gebhart/patrepeval huggingface dataset:
Hydrodynamic properties of the gonadotropin receptor from a murine Leydig tumor cell line are altered by desensitization (1987)

The murine Leydig tumor cell line 1 (MLTC-1) contains gonadotropin receptors (GR) that are coupled to adenylate cyclase through the stimulatory guanine nucleotide binding protein (Gs). The binding of human choriogonadotropin (hCG) causes MLTC-1 cells to accumulate cAMP. With time, the ability of MLTC-1 cells to respond to hCG is attenuated by a process called desensitization. The hydrodynamic properties of GR from control and desensitized MLTC-1 cells were studied. Sucrose density gradient sedimentation in H2O and D2O and gel filtration chromatography were used to estimate the Stokes radius (a), partial specific volume (vc), sedimentation coefficient (S20,w), and molecular weight (Mr) of the detergent-solubilized hormone-receptor complex (hCG-GR). [125I]hCG was bound to MLTC-1 cells under conditions that allow (37 degrees C) or prevent (0 degree C) desensitization, and hCG-GR was solubilized in Triton X-100. In the absence of desensitization, control hCG-GR had a Mr of 213,000 (a = 6.2; vc = 0.76; S20,w = 7.3), whereas desensitized hCG-GR had a Mr of 158,000 (a = 6.1; Vc = 0.71; S20,w = 6.6). Deglycosylated hCG (DG-hCG) is an antagonist that binds to GR with high affinity but fails to stimulate adenylate cyclase or cause desensitization. [125I]DG-hCG was bound to MLTC-1 cells and DG-hCG-GR solubilized in Triton X-100. The hydrodynamic properties of DG-hCG-GR (Mr 213,000; a = 5.8; Vc = 0.77; S20;w = 7.6) were the same as that for control hCG-GR. There was no evidence for the association of adenylate cyclase or Gs with GR in Triton X-100 solubilized preparations.(ABSTRACT TRUNCATED AT 250 WORDS)
Identification of novel neutralizing single‐chain antibodies against vascular endothelial growth factor receptor 2 (2011)

Human vascular endothelial growth factor (VEGF) and its receptor (VEGFR-2/kinase domain receptor [KDR]) play a crucial role in angiogenesis, which makes the VEGFR-2 signaling pathway a major target for therapeutic applications. In this study, a single-chain antibody phage display library was constructed from spleen cells of mice immunized with recombinant human soluble extracellular VEGFR-2/KDR consisting of all seven extracellular domains (sKDR D1-7) to obtain antibodies that block VEGF binding to VEGFR-2. Two specific single-chain antibodies (KDR1.3 and KDR2.6) that recognized human VEGFR-2 were selected; diversity analysis of the clones was performed by BstNI fingerprinting and nucleotide sequencing. The single-chain variable fragments (scFvs) were expressed in soluble form and specificity of interactions between affinity purified scFvs and VEGFR-2 was confirmed by ELISA. Binding of the recombinant antibodies for VEGFR-2 receptors was investigated by surface plasmon resonance spectroscopy. In vitro cell culture assays showed that KDR1.3 and KDR2.6 scFvs significantly suppressed the mitogenic response of human umbilical vein endothelial cells to recombinant human VEGF(165) in a dose-dependent manner, and reduced VEGF-dependent cell proliferation by 60% and 40%, respectively. In vivo analysis of these recombinant antibodies in a rat cornea angiogenesis model revealed that both antibodies suppressed the development of new corneal vessels (p < 0.05). Overall, in vitro and in vivo results disclose strong interactions of KDR1.3 and KDR2.6 scFvs with VEGFR-2. These findings indicate that KDR1.3 and KDR2.6 scFvs are promising antiangiogenic therapeutic agents.
Continuous flow in open microfluidics using controlled evaporation (2005)

This paper presents a method for programming the flow rate of liquids inside open microfluidic networks (MFNs). A MFN comprises a number of independent flow paths, each of which starts with an open filling port, has a sealed microchannel in which assays can be performed, and an open capillary pump (CP). The MFN is placed over Peltier elements and its flow paths initially fill owing to capillary forces when liquids are added to the filling ports. A cooling Peltier element underneath the filling ports dynamically prevents evaporation in all filling ports using the ambient temperature and relative humidity as inputs. Another Peltier element underneath the CPs heats the pumps thereby inducing evaporation in the CPs and setting the flow rate in the microchannels. This method achieves flow rates in the microchannels ranging from approximately 1.2 nL s(-1) to approximately 30 pL s(-1), and is able to keep 90% of a 0.6 microL solution placed in an open filling port for 60 min. This simple and efficient method should be applicable to numerous assays or chemical reactions that require small and precise flow of liquids and reagents inside microfluidics.
Carbohydrate structure and differential binding of prostate specific antigen to Maackia amurensis lectin between prostate cancer and benign prostate hypertrophy (2004)

