gebhart/patrepeval huggingface dataset:
Fatty acids and hypolipidemic drugs regulate peroxisome proliferator-activated receptors α- and γ-mediated gene expression via liver fatty acid binding protein: A signaling path to the nucleus (2001)

Peroxisome proliferator-activated receptor alpha (PPARalpha) is a key regulator of lipid homeostasis in hepatocytes and target for fatty acids and hypolipidemic drugs. How these signaling molecules reach the nuclear receptor is not known; however, similarities in ligand specificity suggest the liver fatty acid binding protein (L-FABP) as a possible candidate. In localization studies using laser-scanning microscopy, we show that L-FABP and PPARalpha colocalize in the nucleus of mouse primary hepatocytes. Furthermore, we demonstrate by pull-down assay and immunocoprecipitation that L-FABP interacts directly with PPARalpha. In a cell biological approach with the aid of a mammalian two-hybrid system, we provide evidence that L-FABP interacts with PPARalpha and PPARgamma but not with PPARbeta and retinoid X receptor-alpha by protein-protein contacts. In addition, we demonstrate that the observed interaction of both proteins is independent of ligand binding. Final and quantitative proof for L-FABP mediation was obtained in transactivation assays upon incubation of transiently and stably transfected HepG2 cells with saturated, monounsaturated, and polyunsaturated fatty acids as well as with hypolipidemic drugs. With all ligands applied, we observed strict correlation of PPARalpha and PPARgamma transactivation with intracellular concentrations of L-FABP. This correlation constitutes a nucleus-directed signaling by fatty acids and hypolipidemic drugs where L-FABP acts as a cytosolic gateway for these PPARalpha and PPARgamma agonists. Thus, L-FABP and the respective PPARs could serve as targets for nutrients and drugs to affect expression of PPAR-sensitive genes.
Isotype-specific antibody-secreting cells to transmissible gastroenteritis virus and porcine respiratory coronavirus in gut- and bronchus-associated lymphoid tissues of suckling pigs (1993)

Antibody-secreting cells (ASC) were enumerated in gut- and bronchus-associated lymphoid tissues of pigs exposed to three antigenically related coronaviruses: virulent transmissible gastroenteritis virus (TGEV), attenuated TGEV, and porcine respiratory coronavirus (PRCV). Exposure of 11-day-old pigs to virulent TGEV resulted in severe gastroenteritis and virus shedding mainly in feces but also to a limited extent in nasal secretions. PRCV and attenuated TGEV exposure produced no clinical signs and only one pig given a high dose of attenuated TGEV shed virus in feces, but virus was shed from the nasal passages. Nasal virus titers were highest after PRCV inoculation of pigs. Mononuclear cells were isolated from spleens, mesenteric, and bronchial lymph nodes of pigs and assayed for virus-specific IgG and IgA antibody secretion by an enzyme-linked immunospot assay. Virus-specific ASC peaked at postinoculation days 12 to 24 and IgG-ASC outnumbered IgA-ASC in all tissues tested. The greatest numbers of ASC were in mesenteric lymph nodes of virulent TGEV-exposed pigs and in BLN of PRCV-exposed pigs. Attenuated TGEV induced intermediate ASC responses in the gut and respiratory tract. Secondary in vitro ASC responses to inactivated TGEV or PRCV paralleled the primary responses except in BLN where the numbers of memory ASC were high for both TGEV- and PRCV-exposed pigs. We conclude that: 1) a single exposure of pigs to PRCV either oral-nasally or by aerosol leads to potent systemic and bronchus-associated, but not gut-associated, ASC responses; 2) a high dose of attenuated TGEV (4 x 10(8) plaque-forming units) is more effective than PRCV (6 x 10(5) or 2 x 10(8) plaque-forming units) or a lower dose of attenuated TGEV (7 x 10(6) plaque-forming units) in eliciting gut-associated ASC; 3) although virulent and a high dose of attenuated TGEV induce high numbers of ASC in the tissues tested, virulent TGEV induces the most ASC in the gut and IgA-ASC in all lymphoid tissues; and 4) virus replication in the gut or respiratory tract is a major factor affecting the magnitude of an ASC response at that site and may be necessary for the recruitment of IgG- and IgA-ASC and memory cells in large numbers from other mucosal inductive sites. This unique model of mucosal immunity using antigenically related viruses with distinct tissue tropisms may help to clarify interactions of the various components of the common mucosal immune system.
Mapping of the C3b-binding site of CR1 and construction of a (CR1)2-F(ab')2 chimeric complement inhibitor. (1991)

