gebhart/patrepeval huggingface dataset:
Synthesis and Reactions of Fluorous Carbobenzyloxy (FCbz) Derivatives of α-Amino Acids (2003)

Fluorous carbobenzyloxy ((F)Cbz) reagents RfCH(2)CH(2)C(6)H(4)CH(2)OC(O)OSu (where Su is succinimidoyl and Rf is C(6)F(13) and C(8)F(17)) have been used to make (F)Cbz derivatives of 18 of the 20 natural amino acids. The potential utility of this new family of reagents in both standard fluorous synthesis with spe separation and fluorous quasiracemic synthesis is illustrated with representative reactions of the (F)Cbz-Phe derivatives.
Identification of Novel Genes Involved in the Plasticity of Pituitary Melanotropes in Amphibians (2009)

Melanotrope cells from the amphibian intermediate lobe are composed of two subpopulations that exhibit opposite secretory behavior: hypersecretory and hormone-storage hyposecretory melanotropes. Isolation of these subpopulations allowed a comparison of their gene expression profiles by differential display, leading to the identification of a number of genes differentially expressed in hypersecretory or hyposecretory melanotropes. Among them, we chose two (preferentially expressed in hyposecretory cells) of unknown function but structurally related to proteins involved in the secretory process: Rab18 and KIAA0555. We demonstrate that, upon activation of the regulated secretory pathway, Rab18 associates with secretory granules, inhibits their mobilization, and, consequently, reduces the secretory capacity of neuroendocrine cells. The other gene, KIAA0555, was predicted by in silico analysis to encode a protein with a long coiled-coil domain, a structural feature also shared by different proteins related to intracellular membrane traffic (i.e., golgins), and a hydrophobic C-terminal domain that could function as a transmembrane domain. A database search unveiled the existence of a KIAA0555 paralogue, KIAA4091, displaying a long coiled-coil region highly similar to that of KIAA0555 and an identical C-terminal transmembrane domain. Both KIAA0555 and KIAA4091 were found to be predominantly expressed in tissues containing cells with regulated secretory pathway, that is, endocrine and neural tissues. Moreover, when exogenously expressed in HEK293 cells, both proteins showed a yuxtanuclear distribution, which partially overlaps with that of a Golgi complex marker, thus suggesting a possible role of these two proteins in the control of the secretory process.
Semantically Conditioned LSTM-based Natural Language Generation for Spoken Dialogue Systems (2015)

Natural language generation (NLG) is a critical component of spoken dialogue and it has a significant impact both on usability and perceived quality. Most NLG systems in common use employ rules and heuristics and tend to generate rigid and stylised responses without the natural variation of human language. They are also not easily scaled to systems covering multiple domains and languages. This paper presents a statistical language generator based on a semantically controlled Long Short-term Memory (LSTM) structure. The LSTM generator can learn from unaligned data by jointly optimising sentence planning and surface realisation using a simple cross entropy training criterion, and language variation can be easily achieved by sampling from output candidates. With fewer heuristics, an objective evaluation in two differing test domains showed the proposed method improved performance compared to previous methods. Human judges scored the LSTM system higher on informativeness and naturalness and overall preferred it to the other systems.
Delineation of the transcriptional boundaries of the lux operon of Vibrio harveyi demonstrates the presence of two new lux genes. (1990)

The 5' and 3' ends of the lux mRNA of Vibrio harveyi, which extends over 8 kilobases, have been mapped, and two new genes, luxG and luxH, were identified at the 3' end of the lux operon. Both S1 nuclease and primer extension mapping demonstrated that the start site for the lux mRNA was 26 bases before the initiation codon of the first gene, luxC. The promoter region contained a typical -10 but not a recognizable -35 consensus sequence. By using S1 nuclease mapping the mRNA was found to be induced in a cell density- and arginine-dependent manner. The DNA downstream of the five known V. harveyi lux genes, luxCDABE, was sequenced and found to contain coding regions for two new genes, designated luxG and luxH, followed by a classical rho-independent termination signal for RNA polymerase. luxG codes for a protein of 233 amino acids with a molecular weight of 26,108, and luxH codes for a protein of 230 amino acids with a molecular weight of 25,326. The termination signal is active in vivo as demonstrated by 3' S1 nuclease mapping, confirming that the two genes are part of the V. harveyi lux operon. Comparison of the luxG amino acid sequence with coding regions immediately downstream from luxE in other luminescent bacteria has demonstrated that this gene may be a common component of the luminescent systems in different marine bacteria.
Preclinical safety, pharmacokinetics and antitumor efficacy profile of liposome-entrapped SN-38 formulation. (2005)

