gebhart/patrepeval huggingface dataset:
Alzheimer’s disease: A matter of blood–brain barrier dysfunction? (2017)

The blood-brain barrier (BBB) keeps neurotoxic plasma-derived components, cells, and pathogens out of the brain. An early BBB breakdown and/or dysfunction have been shown in Alzheimer's disease (AD) before dementia, neurodegeneration and/or brain atrophy occur. However, the role of BBB breakdown in neurodegenerative disorders is still not fully understood. Here, we examine BBB breakdown in animal models frequently used to study the pathophysiology of AD, including transgenic mice expressing human amyloid-β precursor protein, presenilin 1, and tau mutations, and apolipoprotein E, the strongest genetic risk factor for AD. We discuss the role of BBB breakdown and dysfunction in neurodegenerative process, pitfalls in BBB measurements, and how targeting the BBB can influence the course of neurological disorder. Finally, we comment on future approaches and models to better define, at the cellular and molecular level, the underlying mechanisms between BBB breakdown and neurodegeneration as a basis for developing new therapies for BBB repair to control neurodegeneration.
The Insulin-like Growth Factor II/Mannose 6-Phosphate Receptor Utilizes the Same Membrane Compartments as GLUT4 for Insulin-dependent Trafficking to and from the Rat Adipocyte Cell Surface (1996)

The insulin-like growth factor II (IGF-II)/mannose 6-phosphate (Man-6-P) receptor recycles in adipose cells between the cell surface and an intracellular storage pool, and the rate of this trafficking is markedly enhanced by insulin. We show here that the IGF-II/Man-6-P receptor is a constituent of the GLUT4-containing compartment ("GLUT4 vesicles") where it represents gp230, a major recycling protein detected earlier by cell surface biotinylation (Kandror, K. V., and Pilch, P. F. (1994) J. Biol. Chem. 269, 138-142). The GLUT4 vesicles include 10-15% of the total and all of the acutely insulin-responsive recycling population of the IGF-II/Man-6-P receptor. The main part of the IGF-II/Man-6-P receptor population is excluded from the pathway of GLUT4 trafficking and either resides permanently in intracellular membranes or has a much slower rate of cycling to the cell surface. Thus, GLUT4 vesicles mediate the insulin-dependent delivery to the cell surface of the IGF-II/Man-6-P receptor as well as the other recyclable proteins with extracellular functional domains (GLUT4 and the aminopeptidase gp160).
Structure-Based Improvement of the Biophysical Properties of Immunoglobulin VH Domains with a Generalizable Approach (2003)

In a systematic study of V gene families carried out with consensus V(H) and V(L) domains alone and in combinations in the scFv format, we found comparatively low expression yields and lower cooperativity in equilibrium unfolding in antibody fragments containing V(H) domains of human germline families 2, 4, and 6. From an analysis of the packing of the hydrophobic core, the completeness of charge clusters, the occurrence of unsatisfied hydrogen bonds, and residues with low beta-sheet propensities, positive Phi angles, and exposed hydrophobic side chains, we pinpointed residues potentially responsible for the unsatisfactory properties of these germline-encoded sequences. Several of those are in common between the domains of the even-numbered subgroups, but do not occur in the odd-numbered ones. In this study, we have systematically exchanged those residues alone and in combination in two different scFvs using the V(H)6 framework, and we describe their effect on equilibrium stability and folding yield. We improved the stability by 20.9 kJ/mol and the expression yield by a factor of 4 and can now use these data to rationally engineer antibodies derived from this and similar germline families for better biophysical properties. Furthermore, we provide an improved design for libraries exploiting the significant additional diversity provided by these frameworks. Both antibodies studied here completely retain their binding affinity, demonstrating that the CDR conformations were not affected.
Expression of genes for B7-H3 and other T cell ligands by nasal epithelial cells during differentiation and activation (2004)