CR1/CR2 chimeric receptors in which various short consensus repeats (SCRs) of CR1 were attached to CR2 were transiently expressed on COS cells, and assessed for the binding of polymerized C3b (pC3b) and anti-CR2 by immunofluorescence. Of COS cells expressing chimeras containing SCR 1-4, 1-3, 2-4, 1-2, and 2-3 of the long homologous repeats (LHRs) -B or -C, 96%, 66%, 23%, 0%, and 0%, respectively, bound pC3b. K562 cells were stably transfected with wild-type CR1, deletion mutants of CR1, and the CR1/CR2 chimeras, respectively, and assayed for binding of 125I-pC3b. The dissociation constants (Kd) for pC3b of wild-type CR1 and the LHR-BD and -CD constructs were in the range of 1.0-2.7 nM, and of the CR1/CR2 chimeras containing SCRs 1-4, 1-3, and 2-4 of LHR-B or -C were 1.8-2.4, 6-9, and 22-36 nM, respectively. The factor I-cofactor function of the CR1/CR2 chimeras paralleled the C3b-binding function of the constructs. A CR1/immunoglobulin (Ig) chimeric protein was prepared by fusing SCRs 1-4 of LHR-B to the heavy chains of a murine F(ab')2 anti-nitrophenacetyl (NP) monoclonal antibody. The (CR1)2-F(ab')2 chimera, which retained its specificity for NP, was as effective as soluble, full-length CR1 in binding pC3b, serving as a cofactor for factor I-mediated cleavage of C3b, and inhibiting activation of the alternative pathway, indicating that the bivalent expression of these SCRs reconstitutes the alternative pathway inhibitory function of CR1. The feasibility of creating CR1/Ig chimeras makes possible a new strategy of targeting complement inhibition by the use of Ig fusion partners having particular antigenic specificities.
Inhibition of integrin function prevents restenosis following vascular injury. (1995)

Activation of platelets leads to thrombosis and secretion of PDGF and other stimulators of smooth muscle cell (SMC) migration/proliferation, resulting in neointima formation. RGD-containing peptides can prevent the binding of several integrins including alpha II b/beta 3 (GP II b/III a) in platelet aggregation and alpha v/beta 3 in smooth muscle cell migration, both of which are involved in neointima formation. Thrombus formation was measured by transillumination and image analysis at 30 min, 24 hr and 72 hr after vascular injury and neointima was quantified in the same carotid arteries in hamsters at 2 weeks. The proliferation index of SMC was determined at 1, 3, 5, 7, and 14 days after denudation following four injections of BrdU. After treatment with G4120 at a dose of 100 micrograms/kg/hr, both thrombus size (89.2 +/- 5.5% inhibition vs control) and neointima formation (60.2 +/- 6.6% inhibition vs control) were significantly reduced. Pooling individual data for treated hamsters with those obtained for the untreated animals still resulted in a significant correlation (r = 0.64, n = 47, P < 0.001). Reduction of neointima by G4120 is linked to a lower percentage of proliferating cells in the media and neointima from 16.5 +/- 9.7% on day 1 (media) and 20.2 +/- 7.3% on day 5 (intima) in the control animals to 9.9 +/- 6.1% on day 1 (media) and 13.4 +/- 9.0 on day 5 (intima) in the G4120 treated animals. In conclusion, inhibition of integrin function results in reductions of thrombus and neointima formations.(ABSTRACT TRUNCATED AT 250 WORDS)
Parasympathetic-mediated atrial fibrillation during tilt test associated with increased baroreflex sensitivity (2006)

The autonomic mechanism that triggered atrial fibrillation in a patient during tilt test was investigated. Neurocardiogenic syncope is often characterized by diminished baroreflex sensitivity during the hypotension period. Increased barorereflex sensitivity preceding the onset of atrial fibrillation in tilt testing may indicate the involvement of a vagally mediated mechanism, as shown in the present case.
Examining the Lacunar Hypothesis With Diffusion and Perfusion Magnetic Resonance Imaging (2002)

DWI and PWI altered the final diagnosis of infarct pathogenesis from small perforating artery occlusion to large artery embolism in 13 of 19 patients presenting with lacunar syndromes. Lacunes cannot be reliably diagnosed on clinical grounds.
Handbook of theoretical computer science (1990)

