gebhart/patrepeval huggingface dataset:
Atrial natriuretic peptide promotes cardiomyocyte survival by cGMP-dependent nuclear accumulation of zyxin and Akt (2005)

This study delineates a mechanism for antiapoptotic signaling initiated by atrial natriuretic peptide (ANP) stimulation leading to elevation of cGMP levels and subsequent nuclear accumulation of Akt kinase associated with zyxin, a cytoskeletal LIM-domain protein. Nuclear targeting of zyxin induces resistance to cell death coincident with nuclear accumulation of activated Akt. Nuclear translocation of zyxin triggered by cGMP also promotes nuclear Akt accumulation. Additional supportive evidence for nuclear accumulation of zyxin-enhancing cardiomyocyte survival includes the following: (a) promotion of zyxin nuclear localization by cardioprotective stimuli; (b) zyxin association with phospho-Akt473 induced by cardioprotective stimuli; and (c) recruitment of zyxin to the nucleus by activated nuclear-targeted Akt as well as recruitment of Akt by nuclear-targeted zyxin. Nuclear accumulation of zyxin requires both Akt activation and nuclear localization. Potentiation of cell survival is sensitive to stimulation intensity with high-level induction by ANP or cGMP signaling leading to apoptotic cell death rather than enhancing resistance to apoptotic stimuli. Myocardial nuclear accumulation of zyxin and Akt responds similarly in vivo following treatment of mice with ANP or cGMP. Thus, zyxin and activated Akt participate in a cGMP-dependent signaling cascade leading from ANP receptors to nuclear accumulation of both molecules. Nuclear accumulation of zyxin and activated Akt may represent a fundamental mechanism that facilitates nuclear-signal transduction and potentiates cell survival.
A Novel Candidate Tumour Suppressor Locus at 9q32–33 in Bladder Cancer: Localization of the Candidate Region Within a Single 840 kb YAC (1997)

Loss of heterozygosity (LOH) on chromosome 9q is the most frequent genetic alteration in transitional cell carcinoma (TCC) of the bladder, implicating the presence of a tumour suppressor gene or genes on 9q. To define the location of a tumour suppressor locus on 9q in TCC, we screened 156 TCCs of the bladder and upper urinary tract by detailed deletion mapping using 31 microsatellite markers on 9q. Partial deletions of 9q were found in 10 TCCs (6%), and LOH at all informative loci on 9q was found in 77 TCCs (49%). In five low grade superficial bladder tumours, the partial deletion was localized to D9S195 located at 9q32-33, with retention of heterozygosity at all other informative loci including D9S103, D9S258, D9S275 and GSN. We constructed a yeast artificial chromosome (YAC) contig covering the deleted region in these five tumours and placed another four unmapped microsatellite markers on this contig map. Using these markers, we further defined the common deleted region to the interval between D9S1848 and AFMA239XA9. The region is covered by a single YAC (852e11), whose size is estimated to be 840 kb. Our data should expedite further fine mapping and identification of the candidate tumour suppressor gene at 9q32-33.
Rapid Identification of Emerging Infectious Agents Using PCR and Electrospray Ionization Mass Spectrometry (2007)

Newly emergent infectious diseases are a global public health problem. The population dense regions of Southeast Asia are the epicenter of many emerging diseases, as evidenced by the outbreak of Nipah, SARS, avian influenza (H5N1), Dengue, and enterovirus 71 in this region in the past decade. Rapid identification, epidemiologic surveillance, and mitigation of transmission are major challenges in ensuring public health safety. Here we describe a powerful new approach for infectious disease surveillance that is based on polymerase chain reaction (PCR) to amplify nucleic acid targets from large groupings of organisms, electrospray ionization mass spectrometry (ESI-MS) for accurate mass measurements of the PCR products, and base composition signature analysis to identify organisms in a sample. This approach is capable of automated analysis of more than 1,500 PCR reactions a day. It is applicable to the surveillance of bacterial, viral, fungal, or protozoal pathogens and will facilitate rapid characterization of known and emerging pathogens.
Regulation of Akt and Wnt signaling by the group II metabotropic glutamate receptor antagonist LY341495 and agonist LY379268 (2011)

