gebhart/patrepeval huggingface dataset:
Development of an Antifertility Vaccine for Pets Based on Active Immunization against Luteinizing Hormone-Releasing Hormone1 (1994)

Male dogs and cats were immunized against LHRH in order to evaluate the feasibility of an immunological approach to pet contraception. In the first study, dogs were immunized with 100, 500, or 2500 micrograms of LHRH conjugated to tetanus toxoid. A significant decline in serum testosterone (T) levels was observed in all immunized dogs, reaching castration levels in some animals by Week 4 and remaining suppressed in all the immunized dogs through the course of the study. Testicular histology suggested arrest of spermatogenesis (infertility). The effects of "immunological castration" were reversible (study 2): steroidogenesis suppressed by "immunological castration" was restored as antibody titers declined. Effective antibodies were rapidly reinduced in dogs by a single injection of LHRH1-TT. In contrast, the level of antibodies induced in male cats (study 3) was not sufficient for "immunological castration." The conclusion was that active immunization against LHRH could provide a cost-effective, nonsurgical, reversible means to control the fertility of companion animals.
Targeted Nanoparticles for Imaging Incipient Pancreatic Ductal Adenocarcinoma (2008)

Our approach exploited a well-defined model of PDAC, enabling rapid identification and validation of PTP. The developed specific imaging probe, along with the discovery of plectin-1 as a novel biomarker, may have clinical utility in the diagnosis and management of PDAC in humans.
Developmental and Pathological Angiogenesis (2011)

The formation of the vascular network is an intricate and complex process that is an obligate requirement during vertebrate development. The cardiovascular system is the first organ to develop and reach a functional state, which underscores the crucial role of the vasculature in the developing embryo. The development of the vasculature into highly branched conduits needs to occur in numerous sites and in precise patterns to supply oxygen and nutrients to the rapidly expanding tissue of the embryo. This process is mediated by the coordinated response of vascular endothelial and mural cells to the heterogeneous angiogenic cues provided by tissues and organs, whereas aberrant regulation and coordination of angiogenic signals during development result in lethality, impaired organ development, or disease states. This article reviews the essential signaling pathways required for establishment of the vertebrate vasculature with a major focus on a key regulatory factor, vascular endothelial growth factor (VEGF). We also discuss current knowledge of physiological angiogenic processes as well as their disruptions in pathological processes, particularly tumorigenesis.
Effects of ACE-inhibitors on learning and memory processes in rats. (2000)

The ACE inhibitors captopril and trandolapril improve learning and memory in active and passive avoidance tests comparable to the effect of the nootropic drug oxiracetam.
CD40 ligand‐independent B cell activation revealed by CD40 ligand‐deficient T cell clones: evidence for distinct activation requirements for antibody formation and B cell proliferation (1995)

We report the capacity of CD40 ligand (CD40L)-negative T cell clones to activate human B cells. CD40L-negative T cells induce a level of B cell proliferation 10-20% of that seen with normal T cells. The signal provided by the negative clones is synergistic with that derived from a CD40L transfectant, and restores B cell proliferation to normal levels, showing that CD40L-negative T cell clones are not inherently inhibitory for B cells. Although their capacity to induce proliferation was much reduced, CD40L-negative T cell clones were still strong inducers of B cell differentiation to plasma cells. This differentiation to plasma cells was inhibited by a CD40L transfectant. The data are discussed with regard to the normal in vivo mechanism for maintaining B cell memory and memory antibody responses to T-dependent antigens.
Endoglin Structure and Function (2006)