Epithelial cells of the human respiratory tract express human leukocyte antigen (HLA) and the costimulatory molecules B7-1 and B7-2. Little is known, however, about the constitutive expression of genes encoding for the more recently identified members of the B7 homolog family of costimulatory molecules or about the influence of cellular differentiation and cytokines on their activity or on that of HLA or B7-1 and B7-2. Human nasal epithelial (HNE) cells were grown at the air-liquid interface (ALI) for 2 or 21 days to model in vivo conditions. Expression of genes for HLA-B and HLA-DR1 increased during mucociliary differentiation during this period and became more similar to HNE cells obtained fresh by brush biopsy from nasal turbinates. Gene transcripts for B7-H3 and B7-H2 were abundantly expressed in cells cultured at the ALI, but neither their activities nor that of B7-2 was significantly altered during differentiation. IFN-gamma and TNF-alpha upregulated mRNA encoding for both HLA molecules, but not for the B7 molecules. This study describes, for the first time, the expression of B7-H3 and B7-H2 by HNE cells and thus expands the range of potential costimulatory signals through which these cells may interact with activated mucosal T lymphocytes. In addition, the results suggest that the extent of mucociliary differentiation of cultured cells may influence this capability.
Developing IoT applications in the Fog: A Distributed Dataflow approach (2015)

In this paper we examine the development of IoT applications from the perspective of the Fog Computing paradigm, where computing infrastructure at the network edge in devices and gateways is leverage for efficiency and timeliness. Due to the intrinsic nature of the IoT: heterogeneous devices/resources, a tightly coupled perception-action cycle and widely distributed devices and processing, application development in the Fog can be challenging. To address these challenges, we propose a Distributed Dataflow (DDF) programming model for the IoT that utilises computing infrastructures across the Fog and the Cloud. We evaluate our proposal by implementing a DDF framework based on Node-RED (Distributed Node-RED or D-NR), a visual programming tool that uses a flow-based model for building IoT applications. Via demonstrations, we show that our approach eases the development process and can be used to build a variety of IoT applications that work efficiently in the Fog.
In vitro evidence for the interaction of tRNA3Lys with U3 during the first strand transfer of HIV-1 reverse transcription (2000)

Over the course of its evolution, HIV-1 has taken maximum advantage of its tRNA(3)(Lys)primer by utilizing it in several steps of reverse transcription. Here, we have identified a conserved nonanucleotide sequence in the U3 region of HIV-1 RNA that is complementary to the anticodon stem of tRNA(3)(Lys). In order to test its possible role in the first strand transfer reaction, we applied an assay using a donor RNA corresponding to the 5'-part and an acceptor RNA spanning the 3'-part of HIV-1 RNA. In addition, we constructed two acceptor RNAs in which the nonanucleotide sequence complementary to tRNA(3)(Lys)was either substituted (S) or deleted (Delta). We used either natural tRNA(3)(Lys)or an 18 nt DNA as primer and measured the efficiency of (-) strand strong stop DNA transfer in the presence of wild-type, S or Delta acceptor RNA. Mutations in U3 did not decrease the transfer efficiency when reverse transcription was primed with the 18mer DNA. However, they significantly reduced the strand transfer efficiency in the tRNA(3)(Lys)-primed reactions. This reduction was also observed in the presence of nucleocapsid protein. These results suggest that tRNA(3)(Lys)increases (-) strand strong stop transfer by interacting with the U3 region of the genomic RNA. Sequence comparisons suggest that such long range interactions also exist in other lentiviruses.
Design considerations for usage accounting and feedback in internetworks (1990)

This paper investigates the design of resource usage feedback mechanisms for packet switched internetworks. After a discussion of the motivations for feedback mechanisms, feedback channels and policies are described. We then outline issues raised by the design of mechanisms to realize these policies, including: network service disciplines, accounting granularity, metrics, authentication, and coordination among transit carriers.Usage-based charging is only one means of feedback. Our purpose is to begin a systematic discussion of the technical issues associated with a range of usage feedback alternatives. Therefore the paper should not be read as a policy statement promoting usage sensitive charging in internets. In fact, one of the goals of the feedback mechanisms explored in this paper is to allow network service providers and users to avoid the introduction of usage sensitive charges if they so wish; while still realizing the benefits of statistical resource sharing offered by packet switching and the benefits of efficient resource utilization offered by usage feedback.
Arzoxifene, a new selective estrogen receptor modulator for chemoprevention of experimental breast cancer. (2001)