Metabotropic glutamate receptors 2/3 (mGlu(2/3)) have been implicated in schizophrenia and as a novel treatment target for schizophrenia. The current study examined whether mGlu(2/3) regulates Akt (protein kinase B) and Wnt (Wingless/Int-1) signaling, two cascades associated with schizophrenia and modified by antipsychotics. Western blotting revealed increases in phosphorylated Akt (pAkt) and phosphorylated glycogen synthase kinase-3 (pGSK-3) following acute and repeated treatment of LY379268 (mGlu(2/3) agonist), whereas increases in dishevelled-2 (Dvl-2), dishevelled-3 (Dvl-3), GSK-3 and β-catenin were only observed following repeated treatment. LY341495 (mGlu(2/3) antagonist) induced the opposite response compared with LY379268. Co-immunoprecipitation experiments showed an association between the mGlu(2/3) complex and Dvl-2 providing a possible mechanism to explain how the mGlu(2/3) can mediate changes in Wnt signaling. However, there was no association between the mGlu(2/3) complex and Akt suggesting that changes in Akt signaling following LY341495 and LY379268 treatments may not be directly mediated by the mGlu(2/3) . Finally, an increase in locomotor activity induced by LY341495 treatment correlated with increased pAkt and pGSK-3 levels and was attenuated by the administration of the GSK-3 inhibitor, SB216763. Overall, the results suggest that mGlu(2/3) regulates Akt and Wnt signaling and LY379268 treatment has overlapping effects with D(2) dopamine receptor antagonists (antipsychotic drugs).
The PI3K p110δ Regulates Expression of CD38 on Regulatory T Cells (2011)

The PI3K pathway has emerged as a key regulator of regulatory T cell (Treg) development and homeostasis and is required for full Treg-mediated suppression. To identify new genes involved in PI3K-dependent suppression, we compared the transcriptome of WT and p110δ(D910A) Tregs. Among the genes that were differentially expressed was the gene for the transmembrane cyclic ADP ribose hydrolase CD38. Here we show that CD38 is expressed mainly by a subset of Foxp3(+)CD25(+)CD4(+) T cells originating in the thymus and on Tregs in the spleen. CD38(high) WT Tregs showed superior suppressive activity to CD38(low) Tregs, which failed to upregulate CD73, a surface protein which is important for suppression. However, Tregs from heterozygous CD38(+/-) mice were unimpaired despite lower levels of CD38 expression. Therefore, CD38 can be used as a marker for Tregs with high suppressive activity and the impaired Treg function in p110δ(D910A) mice can in part be explained by the failure of CD38(high) cells to develop.
Can rheumatoid arthritis responsiveness to methotrexate and biologics be predicted? (2009)

This review briefly recapitulates the existing markers predictive of RA responsiveness to treatment, focusing on MTX alone or combined with a biologic. In addition to the demographic and clinical factors, an update is provided of the predictive biomarkers identified by large-scale gene and protein analyses that generated new insights into the ability of high-throughput analysis of biological systems to select new potential indicators. Among the large-scale analysis tools now available, pharmacogenetics and pharmacogenomics (including transcriptomic and proteomic approaches) have been shown to provide such new putative biomarkers of therapeutic responses.
The Hepatic Sinusoidal Endothelial Cell (2007)

The hepatic sinusoidal endothelial cell (EC) was not recognized as a highly differentiated cell type until the sinusoid was examined by perfusion fixation combined with electron microscopy, as described in Wisse's seminal papers in 1970 and 1972 (1,2). Our understanding of hepatic sinusoidal EC characteristics took an additional step forward with the first description of a method to isolate a highly pure population of these cells (3,4).
Cancer multidrug resistance: a review of recent drug discovery research. (2002)