Determination of the functional relationship between the transforming growth factor-beta (TGFbeta) receptor proteins endoglin and ALK1 is essential to the understanding of the human vascular disease, hereditary hemorrhagic telangiectasia. TGFbeta1 caused recruitment of ALK1 into a complex with endoglin in human umbilical vein endothelial cells (HUVECs). Therefore, we examined TGFbeta receptor-dependent phosphorylation of endoglin by the constitutively active forms of the TGFbeta type I receptors ALK1, ALK5, and the TGFbeta type II receptor, TbetaRII. Of these receptors, TbetaRII preferentially phosphorylated endoglin on cytosolic domain serine residues Ser(634) and Ser(635). Removal of the carboxyl-terminal tripeptide of endoglin, which comprises a putative PDZ-liganding motif, dramatically increased endoglin serine phosphorylation by all three receptors, suggesting that the PDZ-liganding motif is important for the regulation of endoglin phosphorylation. Constitutively active (ca)ALK1, but not caALK5, phosphorylated endoglin on cytosolic domain threonine residues. caALK1-mediated threonine phosphorylation required prior serine phosphorylation, suggesting a sequential mechanism of endoglin phosphorylation. Wild-type, but not a threonine phosphorylation-defective endoglin mutant blocked cell detachment and the antiproliferative effects of caALK1 expressed in HUVECs. These results suggest that ALK1 is a preferred TGFbeta receptor kinase for endoglin threonine phosphorylation in HUVECs and indicate a role for endoglin phosphorylation in the regulation of endothelial cell adhesion and growth by ALK1.
Design of constructs for the expression of biologically active recombinant human factors X and Xa. Kinetic analysis of the expressed proteins (1991)

Activation of vitamin K-dependent plasma proteases occurs by specific interaction with components of the blood coagulation cascade. In this report, we describe the direct expression and enzymatic characterization of the human coagulation zymogen factor X and its activated form, factor Xa, from transformed Chinese hamster ovary fibroblast cell lines. Expression was achieved using either a full-length factor X cDNA or a unique mutant factor Xa cDNA. The functional factor Xa precursor contained a novel tripeptide bridge in place of the native 52-amino acid activation peptide. This mutation allowed for intracellular processing and secretion of the activated form of factor X. Secreted recombinant factors X (rX) and Xa (rXa) were purified by sequential anion-exchange and immunoaffinity chromatography. The enzymatic activities of factors rX and rXa were compared with those of plasma factors X and Xa in three independent assay systems. In comparison to human plasma factor X, the amidolytic, prothrombinase complex, and plasma clotting activities of factor rX were 50, 85, and 43%, respectively. The corresponding comparative activities for factor rXa were 32, 64, and 48%, respectively. The ability to directly express mutant forms of biologically active human factor X will facilitate the structure/function analysis of this important blood coagulation protein and may lead to the development of novel coagulation inhibitors.
Newly Emerging Resource Efficiency Manager Programs (1997)

Many facilities in the northwest such as K--12 schools, community colleges, and military installations are implementing resource-efficiency awareness programs. These programs are generally referred to as resource efficiency manager (REM) or resource conservation manager (RCM) programs. Resource efficiency management is a systems approach to managing a facility`s energy, water, and solid waste. Its aim is to reduce utility budgets by focusing on behavioral changes, maintenance and operation procedures, resource accounting, education and training, and a comprehensive awareness campaign that involves everyone in the organization.
Dihydropyridines in synthesis and biosynthesis. IV. Dehydrosecodine, in vitro precursor of indole alkaloids (1982)

The synthesis of the two isomeric dehydrosecodines is described. Stabilization of these systems is achieved by chromium carbonyl complexation of the dihydropyridine unit in these molecules. Reaction of the complexes with pyridine, or preferably ethylenediamine, allows insitu generation of the dehydrosecodines. A study of their chemistry and conversion to alkaloid systems is presented.
l-Asparaginase from Erwinia carotovora (1972)

