always necessary for malignant progression. Thus, although other factors, including the accumulation of genetic mutations, can change cellular phenotype (e.g., proliferation and invasion rates), this study suggests that these are not required for malignant progression. Simulated results are placed in the context of the current clinical World Health Organization grading scheme for studying specific patient examples. This study suggests that through the application of the proposed model for tumor–microenvironment interactions, predictable patterns of dynamic changes in glioma histology distinct from changes in cellular phenotype (e.g., proliferation and invasion rates) may be identified, thus providing a powerful clinical tool. Cancer Res; 71(24); 7366–75. ©2011 AACR.
β1-Integrin: A Potential Therapeutic Target in the Battle against Cancer Recurrence
Authors: Barkan Dalit , Chambers Ann F. 
Published: September 2011

Abstract
Primary cancer treatment, involving both local and often systemic adjuvant therapy, is often successful, especially if the cancer is detected at an early stage of progression. However, for some patients, the cancer may recur either locally or as distant metastases, in some cases many years after apparently successful primary treatment. Significant tumor dormancy has been documented in several cancers, such as breast, melanoma, and renal cancer. Tumor dormancy has long been recognized as an important problem in management of cancer patients. Recent work has clarified biologic aspects of tumor dormancy and has shown that dormant tumor cells may be resistant to cytotoxic chemotherapy and radiation. This work has led to recognition of a key role for β1-integrin in regulating the switch from a dormant state to active proliferation and metastasis. Here we discuss the role of β1-integrin and its signaling partners in regulating the dormant phenotype. We also consider possible therapeutic approaches, such as small molecules or antibodies (ATN-161, volociximab, and JSM6427), directed against β1-integrin signaling to target dormant cancer cells and to prevent metastatic recurrence. Clin Cancer Res; 17(23); 7219–23. ©2011 AACR.
A Novel, Selective Inhibitor of Fibroblast Growth Factor Receptors That Shows a Potent Broad Spectrum of Antitumor Activity in Several Tumor Xenograft Models
Authors: Zhao Genshi , Li Wei-ying , Chen Daohong , Henry James R. , Li Hong-Yu , Chen Zhaogen , Zia-Ebrahimi Mohammad , Bloem Laura , Zhai Yan , Huss Karen , Peng Sheng-bin , McCann Denis J. 
Published: September 2011

AbstractThe fibroblast growth factor receptors (FGFR) are tyrosine kinases that are present in many types of endothelial and tumor cells and play an important role in tumor cell growth, survival, and migration as well as in maintaining tumor angiogenesis. Overexpression of FGFRs or aberrant regulation of their activities has been implicated in many forms of human malignancies. Therefore, targeting FGFRs represents an attractive strategy for development of cancer treatment options by simultaneously inhibiting tumor cell growth, survival, and migration as well as tumor angiogenesis. Here, we describe a potent, selective, small-molecule FGFR inhibitor, (R)-(E)-2-(4-(2-(5-(1-(3,5-Dichloropyridin-4-yl)ethoxy)-1H-indazol-3yl)vinyl)-1H-pyrazol-1-yl)ethanol, designated as LY2874455. This molecule is active against all 4 FGFRs, with a similar potency in biochemical assays. It exhibits a potent activity against FGF/FGFR-mediated signaling in several cancer cell lines and shows an excellent broad spectrum of antitumor activity in several tumor xenograft models representing the major FGF/FGFR relevant tumor histologies including lung, gastric, and bladder cancers and multiple myeloma, and with a well-defined pharmacokinetic/pharmacodynamic relationship. LY2874455 also exhibits a 6- to 9-fold in vitro and in vivo selectivity on inhibition of FGF- over VEGF-mediated target signaling in mice. Furthermore, LY2874455 did not show VEGF receptor 2–mediated toxicities such as hypertension at efficacious doses. Currently, this molecule is being evaluated for its potential use in the clinic. Mol Cancer Ther; 10(11); 2200–10. ©2011 AACR.
Prothrombin complex concentrate reduces blood loss and enhances thrombin generation in a pig model with blunt liver injury under severe hypothermia
Authors: Rieg Annette , Rossaint Rolf , Braunschweig Till , Spronk Henri , ten Cate Hugo , van Oerle Rene , Tolba Rene , Honickel Markus , Grottke Oliver 
Published: September 2011