Arzoxifene ([6-hydroxy-3-[4-[2-(1-piperidinyl)-ethoxy]phenoxy]-2-(4-methoxyphenyl)]benzo[b]thiophene) is a selective estrogen receptor modulator (SERM) that is a potent estrogen antagonist in mammary and uterine tissue while acting as an estrogen agonist to maintain bone density and lower serum cholesterol. Arzoxifene is a highly effective agent for prevention of mammary cancer induced in the rat by the carcinogen nitrosomethylurea and is significantly more potent than raloxifene in this regard. Arzoxifene is devoid of the uterotrophic effects of tamoxifen, suggesting that, in contrast to tamoxifen, it is unlikely that the clinical use of arzoxifene will increase the risk of developing endometrial carcinoma.
[Compulsive disorder and Gilles de la Tourette syndrome. On the differential diagnosis of organic and psychogenic compulsive symptoms]. (1995)

A high prevalence of obsessions and compulsions is recognized in patients with Gilles-de-la-Tourette syndrome. Comparison of a group of patients with Gilles-de-la-Tourette syndrome with a group with obsessive-compulsive disorder, using the diagnostic criteria of the DSM-III-R, showed significantly higher scores in both groups of patients in the Hamburg obsessive-compulsive inventory (short version) than in a control group. When selected items from this Inventory were entered in a discriminant analysis, it was shown that there were specific differences in the obsessive-compulsive symptoms in the Gilles-de-la-Tourette syndrome compared to an obsessive-compulsive disorder. Eighty-eight percent of the patients were correctly classified with respect to their diagnosis with eight items of the Hamburg obsessive-compulsive inventory. This result leads to the conclusion that differential observation of the psychopathology of obsessions and compulsions can contribute to the differential diagnosis in obsessive-compulsive disorder and Gilles-de-la-Tourette syndrome, which is still underdiagnosed in Germany compared to epidemiological data in the USA. Moreover, the different psychopathology may reflect differences between a neurotic and an organic basis for obsessions and compulsions.
Regulation of early human hematopoietic (BFU-E and CFU-GEMM) progenitor cells in vitro by interleukin 1-induced fibroblast-conditioned medium (1987)

Stimulators of human erythroid burst-forming units (BFU-E) and multipotential colony-forming cells (CFU-GEMM) can be produced by a number of different cell types. A product of human peripheral blood monocytes, interleukin 1 (IL-1), was evaluated for its ability to stimulate fibroblast cultures to produce stimulators of human bone marrow BFU-E and CFU-GEMM colony formation. BFU-E and CFU-GEMM colony formation was evaluated using low-density, nonadherent low-density, and T lymphocyte-depleted nonadherent low-density human bone marrow cells cultured in the presence of a source of pure human erythropoietin. Both human monocyte conditioned medium (MCM) and human recombinant IL-1 (hrIL-1) induced fibroblasts to produce stimulators of BFU-E and CFU-GEMM in a dose-dependent fashion with maximal colony formation occurring when fibroblasts were stimulated by 25% MCM or 140 ng/mL ROO6B hrIL-1, or 1.25 to 5 ng/mL ROO6T hrIL-1. Preincubation of MCM and hrIL-1 with an antibody to IL-1 inactivated the ability of MCM and hrIL-1 to induce the release of erythroid and multipotential colony stimulating activity from fibroblasts. These results suggest that monocyte-derived IL-1 is involved in regulating the production of humoral stimulators of early human hematopoietic progenitors.
Performance of Hybrid Reinforcements in PVC Composites: Part I—Use of Surface-Modified Mica and Wood Pulp as Reinforcements (1993)

Abstract In the present study, the hybird behavior of surfacetreated mica and hardwood chemithermomechanical pulp (CTMP) in PVC composites was investigated. In order to improve the compatibility of wood fibers with PVC and surface-coated mica, CTMP was subjected to different surface modifications by pretreating the fibers with maleic anhydride (MA), a mixture of MA and Na-silicate, and with an inocyanate (PMPPIC). The effect exerted by the concentration of reinforcements, composition of hybrid as well as the treatment of CTMP, on the mechanical properties of the hybrid composites were evaluated. In general, these properties improved compared to those of uncoated CTMP/mica-filled composites. Moreover, PMPPIC treatment renked best followed by MA — and MA + silicat treatments. The optimal concentrations of reinforcements and their compositions, which provided superior properties, varied according to the nature of the trestment of CTMP and of the individual mechanical properties themselves.
Sleep-Disordered Breathing and Mortality: A Prospective Cohort Study (2009)