The enzymatic properties of Erwinia carofovora L-asparaginase have been investigated and the K, and V,,, values for a number of substrates determined.L-Asparaginase has a K,,,of ~10~~ and a V max of 0.9 pmole of ammonia released per min per unit of enzyme for L-asparagine.All other substrates have much higher K, values and less than 25% of the V,,, of L-asparagine.From a study of substrate analogues, it has been established that Erwinia L-asparaginase requires a carboxyl group on the substrate two or three carbon atoms from the carboxamide group which is hydrolyzed.An amino group alpha to the free carboxyl group and in the L-configuration increases the stability of the enzyme-substrate complex but is not essential for catalysis.Small peptides with carboxyl-terminal asparagine residues are deamidated but amino-terminal or internal asparagine residues and large peptides with carboxyl-terminal asparagine residues such as insulin or insulin A chain derivatives are not deamidated.Likewise, glutamine peptides are not deamidated.,&Aspartoalkylamides have been prepared and tested as substrates.Compounds with straight chain alkyl substituents were hydrolyzed, whereas compounds with branched alkyl groups were not hydrolyzed.In addition, @-aspartamidoglycopeptides were not hydrolyzed.Erwinia L-asparaginase catalyzed the exchange of IsO between water and aspartic acid and the hydroxylaminolysis of asparagine and aspartic acid by hydroxylamine.Since the pioneering work of Kidd (1) and of Broome (2), Gasparaginase has been shown to be a powerful antilymphosarcoma agent when used against an asparagine-requiring sarcoma.Although the enzyme has been found in a number of organisms, e.g.serum of guinea pig and related rodents (3)) chicken liver (4)) yeast and molds (5), plants (6), and a number of bacteria (7-9), not all of these enzymes are clinically active (10,11).The antitumor activity has been proposed to be a function of the circulation half-life of the enzyme in the host serum ( 12) and of the enzyme affinity for L-asparagine (13).Two of the enzymes from
Arthroscopic Rotator Cuff Repair with Double-Row Fixation (2007)

Therapeutic Level IV.
Pressure wave propagation in a multibranched model of the human upper limb (1995)

The influence of the large arteries and the peripheral load on pressure wave propagation in the human upper limb was investigated in an anatomically realistic multibranched model based on linear transmission theory. To mimic vascular changes seen in life, the viscoelastic properties of large arteries and the peripheral load properties (represented as modified windkessels) were altered as follows: Young's modulus (from 10.9 x 10(6) to 15.3 x 10(6) dyn/cm2) and phase (from 0 to 15 degrees) of the complex elastance, windkessel time constant (from 0 to 0.6 s), and peripheral reflection coefficient (from 0 to 0.95). The relationship between the central aortic and peripheral radial pressure waveforms was analyzed in the time and the frequency domain. Results indicate that the large arterial properties have less influence (peak systolic pressure changed by 3% and peak of transfer function changed by 29%) than the properties of the peripheral load (systolic pressure changed by 14% and peak of transfer function changed by 74%) on the pressure wave propagation in the upper limb.
Mirk Protein Kinase Is Activated by MKK3 and Functions as a Transcriptional Activator of HNF1α (2002)

Mirk/Dyrk1B is an arginine-directed serine/threonine protein kinase that is expressed at low levels in most normal tissues but at elevated levels in many tumor cell lines and in normal skeletal muscle. Colon carcinoma cell lines stably overexpressing Mirk proliferated in serum-free medium, but the mechanism of Mirk action is unknown. DCoHm (dimerization cofactor of hepatocyte nuclear factor 1alpha ( HNF1alpha) from muscle), a novel gene of the DCoH family with 78% amino acid identity to DCoH, was identified as a Mirk-binding protein by yeast two-hybrid analysis and cloned. Mirk co-immunoprecipitated with DCoHm and bound to DCoHm in glutathione S-transferase pull-down assays. DCoH stabilizes HNF1alpha as a dimer and enhances its transcriptional activity on the beta-fibrinogen promoter reporter, and DCoHm had similar activity. Mirk enhanced HNF1alpha transcriptional activity in a dose-dependent manner, whereas two kinase-inactive Mirk mutants and a Mirk N-terminal deletion mutant did not. Mirk, DCoHm, and HNF1alpha formed a complex. Mirk bound to a specific region within the CREB-binding protein-binding region of HNF1alpha and phosphorylated HNF1alpha at a site adjacent to the Mirk-binding region. Conversely, the HNF1alpha binding domain was located within the first five conserved kinase subdomains of Mirk. Mirk co-immunoprecipitated with the MAPK kinase MKK3, an upstream activator of p38. MKK3 enhanced Mirk kinase activity and the transcriptional activation of HNF1alpha by Mirk, suggesting that Mirk, like p38, is activated by certain environmental stress agents. The Mirk-binding protein DCoH has been shown to be selectively expressed in colon carcinomas but not in normal tissue. Mirk may function as an HNF1alpha transcriptional activator in response to an MKK3-mediated stress signal, and the selective expression of DCoH could restrict the Mirk response to carcinoma cells.
Splenic requirement for antigenic variation and expression of the variant antigen on the erythrocyte membrane in cloned Plasmodium knowlesi malaria (1983)

