gebhart/patrepeval huggingface dataset:
Dual Enantioselective Control in Asymmetric Synthesis (2001)

It is desirable and practical to produce both enantiomers of a target from the same chiral starting material by stereodifferentiation of prochiral compounds, for instance utilizing a chiral ligand derived from a natural (L) amino acid. During the past 7 years, excellent results have been achieved in several cases by multiple stereodifferentiation of chiral ligands derived from (S)-indoline-2-carboxylic acid: highly diastereo- and enantioselective pinacol coupling reactions of chiral alpha-ketoamides gave both (S,S)- and (R,R)-quaternary tartaric acid for the first time; asymmetric Diels-Alder cyclization of chiral acrylamides in the presence of Lewis acid afforded extremely high diastereoselectivities of both opposite configurations of the cyclized diastereomers depending upon the structures of chiral ligands and Lewis acids; and asymmetric alkylation of aldehydes to both enantiomers of secondary alcohols and asymmetric hydrogenation of ketones to both enantiomers of chiral secondary alcohols have been achieved using catalysts derived from (S)-indoline-2-carboxylic acid.
β‐Amyloid peptide potentiates inflammatory responses induced by lipopolysaccharide, interferon ‐γ and ‘advanced glycation endproducts’ in a murine microglia cell line (2003)

beta-Amyloid (Abeta) plaques are characteristic hallmarks of Alzheimer's disease (AD). In AD, it has been suggested that activation of microglial cells might be the link between Abeta deposition and neuronal degeneration. Activated microglia are associated with senile plaques and produce free radicals and inflammatory cytokines. However, it is still not clear whether Abeta needs a prestimulated environment to exert its proinflammatory potential. Advanced glycation endproducts (AGEs), protein-bound oxidation products of sugars, have been shown to accumulate in senile plaques and could induce a silent but chronic inflammation in the AD brain. We tested whether Abeta acts as an amplifier of a submaximal proinflammatory response initiated by exposure to chicken egg albumin-AGE, lipopolysaccharide or interferon-gamma. Synthetic Abeta was used to produce three different samples (Abeta-fibrilar; Abeta-aggregated; Abeta-AGE), which were characterized for beta-sheeted fibrils by the thioflavin-T test and electron microscopy. As markers of microglial activation, nitric oxide, interleukin-6, macrophage-colony stimulation factor and tumour necrosis factor-alpha production was measured. All three Abeta samples alone could not induce a detectable microglial response. The combination of Abeta preparations, however, with the coinducers provoked a strong microglial response, whereby Abeta-AGE and fibrilar Abeta were more potent inflammatory signals than aggregated Abeta. Thus, Abeta in senile plaques can amplify microglial activation by a coexisting submaximal inflammatory stimulus. Hence, anti-inflammatory therapeutics could either target the primary proinflammatory signal (e.g. by limiting AGE-formation by AGE inhibitors or cross-link breakers) or the amplifyer Abeta (e.g. by limiting Abeta production by beta- or gamma-secretase inhibitors).
Structural comparison of the Pichia pastoris alcohol oxidase genes (1989)

In methylotrophic yeasts, alcohol oxidase is the first enzyme in the methanol-utilization pathway. The genome of one such yeast, Pichia pastoris, contains two alcohol oxidase genes, AOX1 and AOX2. Sequence analysis indicated that each gene encodes a similar protein of 663 amino acids. The protein-coding regions of the genes were 92% and 97% homologous at the nucleotide and predicted amino acid sequence levels, respectively. In contrast to homology observed within the protein-coding portions of the AOX genes, no homology was found in either the 5' or 3' non-coding regions. Although alcohol oxidase is found in peroxisomes of P. pastoris, the AOX amino acid sequences did not contain a peptide sequence similar to the peroxisomal transport sequence found at the C-terminus of some peroxisomally located proteins in higher eukaryotes.
Dys-synchronous regulation of XPC and XPA in trigeminal ganglion neurons following cisplatin treatment cycles. (2008)

The hyper-vulnerability of peripheral neurons to cisplatin chemotherapy may relate to the dys-synchronous regulation of XPC and XPA.
Myeloid Cell Leukemia-1 Inversely Correlates with Glycogen Synthase Kinase-3β Activity and Associates with Poor Prognosis in Human Breast Cancer (2007)

