bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stumbling blocks on the Hydrogen road in Norway
Authors: Kårstein A. 
Published: November 2010

This paper analyses a quite comprehensive Norwegian experiment to provide hydrogen as a fuel for transportation. The programme, called HyNor (short for ‘the Hydrogen road in Norway’), was a Norwegian joint industry initiative to demonstrate a real-life implementation of hydrogen energy infrastructure along a 580 km route between Oslo and Stavanger. The paper analyses the stumbling blocks that could potentially throw the project off balance. Initially the expectation was that non-technological issues, related to hindrances on the one hand and opportunities on the other, would be at the centre of attention when it came to implementing hydrogen in the Norwegian transportation sector. However, issues related to what is described as socio-technical synchronisation were found to be the most challenging to the project.
Biochemical responses in gills of rainbow trout exposed to propiconazole
Authors: Li Zhi-Hua , Zlabek Vladimir , Grabic Roman , Li Ping , Randak Tomas 
Published: November 2010

Abstract
The aim of this study is to investigate the toxic effect of PCZ, a triazole fungicide commonly present in surface and ground water, on the ROS defense system and Na+-K+-ATPase in gills of rainbow trout exposed to sublethal concentrations (0.2, 50 and 500 μg L−1) for 7, 20 and 30 days. After prolonged exposure of PCZ at higher test concentrations (50 and 500 μg L−1), oxidative stress was apparent as reflected by the significant higher ROS levels in fish gill, as well as the significant inhibition of SOD and CAT activities. In addition, Na+-K+-ATPase activities were significantly lower than those of the control with increasing PCZ concentration and prolonged exposure period. The results of this study indicate that chronic exposure to PCZ has altered multiple physiological indices in fish gill; however, before these parameters are used as unique biomarkers for monitoring residual pharmaceuticals in aquatic environments, more detailed laboratory experiments need to be performed.
Human IgG1 Monoclonal Antibody against Human Collagen 17 Noncollagenous 16A Domain Induces Blisters via Complement Activation in Experimental Bullous Pemphigoid Model
Authors: Li Qiang , Ujiie Hideyuki , Shibaki Akihiko , Wang Gang , Moriuchi Reine , Qiao Hong-jiang , Morioka Hiroshi , Shinkuma Satoru , Natsuga Ken , Long Heather A. , Nishie Wataru , Shimizu Hiroshi 
Published: November 2010

AbstractBullous pemphigoid (BP) is an autoimmune blistering disease caused by IgG autoantibodies targeting the noncollagenous 16A (NC16A) domain of human collagen 17 (hCOL17), which triggers blister formation via complement activation. Previous in vitro analysis demonstrated that IgG1 autoantibodies showed much stronger pathogenic activity than IgG4 autoantibodies; however, the exact pathogenic role of IgG1 autoantibodies has not been fully demonstrated in vivo. We constructed a recombinant IgG1 mAb against hCOL17 NC16A from BP patients. In COL17-humanized mice, this mAb effectively reproduced a BP phenotype that included subepidermal blisters, deposition of IgG1, C1q and C3, neutrophil infiltration, and mast cell degranulation. Subsequently, alanine substitutions at various C1q binding sites were separately introduced to the Fc region of the IgG1 mAb. Among these mutated mAbs, the one that was mutated at the P331 residue completely failed to activate the complement in vitro and drastically lost pathogenic activity in COL17-humanized mice. These findings indicate that P331 is a key residue required for complement activation and that IgG1-dependent complement activation is essential for blister formation in BP. This study is, to our knowledge, the first direct evidence that IgG1 Abs to hCOL17 NC16A can induce blister formation in vivo, and it raises the possibility that IgG1 mAbs with Fc modification may be used to block pathogenic epitopes in autoimmune diseases.
Preexisting Vaccinia Virus Immunity Decreases SIV-Specific Cellular Immunity but Does Not Diminish Humoral Immunity and Efficacy of a DNA/MVA Vaccine
Authors: Kannanganat Sunil , Nigam Pragati , Velu Vijayakumar , Earl Patricia L. , Lai Lilin , Chennareddi Lakshmi , Lawson Benton , Wilson Robert L. , Montefiori David C. , Kozlowski Pamela A. , Moss Bernard , Robinson Harriet L. , Amara Rama Rao 
Published: November 2010

