gebhart/patrepeval huggingface dataset:
Dual effect of transforming growth factor beta on rat thyroid cells: inhibition of thyrotropin-induced proliferation and reduction of thyroid-specific differentiation markers. (1989)

Transforming growth factor beta (TGF beta) is now known to have a number of effects other than inducing phenotypic transformation of fibroblastic cells: TGF beta controls proliferation, differentiation, and other functions in many cell types. In this paper we have analyzed the action of TGF beta 1 on a system of differentiated epithelial rat thyroid cells in culture (FRTL5), which depend on the addition of thyrotropin for their growth. TGF beta 1 is able to inhibit the growth of thyroid cells by reducing cell response to thyrotropin. Moreover, in analogy to the effect produced upon other differentiated cells in culture, such as myoblasts and adipocytes, TGF beta 1 modulates the expression of FRTL5-specific thyroid markers, reducing thyroglobulin biosynthesis and the ability to concentrate the iodide.
Gene Regulatory Networks in the Evolution and Development of the Heart (2006)

The heart, an ancient organ and the first to form and function during embryogenesis, evolved by the addition of new structures and functions to a primitive pump. Heart development is controlled by an evolutionarily conserved network of transcription factors that connect signaling pathways with genes for muscle growth, patterning, and contractility. During evolution, this ancestral gene network was expanded through gene duplication and co-option of additional networks. Mutations in components of the cardiac gene network cause congenital heart disease, the most common human birth defect. The consequences of such mutations reveal the logic of organogenesis and the evolutionary origins of morphological complexity.
Rational design of nonnatural peptides as high-affinity ligands for the HLA-B*2705 human leukocyte antigen. (1995)

From the three-dimensional structure of the class I major histocompatibility complex (MHC) HLA-B*2705 protein, several nonnatural peptides were designed either to optimize the interactions of one peptide amino acid (position 3) with its HLA binding pocket (pocket D) or to simplify the T-cell receptor-binding part by substitution with organic spacers. The stability of each MHC-ligand complex was simulated by 150-ps molecular dynamics in a water environment and compared with that of the natural complexes. All peptides were synthesized and tested for binding to the class I MHC protein in an in vitro assembly assay. As predicted from the computed atomic fluctuations and buried surface areas of MHC-bound ligands, bulky hydrophobic side chains at position 3 enhance the binding of a nonameric peptide to the HLA-B27 protein. Furthermore, it was possible to simplify half of the peptide sequence (residues 4-8) by replacement with organic fragments without altering the affinity of the designed ligands for the class I MHC protein. This study constitutes an initial step toward the rational design of nonpeptide class I MHC ligands for use in the selective immunotherapy of autoimmune diseases associated with particular HLA alleles.
On the Origin of the Extra Electrochemical Capacity Displayed by MO/Li Cells at Low Potential (2002)

We report that the room temperature cycling of CoO/Li cells involving two processes, the reduction of and the growth of a polymer/gel-like film at high and low potentials, respectively, is extremely sensitive to cycling voltage ranges with the best results obtained when the cells are fully discharged. The low-voltage process is quite reversible over the 0.02 to 1.8 V range with a sustained capacity of about 150 mAh/g over a few hundred cycles. Within such a range of potential the polymer/gel-like is barely evolving while it vanishes as the oxidation potential is increased above 2 V. From the cyclic-voltammogram profiles we conclude that the origin of the low-voltage capacity is nested in the pseudocapacitive character of the in situ made polymeric/gel film. Tentative explanations based on comparisons with existing literature are made to explain such an unusual finding. © 2002 The Electrochemical Society. All rights reserved.
CAPC: A Road-Departure Prevention System (1996)

The Crewman's Associate for Path Control (CAPC) is an automatic road-departure warning system for motor vehicle drivers. This article presents the design of, and preliminary field results from, the CAPC prototype vehicle, a modified 1995 Ford Taurus SHO. The CAPC system is intended for highway drivers who are drifting off the roadway at a shallow angle of departure due to inattention, drowsiness, intoxication, or other causes. A camera senses the roadway ahead, and a suite of transducers provide measurements of vehicle motion and driver steering commands. These are used to anticipate unintended road departures and warn the driver. Warning and intervention functions for CAPC have been developed during ongoing research at the University of Michigan; the algorithms are reviewed here in the context of the prototype. The prototype hardware and software are described in detail, and preliminary experimental data from the field is presented.
Licofelone-A Novel Analgesic and Anti-Inflammatory Agent (2007)

