gebhart/patrepeval huggingface dataset:
Androgen receptor expression in androgen-independent prostate cancer is associated with increased expression of androgen-regulated genes. (1998)

The human prostate cancer (CaP) xenograft, CWR22, mimics human CaP. CWR22 grows in testosterone-stimulated nude mice, regresses after castration, and recurs after 5-6 months in the absence of testicular androgen. Like human CaP that recurs during androgen deprivation therapy, the recurrent CWR22 expresses high levels of androgen receptor (AR). Immunohistochemical, Western, and Northern blot analyses demonstrated that AR expression in the androgen-independent CWR22 is similar to AR expression in the androgen-dependent CWR22 prior to castration. Expression of prostate-specific antigen and human kallikrein-2 mRNAs, two well-characterized androgen-regulated genes in human CaP, was androgen dependent in CWR22. Despite the absence of testicular androgen, prostate-specific antigen and human kallikrein-2 mRNA levels in recurrent CWR22 were higher than the levels in regressing CWR22 tumors from 12-day castrate mice and similar to those in the androgen-stimulated CWR22. Other AR-regulated genes followed a similar pattern of expression. Differential expression screening identified androgen regulation of alpha-enolase and alpha-tubulin as well as other unknown mRNAs. Insulin-like growth factor binding protein-5, the homeobox gene Nkx 3.1, the AR coactivator ARA-70, and cell cycle genes Cdk1 and Cdk2 were androgen regulated in CWR22. In recurrent CWR22, the steady-state levels of all these AR-dependent mRNAs were similar to those in the androgen-stimulated CWR22, despite the absence of testicular androgen. Expression of AR and AR-regulated genes in the androgen-deprived recurrent CWR22 at levels similar to the androgen-stimulated CWR22 suggests that AR is transcriptionally active in recurrent CWR22. Induction of these AR-regulated genes may enhance cellular proliferation in relative androgen absence but through an AR-dependent mechanism. Alternatively, in androgen-independent tumors, induced expression of the AR-regulated gene network might result from a non-AR transcription control mechanism common to these genes.
Oligodeoxynucleotides lacking CpG dinucleotides mediate Toll‐like receptor 9 dependent T helper type 2 biased immune stimulation (2004)

Oligodeoxynucleotides (ODN) with unmethylated CpG dinucleotides mimic the immune stimulatory activity of bacterial DNA in vertebrates and are recognized by Toll-like receptor 9 (TLR9). It is also possible to detect immune activation with certain phosphorothioate sequences that lack CpG motifs. These ODN are less potent than CpG ODN and the mechanism by which they stimulate mammalian leucocytes is not understood. We here provide several lines of evidence demonstrating that the effects induced by non-CpG ODN are mediated by TLR9. First, non-CpG ODN could not stimulate cytokine secretion from the splenocytes of TLR9-deficient (TLR9(-/-)) mice. Second, immunization of TLR9(+/+) but not TLR9(-/-) mice with non-CpG ODN enhanced antigen-specific antibody responses, although these were T helper type 2 (Th2)-biased. Third, reactivity to non-CpG ODN could be reconstituted by transfection of human TLR9 into non-responsive cells. In addition, we define a new efficient immune stimulatory motif aside from the CpG dinucleotide that consists of a 5'-TC dinucleotide in a thymidine-rich background. Non-CpG ODN containing this motif induced activation of human B cells, but lacked stimulation of Th1-like cytokines and chemokines. Our study indicates that TLR9 can mediate either efficient Th1- or Th2-dominated effects depending on whether it is stimulated by CpG or certain non-CpG ODN.
Effects of ( R )-9-(2-Phosphonylmethoxypropyl)adenine Monotherapy on Chronic SIV Infection in Macaques (1997)

