gebhart/patrepeval huggingface dataset:
Targeting the prostate for destruction through a vascular address (2002)

Organ specific drug targeting was explored in mice as a possible alternative to surgery to treat prostate diseases. Peptides that specifically recognize the vasculature in the prostate were identified from phage-displayed peptide libraries by selecting for phage capable of homing into the prostate after an i.v. injection. One of the phage selected in this manner homed to the prostate 10-15 times more than to other organs. Unselected phage did not show this preference. The phage bound also to vasculature in the human prostate. The peptide displayed by the prostate-homing phage, SMSIARL (single letter code), was synthesized and shown to inhibit the homing of the phage when co-injected into mice with the phage. Systemic treatment of mice with a chimeric peptide consisting of the SMSIARL homing peptide, linked to a proapoptotic peptide that disrupts mitochondrial membranes, caused tissue destruction in the prostate, but not in other organs. The chimeric peptide delayed the development of the cancers in prostate cancer-prone transgenic mice (TRAMP mice). These results suggest that it may be possible to develop an alternative to surgical prostate resection and that such a treatment may also reduce future cancer risk.
APP717, APP693, and PRIP gene mutations are rare in Alzheimer disease. (1991)

The amyloid precursor protein (APP) gene codes for the precursor to the beta-protein found in the amyloid deposits of Alzheimer disease (AD). Recently Goate et al. identified in codon 717 of this gene a missense mutation which segregates with AD in a familial AD (FAD) kindred. The same mutation was also found in affected subjects from a second FAD family but not in other FAD families or in normal controls. The following work was undertaken to determine the frequency of the codon 717 mutation in FAD and nonfamilial AD cases and in normal controls. We tested 76 FAD families, 127 "sporadic" AD subjects, 16 Down syndrome cases, and 256 normal controls for this mutation, and none were positive. We also tested for the APP codon 693 mutation associated with hereditary cerebral hemorrhage with amyloidosis-Dutch type, for PRIP gene missense mutations at codons 102, 117, and 200, and for the PRIP insertion mutations which are associated with Creutzfeld-Jakob disease and Gerstmann-Straussler Scheinker syndrome. No examples of these mutations were found in our population. Thus these APP and PRIP mutations are rare in both FAD and nonfamilial AD.
Role of receptors in the trabecular meshwork of the eye as targeted to the development of antiglaucoma therapy (1992)

Abstract The major pathway for the outflow of aqueous humor from the anterior chamber of the eye is the trabecular meshwork/Schlemm's canal system. The meshwork is composed of connective tissue beams that are ensheathed by trabecular cells; these cells derive their nutrition from the aqueous humor and thus are uniquely susceptible to morphologic and biochemical regulation by bioactive substances that are present or released in this fluid and to pharmacologic agents that are targeted to act on the tissue. The receptors that have been detected on trabecular cells include those for growth modulatory peptides (bFGF, TGF‐βI, transferrin, IGF‐1, and EGF), epinephrine, dopamine, glucocorticoids, benzodiazepines, prostanoids, biogenic amines, the Fc portion of IgGs, and probably those for molecules of the extracellular matrix (integrins). Selective up‐ or down‐regulation of the receptors on the trabecular cells would facilitate an effective control of the intraocular pressure in diseased conditions of the eye. We discuss the prospects and hurdles in the utilization of receptor targeting as a therapeutic modality for trabecular cell regeneration in glaucoma as well as for pharmacologic trabeculectomy and as a treatment for hypotony after glaucoma filtration surgery. We believe that regulation of receptor expression is a novel method for the development of new antiglaucoma agents and for minimizing the side effects of drugs that are administered topically and systemically for the control of the intraocular pressure. © 1992 Wiley‐Liss, Inc.
L-asparagine uptake in Escherichia coli (1975)

