gebhart/patrepeval huggingface dataset:
Tissue Injury Regulates Serotonin 1D Receptor Expression: Implications for the Control of Migraine and Inflammatory Pain (2006)

The anti-migraine action of "triptan" drugs involves the activation of serotonin subtype 1D (5-HT1D) receptors expressed on "pain-responsive" trigeminal primary afferents. In the central terminals of these nociceptors, the receptor is concentrated on peptidergic dense core vesicles (DCVs) and is notably absent from the plasma membrane. Based on this arrangement, we hypothesized that in the resting state the receptor is not available for binding by a triptan, but that noxious stimulation of these afferents could trigger vesicular release of DCVs, thus externalizing the receptor. Here we report that within 5 min of an acute mechanical stimulus to the hindpaw of the rat, there is a significant increase of 5-HT1D-immunoreactivity (IR) in the ipsilateral dorsal horn of the spinal cord. We suggest that these rapid immunohistochemical changes reflect redistribution of sequestered receptor to the plasma membrane, where it is more readily detected. We also observed divergent changes in 5-HT1D-IR in inflammatory and nerve-injury models of persistent pain, occurring at least in part through the regulation of 5-HT1D-receptor gene expression. Finally, we found that 5-HT1D-IR is unchanged in the spinal cord dorsal horn of mice with a deletion of the gene encoding the neuropeptide substance P. This result differs from that reported for the partial differential-opioid receptor, which is also sorted to DCVs, but is greatly reduced in preprotachykinin mutant mice. We suggest that a "pain"-triggered regulation of 5-HT1D-receptor expression underlies the effectiveness of triptans for the treatment of migraine. Moreover, the widespread expression of 5-HT1D receptor in somatic nociceptive afferents suggests that triptans could, in certain circumstances, treat pain in nontrigeminal regions of the body.
The frequency assignment problem: A solution via nonlinear programming (1987)

This paper gives a mathematical programming model for the problem of assigning frequencies to nodes in a communications network. The objective is to select a frequency assignment which minimizes both cochannel and adjacent-channel interference. In addition, a design engineer has the option to designate key links in which the avoidance of jamming due to self interference is given a higher priority. The model has a nonconvex quadratic objective function, generalized upper-bounding constraints, and binary decision variables. We developed a special heuristic algorithm and software for this model and tested it on five test problems which were modifications of a real-world problem. Even though most of the test problems had over 600 binary variables, we were able to obtain a near optimum in less than 12 seconds of CPU time on a CDC Cyber-875.
Polymorphic CSP type checking (2001)

Communicating Sequential Processes (CSP) is a language used to describe and reason about concurrent systems. It consists of a process algebra combined with a functional language. This combination poses unique problems when attempting to design a type checker. In this paper the differences between a conventional functional language type checker and a type checker for the CSP language are discussed. This type checker was developed to identify polymorphic types, an important first step towards the goal of automating data independence [4]. The result of this work has been incorporated into the Adelaide Refinement Checker [8] (ARC) - a CSP based tool suite for model checking concurrent systems.
Lipopolysaccharide and Double-stranded RNA Up-regulate Toll-like Receptor 2 Independently of Myeloid Differentiation Factor 88 (2004)

Toll-like receptor 2 (TLR2) is a signaling receptor for a variety of microbial products, including bacterial lipoproteins and peptidoglycan, and is central in initiating immune responses toward Gram-positive bacteria, spirochetes, and mycobacteria. The mechanisms behind regulation of TLR2 protein expression are still not well understood. By using a newly developed monoclonal antibody against mouse TLR2, we detected TLR2 protein expression on macrophages, neutrophils, and dendritic cells. Endogenous macrophage TLR2 localized mostly to the cell membrane, with particular accumulation around phagosomes containing zymosan. Treatment of macrophages with the TLR2 antibody diminished cellular response to lipoproteins and down-regulated membrane TLR2. Marked up-regulation of surface TLR2 was observed on macrophages in response to whole bacteria, lipoproteins, lipopolysaccharide, poly(I-C) (double-stranded RNA), R848, and CpG DNA, and this up-regulation appeared to be a very sensitive marker for the presence of microbial products. Up-regulation of TLR2 in response to stimuli correlated with an increased response to secondary lipoprotein exposure following a low concentration of primary lipoprotein challenge. By comparison, exposure to a larger primary challenge induced a hyporeactive state. Most interestingly, lipopolysaccharide- and double-stranded RNA-induced up-regulation of surface TLR2 in macrophages was found to be MyD88-independent, whereas the up-regulation in response to lipoproteins, R848, and CpG DNA was absent in MyD88-deficient cells. We conclude that complex mechanisms regulate expression and signaling via TLR2. Up-regulation of TLR2 in the presence of low, yet clinically relevant amounts of microbial products may be an important mechanism by which the immune system boosts its response to a beginning infection.
Cellular and molecular aspects of PECAM-1. (1992)