(R)-9-(2-Phosphonylmethoxypropyl)adenine (PMPA) acts as a reverse transcriptase inhibitor of retroviruses and has been shown to be effective against acute simian immunodeficiency virus (SIV) infection in macaques. To study its efficacy at different stages of infection, we tested PMPA in cynomolgus macaques (Macaca fascicularis) that had been chronically infected with SIVMne for at least 19 weeks before treatment was begun. PMPA was administered subcutaneously in a single daily dose of either 30 or 75 mg/kg body weight for 28 days. Within < or = 2 weeks of treatment, PMPA in both dosing regimens reduced SIV levels by >99% in the plasma or peripheral blood mononuclear cells; in some macaques SIV levels were reduced to below the lower quantitation limit. At a dose of 30 mg/kg/day PMPA was well tolerated, causing no side effects while increasing the mean CD4+ cell counts in animals that received this dose. Thus PMPA seems to be a promising agent for use against retroviral infections.
Mechanistic Basis for Suicide Inactivation of Porphobilinogen Synthase by 4,7-Dioxosebacic Acid, an Inhibitor That Shows Dramatic Species Selectivity (2001)

4,7-Dioxosebacic acid (4,7-DOSA) is an active site-directed irreversible inhibitor of porphobilinogen synthase (PBGS). PBGS catalyzes the first common step in the biosynthesis of the tetrapyrrole cofactors such as heme, vitamin B(12), and chlorophyll. 4,7-DOSA was designed as an analogue of a proposed reaction intermediate in the physiological PBGS-catalyzed condensation of two molecules of 5-aminolevulinic acid. As shown here, 4,7-DOSA exhibits time-dependent and dramatic species-specific inhibition of PBGS enzymes. IC(50) values vary from 1 microM to 2.4 mM for human, Escherichia coli, Bradyrhizobium japonicum, Pseudomonas aeruginosa, and pea enzymes. Those PBGS utilizing a catalytic Zn(2+) are more sensitive to 4,7-DOSA than those that do not. Weak inhibition of a human mutant PBGS establishes that the inactivation by 4,7-DOSA requires formation of a Schiff base to a lysine that normally forms a Schiff base intermediate to one substrate molecule. A 1.9 A resolution crystal structure of E. coli PBGS complexed with 4,7-DOSA (PDB code ) shows one dimer per asymmetric unit and reveals that the inhibitor forms two Schiff base linkages with each monomer, one to the normal Schiff base-forming Lys-246 and the other to a universally conserved "perturbing" Lys-194 (E. coli numbering). This is the first structure to show inhibitor binding at the second of two substrate-binding sites.
Method for determining reservoir fluid saturations using field production data (1972)

Reliable reservoir fluid saturation data are important to the overall planning for prospective supplemental recovery projects. Average oil, water, and gas saturations for a reservoir as a whole are usually determined by a pressure-production history match using conventional material balance methods. More sophisticated numerical simulation techniques are generally employed to determine reservoir saturation distributions. Simulation work can be time-consuming and expensive when efforts are made to accurately determine the saturation distribution by attempting to match the individual performance of a large number of wells. A trial-and-error graphical procedure has been developed as an alternative to the more sophisticated methods. Because of its ease in application, it may be considered as an efficient and economical application of engineering effort for planning purposes. An application of this technique is illustrated for the Ten Section field, Kern County, California.
Activation of a Proteolytic System by a Membrane Lipoprotein: Mechanism of Action of Tissue Factor (1973)

One pathway of blood coagulation, the extrinsic system, is initiated by a specific interaction between tissue factor, which is a membrane lipoprotein, and factor VII, one of the plasma coagulation factors. Factor VII was prepared from bovine plasma by adsorption onto and elution from BaSO(4). The eluate was chromatographed on DEAE-Sephadex and purified by preparative disc-gel electrophoresis. Factor VII complexed with purified bovine-brain tissue factor and, when eluted from the complex, factor VII had a greater mobility in acrylamide-gel electrophoresis in the presence of sodium dodecyl sulfate, i.e., it had a reduced molecular weight. Factor VII was also cleaved in the presence of orthophenanthroline, an inhibitor of the peptidase activity of tissue factor. Prior treatment of factor VII with diisopropylphosphorofluoridate, however, completely blocked its cleavage and the development of coagulant activity, although factor VII treated with diisopropylphosphorofluoridates complexed equally well as the native protein with tissue factor. Factor VII in whole bovine plasma was also inhibited by the drug. Factor VII labeled with [(32)P]diisopropylphosphorofluoridate and radioautographed after electrophoresis in gels showed two major components, only one of which was labeled. We conclude that tissue factor initiates blood coagulation by facilitating a proteolytic attack within the factor VII "complex." The most likely mechanism is proteolysis of one form of factor VII by the diisopropylphosphorofluoridate-sensitive enzyme, although additional intramolecular proteolysis may be involved.
Structure of the receptor-binding domain of human thrombopoietin determined by complexation with a neutralizing antibody fragment (2004)

