gebhart/patrepeval huggingface dataset:
Simultaneous, sequential quantitative achiral–chiral analysis by two‐dimensional liquid chromatography (2012)

In general, chromatographic analysis of chiral compounds involves a minimum of two methods; a primary achiral method for assay and impurity analysis and a secondary chiral method for assessing chiral purity. Achiral method resolves main enantiomeric pairs of component from potential impurities and degradation products and chiral method resolves enantiomeric pairs of the main component and diastereomer pairs. Reversed-phase chromatographic methods are preferred for assay and impurity analysis (high efficiency and selectivity) whereas chiral separation is performed by reverse phase, normal phase, or polar organic mode. In this work, we have demonstrated the use of heart-cutting (LC-LC) and comprehensive two-dimensional liquid chromatography (LC × LC) in simultaneous, sequential achiral and chiral analysis and quantitation of minor, undesired enantiomer in the presence of major, desired enantiomer using phenylalanine as an example. The results were comparable between LC-LC and LC × LC with former offering better sensitivity and accuracy. The quantitation range was over three orders of magnitude with undesired D-phenylalanine detected at approximately 0.3% in the presence of predominant, desired L-phenylalanine (99.7%). The limit of quantitation was comparable to conventional high-performance liquid chromatography. A reversed-phase C18 achiral column in the primary and reversed-phase Chirobiotic Tag chiral column in the secondary dimension were used with a compatible mobile phase.
Functional human induced hepatocytes (hiHeps) with bile acid synthesis and transport capacities: A novel in vitro cholestatic model (2016)

Drug-induced cholestasis is a leading cause of drug withdrawal. However, the use of primary human hepatocytes (PHHs), the gold standard for predicting cholestasis in vitro, is limited by their high cost and batch-to-batch variability. Mature hepatocyte characteristics have been observed in human induced hepatocytes (hiHeps) derived from human fibroblast transdifferentiation. Here, we evaluated whether hiHeps could biosynthesize and excrete bile acids (BAs) and their potential as PHH alternatives for cholestasis investigations. Quantitative real-time PCR (qRT-PCR) and western blotting indicated that hiHeps highly expressed BA synthases and functional transporters. Liquid chromatography tandem mass spectrometry (LC-MS/MS) showed that hiHeps produced normal intercellular unconjugated BAs but fewer conjugated BAs than human hepatocytes. When incubated with representative cholestatic agents, hiHeps exhibited sensitive drug-induced bile salt export pump (BSEP) dysfunction, and their response to cholestatic agent-mediated cytotoxicity correlated well with that of PHHs (r<sup>2</sup> = 0.8032). Deoxycholic acid (DCA)-induced hepatotoxicity in hiHeps was verified by elevated aspartate aminotransferase (AST) and γ-glutamyl-transferase (γ-GT) levels. Mitochondrial damage and cell death suggested DCA-induced toxicity in hiHeps, which were attenuated by hepatoprotective drugs, as in PHHs. For the first time, hiHeps were reported to biosynthesize and excrete BAs, which could facilitate predicting cholestatic hepatotoxicity and screening potential therapeutic drugs against cholestasis.
Vertical cavity surface emitting lasers for integrated optoelectronics (2005)

Within the past two years vertical-cavity surface-emitting lasers (VCSELs) have transitioned from being the subject of exploratory research in a few scattered groups around the world to the focus of serious development efforts in numerous major corporations. In fact, the turning point seemed to occur about two years ago--perhaps due in part to the important talks and discussions at the last Semiconductor Laser Conference in Davos[I-61. At that time the 'main-stream' diode laser worker harbored many doubts about the viability of this new device. The modest performance that then existed was seen by many as indicative of what could be expected. Needless to say, we now know that VCSELs have emerged as completely viable sources, which might even fulfill the outlandish predictions made at Davos that VCSELs would be the dominate diode laser by the turn of the century. Although their performance still falls short of in-plane devices, theoretical models predict that significant improvements should be soon forthcoming. Moreover, the inherent advantages of wafer-scale manufacturability and testability as well as efficient coupling to fibers or other low numerical aperture optics suggests that many niches for VCSELs will emerge.
A General Equilibrium Model of International Portfolio Choice (1993)