Myeloid cell leukemia-1 (Mcl-1), an antiapoptotic Bcl-2 family member, is overexpressed in many types of human cancer and associates with cell immortalization, malignant transformation, and chemoresistance. Glycogen synthase kinase-3beta (GSK-3beta), a key component of the Wnt signaling pathway, is involved in multiple physiologic processes such as protein synthesis, tumorigenesis, and apoptosis. Here, we report that expression of Mcl-1 was correlated with phosphorylated GSK-3beta (p-GSK-3beta) at Ser(9) (an inactivated form of GSK-3beta) in multiple cancer cell lines and primary human cancer samples. In addition, Mcl-1 was strikingly linked with poor prognosis of human breast cancer, in which the high level of Mcl-1 was related to high tumor grade and poor survival of breast cancer patients. Furthermore, we found that activation of GSK-3beta could down-regulate Mcl-1 and was required for proteasome-mediated Mcl-1 degradation. Under some physiologic conditions, such as UV irradiation, anticancer drug treatment, and inhibition of growth factor pathways, Mcl-1 was down-regulated through activation of GSK-3beta. Our results indicate that Mcl-1 stabilization by GSK-3beta inactivation could be involved in tumorigenesis and serve as a useful prognostic marker for human breast cancer.
Multiple objective scheduling of HPC workloads through dynamic prioritization (2013)

We have developed an efficient single queue scheduling system that utilizes a greedy knapsack algorithm with dynamic job priorities. Our scheduler satisfies high level objectives while maintaining high utilization of the HPC system or collection of distributed resources such as a computational GRID. We provide simulation analysis of our approach in contrast with various scheduling strategies of shortest job first; longest waiting jobs first; and large jobs first. Further, we look at the effects of system size on the total workload response time and find that for real workloads, the relationship between response time and system size follows an inverse power law. Our approach does not require system administrators or users to identify a specific priority queue for each of their jobs. The proposed scheduler performs an exhaustive parameter search for a priority calculation per job to balance high level objectives and provide guaranteed performance jobs in a workload. The system administrator needs only tune the prioritization parameters (knobs) and the system scheduler will behave accordingly, such as reducing wait time for jobs that are above average size with small runtimes. We demonstrate that our approach works very well on workloads that have many independent tasks. We evaluate our scheduler on a realistic mixed scientific data processing workload and with a realistic HPC workload trace from the parallel workloads archive.
Fatigue crack propagation behavior of ultrahigh molecular weight polyethylene (1984)

The relative fatigue crack propagation resistance of plain and carbon fiber-reinforced ultrahigh molecular weight polyethylene (UHMWPE) was determined from cyclic loading tests performed on compact tension specimens machined from the tibial components of total knee prostheses. Both materials were characterized by dynamic mechanical spectroscopy, X-ray diffraction, and differential scanning calorimetry. The cyclic tests used loading in laboratory air at 5 Hz using a sinusoidal wave form. Dynamic mechanical spectroscopy showed that the reinforced UHMWPE had a higher elastic storage modulus than the plain UHMWPE, whereas X-ray diffraction and differential scanning calorimetry showed that the percent crystallinity and degree of order in the crystalline regions were similar for the two materials. Fatigue crack propagation in both materials proved to be very sensitive to small changes in the applied cyclic stress intensity range. A 10% increase in stress intensity resulted in approximately an order of magnitude increase in fatigue crack growth rate. The fatigue crack propagation resistance of the reinforced UHMWPE was found to be significantly worse than that of the plain UHMWPE. This result was attributed to poor bonding between the carbon fibers and the UHMWPE matrix and the ductile nature of the matrix itself.
An Immunodominant Epitope in a Functional Domain Near the N-Terminus of Human Granulocyte-Macrophage Colony-Stimulating Factor Identified by Cross-Reaction of Synthetic Peptides with Neutralizing Anti-Protein and Anti-Peptide Antibodies (1994)

