gebhart/patrepeval huggingface dataset:
Site‐Specific Functionalization of Proteins by Organopalladium Reactions (2006)

A new carbon-carbon bond has been regioselectively introduced into a target position (position 32 or 174) of the Ras protein by two types of organopalladium reactions (Mizoroki-Heck and Sonogashira reactions). Reaction conditions were screened by using a model peptide, and the stability of the Ras protein under the reaction conditions was examined by using the wild-type Ras protein. Finally, the iF-Ras proteins containing a 4-iodo-L-phenylalanine residue were subjected to organopalladium reactions with vinylated or propargylated biotin. Site-specific biotinylations of the Ras protein were confirmed by Western blot and LC-MS/MS.
Prostate Tissue Specificity of the Prostate-Specific Antigen Promoter Isolated from a Patient with Prostate Cancer (1995)

We have cloned and characterized a 620-bp fragment of DNA that flanks 5' of the prostate-specific antigen (PSA) gene from a prostate cancer patient. Using DNA transfection, the efficacy of this putative promoter in regulating gene expression was quantitated in several prostate and nonprostate tissue cell lines. Our results demonstrated that the 620-dp DNA fragment actively drives gene expression in LNCaP, a PSA-producing prostate tumor cell line. No promoter activity was detected in the non-PSA-producing prostate tumor lines, DU145 and PC-3, nor in a renal (R11) or breast (MCF-7) cancer cell line. Furthermore, the promoter activity could be regulated in vitro by androgen stimulation. Dihydrotestosterone (DHT) concentrations between 3 and 30 nM induced the highest promoter activity in the transfected LNCaP cells, which parallels the expression profile of the androgen receptor in LNCaP cells. In addition, our PSA promoter exhibited competitive inhibition of the endogenous genomic PSA promoter in transfected LNCaP cells, suggesting that prostate cell-specific DNA-binding proteins are required to activate the PSA promoter. increased its potency four- to five-fold while retaining tissue specificity. Our data suggest that a strong tissue-specific negative regulatory element capable of overriding the nonspecific CMV promoter is present in the PSA promoter and confers its tissue specificity. The use of a highly specific promoter-driven gene vector will allow selective expression of therapeutic genes within PSA-producing prostate cancer cells, providing a unique strategy for prostate cancer gene therapy.
Detection of the Inflammation Biomarker C-Reactive Protein in Serum Samples: Towards an Optimal Biosensor Formula (2014)

The development of an electrochemical immunosensor for the biomarker, C-reactive protein (CRP), is reported in this work. CRP has been used to assess inflammation and is also used in a multi-biomarker system as a predictive biomarker for cardiovascular disease risk. A gold-based working electrode sensor was developed, and the types of electrode printing inks and ink curing techniques were then optimized. The electrodes with the best performance parameters were then employed for the construction of an immunosensor for CRP by immobilizing anti-human CRP antibody on the working electrode surface. A sandwich enzyme-linked immunosorbent assay (ELISA) was then constructed after sample addition by using anti-human CRP antibody labelled with horseradish peroxidase (HRP). The signal was generated by the addition of a mediator/substrate system comprised of 3,3,5',5'-Tetramethylbenzidine dihydrochloride (TMB) and hydrogen peroxide (H2O2). Measurements were conducted using chronoamperometry at -200 mV against an integrated Ag/AgCl reference electrode. A CRP limit of detection (LOD) of 2.2 ng·mL(-1) was achieved in spiked serum samples, and performance agreement was obtained with reference to a commercial ELISA kit. The developed CRP immunosensor was able to detect a diagnostically relevant range of the biomarker in serum without the need for signal amplification using nanoparticles, paving the way for future development on a cardiac panel electrochemical point-of-care diagnostic device.
Selective Synthesis of Epolactaene Featuring Efficient Construction of Methyl (Z)-2-Iodo-2-butenoate and (2R,3S,4S)-2-Trimethylsilyl-2,3-epoxy-4-methyl- γ-butyrolactone (2006)