ABSTRACT We investigate, in a two‐country general equilibrium model, whether a bias in consumption towards domestic goods will necessarily lead to a preference for domestic securities. We develop a model where investors are constrained to consume only from their domestic capital stock and where it is costly to transfer capital across countries. In this model, investors less risk averse than an investor with log utility bias their portfolios towards domestic assets. Investors more risk averse than log, however, prefer foreign assets. Thus, this model suggests that it is unlikely that the portfolios observed empirically can be explained by the high proportion of domestic goods in total consumption.
Vorinostat for Treatment of Cutaneous Manifestations of Advanced Primary Cutaneous T-Cell Lymphoma (2007)

Vorinostat showed activity in CTCL, and skin responses were a clinical benefit. Vorinostat was approved for treatment of cutaneous manifestations of CTCL. A nonblinded, single-arm trial did not allow a reliable assessment of pruritus relief.
Gene Amplification and Expression of the Steroid Receptor Coactivator SRC3 (AIB1) in Sporadic Breast and Endometrial Carcinomas (2001)

Steroid receptor coactivator 3 (SRC3) functions as a coactivator for nuclear receptor mediated transcriptional activation. It binds to nuclear receptors in a ligand-dependent fashion and recruits other factors such as CBP and p300 to the transactivation complex. Due to its function as activator of nuclear receptors, overexpression of SRC3 might enhance their effects. Gene amplification is a common mechanism that causes overexpression, already described for oncogenes like c-erbB2, c-myc and int2. In this study, SRC3 gene amplification and expression levels were analyzed in 127 sporadic breast carcinomas, 30 endometrial carcinomas and different cell lines (MCF7, HeLa, Ishikawa, T47D, BT-20, SK-BR-3, HEC-1a, RL 95-2, OVCAR3 and A-431). To determine gene amplification and mRNA expression levels, quantitative differential PCR and RT-PCR were performed in combination with fluorescent DNA technology. Gene amplification was not found in any of the breast and endometrial carcinomas, but was found in the carcinoma cell lines MCF7 (10-fold) and HeLa (3-fold). SRC3 overexpression was detected in 13% (3/23) of breast carcinomas and 17% (5/30) of endometrial carcinomas, as well as in MCF7 and HeLa cells. Thus, SRC3 overexpression found in breast and endometrial tumors is not caused by SRC3 gene amplification. A carcinogenic potential provided by SRC3 overexpression has to be elucidated in further studies.
Structural and Functional Features of the B-Cell Receptor in IgG-Positive Chronic Lymphocytic Leukemia (2006)

IgG+ CLL is likely to arise from an age-related expanded pool of B cells, on a path parallel to M-CLL, and perhaps with a similar clinical course.
Cigarette Smoking, Obesity, Diuretic Use, and Coffee Consumption as Risk Factors for Renal Cell Carcinoma<xref ref-type="fn" rid="FN1">2</xref> (1986)

One hundred sixty incident cases of renal cell carcinoma under the age of 55 years and an equal number of age-(within 5 yr), race-, and sex-matched neighborhood controls were interviewed. Cigarette smoking was a risk factor for renal cell carcinoma in males [relative risk (RR) = 2.1, one-sided P = .02] but not in females (RR = 1.1, P = .50). Obesity was a significant risk factor in both males and females: The RR for a 4th quartile compared to a 1st quartile Quetelet's Index 10 years ago was 2.5 for males and 3.3 for females. Additional risk factors in females were diuretic use (RR = 4.5, P = .002) and daily coffee consumption (RR = 2.3, P = .06).
Oligodendrocytes lack glycolipid anchored proteins which protect them against complement lysis. Restoration of resistance to lysis by incorporation of CD59. (1992)

Rat oligodendrocytes, which activate the classical pathway of complement in the absence of antibody, are highly sensitive in a reactive lysis assay using human C5b6 and EDTA serum. Oligodendrocytes may be relatively deficient in glycolipid-linked complement regulatory protein(s), since digestion with phosphatidylinositol-specific phospholipase C (PI-PLC) failed to increase their sensitivity to serum, whereas complement-insensitive astrocytes, when treated with PI-PLC, became strikingly sensitive. To test the hypothesis that oligodendrocytes lack terminal complement regulatory molecule(s), human erythrocyte CD59, a recently described complement regulatory protein, was purified to homogeneity. The biological activity of the preparation was confirmed by reincorporating the protein into guinea-pig erythrocytes through its glycolipid anchor, which resulted in dose-dependent protection against human C5b6 and EDTA serum. Incorporation of 10(5) molecules of human CD59 into rat oligodendrocytes resulted in good protection against homologous human complement (76%), and significant protection against rat complement homologous to the cell (36%). Protection could be reversed using an antibody to CD59.
Synthesis of oligo(thienylenevinylenes) substituted with alkoxy groups (2001)