Dual inhibitors that block both cyclooxygenase (COX) and lipoxygenase (LOX) metabolic pathways of arachidonic acid are expected to possess clinical advantages over the selective inhibitors of COX enzyme. One of the most promising compounds belonging to this category is licofelone ([2,2 -dimethyl -6-(4-chloropheny-7-phenyl-2,3-dihydro-1H-pyrrazoline-5-yl] acetic acid). Originally discovered by Merckle GmbH and developed by EuroAllaince, licofelone (IC(50) COX=0.21 microM, IC(50) 5-LOX=0.18 microM) possesses significant analgesic, anti-inflammatory, and antiasthmatic effects at doses that cause no gastrointestinal (GI) side effects. The pharmacodynamic profile of licofelone has been assessed and compared with widely used NSAIDs in different animal models. The ED(50) value of licofelone is reported to be 11.22-27.07 mg/kg, po and 39.5-55-8 mg/kg, po against carrageenan-induced paw oedema and Randal Selitto hyperalgesic assay in rats, respectively. Licofelone showed analgesic effect (ED(50) = 31.33 mg/kg) against acetic acid-induced writhing in mice. Licofelone has long duration of action and more effective than indomethacin and zileuton with ED(50) values of 2.92 mg/kg, po and 36.77 mg/kg, po, in the mechanical hyperalgesia and cold allodynia testing, respectively, against rat model of incisional pain. Licofelone significantly ameliorated indomethacin-induced gastric ulceration, neutrophil adhesion in mesentery, and lipid peroxides in rat gastric mucosa. Also, licofelone reversed the altered vascular permeability, morphological changes, and prevented NSAIDs-related increase in leukotriene levels in gastric mucosa. The preclinical studies have shown that licofelone not only has convincing pharmacodynamic effect but also it is well tolerated. It is currently under clinical evaluation in osteoarthritis (OA), the most common form of arthritis. The present review describes pharmacological and clinical development of licofelone as a dual inhibitor.
Copper Complexes of Nitrogen-Anchored Tripodal N-Heterocyclic Carbene Ligands (2003)

Incorporation of a nitrogen functionality into a tripodal N-heterocyclic carbene ligand system affords the first N-anchored tetradentate tris-carbene ligands TIMEN(R) (R = Me (5a), t-Bu (5b), Bz (5c)). Treatment of the methyl derivatized [H(3)TIMEN(Me)](PF(6))(3) imidazolium salt (H(3)5a) with silver oxide yields the silver complex [(TIMEN(Me))(2)Ag(3)](PF(6))(3) (9), which, in a ligand transfer reaction, reacts with copper(I) bromide to give the trinuclear copper(I) complex [(TIMEN(Me))(2)Cu(3)](PF(6))(3) (10). Deprotonation of the tert-butyl and benzyl derivatives [H(3)TIMEN(t-Bu)](PF(6))(3) and [H(3)TIMEN(Bz)](PF(6))(3) yields the free tris-carbenes TIMEN(t-Bu) (5b) and TIMEN(Bz) (5c), which react readily with copper(I) salts to give mononuclear complexes [(TIMEN(t-Bu))Cu](PF(6)) (11b) and [(TIMEN(Bz))Cu]Br (11c). The solid-state structures of 10, 11b, and 11c were determined by single-crystal X-ray diffraction. While the TIMEN(Me) ligand yields trinuclear complex 10, with both T-shaped three-coordinate and linear two-coordinate copper(I) centers, the TIMEN(t-Bu) and TIMEN(Bz) ligands induce mononuclear complexes 11b and 11c, rendering the cuprous ion in a trigonal planar ligand environment of three carbenoid carbon centers and an additional, weak axial nitrogen interaction. Complexes 11b and 11c exhibit reversible one-electron redox events at half-wave potentials of 110 and -100 mV vs Fc/Fc(+), respectively, indicating sufficient electronic and structural flexibility of both TIMEN(R) ligands (R = t-Bu, Bz) to stabilize copper(I) and copper(II) oxidation states. Accordingly, a copper(II) NHC complex, [(TIMEN(Bz))Cu](OTf)(2) (12), was synthesized. Paramagnetic complex 12 was characterized by elemental analysis, EPR spectroscopy, and SQUID magnetization measurements.
FcγR requirements leading to successful immunotherapy (2015)