We produced polyclonal and monoclonal antibodies (MAbs) against recombinant human (rh) granulocyte-macrophage colony-stimulating factor (GM-CSF) and performed studies of epitope mapping by ELISA, using five synthetic peptides corresponding to sequences along this molecule. Additionally, anti-peptide MAbs were generated. The antibody ability to inhibit rhGM-CSF activity was determined using as bioassay the MO7e cell line, which is dependent on hGM-CSF for growth in vitro. An immunodominant epitope able to induce the highest neutralization antibody titers was identified near the N terminus of hGM-CSF. A synthetic peptide 14-24, homologous to a sequence including part of the first alpha-helix of the molecule, was recognized by neutralizing anti-protein antibodies. Similarly, MAbs anti- 14-24 cross-reacted with rhGM-CSF and specifically blocked its function. Replacement of Val16 or Asn17 with alanine greatly reduced the antibody-binding capacity to peptide 14-24, whereas substitution of Gln20 or Glu21 was less critical. Monoclonal antibodies generated against residues 30-41 (corresponding to an intrahelical loop) and 79-91 (homologous to a sequence including part of the third alpha-helix) or its analog [Ala88](79-91)beta Ala-Cys, were conformation dependent and nonneutralizing: they failed to react or bound poorly to rhGM-CSF in ELISA, but readily recognized the homologous sequence in the denatured protein, by Western blotting.
Enhancement of the reflectivity of Mo/Si multilayer x-ray mirrors by thermal treatment (1991)

Thermal treatment of a Mo/Si multilayer stack enhances its reflectivity in the soft x-ray region. The multilayer x-ray mirrors are fabricated by electron beam evaporation in ultrahigh vacuum. In situ measurement of the reflectivity during the deposition allows thickness control and an observation of changes in quality of the boundaries. By heating the substrates during deposition we obtain a smoothing of the interfaces. This leads to x-ray mirrors with peak reflectivity around 50% for normal incident radiation of wavelengths between 130 and 140 Å.
REVIEW ARTICLE: Secreted Heat Shock Protein gp96‐Ig: An Innovative Vaccine Approach (2008)

Heat shock proteins (HSPs) are a large family of proteins with different molecular weights and different intracellular localizations. These proteins undertake crucial functions in maintaining cell homeostasis, and therefore they have been conserved during evolution. HSP gp96 also known as glucose-regulated protein grp94, is the primary chaperone of the endoplasmatic reticulum. Gp96/grp94, because of its peptide chaperone capacity and its ability to interact actively with professional antigen-presenting cells (APCs), is also endowed with crucial immunological functions such as natural adjuvant for priming innate and adaptive immunity. To make gp96 accessible to the immune system without biochemical purification and without cell lysis, we generated a secreted form of gp96. The immunological properties of secreted gp96 and its implications for vaccine in human cancer and infectious diseases will be discussed.
Genetic contributions to yield gains of five major crop plants : proceedings of a symposium sponsored by Division C-1 of the Crop Science Society of America, 2 December 1981, in Atlanta, Georgia (1984)

Genetic contributions to yield gains of five major crop plants : proceedings of a symposium sponsored by Division C-1 of the Crop Science Society of America, 2 December 1981, in Atlanta, Georgia , Genetic contributions to yield gains of five major crop plants : proceedings of a symposium sponsore... , مرکز فناوری اطلاعات و اطلاع رسانی کشاورزی
Identification of Tetrapeptides from a Mixture Based Positional Scanning Library That Can Restore nM Full Agonist Function of the L106P, I69T, I102S, A219V, C271Y, and C271R Human Melanocortin-4 Polymorphic Receptors (hMC4Rs) (2014)

Human obesity has been linked to genetic factors and single nucleotide polymorphisms (SNPs). Melanocortin-4 receptor (MC4R) SNPs have been associated with up to 6% frequency in morbidly obese children and adults. A potential therapy for individuals possessing such genetic modifications is the identification of molecules that can restore proper receptor signaling and function. These compounds could serve as personalized medications improving quality of life issues as well as alleviating diseases symptoms associated with obesity including type 2 diabetes. Several hMC4 SNP receptors have been pharmacologically characterized in vitro to have a decreased, or a lack of response, to endogenous agonists such as α-, β-, and γ2-melanocyte stimulating hormones (MSH) and adrenocorticotropin hormone (ACTH). Herein we report the use of a mixture based positional scanning combinatorial tetrapeptide library to discover molecules with nM full agonist potency and efficacy to the L106P, I69T, I102S, A219V, C271Y, and C271R hMC4Rs. The most potent compounds at all these hMC4R SNPs include Ac-His-(pI)DPhe-Tic-(pNO2)DPhe-NH2, Ac-His-(pCl)DPhe-Tic-(pNO2)DPhe-NH2, Ac-His-(pCl)DPhe-Arg-(pI)Phe-NH2, and Ac-Arg-(pCl)DPhe-Tic-(pNO2)DPhe-NH2, revealing new ligand pharmacophore models for melanocortin receptor drug design strategies.
Robust, Functional Nanocrystal Solids by Infilling with Atomic Layer Deposition (2011)