Variant antigens appear on the surface of Plasmodium knowlesi-infected erythrocytes as the asexual parasite matures and are detected by antibody-mediated schizont-infected cell agglutination (SICA). We now show that cloned parasites can undergo antigenic variation in nonsplenectomized monkeys. In addition, we previously described a new P. knowlesi phenotype in which uncloned parasites passaged in splenectomized monkeys were no longer agglutinable by immune sera. We have designated this new phenotype SICA[-] and the one expressing the variant antigen SICA[+]. Cloned parasites can also switch from SICA[+] to SICA[-] in splenectomized monkeys. The switch from SICA[+] to SICA[-] is a gradual process that requires sequential subpassage in several monkeys. After passage in one monkey, the agglutination titer decreased 4- to 16-fold. Decreased agglutination was associated with decreased antibody binding on all infected erythrocytes as measured by fluorescein-conjugated anti-rhesus monkey immunoglobulin. The asexual malaria parasite can therefore alter its expression of variant antigen in response to the host environment (antivariant antibody or splenectomy). When cloned SICA[-] parasites were inoculated into intact monkeys, two courses of parasitemia were observed: fulminant parasitemia (greater than 20%) and parasitemia that was controlled. Fulminant infections were associated with conversion of the parasite from SICA[-] to SICA[+], i.e., from nonexpression to expression of the variant antigen on the erythrocyte surface. Parasitized erythrocytes remained SICA[-] in those infections that were controlled. It appears, therefore, that the expression of the variant antigen on the erythrocyte surface may influence parasite virulence.
Biosynthesis of the neural cell adhesion molecule: characterization of polypeptide C. (1985)

The biosynthesis of the neural cell adhesion molecule (N-CAM) was studied in primary cultures of rat cerebral glial cells, cerebellar granule neurons, and skeletal muscle cells. The three cell types produced different N-CAM polypeptide patterns. Glial cells synthesized a 135,000 Mr polypeptide B and a 115,000 Mr polypeptide C, whereas neurons expressed a 200,000 Mr polypeptide A as well as polypeptide B. Skeletal muscle cells produced polypeptide B. The polypeptides synthesized by the three cell types were immunochemically identical. The membrane association of polypeptide C was investigated with methods that distinguish peripheral and integral membrane proteins. Polypeptide C was found to be a peripheral membrane protein, whereas polypeptides A and B were integral membrane proteins with cytoplasmic domains of approximately 50,000 and approximately 25,000 Mr, respectively. The affinity of the membrane binding of polypeptide C increased during postnatal development. The posttranslational modifications of polypeptide C were investigated in glial cell cultures, and it was found to be N-linked glycosylated and sulfated.
Deleterious effects ofEchinacea purpureaand melatonin on myeloid cells in mouse spleen and bone marrow (2001)