The uptake of L-asparagine by Escherichia coli K-12 is characterized by two kinetic components with apparent Km values of 3.5 muM and 80 muM. The 3.5 muM Km system displays a maximum velocity of 1.1 nmol/min per mg of protein, which is a low value when compared with derepressed levels of other amino acid transport systems but is relatively specific for L-asparagine. Compounds providing effective competition for L-asparagine uptake were 4-carbon analogues of the L-isomer with alterations at the beta-amide position, i.e., 5-diazo-4-oxo-L-norvaline (Ki = 4.6 muM), beta-hydroxyamyl-L-aspartic acid (Ki = 10 muM), and L-aspartic acid (Ki = 50 muM). Asparagine uptake is energy dependent and is inhibited by a number of metabolic inhibitors. In a derived strain of E. coli deficient in cytoplasmic asparaginase activity asparagine can be accumulated several-fold above the apparent biosynthetic pool of the amino acid and 100-fold above the external medium. The high affinity system is repressed by culture of cells with L-asparagine supplements in excess of 1 mM and is suggested to be necessary for growth of E. coli asparagine auxotrophs with lower supplement concentrations.
PEGylated Dendritic Architecture for Development of a Prolonged Drug Delivery System for an Antitubercular Drug (2006)

The present study was aimed at developing and exploring the use of PEGylated poly (propylene imine) dendritic architecture for the delivery of an anti-tuberculosis drug, rifampicin. For this study, PEGylated poly(propylene imine) dendritic architecture was synthesized and loaded with rifampicin. Various physicochemical and physiological parameters UV, IR, NMR, TEM, DSC, drug entrapment, drug release and hemolytic toxicity of both PEGylated and non-PEGylated systems were determined and compared. The PEGylation of the systems was found to have increased their drug-loading capacity, reduced their drug release rate and hemolytic toxicity. The systems were found suitable for prolonged delivery of rifampicin.
Activation of endothelial intrinsic NF-κB pathway impairs protein C anticoagulation mechanism and promotes coagulation in endotoxemic mice (2009)

Although the role of systemic activation of the nuclear factor kappaB (NF-kappaB) pathway in septic coagulation has been well documented, little is known about the contribution of endothelial-specific NF-kappaB signaling in this pathologic process. Here, we used transgenic mice that conditionally overexpress a mutant I-kappaBalpha, an inhibitor of NF-kappaB, selectively on endothelium, and their wild-type littermates to define the role of endothelial-specific NF-kappaB in septic coagulation. In wild-type mice, lipopolysaccharide (LPS) challenge (5 mg/kg intraperitoneally) caused markedly increased plasma markers of coagulation, decreased plasma fibrinogen level, and widespread tissue fibrin deposition, which were abrogated by endothelial NF-kappaB blockade in transgenic mice. Endothelial NF-kappaB blockade inhibited tissue factor expression in endothelial cells, but not in leukocytes. Endothelial NF-kappaB blockade did not inhibit LPS-induced tissue factor expression in heart, kidney, and liver. Endothelial NF-kappaB blockade prevented LPS down-regulation of endothelial protein C receptor (EPCR) and thrombomodulin protein expressions, inhibited tissue tumor necrosis factor-alpha converting enzyme activity, reduced EPCR shedding, and restored plasma protein C level. Our data demonstrate that endothelial intrinsic NF-kappaB signaling plays a pivotal role in septic coagulation and suggests a link between endothelial-specific NF-kappaB activation and the impairment of the thrombomodulin-protein C-EPCR anticoagulation pathway.
Streaming in thermoacoustic engines and refrigerators (2000)

The efficiency of thermoacoustic engines and refrigerators is now approaching 40% of the ideal efficiency allowed by the laws of thermodynamics. To achieve such high efficiency requires understanding and control of streaming. Sometimes, thermoacoustic phenomena cause unwanted streaming-driven convection of heat, which we strive to eliminate; in other cases, deliberate use of second-order mass flow may be the key to simplification and improved efficiency. Some features of this streaming are quantitatively understood, but many issues must still be resolved before thermoacoustic devices reach their full potential.
A Widespread Outbreak ofYersinia pseudotuberculosisO:3 Infection from Iceberg Lettuce (2004)

Iceberg lettuce was implicated as the vehicle of a widespread foodborne Y. pseudotuberculosis outbreak. Ongoing laboratory-based surveillance and serotype analysis were essential in the rapid detection of infection. Cases of yersiniosis, which appear to be sporadic, may be part of unrecognized outbreaks caused by contaminated fresh produce.
Pharmaceutical Packaging Technology (2000)

Pharmaceutical packaging requires a greater knowledge of materials and a greater intensity of testing than most other packed products, not to mention a sound knowledge of pharmaceutical products and an understanding of regulatory requirements. Structured to meet the needs of the global market, this volume provides an assessment of a wide range of i
Phosphate-containing proteins and glycoproteins of the cell wall of Candida albicans (1991)