PECAM-1 is a surface membrane glycoprotein of 130,000 daltons found on platelets, endothelial cells, monocytes, neutrophils, and certain T-cell subsets. Except for bone marrow precursor cells, it does not seem to be found outside the vasculature. Previous studies have shown that PECAM-1 is a member of the immunoglobulin gene superfamily that localizes to the intercellular junction in cells, like endothelial cells, that grow in monolayers. We and other laboratories have been involved in studies designed to define the role of PECAM-1 in various cell types. Mammalian expression vectors have been constructed that express all, or selected domains, of the PECAM-1 protein. These vectors have been used to induce PECAM-1 expression in a variety of both monolayer and suspension cell types. Domain-specific anti-PECAM-1 monoclonal antibodies, synthetic peptides, and heparin were also used to define structurally and functionally important domains of this membrane glycoprotein. Protein synthesis, subcellular localization, and association with the cytoskeletons of various cells expressing PECAM-1 were examined. From these studies we have obtained evidence that: (1) PECAM-1 redistributes to the border of monolayer cells when they contact each other. (2) Border localization may result from homophilic interactions, i.e. PECAM-1 on one cell binds PECAM-1 on the adjacent cell. (3) Suspension cells such as L-cells or neutrophils may also interact via PECAM-1 mediated interactions, but an as yet unidentified ligand probably participates in a heterophilic, rather than homophilic, type of interaction. (4) Intracellular movement of PECAM-1 in both monolayer and suspension cell types requires active participation of the cytoskeleton.(ABSTRACT TRUNCATED AT 250 WORDS)
Accumulation of Sialic Acid in Endocytic Compartments Interferes with the Formation of Mature Lysosomes (1999)

The impact of an altered endocytic environment on the biogenesis of lysosomes was studied in fibroblasts of patients suffering from sialic acid storage disease (SASD). This inherited disorder is characterized by the accumulation of acidic monosaccharides in lysosomal compartments and a concomitant decrease of their buoyant density. We demonstrate that C-terminal trimming of the lysosomal cysteine proteinase cathepsin B is inhibited in SASD fibroblasts. This late event in the biosynthesis of cathepsin B normally takes place in mature lysosomes, suggesting an impaired biogenesis of these organelles in SASD cells. When normal fibroblasts are loaded with sucrose, which inhibits transport from late endosomes to lysosomes, C-terminal cathepsin B processing is prevented to the same extent. Further characterization of the terminal endocytic compartments of SASD cells revealed properties usually associated with late endosomes/prelysosomes. In addition to a decreased buoyant density, SASD "lysosomes" show a reduced acidification capacity and appear smaller than their normal counterparts. We conclude that the accumulation of small non-diffusible compounds within endocytic compartments interferes with the formation of mature lysosomes and that the acidic environment of the latter organelles is a prerequisite for C-terminal processing of lysosomal hydrolases.
A novel chemosensor with visible light excitability for sensing Zn<sup>2+</sup>in physiological medium and in HeLa cells (2014)

In the present study a novel imine-hydrazone based fluorescent chemosensor () for efficient and selective sensing of Zn(2+) over other biologically important metal ions under physiological conditions is reported. An enhancement in fluorescence emission intensity of the developed probe with a red shift of ∼25 nm was observed for Zn(2+), whereas other metal ions failed to reveal any significant change in the emission spectra. Interestingly, the receptor functioned under completely physiological conditions (99.7% HEPES buffer) and has visible light excitability. Sensing of Zn(2+) was investigated in detail by absorption spectroscopy, emission spectroscopy, DFT calculation, (1)H-NMR titration experiment and ESI-MS experiment. The association constant between and Zn(2+) was found to be 5.58 × 10(5) M(-1). The receptor could detect as low as 69 ppb Zn(2+). Sensing of Zn(2+) is proposed through switch-on of intramolecular charge transfer (ICT) and chelation enhanced fluorescence (CHEF) processes after the introduction of Zn(2+) into the free ligand. The developed receptor was non-toxic and rendered intracellular sensing of Zn(2+) in HeLa cells through fluorescence imaging studies.
Activation of the silent endogenous cholesterol-7-alpha-hydroxylase gene in rat hepatoma cells: a new complementation group having resistance to 25-hydroxycholesterol. (1991)

