gebhart/patrepeval huggingface dataset:
Isolation of cDNAs of scrapie-modulated RNAs by subtractive hybridization of a cDNA library. (1988)

We have developed a subtractive cloning procedure based on the hybridization of single-stranded cDNA libraries constructed in pi H3M, a vector containing the phage M13 origin of replication. We have used this strategy to isolate three transcripts whose abundance is increased in scrapie-infected brain. DNA sequence analysis showed that they represent glial fibrillary acidic protein, metallothionein II, and the B chain of alpha-crystallin; the latter two may represent a response to stress.
Therapy of murine tumors with tumor peptide-pulsed dendritic cells: dependence on T cells, B7 costimulation, and T helper cell 1-associated cytokines. (1996)

Antigen presentation by host dendritic cells (DC) is critical for the initiation of adaptive immune responses. We have previously demonstrated in immunogenic murine tumor models that bone marrow (BM)-derived DC pulsed ex vivo with synthetic tumor-associated peptides, naturally expressed by tumor cells, serve as effective antitumor vaccines, protecting animals against an otherwise lethal tumor challenge (Mayordomo, J.I., T. Zorina, W.J. Storkus, C. Celluzzi, L.D. Falo, C.J. Melief, T. Ildstad, W.M. Kast, A.B. DeLeo, and M.T. Lotze. 1995. Nature Med. 1:1297-1302). However, T cell-defined epitopes have not been identified for most human cancers. To explore the utility of this approach in the treatment of tumors expressing as yet uncharacterized epitopes, syngeneic granulocyte/macrophage colony-stimulating factor-stimulated and BM-derived DC, pulsed with unfractionated acid-eluted tumor peptides (Storkus, W.J., H.J. Zeh III, R.D. Salter, and M.T. Lotze. 1993. J. Immunother. 14:94-103) were used to treat mice bearing spontaneous, established tumors. The adoptive transfer of 5 x 10(5) tumor peptide-pulsed DC dramatically suppressed the growth of weakly immunogenic tumors in day 4 to day 8 established MCA205 (H-2b) and TS/A (H-2d) tumor models, when applied in three biweekly intravenous injections. Using the immunogenic C3 (H-2b) tumor model in B6 mice, tumor peptide-pulsed DC therapy resulted in the erradication of established d14 tumors and long-term survival in 100% of treated animals. The DC-driven antitumor immune response was primarily cell mediated since the transfer of spleen cells, but not sera, from immunized mice efficiently protected sublethally irradiated naive mice against a subsequent tumor challenge. Furthermore, depletion of either CD4+ or CD8+ T cells from tumor-bearing mice before therapy totally suppressed the therapeutic efficacy of DC pulsed with tumor-derived peptides. Costimulation of the host cell-mediated antitumor immunity was critical since inoculation of the chimeric fusion protein CTLA4-Ig virtually abrogated the therapeutic effects of peptide-pulsed DC in vivo. The analysis of the cytokine pattern in the draining lymph nodes and spleens of tumor-bearing mice immunized with DC pulsed with tumor-eluted peptides revealed a marked upregulation of interleukin (IL) 4 and interferon (IFN) gamma production, as compared with mice immunized with DC alone or DC pulsed with irrelevant peptides. DC-induced antitumor effects were completely blocked by coadministration of neutralizing monoclonal antibody directed against T helper cell 1-associated cytokines (such as IL-12, tumor necrosis factor alpha, IFN-gamma), and eventually, but not initially, blocked by anti-mIL-4 mAb. Based on these results, we believe that DC pulsed with acid-eluted peptides derived from autologous tumors represents a novel approach to the treatment of established, weakly immunogenic tumors, and serves as a basis for designing clinical trials in cancer patients.
Dexmedetomidine: An adjuvant making large inroads into clinical practice (2013)