Sleep-disordered breathing is associated with all-cause mortality and specifically that due to coronary artery disease, particularly in men aged 40-70 y with severe sleep-disordered breathing. Please see later in the article for the Editors' Summary.
Descriptive Simplicity in Parallel Computing (1997)

and there currently exist a wide selection of parallel programming languages and environments. This thesis presents and examines the Hierarchical Skeleton Model (HSM), a model of parallel programming that combines ease of use, portability and flexibility.
Kras activation in p53-deficient myoblasts results in high-grade sarcoma formation with impaired myogenic differentiation (2015)

While genomic studies have improved our ability to classify sarcomas, the molecular mechanisms involved in the formation and progression of many sarcoma subtypes are unknown. To better understand developmental origins and genetic drivers involved in rhabdomyosarcomagenesis, we describe a novel sarcoma model system employing primary murine p53-deficient myoblasts that were isolated and lentivirally transduced with KrasG12D. Myoblast cell lines were characterized and subjected to proliferation, anchorage-independent growth and differentiation assays to assess the effects of transgenic KrasG12D expression. KrasG12D overexpression transformed p53-/- myoblasts as demonstrated by an increased anchorage-independent growth. Induction of differentiation in parental myoblasts resulted in activation of key myogenic regulators. In contrast, Kras-transduced myoblasts had impaired terminal differentiation. p53-/- myoblasts transformed by KrasG12D overexpression resulted in rapid, reproducible tumor formation following orthotopic injection into syngeneic host hindlimbs. Pathological analysis revealed high-grade sarcomas with myogenic differentiation based on the expression of muscle-specific markers, such as Myod1 and Myog. Gene expression patterns of murine sarcomas shared biological pathways with RMS gene sets as determined by gene set enrichment analysis (GSEA) and were 61% similar to human RMS as determined by metagene analysis. Thus, our novel model system is an effective means to model high-grade sarcomas along the RMS spectrum.
Biosynthetic Studies of ω-Cycloheptyl Fatty Acids in Alicyclobacillus cycloheptanicus. Formation of Cycloheptanecarboxylic Acid from Phenylacetic Acid (1997)

The formation of the structurally novel, mono-substituted cycloheptane ring in ω-cycloheptyl fatty acids in Alicyclobacillus cycloheptanicus (formerly Bacillus cycloheptanicus) has been examined. Feeding experiments with 13C- and 2H-labeled intermediates demonstrated that cycloheptanecarboxylic acid (3), probably as its CoA thioester, is the starter unit for ω-cycloheptyl fatty acid biosynthesis. Analysis of the resultant labeling pattern from a feeding experiment with [U-13C6]glucose suggested a shikimate pathway origin of 3 via aromatic amino acids. [1,2-13C2]Phenylacetic acid (6) was efficiently metabolized into the 3-derived moiety in a manner reminiscent of the seven-membered ring Pseudomonas metabolite thiotropocin. The fates of the aromatic and benzylic hydrogens of 6 were determined; these dictated various boundary conditions for the biosynthetic pathway from 6 to 3. Taken together with the results from feeding experiments with postulated cycloheptenylcarboxylate biosynthetic intermediates, the data lead us to propose a pathway which involves an oxidative ring-expansion of 6 to a hydroxynorcaradiene intermediate followed by a series of double bond reductions and dehydrations to the saturated 3.
Applications of New Sequencing Technologies for Transcriptome Analysis (2009)

Transcriptome analysis has been a key area of biological inquiry for decades. Over the years, research in the field has progressed from candidate gene-based detection of RNAs using Northern blotting to high-throughput expression profiling driven by the advent of microarrays. Next-generation sequencing technologies have revolutionized transcriptomics by providing opportunities for multidimensional examinations of cellular transcriptomes in which high-throughput expression data are obtained at a single-base resolution.
Efficient production of soluble recombinant single chain Fv fragments by a Pseudomonas putida strain KT2440 cell factory (2011)

Pseudomonas putida KT2440 is a good cell factory for the production of scFvs, and the broad host range constructs we have produced allow yield assessment in a number of different expression hosts when yields in one initially selected are insufficient. High cell density cultivation and further optimization and refinement of the KT2440 cell factory will achieve additional increases in the yields of scFvs.
The Ethnography of the University Initiative: A decade of student research on the university (2013)