SummaryAlthough prothrombin complex concentrate (PCC) is increasingly used for the treatment of trauma-induced coagulopathy, few studies have investigated the impact and safety of PCC for this indication. The present study was performed to assess PCC for treatment of coagulopathy after blunt liver injury under severe hypothermia. Coagulopathy in 14 anaesthetised pigs was induced by haemodilution. Subsequently, standardised blunt liver injury was induced under severe hypothermia (32.8–33.2°C). Animals were randomised to receive either PCC (35 IU kg-1) or saline (control). Coagulation was assessed over the following 2 hours by thromboelastometry and thrombin generation. Internal organs were examined to determine presence of emboli. The administration of PCC showed a significant reduction in blood loss (p=0.002 vs. controls) and a significant increase in the rate of survival (p=0.022 vs. controls). Plasma thrombin generation in the PCC group increased considerably above baseline levels, with significant increases in peak thrombin levels and endogenous thrombin potential versus controls throughout the follow-up period. In addition, PT decreased significantly in the PCC group versus the control group. However, only slight improvements in thromboelastometry variables were observed. Histology showed an equal degree of liver injury in both groups, and no thromboembolism. In severely hypothermic pigs, the application of PCC corrected trauma-induced coagulopathy and reduced blood loss. Thus, the infusion of PCC might be a reasonable approach to reduce the need for blood cell transfusion in trauma. Furthermore, the impact and safety of PCC application can be monitored through thrombin generation and thromboelastometry under hypothermia.Note: This study was performed at the RWTH Aachen University Hospital, Pauwelsstrasse 30, D-52074 Aachen, Germany.
Dendritic cells in atherosclerosis: Functions in immune regulation and beyond
Authors: Manthey Helga , Zernecke Alma 
Published: September 2011

SummaryChronic inflammation drives the development of atherosclerosis. Dendritic cells (DCs) are known as central mediators of adaptive immune responses and the development of immunological memory and tolerance. DCs are present in non-diseased arteries, and accumulate within atherosclerotic lesions where they can be localised in close vicinity to T cells. Recent work has revealed important functions of DCs in regulating immune mechanisms in atherogenesis, and vaccination strategies using DCs have been explored for treatment of disease. However, in line with a phenotypical and functional overlap with plaque macrophages vascular DCs were also identified to engulf lipids, thus contributing to lipid burden in the vessel wall and initiation of lesion growth. Furthermore, a function of DCs in regulating cholesterol homeostasis has been revealed. Finally, phenotypically distinct plasmacytoid dendritic cells (pDCs) have been identified within atherosclerotic lesions. This review will dissect the multifaceted contribution of DCs and pDCs to the initiation and progression of atherosclerosis and the experimental approaches utilising DCs in therapeutic vaccination strategies.
Novel recombinant glycosylphosphatidylinositol (GPI)-anchored ADAMTS13 and variants for assessment of anti-ADAMTS13 autoantibodies in patients with thrombotic thrombocytopenic purpura
Authors: Li Dengju , Xiao Juan , Paessler Michele , Zheng X. 
Published: September 2011

SummaryImmunoglobulin Gs (IgGs) against ADAMTS13 are major causes of acquired (idiopathic) thrombotic thrombocytopenic purpura (TTP). We report here a novel cell-based assay using glycosylphosphatidylinositol (GPI)-anchored ADAMTS13 or variants expressed on cell membrane for assessment of autoantibodies in patients with TTP. We showed that IgGs from all 26 patients with acquired TTP bound to cells expressing a GPI anchored full-length ADAMTS13 (gFL) and a variant truncated after the spacer domain (gS). Also, IgGs from 25/26 (96.7%) of these TTP patients bound to cells expressing a GPI-anchored C-terminal fragment, TSP1 2–8 plus CUB (gT2C). In contrast, none of the 20 healthy blood donors showed detectable binding of their IgGs to the cells expressing gFL, gS, and gT2C. A moderate, but statistically significant correlation was observed between plasma concentrations of anti-ADAMTS13 IgG and positive cells expressing gFL (r=0.65), gS (r=0.67), and gT2C (r=0.42). These results suggest that the microtiter-plate assay and the cell-based assay may detect differential antigenic epitopes. Moreover, antigens clustered on cell membranes may enhance antibody binding affinity, thereby increasing analytical sensitivity. Finally, our assay was able to determine kinetic changes of plasma levels of anti-ADAMTS13 IgGs in TTP patients during plasma therapy. Together, our findings suggest that the novel cell-based assay may be applicable for rapid identification and mapping of anti-ADAMTS13 autoantibodies in patients with acquired TTP.
Recombinant activated protein C attenuates coagulopathy and inflammation when administered early in murine pneumococcal pneumonia
Authors: van ’t Veer Cornelis , Roelofs Joris , Gerlitz Bruce , Grinnell Brian , Levi Marcel , der Poll Tom , Schouten Marcel 
Published: September 2011