Of all the books I have covered in the Forum to date, this set is the most unique and possibly the most useful to the community, in support both of teaching and research.... The books can be used by anyone wanting simply to gain an understanding of one of these areas, or by someone desiring to be in research in a topic, or by instructors wishing to find timely information on a subject they are teaching outside their major areas of expertise. -- Rocky Ross, SIGACT News This is a reference which has a place in every computer science library. -- Raymond Lauzzana, Languages of Design The Handbook of Theoretical Computer Science provides professionals and students with a comprehensive overview of the main results and developments in this rapidly evolving field. Volume A covers models of computation, complexity theory, data structures, and efficient computation in many recognized subdisciplines of theoretical computer science. Volume B takes up the theory of automata and rewriting systems, the foundations of modern programming languages, and logics for program specification and verification, and presents several studies on the theoretic modeling of advanced information processing. The two volumes contain thirty-seven chapters, with extensive chapter references and individual tables of contents for each chapter. There are 5,387 entry subject indexes that include notational symbols, and a list of contributors and affiliations in each volume.
ChemInform Abstract: (tert.‐Butyldimethylsilyloxy)methyl Chloride: Synthesis and Use as N‐Protecting Group in Pyrimidinones. (1988)

Abstract The new title reagent (IV) is synthesized by SO 2 Cl 2 cleavage of the sulfide (III) which in turn is available from the components (I) and (II).
An Unexpected Benefit of Horizontal Wells on Offset Vertical Well Productivity in Vertical Miscible Floods (1994)

ABSTRACT Since 1989, Husky Oil has drilled twelve horizontal wells in six maturevertical hydrocarbon miscible floods. To date, these horizontal wells have beenvery successful in reducing gas coning in the horizontal well and in improvingoil productive as originally intended. However; actual field performanceindicates that in some cases horizontal wells also considerably improveproductivities of adjacent vertical wells. This paper presents a case history which shows that drilling a horizontalwell in Rainbow Keg River E Pool resulted in benefiting the offset verticalwells with a 10–15% increase in oil production and a temporary cessation in therising trend of producing gas-oil ratio. Such unexpected benefits are believedto be improved drainage to the vertical wells induced by the drilling of thehorizontal well along with healing and/or reduction of gas coning tendency nearthe vertical wellbores. These hypothesized causes for the unexpected benefitswere qualitatively confirmed with a 3-D simulation. It is concluded that drilling of horizontal wells could improve adjacentvertical wells' productivities. The key implication for future fieldapplications towards further enhancing oil recovery is that under mostsituations the fear of drawing gas from a vertical well to a horizontal well ifthe horizontal well is placed too close to existing vertical well(s) can besomewhat reduced. After placing a horizontal lateral in a target area, the wellcan be extended to cover areas near offset vertical well(s) to improve drainageand reduce some of the gas coning tendency around the offset verticalwellbore(s). INTRODUCTION Since 1989, Husky Oil has drilled twelve horizontal wells in six maturevertical hydrocarbon miscible floods (Figure 1). The original intent of thehorizontal drilling technology in these reservoirs are two fold:to minimize coning and channeling of gas and water, and,to attain larger drainage area, resulting in incremental oil sandwichrecovery and improving the oil productivity. To date, all of these horizontal wells have been extremely successful inreducing gas coning and in improving oil productivity. On average, initial capital investment is paid out within oneyear. The length of the lateral sections has increased from 178 m in the firstwell to as long as 720 m and each well was drilled into a progressively riskiertargets.
Theory of gain, modulation response, and spectral linewidth in AlGaAs quantum well lasers (1985)

We investigate theoretically a number of important issues related to the performance of AlGaAs quantum well (QW) semiconductor lasers. These include a basic derivation of the laser gain, the linewidth enhancement factor α, and the differential gain constant in single and multiple QW structures. The results reveal the existence of gain saturation with current in structures with a small number of wells. They also point to a possible two-fold increase in modulation bandwidth and a ten-fold decrease in the spectral laser linewidth in a thin QW laser compared to a conventional double heterostructure laser.
Immunotherapy with low and high affinity monoclonal antibodies 17-1A and 323/A3 in a nude mouse xenograft carcinoma model. (1995)

