gebhart/patrepeval huggingface dataset:
Transcriptional Activation of the Human p21 Gene by Retinoic Acid Receptor (1996)

We reported previously that the induced differentiation of the myelomonocytic cell line U937 by vitamin D3 is facilitated by the transcriptional induction of the p21(WAF1/CIP1) gene by the vitamin D3 receptor (Liu, M., Lee, M.-H., Cohen, M., and Freedman, L. P. (1996) Genes Dev. 10, 143-153). Retinoic acid (RA), a physiological metabolite of vitamin A, is also a potent inducer of differentiation of several cell types, including myeloid leukemic cells. Like vitamin D3, RA acts through a subfamily of nuclear hormone receptors, RARs and RXRs (retinoid X receptors), which regulate the expression of target genes by binding to specific DNA elements and modulating transcription initiation. In this report we demonstrate that the gene encoding p21 is also a RA-responsive target gene, and we describe a functional RA response element in this gene's promoter which is required to confer RA induction through RAR.RXR heterodimers. These results correlate the RA induction of monocytic differentiation of U937 cells with the transcriptional activation of the p21 gene and suggest a role for this cyclin/cyclin-dependent kinase complex inhibitor in facilitating this differentiation pathway.
Refolding human serum albumin at relatively high protein concentration (1989)

The conditions for refolding reduced and denatured human serum albumin (HSA) were investigated with a view to maximising the yield of native monomeric albumin. Refolding by dialysis was found to be preferable to dilution as a means of chaotrope (urea) and reductant (2-mercaptoethanol) removal. Dialysis of denatured HSA solutions containing 4-8 M urea and 14 mM 2-mercaptoethanol at pH 10.0 was found to be optimal for HSA refolding. The yield of monomeric HSA was maximal (94%) for dialysis in the presence of EDTA (1 mM) and sodium palmitate (20 microM). Using this protocol it was possible to refold HSA at concentrations in excess of 5 mg.ml-1 whilst maintaining a high recovery of native monomer. These results represent a considerable improvement on established methods of HSA refolding.
The synthesis of 5‐arylpyrrolo[3,2‐b]pyridines and 7‐arylpyrrolo[3,2‐b]pyridines: Addition of 3‐aminopyrroles to aryl enaminones (1995)

Abstract A series of 5‐arylpyrrolo[3,2‐ b ]pyridines 1 was synthesized by addition of 3‐aminopyrroles to aryl enaminones. One example of a 7‐arylpyrrolo[3,2‐ b ]pyridine 2 was obtained as a minor product along with the 5‐aryl isomer, by a modification of the reaction sequence.
Antigen Presentation and T Cell Development in H2-M-Deficient Mice (1996)

HLA-DM (DM) facilitates peptide loading of major histocompatibility complex class II molecules in human cell lines. Mice lacking functional H2-M, the mouse equivalent of DM, have normal amounts of class II molecules at the cell surface, but most of these are associated with invariant chain-derived CLIP peptides. These mice contain large numbers of CD4 + T cells, which is indicative of positive selection in the thymus. Their CD4 + cells were unresponsive to self H2-M-deficient antigen-presenting cells (APCs) but were hyperreactive to wild-type APCs. H2-M-deficient APCs failed to elicit proliferative responses from wild-type T cells.
Human immunodeficiency virus type 1 major neutralizing determinant exposed on hepatitis B surface antigen particles is highly immunogenic in primates (1992)

Hepatitis B surface antigen (HBsAg) produced by recombinant DNA technology is now widely and safely used worldwide for hepatitis B vaccination. We used the HBsAg particle as a carrier molecule for presentation of selected human immunodeficiency virus type 1 (HIV-1) determinants to the immune system. Immunization of rhesus monkeys with an HBsAg chimera carrying the HIV-1 envelope major neutralizing determinant allowed us to generate proliferative T-cell responses and, in some cases, neutralizing antibodies and antibody-dependent cellular cytotoxicity. Since there is an overlap between populations at risk for hepatitis B virus and HIV, HBsAg recombinant particles may be relevant carriers for HIV-1 epitopes and could offer a new approach to the development of an AIDS vaccine.
Very fast empirical prediction and rationalization of protein pKa values (2005)