Monoclonal antibody (mAb) immunotherapy is currently experiencing an unprecedented amount of success, delivering blockbuster sales for the pharmaceutical industry. Having experienced several false dawns and overcoming technical issues which limited progress, we are now entering a golden period where mAbs are becoming a mainstay of treatment regimes for diseases ranging from cancer to autoimmunity. In this review, we discuss how these mAbs are most likely working and focus in particular on the key receptors that they interact with to precipitate their therapeutic effects. Although their targets may vary, their engagement with Fcγ receptors (FcγRs) on numerous immune effector cells is almost universal, and here we review their roles in delivering successful immunotherapy.
A strategy for rapid sequencing of heparan sulfate and heparin saccharides (1999)

Sulfated glycosaminoglycans (GAGs) are linear polysaccharides of repeating disaccharide sequences on which are superimposed highly complex and variable patterns of sulfation, especially in heparan sulfate (HS). HS and the structurally related heparin exert important biological functions, primarily by interacting with proteins and regulating their activities. Evidence is accumulating that these interactions depend on specific saccharide sequences, but the lack of simple, direct techniques for sequencing GAG saccharides has been a major obstacle to progress. We describe how HS and heparin saccharides can be sequenced rapidly by using an integrated strategy with chemical and enzymic steps. Attachment of a reducing-end fluorescent tag establishes a reading frame. Partial selective chemical cleavage at internal N-sulfoglucosamine residues with nitrous acid then creates a set of fragments of defined sizes. Subsequent digestion of these fragments with combinations of exosulfatases and exoglycosidases permits the selective removal of specific sulfates and monosaccharides from their nonreducing ends. PAGE of the products yields a pattern of fluorescent bands from which the saccharide sequence can be read directly. Data are presented on sequencing of heparin tetrasaccharides and hexasaccharides of known structure; these data show the accuracy and versatility of this sequencing strategy. Data also are presented on the application of the strategy to the sequencing of an HS decasaccharide of unknown structure. Application and further development of this sequencing strategy, called integral glycan sequencing, will accelerate progress in defining the structure-activity relationships of these complex GAGs and lead to important insights into their biological functions.
Single Nucleotide Polymorphisms in SULT1A1 and SULT1A2 in a Korean Population (2013)

SULT1A1 and SULT1A2 are encoded on the same chromatid, and exhibit a 96% amino acid similarity. To screen for genetic variants in these two closely related genes, SULT1A1 and SULT1A2 were directly sequenced in 50 healthy Koreans. A total of 30 variations were identified in SULT1A1: eight in exons, thirteen in introns, and nine in the 5'-untranslated region. With regard to SULT1A2, 21 variants were identified, comprising seven in exons, five in introns, and nine in the 5'-untranslated region. Among these 51 variations, one in SULT1A1 and eight in SULT1A2 were previously unidentified, which include three coding variants (SULT1A2 R37Q, 110G>A; SULT1A2 G50S, 148G>A; SULT1A2 F286L, 3819C>A) and one null allele (SULT1A2 E217Stop, 3542G>T). Two LD blocks, major haplotype structures, and 7 haplotype-tagging SNPs were determined together for SULT1A1 and SULT1A2 as a single set. Frequencies of common functional variants were compared among ethnic groups. Since these two SULT enzymes are on the same chromatid in a parallel direction with overlapping substrate specificities, a combined analysis using LD and haplotype-tagging single-nucleotide polymorphisms (SNPs) will facilitate understanding of the variations in the sulfation reactions of a wide range of substrates, as compared with analysis of individual genes.
Planning for landing site selection in the aerial supply delivery (2011)

In the aerial supply delivery problem, an unmanned aircraft needs to deliver supplies as close as possible to the desired location. This involves choosing, flying to, sensing, and landing at a safe landing site that is most accessible from the goal. The problem is often complicated by the fact that the availability of these landing sites may be unknown before the mission begins. Therefore, the aircraft needs to compute a sequence of actions that will minimize the expected value of the objective function. The problem of computing this sequence corresponds to planning under uncertainty in the environment. In this paper, we show how it can be solved efficiently via a recently developed probabilistic planning framework, called Probabilistic Planning with Clear Preferences (PPCP). We show that the problem satisfies the Clear Preferences assumption required by PPCP, and therefore all the theoretical guarantees continue to hold. The experimental results in simulation demonstrate that our approach can solve large-scale problems in realtime while experiments on our custom quad-rotor helicopter provide a proof of concept for the planner.
Alternative splicing and differential gene expression in colon cancer detected by a whole genome exon array (2006)

