gebhart/patrepeval huggingface dataset:
Computer design of bioactive molecules: A method for receptor‐based de novo ligand design (1991)

The design of molecules to bind specifically to protein receptors has long been a goal of computer-assisted molecular design. Given detailed structural knowledge of the target receptor, it should be possible to construct a model of a potential ligand, by algorithmic connection of small molecular fragments, that will exhibit the desired structural and electrostatic complementarity with the receptor. However, progress in this area of receptor-based, de novo ligand design has been hampered by the complexity of the construction process, in which potentially huge numbers of structures must be considered. By limiting the scope of the structure-space examined to one particular class of ligands--namely, peptides and peptide-like compounds--the problem complexity has been reduced to the point that successful, de novo design is now possible. The methodology presented employs a large template set of amino acid conformations which are iteratively pieced together in a model of the target receptor. Each stage of ligand growth is evaluated according to a molecular mechanics-based energy function, which considers van der Waals and coulombic interactions, internal strain energy of the lengthening ligand, and desolvation of both ligand and receptor. The search space is managed by use of a data tree which is kept under control by pruning according to the energy evaluation. Ligands grown by this procedure are subjected to follow-up evaluation in which an approximate binding enthalpy is determined. This methodology has proven useful as a precise model-builder and has also shown the ability to design bioactive ligands.
CAN BACTERIAL PROBIOTICS INFLUENCE FISH FECUNDITY AND PREVENT ITS MICROBIAL INFECTION (2009)

To investigate the effect of Bacillus subtilus probiotics on fish fecundity, 160 Oreochromis niloticus females were fed incorporated with basal diets for 30 days. After microscopic examinations of their ova, fish were classified into prespawning or spawning eight groups: two control fed basal diet only (one prespawning + one spawning), two fed basal diet + B. subtilus for one month, two challenged with dose of 0.3 I/P V. anguillarum for one week and two fed B. subtilus + challenged with dose of 0.3 I/P V.anguillarum for one week. The results indicate that fecundity was improved among prespawning fish fed B. subtilus compared to those of the control group. From the immunological point of view, B.subtilus increased total globulins and decreased mortality among prespawning fish fed B.subtilus only or fed B.subtilus + V. anguillarum compared to the control ones or those challenged V. anguillarum only. In contrast, spawning fish fed B.subtilus + V. anguillarum appeared to be more stressed than those fed B. subtilus as indicated from the highly significant decrease in their total globulins. It is recommended that B. subtilus could be supplemented to prespawning fish diets only while it's unprofitable within spawning periods. In addition full care and concern should be given to fish during spawning period to avoid fecundity decline by any virulent pathogen as V.anguillarum which cause damage to ovaries during prespawning and spawning periods.
Asymmetric hydrogenation, transfer hydrogenation and hydrosilylation of ketones catalyzed by iron complexes (2009)

The conventional homogeneous catalysts for the enantioselective hydrogenation or transfer hydrogenation of ketones are based on platinum metals and, in particular, ruthenium. This method provides valuable enantiopure alcohols for the fine chemical industries. This tutorial review summarizes recent successes in replacing expensive and toxic ruthenium in these catalysts with “greener” iron substitutes including my lab’s recent progress in this area using iron complexes containing readily-prepared tetradentate ligands. It will enlighten chemists interested in homogeneous catalysis and asymmetric synthesis.
Estimating accuracy of RNA-Seq and microarrays with proteomics (2009)

Our result shows that in terms of overall technical performance, RNA-Seq is the technique of choice for studies that require accurate estimation of absolute transcript levels.
A Vasculature-Targeting Regimen of Preoperative Docetaxel with or without Bevacizumab for Locally Advanced Breast Cancer: Impact on Angiogenic Biomarkers (2009)

Bevacizumab plus docetaxel caused a greater increase in vascular endothelial growth factor and VCAM-1, and a greater reduction in tumor perfusion by DCE-MRI compared with docetaxel. Clinical outcomes of inoperable breast cancer were predicted by changes in VCAM-1 and E-selectin.
On the main reservoir host of Fasciola in Dakahlia Governorate, Egypt. (2005)