The distribution of phosphate, carbohydrate, and protein in the cell wall components extracted from intact yeast cells of Candida albicans by beta-mercaptoethanol (beta ME) at pH 8.6 was examined by analysis of the material separated by DEAE-cellulose chromatography. All protein peaks did not coincide with peaks of both carbohydrate and phosphate. Subsequent analysis was performed on material obtained from yeast cells and germ tubes which were grown in medium containing [32P]phosphate. Two extracts were obtained by treating cells with beta ME or with zymolyase following beta ME. The extracts were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, followed by autoradiography. beta ME-extracted material contained high-molecular-mass (HMM), greater than or equal to 200 kDa, polydisperse material and a major and minor band of 19 to 20 kDa, Zymolyase extracts contained (i) three components of less than or equal to 40 kDa, one of which may correspond to the major beta ME band; (ii) four bands within the HMM region which may correspond to previously reported bands; and (iii) one band of 100 to 120 kDa. After longer exposures, additional midrange bands were detected in the zymolyase extract. In extracts treated with endo-beta-N-acetylglucosaminidase H, the HMM polydisperse material increased in mobility although retaining sufficient radiolabel for detection. Western immunoblot analysis of extracts with germ tube-specific antiserum and a germ tube-specific monoclonal antibody and concanavalin A showed that not all components contained detectable phosphate, not all glycoproteins contained detectable phosphate, and at least one 19- to 20-kDa protein may be phosphorylated in the absence of carbohydrate.
The major 85-kD surface antigen of the mammalian form of Trypanosoma cruzi is encoded by a large heterogeneous family of simultaneously expressed genes. (1990)

Trypanosoma cruzi is an obligate intracellular protozoan parasite. The parasite mammalian stage surface antigens exhibit extensive antigenic diversity. We have characterized a family of T. cruzi genes that code for a polymorphic set of 85-kD surface antigens, the SA85-1 antigens. The family contains greater than 100 genes and pseudogenes, of which a minimum of nine are transcribed. The gene family is expressed in the mammalian stage only. A subset of the gene family is present in two telomere-linked copies in the genome. Telomere linkage of other expressed SA85-1 genes has not been demonstrated. We have shown that at least three members of the SA85-1 gene family encode antigens at the surface of the mammalian stage of the parasite. Interestingly, these three antigens are expressed on all the trypanosomes examined. This suggests that T. cruzi simultaneously expresses a large repertoire of similar, but diverse antigens at its surface. Thus, T. cruzi exhibits extensive antigenic diversity in a system unique from that of African trypanosomes, perhaps reflecting its intracellular niche.
CREBRF is a potent tumor suppressor of glioblastoma by blocking hypoxia-induced autophagy via the CREB3/ATG5 pathway (2016)

Hypoxia induces protective autophagy in advanced glioblastoma cells, and targeting this process may improve the outcome for glioblastoma patients. Recent studies have suggested that the autophagic process is upregulated in glioblastoma cells in response to extensive hypoxia. Here, we describe a novel tumor suppressor in glioblastoma cells, whereby hypoxia downregulated CREBRF expression and acts as a potent inhibitor of autophagy in glioblastoma cells via the CREB3/ATG5 pathway. Our results demonstrate that CREBRF expression negatively correlates with autophagic and HIF-1α levels in different grade gliomas. Given that CREBRF is a negative regulator of CREB3, CREB3 knockdown also repressed hypoxia-induced autophagy in glioblastoma cells in vitro. Collectively, our findings provide new insight into the molecular mechanisms underlying hypoxia-induced glioblastoma cell autophagy and indicate that the hypoxia/CREBRF/CREB3/ATG5 pathway plays a central role in malignant glioma progression.
Unexpected Sensitivity of sst2 Antagonists to N-Terminal Radiometal Modifications (2012)