Serum prostate-specific antigen (PSA) assay is widely used for detection of prostate cancer. Because PSA is also synthesized from normal prostate, false positive diagnosis cannot be avoided by the conventional serum PSA test. To apply the cancer-associated carbohydrate alteration to the improvement of PSA assay, we first elucidated the structures of PSA purified from human seminal fluid. The predominant core structure of N-glycans of seminal fluid PSA was a complex type biantennary oligosaccharide and was consistent with the structure reported previously. However, we found the sialic acid alpha2-3 galactose linkage as an additional terminal carbohydrate structure on seminal fluid PSA. We then analyzed the carbohydrate moiety of serum PSA from the patients with prostate cancer and benign prostate hypertrophy using lectin affinity chromatography. Lectin binding was assessed by lectin affinity column chromatography followed by determining the amount of total and free PSA. Concanavalin A, Lens culinaris, Aleuria aurantia, Sambucus nigra, and Maackia amurensis lectins were tested for their binding to the carbohydrates on PSA. Among the lectins examined, the M. amurensis agglutinin-bound fraction of free serum PSA is increased in prostate cancer patients compared to benign prostate hypertrophy patients. The binding of PSA to M. amurensis agglutinin, which recognizes alpha2,3-linked sialic acid, was also confirmed by surface plasmon resonance analysis. These results suggest that the differential binding of free serum PSA to M. amurensis agglutinin lectin between prostate cancer and benign prostate hypertrophy could be a potential measure for diagnosis of prostate cancer.
Bacillus subtilis genome project: cloning and sequencing of the 97 kb region from 325° to 333deg; (1993)

In the framework of the European project aimed at the sequencing of the Bacillus subtilis genome the DNA region located between gerB (314°) and sacXV (333°) was assigned to the Institut Pasteur. In this paper we describe the cloning and sequencing of a segment of 97 kb of contiguous DNA. Ninety-two open reading frames were predicted to encode putative proteins among which only forty-two were found to display significant similarities to known proteins present in databanks, e.g. amino acid permeases, proteins involved in cell wall or antibiotic biosynthesis, various regulatory proteins, proteins of several dehydrogenase families and enzymes II of the phosphotransferase system involved in sugar transport. Additional experiments led to the identification of the products of new B. subtilis genes, e.g. galactokinase and an operon involved in thiamine biosynthesis.
Systemic complement activation following human acute ischaemic stroke (2004)

The brain tissue damage after stroke is mediated partly by inflammation induced by ischaemia-reperfusion injury where the complement system plays a pivotal role. In the present study we investigated systemic complement activation and its relation to C-reactive protein (CRP), a known complement activator, and other inflammatory mediators after acute ischaemic stroke. Sequential plasma samples from 11 acute stroke patients were obtained from the time of admittance to hospital and for a follow-up period of 12 months. Nine healthy gender- and age-matched subjects served as controls. The terminal SC5b-9 complement complex (TCC), CRP, soluble adhesion molecules (L-, E- and P- selectin, ICAM, VCAM) and cytokines [tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-8] were analysed. All parameters were within normal values and similar to the controls the first hours after stroke. Terminal complement complex (TCC) increased significantly from 0.54 to 0.74 AU/ml at 72 h (P = 0.032), reached maximum at 7 days (0.90 AU/ml, P < 0.001), was still significantly increased at 12 days (0.70 AU/ml, P = 0.009) and thereafter normalized. CRP increased significantly from 1.02 to 2.11 mg/l at 24 h (P = 0.023), remained significantly increased for 1 week (2.53-2.94 mg/l, P = 0.012-0.017) and thereafter normalized. TCC and C-reactive protein (CRP) correlated significantly (r = 0.36, P < 0.001). The increase in TCC and CRP correlated to the size of infarction (r = 0.80 and P = 0.017 for TCC; r = 0.72 and P = 0.043 for CRP). No significant changes were seen for adhesion molecules and cytokines. In conclusion, transitory systemic complement activation takes place after stroke. The early rise in CRP and the following TCC increase suggest a possible role for CRP in complement activation, which may contribute to inflammation after stroke.
STATUS OF THE SNS BEAM POWER UPGRADE PROJECT (2006)