LE-SN38 showed a favorable pharmacokinetics profile and can be administered safely at therapeutically effective doses.
Digital Mammography (2005)

In digital mammography, the processes of image acquisition, display, and storage are separated, which allows optimization of each. Radiation transmitted through the breast is absorbed by an electronic detector, the response of which is faithful over a wide range of intensities. Once this information is recorded, it can be displayed by using computer image-processing techniques to allow arbitrary settings of image brightness and contrast, without the need for further exposure to the patient. In this article, the current state of the art in technology for digital mammography and data from clinical trials that support the use of the technology will be reviewed. In addition, several potentially useful applications that are being developed with digital mammography will be described.
Lyme disease update (1998)

A rational approach to diagnosis and treatment of Lyme disease requires an understanding of the endemic range of the tick vectors for B burgdorferi, the epidemiologic risk factors, and the spectrum of clinical manifestations. A two-step approach to serologic testing (ELISA followed by Western blot analysis of positive or equivocal results) can be useful if the pretest likelihood of Lyme disease is higher than 20%. Consideration should be given to the possibility of (1) a noninfectious disease with clinical features similar to those of Lyme disease or (2) coinfection with a second tick-transmitted organism. Late Lyme disease must be distinguished by clinical characteristics from fibromyalgia (the commonest source of misdiagnosis in several studies). Antibiotic therapy should be tailored to the extent of disease and limited to 4 weeks in most cases. Human vaccines based on an outer-surface protein from B burgdorferi have been tested in large-scale US clinical trials and may soon be approved for use in persons whose occupational or recreational activities place them at risk for B burgdorferi exposure.
Phosphorylation of the glucose transporter in rat adipocytes. Identification of the intracellular domain at the carboxyl terminus as a target for phosphorylation in intact-cells and in vitro. (1990)

Phosphorylation of the insulin-regulatable glucose transporter (IRGT) is increased by incubating rat adipocytes with isoproterenol or by incubating microsomal membranes with cAMP-dependent protein kinase. To attempt to locate the sites of phosphorylation, the IRGT (apparent Mr = 46,000) was immunoprecipitated from 32P-labeled adipocytes and cleaved with CNBr or trypsin. Essentially all of the 32P could be recovered in a single CNBr fragment, denoted CB-T (Mr = 8,000), which bound a polyclonal antibody (R820) against a peptide having the sequence of the last 12 amino acids in the COOH terminus of the IRGT. 32P-Labeling of the IRGT was also confined to CB-T when membranes were incubated with [gamma-32P]ATP and cAMP-dependent protein kinase. Isoproterenol increased phosphorylation of CB-T, but insulin was without effect. To resolve phosphorylation sites further, IRGT from 32P-labeled cells was subjected to exhaustive proteolysis with trypsin. Samples were applied to a C-18 column, and 32P-labeled fragments were resolved into three peak fractions by elution with an increasing gradient of acetonitrile. [32P]Phosphoserine was the only phosphoamino acid detected in any of the peaks. Peak III contained approximately 80% of the 32P and was increased by isoproterenol. Almost all of the 32P introduced by cAMP-dependent protein kinase in vitro eluted in Peak III. In all cases, the 32P-labeled species in Peak III were quantitatively immunoprecipitated by R820. Digesting the peptide(s) in Peak III with V8 protease generated a single peak of 32P which eluted at lower acetonitrile than Peak III and contained 32P-labeled species that did not interact with R820. Automated Edman degradation indicated that the serine residue in Peak III phosphorylated by cAMP-dependent protein kinase was the 3rd or 4th residue from the NH2 terminus of the peptide. These findings indicate that phosphorylation of the IRGT is restricted to the presumed intracellular domain at the COOH terminus and that Ser488 is a major site phosphorylated both by cAMP-dependent protein kinase in vitro and in response to isoproterenol in vivo.
Cloning of a cDNA coding for human factor V, a blood coagulation factor homologous to factor VIII and ceruloplasmin. (1986)