[reaction: see text] (+)-Epolactaene was synthesized in 14 steps in the longest linear sequence. The synthesis is highlighted by a highly efficient preparation of the lactone intermediate 4, which only requires three steps from the commercially available (S)-3-butyn-2-ol. It also features a fully stereocontrolled synthesis of the intermediate 9, which was constructed through the use of Zr-catalyzed methylalumination of alkynes and a series of Pd-catalyzed organozinc cross-coupling reactions, such as homopropargylation, direct ethynylation, and alkenylation of the methyl ester of (Z)-alpha-iodocrotonic acid (3).
Insect immune response to bacterial infection is mediated by eicosanoids. (1991)

Inhibition of eicosanoid formation in larvae of the tobacco hornworm Manduca sexta, using specific inhibitors of phospholipase A2, cyclooxygenase, and lipoxygenase, severely weakened the ability of larvae to clear the bacterium Serratia marscescens from their hemolymph. The reduced capability to remove bacteria is associated with increased mortality due to these bacteria. There is a dose-dependent relationship between the phospholipase A2 inhibitor dexamethasone and both the reduced bacterial clearance and increased larval mortality. The dexamethasone effects on larval survival were reversed by treatment with arachidonic acid. Maleic acid, a nonspecific antioxidant, did not interfere with the insects' ability to remove bacterial cells from hemolymph. The larvae were shown to contain all of the C20 polyunsaturated fatty acids necessary for eicosanoid biosynthesis and to be capable of converting radioactive arachidonic acid into several primary prostaglandins. These results strongly suggest that eicosanoids mediate transduction of bacterial infection signals into the complex of cellular and humoral responses that comprise invertebrate immunity.
The molecular biology of the human anaplastic thyroid carcinoma cell. (1991)

In the present investigation we show data from our studies of anaplastic human thyroid carcinoma cell lines. The cell lines employed in the study were HTh 7, HTh 74, C 643 and SW 1736, all derived from tumours diagnosed as anaplastic thyroid carcinomas. Northern blot analysis with four different thyroid specific cDNA probes showed a varying pattern of expression. Thyroglobulin mRNA was found in three of the carcinoma cell lines, although the signal was very weak compared to the expression in tissue from a toxic goitre, used as positive control. Interestingly, two of the cell lines expressed the receptor for thyrotropin, but none of them contained thyroperoxidase mRNA. Three of the cell lines expressed mRNA for receptors platelet-derived growth factor, PDGFR-alpha and/or PDGFR-beta type. Messenger RNA of a thyroid specific transcription factor, TTF-1, known to regulate the normal function of thyrocytes, was found in the toxic goitre but not in the anaplastic thyroid carcinoma cell lines. Lack of expression of TTF-1 might the immediate cause of the anaplastic phenotype, considering the possibility that TTF-1 functions as a master regulatory gene in thyroid cell differentiation.
THE STABILITY OF SIMPLIFIED OMEPRAZOLE SUSPENSION (SOS) (1998)

Society of Critical Care Medicine; 27th Educational and Scientific Symposium; San Antonio, Texas, USA; February 4-8, 1998: Poster Hall: Thursday, February 5, 1998 5: 45-7: 15 pm; Friday, February 6, 1998 11: 40 am-1: 00 pm; Saturday, February 7, 1998 11: 40 am-1: 00 pm: Poster Presentations: Pharmacology
Laminin and α-Dystroglycan Mediate Acetylcholine Receptor Aggregation via a MuSK-Independent Pathway (1998)