The baseline Spallation Neutron Source (SNS) accelerator complex, consisting of an H- injector, a 1 GeV linear accelerator, and an accumulator ring, will provide a 1 GeV, 1.44 MW proton beam to a liquid mercury target for neutron production. Even in the baseline design, many of the accelerator subsystems are capable of supporting higher beam intensities and higher beam energy. Upgrades to the SNS accelerator and target systems to increase the beam power to at least 2 MW, with a design goal of 3 MW, are in the planning stages. The upgrade beam parameters will be presented and the required hardware modifications will be described.
Passive immunization of mice against Klebsiella aerogenes. (1986)

Klebsiella vaccines were isolated by mild diafiltration techniques from culture filtrates of nine capsular types of K. aerogenes (K1, K2, K3, K15, K20, K35, K36, K44 & K63). The bacteria were grown in a chemically defined medium in standardized conditions in a fermenter. The vaccines had a molecular weight of more than 20 000, a carbohydrate content of 40-89%, a protein content of between less than 1 and 16% and small amounts (0.6-1.2%) of lipopolysaccharide. Antisera raised in rabbits to the nine klebsiella vaccines were standardized by passive haemagglutination, immunoglobulin G enzyme-linked immunosorbent assay and by autologous passive protection tests. Each rabbit antiserum when passively transferred to mice showed a variable capacity to passively protect mice against lethal infections by a panel of ten capsular types of K. aerogenes (K1-K10). Seven of the rabbit antisera protected mice against more than half of the challenge strains. A pool of six rabbit antisera (anti-K1, K2, K3, K20, K35 & K44) passively protected mice against lethal infections from strains of bacteria representing each of 77 capsular types of K. aerogenes.
Synthesis of High Surface Area Hydroxyapatite Nanoparticles by Mixed Surfactant-Mediated Approach (2005)

A new surfactant-mediated approach was developed to synthesize hydroxyapatite (HAp) nanoparticles with high surface areas by calcination of their precursors encapsulated with calcium stearate using mixed surfactant-containing reaction mixtures. Acidic aqueous solution of calcium phosphate was mixed with both or either nonaoxyethylene dodecyl ether (C12EO9) and polyoxyethylene(20) sorbitan monostearate (Tween 60) and then was treated with aqueous ammonium at 25 degrees C. The C12EO9-based single surfactant system yielded an aggregate of platy HAp nanoparticles 20-40 nm in size, whereas the Tween 60-based single and mixed systems led to lath-shaped HAp nanoparticles 2-8 nm wide and encapsulated with calcium stearate. On calcination at 500 degrees C, the stearate-encapsulated HAp nanoparticles in the latter two systems were deorganized into high surface area HAp nanoparticles. Particularly, the HAp nanoparticles in the mixed system exhibited a specific surface area as high as 364 m2 g(-1) that is roughly 3 times larger than 160 m2 g(-1) for those in the single system. The significantly high surface area for the former is attributed to much less adhesion of decapsulated HAp nanoparticles, which originated from the particle-separating effect of the C12EO9 molecules adsorbed on the outer surface of the stearate-encapsulated HAp nanoparticles to inhibit their agglomeration or interfacial coordination. The present results demonstrate that the mixed use of two different surfactants as a source of encapsulating and templating agent and a particle-separating agent is specifically effective for the synthesis of high surface area HAp nanoparticles.
Vitronectin-driven human keratinocyte locomotion is mediated by the alpha v beta 5 integrin receptor. (1994)