Thin films of colloidal semiconductor nanocrystals (NCs) are inherently metatstable materials prone to oxidative and photothermal degradation driven by their large surface-to-volume ratios and high surface energies. (1) The fabrication of practical electronic devices based on NC solids hinges on preventing oxidation, surface diffusion, ripening, sintering, and other unwanted physicochemical changes that can plague these materials. Here we use low-temperature atomic layer deposition (ALD) to infill conductive PbSe NC solids with metal oxides to produce inorganic nanocomposites in which the NCs are locked in place and protected against oxidative and photothermal damage. Infilling NC field-effect transistors and solar cells with amorphous alumina yields devices that operate with enhanced and stable performance for at least months in air. Furthermore, ALD infilling with ZnO lowers the height of the inter-NC tunnel barrier for electron transport, yielding PbSe NC films with electron mobilities of 1 cm2 V(-1) s(-1). Our ALD technique is a versatile means to fabricate robust NC solids for optoelectronic devices.
Nucleotide Sequence Analysis of the env Gene of a New Zairian Isolate of HIV-1 (1988)

As a further step in the continuing process of defining the extent and nature of variability of the envelope (env) gene of HIV-1, we have cloned a new Zairian isolate, JY1, and sequenced the env gene of this isolate. Although the restriction map of the env region of JY1 was found to be more similar to that of the American prototype, BH10, than maps of all previously reported Zairian isolates and some American isolates, nucleotide sequencing of the JY1 env gene showed that it is among the most divergent from BH10 yet reported and that it differs from previously reported Zairian isolates almost to the same extent that it differs from BH10. A typical pattern of variable and constant regions was seen. A number of complex duplications were found in the hypervariable regions of JY1. The unique and highly divergent nature of the env gene of JY1 enhances its usefulness as part of a panel of HIV-1 isolates being evaluated in biologic and immunologic studies toward vaccine development.
Characterization of tryptic casein phosphopeptides prepared under industrially relevant conditions (1995)

Anticariogenic casein phosphopeptides (ACPP) contain the cluster sequence -Ser(P)-Ser(P)-Ser(P)-Glu-Glu- and have commercial potential as toothpaste, mouthwash, and food additives for the prevention of dental caries. In an approach to develop a commercial-scale process for the production of ACPP we have comprehensively characterized casein phosphopeptides (CPP) produced under industrially relevant conditions. Sodium caseinate (10% w/v) was hydrolyzed by Novo trypsin (commercial grade) at 50 degrees C for 2 h and CPP were purified from the acid clarified hydrolysate by a single-step selective precipitation procedure involving Ca(2+) (20 mol/mol casein) and ethanol (50% v/v) at pH 4.6 or 8.0. The individual peptides of the CPP preparations were purified by reversed-phase high-performance liquid chromatography (HPLC) and then identified by amino acid composition and sequence analyses. The yield of the pH 8.0 precipitate (13.85 +/- 0.48 wt % of the caseinate) was slightly higher than that of the pH 4.6 precipitate (11.04 +/- 0.30 wt % of the caseinate). However, the pH 4.6 precipitate contained predominantly (86.4 mol %) ACPP cluster peptides with small amounts of the diphosphorylated peptides (13.6 mol %), alpha(s1)(43-58) and alpha(s2)(126-136). In the pH 8.0 precipitate the cluster peptides represented a smaller proportion of the total peptides (61.9 mol %) due to increased recoveries of the diphosphorylated peptides (24.4 mol %) as well as the additional recovery of the monophosphorylated peptide beta(33-48) (13.7 mol %) indicating increased cross-linking by Ca(2+) at the higher pH. The recovery of the ACPP from the original caseinate was similar for both the pH 4.6 and 8.0 precipitates. Slight chymotryptic activity was detected in the industrial-grade enzyme, resulting in minor truncation of some peptides. Also some deamidation and methionine oxidation of one peptide, alpha(s1)(59-79), were detected. In conclusion, ACPP can be produced under industrially relevant conditions with only minor modifications such as slight truncation, deamidation, and methionine oxidation. However, in order to prepare casein phosphopeptides predominantly containing the cluster sequence -Ser(P)-Ser(P)-Ser(P)-Glu-Glu-, the single-step selective precipitation with Ca(2+)/ethanol should be performed at pH 4.6 rather than pH 8.0. (c) 1995 John Wiley & Sons, Inc.
SPARC Suppresses Apoptosis of Idiopathic Pulmonary Fibrosis Fibroblasts through Constitutive Activation of β-Catenin (2010)

