gebhart/patrepeval huggingface dataset:
Fully X-tolerant, very high scan compression (2010)

This paper presents a new X-blocking system which allows very high compression and full coverage even if the density of unknown values is very high and varies every shift. Despite the presence of Xs in scan cells, compression can be maximized by using PRPG and MISR structures. Results on industrial designs with various X densities demonstrate consistently high compression and full test coverage.
Total, LDL, and HDL Cholesterol Decrease With Age in Older Men and Women (1997)

Cross-sectional decrements in TC and LDL-C with age in men are not explained by survivor bias because they are also observed prospectively. Although weight change was the most important explanatory variable, TC, LDL-C, and HDL-C levels also decreased in those who lost or gained weight. Age was not an independent predictor of change. Other prospective studies are recommended to better define the causes and consequences of cholesterol and lipoprotein changes in old age.
Improving the Scalability of Data Center Networks with Traffic-aware Virtual Machine Placement (2010)

The scalability of modern data centers has become a practical concern and has attracted significant attention in recent years. In contrast to existing solutions that require changes in the network architecture and the routing protocols, this paper proposes using traffic-aware virtual machine (VM) placement to improve the network scalability. By optimizing the placement of VMs on host machines, traffic patterns among VMs can be better aligned with the communication distance between them, e.g. VMs with large mutual bandwidth usage are assigned to host machines in close proximity. We formulate the VM placement as an optimization problem and prove its hardness. We design a two-tier approximate algorithm that efficiently solves the VM placement problem for very large problem sizes. Given the significant difference in the traffic patterns seen in current data centers and the structural differences of the recently proposed data center architectures, we further conduct a comparative analysis on the impact of the traffic patterns and the network architectures on the potential performance gain of traffic-aware VM placement. We use traffic traces collected from production data centers to evaluate our proposed VM placement algorithm, and we show a significant performance improvement compared to existing general methods that do not take advantage of traffic patterns and data center network characteristics.
Pyrosequencing enumerates and contrasts soil microbial diversity (2007)

Estimates of the number of species of bacteria per gram of soil vary between 2000 and 8.3 million (Gans et al., 2005; Schloss and Handelsman, 2006). The highest estimate suggests that the number may be so large as to be impractical to test by amplification and sequencing of the highly conserved 16S rRNA gene from soil DNA (Gans et al., 2005). Here we present the use of high throughput DNA pyrosequencing and statistical inference to assess bacterial diversity in four soils across a large transect of the western hemisphere. The number of bacterial 16S rRNA sequences obtained from each site varied from 26,140 to 53,533. The most abundant bacterial groups in all four soils were the Bacteroidetes, Betaproteobacteria and Alphaproteobacteria. Using three estimators of diversity, the maximum number of unique sequences (operational taxonomic units roughly corresponding to the species level) never exceeded 52,000 in these soils at the lowest level of dissimilarity. Furthermore, the bacterial diversity of the forest soil was phylum rich compared to the agricultural soils, which are species rich but phylum poor. The forest site also showed far less diversity of the Archaea with only 0.009% of all sequences from that site being from this group as opposed to 4%-12% of the sequences from the three agricultural sites. This work is the most comprehensive examination to date of bacterial diversity in soil and suggests that agricultural management of soil may significantly influence the diversity of bacteria and archaea.
A leaf‐based assay using interchangeable design principles to rapidly assemble multistep recombinant pathways (2009)

The assembly of multistep recombinant pathways in stably transformed plants is a cornerstone of crops producing new products yet can be a laborious and time-consuming process. Any heterologous expression platform capable of providing a rapid estimation of the functional assembly of an entire pathway would guide the design of such transgenic traits. In this study, we use a Nicotiana benthamiana transient leaf expression system to simultaneously express five genes, from five independent T(DNA) binary vectors, to assemble a complete recombinant pathway in five days. In this study, we demonstrate the production of long-chain polyunsaturated fatty acids (LC-PUFA) requiring five transgene-encoded reactions to convert endogenous fatty acids to LC-PUFA. The addition of a triacylglycerol assembly enzyme, Arabidopsis thaliana diacylglyceride-O-acyltransferase, and fractionation of the total lipid profile demonstrated that leaf oils contained 37% newly synthesised LC-PUFA, including 7% arachidonic acid (AA), 6% eicosopentaenoic acid and 3% docosahexaenoic acid. The calculation of enzymatic conversion efficiencies at each step of LC-PUFA synthesis suggests that this transient assembly of a complicated multistep pathway is highly efficient. Unlike experiments using stably transformed plants our assembly of an intricate pathway maintained full gene-for-gene interchangeability and required a fraction of the time and glasshouse space. Furthermore, an exogenous LC-PUFA fatty acid substrate, AA, was fed and metabolised by a transiently expressed Delta17-desaturase enzyme, and provided results similar to those obtained in yeast feeding experiments. Although the assay was ideal for LC-PUFA pathways, this assay format may become a powerful tool for the characterisation and step-wise improvement of other recombinant pathways and multigenic traits.
The black silicon method. IV. The fabrication of three-dimensional structures in silicon with high apect ratios for scanning probe microscopy and other applications (2005)