The oxysterol 25-hydroxycholesterol acts both as a regulatory sterol determining the expression of genes governed by sterol regulatory elements and as a substrate for 7-alpha-hydroxylase, the first and rate-limiting enzyme in the bile acid synthetic pathway. Most wild-type nonhepatic cells are killed by the cytotoxic action of 25-hydroxycholesterol. In contrast, liver cells, which express 7-alpha-hydroxylase activity, are resistant to killing by 25-hydroxycholesterol. We examined the possibility that selection for resistance to 25-hydroxycholesterol might lead to the derivation of a cell line expressing 7-alpha-hydroxylase. A rat hepatoma cell line (7-alpha-hydroxylase minus) was transfected with human DNA and screened for resistance to 25-hydroxycholesterol. Although parental hepatoma cells were all killed within a week, a 25-hydroxycholesterol-resistant cell line (L35 cells) which showed stable expression of 7-alpha-hydroxylase activity and mRNA was obtained. These cells exhibited normal inhibition of cholesterol biosynthesis by 25-hydroxycholesterol. Blocking 7-alpha-hydroxylase activity with ketoconazole also blocked the resistance of L35 cells to 25-hydroxycholesterol. Isolation of microsomes from these cells showed levels of 7-alpha-hydroxylase activity (22.9 pmol/min/mg of protein) that were comparable to the activity (33.2 pmol/min/mg) of microsomes isolated from the livers of rats killed during the high point of the diurnal cycle. Parental cells had no detectable activity. These data show a new complementation group for 25-hydroxycholesterol resistance: expression of 7-alpha-hydroxylase. Dexamethasone increased both the activity and the cellular content of mRNA coding for 7-alpha-hydroxylase. Since dactinomycin blocked the ability of dexamethasone to induce mRNA, active transcription is required. Southern analysis of genomic DNA showed that L35 cells contain the rat (endogenous) gene but not the human gene. Furthermore, the RNA expressed by L35 cells is similar in size to rat RNA and is distinct from the human form of 7-alpha-hydroxylase. The combined data indicate that L35 cells are resistant to 25-hydroxycholesterol because they express 7-alpha-hydroxylase. The mechanism responsible involves activation of the endogenous (silent) gene of the parental rat hepatoma cell.
L-Deprenyl increases GFAP immunoreactivity selectively in activated astrocytes in rat brain (1993)

L-deprenyl is a selective inhibitor of monoamine oxidase (MAO) B, an enzyme predominantly localized in astrocytes. We have investigated the effect of treatment with L-deprenyl (0.25 mg kg-1 day-1) on glial fibrillary acidic protein (GFAP) immunoreactivity (IR) after lesioning the rat striatum with an injection cannula. No effect of drug treatment on GFAP IR was found in unlesioned striata. A significant increase (p < 0.01 vs saline treated rats) in GFAP IR was found in the tissue surrounding the lesion in striata of rats treated with L-deprenyl for 4 days after the lesion. When post-treated for 42 days, however, L-deprenyl no longer increased GFAP IR although reactive astrocytes were still present in the lesioned area. These results suggest that L-deprenyl can enhance the activation of astrocytes during a critical time-period following a striatal injury.
Rational bases for using oxygen-ozonetherapy as a biological response modifier in sickle cell anemia and beta-thalassemia: a therapeutic perspective. (2005)

We are proposing to evaluate whether a complementary approach based on cycles of oxygen-ozone autohemotherapy (O3-AHT) already performed in millions of patients, can abate the chronic oxidative stress and improve the quality of life of serious hemoglobinopathic patients. Although a preliminary study has yielded encouraging results, it appears appropriate to perform a controlled, randomized and possibly multicentre clinical trial. The long use of this approach in other pathologies has proved to be very useful and it is hoped that scepticism will not prevail over scientific rationale. Ozone, as any other drug, has an intrinsic toxicity that, in the proposed application, is fully tamed by the blood antioxidant system.
DNA helicase III from HeLa cells: an enzyme that acts preferentially on partially unwound DNA duplexes (1992)