Conventional cancer chemotherapy is seriously limited by tumor cells exhibiting multidrug resistance (MDR), caused by changes in the level or activity of membrane transporters that mediate energy-dependent drug efflux and of other proteins that affect drug metabolism and/or drug action. Many inhibitors of MDR transporters have been identified and some are undergoing clinical trials, but currently none are in clinical use. Here we briefly review the status of MDR drugs, outline novel approaches designed to suppress or circumvent MDR mechanisms and discuss the future of MDR therapy in oncology.
A TEL-JAK2 Fusion Protein with Constitutive Kinase Activity in Human Leukemia (1997)

The Janus family of tyrosine kinases (JAK) plays an essential role in development and in coupling cytokine receptors to downstream intracellular signaling events. A t(9;12)(p24;p13) chromosomal translocation in a T cell childhood acute lymphoblastic leukemia patient was characterized and shown to fuse the 3' portion of JAK2 to the 5' region of TEL, a gene encoding a member of the ETS transcription factor family. The TEL-JAK2 fusion protein includes the catalytic domain of JAK2 and the TEL-specific oligomerization domain. TEL-induced oligomerization of TEL-JAK2 resulted in the constitutive activation of its tyrosine kinase activity and conferred cytokine-independent proliferation to the interleukin-3-dependent Ba/F3 hematopoietic cell line.
Cloning of the gene and amino acid sequence for glucose 6-phosphate dehydrogenase from Leuconostoc mesenteroides (1991)

Amino acid sequencing of glucose 6-phosphate dehydrogenase (Glc6PD) from Leuconostoc mesenteroides yielded sequence for over 75% of the protein. Two oligonucleotides based on the amino acid sequence were used to isolate a partial Glc6PD gene clone (pLmz delta N65), from a pUC9 library, containing 85% of the coding sequence and the 3'-untranslated DNA, but lacking the 5'-noncoding DNA sequence and the portion of the gene encoding the 65 N-terminal amino acids. Attempts to obtain a full-length clone from lambda libraries were unsuccessful, possibly due to restriction of L. mesenteroides DNA by Escherichia coli host cells. The 5'-untranslated DNA was amplified by the polymerase chain reaction and partially sequenced. To obtain unmodified DNA for the gene, oligonucleotides corresponding to the 5'- and 3'-noncoding sequences were used to amplify the gene by the polymerase chain reaction, and a 1.8-kilobase pair fragment was isolated and cloned into pUC19. The recombinant plasmid, pLmz, contains the entire Glc6PD gene and expresses the gene in E. coli. pLmz was sequenced showing that the enzyme consists of 485 amino acids. L. mesenteroides Glc6PD is 31% identical to the human enzyme.
Effects of noise on quantum error correction algorithms (1997)

It has recently been shown that there are efficient algorithms for quantum computers to solve certain problems, such as prime factorization, which are intractable to date on classical computers. The chances for practical implementation, however, are limited by decoherence, in which the effect of an external environment causes random errors in the quantum calculation. To combat this problem, quantum error correction schemes have been proposed, in which a single quantum bit (qubit) is ``encoded'' as a state of some larger number of qubits, chosen to resist particular types of errors. Most such schemes are vulnerable, however, to errors in the encoding and decoding itself. We examine two such schemes, in which a single qubit is encoded in a state of $n$ qubits while subject to dephasing or to arbitrary isotropic noise. Using both analytical and numerical calculations, we argue that error correction remains beneficial in the presence of weak noise, and that there is an optimal time between error correction steps, determined by the strength of the interaction with the environment and the parameters set by the encoding.
Existence of distinct tyrosylprotein sulfotransferase genes: Molecular characterization of tyrosylprotein sulfotransferase-2 (1998)