The recently developed black silicon method (BSM) is presented as a powerful tool in finding recipes for the fabrication of MEMS building blocks such as Ay-stages. scanning probe tips, inkjet filters, multi-electrodes for neuro-electronic interfaces, and mouldings Lor direct patterning into polymers. The fabrication of these blocks in silicon with high aspect ratios and smooth surface textures will be described and discussed by using the BSM and standard reactive ion etching (ME).
Generation of tumor antigen-specific CD4+ and CD8+ T cells by simultaneous MHC-I and -II epitope presentation in vitro and in vivo (2014)

Meeting abstracts In recent years, activation of the patient's immune system to defend against tumors was demonstrated to be a promising alternative strategy to classical cancer treatments. Dendritic cells (DCs) can present antigens on MHC-II and -I leading to the activation of CD4+ or CD8+ T cells
Regulation of murine in vivo lgG and lgE responses by a monoclonal anti-IL-4 receptor antibody (1991)

Although the cytokine interleukin 4 (IL-4) stimulates LPS-activated mouse B lymphocytes to secrete both IgG1 and IgE, an anti-IL-4 antibody completely inhibits IgE responses but has little or no effect on several in vivo IgG responses. IL-4 might, therefore, have a restricted role in the generation of in vivo humoral immune responses. Alternatively, IgG1 responses might be stimulated by IL-4 secreted by T cells that are interacting directly with B cells, so that anti-IL-4 antibody cannot neutralize IL-4 before it binds to a B cell IL-4 receptor. In contrast, an antibody that blocks the IL-4 receptor (IL-4R) should equally inhibit responses to IL-4 produced proximal to or distant from a B cell. This reasoning led us to determine the ability of an anti-IL-4R mAb to affect antibody production in mice injected with a goat antibody to mouse IgD (GaM delta) or inoculated with the nematode parasite Heligmosomoides polygyrus. Anti-IL-4R mAb, like anti-IL-4 mAb, blocked IgE responses by greater than 95% and enhanced IgG2a responses to a variable extent. Anti-IL-4R mAb, however, had only a modest and variable inhibitory effect on the induction of IgG1 responses, although it caused these responses to terminate more rapidly. A combination of anti-IL-4 and anti-IL-4R mAbs totally blocked goat anti-mouse IgD antibody (GaM delta)-induced IgE production but had no additive inhibitory effect on IgG1 production. These observations are most consistent with the view that IL-4 is required for a primary IgE response, but has relatively little role in the induction of IgG1 responses in the in vivo systems studied.
Proteasome inhibition in oxidative stress neurotoxicity: implications for heat shock proteins (2001)

Recent studies have demonstrated that inhibition of the proteasome, an enzyme responsible for the majority of intracellular proteolysis, may contribute to the toxicity associated with oxidative stress. In the present study we demonstrate that exposure to oxidative injury (paraquat, H(2)O(2), FeSO(4)) induces a rapid increase in reactive oxygen species (ROS), loss of mitochondrial membrane potential, inhibition of proteasome activity, and induction of cell death in neural SH-SY5Y cells. Application of proteasome inhibitors (MG115, epoxomycin) mimicked the effects of oxidative stressors on mitochondrial membrane potential and cell viability, and increased vulnerability to oxidative injury. Neural SH-SY5Y cells stably transfected with human HDJ-1, a member of the heat shock protein family, were more resistant to the cytotoxicity associated with oxidative stressors. Cells expressing increased levels of HDJ-1 displayed similar degrees of ROS formation following oxidative stressors, but demonstrated a greater preservation of mitochondrial function and proteasomal activity following oxidative injury. Cells transfected with HDJ-1 were also more resistant to the toxicity associated with proteasome inhibitor application. These data support a possible role for proteasome inhibition in the toxicity of oxidative stress, and suggest heat shock proteins may confer resistance to oxidative stress, by preserving proteasome function and attenuating the toxicity of proteasome inhibition.
Prolyl Aminopeptidase Is Also Present in Enterobacteriaceae: Cloning and Sequencing of the Hafnia alvei Enzyme-Gene and Characterization of the Expressed Enzyme (1996)