AbstractThe influence of preexisting immunity to viral vectors is a major issue for the development of viral-vectored vaccines. In this study, we investigate the effect of preexisting vaccinia virus immunity on the immunogenicity and efficacy of a DNA/modified vaccinia Ankara (MVA) SIV vaccine in rhesus macaques using a pathogenic intrarectal SIV251 challenge. Preexisting immunity decreased SIV-specific CD8 and CD4 T cell responses but preserved the SIV-specific humoral immunity. In addition, preexisting immunity did not diminish the control of an SIV challenge mediated by the DNA/MVA vaccine. The peak and set point viremia was 150- and 17-fold lower, respectively, in preimmune animals compared with those of control animals. The peak and set point viremia correlated directly with colorectal virus at 2 wk postchallenge suggesting that early control of virus replication at the site of viral challenge was critical for viral control. Factors that correlated with early colorectal viral control included 1) the presence of anti-SIV IgA in rectal secretions, 2) high-avidity binding Ab for the native form of Env, and 3) low magnitude of vaccine-elicited SIV-specific CD4 T cells displaying the CCR5 viral coreceptor. The frequency of SIV-specific CD8 T cells in blood and colorectal tissue at 2 wk postchallenge did not correlate with early colorectal viral control. These results suggest that preexisting vaccinia virus immunity may not limit the potential of recombinant MVA vaccines to elicit humoral immunity and highlight the importance of immunodeficiency virus vaccines achieving early control at the mucosal sites of challenge.
Antibodies and Lentiviruses That Specifically Recognize a T Cell Epitope Derived from HIV-1 Nef Protein and Presented by HLA-C
Authors: Herschhorn Alon , Marasco Wayne A. , Hizi Amnon 
Published: November 2010

AbstractHIV selectively downregulates HLA-A and -B from the surfaces of infected cells to avoid detection by the immune system. In contrast, the HLA-C molecules are highly resistant to this downregulation. High expression level of HLA-C on the cell surface, which correlates with a single nucleotide polymorphism, is also associated with lower viral loads and slower progression to AIDS. These findings strongly suggest that HIV-1–derived peptides are efficiently presented by HLA-C and trigger the elimination of infected cells. Accordingly, the ability to detect these HLA-C–peptide complexes may be used for therapeutic targeting of HIV-1–infected cells and for measuring effective presentation of vaccine candidates after immunization with HIV-1–related proteins or genes. However, low level of HLA-C expression on the cell surface has impeded the development of such complex-recognizing reagents. In this study, we describe the development of a high-affinity human Ab that specifically interacts, at low pM concentrations, with a conserved viral T cell epitope derived from HIV-1 Nef protein and presented by HLA-C. The human Ab selectively detects this complex on different cells and does not interact with a control complex that differed only in the presented peptide. Engineering lentiviruses to display this Ab endowed them with the same specificity as the Ab, whereas coexpressing the Ab and Fas ligand enables the lentiviruses to kill specifically Nef-presenting cells. Abs and pseudoviruses with such specificity are likely to be highly valuable as building blocks for specific targeting and killing of HIV-1–infected cells.
CD8 T Cell-Intrinsic GITR Is Required for T Cell Clonal Expansion and Mouse Survival following Severe Influenza Infection
Authors: Snell Laura M. , McPherson Ann J. , Lin Gloria H. Y. , Sakaguchi Shimon , Pandolfi Pier Paolo , Riccardi Carlo , Watts Tania H. 
Published: November 2010