The therapeutic effects of the low and high affinity mAbs 17-1A and 323/A3 were investigated in nude mice xenografted with LS 180 human colorectal carcinoma cells. Treatment of mice grafted with dispersed tumor cells, before formation of a tumor nodule, was started 1 day after s.c. injection of tumor cells and consisted of a single i.p. injection of murine 17-1A or 323/A3 mAb. Tumor appearance after a single injection of either 17-1A or 323/A3 was delayed as compared to injection of an irrelevant mAb. Both 17-1A and 323/A3 reduced the tumor growth rate, and both mAbs decreased the total number of mice that eventually developed a tumor. In all experiments, 323/A3 showed consistently better treatment effects on xenografted mice than mAb 17-1A. For treatment of established tumors with mAb 17-1A or 323/A3 therapy was delayed until a tumor nodule was macroscopically detectable. One single i.p. injection of mAb 17-1A had no effect on further tumor growth and mean tumor size as compared to the control group injected with irrelevant mAb. One single i.p. injection with mAb 323/A3 reduced the tumor growth rate in some mice with established tumors and resulted in a significant difference of mean tumor size of this group as compared to the 17-1A treated mice and the control groups. Multiple injections with mAb 17-1A also had no effects on established tumors, in contrast to mAb 323/A3, where serial injections resulted in tumor growth reduction and, eventually, in some mice reduction in tumor size. In summary, we showed that in nude mice mAb 323/A3 (Ka = 2 x 10(9) M-1) is much more potent than mAb 17-1A (Ka = 5 x 10(7) M-1) in eradication of nonestablished tumor cells and treatment of small established tumors. These results suggest that high affinity mAbs like 323/A3 might dramatically improve the clinical results obtained thus far with the low affinity mAb 17-1A in the adjuvant treatment of surgically resected Dukes C colorectal cancer patients with minimal residual disease.
Interference reflection microscopy in cell biology: methodology and applications (1985)

Since its introduction into cell biology by Curtis in 1964, interference reflection microscopy (IRM) has been used by an increasing number of researchers to study cell-substrate interactions in living cells in culture. With the use of antiflex objectives, high-contrast IRM images can now be readily obtained. From the different theories on image formation in IRM that have been put forward, it can be seen that a zero-order interference pattern is generated at high illuminating numerical aperture. This yields information on the closeness of contact between cell and substrate, with only minor perturbation by reflections from the dorsal cell surface. Therefore, the proper use of illuminating apertures is crucial. Nevertheless, IRM images have to be interpreted with caution, especially under thin cytoplasmic sheets. Quantitative IRM is possible only with a mathematical model for finite illuminating aperture interferometry and with an independent measurement of cell thickness for values up to 1 micron. IRM has been applied qualitatively to a large number of cell types, and it seems that there are two universal types of adhesion. Focal contacts are small regions of closest cell-substrate apposition, possibly of immediate contact, that are associated with the distal end of actin filament bundles. They are firm attachment structures that hold the cell in place and in its spread shape. Close contacts are broad areas of reduced cell-to-substrate distance. They are weaker but highly dynamic adhesions that sustain rapid movements of cells or cell parts over the substrate. Although a number of independent observations suggest that adhesion patterns of malignantly transformed cells differ from those of their normal counterparts, there is no simple correlation between malignancy in vivo and altered contact formation in vitro. The adhesion pattern seems to be determined by the locomotory state of the cells rather than by their tissue of origin. Finally, IRM can also be used to enhance contrast in images of fixed preparations.
Two homologous mitochondrial introns from closely related Saccharomyces species differ by only a few amino acid replacements in their Open Reading Frames: one is mobile, the other is not. (1992)

We have undertaken a comprehensive study of the gene conversion of all the mitochondrial introns of Saccharomyces capensis. The approach used involved the measurements of intron transmission amongst the progeny of crosses between a recipient strain (Saccharomyces cerevisiae intronless mitochondria) and various donor strains (Saccharomyces capensis, with various combinations of mitochondrial introns). We have shown that the S. capensis second intron (bi2 of cytochrome b gene) is extremely active as a donor in gene conversion whereas its homologous S. cerevisiae intron is not. Determination of sequence of the S. capensis intron demonstrates that it differs from that of the homologous S. cerevisiae intron (bi2) by a very small number of nucleotide substitutions.
MAOA‐uVNTR polymorphism in a Brazilian sample: Further support for the association with impulsive behaviors and alcohol dependence (2006)