A very fast empirical method is presented for structure-based protein pKa prediction and rationalization. The desolvation effects and intra-protein interactions, which cause variations in pKa values of protein ionizable groups, are empirically related to the positions and chemical nature of the groups proximate to the pKa sites. A computer program is written to automatically predict pKa values based on these empirical relationships within a couple of seconds. Unusual pKa values at buried active sites, which are among the most interesting protein pKa values, are predicted very well with the empirical method. A test on 233 carboxyl, 12 cysteine, 45 histidine, and 24 lysine pKa values in various proteins shows a root-mean-square deviation (RMSD) of 0.89 from experimental values. Removal of the 29 pKa values that are upper or lower limits results in an RMSD = 0.79 for the remaining 285 pKa values.
Phase II study of metronomic chemotherapy for recurrent malignant gliomas in adults (2007)

Preclinical evidence suggests that continuous low-dose daily (metronomic) chemotherapy may inhibit tumor endothelial cell proliferation (angiogenesis) and prevent tumor growth. This phase II study evaluated the feasibility of this antiangiogenic chemotherapy regimen in adults with recurrent malignant gliomas. The regimen consisted of low-dose etoposide (35 mg/m2 [maximum, 100 mg/day] daily for 21 days), alternating every 21 days with cyclophosphamide (2 mg/kg [maximum, 100 mg/day] daily for 21 days), in combination with daily thalidomide and celecoxib, in adult patients with recurrent malignant gliomas. Serum and urine samples were collected for measurement of angiogenic peptides. Forty-eight patients were enrolled (15 female, 33 male). Twenty-eight patients had glioblastoma multiforme (GBMs), and 20 had anaplastic gliomas (AGs). Median age was 53 years (range, 33-74 years), and median KPS was 70 (range, 60-100). Therapy was reasonably well tolerated in this heavily pretreated population. Two percent of patients had partial response, 9% had a minor response, 59% had stable disease, and 30% had progressive disease. For GBM patients, median progression-free survival (PFS) was 11 weeks, six-month PFS (6M-PFS) was 9%, and median overall survival (OS) was 21 weeks. For AG patients, median PFS was 14 weeks, 6M-PFS was 26%, and median OS was 41.5 weeks. In a limited subset of patients, serum and urine angiogenic peptides did not correlate with response or survival (p > 0.05). Although there were some responders, this four-drug, oral metronomic regimen did not significantly improve OS in this heavily pretreated group of patients who were generally not eligible for conventional protocols. While metronomic chemotherapy may not be useful in patients with advanced disease, further studies using metronomic chemotherapy combined with more potent antiangiogenic agents in patients with less advanced disease may be warranted.
Augmentation of antitumor effects by NK cell inhibitory receptor blockade in vitro and in vivo (2001)

Subsets of natural killer (NK) cells are characterized by the expression of inhibitory and/or stimulatory receptors specific for major histocompatibility complex (MHC) class I determinants. In mice, these include the Ly49 family of molecules. One mechanism by which tumor cells may evade NK cell killing is by expressing the appropriate MHC class I and binding inhibitory Ly49 receptors. Therefore, the question of whether blocking the interaction between the Ly49 inhibitory receptors on NK and MHC class I cells on tumor cells augments antitumor activity was investigated. Blockade of Ly49C and I inhibitory receptors using F(ab')(2) fragments of the 5E6 monoclonal antibody (mAb) resulted in increased cytotoxicity against syngeneic tumors and decreased tumor cell growth in vitro. The effect of 5E6 F(ab')(2) was specific for the MHC of the tumor, as the use of F(ab')(2) of the mAb against Ly49G2 failed to increase NK activity. Treatment of leukemia-bearing mice with 5E6 F(ab')(2) fragments or adoptive transfer of NK cells treated ex vivo with the F(ab')(2) resulted in significant increases in survival. These results demonstrate that blockade of NK inhibitory receptors enhances antitumor activity both in vitro and in vivo, suggesting that NK inhibitory receptors can be responsible for diminishing antitumor responses. Therefore, strategies to block inhibitory receptors may be of potential use in increasing the efficacy of immunotherapy. (Blood. 2001;97:3132-3137)
Low lying singlet states of α, ω-dithienylpolyenes: α, ω-dithienylbutadiene, α, ω-dithienylhexatriene, and α, ω-dithienyloctatetraene (1991)

Fluorescence and fluorescence excitation spectra for low temperature n-alkane solutions of α,ω-dithenylpolyenes with two, three, and four polyene double bonds have been measured. The fundamental frequencies in the vibronic development of the fully resolved spectra are either nearly identical to modes seen for unsubstituted polyenes or nearly identical to modes seen for polythiophene oligomers. The degree to which thiophene ring modes contribute to the spectra decreases with increasing polyene chain length. In the tetraene, the 2 1Ag state is 2760 cm−1 lower in energy than the 1 1Bu state, in the triene it is 1570 cm−1 lower, and in the diene these two states are nearly degenerate. The 2 1Ag and 1 1Bu excitation energies are well fit by a simple theoretical model which also gives a description of the π-electron distributions in the 1 1Ag, 2 1Ag, and 1 1Bu states.
Identification and characterization of human TP53I5 and mouse Tp53i5 genes in silico (2004)