AbstractThe regulation of T cell expansion by TNFR family members plays an important role in determining the magnitude of the immune response to pathogens. As several members of the TNFR family, including glucocorticoid-induced TNFR-related protein (GITR), are found on both regulatory and effector T cells, there is much interest in understanding how their effects on these opposing arms of the immune system affect disease outcome. Whereas much work has focused on the role of GITR on regulatory T cells, little is known about its intrinsic role on effector T cells in an infectious disease context. In this study, we demonstrate that GITR signaling on CD8 T cells leads to TNFR-associated factor (TRAF) 2/5-dependent, TRAF1-independent NF-κB induction, resulting in increased Bcl-xL. In vivo, GITR on CD8 T cells has a profound effect on CD8 T cell expansion, via effects on T cell survival. Moreover, GITR is required on CD8 T cells for enhancement of influenza-specific CD8 T cell expansion upon administration of agonistic anti-GITR Ab, DTA-1. Remarkably, CD8 T cell-intrinsic GITR is essential for mouse survival during severe, but dispensable during mild respiratory influenza infection. These studies highlight the importance of GITR as a CD8 T cell costimulator during acute viral infection, and argue that despite the similarity among several TNFR family members in inducing T lymphoctye survival, they clearly have nonredundant functions in protection from severe infection.
A Dendritic Cell Population Generated by a Fusion of GM-CSF and IL-21 Induces Tumor-Antigen–Specific Immunity
Authors: Williams Patrick , Bouchentouf Manaf , Rafei Moutih , Romieu-Mourez Raphaëlle , Hsieh Jeremy , Boivin Marie-Noëlle , Yuan Shala , Forner Kathy Ann , Birman Elena , Galipeau Jacques 
Published: November 2010

AbstractWe have previously shown that the fusion of GM-CSF and IL-21 (GIFT-21) possesses a potent immune stimulatory effect on myeloid cells. In this study, we define the effect of GIFT-21 on naive murine monocytes (GIFT-21 dendritic cells [DCs]), which express increased levels of Gr-1, CD45R, MHC class I, CD80, CD86, and CXCR4 and suppress CD11c and MHC class II. Compared with conventional dendritic cells, GIFT-21 DCs produced substantially more CCL2, IL-6, TNF-α, and IFN-α and induced significantly greater production of IFN-γ by CD8+ T cells in MHC class I-restricted Ag presentation assays. B16 melanoma and D2F2 Neu breast cancer growth was inhibited in mice treated with Ag-naive GIFT-21 DCs. This effect was lost in CD8−/− and CCR2−/− mice and when mice were treated with β2-microglobulin–deficient GIFT-21 DCs, indicating that GIFT-21 DCs migrated to and sampled from the tumors to present tumor Ags to CCL2 recruited CD8+ T cells via MHC class I. We propose that autologous GIFT-21 DCs may serve as a cell therapy platform for the treatment of cancer.
Immunological Effects of Sublingual Immunotherapy: Clinical Efficacy Is Associated with Modulation of Programmed Cell Death Ligand 1, IL-10, and IgG4
Authors: Piconi Stefania , Trabattoni Daria , Rainone Veronica , Borgonovo Linda , Passerini Simone , Rizzardini Giuliano , Frati Franco , Iemoli Enrico , Clerici Mario 
Published: November 2010

AbstractSublingual immunotherapy (SLIT) is an alternate route of administration of allergen-specific immunotherapy with an improved safety profile; to clarify the immune mechanisms elicited by this therapy, we analyzed the clinical and immunologic effects of SLIT in patients with a clinical history of ragweed sensitization. To analyze possible difference among immunotherapeutic protocols, we also compared patients receiving preseasonal, seasonal, or prolonged sublingual therapy (≥3 y); patients receiving symptomatic therapy alone were enrolled as well in the study. Clinical and immunological parameters were measured twice in and out of the pollination period. Clinical benefits, as measured by the visual analog scale for symptoms and for use of drugs, were evident in all three groups of individuals receiving immunotherapy, but were significantly better in patients undergoing prolonged SLIT. Immunologically, SLIT resulted in increased IL-10 production, programmed cell death ligand 1 expression, and concentration of allergen-specific IgG4, as well as in the reduction of CD80 and CD86 expression and IL-4 production. SLIT, thus, is associated with modulation of programmed cell death ligand 1 expression and IL-10 synthesis and favors the production of allergen-specific IgG4. These effects are evident from the first pollen season, independently from therapeutic regimen (preseasonal or seasonal) even if a prolonged treatment is necessary to obtain full clinical efficacy. A more detailed understanding of the interaction of allergen and APCs within the oral mucosa will allow improved targeting of allergy vaccine.
NKG2D Is Required for NK Cell Activation and Function in Response to E1-Deleted Adenovirus
Authors: Zhu Jiangao , Huang Xiaopei , Yang Yiping 
Published: November 2010