Chelated somatostatin agonists have been shown to be sensitive to N-terminal radiometal modifications, with Ga-DOTA agonists having significantly higher binding affinity than their Lu-, In-, and Y-DOTA correlates. Recently, somatostatin antagonists have been successfully developed as alternative tracers to agonists. The aim of this study was to evaluate whether chelated somatostatin antagonists are also sensitive to radiometal modifications and how. We have synthesized 3 different somatostatin antagonists, DOTA-p-NO(2)-Phe-c[D-Cys-Tyr-D-Aph(Cbm)-Lys-Thr-Cys]-D-Tyr-NH(2), DOTA-Cpa-c[D-Cys-Aph(Hor)-D-Aph(Cbm)-Lys-Thr-Cys]-D-Tyr-NH(2) (DOTA-JR11), and DOTA-p-Cl-Phe-c[D-Cys-Tyr-D-Aph(Cbm)-Lys-Thr-Cys]-D-Tyr-NH(2), and added various radiometals including In(III), Y(III), Lu(III), Cu(II), and Ga(III). We also replaced DOTA with 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA) and added Ga(III). The binding affinity of somatostatin receptors 1 through 5 was evaluated in all cases. In all 3 resulting antagonists, the Ga-DOTA analogs were the lowest-affinity radioligands, with a somatostatin receptor 2 binding affinity up to 60 times lower than the respective Y-DOTA, Lu-DOTA, or In-DOTA compounds. Interestingly, however, substitution of DOTA by the NODAGA chelator was able to increase massively its binding affinity in contrast to the Ga-DOTA analog. The 3 NODAGA analogs are antagonists in functional tests. In vivo biodistribution studies comparing (68)Ga-DOTATATE agonist with (68)Ga-DOTA-JR11 and (68)Ga-NODAGA-JR11 showed not only that the JR11 antagonist radioligands were superior to the agonist ligands but also that (68)Ga-NODAGA-JR11 was the tracer of choice and preferable to (68)Ga-DOTA-JR11 in transplantable HEK293-hsst(2) tumors in mice. One may therefore generalize that somatostatin receptor 2 antagonists are sensitive to radiometal modifications and may preferably be coupled with a (68)Ga-NODAGA chelator-radiometal complex.
NZB mouse system for production of monoclonal antibodies to weak bacterial antigens: isolation of an IgG antibody to the polysaccharide capsules of Escherichia coli K1 and group B meningococci. (1985)

A system for the production of monoclonal antibodies, particularly of the IgG type, against weakly immunogenic bacterial polysaccharide antigens is described. This system, which is based on the autoimmune NZB mouse strain, has been used to produce a monoclonal IgG2a antibody against the meningococcus group B and Escherichia coli K1 polysaccharides, identical homopolymers of alpha (2----8)-linked units of N-acetylneuraminic acid that are extremely poor immunogens. Comparison of the humoral immune responses of normal BALB/c mice and autoimmune NZB mice to hyperimmunization with group A, B, and C meningococci showed that, although both strains mounted a weak meningococcal B polysaccharide-specific IgM response, only the NZB strain mounted an IgG response. Similarly, NZB mice mounted a stronger IgG response to the more immunogenic group C meningococcal polysaccharide than did BALB/c mice, although this difference was less pronounced than that observed with meningococcal B polysaccharide. No difference between the two strains of mice was demonstrable with the strongly antigenic group A meningococcal polysaccharide. These results indicate that the NZB system may be generally useful for the production of monoclonal antibodies against weakly antigenic bacterial determinants.
IL-18 binding and inhibition of interferon γ induction by human poxvirus-encoded proteins (1999)

Molluscum contagiosum virus (MCV) is a common, human poxvirus that causes small papular skin lesions that persist for long periods without signs of inflammation. Previous studies revealed that MCV encodes a family of proteins with homology to mammalian IL-18 binding proteins. IL-18 is a proinflammatory cytokine that induces synthesis of interferon gamma, activates NK cells, and is required for a T-lymphocyte helper type 1 response. We expressed and purified the proteins encoded by the MC53L and MC54L genes of MCV, as well as their human and murine homologs. All four recombinant proteins were able to bind with high affinity to human and murine IL-18 molecules and inhibited IL-18 mediated interferon gamma production in a dose-dependent manner. The pirating of IL-18 binding proteins by poxviruses and their use as decoy receptors is consistent with the critical role of IL-18 in defense against virus infections and provides a mechanism for evasion of the immune system by MCV.
Distinct Time Effects of Vaccination on Long-Term Proliferative and IFN-γ–producing T Cell Memory to Smallpox in Humans (2004)