TP53 gene, encoding tumor protein P53, is frequently inactivated in various types of human cancer, including colorectal, lung, and gastric cancer. Cancer cells with TP53 mutation acquire malignant potentials, such as selective growth advantage, genomic instability, resistance to apoptosis, and promotion of angiogenesis. U33271 partial cDNA isolated from HPV-18 E6/E7 immortalized keratinocytes is derived from one of P53-traget genes. Here, we identified and characterized the TP53I5 (tumor protein P53 inducible protein 5) gene corresponding to U33271 partial cDNA by using bioinformatics. FLJ23270 (AK026923.1) was the representative human TP53I5 cDNA. TP53I5 gene, consisting of 23 exons, was located at human chromosome 11p15.5. TP53I5 mRNA was expressed in human colorectal, lung, and breast cancer. IMAGE5352905 (BC025477.1) and IMAGE6508837 (NM_178381.2) were aberrant mouse Tp53i5 cDNAs with multiple frameshifts due to retention of intronic sequences. Complete coding sequence of mouse Tp53i5 cDNA was determined by assembling nucleotide positions 1-1213, 1293-1740, 1745-2045, and 2071-3088 of BC025477.1. Tp53i5 gene was located at mouse chromosome 7F5. Human TP53I5 (782 aa) and mouse Tp53i5 (747 aa), showing 71.1% total-amino-acid identity, were eight-transmembrane proteins with N- and C-terminal tails facing the cytoplasm. TP53I5 orthologs were homologous to TMEM16A (FLJ10261 or ORAOV2), TMEM16B, TMEM16C, TMEM16D, TMEM16E and TMEM16F with the TM16H1, TM16H2, and TM16H3 domains. TP53I5 was identified as a novel member of the TMEM16 family based on membrane topology and TM16H1-3 domains. This is the first report on the human TP53I5 and mouse Tp53i5 genes.
Inhibition of LFA‐1/ICAM‐1 and VLA‐4/VCAM‐1 as a therapeutic approach to inflammation and autoimmune diseases (2002)

This review focuses on providing insights into the structural basis and clinical relevance of LFA-1 and VLA-4 inhibition by peptides and small molecules as adhesion-based therapeutic strategies for inflammation and autoimmune diseases. Interactions of cell adhesion molecules (CAM) play central roles in mediating immune and inflammatory responses. Leukocyte function-associated antigen (LFA-1, alpha(L)beta(2), and CD11a/CD18) and very late antigen (VLA-4, alpha(4)beta(1), and CD49d/CD29) are members of integrin-type CAM that are predominantly involved in leukocyte trafficking and extravasation. LFA-1 is exclusively expressed on leukocytes and interacts with its ligands ICAM-1, -2, and -3 to promote a variety of homotypic and heterotypic cell adhesion events required for normal and pathologic functions of the immune systems. VLA-4 is expressed mainly on lymphocyte, monocytes, and eosinophils, but is not found on neutrophils. VLA-4 interacts with its ligands VCAM-1 and fibronectin (FN) CS1 during chronic inflammatory diseases, such as rheumatoid arthritis, asthma, psoriasis, transplant-rejection, and allergy. Blockade of LFA-1 and VLA-4 interactions with their ligands is a potential target for immunosuppression. LFA-1 and VLA-4 antagonists (antibodies, peptides, and small molecules) are being developed for controlling inflammation and autoimmune diseases. The therapeutic intervention of mostly mAb-based has been extensively studied. However, due to the challenging relative efficacy/safety ratio of mAb-based therapy application, especially in terms of systemic administration and immunogenic potential, strategic alternatives in the forms of peptide, peptide mimetic inhibitors, and small molecule non-peptide antagonists are being sought. Linear and cyclic peptides derived from the sequences of LFA-1, ICAM-1, ICAM-2, VCAM-1, and FN C1 have been shown to have inhibitory effects in vitro and in vivo. Finally, understanding the mechanism of LFA-1 and VLA-4 binding to their ligands has become a fundamental basis in developing therapeutic agents for inflammation and autoimmune diseases.
Nonenzymatic sequence-specific cleavage of single-stranded DNA. (1985)