The cytokine thrombopoietin (TPO), the ligand for the hematopoietic receptor c-Mpl, acts as a primary regulator of megakaryocytopoiesis and platelet production. We have determined the crystal structure of the receptor-binding domain of human TPO (hTPO(163)) to a 2.5-A resolution by complexation with a neutralizing Fab fragment. The backbone structure of hTPO(163) has an antiparallel four-helix bundle fold. The neutralizing Fab mainly recognizes the C-D crossover loop containing the species invariant residue Q111. Titration calorimetric experiments show that hTPO(163) interacts with soluble c-Mpl containing the extracellular cytokine receptor homology domains with 1:2 stoichiometry with the binding constants of 3.3 x 10(9) M(-1) and 1.1 x 10(6) M(-1). The presence of the neutralizing Fab did not inhibit binding of hTPO(163) to soluble c-Mpl fragments, but the lower-affinity binding disappeared. Together with prior genetic data, these define the structure-function relationships in TPO and the activation scheme of c-Mpl.
PmrA(Con) Confers pmrHFIJKL -Dependent EGTA and Polymyxin Resistance on msbB Salmonella by Decorating Lipid A with Phosphoethanolamine (2007)

Mutations in pmrA were recombined into Salmonella strain ATCC 14028 msbB to determine if pmrA-regulated modifications of lipopolysaccharide could suppress msbB growth defects. A mutation that functions to constitutively activate pmrA [pmrA(Con)] suppresses msbB growth defects on EGTA-containing media. Lipid A structural analysis showed that Salmonella msbB pmrA(Con) strains, compared to Salmonella msbB strains, have increased amounts of palmitate and phosphoethanolamine but no aminoarabinose addition, suggesting that aminoarabinose is not incorporated into msbB lipid A. Surprisingly, loss-of-function mutations in the aminoarabinose biosynthetic genes restored EGTA and polymyxin sensitivity to Salmonella msbB pmrA(Con) strains. These blocks in aminoarabinose biosynthesis also prevented lipid A phosphoethanolamine incorporation and reduced the levels of palmitate addition, indicating previously unknown roles for the aminoarabinose biosynthetic enzymes. Lipid A structural analysis of the EGTA- and polymyxin-resistant triple mutant msbB pmrA(Con) pagP::Tn10, which contains phosphoethanolamine but no palmitoylated lipid A, suggests that phosphoethanolamine addition is sufficient to confer EGTA and polymyxin resistance on Salmonella msbB strains. Additionally, palmitoylated lipid A was observed only in wild-type Salmonella grown in the presence of salt in rich media. Thus, we correlate EGTA resistance and polymyxin resistance with phosphoethanolamine-decorated lipid A and demonstrate that the aminoarabinose biosynthetic proteins play an essential role in lipid A phosphoethanolamine addition and affect lipid A palmitate addition in Salmonella msbB strains.
Protein S binds to and inhibits factor Xa. (1994)

Although human protein S binds to human factor Va and inhibits prothrombinase activity, this inhibition is not totally dependent on factor Va. Hence, we investigated possible interaction of protein S with human factor Xa. Factor Xa, diisopropylphospho-factor Xa and their biotin derivatives ligand blotted specifically to protein S and protein S ligand blotted specifically to factor X and factor Xa. Biotinylated factors X and Xa bound to immobilized protein S and, reciprocally, protein S bound to immobilized factor Xa with a Kd of approximately 19 nM. In fluid phase, protein S bound to factor Xa with a Kd of approximately 18 nM. Protein S at 33 nM reversibly inhibited 50% of factor Xa amidolytic activity. Protein S inhibition of prothrombin conversion to thrombin by factor Xa was phospholipid-independent and was 1.6 times stimulated by Ca2+ ions. Inhibition of prothrombinase activity by protein S was 2.3-fold more potent in the presence of factor Va, with 50% inhibition at approximately 8 nM protein S. Protein S prolonged the factor Xa one-stage clotting time of protein S-depleted plasma in a dose-dependent manner. These data demonstrate mechanisms of anticoagulant action for protein S that are independent of activated protein C and that involve direct binding to factors Xa and Va and direct inhibition of factor Xa.
Expansion of CREB's DNA recognition specificity by Tax results from interaction with Ala-Ala-Arg at positions 282-284 near the conserved DNA-binding domain of CREB. (1994)