Vitronectin is a soluble serum factor that is known to promote epiboly of keratinocytes in explant cultures and enhance cell spreading and attachment to matrix. Recently, vitronectin was demonstrated to promote human keratinocyte locomotion. The mechanism(s) by which vitronectin enhances keratinocyte migration is unknown. In this study, we quantitated the vitronectin-driven migration of human keratinocytes in the presence of antibodies to vitronectin receptors. We found that vitronectin's effect of promoting human keratinocyte migration was inhibited by antibody-directed against the alpha v beta 5 receptor. In addition, we surface-labeled human keratinocytes, chromatographed extracts of the cell membranes on a vitronectin column, and then immunoprecipitated the bound and eluted proteins with antibodies to specific vitronectin receptors. We identified the vitronectin receptors on human keratinocytes as bands of 150,000 and 100,000 daltons without reduction and as 125,000 and 110,000 daltons under reducing conditions. Immunoprecipitation with specific antibodies identified the major receptor to be the alpha v beta 5 integrin. In addition, we quantitated vitronectin-driven migration of human keratinocytes in the presence of Arg-Gly-Asp (RGD) and control peptides. We found that the presence of RGD, but not control peptide, inhibited vitronectin-driven migration of human keratinocytes. These studies demonstrate that human keratinocytes express vitronectin receptors and use the alpha v beta 5 receptor for cellular locomotion.
Cellular and Subcellular Localization of Six Retinoid Receptors in Rat Testis During Postnatal Development: Identification of Potential Heterodimeric Receptors1 (1999)

Vitamin A is required in the testis for germ cell development. It acts through two families of retinoid receptors, retinoic acid receptors (RAR) and retinoid X receptors (RXR), each with three subtypes alpha, beta, and gamma. These receptors are postulated to dimerize and regulate the transcription of retinoid-responsive genes that are crucial for germ cell development. In this study, we determined the cellular and subcellular localization of six retinoid receptors in the developing rat testis to identify the specific cellular sites and times of receptor expression. Immunohistochemical results revealed the expression of RARalpha, RARbeta, RXRalpha, and RXRgamma proteins in somatic and germ cells throughout postnatal development. In contrast, the expression of RARgamma and RXRbeta did not increase until 30-35 days of age in somatic cells from the testis. Interestingly, RARalpha and RXRalpha had a similar subcellular localization pattern in Sertoli cells throughout postnatal testis development, while RARalpha and RXRgamma were both present in the nucleus of spermatocytes and elongating spermatids. These results suggest that RARalpha may potentially dimerize with RXRalpha in Sertoli cells and with RXRgamma in germ cells. In addition, we demonstrate that the only RAR in the nucleus of early meiotic germ cells is RARalpha.
A highly conserved protein family interacting with the fragile X mental retardation protein (FMRP) and displaying selective interactions with FMRP-related proteins FXR1P and FXR2P (2001)

The absence of the fragile X mental retardation protein (FMRP), encoded by the FMR1 gene, is responsible for pathologic manifestations in the Fragile X Syndrome, the most frequent cause of inherited mental retardation. FMRP is an RNA-binding protein associated with polysomes as part of a messenger ribonucleoprotein (mRNP) complex. Although its function is poorly understood, various observations suggest a role in local protein translation at neuronal dendrites and in dendritic spine maturation. We present here the identification of CYFIP1/2 (Cytoplasmic FMRP Interacting Proteins) as FMRP interactors. CYFIP1/2 share 88% amino acid sequence identity and represent the two members in humans of a highly conserved protein family. Remarkably, whereas CYFIP2 also interacts with the FMRP-related proteins FXR1P/2P, CYFIP1 interacts exclusively with FMRP. FMRP--CYFIP interaction involves the domain of FMRP also mediating homo- and heteromerization, thus suggesting a competition between interaction among the FXR proteins and interaction with CYFIP. CYFIP1/2 are proteins of unknown function, but CYFIP1 has recently been shown to interact with the small GTPase Rac1, which is implicated in development and maintenance of neuronal structures. Consistent with FMRP and Rac1 localization in dendritic fine structures, CYFIP1/2 are present in synaptosomal extracts.
Usual ductal hyperplasia of the breast is a committed stem (progenitor) cell lesion distinct from atypical ductal hyperplasia and ductal carcinoma in situ (2002)