Coagulation factor V is a high molecular weight plasma glycoprotein that participates as a cofactor in the conversion of prothrombin to thrombin by factor Xa. A phage lambda gt11 Hep G2 cell cDNA expression library was screened by using an affinity-purified antibody to human factor V, and 11 positive clones were isolated and plaque-purified. The clone containing the largest cDNA insert contained 2970 nucleotides and coded for 938 amino acids, a stop codon, and 155 nucleotides of 3' noncoding sequence including a poly(A) tail. The coding region includes 651 amino acids from the carboxyl terminus that constitute the light chain of human factor Va and 287 amino acids that are part of the connecting region of the protein. The predicted amino acid sequence agreed completely with 147 amino acid residues that were identified by Edman degradation of cyanogen bromide peptides isolated from the light chain. During the activation of factor V, several peptide bonds are cleaved by thrombin, giving rise to a heavy chain, a connecting fragment(s), and a light chain. The light chain is generated by the cleavage of an Arg-Ser peptide bond. The amino acid sequence of the light chain is homologous (40%) with the carboxyl-terminal fragment (Mr, 73,000) of human factor VIII. Both fragments have a similar domain structure that includes a single ceruloplasmin-related domain followed by two C domains. The carboxyl terminus of the connecting region, however, shows no significant amino acid sequence homology with factor VIII. It is very acidic and contains a number of potential N-linked glycosylation sites. It also contains about 20 tandem repeats of nine amino acids.
Serum Metabolomic Analysis of Coronary Heart Disease Patients with Stable Angina Pectoris Subtyped by Traditional Chinese Medicine Diagnostics Reveals Biomarkers Relevant to Personalized Treatments (2021)

To improve the treatment of patients with coronary heart disease (CHD), personalized treatments based on potential biomarkers could make a difference. To investigate if such potential biomarkers could be found for CHD inhomogeneous, we combined traditional Chinese medicine based diagnosis with untargeted and targeted metabolomics analyses. Shi and Xu patient subtype groups of CHD with angina pectoris were identified. Different metabolites including lipids, fatty acids and amino acids were further analyzed with targeted metabolomics and mapped to disease-related pathways. The long-chain unsaturated lipids ceramides metabolism, bile acid metabolism were differentially affected in the Xu subtype groups. While, Shi-subtype patients seemed to show inflammation, anomalous levels of bioactive phospholipids and antioxidant molecules. Furthermore, variations in the endothelial damage response and energy metabolism found based on ELISA analysis are the key divergence points between different CHD subtypes. The results showed Xu subtype patients might benefit from long-chain unsaturated lipids ceramides as therapeutic targets. Shi subtype patients might benefit more from levels of polyunsaturated fatty acid consumption and treatments that help in restoring energy balance. Metabolic differences can be essential for treatment protocols. Thus, patient group specific differences can serve as important information to refine current treatment approaches in a personalized manner.
Activation of Hematopoietic Progenitor Kinase 1 Involves Relocation, Autophosphorylation, and Transphosphorylation by Protein Kinase D1 (2005)

Adaptive immune signaling can be coupled to stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK) and NF-kappaB activation by the hematopoietic progenitor kinase 1 (HPK1), a mammalian hematopoiesis-specific Ste20 kinase. To gain insight into the regulation of leukocyte signal transduction, we investigated the molecular details of HPK1 activation. Here we demonstrate the capacity of the Src family kinase Lck and the SLP-76 family adaptor protein Clnk (cytokine-dependent hematopoietic cell linker) to induce HPK1 tyrosine phosphorylation and relocation to the plasma membrane, which in lymphocytes results in recruitment of HPK1 to the contact site of antigen-presenting cell (APC)-T-cell conjugates. Relocation and clustering of HPK1 cause its enzymatic activation, which is accompanied by phosphorylation of regulatory sites in the HPK1 kinase activation loop. We show that full activation of HPK1 is dependent on autophosphorylation of threonine 165 and phosphorylation of serine 171, which is a target site for protein kinase D (PKD) in vitro. Upon T-cell receptor stimulation, PKD robustly augments HPK1 kinase activity in Jurkat T cells and enhances HPK1-driven SAPK/JNK and NF-kappaB activation; conversely, antisense down-regulation of PKD results in reduced HPK1 activity. Thus, activation of major lymphocyte signaling pathways via HPK1 involves (i) relocation, (ii) autophosphorylation, and (iii) transphosphorylation of HPK1 by PKD.
Discussion of Two Ways of Optically Modeling Indium–Tin–Oxide Layers in Slot Waveguides for Waveguide Analysis (2015)