The introduction of newer more selective α(-2) adrenergic agonist, dexmedetomidine has made a revolution in the field of anesthesia owing to its varied application. The aim of the current review is to highlight the various clinical and pharmacological aspects of dexmedetomidine in daily routine practice of anesthesiology and intensive care besides its potential role in other clinical specialties. This review of dexmedetomidine was carried out after searching the medical literature in Pubmed, Science direct, Scopus, Google scholar and various text books and journal articles using keywords anesthesia, dexmedetomidine, neurosurgery, pediatric surgery, regional dexmedetomidine, anesthesia, regional, neurosurgery, and pediatric surgery. Dexmedetomidine has made its application from a novel sedating agent in the intensive care unit to its use as an adjuvant in various regional anesthetic techniques because of its "cooperative sedation" without any respiratory depression. It has a favorable pharmacokinetic profile suitable to be used in the perioperative period to reduce the requirements of opioids and anesthetic drugs. There are few side-effects of dexmedetomidine, which should always be kept in mind before choosing the patients for its use. The various side-effects associated with dexmedetomidine include, but are not limited to hypotension, bradycardia, worsening of heart block, dry mouth, and nausea. However, large scale randomized controlled trials are still needed to establish various effects of dexmedetomidine and to clearly define its safety profile.
A possible route to the production of free l-tyrosine O-sulphate by the rat (1966)

1. l-Tyrosylglycine O[(35)S]-sulphate is metabolized by the rat to yield the O[(35)S]-sulphate esters of l-tyrosine, p-hydroxyphenylpyruvic acid and p-hydroxyphenylacetic acid. 2. The proportion of the administered peptide which is excreted as l-tyrosine O[(35)S]-sulphate is greater at a higher dose. 3. An enzyme capable of hydrolysing the peptide bond of l-tyrosylglycine O[(35)S]-sulphate to yield l-tyrosine O[(35)S]-sulphate has been detected in rat liver and kidney. 4. The activity of this enzyme is completely inhibited by a large excess of l-tyrosylglycine.
7-Fluoroindazoles as Potent and Selective Inhibitors of Factor Xa (2007)

We have developed a novel series of potent and selective factor Xa inhibitors that employ a key 7-fluoroindazolyl moiety. The 7-fluoro group on the indazole scaffold replaces the carbonyl group of an amide that is found in previously reported factor Xa inhibitors. The structure of a factor Xa cocrystal containing 7-fluoroindazole 51a showed the 7-fluoro atom hydrogen-bonding with the N-H of Gly216 (2.9 A) in the peptide backbone. Thus, the 7-fluoroindazolyl moiety not only occupied the same space as the carbonyl group of an amide found in prior factor Xa inhibitors but also maintained a hydrogen bond interaction with the protein's beta-sheet domain. The structure-activity relationship for this series was consistent with this finding, as the factor Xa inhibitory potencies were about 60-fold greater (DeltaDelta G approximately 2.4 kcal/mol) for the 7-fluoroindazoles 25a and 25c versus the corresponding indazoles 25b and 25d. Highly convergent synthesis of these factor Xa inhibitors is also described.
Germ-line passage is required for establishment of methylation and expression patterns of imprinted but not of nonimprinted genes. (1996)

Embryonic stem (ES) cells homozygous for a disruption of the DNA (cytosine-5)-methyltransferase gene (Dnmt) proliferate normally with their DNA highly demethylated but die upon differentiation. Expression of the wild-type Dnmt cDNA in mutant male ES cells caused an increase in methylation of bulk DNA and of the Xist and Igf2 genes to normal levels, but did not restore the methylation of the imprinted genes H19 and Igf2r. These cells differentiated normally in vitro and contributed substantially to adult chimeras. While the Xist gene was not expressed in the remethylated male ES cells, no restoration of the normal expression profile was seen for H19, Igf2r, or Igf2. This indicates that ES cells can faithfully reestablish normal methylation and expression patterns of nonimprinted genes but lack the ability to restore those of imprinted genes. Full restoration of monoallelic methylation and expression was imposed on H19, Igf2, and Igf2r upon germ-line transmission. These results are consistent with the presence of distinct de novo DNA methyltransferase activities during oogenesis and spermatogenesis, which specifically recognize imprinted genes but are absent in the postimplantation embryo and in ES cells.
Increasing the Action Gap: New Operators for Reinforcement Learning (2016)