The Hafnia alvei prolyl aminopeptidase gene (hpap) was cloned and sequenced, the expressed enzyme (HPAP) was purified to homogeneity and thoroughly characterized. An open reading frame of 1,281 bp was found to code for the enzyme, resulting in a protein of 427 amino acids with a molecular weight of 48,577. HPAP resembles the Aeromonas sobria enzyme, having 45% identity and the same distinctive properties with respect to size and substrate specificities. Both enzyme show similar chromatographic behavior, and HPAP could be purified following the procedure previously described for the Aeromonas enzyme. HPAP was found to be resistant to diisopropylphosphofluoridate as are most of the prolyl aminopeptidases hitherto described. In spite of this similarity, no inhibition by 1 mM p-chloromercuribenzoate solution could be detected. Significant inhibition was, however, observed when the enzyme was incubated with 3,4-dichloroisocoumarin. This study confirms the presence of two types of prolyl aminopeptidases, of which the Hafnia and Aeromonas enzymes constitute one group and the Bacillus, Neisseria, and Lactobacillus enzymes the other, and describes the cloning of the first prolyl aminopeptidase gene from an Enterobacteriaceae.
Hyaluronan-CD44 Interaction Activates Stem Cell Marker Nanog, Stat-3-mediated MDR1 Gene Expression, and Ankyrin-regulated Multidrug Efflux in Breast and Ovarian Tumor Cells (2008)

Hyaluronan (HA) is a major glycosaminoglycan in the extracellular matrix whose expression is tightly linked to multidrug resistance and tumor progression. In this study we investigated HA-induced interaction between CD44 (a HA receptor) and Nanog (an embryonic stem cell transcription factor) in both human breast tumor cells (MCF-7 cells) and human ovarian tumor cells (SK-OV-3.ipl cells). Using a specific primer pair to amplify Nanog by reverse transcriptase-PCR, we detected the expression of Nanog transcript in both tumor cell lines. In addition, our results reveal that HA binding to these tumor cells promotes Nanog protein association with CD44 followed by Nanog activation and the expression of pluripotent stem cell regulators (e.g. Rex1 and Sox2). Nanog also forms a complex with the "signal transducer and activator of transcription protein 3" (Stat-3) in the nucleus leading to Stat-3-specific transcriptional activation and multidrug transporter, MDR1 (P-glycoprotein) gene expression. Furthermore, we observed that HA-CD44 interaction induces ankyrin (a cytoskeletal protein) binding to MDR1 resulting in the efflux of chemotherapeutic drugs (e.g. doxorubicin and paclitaxel (Taxol)) and chemoresistance in these tumor cells. Overexpression of Nanog by transfecting tumor cells with Nanog cDNA stimulates Stat-3 transcriptional activation, MDR1 overexpression, and multidrug resistance. Down regulation of Nanog signaling or ankyrin function (by transfecting tumor cells with Nanog small interfering RNA or ankyrin repeat domain cDNA) not only blocks HA/CD44-mediated tumor cell behaviors but also enhances chemosensitivity. Taken together, these findings suggest that targeting HA/CD44-mediated Nanog-Stat-3 signaling pathways and ankyrin/cytoskeleton function may represent a novel approach to overcome chemotherapy resistance in some breast and ovarian tumor cells displaying stem cell marker properties during tumor progression.
DNA as a Material for Nanotechnology (1997)

Nanostructured systems and functionalized supramolecular aggregates are accessible by DNA hybridization. The nanocrystalline molecule (see schematic representation below) is constructed from gold clusters (shaded spheres) and oligonucleotides (ladderlike framework) by self-assembly. Complex DNA networks could serve as high-resolution matrices for the production of microchips. DNA technology is thus in the process of expanding to include applications in microelectronics.
Complement and Complement Regulatory Proteins as Potential Molecular Targets for Vascular Diseases (2004)