In the present work, a total of 4180 sheep were obtained from different localities at Dakahlia Governorate. One hundred and eighty male sheep were investigated for Fasciola worms (the adult and juvenile forms) at Mansoura governmental abattoir. Four hundred grazing sheep were screened by the coprological examination from ten centers. The mean number of eggs per gm in a group of ten sheep ranged from 2.9-10.8 egg/gm. The number of worms ranged from 5-84. In the Mansoura abattoir, it was found that 37 sheep were infected (20.56%). Fasciola worms were recovered from the livers in 100%, common bile ducts in 60%, gall bladder in 80%, two sites in 50% and three sites in 40% of infected biliary tracts. According to the coprological examination, the infection rate was the highest in El-Manzalla Center (15.75) and the lowest was in Mansoura Center (3.25%). According to the prevalence and egg output results, it is concluded that sheep are the main reservoir host for fascioliasis among the edible animals in Dakahlia Governorate. However, examination of the non-edible animals and the domestic and wild rodents are ongoing and will be published soon elsewhere.
0.15&#x00B5;m BiC-DMOS technology with novel stepped-STI N-channel LDMOS (2009)

We developed a state-of-the-art BiC-DMOS process using 0.15µm technology. High-voltage MOSFETs were embedded in our standard 0.15µm CMOS process with a 0.13µm high density NVM. More intelligent mixed signal devices can flexibly be realized by this technology. Moreover, the reliability of n-ch LDMOS is markedly improved by the novel structure of stepped-STI LDMOS.
Prostate-specific antigen: characterization of epitopes by synthetic peptide mapping and inhibition studies (1997)

To improve our understanding of the prostate-specific antigen (PSA) antigenic regions, we studied the association targets of one anti-PSA polyclonal antibody and 10 anti-PSA monoclonal antibodies (mAbs). We also examined the ability of the mAbs to inhibit PSA enzymatic activity and block the association of PSA with alpha 1-antichymotrypsin (ACT). Linear epitope mapping with a polyclonal antibody indicated the presence of six major antigenic regions in PSA. Examination of the panel of mAbs established that three of them bind to linear epitopes. Five of the mAbs inhibited > 90% of PSA enzymatic activity. However, inhibition of PSA enzymatic activity and hindrance of PSA-ACT association by mAbs cannot be used to predict whether the mAbs bind to free PSA, the PSA-ACT complex, or both. Some of the mAbs may block PSA-ACT association through peripheral occlusion of the binding site, or through induction of conformational changes in PSA.
Distinct roles for B7-1 and B7-2 determinants during priming of effector CD8+ Tc1 and regulatory CD4+ Th2 cells for contact hypersensitivity (1997)

Contact hypersensitivity (CHS) is a CD8+ T cell-mediated response to hapten sensitization and challenge of the epidermis. Both the IFN-gamma-producing effector CD8+ T cells and the IL-4/IL-10-producing CD4+ T (Th2) cells that restrict the magnitude and duration of the response are primed by hapten-presenting Langerhans cells (hpLC). hpLC isolated from hapten-sensitized animals expressed high levels of B7-2 and lower levels of B7-1, suggesting the availability of each molecule to provide costimulation during CD8+ and CD4+ T cell priming for CHS. Anti-B7-2 Ab given during hapten sensitization inhibited effector CD8+ and regulatory CD4+ T cell development and the magnitude of the CHS response. Cytokine production by CD8+ and CD4+ T cells was reduced in anti-B7-2 Ab-treated animals, indicating that costimulation for T cell development was not compensated by hpLC-expressed B7-1. Anti-B7-1 Ab inhibited CHS and increased the number of Th2 cells primed during hapten sensitization without inhibiting development of the IFN-gamma-producing CD8+ T cells. Depletion of CD4+ T cells, however, abrogated the inhibitory effect of anti-B7-1 Ab on the CHS response, indicating the amplified Th2 response mediated this inhibition. These results indicate a requirement for B7-2 costimulation by effector CD8+ and regulatory CD4+ T cells during priming for CHS. The ability of anti-B7-1 Abs to amplify the regulatory CD4+ Th2 component and inhibit CHS suggests a strategy to inhibit unwanted CD8+ T cell-mediated immune responses to Ags in the skin.
Second generation logarithmic estimates of single-pool variable volume Kt/V (1993)