Tyrosylprotein sulfotransferase (TPST) is a 54- to 50-kDa integral membrane glycoprotein of the trans-Golgi network found in essentially all tissues investigated, catalyzing the tyrosine O-sulfation of soluble and membrane proteins passing through this compartment. Here we describe (i) an approach to identify the TPST protein, referred to as MSC (modification after substrate crosslinking) labeling, which is based on the crosslinking of a substrate peptide to TPST followed by intramolecular [35S]sulfate transfer from the cosubstrate 3'-phosphoadenosine 5'-phosphosulfate (PAPS); and (ii) the molecular characterization of a human TPST, referred to as TPST-2, whose sequence is distinct from that reported [TPST-1; Ouyang, Y.-B., Lane, W. S. & Moore, K. L. (1998) Proc. Natl. Acad. Sci. USA 95, 2896-2901] while this study was in progress. Human TPST-2 is a type II transmembrane protein of 377 aa residues that is encoded by a ubiquitously expressed 1.9-kb mRNA originating from seven exons of a gene located on chromosome 22 (22q12.1). A 304-residue segment in the luminal domain of TPST-2 shows 75% amino acid identity to the corresponding segment of TPST-1, including conservation of the residues implicated in the binding of PAPS. Expression of the TPST-2 cDNA in CHO cells resulted in an approximately 13-fold increase in both TPST protein, as determined by MSC labeling, and TPST activity. A predicted 359-residue type II transmembrane protein in Caenorhabditis elegans with 45% amino acid identity to TPST-2 in a 257-residue segment of the luminal domain points to the evolutionary conservation of the TPST protein family.
Effect of Feed Additives on Production and Quality of Bile Powder Obtained with Tubeless Method from Black Bear (2002)

Nine black bears with similar live weight and yield of bile powder were randomly divided into 3 groups of 3 and fed a basal diet (control group), basal diet supplemented with 0.5% green feed additive (experimental group Ⅰ) and 0.5% German made feed additive PINA T (experimental group Ⅱ). The results showed that bile production, dry matter content of bile and bile powder production for group Ⅰ were significantly higher than those for control group ( P 0.01 ), while there were no significant differences between group Ⅱ and control group ( P 0.05). Crude fat digestibility for group Ⅰ and Ⅱ increased 2.15% and 44.92% compared with control group. Data of bile powder analysis showed that there were no significant differences in UDCA between groups ( P 0.05), while the pick areas of UDCA and CDCA in HPLC chromatogram for groups Ⅰ and Ⅱ increased 29.65% and 14.62%; and 34.50% and 7.09% compared with control group, respectively. Amino acid content of different groups did not differ significantly.
Human Computer Giraffe Interaction: HCI in the Field (1998)

This paper presents some findings and proposals for new research that have arisen from our work on the ''Mobile Computing in Fieldwork Environments'' project at the University of Kent at Canterbury [1]: a project that is sponsored by JTAP (JISC Technology Applications Programme) [2]. Our main research interest is in the development of novel software tools for the mobile fieldworker that exploit existing handheld computing and sensor technology. The work described in this paper concentrates on examining the special needs and environment of the fieldworker, reflecting on the HCI features required for a successful PDA (Personal Digital Assistant) for use in the field.
A recombinant single-chain immunotoxin composed of anti-Tac variable regions and a truncated diphtheria toxin. (1990)

To kill human or primate cells expressing the p55 subunit of the interleukin 2 receptor, we have constructed a single-chain immunotoxin. DNA sequences encoding the first 388 amino acids of diphtheria toxin (DT) were fused to DNA elements encoding the antigen-binding portion (variable region or Fv) of the anti-Tac monoclonal antibody. The antigen-binding portion consists of 116 amino acids of the heavy-chain variable region connected by a 15-amino acid linker to 106 amino acids of the variable region of the light chain. The single-chain immunotoxin DT388-anti-Tac(Fv) was expressed in Escherichia coli and found in inclusion bodies. The monomeric form was then purified to near homogeneity with a high yield (3-5 mg/liter). Monomeric DT388-anti-Tac(Fv) was highly cytotoxic to cell lines bearing the p55 subunit of the human interleukin 2 receptor but not to cells without this subunit. DT388-anti-Tac(Fv) was also very effective in killing proliferating human T cells produced in a mixed leukocyte reaction.
Improved efficiencies in light emitting diodes made with CdSe(CdS) core/shell type nanocrystals and a semiconducting polymer (1997)