By-products of complement activation and complement regulatory proteins are increasingly recognized to play an important pathogenic role in a variety of vascular diseases including atherosclerosis, ischemia and reperfusion injury, hyperacute graft rejection, vasculitis, and the vascular complications of human diabetes. "Self" damage by autologous complement is mediated by activation products of the complement cascades or by direct insertion of the membrane attack complex (MAC) into cell membranes. Specifically, insertion of MAC complexes into endothelial cells results in the release of an array of growth factors and cytokines that induces proliferation, inflammation and thrombosis in the vascular wall. This paper reviews complement and complement regulatory proteins with specific focus on the vasculature and vascular diseases; it highlights complement and its regulators as potential targets for the rational design of mechanism-specific drugs for the treatment of some of the most prevalent human diseases.
A Stepwise Huisgen Cycloaddition Process: Copper(I)‐Catalyzed Regioselective “Ligation” of Azides and Terminal Alkynes. (2002)

Abstract For Abstract see ChemInform Abstract in Full Text.
Differential regulation of the p72-74 RAF-1 kinase in 3T3 fibroblasts expressing ras or src oncogenes. (1991)

The c-raf-1 protooncogene encodes a p72-74 serine/threonine-specific kinase that has been implicated in growth factor-mediated signal transduction and malignant transformation. Here, we compared the effects of Ha-c-ras and v-src oncogenes on the regulation of p72-74 RAF-1 kinase in NIH3T3 cells. In both serum-starved and platelet-derived growth factor-treated v-src-transformed cells, the RAF-1 kinase was constitutively activated, displaying characteristic retarded mobility in electrophoretic gels and elevated activity in in vitro kinase assays. In contrast, the RAF-1 protein from quiescent ras-transformed cells did not exhibit constitutively shifted gel mobility or elevated kinase activity but did respond normally with regard to platelet-derived growth factor- and phorbol myristate acetate-induced changes in p72-74 RAF-1 phosphorylation and kinase activity. 3T3 cells transformed by ras, however, contained elevated levels of p72-74 RAF-1 protein (as determined by immunoblotting), suggesting an indirect influence on this kinase. Quantitative differences in the levels and subcellular distribution of immunodetectable protein kinase C enzymes did not account for the differences between src- and ras-transformed 3T3 cells with regard to regulation of the RAF kinase. These findings in serum-deprived 3T3 cells demonstrate that expression of a ras oncogene can be insufficient for full activation of the p72-74 RAF-1 kinase, implying necessity for an additional growth factor-mediated stimulus.
Donepezil for the symptomatic treatment of patients with mild to moderate Alzheimer's disease: a meta‐analysis of individual patient data from randomised controlled trials (2004)

Donepezil (5 and 10 mg/day) provides meaningful benefits in alleviating deficits in cognitive and clinician-rated global function in AD patients relative to placebo. Increased improvements in cognition were indicated for the higher dose.
Expression of a Bacterial Gene in Mammalian Cells (1980)

Transfection of cultured monkey kidney cells with recombinant DNA constructed with a cloned Escherichia coli gene that codes for xanthine-guanine phosphoribosyltransferase and several different SV40 DNA-based vectors, results in the synthesis of readily measurable quantities of the bacterial enzyme. Moreover, the physiological defect in purine nucleotide synthesis characteristic of human Lesch-Nyhan cells can be overcome by the introduction of the bacterial gene into these cells.
Unmodified Cre recombinase crosses the membrane (2002)

Site-specific recombination in genetically modified cells can be achieved by the activity of Cre recombinase from bacteriophage P1. Commonly an expression vector encoding Cre is introduced into cells; however, this can lead to undesired side-effects. Therefore, we tested whether cell-permeable Cre fusion proteins can be directly used for lox-specific recombination in a cell line tailored to shift from red to green fluorescence after loxP-specific recombination. Comparison of purified recombinant Cre proteins with and without a heterologous 'protein transduction domain' surprisingly showed that the unmodified Cre recombinase already possesses an intrinsic ability to cross the membrane border. Addition of purified recombinant Cre enyzme to primary bone marrow cells isolated from transgenic C/EBPalpha(fl/fl) mice also led to excision of the 'floxed' C/EBPalpha gene, thus demonstrating its potential for in vivo applications. We conclude that Cre enyzme itself or its intrinsic membrane-permeating moiety are attractive tools for direct manipulation of mammalian cells.
CCL28 Has Dual Roles in Mucosal Immunity as a Chemokine with Broad-Spectrum Antimicrobial Activity (2003)