Human DNA helicase III, a novel DNA unwinding enzyme, has been purified to apparent homogeneity from nuclear extracts of HeLa cells and characterized. The activity was measured by using a strand displacement assay with a 32P labeled oligonucleotide annealed to M13 ssDNA. From 305 grams of cultured cells 0.26 mg of pure protein was isolated which was free of DNA topoisomerase, ligase, nicking and nuclease activities. The apparent molecular weight is 46 kDa on SDS polyacrylamide gel electrophoresis. The enzyme shows also DNA dependent ATPase activity and moves unidirectionally along the bound strand in 3' to 5' direction. It prefers ATP to dATP as a cofactor and requires a divalent cation (Mg2+ > Mn2+). Helicase III cannot unwind either blunt-ended duplex DNA or DNA-RNA hybrids and requires more than 84 bases of ssDNA in order to exert its unwinding activity. This enzyme is unique among human helicases as it requires a fork-like structure on the substrate for maximum activity, contrary to the previously described human DNA helicases I and IV, (Tuteja et al. Nucleic Acids Res. 18, 6785-6792, 1990; Tuteja et al. Nucleic Acids Res. 19, 3613-3618, 1991).
Clinical effects of azelastine hydrochloride in hemodialysis patients with pruritus cutaneous. (1995)

皮膚〓痒症, 湿疹・皮膚炎を合併した186例の透析患者を対象に塩酸アゼラスチン2mg/日を投与し, 〓痒, 皮膚症状に対する臨床効果を検討した. 〓痒は, 発現時期別に日中, 夜間, 透析中の3つに分け観察し, その程度は白取の「〓痒重症度の基準」に準じて5段階に分類・判定した. 〓痒に対する塩酸アゼラスチンの効果は, 投与8週後まで投与期間に比例して高まっていった. この傾向は, 日中, 夜間, 透析中のすべての〓痒感に共通しており, 投与8週目まで〓痒重症度の症状なし, 軽微の患者が徐々に増加していった. 週別改善度においても投与7週目まで週を追う毎に改善度の上昇が見られ, 投与8週後の最終全般改善度は, 著明改善14.2%, 中等度改善29.0%, 軽度改善27.9%という成績であった. 副作用および血液検査の異常は10例, 5.4%に認められ, その主なものは, 眠気, 味覚異常, 口渇などであった.以上の成績から, 塩酸アゼラスチンは, 透析患者の皮膚〓痒症に優れた効果を示し, 安全性も高く有用な薬剤と考えられる.
Distributed object-oriented schema for XML-based electronic catalog sharing semantics among businesses (2002)

Internet commerce is increasing the demands of service integrations by sharing XML-based catalogs. We propose the PCO (Portable Compound Object) data model supporting semantic inheritance to ensure the synonymy of heterogeneous semantics among distributed schemas that different authors define independently. Also, the PCO model makes semantic relationships independent of an initial class hierarchy, and it enables rapid schema evolution across the entire Internet business. This preserves semantic interoperability without changing pre-defined classes. We have also encoded the PCO model into two XML-based languages: the PCO Specification Language (PSL) and the Portable Composite Language (PCL). This paper demonstrates that intermediaries defining service semantics in PSL can automatically integrate multiple suppliers' PCL catalogs for their agent-mediated services.
Antibacterial effect of water-soluble chitosan on representative dental pathogens Streptococcus mutans and Lactobacilli brevis (2012)

This study illustrated that water-soluble chitosan may be a viable alternative to commercial mouthwashes in the future.
Efficient in vivo delivery of antisense oligonucleotide to choroid plexus. (2013)

The choroid plexus (CP) is present on the ventricular walls of the brain, produces cerebrospinal fluid (CSF), contains many blood vessels, and is a major functional component of the blood-CSF barrier. The CP is an important site in the pathophysiology of various neurological diseases, including Alzheimer's disease and meningeal amyloidosis. We performed gene silencing in the CP in vivo by using an antisense oligonucleotide (ASO). A short ASO of length 12 nucleotides was intravenously injected into rats. The ASO was not delivered to neurons or glia in the central nervous system, but was successfully delivered into the CP, and resulted in a significant reduction of endogenous target gene expression in epithelial cells within the CP. Although the mechanism of uptake of the ASO by the CP was not elucidated, the ASO bound to albumin in vivo, and the distribution of ASO delivery was similar to that of albumin delivery. These findings suggest that we inhibited target gene expression in the epithelial cells of the CP via albumin-ASO conjugates. This strategy should be useful for investigations of the function of CP, and for the development of new gene-silencing therapies for diseases with pathophysiology related to the CP.
In vitro binding of purified murine ecotropic retrovirus envelope surface protein to its receptor, MCAT-1 (1997)