Abstract Conjugated oligomers based on a combination of thiophene and 3,4‐dialkoxythiophene moieties have been synthesized via the Vilsmeier formylation, Wittig‐Honer reaction, and McMurry coupling reaction starting from dimethyl 3,4‐dihydroxythiophene‐2,5‐dicarboxylates. Comparison of the optical and electrochemical properties shows that the mixed π‐conjugated oligomers of thiophene and 3,4‐dialkoxythiophene produces a decrease of the highest occupied molecular orbital‐lowest unoccupied molecular orbital gap that is attributed to the electron‐donating property of the alkoxy groups. © 2001 John Wiley &amp; Sons, Inc. Heteroatom Chem 12:414–417, 2001
FlashExtract (2014)

Various document types that combine model and view (e.g., text files, webpages, spreadsheets) make it easy to organize (possibly hierarchical) data, but make it difficult to extract raw data for any further manipulation or querying. We present a general framework FlashExtract to extract relevant data from semi-structured documents using examples. It includes: (a) an interaction model that allows end-users to give examples to extract various fields and to relate them in a hierarchical organization using structure and sequence constructs. (b) an inductive synthesis algorithm to synthesize the intended program from few examples in any underlying domain-specific language for data extraction that has been built using our specified algebra of few core operators (map, filter, merge, and pair). We describe instantiation of our framework to three different domains: text files, webpages, and spreadsheets. On our benchmark comprising 75 documents, FlashExtract is able to extract intended data using an average of 2.36 examples in 0.84 seconds per field.
Production of human and murine interleukin-2 by toxic shock syndrome toxin-1. (1986)

Toxic shock syndrome toxin-1 (TSST-1), isolated from Staphylococcus aureus strains associated with toxic shock syndrome (TSS), is known as a potent mitogen and interleukin-1 inducer. The potential of TSST-1 as an interleukin-2 (IL-2) inducer was tested on human peripheral blood lymphocytes (HPBL) and murine spleen lymphocytes (MSL). These cells were incubated with TSST-1 and the supernatants analysed for IL-2 production. Preincubation of IL-2-dependent indicator cells (IC) with a monoclonal antibody specific for murine IL-2 receptors inhibited their proliferation by supernatants of TSST-1-treated MSL, thus strongly suggesting that they contain IL-2. The concentrations of TSST-1 required for HPBL or MSL to produce IL-2 ranged between 10(-1) and 10(-4) micrograms/ml. The amount of IL-2 units/ml varied little from one experiment to another. In contrast, IL-2 production by PHA-stimulated HPBL or Con A-stimulated MSL showed great variability and dependence on mitogen concentration. T-cell depleted MSL exposed to TSST-1 produced less IL-2. Experiments with germ-free mice and TSST-1-primed mice demonstrated that IL-2 production is not related to TSST-1 antigenicity.
Polysaccharide production in Pseudomonas cepacia (1994)

The effects of glucose, osmolarity, temperature and mode of growth on exopolysaccharide production in Pseudomonas cepacia was studied in batch culture using a chemically defined growth medium. Polymer production was maximal under conditions of a 2% (w/v) glucose supplement, 0.4 M NaCl and an incubation temperature of 35 degrees C. In addition, polysaccharide composition and molecular weight varied with mode of growth. On agar culture there was a decrease in pyruvate and rhamnose content yet an increase in the amount of acetate compared to the polymer isolated from broth culture equivalents. The clinical implications of these results are discussed in relation to the potential pathogenicity of P. cepacia in cystic fibrosis patients.
Overexpression of a cytosolic chaperone to improve solubility and secretion of a recombinant IgG protein in insect cells (1998)