The original formula proposed to estimate variable-volume single-pool (VVSP) Kt/V was Kt/V = -In(R - 0.008 * t - f * UF/W), where in the Kt/V range of 0.7 to 1.3, f = 1.0 (* denotes multiplication). This formula tends to overestimate Kt/V as the Kt/V increases above 1.3. Because higher Kt/V values are now commonly delivered, the validity of both the urea generation term (0.008 * f) and correction for UF/W were explored by solving VVSP equations for simulated hemodialysis situations, with Kt/V ranging from 0.6 to 2.6. The analysis led to the development of a second-generation formula, namely: Kt/V = -In(R - 0.008 * t) + (4-3.5 * R) * UF/W. The first and second generation formulas were then used to estimate the modeled VVSP Kt/V in 500 modeling sessions in which the Kt/V ranged widely from 0.7 to 2.1. An analysis of error showed that this second-generation formula eliminated the overestimation of Kt/V in the high ranges found with the first-generation formula. Also, total error (absolute value percent error + 2 SD) was reduced with the second-generation formula. These results led to the proposal of a new formula that can be used for a very wide range of delivered Kt/V.
Specific IgE antibodies to nickel in workers with known reactivity to cobalt (1992)

Twenty-one workers with hard metal asthma, including eight atopics, diagnosed on the basis of peak flow diaries and positive reaction to cobalt chloride (CoCl2) and/or nickel sulphate (NiSO4) in skin and provocation tests were studied for sensitization by detection of specific antibodies to nickel-conjugated human serum albumin (Ni-HSA), and nickel-conjugated exchange resin (Ni-resin). Their results were compared with those of sera obtained from control sera from 60 asthmatic patients and pair-matched asymptomatic control workers in the hard metal plant. In the RASTs (radioallergosorbent tests), sera from the same six subjects developed positive reactions both to Ni-HSA (RAST index greater than 2.0, P less than 0.01) and Ni-resin (RAST index greater than 2.0, P less than 0.01), while the counts measured for the others of the 15 subjects (RAST index less than 1.52) were about the same as those for control groups (RAST index less than 1.58). Subject HSA RAST and resin RAST results (378 +/- 52 c.p.m. in HSA RAST and 324 +/- 56 in the resin RAST) were about the same as those of the control sera (388 +/- 65 c.p.m. and 398 +/- 59 c.p.m., respectively). There was no difference in the prevalence of smoking habit and high IgE between Ni-RAST positive and negative subjects. However, subjects with simultaneous sensitivity to nickel and/or cobalt still developed asthmatic attacks following medications, while those without sensitivity to these metals were almost symptom free. The positive sera had simultaneous sensitivity to both cobalt and nickel, suggesting the presence in them of specific IgE antibodies to nickel playing some role in the aetiology of hard metal asthma.
A Nonviral DNA Delivery System Based on Surface Modified Silica-Nanoparticles Can Efficiently Transfect Cells in Vitro (2000)

Diverse polycationic polymers have been used as nonviral transfection agents. Here we report the ability of colloidal silica particles with covalently attached cationic surface modifications to transfect plasmid DNA in vitro and make an attempt to describe the structure of the resulting transfection complexes. In analogy to the terms lipoplex and polyplex, we propose to describe the nanoparticle−DNA complexes by the term “nanoplex”. Three batches, Si10E, Si100E, and Si26H, sized between 10 and 100 nm and with ζ potentials ranging from +7 to +31 mV at pH 7.4 were evaluated. The galactosidase expression plasmid DNA pCMVβ was immobilized on the particle surface and efficiently transfected Cos-1 cells. The transfection activity was accompanied by very low cytotoxicity, with LD50 values in the milligrams per milliliter range. The most active batch, Si26H, was produced by modification of commercially available silica particles with N-(6-aminohexyl)-3-aminopropyltrimethoxysilane, yielding spherical nanoparticles with a mean diameter of 26 nm and a ζ potential of +31 mV at pH 7.4. Complexes of Si26H and pCMVβ plasmid DNA formed at w/w ratios of 10 were most effective in promoting transfection of Cos-1 cells in the absence of serum. At this ratio, >90% of the DNA was associated with the particles, yielding nanoplexes with a net negative surface charge. When the transfection medium was supplemented with 10% serum, maximum gene expression was observed at a w/w ratio of 30, at which the resulting particle−DNA complexes possessed a positive surface charge. Transfection was strongly increased in the presence of 100 μM chloroquine in the incubation medium and reached approximately 30% of the efficiency of a 60 kDa polyethylenimine. In contrast to polyethylenimine, no toxicity was observed at the concentrations required. Atomic force microscopy of Si26H−DNA complexes revealed a spaghetti-meatball-like structure. The surface of complexes prepared at a w/w ratio of 30 was dominated by particles half-spheres. Complex sizes correlated well with those determined previously by dynamic light scattering.
[Preventive treatment of diabetic microangiopathy: blocking the pathogenic mechanisms]. (1994)

