gebhart/patrepeval huggingface dataset:
Genomic and Expression Analysis of the 3q25-q26 Amplification Unit Reveals TLOC1/SEC62 as a Probable Target Gene in Prostate Cancer (2006)

Gain at chromosome 3q25-q26 has been reported to commonly occur in prostate cancer. To map the 3q25-q26 amplification unit and to identify the candidate genes of amplification, we did fluorescence in situ hybridization and quantitative real-time PCR for gene copy number and mRNA expression measurements in prostate cancer cell lines and prostate cancer samples from radical prostatectomy specimens. The minimal overlapping region of DNA copy number gains in the cell lines could be narrowed down to 700 kb at 3q26.2. Of all positional and functional candidates in this region, the gene TLOC1/SEC62 revealed the highest frequency (50%) of copy number gains in the prostate cancer samples and was found to be up-regulated at the mRNA level in all samples analyzed. TLOC1/Sec62 protein was also shown to be overexpressed by Western blot analysis. Intriguingly, the TLOC1/SEC62 gene copy number was increased in prostate tumors from patients who had a lower risk of and a longer time to progression following radical prostatectomy. These findings make TLOC1/SEC62 the best candidate within the 3q amplification unit in prostate cancer. TLOC1/Sec62 protein is a component of the endoplasmic reticulum protein translocation machinery, whose function during prostate carcinogenesis remains to be determined.
Mode of action of anti-lipopolysaccharide-binding protein antibodies for prevention of endotoxemic shock in mice. (1994)

Lipopolysaccharide (LPS)-binding protein (LBP) has been shown to regulate the response of monocytes to LPS in vitro. In a previous study, polyclonal anti-LBP IgGs were found to protect D-galactosamine-sensitized mice against a lethal endotoxemic shock induced by a low challenge of LPS or lipid A when administered simultaneously with endotoxin. In the present study, we investigated the mode of action of these anti-LBP IgGs. In vitro, we demonstrated that they interfere with LPS binding to monocytes or polymorphonuclear cells in different ways: by the mere prevention of binding of LPS to LBP thus preventing the binding of LPS to CD14, or by reacting with LPS-LBP complexes thus mediating their binding to complement or Fc receptors on monocytes and on polymorphonuclear cells. In vivo, we demonstrated that anti-LBP IgGs afforded protection against lethal endotoxemic shock by one of two mechanisms. First, LBP blockade by pretreatment with anti-LBP IgG allowed protection against a low dose of LPS (100 ng). This protection occurred despite LPS levels in blood similar to those in control mice but in the absence of detectable tumor necrosis factor (TNF). This demonstrated that anti-LBP IgG could block the LBP-mediated TNF release upon LPS challenge. In contrast, anti-LBP IgG did not afford protection in mice not sensitized with D-galactosamine and challenged with high-dose LPS (1 mg), confirming that LPS at high concentrations could stimulate cells independently of the LBP pathway. Second, anti-LBP treatment administered simultaneously with LPS challenge protected mice against both low and high doses of LPS. Unlike after pretreatment with anti-LBP IgG, this protection was accompanied by a decrease of circulating LPS, suggesting that anti-LBP IgG in these conditions facilitated clearance of LPS probably by clearing LPS-LBP complexes. These data and the fact that LBP binds to all LPS through lipid A suggest that antibody directed to LBP could be a candidate for therapeutic strategies in endotoxemic shock.
Modification of the Bankart reconstruction with a suture anchor (1991)

We assessed the effectiveness of a new suture anchor that has been designed to anchor sutures into a blind, straight hole drilled in bone. The strength of fixation in glenoid bone is 67 N for the No. 0 anchor and suture, and 82 N for the No. 2 device with suture. During 1988 and 1989, 32 patients underwent a modified Bankart reconstruction for recurrent anterior glenohumeral instability at two centers as part of a prospective study of this modified technique. There were no complications as a result of the technique. The four surgeons involved agreed that the suture anchor simplified the procedure. Seventeen patients have been reviewed, with more than 1 year followup. Ninety-four percent had good to excellent results according to the Bankart rating scale. There was one recurrent dislocation in a football player.
Inhibition of the Phosphatidylinositol 3-Kinase/p70S6-Kinase Pathway Induces B16 Melanoma Cell Differentiation (1996)