The secretion of heterologous IgG proteins in the baculovirus-insect cell expression system is accompanied by substantial insoluble immunoglobulin in the infected cells. The accumulation of these insoluble forms suggests a limitation in the processing and secretory pathway of the infected cells. As a result, cytosolic hsp70 chaperones, which are known to associate and prevent aggregation of polypeptides in vitro, have been coexpressed in the infected cells. The hsp70 protein coprecipitated with the immunoglobulin to indicate the formation of a specific hsp70-immunoglobulin complex in vivo. Immunoblot and pulse chase studies indicated that coexpression of hsp70 increased intracellular immunoglobulin solubility. Metabolic labeling experiments revealed that hsp70 increased secreted immunoglobulin levels after several days infection as compared to infection with control baculoviruses. Pulse chase studies indicated that hsp70 increases the solubility of immunoglobulin precursors that are then processed and assembled into the complete antibody oligomer. A comparison of the action of cytosolic hsp70 chaperone to the endoplasmic reticulum chaperone BiP suggests sequential action in which hsp70 increases the solubility of preprocessed immunoglobulin, while BiP enhances the solubility of processed immunoglobulin chains.
Mapping the conformational itinerary of β-glycosidases by X-ray crystallography (2003)

The conformational agenda harnessed by different glycosidases along the reaction pathway has been mapped by X-ray crystallography. The transition state(s) formed during the enzymic hydrolysis of glycosides features strong oxocarbenium-ion-like character involving delocalization across the C-1-O-5 bond. This demands planarity of C-5, O-5, C-1 and C-2 at or near the transition state. It is widely, but incorrectly, assumed that the transition state must be (4)H(3) (half-chair). The transition-state geometry is equally well supported, for pyranosides, by both the (4)H(3) and (3)H(4) half-chair and (2,5)B and B(2,5) boat conformations. A number of retaining beta-glycosidases acting on gluco -configured substrates have been trapped in Michaelis and covalent intermediate complexes in (1)S(3) (skew-boat) and (4)C(1) (chair) conformations, respectively, pointing to a (4)H(3)-conformed transition state. Such a (4)H(3) conformation is consistent with the tight binding of (4)E- (envelope) and (4)H(3)-conformed transition-state mimics to these enzymes and with the solution structures of compounds bearing an sp (2) hybridized anomeric centre. Recent work reveals a (1)S(5) Michaelis complex for beta-mannanases which, together with the (0)S(2) covalent intermediate, strongly implicates a B(2,5) transition state for beta-mannanases, again consistent with the solution structures of manno -configured compounds bearing an sp (2) anomeric centre. Other enzymes may use different strategies. Xylanases in family GH-11 reveal a covalent intermediate structure in a (2,5)B conformation which would also suggest a similarly shaped transition state, while (2)S(0)-conformed substrate mimics spanning the active centre of inverting cellulases from family GH-6 may also be indicative of a (2,5)B transition-state conformation. Work in other laboratories on both retaining and inverting alpha-mannosidases also suggests non-(4)H(3) transition states for these medically important enzymes. Three-dimensional structures of enzyme complexes should now be able to drive the design of transition-state mimics that are specific for given enzymes, as opposed to being generic or merely fortuitous.
A pentapeptide from type I procollagen promotes extracellular matrix production (1993)

The NH2 and COOH propieces of fibril-forming collagens are cleaved off extracellularly and have been implicated in feedback regulation of their own synthesis. Recently, we showed that a subfragment of the carboxyl-terminal propeptide of type I collagen (residues 197-241) dramatically augments extracellular matrix production in subconfluent fibroblasts. This stimulation of type I collagen, type III collagen, and fibronectin production occurred in a dose- and time-dependent manner with no effect on total protein synthesis or on the ratio of secreted proteins to cell-associated proteins (Katayama, K., Seyer, J.M., Raghow, R., and Kang, A.H. (1991) Biochemistry 30, 7097-7104). In the present report, we have extensively dissected this subfragment of the propeptide and found that the pentapeptide Lys-Thr-Thr-Lys-Ser (residues 212-216) is the minimum sequence necessary for potent stimulation of collagen and fibronectin production in a variety of mesenchymal cells. We postulate that the extracellular matrix production in fibroblasts may be subject to either positive or negative feedback regulation depending on the repertoire of specific proteases during postinflammatory tissue regeneration and fibrosis.
A nonlinear approach to control instantaneous power for single-phase grid-connected photovoltaic systems (2009)

This paper presents a novel nonlinear control algorithm to connect a single-phase distributed generation (DG) system to the utility grid using a power electronic converter. The control system receives the commands of active and reactive powers and generates an appropriate reference signal for the converter to ensure desired injection of the power to the grid. The proposed technique is based on controlling the instantaneous power and avoids double-frequency ripples which are observed in the conventional controllers. The mathematics of the control algorithm and guidelines to adjust the parameter values are presented. The method is then successfully applied to a photovoltaic (PV) system and the robustness of the proposed method is verified through different operating conditions and uncertainties. A controller based on internal model principle (IMP) is implemented and optimally designed using the LQR concept in this paper. The performance evaluation results are presented to validate the controller concept.
Radical Reactions in Organoboron Chemistry. III -Addition Reactions to Alkynylboranes as Efficient Routes to New Regio- and Stereodefined Alkenyl Diamino- and Dialkoxyboranes (1996)