An amino-terminal portion of the Friend murine leukemia virus (MLV) envelope surface protein [SU, residues 1 to 236 [SU:(1-236)]] and its receptor, MCAT-1, were each purified from insect cells after expression by using recombinant baculoviruses. Friend SU:(1-236) bound specifically to Xenopus oocytes that expressed MCAT-1 with an affinity (Kd, 55 nM) similar to that of viral SU binding to permissive cells. Direct binding of Friend SU:(1-236) to purified MCAT-1 was observed in detergent and after reconstitution into liposomes. Analysis of binding demonstrated that MCAT-1 and Friend SU:(1-236) interact with a stoichiometry of near 1:1. These findings demonstrate that the amino-terminal domain from the SU of ecotropic murine retroviruses contains an MCAT-1 binding domain.
Designing a DHT for low latency and high throughput (2004)

Designing a wide-area distributed hash table (DHT) that provides high-throughput and low-latency network storage is a challenge. Existing systems have explored a range of solutions, including iterative routing, recursive routing, proximity routing and neighbor selection, erasure coding, replication, and server selection. This
First-Principle Study of Hydroxyl Functional Groups on Pristine, Defected Graphene, and Graphene Epoxide (2010)

Oxygen-containing functional groups can be present in considerable amount intentionally or unintentionally on graphene, and a complete reduction of graphene oxide is difficult to achieve. To address the origin of this behavior, we have performed pseudopotential density functional theory calculations to investigate in particular the adsorption of hydroxyl (OH) on perfect and defected graphene, individually and in the presence of other coadsorbed functional groups. We found that hydroxyl groups weakly adsorb on perfect graphene, easily aggregate, also with coadsorbed epoxy groups, and can react with each other with a barrier of about 0.5 eV forming water. Defect sites are more reactive for OH adsorption but play different roles. At variance with single vacancy defects where the OH adsorption is highly dissociative, Stone−Wales defects could stabilize the hydroxyl groups on the graphene basal plane, with a much stronger binding and higher barriers for recombination and water formation than pristine.
Comparisons of Familial DNA Database Searching Strategies (2011)

The current familial searching strategies are generally based on either Identity-By-State (IBS) (i.e., number of shared alleles) or likelihood ratio (i.e., kinship index [KI]) assessments. In this study, the expected IBS match probabilities given relationships and the logic of the likelihood ratio method were addressed. Further, the false-positive and false-negative rates of the strategies were compared analytically or by simulations using Caucasian population data of the 13 CODIS Short Tandem Repeat (STR). IBS ≥ 15, IBS ≥ 16, KI ≥ 1000, or KI ≥ 10,000 were found to be good thresholds for balancing false-positive and false-negative rates. IBS ≥ 17 and/or KI ≥ 1,000,000 can exclude the majority of candidate profiles in the database, either related or not, and may be an initial screening option if a small candidate list is desired. Polices combining both IBS and KI can provide higher accuracy. Typing additional STRs can provide better searching performance, and lineage markers can be extremely useful for reducing false rates.
Crisis management during anaesthesia: pneumothorax (2005)

Any pneumothorax may become a dangerous tension pneumothorax with the application of positive pressure ventilation. Limited access to the chest during anaesthesia may compromise the diagnosis. Recognition of any preoperative predisposition to a pneumothorax (for example, iatrogenic or traumatic penetrating procedures around the base of the neck) and close communication with the surgeon are important. Aspiration diagnosis in suspected cases and correct insertion of a chest drain are essential for the safe conduct of anaesthesia and surgery.
Total joint arthroplasty. The ankle. (1979)

When conservative measures fail to relieve significant disability due to ankle joint disease, the only surgical method of treatment has been arthrodesis. Because of less than ideal results and other long-term problems with ankle arthrodesis, and after numerous investigation to characterize the ankle mechanically, we developed a prosthetic ankle joint replacement. The Mayo total ankle replacement is a metal-on-polyethylene, congruent, constrained prosthesis. Analysis of 94 patients (102 ankle prostheses) revealed good clinical results in patients with rheumatoid arthritis and in older persons with posttraumatic degenerative disease. Younger, more active patients in the latter category had more disappointing results. Further design development is under way to improve range-of-motion characteristics, decrease constraint forces, and improve bone fixation of the prosthetic components.