The neurohormone, melatonin, a product of the pineal gland, is a potent immune cell stimulant. Phytochemicals contained in root extracts of the plant species Echinacea purpurea are also potent as immune cell stimulants. Both agents are potent stimulants of T, B, and/or natural killer cells, but little is known of their effect on other hemopoietic cells, specifically granular leukocytes, also participants in a wide variety of disease defense processes. Given their current popularity and availability for amelioration of a) jet lag and sleep disorders (melatonin) and b) virus-mediated respiratory infections (E. purpurea), we investigated the effects of these agents on granular leukocytes and their precursors, myeloid cells. Mice received these agents daily for 7 or 14 days via the diet, thus mimicking human administration, after which spleens and bone marrow were removed and assessed for mature, differentiated granulocytes and their myeloid progenitors. The influence of these agents was directly related to the stage of cell maturity. Administration of both agents together resulted in significantly elevated levels of myeloid progenitor cells in both bone marrow and spleen and significantly reduced levels of mature, functional granulocyte progeny in both organs, suggesting a) increased precursor proliferation, b) antiapoptosis among the progenitors, and/or c) inhibition of precursor maturation-the latter readily explaining the paucity of mature granulocyte progeny. In conclusion, individual administration of either the herbal derivative and melatonin was either without effect (E. purpurea) or even advantageous (melatonin) to cells of this lineage, but when administered together, these agents significantly perturbed myelopoiesis.
CD38 enhances the proliferation and inhibits the apoptosis of cervical cancer cells by affecting the mitochondria functions (2017)

Cervical cancer is one of the most common malignant tumors in women all over the world. The exact mechanism of occurrence and development of cervical cancer has not been fully elucidated. CD38 is a type II transmembrane glycoprotein, which was found to mediate diverse activities, including signal transduction, cell adhesion, and cyclic ADP‐ribose synthesis. Here, we reported that CD38 promoted cell proliferation and inhibited cell apoptosis in cervical cancer cells by affecting the mitochondria functions. We established stable cervical cancer cell lines with CD38 over‐expressed. CCK8 assay and colony formation assay indicated that CD38 promoted cervical cancer cell proliferation. Nude mouse tumorigenicity assay showed that CD38 significantly promotes tumor growth in vivo. CD38 also induced S phase accumulation in cell cycle analysis and suppressed cell apoptosis in cervical cancer cells. Meanwhile, flow cytometry analysis of mitochondria functions suggested that CD38 decreased intracellular Ca 2+ levels in cervical cancer cells and CD38 was involved in down‐regulation of ROS levels and prevented mitochondrial apoptosis in cervical cancer cells. The percentage of cells with loss of mitochondrial membrane potential (Δψm) in CD38‐overexpressed cervical cancer cells was less than control groups. Furthermore, we found an up‐regulation of MDM2, cyclinA1, CDK4, cyclinD1, NF‐kB P65, c‐rel, and a downregulation of P53, P21, and P38 by Western blot analysis. These results indicated that CD38 enhanced the proliferation and inhibited the apoptosis of cervical cancer cells by affecting the mitochondria functions.
Effects of Short-Chain Fatty Acids on Gastrointestinal Motility (1997)

Besides their action on gut morphology and function, short-chain fatty acids (SCFAs), produced by bacterial fermentation of carbohydrates in the colon, influence gastrointestinal motility. As they are not present in the stomach and proximal small intestine, SCFAs do not directly affect motility of these segments. However, caecal infusion of SCFAs as well as colonic fermentation of lactulose induce a relaxation of the proximal stomach in humans, indicating that SCFAs can affect motility at a distance from their site of production. Moreover, this suggests that SCFAs may be involved in the so-called "ileocolonic brake', i.e. the inhibition of gastric emptying by nutrients reaching the ileo-colonic junction. In the terminal ileum, where their concentration may increase following a colo-ileal reflux, SCFAs stimulate contractions and shorten ileal emptying, which may protect ileal mucosa against the potentially harmful effects of the reflux of colonic contents. Although SCFAs are produced and concentrated in the colon, their action on motility of this organ is not clearly understood and may depend on concentration, molecular structure of the acids, responsiveness of the colonic segments and animal species. The mechanisms of action of SCFAs on gastrointestinal motility are not completely elucidated. They may involve systemic humoral and neural pathways as well as local reflexes and myogenic responses.