CCL28 is a CC chemokine signaling via CCR10 and CCR3 that is selectively expressed in certain mucosal tissues such as exocrine glands, trachea, and colon. Notably, these tissues commonly secrete low-salt fluids. RT-PCR analysis demonstrated that salivary glands expressed CCL28 mRNA at the highest levels among various mouse tissues. Single cells prepared from mouse parotid glands indeed contained a major fraction of CD3(-)B220(low) cells that expressed CCR10 at high levels and CCR3 at low levels and responded to CCL28 in chemotaxis assays. Morphologically, these cells are typical plasma cells. By immunohistochemistry, acinar epithelial cells in human and mouse salivary glands were strongly positive for CCL28. Furthermore, human saliva and milk were found to contain CCL28 at high concentrations. Moreover, the C terminus of human CCL28 has a significant sequence similarity to histatin-5, a histidine-rich candidacidal peptide in human saliva. Subsequently, we demonstrated that human and mouse CCL28 had a potent antimicrobial activity against Candida albicans, Gram-negative bacteria, and Gram-positive bacteria. The C-terminal 28-aa peptide of human CCL28 also displayed a selective candidacidal activity. In contrast, CCL27, which is most similar to CCL28 and shares CCR10, showed no such potent antimicrobial activity. Like most other antimicrobial peptides, CCL28 exerted its antimicrobial activity in low-salt conditions and rapidly induced membrane permeability in target microbes. Collectively, CCL28 may play dual roles in mucosal immunity as a chemoattractant for cells expressing CCR10 and/or CCR3 such as plasma cells and also as a broad-spectrum antimicrobial protein secreted into low-salt body fluids.
ZO-3, a Novel Member of the MAGUK Protein Family Found at the Tight Junction, Interacts with ZO-1 and Occludin (1998)

A 130-kD protein that coimmunoprecipitates with the tight junction protein ZO-1 was bulk purified from Madin-Darby canine kidney (MDCK) cells and subjected to partial endopeptidase digestion and amino acid sequencing. A resulting 19-amino acid sequence provided the basis for screening canine cDNA libraries. Five overlapping clones contained a single open reading frame of 2,694 bp coding for a protein of 898 amino acids with a predicted molecular mass of 98,414 daltons. Sequence analysis showed that this protein contains three PSD-95/SAP90, discs-large, ZO-1 (PDZ) domains, a src homology (SH3) domain, and a region similar to guanylate kinase, making it homologous to ZO-1, ZO-2, the discs large tumor suppressor gene product of Drosophila, and other members of the MAGUK family of proteins. Like ZO-1 and ZO-2, the novel protein contains a COOH-terminal acidic domain and a basic region between the first and second PDZ domains. Unlike ZO-1 and ZO-2, this protein displays a proline-rich region between PDZ2 and PDZ3 and apparently contains no alternatively spliced domain. MDCK cells stably transfected with an epitope-tagged construct expressed the exogenous polypeptide at an apparent molecular mass of approximately 130 kD. Moreover, this protein colocalized with ZO-1 at tight junctions by immunofluorescence and immunoelectron microscopy. In vitro affinity analyses demonstrated that recombinant 130-kD protein directly interacts with ZO-1 and the cytoplasmic domain of occludin, but not with ZO-2. We propose that this protein be named ZO-3.
New approaches for modelling sporadic genetic disease in the mouse (2009)

Sporadic diseases, which occur as single, scattered cases, are among the commonest causes of human morbidity and death. They result in a variety of diseases, including many cancers, premature aging, neurodegeneration and skeletal defects. They are often pathogenetically complex, involving a mosaic distribution of affected cells, and are difficult to model in the mouse. Faithful models of sporadic diseases require innovative forms of genetic manipulation to accurately recreate their initiation and pathogenesis. Such modelling is crucial to understanding these diseases and, by extension, to the development of therapeutic approaches to treat them. This article focuses on sporadic diseases with a genetic aetiology, the challenges they pose to biomedical researchers, and the different current and developing approaches used to model such disorders in the mouse.