Residual immunity to the smallpox virus raises key questions about the persistence of long-term immune memory in the absence of antigen, since vaccination ended in 1980. IFN-gamma-producing effector-memory and proliferative memory T cells were compared in 79 vaccinees 13-25 yr after their last immunization and in unvaccinated individuals. Only 20% of the vaccinees displayed both immediate IFN-gamma-producing effector-memory responses and proliferative memory responses at 6 d; 52.5% showed only proliferative responses; and 27.5% had no detectable vaccinia-specific responses at all. Both responses were mediated by CD4 and CD8 T cells. The vaccinia-specific IFN-gamma-producing cells were composed mainly of CD4Pos CD45RANeg CD11aHi CD27Pos and CCR7Neg T cells. Their frequency was low but could be expanded in vitro within 7 d. Time since first immunization affected their persistence: they vanished 45 yr after priming, but proliferative responses remained detectable. The number of recalls did not affect the persistence of residual effector-memory T cells. Programmed revaccination boosted both IFN-gamma and proliferative responses within 2 mo of recall, even in vaccinees with previously undetectable residual effector-memory cells. Such long-term maintenance of vaccinia-specific immune memory in the absence of smallpox virus modifies our understanding of the mechanism of persistence of long-term memory to poxviruses and challenges vaccination strategies.
NOISE ROBUST SPEECH RECOGNITION MAKES IN-CAR NAVIGATION SAFE AND AFFORDABLE (1995)

Most automotive systems incorporate sensors, keypads, and displays, all of which contribute to high cost and installation complexity and compromise safety when the navigator is used while driving. A complete voice activated, voice response navigator has recently been introduced to overcome these disadvantages. This paper describes how robust speech recognition help achieve the goals of low cost and safe usage, addressing the problems of speaker independent speech recognition in the presence of wind, engine, and road noise and the influence of the vehicle acoustics and the placement of the microphones. The solution of the problem of recognizing street names from large lists by a combination of alphabet recognizer and a spelling corrector is described. The resulting navigator is a single-board electronic add-on to the vehicle audio system. The recognition and speaking system runs on a low cost digital signal processor, with a micro controller used for audio system control, spelling correction, and route calculation. The navigator's database and software are stored on a standard audio compact disc.
Spermatogonia: stem cells with a great perspective (2001)

Interest in spermatogonia has grown in recent years as a result of exciting developments in stem cell research in general and the development of new research tools allowing the isolation, culture and transplantation of these cells. This review focuses on the methodological breakthroughs and highlights the recent findings that have substantially increased understanding of spermatogonial physiology. The article provides a comprehensive overview of the hormonal regulation of spermatogonia and presents several new approaches to the use of spermatogonia in basic science and medicine. In the near future these techniques will allow the development of novel routes for the generation of transgenic lifestock, the treatment of infertility, the targeting for male contraception, and an alternative strategy for fertility preservation of oncological patients.
In vivo modulation with anti-interleukin-1 (IL-1) receptor (p80) antibody 35F5 of the response to IL-1. The relationship of radioprotection, colony-stimulating factor, and IL-6 (1990)

Interleukin-1 (IL-1) is radioprotective and induces both circulating colony-stimulating factor(s) (CSF) and IL-6 in mice. We evaluated the relationship among these three responses to IL-1 using anti-IL-1 receptor antibody 35F5. This antibody in vitro blocks responses of T cells and fibroblasts, but not of B cells or myeloid cell lines, to IL- 1. Administration of 35F5 alone before irradiation reduced the number of surviving mice compared with those not treated with 35F5, demonstrating that endogenous IL-1 participates in the natural resistance to radiation. Thirty micrograms of 35F5 per mouse also reduced by 92% the survival of irradiated mice pretreated with 0.3 micrograms of IL-1. Similarly, 30 micrograms of 35F5 reduced by 96% to 98% the induction of IL-6 by IL-1. In contrast, 30 micrograms of 35F5 resulted in only moderate reduction of circulating CSF. Consequently, the level of circulating CSF after 35F5 treatment was still equivalent to levels of CSF that were induced by doses of IL-1 in the radioprotective range. Because treatment with 35F5 antibody resulted in the blocking of IL-1-reduced radioprotection, the above results suggest that circulating CSF, by itself, may not be sufficient for radioprotection. This conclusion supports our previous results which showed that granulocyte-macrophage CSF (GM-CSF) and G-CSF were radioprotective only when administered with suboptimal doses of IL-1.