This paper introduces new optimality-preserving operators on Q-functions. We first describe an operator for tabular representations, the consistent Bellman operator, which incorporates a notion of local policy consistency. We show that this local consistency leads to an increase in the action gap at each state; increasing this gap, we argue, mitigates the undesirable effects of approximation and estimation errors on the induced greedy policies. This operator can also be applied to discretized continuous space and time problems, and we provide empirical results evidencing superior performance in this context. Extending the idea of a locally consistent operator, we then derive sufficient conditions for an operator to preserve optimality, leading to a family of operators which includes our consistent Bellman operator. As corollaries we provide a proof of optimality for Baird's advantage learning algorithm and derive other gap-increasing operators with interesting properties. We conclude with an empirical study on 60 Atari 2600 games illustrating the strong potential of these new operators.
Prostatic neoplasia in transgenic mice with prostate-directed overexpression of the c-myc oncoprotein (2000)

Chronic overexpression of c-myc in the ventral prostate epithelial cells of C3(1)-c-myc transgenic mice leads to the development of epithelial cell abnormalities similar to those seen in low-grade prostatic intraepithelial neoplasia in humans. These abnormalities were not found to progress to adenocarcinoma over the lifetimes of the transgenic mice, suggesting the need for additional oncogenic changes in the pathway to prostatic adenocarcinomas. Furthermore, our cumulative experience with the use of the C3(1) gene promoter in the generation of transgenic mice suggests that the probasin promoter element provides a much more specific and effective means to target transgenes to the prostate glands of mice.
CRISPR: New Horizons in Phage Resistance and Strain Identification (2012)

Bacteria have been widely used as starter cultures in the food industry, notably for the fermentation of milk into dairy products such as cheese and yogurt. Lactic acid bacteria used in food manufacturing, such as lactobacilli, lactococci, streptococci, Leuconostoc, pediococci, and bifidobacteria, are selectively formulated based on functional characteristics that provide idiosyncratic flavor and texture attributes, as well as their ability to withstand processing and manufacturing conditions. Unfortunately, given frequent viral exposure in industrial environments, starter culture selection and development rely on defense systems that provide resistance against bacteriophage predation, including restriction-modification, abortive infection, and recently discovered CRISPRs (clustered regularly interspaced short palindromic repeats). CRISPRs, together with CRISPR-associated genes (cas), form the CRISPR/Cas immune system, which provides adaptive immunity against phages and invasive genetic elements. The immunization process is based on the incorporation of short DNA sequences from virulent phages into the CRISPR locus. Subsequently, CRISPR transcripts are processed into small interfering RNAs that guide a multifunctional protein complex to recognize and cleave matching foreign DNA. Hypervariable CRISPR loci provide insights into the phage and host population dynamics, and new avenues for enhanced phage resistance and genetic typing and tagging of industrial strains.
ApoA-I knockout mice: characterization of HDL metabolism in homozygotes and identification of a post-RNA mechanism of apoA-I up-regulation in heterozygotes (1997)

The major high density lipoprotein (HDL) apolipoprotein, apoA-I, was knocked out by gene targeting in ES cells to provide a model for the study of HDL metabolism and its relationship to plasma and tissue cholesterol metabolism. HDL and non-HDL cholesterol (HDL-C) were reduced in apoA-I-deficient mice. Feeding a high fat-high cholesterol diet raised HDL-C minimally in apoA-I knockout compared to the large increase seen in control mice, suggesting an interaction between diet and apoA-I genotype. In apoA-I-deficient mice, HDL was normal in size but altered in composition. Compared to control mice there was more triglyceride and free cholesterol and less cholesteryl ester (CE), suggesting that apoA-I-deficient HDL is a poor substrate for hepatic lipase and lecithin:cholesterol acyltransferase (LCAT). The metabolic basis of the low HDL-C levels in the apoA-I knockout mice was decreased flux into the HDL CE pool. The absolute delivery of HDL CE to both peripheral tissues and liver was also decreased. As tissue cholesterol levels and synthesis were unchanged, the decreased flux of cholesterol into the HDL CE pool was most likely due to decreased efflux of cholesterol from the peripheral tissues and decreased functional LCAT activity. The low HDL-C state in the apoA-I-deficient mouse was associated with an absolute decrease in unidirectional transport of cholesterol from peripheral tissues to the liver but this did not lead to cholesterol accumulation in the periphery or a cholesterol deficit in the liver; nor was there altered peripheral tissue HMG-CoA reductase activity. The only sign of decreased cholesterol flux to the liver was a 2.3-fold decrease in liver cholesterol 7 alpha-hydroxylase mRNA, suggesting decreased bile acid synthesis. In the apoA-I knockout mouse model it appears that low HDL levels create a new steady state in which decreased cholesterol is delivered to both peripheral tissues and the liver.
A survey of magnetooptic effects (1968)