Abstract
Despite high transduction efficiency in vivo, the application of recombinant E1-deleted adenoviral vectors for in vivo gene therapy has been limited by the attendant innate and adaptive immune responses to adenoviral vectors. NK cells have been shown to play an important role in innate immune elimination of adenoviral vectors in vivo. However, the mechanisms underlying NK cell activation and function in response to adenoviral vectors remain largely undefined. In this study, we showed that NK cell activation upon adenoviral infection was dependent on accessory cells such as dendritic cells and macrophages and that cell contact-dependent signals from the accessory cells are necessary for NK cell activation. We further demonstrated that ligands of the NK activating receptor NKG2D were upregulated in accessory cells upon adenoviral infection and that blockade of NKG2D inhibited NK cell activation upon adenoviral infection, leading to a delay in adenoviral clearance in vivo. In addition, NKG2D was required for NK cell-mediated cytolysis on adenovirus-infected targets. Taken together, these results suggest that efficient NK cell activation and function in response to adenoviral infection is critically dependent on the NKG2D pathway, which understanding may assist in the design of effective strategies to improve the outcome of adenovirus-mediated gene therapy.
Cutting Edge: Lymphoproliferation Caused by Fas Deficiency Is Dependent on the Transcription Factor Eomesodermin
Authors: Kinjyo Ichiko , Gordon Scott M. , Intlekofer Andrew M. , Dowdell Kennichi , Mooney Erin C. , Caricchio Roberto , Grupp Stephan A. , Teachey David T. , Rao V. Koneti , Lindsten Tullia , Reiner Steven L. 
Published: November 2010

AbstractA hallmark of autoimmune lymphoproliferative syndrome (ALPS), caused by mutation of the Fas death receptor, is massive lymphadenopathy from aberrant expansion of CD4−CD8− (double-negative [DN]) T cells. Eomesodermin (Eomes) is a member of the T-box family of transcription factors and plays critical roles in effector cell function and memory cell fitness of CD8+ T lymphocytes. We provide evidence in this study that DN T cells exhibit dysregulated expression of Eomes in humans and mice with ALPS. We also find that T cell-specific deletion of Eomes prevents lymphoid hypertrophy and accumulation of DN T cells in Fas-mutant mice. Although Eomes has critical physiological roles in the function and homeostasis of CD8+ T cells, overexpression of Eomes appears to enable pathological induction or expansion of unusual CD8-related T cell subsets. Thus, antagonism of Eomes emerges as a therapeutic target for DN T cell ablation in ALPS.
Specific coping behaviors in relation to adolescent depression and suicidal ideation
Authors: Horwitz Adam G. , Hill Ryan M. , King Cheryl A. 
Published: November 2010

ABSTRACTThe coping strategies used by adolescents to deal with stress may have implications for the development of depression and suicidal ideation. This study examined coping categories and specific coping behaviors used by adolescents to assess the relation of coping to depression and suicidal ideation. In hierarchical regression models, the specific coping behaviors of behavioral disengagement and self‐blame were predictive of higher levels of depression; depression and using emotional support were predictive of suicidal ideation. Results suggest that specific behaviors within the broad coping categories of emotion‐focused coping (e.g., self‐blame) and avoidant coping (e.g., behavioral disengagement) account for these categories’ associations with depression and suicidal ideation. Specific problem‐focused coping strategies did not independently predict lower levels of depression or suicidal ideation. It may be beneficial for interventions to focus on eliminating maladaptive coping behaviors in addition to introducing or enhancing positive coping behaviors.
Using discrete choice experiments to inform randomised controlled trials: an application to chronic low back pain management in primary care
Authors: Yi Deokhee , Ryanl Mandy , Campbelll Susan , Elliottl Alison , Torrancel Nicola , Chambersl Alastair , Johnstonl Marie , Hannafordl Philip , Smithl Blair H. 
Published: November 2010