Specific isoforms of laminin (LN) are concentrated at neuromuscular junctions (NMJs) where they may participate in synaptic organization or function. In myotubes from C2 cells, LN is concentrated within the majority of spontaneous acetylcholine receptor (AChR) aggregates. Neural agrin substantially increases this colocalization, suggesting that agrin can recruit LN into AChR aggregates. Addition of LN to C2 myotubes induces a more than twofold increase in the number of AChR aggregates. These aggregates have a larger size and are more dense than are those induced by agrin, suggesting that LN is involved in the growth and/or stabilization of AChR aggregates. Consistent with this hypothesis, an antiserum to LN reduces the size of individual AChR aggregates but increases their number. In C2 myotubes, extracellular matrix receptors containing the integrin beta1 subunit are poorly colocalized with AChR aggregates, suggesting that integrins may not be involved in LN-induced aggregation. In contrast, almost all AChR aggregates are associated with dystroglycan immunoreactivity, and monoclonal antibody (mAb) IIH6 against alpha-dystroglycan (alpha-DG), a LN and agrin receptor, causes a concentration-dependent inhibition of LN-induced aggregation. Moreover, S27 cells, which lack a functional alpha-DG, and two C2-derived cell lines expressing antisense DG mRNA fail to aggregate AChRs in response to LN. Finally, LN-induced AChR aggregation does not involve the phosphorylation of the muscle-specific tyrosine kinase receptor (MuSK) or the AChR beta subunit. We hypothesize that the interaction of LN with alpha-DG contributes to the growth and/or stabilization of AChR microaggregates into macroaggregates at the developing NMJ via a MuSK-independent mechanism.
Synthesis of Neutral Molecular Squares Composed of Bis(phosphine)platinum Corner Units and Dialkynyl Linkers. Solid-State Characterization of [Pt(μ-C⋮CC⋮C)(dppp)]4 (2004)

Coupling of dichloroplatinum complexes with ethyne or butadiyne, catalyzed by CuI in the presence of Et2NH, leads to complexes of the types [Pt(C⋮CH)2L2] (L2 = dppe (1), dppp (2); L = PEt3 (3)) and [Pt(C⋮CC⋮CH)2L2] (L2 = dppp (4), dcpe (5); L = PEt3 (6)). Attempts to produce tetraplatinum species with ethynyl edges proved unsuccessful, but further coupling of the butadiynylplatinum complexes with [PtCl2L2] produces the neutral molecular squares [Pt(μ-C⋮CC⋮C)2L2]4 (L2 = dppp (7), dcpe (8); L = PEt3 (9)). This two-step approach allows the synthesis of the unsymmetrical complexes [Pt2(μ-C⋮CC⋮C)2(PEt3)2L2] (L2 = dppp (10); dcpe (11)). The molecular structure of 7 reveals that each square has a puckered, butterfly-like structure. These pack in a face-to-face manner, generating series of channels that accommodate several solvent molecules. Coupling of trans-[Pt(C⋮CC⋮C)2(PEt3)2] (6b) with [PtCl2L2] (L2 = dcpe, dppp) leads to complexes assigned as neutral octaplatinum derivatives. The nitrogen-containing complexes [Pt(C⋮CC5H4N)2(dppp)] (14) and [Pt(C⋮CC6H4CN)2(dppp)] (15) react with AgNO3 to produce Pt4Ag4 adducts.
Constituents of Essential Oils fromNepeta catariaL.,N. grandifloraM.B. andN. nudaL. (1996)

ABSTRACT Essential oils from Bulgarian populations of Nepeta nuda L. and N. cataria L. (two origins) and of the Caucasian endemic N. grandiflora M.B. (Lamiaceae) were analyzed by GC/MS, TLC and chemical transformation. Iridoids of the nepetalactone type were the main constituents, accompanied by other terpenoids. Some of the constituents were found for the first time in the genus Nepeta from natural sources.
A Population of Rat Liver Lysosomes Responsible for the Selective Uptake and Degradation of Cytosolic Proteins (1997)

Two populations of rat liver lysosomes can be distinguished on the basis of their density. A major difference between these populations is that one contains the heat shock cognate protein of 73 kDa (hsc73) within the lysosomal lumen. The lysosomal fraction containing hsc73 exhibits much higher efficiencies in the in vitro uptake and degradation of glyceraldehyde-3-phosphate dehydrogenase and ribonuclease A, two well established substrates of the selective lysosomal pathway of intracellular protein degradation. Preloading of the lysosomal population that is devoid of lumenal hsc73 with hsc73 isolated from cytosol activated the selective transport of substrate proteins into these lysosomes. Furthermore, treatment of animals with leupeptin, an inhibitor of lysosomal cathepsins, or 88 h of starvation also increased the amount of hsc73 within their lysosomal lumen, and these in vivo treatments also activated the selective transport of substrate proteins in vitro. Thus, the hsc73 located within lysosomes appears to be required for efficient uptake of cytosolic proteins by these organelles. The difference in hsc73 content between the lysosomal populations appears to be due to differences in their ability to take up hsc73 combined with differences in the intralysosomal degradation rates of hsc73. The increased stability of hsc73 in one population of lysosomes is primarily a consequence of this lysosomal population's more acidic pH.
Integration of Real-time Services in an IP-ATM Network Architecture (1995)