Slot waveguides (e.g., metal-insulator-metal (MIM) waveguides) with an indium-tin-oxide (ITO) layer in their slot regions are promising as compact intensity modulators. To analyze such waveguides, a uniform-accumulation layer model is usually used. In this model, the ITO layer is treated as a stack of a layer with untuned permittivity and a layer with permittivity tuned by driving voltage, which is called an accumulation layer. However, rigorous analysis requires a gradient-index layer model in which the ITO layer is treated as a layer with a continuously varying permittivity distribution. It is necessary to check whether the uniform-accumulation layer model results in correct analysis in comparison with the gradient-index layer model. This paper analyzes an ITO-based MIM-type slot waveguide using the two models. Compared with the analysis based on the gradient-index layer model, the analysis based on the uniform-accumulation layer model becomes incorrect if the driving voltage is large, particularly when it is around the value for which the real part of the accumulation layer permittivity is equal to zero. Therefore, this paper shows that the uniform-accumulation layer model should be used just for small driving voltage with the accumulation layer thickness determined appropriately. This paper may correct misunderstanding of the properties of ITO-based slot waveguides.
Origin and Seed Phenotype of Maize low phytic acid 1-1 and low phytic acid 2-1 (2000)

Phytic acid (myo-inositol-1, 2, 3, 4, 5, 6-hexakisphosphate or Ins P(6)) typically represents approximately 75% to 80% of maize (Zea mays) seed total P. Here we describe the origin, inheritance, and seed phenotype of two non-lethal maize low phytic acid mutants, lpa1-1 and lpa2-1. The loci map to two sites on chromosome 1S. Seed phytic acid P is reduced in these mutants by 50% to 66% but seed total P is unaltered. The decrease in phytic acid P in mature lpa1-1 seeds is accompanied by a corresponding increase in inorganic phosphate (P(i)). In mature lpa2-1 seed it is accompanied by increases in P(i) and at least three other myo-inositol (Ins) phosphates (and/or their respective enantiomers): D-Ins(1,2,4,5,6) P(5); D-Ins (1,4,5,6) P(4); and D-Ins(1,2,6) P(3). In both cases the sum of seed P(i) and Ins phosphates (including phytic acid) is constant and similar to that observed in normal seeds. In both mutants P chemistry appears to be perturbed throughout seed development. Homozygosity for either mutant results in a seed dry weight loss, ranging from 4% to 23%. These results indicate that phytic acid metabolism during seed development is not solely responsible for P homeostasis and indicate that the phytic acid concentration typical of a normal maize seed is not essential to seed function.
The antioxidant resveratrol protects against chondrocyte apoptosis via effects on mitochondrial polarization and ATP production (2008)

Resveratrol protects against IL-1beta-induced catabolic effects and prevents chondrocyte apoptosis via its inhibition of mitochondrial membrane depolarization and ATP depletion. These beneficial effects of resveratrol are due, in part, to its capacity to inhibit COX-2-derived PGE(2) synthesis. Resveratrol may therefore protect against oxidant injury and apoptosis, which are main features of progressive OA.
Ruthenium Thin Films Grown by Atomic Layer Deposition (2003)

Abstract Thin films of metallic ruthenium were grown by atomic layer deposition (ALD) in the temperature range 275–400 °C using bis(cyclopentadienyl)ruthenium (RuCp 2 ) and oxygen as precursors. The ruthenium films were grown on thin Al 2 O 3 and TiO 2 films on glass. X‐ray diffraction (XRD) analysis indicated that the films were polycrystalline metallic ruthenium and scanning electron microscopy (SEM) studies showed that the films had excellent conformality. The impurity content of the films, as measured by time‐of‐flight elastic recoil detection analysis (TOF‐ERDA), were very low. All the films had resistivities below 20 μΩ cm.
Investigating statistical machine learning as a tool for software development (2008)