The transactivator protein of human T-lymphotropic virus type I (HTLV-I), Tax, forms multiprotein complexes with the ubiquitous transcription factor CREB and the CREB/ATF-1 heterodimer. The interaction between Tax and CREB is highly specific and results in increased binding of the Tax/CREB complexes to the HTLV-I 21-bp repeats. Despite the extensive sequence similarities between CREB and ATF-1, Tax interacts with ATF-1 only marginally. Compared with CREB, Tax/CREB exhibits greatly increased DNA recognition specificity and preferentially assembles on a consensus binding site, GGGGG(T/A)TGACG(T/C)(A/C)TA(T/C)C-CCCC, homologous to the HTLV-I 21-bp repeats. Here we report that Tax affects CREB binding to the Tax-inducible DNA elements by interacting with the basic-leucine zipper (bZip) domain of CREB. We show by domain switching that the basic region in CREB bZip can confer on c-Jun and ATF-1 leucine zippers the ability to interact with Tax in vitro. Mutational analyses further demonstrate that the amino acid residues of CREB critical for Tax/CREB interaction are Ala-Ala-Arg at positions 282-284 (AAR284), immediately upstream of the highly conserved DNA-binding domain (R/K)XX(R/K) N(R/K)XAAXX(S/C)RX(R/K)(K/R) characteristic of all bZip proteins. Specific amino acid substitutions in AAR284 of CREB weakened or abolished Tax/CREB interaction, whereas reciprocal changes in ATF-1 allowed it to interact with Tax. These results support a model in which the specific interaction between Tax and the AAR284 residues near the DNA-binding domain of CREB results in a multiprotein complex with altered DNA recognition property. This protein complex assembles selectively on the viral Tax-responsive 21-bp repeats to augment transcription.
Profiling Microdissected Epithelium and Stroma to Model Genomic Signatures for Cervical Carcinogenesis Accommodating for Covariates (2007)

This study is the first comprehensive, integrated approach to examine grade-specific changes in gene expression along the entire neoplastic spectrum of cervical intraepithelial neoplasia (CIN) in the process of cervical carcinogenesis. This was accomplished by identifying gene expression signatures of disease progression using cDNA microarrays to analyze RNA from laser-captured microdissected epithelium and underlying stroma from normal cervix, graded CINs, cancer, and patient-matched normal cervical tissues. A separate set of samples were subsequently validated using a linear mixed model that is ideal to control for interpatient gene expression profile variation, such as age and race. These validated genes were ultimately used to propose a genomically based model of the early events in cervical neoplastic transformation. In this model, the CIN 1 transition coincides with a proproliferative/immunosuppression gene signature in the epithelium that probably represents the epithelial response to human papillomavirus infection. The CIN 2 transition coincides with a proangiogenic signature, suggesting a cooperative signaling interaction between stroma and tumor cells. Finally, the CIN 3 and squamous cell carcinoma antigen transition coincide with a proinvasive gene signature that may be a response to epithelial tumor cell overcrowding. This work strongly suggests that premalignant cells experience a series of microenvironmental stresses at the epithelium/stroma cell interface that must be overcome to progress into a transformed phenotype and identifies the order of these events in vivo and their association with specific CIN transitions.
Lnaser Welding of Venotomies (1986)