The development of drugs in order to block metabolic pathway of glucose responsible for diabetic vascular dysfunction is in progress. Aldose reductase inhibitors prevent or reduce the different components of vascular dysfunction, cataract, neuropathy and nephropathy in animal models of diabetes. Promising results have been observed in diabetic patients concerning the prevention of neuropathy and of retinopathy. Larger scale studies with the second generation compounds are in progress. Glycation inhibitors, mainly aminoguanidine, have been shown to prevent or reduce vascular dysfunction and microvascular complications in animal models. Trials in diabetic patients with aminoguanidine are just beginning. Anti-oxidant therapy is also at its early stage of development (vitamin E, vitamin C, alpha lipoic acid). Antiplatelet agents (aspirin, ticlopidine) have been demonstrated to reduce the progression of non proliferative diabetic retinopathy. Angiotensin converting enzyme inhibitors are of particular interest in preventing diabetic glomerulopathy.
The phenotype of freshly isolated and cultured human bone marrow allostimulatory cells: possible heterogeneity in bone marrow dendritic cell populations. (1995)

Putative dendritic cells (DC) and their precursors have been obtained from human bone marrow but their origin and relationship to other myeloid cells remains obscure. A minor bone marrow mononuclear cell (BMMC) population, which contains the most potent allostimulatory cells and lacks mature cell lineage markers (CD3, CD11b, CD14, CD15, CD16, CD19, CD57 and glycophorin A; lineage-negative) was enriched by immunoselection. These preparations, which contain cells with similar characteristics to freshly isolated human blood DC, were further subdivided by serial fluorescent-activated cell sorting (FACS). Potent allostimulatory cells were detected in the CD34, CD33 and CD4 positive and negative subpopulations. Cells with putative DC morphology were present in both the CD33 and CD4 positive and negative fractions. No significant CD13 or Thy-1 staining was seen in the lineage-negative population. In vitro culture of lineage-negative BMMC for 7 days in conditioned medium resulted in a up to fivefold expansion of cells and generated many lineage-positive progeny. This lineage-positive population was as allostimulatory as the negative progeny. Likewise, the CD14-positive and the CD14-negative cell progeny were equally allostimulatory. In contrast, the freshly isolated lineage-positive BMMC (containing CD14-positive monocytes) remained poor stimulators of the mixed lymphocyte reaction (MLR), even after culture in the presence of cytokines. These data suggest that there are at least two phenotypically diverse forms of potent allostimulatory cells in the lineage-negative fraction of human BM, at least some of which express the early haemopoietic precursor antigens CD34 or CD33. Some of these precursors generate CD14-positive allostimulatory cells upon in vitro culture, suggesting an intimate link between DC ontogeny and myeloid differentiation.
Signal mixing in a multiple input transistor laser near threshold (2006)

A single-emitter multiple-input transistor laser has been realized and demonstrated in signal mixing, yielding in the stimulated-recombination region near laser threshold frequency conversion with simultaneously an electrical and optical output signal. In the unique nonlinear region of compression of the transistor I-V characteristics (β≡ΔIC∕ΔIB, βspon&amp;gt;βstim), input signals f1=2GHz and f2=2.1GHz are converted into mf1±nf2 ranging from 0.1to8.4GHz. Stimulated emission (enhanced recombination) changes the transistor into a special form of nonlinear element, a special form of electronic processor or “switch.”
Identification of Small Heat Shock Protein B8 (HSP22) as a Novel TLR4 Ligand and Potential Involvement in the Pathogenesis of Rheumatoid Arthritis (2006)