As statistical machine learning algorithms and techniques continue to mature, many researchers and developers see statistical machine learning not only as a topic of expert study, but also as a tool for software development. Extensive prior work has studied software development, but little prior work has studied software developers applying statistical machine learning. This paper presents interviews of eleven researchers experienced in applying statistical machine learning algorithms and techniques to human-computer interaction problems, as well as a study of ten participants working during a five-hour study to apply statistical machine learning algorithms and techniques to a realistic problem. We distill three related categories of difficulties that arise in applying statistical machine learning as a tool for software development: (1) difficulty pursuing statistical machine learning as an iterative and exploratory process, (2) difficulty understanding relationships between data and the behavior of statistical machine learning algorithms, and (3) difficulty evaluating the performance of statistical machine learning algorithms and techniques in the context of applications. This paper provides important new insight into these difficulties and the need for development tools that better support the application of statistical machine learning.
Anti-Laminin Receptor Antibody Targeting of Liposomes With Encapsulated Doxorubicin to Human Breast Cancer Cells In Vitro (1989)

The tumor cell laminin receptor is a cell-surface protein that binds laminin with high affinity (Kd = 1.0 nM). The putative ligand-binding domain of the laminin receptor has been molecularly cloned and sequenced. In the present study, we used the predicted amino acid sequence of the laminin receptor to generate synthetic peptide antigens and produced immunoglobulin M (IgM) anti-laminin receptor monoclonal antibodies. The disulfide bond group of the IgM molecule was used to couple the antibodies to the surface of liposomes encapsulating doxorubicin. The anti-laminin receptor monoclonal antibodies coupled to the liposomes bound avidly to the surface of MDA-MB-435S (MDA-435) human breast carcinoma cells, which have high numbers of laminin receptors. These antibody-coupled liposomes exhibited a low degree of binding to Hs 578Bst (Hs 578) normal human breast epithelial cells, which express a low number of laminin receptors. Excess liposomes competed for the binding of unbound laminin to the tumor cell surface, and excess laminin competed for binding with the liposomes. Antibody-coupled liposomes encapsulating doxorubicin were specifically more efficient in inhibiting colony formation by MDA-435 cells in vitro than unbound doxorubicin or liposomes without anti-laminin receptor monoclonal antibodies. Unbound doxorubicin inhibited thymidine uptake by 10%-20% in both Hs 578 and MDA-435 cells, whereas the antibody-coupled liposomes encapsulating doxorubicin inhibited thymidine uptake by 90% in MDA-435 cells but only 15% in Hs 578 cells. Thus, use of anti-laminin receptor monoclonal antibodies coupled with liposomes encapsulating doxorubicin represents a new strategy for selective targeting of doxorubicin to carcinoma cells with exposed laminin receptors.
CTLA4-Ig and anti-CD40 ligand prevent renal allograft rejection in primates (1997)

Selective inhibition of T cell costimulation using the B7-specific fusion protein CTLA4-Ig has been shown to induce long-term allograft survival in rodents. Antibodies preventing the interaction between CD40 and its T cell-based ligand CD154 (CD40L) have been shown in rodents to act synergistically with CTLA4-Ig. It has thus been hypothesized that these agents might be capable of inducing long-term acceptance of allografted tissues in primates. To test this hypothesis in a relevant preclinical model, CTLA4-Ig and the CD40L-specific monoclonal antibody 5C8 were tested in rhesus monkeys. Both agents effectively inhibited rhesus mixed lymphocyte reactions, but the combination was 100 times more effective than either drug alone. Renal allografts were transplanted into nephectomized rhesus monkeys shown to be disparate at major histocompatibility complex class I and class II loci. Control animals rejected in 5-8 days. Brief induction doses of CTLA4-Ig or 5C8 alone significantly prolonged rejection-free survival (20-98 days). Two of four animals treated with both agents experienced extended (>150 days) rejection-free allograft survival. Two animals treated with 5C8 alone and one animal treated with both 5C8 and CTLA4-Ig experienced late, biopsy-proven rejection, but a repeat course of their induction regimen successfully restored normal graft function. Neither drug affected peripheral T cell or B cell counts. There were no clinically evident side effects or rejections during treatment. We conclude that CTLA4-Ig and 5C8 can both prevent and reverse acute allograft rejection, significantly prolonging the survival of major histocompatibility complex-mismatched renal allografts in primates without the need for chronic immunosuppression.