Idiopathic pulmonary fibrosis (IPF) is a poorly understood progressive disease characterized by the accumulation of scar tissue in the lung interstitium. A hallmark of the disease is areas of injury to type II alveolar epithelial cells with attendant accumulation of fibroblasts in areas called fibroblastic foci. In an effort to better characterize the lung fibroblast phenotype in IPF patients, we isolated fibroblasts from patients with IPF and looked for activation of signaling proteins, which could help explain the exaggerated fibrogenic response in IPF. We found that IPF fibroblasts constitutively expressed increased basal levels of SPARC, plasminogen activator inhibitor-1 (PAI-1), and active beta-catenin compared with control cells. Control of basal PAI-1 expression in IPF fibroblasts was regulated by SPARC-mediated activation of Akt, leading to inhibition of glycogen synthase kinase-3beta and activation of beta-catenin. Additionally, IPF fibroblasts (but not control fibroblasts) were resistant to plasminogen-induced apoptosis and were sensitized to plasminogen-mediated apoptosis by inhibition of SPARC or beta-catenin. These findings uncover a newly discovered regulatory pathway in IPF fibroblasts that is characterized by elevated SPARC, giving rise to activated beta-catenin, which regulates expression of downstream genes, such as PAI-1, and confers an apoptosis-resistant phenotype. Disruption of this pathway may represent a novel therapeutic target in IPF.
Arterial colony stimulating factor-1 influences atherosclerotic lesions by regulating monocyte migration and apoptosis (2010)

Previous studies have shown that colony stimulating factor-1 (CSF-1) deficiency dramatically reduced atherogenesis in mice. In this report we investigate this mechanism and explore a therapeutic avenue based on inhibition of CSF-1 signaling. Lesions from macrophage colony stimulating factor-1 (Csf1)+/- mice showed increased numbers of apoptotic macrophages, decreased overall macrophage content, and inflammation. In vitro studies indicated that CSF-1 is chemotactic for monocytes. Bone marrow transplantation studies suggested that vascular cell-derived, rather than macrophage-derived, CSF-1 is responsible for the effect on atherosclerosis. Consistent with previous studies, CSF-1 affected lesion development in a dose-dependent manner, suggesting that pharmacological inhibition of CSF-1 might achieve similar results. Indeed, we observed that treatment of hyperlipidemic mice with a CSF-1 receptor kinase inhibitor inhibited plaque progression. This observation was accompanied by a reduction in the expression of adhesion factors (ICAM-1), macrophage markers (F4/80), inflammatory cytokines (Il-6, Il-1beta), and macrophage matrix degradation enzymes (MMP-9). We conclude that the M-CSF pathway contributes to monocyte recruitment and macrophage survival and that this pathway is a potential target for therapeutic intervention.
Mouse lymphotoxin and tumor necrosis factor: structural analysis of the cloned genes, physical linkage, and chromosomal position. (1987)

Lymphotoxin (LT) and tumor necrosis factor (TNF) are cytotoxic and immunoregulatory lymphokines which have similar activities but are produced by different cell types. We have cloned the murine LT and TNF genes from a lambda:mouse DNA recombinant library, using as probes synthetic oligonucleotides defined by portions of the human LT or TNF cDNA sequences. Analysis of the genomic clones indicates that the LT and TNF genes are physically linked, i.e., approximately 1.2 kb separates the 3' end of LT from the 5' end of TNF genes. By using, first, a series of recombinant inbred lines, and second, a series of H-2-recombinant congenic strains, we determined that the LT/TNF gene cluster lies on chromosome 17, closely linked to the H-2D end of the murine H-2 complex. Comparison of the primary sequence of murine and human LT revealed that the intron-exon structure of murine LT is similar in these two species. Comparison of the predicted amino acid sequences of murine and human LT indicates that the proteins are about 72% homologous with much greater sequence conservation in regions encoding the COOH-terminal portion. Comparison of the 5' flanking sequence of LT to a number of genes that are specifically expressed in activated T cells reveals a number of conserved sequences that may play a role in control of these genes.