AbstractPain Management Programmes (PMPs) are a multi‐disciplinary approach to the management of chronic low back pain (CLBP). Notwithstanding evidence of effectiveness, successful take‐up of programmes requires acceptability to patients. We used a discrete choice experiment to investigate patient preferences for alternative PMPs for managing CLBP in primary care. Specifically, we estimated the probability of uptake of alternative configurations of PMPs. Potential attributes and associated levels influencing take‐up were identified through a systematic literature review, survey of current PMPs, expert consultation, and focus groups. Five attributes were included: content; provider; schedule; group size; and travel time to clinic. Four hundred and fourteen questionnaires were mailed to patients attending clinics and 124 questionnaires were returned suitable for analysis. Method of delivery influenced probability of take‐up, with small group sizes and low intensity programmes over a prolonged period increasing the probabilities. Travel time was also important. However, providers and contents of PMPs were not main drivers of preferences, though those with more severe pain did prefer PMPs provided by more specialists. Probability of take‐up increases when PMPs better reflect patient preferences. Given preferences, resource constraints, and evidence on clinical outcomes of alternative configurations it is suggested more resource‐intensive PMPs be reserved for those with the most severe and disabling pain and less intensive programmes delivered over a longer time period in smaller groups for those with less severe pain. These findings can inform future randomised trials to evaluate acceptable PMPs in primary care.
Assigning duplication events to relative temporal scales in genome-wide studies
Authors: Huerta-Cepas Jaime , Gabaldón Toni 
Published: November 2010

Abstract
Motivation: In genome-wide analyses, the relative age of gene duplications is often estimated by measuring the rate of synonymous substitutions (dS) between paralogous sequences. On the other hand, recent studies have shown the feasibility of inferring, at genomic scales, the relative age of duplication events from the topology of gene family trees. This represents a promising alternative for large surveys requiring an automatic methodology to establish a timeline of duplication events and that are usually limited to the use of dS, which presents known limitations such as a fast saturation of the signal. However, both measures have never been compared in a common framework.
Results: Topology-based placement of duplications on a relative time scale corresponding to periods between speciation events were found to be highly consistent, providing the same placement for 67–84% of a reliable set of gene pairs duplicated in a single event. For recent evolutionary periods, dS and topological measures showed a strong correlation. We conclude that the topology-based approach is more appropriate for assigning duplications to temporal scales when analyses need to include ancient events, and that the study of recent duplications may benefit from a combination of dS and topology information.
Contact: tgabaldon@crg.es
Supplementary information: Supplementary data are available at Bioinformatics online.
Inference of gene networks—application toBifidobacterium
Authors: Lai Darong , Yang Xinyi , Wu Gang , Liu Yuanhua , Nardini Christine 
Published: November 2010

AbstractMotivation: The reliable and reproducible identification of gene interaction networks represents one of the grand challenges of both modern molecular biology and computational sciences. Approaches based on careful collection of literature data and network topological analysis, applied to unicellular organisms, have proven to offer results applicable to medical therapies. However, when little a priori knowledge is available, other approaches, not relying so strongly on previous literature, must be used. We propose here a novel algorithm (based on ordinary differential equations) able to infer the interactions occurring among genes, starting from gene expression steady state data.Results: The algorithm was first validated on synthetic and real benchmarks. It was then applied to the reconstruction of the core of the amino acids metabolism in Bifidobacterium longum, an essential, yet poorly known player in the human gut intestinal microbiome, known to be related to the onset of important diseases, such as metabolic syndromes. Our results show how computational approaches can offer effective tools for applications with the identification of potential new biological information.Availability: The software is available at www.bioconductor.org and at www.picb.ac.cn/ClinicalGenomicNTW/temp2.html.Contact: christine@picb.ac.cnSupplementary information: Supplementary data are available at Bioinformatics online.
The uniqueome: a mappability resource for short-tag sequencing
Authors: Koehler Ryan , Issac Hadar , Cloonan Nicole , Grimmond Sean M. 
Published: November 2010

Abstract
Summary: Quantification applications of short-tag sequencing data (such as CNVseq and RNAseq) depend on knowing the uniqueness of specific genomic regions at a given threshold of error. Here, we present the ‘uniqueome’, a genomic resource for understanding the uniquely mappable proportion of genomic sequences. Pre-computed data are available for human, mouse, fly and worm genomes in both color-space and nucletotide-space, and we demonstrate the utility of this resource as applied to the quantification of RNAseq data.
Availability: Files, scripts and supplementary data are available from http://grimmond.imb.uq.edu.au/uniqueome/; the ISAS uniqueome aligner is freely available from http://www.imagenix.com/.
Contact: n.cloonan@uq.edu.au
Supplementary information: Supplementary data are available at Bioinformatics online.