The IETF is currently developing an integrated service model which is designed to support real-time services on the Internet. Concurrently, the ATM Forum is developing Asynchronous Transfer Mode networking which similarly provides real-time networking support. The use of ATM in the Internet as a link layer protocol is already occurring, and both the IETF and the ATM Forum are producing specifications for IP over ATM. The purpose of this paper is to provide a clear statement of what issues need to be addressed in interfacing the IP integrated services environment with an ATM service environment so as to create a seamless interface between the two in support of end users desiring real-time networking services.
Discovery and Development of GSK3 Inhibitors for the Treatment of Type 2 Diabetes (2004)

Originally identified as a modulator of glycogen metabolism, glycogen synthase kinase-3 (GSK3) is now understood to play an important regulatory role in a variety of pathways including initiation of protein synthesis, cell proliferation, cell differentiation, apoptosis, and is essential for embryonic development as a component of the Wnt signaling cascade. GSK3 can be considered as a target for both metabolic and neurological disorders. GSK3's association with neuronal apoptosis and hyper-phosphorylation of tau make this kinase an attractive therapeutic target for neurodegenerative conditions such as head trauma, stroke and Alzheimer's disease. While noting GSK3's many associated functions, this review will focus on GSK3 as a central negative regulator in the insulin signaling pathway, its role in insulin resistance, and the utility of GSK3 inhibitors for intervention and control of metabolic diseases including type 2 diabetes. Recent crystal structures, including the active (phosphorylated Tyr-216) form of GSK3beta, provide a wealth of structural information and greater understanding of GSK3's unique regulation and substrate specificity. Many potent and selective small molecule inhibitors of GSK3 have now been identified, and used in vitro to modulate glycogen metabolism and gene transcription, increase glycogen synthase activity and enhance insulin-stimulated glucose transport. The pharmacology of potent and selective GSK3 inhibitors (CT 99021 and CT 20026) is described in a number of in vitro and in vivo models following acute or chronic exposure. The efficacy of clinical candidates in diabetic primates and the implications for clinical development are discussed. The profile of activity is consistent with a unique form of insulin sensitization which is well suited for indications such as metabolic syndrome X and type 2 diabetes.
α-Lipoic Acid Inhibits Adipocyte Differentiation by Regulating Pro-adipogenic Transcription Factors via Mitogen-activated Protein Kinase Pathways (2003)

Obesity is associated with a number of pathological disorders such as non-insulin-dependent diabetes, hypertension, hyperlipidemia, and cardiovascular diseases. alpha-Lipoic acid (LA) has been demonstrated to activate the insulin signaling pathway and to exert insulin-like actions in adipose and muscle cells. Based on this similarity LA is expected to promote adipogenesis in pre-adipocytes. Here, however, we report that LA inhibited differentiation of 3T3-L1 pre-adipocytes induced by a hormonal mixture or troglitazone. Northern blot analysis of cells demonstrated that this inhibition was accompanied with attenuated expression of adipocyte-specific fatty acid-binding protein and lipoprotein lipase. Electrophoretic mobility shift assay and Western blot analysis of cells demonstrated that LA modulates transcriptional activity and/or expression of a set of anti- or pro-adipogenic transcription factors. LA treatment of 3T3-L1 pre-adipocytes also resulted in prolonged activation of major mitogen-activated protein kinase signaling pathways but showed little or no effect on the activity of the insulin receptor/Akt signaling pathway. These findings suggest that LA inhibits insulin or the hormonal mixture-induced differentiation of 3T3-L1 pre-adipocytes by modulating activity and/or expression of pro- or anti-adipogenic transcription factors mainly through activating the MAPK pathways.
A Block Diagram Compiler (1961)

A computer program known as BLODI, which accepts for an input a source program written in the BLODI language, is described. The BLODI source language corresponds closely to an engineer's block diagram of a circuit and is easily learned, even by persons not familiar with computing machines. The input code consists essentially of designating the connectivity of a number of boxes drawn from an alphabet of about 30 types. These types include amplifiers, delay lines, counters, etc., which are familiar to designers of electronic circuits. The principles of the compiler are explained and applications are discussed.
Pseudomonas aeruginosa – a phenomenon of bacterial resistance (2009)