Differential expression of high confidence transcripts correlated extremely well with known cancer genes and pathways, suggesting that the more speculative transcripts, largely based solely on computational prediction and mostly with no previous annotation, might be novel targets in colon cancer. Five of the identified splicing events affect mediators of cytoskeletal organization (ACTN1, VCL, CALD1, CTTN, TPM1), two affect extracellular matrix proteins (FN1, COL6A3) and another participates in integrin signaling (SLC3A2). Altogether they form a pattern of colon-cancer specific alterations that may particularly impact cell motility.
Emerging Transporters of Clinical Importance: An Update From the International Transporter Consortium (2013)

The International Transporter Consortium (ITC) has recently described seven transporters of particular relevance to drug development. Based on the second ITC transporter workshop in 2012, we have identified additional transporters of emerging importance in pharmacokinetics, interference of drugs with transport of endogenous compounds, and drug-drug interactions (DDIs) in humans. The multidrug and toxin extrusion proteins (MATEs, gene symbol SLC47A) mediate excretion of organic cations into bile and urine. MATEs are important in renal DDIs. Multidrug resistance proteins (MRPs or ABCCs) are drug and conjugate efflux pumps, and impaired activity of MRP2 results in conjugated hyperbilirubinemia. The bile salt export pump (BSEP or ABCB11) prevents accumulation of toxic bile salt concentrations in hepatocytes, and BSEP inhibition or deficiency may cause cholestasis and liver injury. In addition, examples are presented on the roles of nucleoside and peptide transporters in drug targeting and disposition.
Structurally Dependent Redox Property of Ribonucleotide Reductase Subunit p53R2 (2006)

p53R2 is a newly identified small subunit of ribonucleotide reductase (RR) and plays a key role in supplying precursors for DNA repair in a p53-dependent manner. Currently, we are studying the redox property, structure, and function of p53R2. In cell-free systems, p53R2 did not oxidize a reactive oxygen species (ROS) indicator carboxy-H2DCFDA, but another class I RR small subunit, hRRM2, did. Further studies showed that purified recombinant p53R2 protein has catalase activity, which breaks down H2O2. Overexpression of p53R2 reduced intracellular ROS and protected the mitochondrial membrane potential against oxidative stress, whereas overexpression of hRRM2 did not and resulted in a collapse of mitochondrial membrane potential. In a site-directed mutagenesis study, antioxidant activity was abrogated in p53R2 mutants Y331F, Y285F, Y49F, and Y241H, but not Y164F or Y164C. The fluorescence intensity in mutants oxidizing carboxy-H2DCFDA, in order from highest to lowest, was Y331F > Y285F > Y49F > Y241H > wild-type p53R2. This indicates that Y331, Y285, Y49, and Y241 in p53R2 are critical residues involved in scavenging ROS. Of interest, the ability to oxidize carboxy-H2DCFDA indicated by fluorescence intensity was negatively correlated with RR activity from wild-type p53R2, mutants Y331F, Y285F, and Y49F. Our findings suggest that p53R2 may play a key role in defending oxidative stress by scavenging ROS, and this antioxidant property is also important for its fundamental enzymatic activity.
An immunodominant antigen of Brugia malayi is an asparaginyl‐tRNA synthetase (1995)

Lymphatic filariasis is caused by infection with the filarial nematodes Brugia malayi, Brugia timori, Wuchereria bancrofti and Onchocerca volvulus which collectively infect about 200 million persons throughout the world. Protein sequence homology analysis of a major nematode antigen suggested that it was a class II aminoacyl-tRNA synthetase. The overproduction, purification and verification that the major B. malayi antigen is an asparaginyl-tRNA synthetase is described.
The role of endovascular grafting technique in the treatment of infrarenal abdominal aortic aneurysm (1995)

The objective of this report is to review the author's initial clinical experience with screening a population of patients with abdominal aortic aneurysm, to describe the selection criteria for endovascular repair and to report results from a single institution. The technique of transfemoral repair of abdominal aortic aneurysm uses the endovascular graft system that is currently in a Food and Drugs Administration approved protocol for investigation in the United States. Some 69 patients with abdominal aortic aneurysm were screened in order to find ten suitable candidates. Ten implantations were carried out, of which eight were successful and two required conversion to conventional open aneurysm repair without complication. There were no deaths or complications. It is concluded that tube graft repair by the transfemoral route is feasible and applicable to approximately one patient in seven. The availability of a bifurcated graft will enhance the percentage of aneurysm patients treatable by this technique. Long-term results, at this time, are unknown.
Clinicopathologic evaluation of immunohistochemical E-cadherin expression in human gastric carcinomas (1995)