The interaction of light with matter involves the electronic structure of the matter. In particular, the interaction is affected by the magnetic state of the medium, and this gives rise to the magnetooptical effects. The Faraday, Kerr, and Voigt effects are described, and their derivation from Maxwell's equations and the constitutive relations are given. The microscopic origins of the effects are discussed heuristically. A few representative applications of the magnetooptic effects to magnetic recording and to the control of light are explained.
An inhibitory monoclonal antibody to factor X that blocks prothrombin activation but not prothrombinase enzyme assembly (1988)

A monoclonal antibody (designated alpha BFX-2b) prepared against bovine factor X inhibited factor X activity in human, bovine, porcine, rabbit, and canine plasma. In assays using purified prothrombinase components, factor Xa, factor Va, phospholipid vesicles, and calcium ion with the fluorescent active site thrombin inhibitor dansylarginyl-N-(3-ethyl-1,5- pentanediyl)amide, the antibody inhibited the conversion of prothrombin to thrombin. Antibody alpha BFX-2b also blocked prothrombinase cleavage of the macromolecular substrates prethrombin 1 and prethrombin 2 but did not inhibit factor Xa hydrolysis of the synthetic substrate benzoyl- Ile-Glu-Gly-Arg-p-nitroanilide. The antibody also prevented the inactivation of factor Xa by antithrombin III but did not prevent the inactivation by soybean trypsin inhibitor. Antibody alpha BFX-2b bound factor Xa with a stoichiometry of 1:1 and an apparent dissociation constant of 9.0 x 10(-11) mol/L as estimated from its inhibition of prothrombinase activity. Antibody alpha BFX-2b did not prevent binding of factor Xa to factor Va-phospholipid as measured by using fluorescence polarization or high-pressure liquid gel chromatography with the fluorescent Factor Xa analogue dansyl-glutamyl-glycyl-arginyl- Xa. Immunoblotting of factor X following electrophoresis on sodium dodecyl sulphate-polyacrylamide gels and transfer to nitrocellulose indicated that the antigenic determinant recognized by antibody alpha BFX-2b was found on the heavy chain of factors X and Xa. From these observations it can be concluded that antibody alpha BFX-2b recognizes a highly conserved epitope on the factor X heavy chain that is remote from the topographic sites required for prothrombinase complex assembly and substrate hydrolysis but may be located at or near a portion of the macromolecular substrate binding site.
Superior Osteogenesis in Transplanted Allogeneic Canine Skull Following Chemical Sterilization (1982)

Sterilization of allogeneic bone increases the availability of this tissue for supplanting skeletal defects and effecting fusions. The optimal sterilant destroys micro-organisms, preserves the physical and chemical integrity of bone and possibly even reduces immunogenicity. Cortical bone of skull heals slowly and is variably resorbed. Of 36 dogs, spontaneous regeneration in 72 paired 20 mm defects was constant but always incomplete, and restored only about one third of the cross-sectional area of the defect at six months. The repair in defects replaced with canine allogeneic bony disc, sterilized with ethylene oxide (n = 9), gamma irradiation (n = 7), or methanol/chloroform/iodoacetic acid (n = 7) and then lyophilizedd, was compared with repair in defects filled with aseptically procured lyophilized only (n = 23) discs from the same donor. Criteria for evaluation of implants at six months included volume of defect filled, radiodensity, extent of fusion around circumference, revascularization, and remodeling. Bony discs sterilized with methanol/chloroform/iodoacetic acid remodeled at a superior rate (p less than 0.01). Radiation sterilization resulted in diminished density and inferentially reduced protection of the brain (p less than 0.025). Ethylene oxide, lyophilized implants, and implants lyophilized only produced comparable repair. Whereas an acceptable cranioplasty was achieved in 86% of methanol/chloroform/iodoacetic acid, lyophilize implants, all other alloimplants served an osteoconductive function with a successful repair occurring in 56% to 58%.
Minocycline Reduces Microglial Activation and Improves Behavioral Deficits in a Transgenic Model of Cerebral Microvascular Amyloid (2007)