Functionalized alkenyl diamino- and dialkoxyboranes were produced regio- and stereoselectively through addition of heteroatom-centered radicals to the corresponding alkynes. The synthetic utility of these reactions was illustrated by the preparation of stereodefined Z- or E-alkenylboronic esters via palladium-catalyzed cross-coupling of the stannylated derivatives.
Lipid acyl hydrolase of patatin (1984)

Patatin, the major protein of potato tubers, was copurified with lipid acyl hydrolase (LAH). The common identity of LAH and patatin was demonstrated by sodium dodecyl sulfate denaturation studies, isoelectric focusing, and the inhibition of LAH activity by patatin antiserum.
Calcium Sensing Receptor Promotes Cardiac Fibroblast Proliferation and Extracellular Matrix Secretion (2014)

Our results are the first report that CaR plays an important role in Ca(2+) signaling involved in cardiac fibrosis through the phospholipase C- inositol 3,4,5 phosphate (PLC-IP3) pathway.
Fc-mOX40L Fusion Protein Produces Complete Remission and Enhanced Survival in 2 Murine Tumor Models (2008)

OX40L is a member of the tumor necrosis factor superfamily that provides a costimulatory signal to CD4+ and CD8+ T cells while inhibiting the effects of suppressive CD4+ CD25+ regulatory T cells. Because of this dual activity, OX40L may provide significant antitumor immunity in tumor-bearing mice. To study its clinical potential, a fusion protein consisting of mOX40L linked to the C-terminus of the Fc fragment of immunoglobulin was genetically engineered. After demonstrating its potency in vitro, several assays were performed to evaluate its antitumor effect in comparison to the OX40 agonist antibody OX86. Dosing studies in Colon 26-bearing and renal cell carcinoma (RENCA)-bearing mice showed that although OX86 produced modest tumor regression, Fc-mOX40L produced complete remission in both tumor models. Survival studies confirmed these results and showed that Fc-mOX40L treatment produced lasting responses throughout the 5-month observation period. Flow cytometric analysis of treated and untreated tumors and tumor-draining lymph nodes identified a qualitative difference in the activity of Fc-mOX40L compared with OX86 treatment as evidenced by differences in lymphoid and macrophage populations. These studies reflect the profound therapeutic potential of Fc-mOX40L, which substantially exceeds the agonist antibody OX86 in ability to produce complete tumor remissions and promote long-term survival in solid tumor models.
Membrane Targeting and Stabilization of Sarcospan Is Mediated by the Sarcoglycan Subcomplex (1999)

The dystrophin-glycoprotein complex (DGC) is a multisubunit complex that spans the muscle plasma membrane and forms a link between the F-actin cytoskeleton and the extracellular matrix. The proteins of the DGC are structurally organized into distinct subcomplexes, and genetic mutations in many individual components are manifested as muscular dystrophy. We recently identified a unique tetraspan-like dystrophin-associated protein, which we have named sarcospan (SPN) for its multiple sarcolemma spanning domains (Crosbie, R.H., J. Heighway, D.P. Venzke, J.C. Lee, and K.P. Campbell. 1997. J. Biol. Chem. 272:31221-31224). To probe molecular associations of SPN within the DGC, we investigated SPN expression in normal muscle as a baseline for comparison to SPN's expression in animal models of muscular dystrophy. We show that, in addition to its sarcolemma localization, SPN is enriched at the myotendinous junction (MTJ) and neuromuscular junction (NMJ), where it is a component of both the dystrophin- and utrophin-glycoprotein complexes. We demonstrate that SPN is preferentially associated with the sarcoglycan (SG) subcomplex, and this interaction is critical for stable localization of SPN to the sarcolemma, NMJ, and MTJ. Our experiments indicate that assembly of the SG subcomplex is a prerequisite for targeting SPN to the sarcolemma. In addition, the SG- SPN subcomplex functions to stabilize alpha-dystroglycan to the muscle plasma membrane. Taken together, our data provide important information about assembly and function of the SG-SPN subcomplex.