The decreased E-cadherin expression correlates with dedifferentiation, infiltrative tumor growth, distant metastasis, and poor survival for patients with gastric carcinoma. Thus, immunohistochemical study of E-cadherin may have clinicopathologic value for patients with gastric carcinoma.
Chronic Exposure to Methylated Arsenicals Stimulates Arsenic Excretion Pathways and Induces Arsenic Tolerance in Rat Liver Cells (2006)

Although inorganic arsenicals are toxic and carcinogenic in humans, inorganic arsenite has recently emerged as a highly effective chemotherapeutic agent for acute promyelocytic leukemia (APL). Inorganic arsenicals are enzymatically methylated to monomethylarsonic acid (MMAs V ), dimethylarsinic acid (DMAs V ), and trimethylarsine oxide (TMAs V O) in mammals. We examined the effects of chronic exposure to methylated arsenicals on arsenic tolerance by using rat normal liver TRL 1215 cells. TRL 1215 cells were exposed for 20 weeks to MMAs V , DMAs V , or TMAs V O at levels that produced submicromolar cellular concentrations of arsenic. On chronic exposure to these methylated arsenicals, the cells acquired tolerance to acute arsenic cytolethality. Cellular arsenic uptake was reduced in these cells compared to passage-matched control cells. The long-term arsenic exposure increased glutathione S-transferase (GST) activity and cellular glutathione (GSH) levels. Glutathione S-transferase, multidrug resistance-associated proteins (Mrps; efflux transporters encoded by Mrp genes), and P-glycoprotein [P-gp; efflux transporter encoded by multidrug resistance gene (MDR)] had also increased in these cells at the transcript and protein levels. The depletion of cellular GSH and the inhibition of Mrps and P-gp functions increased cellular arsenic uptake and reduced arsenic tolerance in these cells. These results indicate that chronic exposure to methylated arsenicals induces a generalized arsenic tolerance that is caused by increased arsenic excretion. Because accumulation of methylated arsenicals may occur in patients with chronic arsenic poisoning and arsenictreated APL patients, this study may provide important information regarding chronic arsenic poisoning and the latent risk of developing multidrug resistance in APL therapy using inorganic arsenite.
The Commensal Bacterium Faecalibacterium prausnitzii Is Protective in DNBS-induced Chronic Moderate and Severe Colitis Models (2014)

We show, for the first time, protective effects of both F. prausnitzii and its SN during both the period of recovery from chronic colitis and colitis reactivation. These results provide further evidence that F. prausnitzii is an anti-inflammatory bacterium with therapeutic potential for patients with inflammatory bowel disease.
Sorption of Butane on Carbon Multiwall Nanotubes at Room Temperature (2001)

Carbon multiwall nanotubes (MWNTs) can be used for separation processes if the mechanisms for sorption and desorption are known. This study describes the sorption mechanism for butane on MWNTs at room temperature and relative pressures ranging from 0 to 0.9. Previous workers have studied the sorption of hydrogen,1-3 neon,4-6 helium,6 nitrogen,7 and methane8-10 on nanotubes for storage purposes. Molecular dynamic simulations have been done to show that carbon nanotubes can be used as a separation tool to selectively separate isomers of monomethylnaphthalenes.11 Experiments have established that refrigerant mixtures, such as CHF2CF3 and CClF2CF3, can be successfully separated by using carbon nanotubes.12 Previous work in this lab has shown that carbon MWNTs can separate butane from methane when both are at low levels in a gas flow. This experimental result is in agreement with recent molecular dynamic simulations made for sorption of alkane mixtures on different types of single-walled carbon nanotubes (SWNTs).13 Morphology characterization of the MWNTs has been used to interpret the sorption data. Most of the butane was sorbed to the external surface of the MWNTs and only a small fraction of the butane condensed in the pores. No hysteresis was observed between sorption and desorption experiments. The weight fraction of butane sorbed depended inversely on the diameter of the MWNTs and was 5.3 wt % for one of the samples studied. Adsorption isotherms were modeled using a modified BET equation with coefficients consistent with the known morphology. Fixed bed adsorption systems that could use the exterior surface of MWNTs might be attractive for separations, particularly if electrical heating could be used for rapid desorption of sorbed molecules.