We report experiments on bilayer light emitting diodes made with organically capped CdSe(CdS) core/shell type semiconductor nanocrystals and an electroluminescent (EL) semiconducting polymer [poly(p-phenylenevinylene) or PPV]. The devices emit from red to green with external quantum efficiencies of up to 0.22% at brightnesses of 600 cd/m2 and current densities of 1 A/cm2. They have operating voltages as low as 4 V and lifetimes under constant current flow of hundreds of hours. Most of these numbers are significant improvements over similar devices made with CdSe nanocrystals. The devices show either nanocrystal-only EL or a combination of nanocrystal and PPV EL, depending on nanocrystal layer thickness. The nanocrystal EL is dependent on nanocrystal size. Some devices show a voltage dependent spectral output. The spectral output is consistent with a field dependent electron range in the nanocrystal layer limited by carrier trapping.
Nickel(ii) pincer complexes demonstrate that the remote substituent controls catalytic carbon dioxide reduction (2018)

The first example of a CNC pincer ligand with a central pyridinol ligand is reported in a nickel(ii) complex. This metal complex can be protonated or deprotonated reversibly in situ to switch on or off the photocatalytic performance towards CO2 reduction. The O- substituent appears essential for catalysis.
Reversible self-assembly and directed assembly of DNA-linked micrometer-sized colloids (2005)

We present a technique for the directed assembly and self-assembly of micrometer-scale structures based on the control of specific DNA linkages between colloidal particles. The use of DNA links combined with polymer brushes provides an effective way to regulate the range and magnitude of addressable forces between pairs (and further combinations) of different particles. We demonstrate that the autoassembly of alternate microbeads as well as their directed assembly, by using laser tweezers, is reversible. The key to reversibility is preventing the particles from falling into their van der Waals well at close distances. This goal is achieved by the use of adsorbed polymers that limit the number of DNA bridges to one to three between adjacent particles.
Vedolizumab as a Novel Treatment for Refractory Collagenous Colitis: A Case Report (2018)

Cushing, Kelly C MD; Mino-Kenudson, Mari MD, PhD; Garber, John MD; Lochhead, Paul MBCh, PhD; Khalili, Hamed MD, MPH Author Information
Synthesis and antimalarial effects of 5,6‐dichloro‐2‐[(4‐||4‐(diethylamino)‐i‐methylbutyl] amino||‐6‐methyl‐2‐pyrirnidinyl)amino] benzimidazole and related benzimidazoles and lH‐imidazo[4,5‐b] pyridines (1973)