We investigated the histologic and biochemical effects of carbon dioxide and neodymium (Nd)-YAG laser welding on the healing of venotomies. Ten canine femoral venotomies 2 cm in length were approximated and welded with 10 600-nm wavelength, 1-W power over 20 to 25 s for CO2 laser, and 1060-nm wavelength, 1-W power over 30 to 40 s for Nd-YAG laser. On removal at one to three weeks, all veins (4/4 welded by CO2 and 6/6 by Nd-YAG) were patent without hematomas. Histologic and biochemical analyses of the venous tissues demonstrated active healing at the venotomy sites. We conclude that the CO2 and Nd-YAG lasers can be used successfully to weld venotomies and may provide an alternative to conventional suture techniques for repair of vascular lesions.
View-based approach to robot navigation (2002)

Recently, view-based or appearance-based approaches have been attracting the interests of computer vision research. Based on a similar idea, we have proposed a view-based navigation method using a model of the route called the "view sequence." It contains a sequence of frontal views along a route memorized in the teaching run, and the recognition of the environment is realized based on the matching of the current view and memorized view sequence. In this paper, we discuss the required characteristics of the view for the view sequence, and evaluate our former method of generating views. Then we confirm that the stereo disparity satisfies the requirement of the view sequence through an experiment, and the disparity view sequence is applied for outdoor navigation. The experimental results indicate such views other than normal camera images can be utilized for our view-based navigation method.
Function of Mucosa-Associated Lymphoid Tissue in Antibody Formation (2010)

Abundant evidence supports the notion that human intestinal plasma cells are largely derived from B cells initially activated in gut-associated lymphoid tissue (GALT). Nevertheless, insufficient knowledge exists about the uptake, processing, and presentation of luminal antigens occurring in GALT to accomplish priming and sustained expansion of mucosal B cells. Also, it is unclear how the germinal center reaction so strikingly promotes class switch to IgA and expression of J chain, although the commensal microbiota appears to contribute to both diversification and memory. B-cell migration from GALT to the intestinal lamina propria is guided by rather well-defined adhesion molecules and chemokines/chemokine receptors, but the cues directing homing to secretory effector sites beyond the gut require better definition. In this respect, the role of human Waldeyer's ring (including adenoids and the palatine tonsils) as a regional mucosa-associated lymphoid tissue must be better defined, although the balance of evidence suggests that it functions as nasopharynx-associated lymphoid tissue (NALT) like the characteristic NALT structures in rodents. Altogether, data suggest a remarkable compartmentalization of the mucosal immune system that must be taken into account in the development of effective local vaccines to protect specifically the airways, small and large intestines, and the female genital tract.
GPR55: a new member of the cannabinoid receptor clan? (2007)

In this issue of the British Journal of Pharmacology, Ryberg et al. present convincing in vitro evidence that the orphan GPCR, GPR55, is a cannabinoid receptor. GPR55 was activated by a range of plant, synthetic and endogenous cannabinoids and blocked by the non-psychoactive phytocannabinoid, cannabidiol. Their experiments have revealed several differences between the pharmacology of GPR55 and the established cannabinoid CB1 and CB2 receptors. For example, the CB1 receptor antagonist, AM251, activated GPR55 and the main psychoactive constituent of cannabis, Delta9-tetrahydrocannabinol, displayed greater efficacy at GPR55 than at CB1 or CB2 receptors. They also compared the distribution of GPR55 and CB1 mRNA in mouse and report that GPR55 couples to Galpha13, that it is activated by virodhamine, palmitoylethanolamide and oleoylethanolamide, and that virodhamine displays relatively high efficacy as a GPR55 agonist. Still to be identified are the main roles played by GPR55 in health and disease and any potential therapeutic benefits of activating or blocking this receptor.
From polymeric particles to multifunctional nanocapsules for biomedical applications using the miniemulsion process (2009)

Abstract The miniemulsions process represents a versatile tool for the formation of polymeric nanoparticles consisting of different kinds of polymer as obtained by a variety of polymerization types ranging from radical, anionic, cationic, enzymatic polymerization to polyaddition, and polycondensation. The process perfectly allows the encapsulation of hydrophilic and hydrophobic liquids and solids in polymeric shells, molecularly dissolved dyes or other components. In combination with a specific functionalization of the nanoparticles' or nanocapsules' surfaces and the possibility to release substances in a defined way from the interior, complex nanoparticles or nanocapsules are obtained, which are ideally suited for application in biomedical application as marker and targeted drug‐delivery system. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 493–515, 2010