Welcome to this special issue of Learning and Teaching: The International Journal of Higher Education in the Social Sciences. As guest editors, we are delighted to be able to share the experiences of the Ethnography of the University Initiative (EUI, www.eui.uiuc.edu), a multi-disciplinary course-based initiative that fosters student research on their own universities and is housed at the University of Illinois at Urbana-Champaign (U of I). EUI is at once a pedagogical approach, a teaching community and a digital archive. EUI also works as a research agenda committed to student engagement with university practice and policy – and thus to institutional critique. In this editorial introduction, we provide an overview of EUI’s history, innovations, organisational structure and guiding values. We also introduce this issue’s authors – faculty members, an administrator and a former student – all of whom have taught with EUI and have documented here the ways in which taking the university as a research subject transformed their courses and teaching, and in some cases, their programmes and learning.
Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): A randomized, controlled trial (2005)

In patients with early RA, initial combination therapy including either prednisone or infliximab resulted in earlier functional improvement and less radiographic damage after 1 year than did sequential monotherapy or step-up combination therapy.
Protein–Protein Interactions Essentials: Key Concepts to Building and Analyzing Interactome Networks (2010)

8 páginas, 3 figuras, 1 tabla.-- This is an open-access article distributed under the terms of the Creative Commons Attribution License.
Effect of Trehalose on the Properties of Mutant γPKC, Which Causes Spinocerebellar Ataxia Type 14, in Neuronal Cell Lines and Cultured Purkinje Cells* (2010)

Several missense mutations in the protein kinase Cγ (γPKC) gene have been found to cause spinocerebellar ataxia type 14 (SCA14), an autosomal dominant neurodegenerative disease. We previously demonstrated that the mutant γPKC found in SCA14 is susceptible to aggregation, which induces apoptotic cell death. The disaccharide trehalose has been reported to inhibit aggregate formation and to alleviate symptoms in cellular and animal models of Huntington disease, Alzheimer disease, and prion disease. Here, we show that trehalose can be incorporated into SH-SY5Y cells and reduces the aggregation of mutant γPKC-GFP, thereby inhibiting apoptotic cell death in SH-SY5Y cells and primary cultured Purkinje cells (PCs). Trehalose acts by directly stabilizing the conformation of mutant γPKC without affecting protein turnover. Trehalose was also found to alleviate the improper development of dendrites in PCs expressing mutant γPKC-GFP without aggregates but not in PCs with aggregates. In PCs without aggregates, trehalose improves the mobility and translocation of mutant γPKC-GFP, probably by inhibiting oligomerization and thereby alleviating the improper development of dendrites. These results suggest that trehalose counteracts various cellular dysfunctions that are triggered by mutant γPKC in both neuronal cell lines and primary cultured PCs by inhibiting oligomerization and aggregation of mutant γPKC.
Studies of the chemical and pore structures of the carbon aerogels synthesized by gelation and supercritical drying in isopropanol (2004)

Abstract The carbon aerogels prepared by a new method through gelation and supercritical drying in isopropanol were characterized by X‐ray photoelectron spectroscopy (XPS), scanning electron microscopy, and a surface area analyzer. Their chemical structure, morphology, and pore structure are discussed. We found that all of these carbon aerogel (CA‐IPA) samples have almost the same carbon and oxygen elemental states, as well as similar oxygen‐containing groups. The curve fitting of the C1s XPS spectra of the samples for characterizing oxygen‐containing surface groups can be performed by assuming the peak type to be a Gaussian–Lorentzian Cross Product, but we cannot obtain good results using a Gaussian lineshape. When the mass density of the CA‐IPA decreases, the mesopores and macropores of the samples are found to grow, but the size and the shape of individual carbon nanoparticles in various CA‐IPA samples do not apparently change. The micropore volume of the CA‐IPA samples increases with a decrease in the mass density, while the mesopore volume has a maximum at a certain mass density. The CA‐IPA samples have a very narrow micropore distribution at about 0.5 nm. The mesopore distribution of the CA‐IPA is widened and the average pore size increases as the mass density of the sample decreases. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 91: 3060–3067, 2004
Testosterone Replacement in Hypogonadal Men With Type 2 Diabetes and/or Metabolic Syndrome (the TIMES2 Study) (2011)

Over a 6-month period, transdermal TRT was associated with beneficial effects on insulin resistance, total and LDL-cholesterol, Lpa, and sexual health in hypogonadal men with type 2 diabetes and/or MetS.