Ethylenediaminetetraacetic acid and diethylenetriaminepentaacetic acid have been attached covalently to the 5' terminus of the deoxynucleotide sequence C-A-C-A-A-T-T-C-C-A-C-A-C-A-A-C (16-mer) via an ethylenediamine linker. In the presence of Fe2+ and dithiothreitol, these reagents bring about the hybridization-dependent cleavage of the sequence T-C-G-T-A-T-G-T-T-G-T-G-T-G-G-A-A-T-T-G-T-G-A-G-C-G-G-A-T-A-A-C-A-A-T-T- T (37-mer), a sequence that contains an internal subsequence complementary to the 16-mer. The principal cleavage sites on the 37-mer are about four residues on each side of the terminal phosphate group of the 16-mer.
GDP-Mannose 3′,5′-Epimerase Forms GDP-L-gulose, a Putative Intermediate for the de Novo Biosynthesis of Vitamin C in Plants (2003)

Despite its importance for agriculture, bioindustry, and nutrition, the fundamental process of L-ascorbic acid (vitamin C) biosynthesis in plants is not completely elucidated, and little is known about its regulation. The recently identified GDP-Man 3',5'-epimerase catalyzes a reversible epimerization of GDP-D-mannose that precedes the committed step in the biosynthesis of vitamin C, resulting in the hydrolysis of the highly energetic glycosyl-pyrophosphoryl linkage. Here, we characterize the native and recombinant GDP-Man 3',5'-epimerase of Arabidopsis thaliana. GDP and GDP-D-glucose are potent competitive inhibitors of the enzyme, whereas GDP-L-fucose gives a complex type of inhibition. The epimerase contains a modified version of the NAD binding motif and is inhibited by NAD(P)H and stimulated by NAD(P)+. A feedback inhibition of vitamin C biosynthesis is observed apparently at the level of GDP-Man 3',5'-epimerase. The epimerase catalyzes at least two distinct epimerization reactions and releases, besides the well known GDP-l-galactose, a novel intermediate: GDP-L-gulose. The yield of the epimerization varies and seems to depend on the molecular form of the enzyme. Both recombinant and native enzymes co-purified with a Hsp70 heat-shock protein (Escherichia coli DnaK and A. thaliana Hsc70.3, respectively). We speculate, therefore, that the Hsp70 molecular chaperones might be involved in folding and/or regulation of the epimerase. In summary, the plant epimerase undergoes a complex regulation and could control the carbon flux into the vitamin C pathway in response to the redox state of the cell, stress conditions, and GDP-sugar demand for the cell wall/glycoprotein biosynthesis. Exogenous L-gulose and L-gulono-1,4-lactone serve as direct precursors of l-ascorbic acid in plant cells. We propose an L-gulose pathway for the de novo biosynthesis of vitamin C in plants.
Rapid speech recognizer adaptation to new speakers (1999)

This paper summarizes the work of the "Rapid Speech Recognizer Adaptation" team in the workshop held at Johns Hopkins University in the summer of 1998. The project addressed the modeling of dependencies between units of speech with the goal of making more effective use of small amounts of data for speaker adaptation. A variety of methods were investigated and their effectiveness in a rapid adaptation task defined on the Switchboard conversational speech corpus is reported.
Specific interaction of the human immunodeficiency virus Rev protein with a structured region in the env mRNA. (1990)

A region of potential complex secondary structure within the human immunodeficiency virus env mRNA has been implicated in Rev-mediated export of viral structural mRNAs from the nucleus to the cytoplasm. By using an RNase protection gel-mobility-shift assay, we demonstrate that purified Rev protein forms a stable complex with this Rev-responsive RNA. RNAs with mutations designed to disrupt formation of a predicted stem structure no longer interact with Rev. However, Rev binding is restored upon annealing of the two complementary RNAs that make up the stem. These results suggest that direct interaction of Rev with the Rev-responsive element could facilitate transport of human immunodeficiency virus structural mRNAs from the nucleus to the cytoplasm.
Bandwidth efficient AMR operation for VoIP (2003)

An example of a bandwidth efficient adaptive multi rate (AMR) system for Voice over IP (VoIP) is presented. In VoIP, packet losses cause degradation of the synthesized speech. The distortions may propagate over several consecutive frames, since predictors in the codec exploit inter-frame correlations to gain coding efficiency. To reduce the effects of packet loss, forward error correction (FEC) that adds redundant information to voice packets can be used. However, while FEC can reduce the effects of packet loss, it will increase the amount of bandwidth used by the voice stream, which is not desirable. In this paper we propose FEC methods like partial redundancy, selective redundancy for the most sensitive frames and parameter interpolation in conjunction with AMR codec mode adaptation, which secure the speech quality when using AMR for VoIP without increasing the bandwidth substantially.
Endogenous vascular remodeling in ischemic skeletal muscle: a role for nitric oxide (2003)