Abstract A group of fifty‐five 2‐[(4‐11[(dialkylamino)alkyI]amino11‐6‐methyl‐2‐pyrimidinyl)amino]‐benzimidazoles (VII) was synthesized in 3‐88% yield by the condensation of the requisite 2‐[(2‐benzimidazolyl)amino]‐4‐chloro‐6‐methylpyrimidine (VI) with the appropriate polyamine in ethanol‐hydrochloric acid or neat with excess amine containing potassium iodide. The 2‐[(2‐benzimidazolyl)amino]‐6‐methyl‐4‐pyrirnidinol precursors (V), obtained in 11‐51% yield by cyclization of 2‐(cyanoamino)‐4‐hydroxy‐6‐methylpyrimidine with a suitably substituted o ‐phenylenediamine, were chlorinated with phosphorus oxychloride to give the intermediate 2‐[(2‐benzimidazolyl)amino]‐4‐chloro‐6‐rnethylpyrimidines (VI) (27‐99%). Oxidation of 5,6‐dichloro‐2‐[(4‐11[4‐(diethylamino)‐l‐methylbutyl] amino 11‐6‐methyl‐2‐pyrimidinyl) amino ]benzimidazole ( 29 ) with m ‐chloroperbenzoic acid gave the distal N 4 '‐oxide ( 31 ) (19%). Fusion of 2,3‐uiaminopyridine with 2‐(cyanoamino)‐4‐hydroxy‐6‐methylpyrimidine provided 2‐[(4‐hydroxy‐6‐tnethyl‐2‐pyrimidinyl)amino]‐l H ‐imitlazo[4,5‐ b ]pyrimidine (VIII) (30%), which upon chlori‐nation with phosphorus oxychloride (63%) followed by amination with i N, N ‐diethylethylene‐diamine afforded 2‐(4‐11[2‐(diethylamino)ethyl] amino 11‐6‐methyl‐2‐pyrimidinyl)‐l H ‐imidazo [4,5‐ b ]pyridine (X) (8%). Thirty‐eight of the novel 2‐[(4‐amino‐6‐methyl‐2‐pyrimidinyl)amino]‐benzimidazoles possessed “curative” activity against Plasmodium berghei at single subcutaneous doses ranging from 20.640 mg./kg. Orally, thirty‐one compounds exhibited suppressive activity against P. berghei comparable with or superior to the reference drugs 1‐( p ‐chlorophenyl)‐3‐(4‐11[2‐(diethylarnino)ethyl]amino 11‐6‐methyl‐2‐pyrimidinyl)guanidine (I) and quinine hydrochloride, while twelve of them were 5 to 28 times as potent as I and quinine hydrochloride. Eight compounds also displayed strong suppressive activity against P. gallinaceum in chicks. 5,6‐Dichloro‐2‐[(4‐112‐(diethylamino)ethyl]amino11‐6‐methyl‐2‐pyrimidinyl] benzimidazole (18) showed marked activity against a cycloguanil‐resistant line of P. berghei , and the most promising member of the series, namely 5,6‐dichloro‐2‐[(4‐11[4‐(diethylamino)‐l‐methylbutyl]amino11‐6‐methyl‐2‐pyrimidinyl)amino]benzimidazole ( 29 ) (Q = 28), was designated for preclinical toxico‐logical studies and clinical trial. Structure‐activity relationships are discussed.
A knob-associated tandem repeat in maize capable of forming fold-back DNA segments: Are chromosome knobs megatransposons? (1998)

A class of tandemly repeated DNA sequences (TR-1) of 350-bp unit length was isolated from the knob DNA of chromosome 9 of Zea mays L. Comparative fluorescence in situ hybridization revealed that TR-1 elements are also present in cytologically detectable knobs on other maize chromosomes in different proportions relative to the previously described 180-bp repeats. At least one knob on chromosome 4 is composed predominantly of the TR-1 repeat. In addition, several small clusters of the TR-1 and 180-bp repeats have been found in different chromosomes, some not located in obvious knob heterochromatin. Variation in restriction fragment fingerprints and copy number of the TR-1 elements was found among maize lines and among maize chromosomes. TR-1 tandem arrays up to 70 kilobases in length can be interspersed with stretches of 180-bp tandem repeat arrays. DNA sequence analysis and restriction mapping of one particular stretch of tandemly arranged TR-1 units indicate that these elements may be organized in the form of fold-back DNA segments. The TR-1 repeat shares two short segments of homology with the 180-bp repeat. The longest of these segments (31 bp; 64% identity) corresponds to the conserved region among 180-bp repeats. The polymorphism and complex structure of knob DNA suggest that, similar to the fold-back DNA-containing giant transposons in Drosophila, maize knob DNA may have some properties of transposable elements.