alpha-Melanocyte-stimulating hormone and cAMP-elevating agents are known to induce B16 cell differentiation, characterized by increased melanin synthesis and dendrite outgrowth. In order to elucidate intracellular signaling pathways involved in this differentiation process, we focused our interest on the phosphatidylinositol 3-kinase/p70(S6)-kinase pathway. The specific inhibition of phosphatidylinositol 3-kinase by LY294002 markedly stimulated dendrite outgrowth, thus mimicking the action of cAMP-elevating agents on B16 cell morphology. In addition, LY294002 and rapamycin, a specific p70(S6)-kinase inhibitor, were found to independently stimulate tyrosinase expression, thus increasing melanin synthesis. In an attempt to better dissect the molecular mechanisms triggered by cAMP to induce melanoma cell differentiation, we examined the effects of a cAMP-elevating agent forskolin, on both phosphatidylinositol 3-kinase and p70(S6)-kinase activities. Specific kinase assays revealed that forskolin partially inhibited phosphatidylinositol 3-kinase activity and completely blocked p70(S6)-kinase activity and phosphorylation. In conclusion, our results clearly demonstrate that the inhibition of phosphatidylinositol 3-kinase and p70(S6)-kinase is involved in the regulation of B16 cell differentiation. Furthermore, we provide evidence which suggests that cAMP-induced melanogenesis and dendricity are, at least partially, mediated by the cAMP inhibition of the phosphatidylinositol 3-kinase/p70(S6)-kinase signaling pathway.
Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis (2017)

In postmenopausal women with osteoporosis who were at high risk for fracture, romosozumab treatment for 12 months followed by alendronate resulted in a significantly lower risk of fracture than alendronate alone. (Funded by Amgen and others; ARCH ClinicalTrials.gov number, NCT01631214 .).
The synthetic peptide WKYMVm attenuates the function of the chemokine receptors CCR5 and CXCR4 through activation of formyl peptide receptor-like 1 (2001)

The G protein-coupled 7 transmembrane (STM) chemoattractant receptors can be inactivated by heterologous desensitization. Earlier work showed that formly peptide receptor-like 1 (FPRL1), an STM receptor with low affinity for the bacterial chemotactic peptide formyl-methionyl-leucyl-phenylalamine (fMLF), is activated by peptide domains derived from the human immunodeficiency virus (HIV)-1 envelope glycoprotein gp120 and its activation results in desensitization and down-regulation of the chemokine receptors CCR5 and CXCR4 from monocyte surfaces. This study investigated the possibility of interfering with the function of CCR5 or CXCR4 as HIV-1 coreceptors by activating FPRL1. Cell lines were established expressing FPRL1 in combination with CD4/CXCR4 or CD4/CCR5 and the effect of a synthetic peptide, WKYMVm, a potent activator of formyl peptide receptors with preference for FPRL1 was determined. Both CXCR4 and CCR5 were desensitized by activation of the cells with WKYMVm via a staurosporine-sensitive pathway. This desensitization of CXCR4 and CCR5 also attenuated their capacity as the fusion cofactors for HIV-1 envelope glycoprotein and resulted in a significant inhibition of p24 production by cell lines infected with HIV-1 that use CCR5 or CXCR4 as coreceptors. Furthermore, WKYMVm inhibited the infection of human peripheral monocyte-derived macrophages and CD4(+) T lymphocytes by R5 or X4 strains of HIV-1, respectively. These results indicate that heterologous desensitization of CCR5 and CXCR4 by an FPRL1 agonist attenuates their major biologic functions and suggest an approach to the development of additional anti-HIV-1 agents. (Blood. 2001;97:2941-2947)
BAY 87‐2243, a highly potent and selective inhibitor of hypoxia‐induced gene activation has antitumor activities by inhibition of mitochondrial complex I (2013)