Current classification systems in proliferative mammary gland pathology are based on a two-cell system, recognizing only glandular and myoepithelial lines of differentiation. A third cell type has recently been characterized in normal breast tissue by double-immunofluorescence analysis to express cytokeratin 5 (Ck5) only. These cells were shown to represent progenitor or adult stem cells that give rise to the glandular and myoepithelial cell lineage. The double-labelling technique has been applied to characterize a spectrum of intraductal epithelial proliferations, namely benign usual ductal hyperplasia, atypical ductal hyperplasia, and ductal carcinoma in situ, all of which are thought to represent the gradual steps of a sequence in the development of breast cancer. Immunofluorescence studies with specific antibodies against Ck5, Ck8/18/19, and smooth muscle actin were complemented by western blotting analysis of Ck5 and Ck8/18/19 expression in normal breast tissue and in proliferative lesions. Usual ductal hyperplasia appears to be a Ck5-positive committed stem (progenitor) cell lesion with the same differentiation potential as seen in the normal breast. This is in sharp contrast to atypical ductal hyperplasia/ductal carcinoma in situ, which display the differentiated glandular immunophenotype (Ck8/18/19-positive, but Ck5-negative). These data require the abandonment of the idea of an obligate biological continuum of intraductal proliferations from benign to malignant. This study provides evidence that cells undergoing malignant transformation tend to be fairly advanced in the glandular lineage of differentiation. The committed stem (progenitor) cell model may contribute to a better understanding of both benign proliferative breast disease and breast cancer development.
Use of the World Wide Web for Multisite Data Collection (1997)

As access to the Internet becomes increasingly available, research applications in medicine will increase. This paper describes the use of the Internet, and, more specifically, the World Wide Web (WWW), as a channel of communication between EDs throughout the world and investigators who are interested in facilitating the collection of data from multiple sites. Data entered into user-friendly electronic surveys can be transmitted over the Internet to a database located at the site of the study, rendering geographic separation less of a barrier to the conduction of multisite studies. The electronic format of the data can enable real-time statistical processing while data are stored using existing database technologies. In theory, automated processing of variables within such a database enables early identification of data trends. Methods of ensuring validity, security, and compliance are discussed.
Stable Association of Presenilin Derivatives and Absence of Presenilin Interactions with APP (1998)

Mutations in two related genes, presenilin 1 and 2 presenilin 2 (PS1 and PS2), cosegregate with Alzheimer's disease. PS1 and PS2 are highly homologous polytopic membrane proteins that are subject to endoproteolytic cleavage in vivo. The resulting N- and C-terminal derivatives are the preponderant PS-related species that accumulate in cultured cells and tissue. In earlier studies, we demonstrated that PS1 N- and C-terminal derivatives accumulate to 1:1 stoichiometry and that the absolute levels of fragments are established by a tightly regulated and saturable mechanism. These findings led to the suggestion that the levels of PS1 derivatives might be determined by their association with limiting cellular components. In this study, we use in situ chemical cross-linking and coimmunoprecipitation analyses to document that the N- and C-terminal derivatives of either PS1 or PS2 can be coisolated. Moreover, and in contrast to published reports which documented that PS1 and PS2 form stable heteromeric assemblies with the beta-amyloid precursor protein (APP), we have failed to provide evidence for physiological complexes between PS1 and PS2 holoproteins or their derivatives with APP.
Side effects of clenbuterol as a repartitioning agent (1987)

Clenbuterol, a synthetic beta-adrenergic agonist drug, can be used to increase the ratio of protein to fat in the carcase of meat animals. During the first one to three days of its administration to sheep or calves clenbuterol increased their heart rate, and in sheep it decreased blood pressure. Continued administration had no further effect on heart rate or blood pressure but in sheep dose levels above 1.5 mg/day depressed appetite for up to five days; at all dose levels clenbuterol brought about a long term increase in metabolic rate.
Enhanced d-Amino Acid Incorporation into Protein by Modified Ribosomes (2003)

By overexpression of modified Escherichia coli 23S rRNAs from multicopy plasmids, ribosomes were prepared that contained mutations in two regions (2447-2450 and 2457-2462) of 23S rRNA. Following mutagenesis and selection, two clones with mutations in the 2447-2450 region (peptidyltransferase center) and six with mutations in the 2457-2462 region (helix 89) were characterized. The mutations were shown to exhibit a high level of homology. Cell-free protein synthesizing systems prepared from these clones were found to exhibit significantly enhanced incorporation of d-methionine and d-phenylalanine into protein. The incorporations involved positions 10, 22, and 54 of E. coli dihydrofolate reductase and positions 247 and 250 of Photinus pyralis firefly luciferase. Interestingly, some of the derived proteins containing the d-amino acids (notably DHFR analogues altered at position 10) functioned as well as those containing the respective l-amino acids, while substitution at other positions resulted in proteins having greatly diminished activity.