Cerebral microvascular amyloid beta protein (Abeta) deposition and associated neuroinflammation is increasingly recognized as an important component leading to cognitive impairment in Alzheimer's disease and related cerebral amyloid angiopathy disorders. Transgenic mice expressing the vasculotropic Dutch/Iowa (E693Q/D694N) mutant human Abeta precursor protein in brain (Tg-SwDI) accumulate abundant cerebral microvascular fibrillar amyloid deposits and exhibit robust neuroinflammation. In the present study, we investigated the effect of the anti-inflammatory drug minocycline on Abeta accumulation, neuroinflammation, and behavioral deficits in Tg-SwDI mice. Twelve-month-old mice were treated with saline or minocycline by intraperitoneal injection every other day for a total of 4 weeks. During the final week of treatment, the mice were tested for impaired learning and memory. Brains were then harvested for biochemical and immunohistochemical analysis. Minocycline treatment did not alter the cerebral deposition of Abeta or the restriction of fibrillar amyloid to the cerebral microvasculature. Similarly, minocycline-treated Tg-SwDI mice exhibited no change in the levels of total Abeta, the ratios of Abeta40 and Abeta42, or the amounts of soluble, insoluble, or oligomeric Abeta compared with the saline-treated control Tg-SwDI mice. In contrast, the numbers of activated microglia and levels of interleukin-6 were significantly reduced in minocycline-treated Tg-SwDI mice compared with saline-treated Tg-SwDI mice. In addition, there was a significant improvement in behavioral performance of the minocycline-treated Tg-SwDI mice. These finding suggest that anti-inflammatory treatment targeted for cerebral microvascular amyloid-induced microglial activation can improve cognitive deficits without altering the accumulation and distribution of Abeta.
Crystal structure of the complex between programmed death-1 (PD-1) and its ligand PD-L2 (2008)

Programmed death-1 (PD-1) is a member of the CD28/B7 superfamily that delivers negative signals upon interaction with its two ligands, PD-L1 or PD-L2. The high-resolution crystal structure of the complex formed by the complete ectodomains of murine PD-1 and PD-L2 revealed a 1:1 receptor:ligand stoichiometry and displayed a binding interface and overall molecular organization distinct from that observed in the CTLA-4/B7 inhibitory complexes. Furthermore, our structure also provides insights into the association between PD-1 and PD-L1 and highlights differences in the interfaces formed by the two PD-1 ligands (PD-Ls) Mutagenesis studies confirmed the details of the proposed PD-1/PD-L binding interfaces and allowed for the design of a mutant PD-1 receptor with enhanced affinity. These studies define spatial and organizational constraints that control the localization and signaling of PD-1/PD-L complexes within the immunological synapse and provide a basis for manipulating the PD-1 pathways for immunotherapy.
Synthesis and characterization of new (N→B) phenyl substituted[N-benzyliminodiacetate-O,O′,N]boranes (2005)

The synthesis of nine (NB) phenyl substituted[N-benzyliminodiacetate-O,O',N]boranes 3a-3i is reported herein. These compounds were characterized by 1 H, 13 C, 11 B, HETCOR, NOESY, infrared spectroscopy, mass spectrometry and in the case of compounds 3d and 3g also by All compounds exhibit a bicyclic structure due to the presence of an intramolecular NB coordination bond. The structure of 4-chlorophenyl[N-benzyliminodiacetate-O,O',N]borane 3e was further established by a single crystal x-ray diffraction study. The correlation between ( 11 B) of compounds 3a, 3d-3i and Hammett values shows that the strength of the NB bond depends on the electronic factors of the substituent on the B-phenyl group.
Measurement of growth of bifidobacteria on inulofructosaccharides (1990)

Journal Article Measurement of growth of bifidobacteria on inulofructosaccharides Get access H. Yamazaki, H. Yamazaki Department of Biology, Carleton University, Ottawa, Ontario, Canada, K1S 5B6 Search for other works by this author on: Oxford Academic Google Scholar N. Dilawri N. Dilawri Department of Biology, Carleton University, Ottawa, Ontario, Canada, K1S 5B6 Search for other works by this author on: Oxford Academic Google Scholar Letters in Applied Microbiology, Volume 10, Issue 6, 1 June 1990, Pages 229–232, https://doi.org/10.1111/j.1472-765X.1990.tb00114.x Published: 01 June 1990 Article history Received: 25 July 1989 Accepted: 10 October 1989 Published: 01 June 1990