Pseudomonas aeruginosa is one of the leading nosocomial pathogens worldwide. Nosocomial infections caused by this organism are often hard to treat because of both the intrinsic resistance of the species (it has constitutive expression of AmpC beta-lactamase and efflux pumps, combined with a low permeability of the outer membrane), and its remarkable ability to acquire further resistance mechanisms to multiple groups of antimicrobial agents, including beta-lactams, aminoglycosides and fluoroquinolones. P. aeruginosa represents a phenomenon of bacterial resistance, since practically all known mechanisms of antimicrobial resistance can be seen in it: derepression of chromosomal AmpC cephalosporinase; production of plasmid or integron-mediated beta-lactamases from different molecular classes (carbenicillinases and extended-spectrum beta-lactamases belonging to class A, class D oxacillinases and class B carbapenem-hydrolysing enzymes); diminished outer membrane permeability (loss of OprD proteins); overexpression of active efflux systems with wide substrate profiles; synthesis of aminoglycoside-modifying enzymes (phosphoryltransferases, acetyltransferases and adenylyltransferases); and structural alterations of topoisomerases II and IV determining quinolone resistance. Worryingly, these mechanisms are often present simultaneously, thereby conferring multiresistant phenotypes. This review describes the known resistance mechanisms in P. aeruginosa to the most frequently administrated antipseudomonal antibiotics: beta-lactams, aminoglycosides and fluoroquinolones.
Bone Marrow–generated Dendritic Cells Pulsed with Tumor Extracts or Tumor RNA Induce Antitumor Immunity against Central Nervous System Tumors (1997)

Recent studies have shown that the brain is not a barrier to successful active immunotherapy that uses gene-modified autologous tumor cell vaccines. In this study, we compared the efficacy of two types of vaccines for the treatment of tumors within the central nervous system (CNS): dendritic cell (DC)-based vaccines pulsed with either tumor extract or tumor RNA, and cytokine gene-modified tumor vaccines. Using the B16/F10 murine melanoma (B16) as a model for CNS tumor, we show that vaccination with bone marrow-generated DCs, pulsed with either B16 cell extract or B16 total RNA, can induce specific cytotoxic T lymphocytes against B16 tumor cells. Both types of DC vaccines were able to protect animals from tumors located in the CNS. DC-based vaccines also led to prolonged survival in mice with tumors placed before the initiation of vaccine therapy. The DC-based vaccines were at least as effective, if not more so, as vaccines containing B16 tumor cells in which the granulocytic macrophage colony-stimulating factor gene had been modified. These data support the use of DC-based vaccines for the treatment of patients with CNS tumors.
Frequency of the TMPRSS2:ERG gene fusion is increased in moderate to poorly differentiated prostate cancers (2007)

This study indicates that TMPRSS2:ERG gene rearrangements in CaP may be used as a diagnostic tool to identify prognostically relevant sub-classifications of these cancers.
Clustering in large graphs and matrices (1999)

We consider the problem of dividing a set of m points in Euclidean n-space into k clusters (m, n are variable while k is fixed), so as to minimize the sum of distances squared of each point to its &amp;quot;cluster center&amp;quot;. This formulation differs in two ways from the most frequently considered clustering problems in the literature, namely, here we have k fixed and m;n variable, and we use the sum of squared distances as our measure; we will argue that our problem is natural in many contexts. We consider a relaxation of the discrete problem: find the k-dimensional subspace V so that the sum of distances squared to V (of the m points) is minimized. We show: (i) The relaxation can be solved by the Singular Value Decomposition (SVD) of Linear Algebra. (ii) The solution of the relaxation can be used to get a 2-approximation algorithm for the original problem. More importantly, (iii) we argue that in fact the relaxation provides a generalized clustering which is useful in its own right....
Non‐invasive prenatal testing for fetal aneuploidies in the first trimester of pregnancy (2014)

NIPT is highly reliable and accurate when applied to maternal DNA samples collected from pregnant women in the first trimester between 8 + 0 and 12 + 6 weeks.