Dendritic cells (DCs) are specialized APCs that can be activated upon pathogen recognition as well as recognition of endogenous ligands, which are released during inflammation and cell stress. The recognition of exogenous and endogenous ligands depends on TLRs, which are abundantly expressed in synovial tissue from rheumatoid arthritis (RA) patients. Furthermore TLR ligands are found to be present in RA serum and synovial fluid and are significantly increased, compared with serum and synovial fluid from healthy volunteers and patients with systemic sclerosis and systemic lupus erythematosus. Identification of novel endogenous TLR ligands might contribute to the elucidation of the role of TLRs in RA and other autoimmune diseases. In this study, we investigated whether five members of the small heat shock protein (HSP) family were involved in TLR4-mediated DC activation and whether these small HSPs were present in RA synovial tissue. In vitro, monocyte-derived DCs were stimulated with recombinant alphaA crystallin, alphaB crystallin, HSP20, HSPB8, and HSP27. Using flow cytometry and multiplex cytokine assays, we showed that both alphaA crystallin and HSPB8 were able to activate DCs and that this activation was TLR4 dependent. Furthermore, Western blot and immunohistochemistry showed that HSPB8 was abundantly expressed in synovial tissue from patients with RA. With these experiments, we identified sHSP alphaA crystallin and HSPB8 as two new endogenous TLR4 ligands from which HSPB8 is abundantly expressed in RA synovial tissue. These findings suggest a role for HSPB8 during the inflammatory process in autoimmune diseases such as RA.
Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action (2007)

Metformin is among the most widely prescribed drugs for the treatment of type 2 diabetes. Organic cation transporter 1 (OCT1) plays a role in the hepatic uptake of metformin, but its role in the therapeutic effects of the drug, which involve activation of AMP-activated protein kinase (AMPK), is unknown. Recent studies have shown that human OCT1 is highly polymorphic. We investigated whether OCT1 plays a role in the action of metformin and whether individuals with OCT1 polymorphisms have reduced response to the drug. In mouse hepatocytes, deletion of Oct1 resulted in a reduction in the effects of metformin on AMPK phosphorylation and gluconeogenesis. In Oct1-deficient mice the glucose-lowering effects of metformin were completely abolished. Seven nonsynonymous polymorphisms of OCT1 that exhibited reduced uptake of metformin were identified. Notably, OCT1-420del (allele frequency of about 20% in white Americans), previously shown to have normal activity for model substrates, had reduced activity for metformin. In clinical studies, the effects of metformin in glucose tolerance tests were significantly lower in individuals carrying reduced function polymorphisms of OCT1. Collectively, the data indicate that OCT1 is important for metformin therapeutic action and that genetic variation in OCT1 may contribute to variation in response to the drug.
Quantification of epithelial cells in coculture with fibroblasts by fluorescence image analysis (2002)

The image analysis-based quantification method we describe here is an easy and reliable way to monitor cells in coculture and should be useful for a variety of cell biological studies.
Leukocyte integrin CD11b promoter directs expression in lymphocytes and granulocytes in transgenic mice (1995)

The human leukocyte integrin subunit CD11b is expressed predominantly on myelomonocytic cells. To identify CD11b promoter sequences important for myelomonocytic gene expression and to assess the utility of the CD11b promoter for expressing heterologous genes in vivo, we generated transgenic mice with a human CD4 reporter gene driven by CD11b promoter constructs composed of 1.5, 0.3, or 0.1 kb of DNA sequence 5' to the transcription start site. Using flow cytometry to detect the human CD4 reporter on murine leukocytes, two of three 1.5-kb CD11b promoter founder lines showed surface expression of the human CD4 transgene in granulocytes and lymphocytes. The transgene expression observed in lymphocytes was inappropriate relative to the normal pattern of CD11b expression. Of the eight 0.3-kb or 0.1-kb founder lines, only one 0.1-kb founder line showed transgene expression. The overall pattern of transgene expression among the 11 founder lines does not parallel expression of the endogenous CD11b gene. These studies indicate that additional CD11b regulatory elements will be required to express a reporter gene in vivo in a lineage-specific pattern that mimics the endogenous CD11b gene.
Modularity and scaling in large phonemic neural networks (1989)

The authors train several small time-delay neural networks aimed at all phonemic subcategories (nasals, fricatives, etc.) and report excellent fine phonemic discrimination performance for all cases. Exploiting the hidden structure of these small phonemic subcategory networks, they propose several technique that make it possible to grow larger nets in an incremental and modular fashion without loss in recognition performance and without the need for excessive training time or additional data. The techniques include class discriminatory learning, connectionist glue, selective/partial learning, and all-net fine tuning. A set of experiments shows that stop consonant networks (BDGPTK) constructed from subcomponent BDG- and PTK-nets achieved up to 98.6% correct recognition compared to 98.3 and 98.7% correct for the BDG- and PTK-nets. Similarly, an incrementally trained network aimed at all consonants achieved recognition scores of about 96% correct. These results are comparable to the performance of the subcomponent networks and significantly better than that of several alternative speech recognition methods.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>