The enzyme monoamine oxidase A (MAO A) plays an important role in the metabolism of neurotransmitters. The MAOA gene presents several polymorphisms, including a 30-bp VNTR in the promoter region (MAOA-uVNTR). Alleles with 3.5 and 4 repeats are 2-10 times more efficient than the 3-repeat allele. Several studies have shown an association between the 3-repeat allele and a cluster of externalizing behaviors including alcoholism, antisocial personality, and impulsivity. The objective of the present study is to replicate in a different culture the associations between the MAOA-uVNTR with alcoholism and other phenotypes. The sample comprises 125 Brazilian alcoholics of European descent and 235 controls. The results suggest that the 3-repeat allele is associated to: (1) alcohol dependence (P < 0.05); (2) an earlier onset of alcoholism (P < 0.01); (3) comorbid drug abuse among alcoholics (P < 0.05); and (4) a higher number of antisocial symptoms (P < 0.02). Our results confirmed previous reports showing an association of the low activity 3-repeat allele of MAOA-uVNTR polymorphism with substance dependence and impulsive/antisocial behaviors. These findings in a different culture further support the influence of the MAOA-uVNTR in psychiatric disorders.
Separation processes in biotechnology. Aqueous two-phase separations. (1990)

Aqueous two-phase systems are useful for separation of a wide range of water-compatible substances (from peptides to cells). The selectivity of the separation normally increases with the size of the partitioned molecules or particles. The partition and separation capacity can be influenced in a number of ways, including electric charge, hydrophobicity, or specific ligand binding. Because of the simpleness in operation and high capacity, aqueous two-phase systems are well suited for large-scale purification of biomaterials such as enzymes and other specific proteins.
Identification of recurrent and novel mutations in the LDL receptor gene in Japanese familial hypercholesterolemia Communicated by: Haig H. Kazazian Online Citation: Human Mutation, Mutation in Brief #248 (1999) Online http://journals.wiley.com/1059-7794/pdf/mutation/248.pdf (1999)

We used the denaturing gradient gel electrophoresis (DGGE) method to investigate 120 Japanese patients with familial hypercholesterolemia (FH) for mutations in the promoter region and the 18 exons and their flanking intron sequence of the low density lipoprotein (LDL) receptor gene. Fourteen aberrant DGGE patterns were found, and the underlying mutations were characterized by DNA sequencing. Five novel missense mutations (C317S, F382L A410T, L547V, and E693K), two nonsense mutations (W512X and K790X), four frameshift mutation (355del7, 1246ins5, 1687ins1, and 2035ins1), one splicing mutation (1845+2 T→C), and two inframe mutations (661ins21 and 1115del9/ins6) were identified. Six of these mutations (L547V, E693K, W512X, 355del7, 1687ins1, and 20354ins1) have not been described before in FH. These newly identified mutations cosegregated in their family members with defective LDL receptor activity and hypercholesterolemia, and are thought to be causal for the FH phenotype. These results demonstrate that there is a broad spectrum of mutations in the LDL receptor gene in the Japanese population. Hum Mutat 14:87, 1999. © 1999 Wiley-Liss, Inc.
Safety and Immunogenicity ofEscherichia coliO157 O‐Specific Polysaccharide Conjugate Vaccine in 2–5‐Year‐Old Children (2006)

The O157-rEPA vaccine was safe and immunogenic in young children. A phase 3 trial of the administration of this conjugate vaccine concurrently with routine immunization in infants is planned.
Structure-Based Design of Novel Chk1 Inhibitors:  Insights into Hydrogen Bonding and Protein−Ligand Affinity (2005)

We report the discovery, synthesis, and crystallographic binding mode of novel furanopyrimidine and pyrrolopyrimidine inhibitors of the Chk1 kinase, an oncology target. These inhibitors are synthetically tractable and inhibit Chk1 by competing for its ATP site. A chronological account allows an objective comparison of modeled compound docking modes to the subsequently obtained crystal structures. The comparison provides insights regarding the interpretation of modeling results, in relationship to the multiple reasonable docking modes which may be obtained in a kinase-ATP site. The crystal structures were used to guide medicinal chemistry efforts. This led to a thorough characterization of a pair of ligand-protein complexes which differ by a single hydrogen bond. An analysis indicates that this hydrogen bond is expected to contribute a fraction of the 10-fold change in binding affinity, adding a valuable observation to the debate about the energetic role of hydrogen bonding in molecular recognition.