SummaryRecombinant human activated protein C (APC), which has both anticoagulant and anti-inflammatory properties, improves survival of patients with severe sepsis. This beneficial effect is especially apparent in patients with pneumococcal pneumonia. Earlier treatment with APC in sepsis has been associated with a better therapeutic response as compared to later treatment. In a mouse model it was recently confirmed that recombinant murine (rm-)APC decreases coagulation activation and improves survival in pneumococcal pneumonia; however, APC did not impact on the inflammatory response. The aim of this study was to determine the effect of APC treatment instigated early in infection on activation of coagulation and inflammation after induction of pneumococcal pneumonia. Mice were infected intranasally with viable S. pneumoniae. Mice were treated with rm-APC (125 μg) or vehicle intraperitoneally 12 hours after infection and were sacrificed after 20 hours, after which blood and organs were harvested for determination of bacterial outgrowth, coagulation activation and inflammatory markers. In this early treatment model, rm-APC treatment inhibited pulmonary and systemic activation of coagulation as reflected by lower levels of throm-bin-antithrombin complexes and D-dimer. Moreover, rm-APC reduced the levels of a large number of cytokines and chemokines in the lung. When administered early in pneumococcal pneumonia, rm-APC inhibits systemic and pulmonary activation of coagulation and moreover exerts various anti-inflammatory effects in the lung.
Right Ventricular Failure in Idiopathic Pulmonary Arterial Hypertension Is Associated With Inefficient Myocardial Oxygen Utilization
Authors: Wong Yeun Ying , Ruiter Gerrina , Lubberink Mark , Raijmakers Pieter G. , Knaapen Paul , Marcus J. Tim , Boonstra Anco , Lammertsma Adriaan A. , Westerhof Nico , van der Laarse Willem J. , Vonk-Noordegraaf Anton 
Published: September 2011

Background—

In idiopathic pulmonary arterial hypertension (IPAH), increased right ventricular (RV) power is required to maintain cardiac output. For this, RV O
2
consumption (MVO
2
) must increase by augmentation of O
2
supply and/or improvement of mechanical efficiency–ratio of power output to MVO
2
. In IPAH with overt RV failure, however, there is evidence that O
2
supply (perfusion) reserve is reduced, leaving only increase in either O
2
extraction or mechanical efficiency as compensatory mechanisms. We related RV mechanical efficiency to clinical and hemodynamic parameters of RV function in patients with IPAH and associated it with glucose metabolism.

Methods and Results—

The patients included were in New York Heart Association (NYHA) class II (n=8) and class III (n=8). They underwent right heart catheterization, MRI, and H
2
15
O-,
15
O
2
-, C
15
O-, and
18
FDG-PET. RV power and O
2
supply were similar in both groups (NYHA class II versus class III: 0.54±0.14 versus 0.47±0.12 J/s and 0.109±0.022 versus 0.128±0.026 mL O
2
/min per gram, respectively). RV O
2
extraction was near-significantly lower in NYHA class II compared with NYHA class III (63±17% versus 75±16%, respectively,
P
=0.10). As a result, MVO
2
was significantly lower (0.066±0.012 versus 0.092±0.010 mL O
2
/min per gram, respectively,
P
=0.006). RV efficiency was reduced in NYHA class III (13.9±3.8%) compared with NYHA class II (27.8±7.6%,
P
=0.001). Septal bowing, measured by MRI, correlated with RV efficiency (
r
=−0.59,
P
=0.020). No relation was found between RV efficiency and glucose uptake rate. RV mechanical efficiency and ejection fraction were closely related (
r
=0.81,
P
<0.001).

Conclusions—
RV failure in IPAH was associated with reduced mechanical efficiency that was partially explained by RV mechanical dysfunction but not by a metabolic shift.
On Trade Wind Cumulus Cold Pools
Authors: Zuidema Paquita , Li Zhujun , Hill Reginald J. , Bariteau Ludovic , Rilling Bob , Fairall Chris , Brewer W. Alan , Albrecht Bruce , Hare Jeff 
Published: September 2011

Abstract
Shallow precipitating cumuli within the easterly trades were investigated using shipboard measurements, scanning radar data, and visible satellite imagery from 2 weeks in January 2005 of the Rain in Cumulus over the Ocean (RICO) experiment. Shipboard rainfall rates of up to 2 mm h−1 were recorded almost daily, if only for 10–30 min typically, almost always from clouds within mesoscale arcs. The precipitating cumuli, capable of reaching above 4 km, cooled surface air by 1–2 K, in all cases lowered surface specific humidities by up to 1.5 g kg−1, reduced surface equivalent potential temperatures by up to 6 K, and were often associated with short-lived increases in wind speed. Upper-level downdrafts were inferred to explain double-lobed moisture and temperature sounding profiles, as well as multiple inversions in wind profiler data. In two cases investigated further, the precipitating convection propagated faster westward than the mean surface wind by about 2–3 m s−1, consistent with a density current of depth ~200 m. In their cold pool recovery zones, the surface air temperatures equilibrated with time to the sea surface temperatures, but the surface air specific humidities stayed relatively constant after initial quick recoveries. This suggested that entrainment of drier air from above fully compensated the moistening from surface latent heat fluxes. Recovery zone surface wind speeds and latent heat fluxes were not higher than environmental values. Nonprecipitating clouds developed after the surface buoyancy had recovered (barring encroachment of other convection). The mesoscale arcs favored atmospheres with higher water vapor paths. These observations differed from those of stratocumulus and deep tropical cumulus cold pools.