The activation of the transcription factor hypoxia-inducible factor-1 (HIF-1) plays an essential role in tumor development, tumor progression, and resistance to chemo- and radiotherapy. In order to identify compounds targeting the HIF pathway, a small molecule library was screened using a luciferase-driven HIF-1 reporter cell line under hypoxia. The high-throughput screening led to the identification of a class of aminoalkyl-substituted compounds that inhibited hypoxia-induced HIF-1 target gene expression in human lung cancer cell lines at low nanomolar concentrations. Lead structure BAY 87-2243 was found to inhibit HIF-1α and HIF-2α protein accumulation under hypoxic conditions in non-small cell lung cancer (NSCLC) cell line H460 but had no effect on HIF-1α protein levels induced by the hypoxia mimetics desferrioxamine or cobalt chloride. BAY 87-2243 had no effect on HIF target gene expression levels in RCC4 cells lacking Von Hippel-Lindau (VHL) activity nor did the compound affect the activity of HIF prolyl hydroxylase-2. Antitumor activity of BAY 87-2243, suppression of HIF-1α protein levels, and reduction of HIF-1 target gene expression in vivo were demonstrated in a H460 xenograft model. BAY 87-2243 did not inhibit cell proliferation under standard conditions. However under glucose depletion, a condition favoring mitochondrial ATP generation as energy source, BAY 87-2243 inhibited cell proliferation in the nanomolar range. Further experiments revealed that BAY 87-2243 inhibits mitochondrial complex I activity but has no effect on complex III activity. Interference with mitochondrial function to reduce hypoxia-induced HIF-1 activity in tumors might be an interesting therapeutic approach to overcome chemo- and radiotherapy-resistance of hypoxic tumors.
Cumulus oophorus extracellular matrix in the human oocyte: a role for adhesive proteins. (2005)

A viscous elastic matrix secreted by the cumulus oophorus cells represent the "extracellular matrix" surrounding the human mature oocyte obtained from assisted reproductive technology (ART). The cumulus matrix is involved in several reproductive processes, including the pick-up of the oocyte-cumulus complex by the oviduct, the final maturation of the ovum and sperm-egg interaction. As showed by some Authors, the cumulus matrix is rich in hyaluronan, as well as in other proteins including inter-alpha-trypsin inhibitor, a dermatan sulfate proteoglycan, and a pentraxin-3. Proteins and hyaluronan are linked together to form a meshwork comprised of granules and filaments. We found in human cumulus oocyte complexes the presence of specialized cells still capable of producing fibronectin and tenascin-c in the post-ovulatory period. Moreover, fibronectin and tenascin-c are present within the hyaluronan matrix at fertilization during the tubal sojourn of the ovum and the embryo. Since pentraxin3 is important in matrix stabilization and gamete interactions, a possible role for fibronectin and tenascin-c may be postulated in the final maturation of the ovum, in the tubal pick-up and in the complex dialogue with the tubal epithelium.
Protective immunity against Salmonella typhimurium elicited in mice by oral vaccination with phosphorylcholine encapsulated in poly(DL-lactide-co-glycolide) microspheres (1997)

Encapsulation of vaccines in biodegradable microspheres provides excellent mucosal immunogens with a high potential for immunization against bacterial infections. We tested the protective immunity elicited by intragastric vaccination with phosphorylcholine (PC) encapsulated in poly(DL-lactide-co-glycolide) (DL-PLG) microspheres against Salmonella typhimurium in a mouse model of invasive intestinal infection. We chose PC as the antigen because it was found to elicit an immune response after intestinal exposure of mice to PC-bearing S. typhimurium and because anti-PC immunity protects mice against Streptococcus pneumoniae, another PC-bearing microorganism. Mice were primed intragastrically on days 1, 2, and 3 and boosted on days 28, 29, and 30 with PC (280 microg) coupled to porcine thyroglobulin (PC-thyr) encapsulated in DL-PLG microspheres, free PC-thyr, or blank microspheres. A significant rise in anti-PC immunoglobulin A (IgA) titers, as measured by an enzyme-linked immunosorbent assay, was observed in the intestinal secretions after immunization with PC-loaded microspheres, compared to the titers of mice immunized with free PC-thyr or blank microspheres. This antibody response peaked 14 days after the last boost and correlated with a highly significant resistance to oral challenge by S. typhimurium C5 (P < 10(-3)). Control mice were primed intraperitoneally on day 1 with 15 microg of PC in complete Freund's adjuvant and boosted on days 10, 14, and 20 with the same dose without adjuvant but via the same route. In these mice, the levels of anti-PC IgA in intestinal secretions were equivalent to those of the mice intragastrically immunized with PC-loaded microspheres, but protection was significantly weaker, suggesting that either the IgAs were not functional or that other immune mechanisms are important in protection. Taken together, our results highlight the potential of antigen encapsulation in DL-PLG microspheres for eliciting protective immunity against invasive intestinal bacterial diseases and suggest that a similar strategy could be used against diseases caused by other PC-bearing microorganisms.
Fractals and Chaos (1997)