To test the hypothesis that nitric oxide (NO) production is essential for endogenous vascular remodeling in ischemic skeletal muscle, 22 New Zealand White rabbits were chronically instrumented with transit-time flow probes on the common iliac arteries and underwent femoral ligation to produce unilateral hindlimb ischemia. Iliac blood flow and arterial pressure were recorded at rest and during a graded exercise test. An osmotic pump connected to a femoral arterial catheter continuously delivered N-nitro-l-arginine methyl ester (a NO synthase inhibitor) or a control solution (N-nitro-d-arginine methyl ester or phenylephrine) to the ischemic limb over a 2-wk period. At 1, 3, and 6 wk after femoral ligation, maximal treadmill exercise blood flow in the ischemic limb was reduced compared with baseline in each group. However, maximal exercise blood flow was significantly (P < 0.05) lower in the l-NAME-treated group than in controls for the duration of the study: 48 +/- 4 vs. 60 +/- 5 ml/min at 6 wk. Consistent with the reduction in maximal blood flow response, the duration of voluntary exercise was also substantially (P < 0.05) shorter in the l-NAME-treated group: 539 +/- 67 vs. 889 +/- 87 s. Resting blood flow was unaffected by femoral ligation in either group. The results of this study show that endogenous vascular remodeling, which partially alleviated the initial deficit in blood flow, was interrupted by NO synthase inhibition. Therefore, we conclude that NO is essential for endogenous collateral development and angiogenesis in ischemic skeletal muscle in the rabbit.
Inhibition of transforming growth factor-β signalling attenuates interleukin (IL)-18 plus IL-2-induced interstitial lung disease in mice (2010)

Interstitial lung disease (ILD) is an intractable disease induced by various factors in humans. However, there is no universally effective treatment for ILD. In this study, we investigated the role of transforming growth factor (TGF)-beta signalling in the pathogenesis of ILD by using model mice. Injection of interleukin (IL)-18 plus IL-2 in C57BL6 (B6) mice resulted in acute ILD by infiltration of natural killer (NK) cells and a significant increase of TGF-beta mRNA in the lung. To examine the pathogenetic role of TGF-beta in ILD mice, we used SB-431542 (4-[4-(1,3-benzodioxol-5-yl)-5-(2-pyridinyl)-1H-imidazol-2-yl]-benzamide), which is a potent and selective inhibitor of TGF-beta receptor I (TbetaRI), also known as activin receptor-like kinase 5 (ALK5). Treatment of B6-ILD mice with SB-431542 resulted in improvement of ILD, delay in mortality, reduction of the expression of interferon (IFN)-gamma and IL-6 in the lungs. The same treatment also decreased significantly the percentage of natural killer (NK) cells in the lungs (P < 0.05) and mRNA expression levels of certain chemokines such as CCL2, CCL3, CCL4, CCL5 and CXCL10 in B6-ILD. These findings were confirmed by IL-18 plus IL-2 treatment of Smad3-deficient (Smad3(-/-)) mice (P < 0.05). Our results showed that inhibition of TGF-beta signalling reduced the percentage of NK cells and the expression of certain chemokines in the lungs, resulting in improvement of ILD. The findings suggest that TGF-beta signalling may play an important role in the pathogenesis of IL-18 plus IL-2-induced ILD in mice.
Distributed Space-Time Block Coding for Cooperative Networks with Multiple-Antenna Nodes (2006)

We present an extension to our previous work on distributed space-time block coding where we considered cooperative networks with a large set of single-antenna decode-and-forward relays N. Here, we consider the general case where each relay node is equipped with N/sub T/ antennas and the destination node has N/sub R/ antennas. It is assumed that at any given time only a small, a priori unknown subset of nodes S C N is active. In the proposed scheme, the signal transmitted by an active node is the product of an information-carrying space-time block code (STBC) matrix, which is identical for all nodes, and a unique node signature matrix. It is shown that existing STBCs designed for N/sub c/ /spl ges/ 2 co-located antennas are a favorable choice for the code matrix guaranteeing a diversity order of d = min {N/sub c/N/sub R/, N/sub T/N/sub S/N/sub R/} if ns nodes are active. Simulation results show that a considerable gain can be achieved by using multiple-antenna nodes even if the antennas are highly correlated.