Fractals and Chaos: An Illustrated Course provides you with a practical, elementary introduction to fractal geometry and chaotic dynamics-subjects that have attracted immense interest throughout the scientific and engineering disciplines. The book may be used in part or as a whole to form an introductory course in either or both subject areas. A prominent feature of the book is the use of many illustrations to convey the concepts required for comprehension of the subject. In addition, plenty of problems are provided to test understanding. Advanced mathematics is avoided in order to provide a concise treatment and speed the reader through the subject areas. The book can be used as a text for undergraduate courses or for self-study.
Cloning of two members of the SIRPα family of protein tyrosine phosphatase binding proteins in cattle that are expressed on monocytes and a subpopulation of dendritic cells and which mediate binding to CD4 T cells (1998)

Recent experimental studies have greatly clarified the function of cell surface molecules in the induction and modulation of T cell responses by antigen-presenting cells (APC). However, the differences in ability to stimulate T cells evident for different types and subpopulations of the same APC, such as dendritic cell subsets, is less well understood. This report details an investigation of an antigen expressed on monocytes that is also expressed on a subset of cattle afferent lymph veiled cells (ALVC). A cDNA library derived from cattle monocytes was screened with monoclonal antibodies (mAb) for expression in COS-7 cells. Using separate mAb for screening, two cDNA were cloned, the sequences of which showed a single long open reading frame encoding a predicted type I glycoprotein of 506 amino acids that contained three immunoglobulin superfamily domains and a long 112-amino acid cytoplasmic tail. We have termed this antigen MyD-1, reflecting its myeloid and dendritic cell distribution. Analysis of the EMBL database revealed that the molecule is a member of the recently described family of signal regulatory proteins (SIRP). The outeremost Ig domain was of the adhesion/receptor I-type, suggesting that MyD-1 might bind to a ligand on another cell. Evidence for this was subsequently obtained by demonstrating that COS-7 cells transfected with MyD-1 cDNA bound CD4 T cells and this binding was blocked by specific mAb. The potential importance of this interaction was supported by the finding that the proliferation of resting memory CD4 T cells to ovalbumin-pulsed monocytes was significantly reduced in the presence of mAb to MyD-1. A role for the molecule in the modulation of the monocyte/dendritic APC response is also predicted from the existence of multiple potential tyrosine phosphorylation sites in the cytoplasmic domain, including the presence of an immunoreceptor tyrosine-based inhibitory motif (ITIM) and the observation that the SIRP alpha family members have been shown to bind to SHP-1 and SHP-2. Together these data indicate a possible functional importance for MyD-1 in the regulation of monocyte and dendritic cell function.
Mild therapeutic hypothermia in patients after out-of-hospital cardiac arrest due to acute ST-segment elevation myocardial infarction undergoing immediate percutaneous coronary intervention* (2008)

MTH in combination with primary PCI is feasible and safe in patients resuscitated after cardiac arrest due to acute myocardial infarction. A combination of these therapeutic procedures should be strongly considered as standard therapy in patients after out-of-hospital cardiac arrest due to STEMI.
Formation of heterodimers from three neurotrophins, nerve growth factor, neurotrophin-3, and brain-derived neurotrophic factor. (1994)

Three neurotrophic factors, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and nerve growth factor (NGF) form noncovalent homodimers in solution. Since they are highly homologous proteins, it seemed probable that two monomers of these proteins might associate together to form a heterodimer. This was tested by denaturing the two different proteins together in 6 M guanidine HCl and refolding them in phosphate-buffered saline. When the refolded mixture of BDNF and NT-3 was subjected to Mono S cation exchange chromatography, a new peak was observed eluting between NT-3 and BDNF, which accounted for about 30% of the protein used. This new protein species migrated as a single band upon native gel electrophoresis with mobility between that of the NT-3 homodimer and the BDNF homodimer, indicating that a complex had been formed. Sedimentation equilibrium data show that the dissociation constant of this heterodimer is < 3 x 10(-10) M. The heterodimer was stable upon incubation at 37 degrees C in phosphate-buffered saline over 11 days. Having determined that the heterodimer is highly stable, it was subjected to various biological assays. Autophosphorylation assay using TrkB receptor showed that the heterodimer is indistinguishable from the BDNF or NT-3 homodimer in the ability to induce phosphorylation of the receptor. It was also indistinguishable from the homodimers in the neurotrophic activity using chick dorsal root ganglion explant. In the sympathetic neuron survival assay, the heterodimer behaved more similarly to NT-3, whereas in the dopamine uptake assay, it was intermediate between the two homodimers. In addition, the heterodimer was shown to be retrogradely transported in the dorsal root ganglion neurons. A heterodimer between NGF and BDNF is formed but much less effectively than the NT-3.BDNF heterodimer, and it is not stable even at 4 degrees C. These results indicate that BDNF and NT-3 have an intersubunit contact surface for dimerization resembling each other's but different from the contact surface of NGF.
Large-scale superconductivity-induced conductance suppression in mesoscopic normal-superconducting structures (1997)

Experiments on hybrid superconducting normal-metal structures have revealed that even in the absence of tunnel junctions the onset of superconductivity can lead to a decrease in the electrical conductance by an amount many orders of magnitude greater than $e^2/h$. In this Letter we provide a theory of this phenomenon which shows that it originates from an instability in 4 - probe conductance measurements which is absent from 2-probe measurements. We compare the zero-bias,zero-temperature 4-probe conductances $G_{N}$ and $G_{S}$ of a normal diffusive metal in contact with a superconductor in both the normal (N) and superconducting (S) states respectively. In the absence of tunnel barriers, the ensemble average of the difference $δG=G_{S}-G_N$ vanishes, in agreement with quasi-classical theory. However we also predict that there exists macroscopic sample specific fluctuations in $δG$, which lie beyond quasi-classical theory and allow large negative values of $δG$ to occur.
Layer-by-Layer Poly(phenylene ethynylene) Films on Silica Microspheres for Enhanced Sensory Amplification (2005)

Alternating polyelectrolyte “layer-by-layer” deposition has been used to create emissive thin films of a weakly anionic, nonaggregating poly(phenylene ethynylene) on silica microspheres. The resulting particles are smooth and emit fluorescence solely from the outside polymer-coated surface. Suspensions of the coated microspheres show similar fluorescence properties to polymers in solution, but with enhanced sensitivity (up to 200-fold) to nitroaromatic quenchers. These enhancements are attributed to a combination of surface and electronic effects.
Cloning and sequence of several alpha 2u-globulin cDNAs. (1981)

We describe a simple cloning procedure for alpha 2u-globulin that requires neither enrichment of mRNA for cloning nor purification of a specific probe for screening recombinant colonies. Total adult male liver poly(A)+RNA was used as template for cloning, and the subsequent recombinant colonies were screened by comparing hybridization to radioactive cDNA probes prepared from hepatic male and female mRNA, respectively. Almost all of the selected "male-specific" clones were later shown to contain alpha 2u-globulin sequences. This cloned alpha 2u-globulin cDNA has been shown to specifically hybridize to male rat liver RNA, which, when isolated and translated in vitro, codes for a 21,000-dalton protein (pro-alpha 2u-globulin) immunologically identical to alpha 2u-globulin. When translation occurs in the presence of pancreatic microsomes this in vitro synthesized pro-alpha 2u-globulin is processed to the 19,000-dalton mature form of alpha 2u-globulin. The nucleotide sequence of the alpha 2u-globulin cDNA has been determined, thus elucidating the complete amino acid sequence of alpha 2u-globulin and most of the hydrophobic "leader" sequence of pro-alpha 2u-globulin. The amino acid sequence deduced from the cDNA is in agreement with the partial sequence that we previously determined by sequential Edman degradation of the purified protein. alpha 2u-Globulin cDNA clones contain within the 3'-untranslated region one or both of the two putative polyadenylylation/transcription termination sites (A-A-T-A-A-A and A-A-T-T-A-A-A). Either of these can be used, generating alpha 2u-globulin mRNA species of two lengths. A codon usage analysis of the cDNA showed that, although all six leucine codons are used for the 14 leucine residues in mature alpha 2u-globulin, the seven leucines in the partial leader sequence reported are all encoded by the same codon, CTG. The primary amino acid sequence contains a unique Asn-Gly-Ser sequence, likely to be in beta-turn conformation, as the probable site of glycosylation for this glycoprotein.