gebhart/patrepeval huggingface dataset:
The proteoglycan decorin binds C1q and inhibits the activity of the C1 complex (1992)

Decorin, a small collagen-binding dermatan sulfate proteoglycan, is widely distributed as a component of extracellular matrices. Using a solid phase binding assay, we showed that decorin bound C1q at physiologic pH and ionic strength. The interaction did not require divalent cations and was time and temperature dependent reaching equilibrium in 4 h at 37 degrees C. Binding was specific and saturable with an apparent dissociation constant of 7.6 x 10(-9) M. Decorin was shown to bind pepsin-derived fragments containing the collagenous domain of C1q and collagenase-derived fragments containing the globular domain of C1q. Because these fragments share a short sequence of amino acids, this finding suggests that decorin binds to a region of C1q located near the junction of the two domains. Competition studies using purified preparations of the decorin core protein and the glycosaminoglycan chains showed that only the former inhibited binding of decorin to C1q indicating that the interaction is mediated by the decorin core protein. Decorin was shown to inhibit the hemolytic activity of purified C1 as well as C1 in normal human serum. Approximately 50% inhibition was observed at a decorin concentration of 2 micrograms/ml. Inhibition was not observed if C1 was bound to Ag-complexed antibody. Furthermore, neither the core protein nor the glycosaminoglycan chain of decorin inhibited C1, indicating that the intact proteoglycan is necessary for functional activity.
From Genes to Proteins in Mendelian Parkinson's Disease: An Overview (2009)

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. A progressive movement disorder typified by the production of bradykinesia, tremor, rigidity, and impairment of postural reflexes, PD is characterized by a depletion of dopamine in the striatum. For the last decade, several Mendelian forms of PD have been identified. Mutations in these genes potentially lead to autosomal dominant (alpha-synuclein and LRRK2), or autosomal recessive PD (Parkin, PINK1, DJ1, and ATP13A2). This article will spotlight these six distinct genes unambiguously associated with Mendelian PD and the function of their encoded proteins.
Inhibition of mechanosensitive signaling in myofibroblasts ameliorates experimental pulmonary fibrosis (2013)

Matrix stiffening and myofibroblast resistance to apoptosis are cardinal features of chronic fibrotic diseases involving diverse organ systems. The interactions between altered tissue biomechanics and cellular signaling that sustain progressive fibrosis are not well defined. In this study, we used ex vivo and in vivo approaches to define a mechanotransduction pathway involving Rho/Rho kinase (Rho/ROCK), actin cytoskeletal remodeling, and a mechanosensitive transcription factor, megakaryoblastic leukemia 1 (MKL1), that coordinately regulate myofibroblast differentiation and survival. Both in an experimental mouse model of lung fibrosis and in human subjects with idiopathic pulmonary fibrosis (IPF), we observed activation of the Rho/ROCK pathway, enhanced actin cytoskeletal polymerization, and MKL1 cytoplasmic-nuclear shuttling. Pharmacologic disruption of this mechanotransduction pathway with the ROCK inhibitor fasudil induced myofibroblast apoptosis through a mechanism involving downregulation of BCL-2 and activation of the intrinsic mitochondrial apoptotic pathway. Treatment with fasudil during the postinflammatory fibrotic phase of lung injury or genetic ablation of Mkl1 protected mice from experimental lung fibrosis. These studies indicate that targeting mechanosensitive signaling in myofibroblasts to trigger the intrinsic apoptosis pathway may be an effective approach for treatment of fibrotic disorders.
Sublingual Buprenorphine Is Effective in the Treatment of Chronic Pain Syndrome (2005)

Many patients with chronic pain have less than optimal therapeutic outcomes after prolonged treatment with opiate analgesics. Worsening of pain perception, functional capacity, and mood often result. Medical detoxification is often undertaken in this situation. Ninety-five consecutive patients (49 men and 46 women; age range, 26-84) with chronic noncancer pain (maldynia) were referred by local pain clinics for detoxification from long-term opiate analgesic (LTOA) therapy. All patients had failed treatment as manifest by increasing pain levels, worsening functional capacity, and, in 8%, the emergence of opiate addiction. Length of prior LTOA therapy ranged from 1.5 to 27 years (mean, 8.8 years). After a minimum of 12 hours of abstinence from all opiate analgesics, patients were given low doses of sublingual (SL) buprenorphine or buprenorphine/naloxone (Reckitt Benckiser). Maintenance dosing was individualized to treat chronic pain. Daily SL dose of buprenorphine ranged from 4 to 16 mg (mean, 8 mg) in divided doses. Mean duration of treatment is 8.8 months (range, 2.4-16.6 months). At clinic appointments, patients were assessed for pain reports, functional capacity, and mood inventory. Eighty-six percent of patients experienced moderate to substantial relief of pain accompanied by both improved mood and functioning. Patient and family satisfaction was robust. Only 6 patients discontinued therapy secondary to side effects and/or exacerbation of pain. In this open-label study, SL buprenorphine and buprenorphine/naloxone were well tolerated and safe and appeared to be effective in the treatment of chronic pain patients refractory to LTOA.
Neural injury repair: hope for the future as barriers to effective CNS regeneration become clearer (1995)

In this review the author outlines the early history of clinical and scientific research upon the inability of the CNS in man to successfully regenerate following injury. As we proceed into the 21st Century we have gained a far greater understanding of the molecular biology, pathology and other factors that lead to the adult CNS being non-supportive and indeed actively inhibitory to axonal regrowth. On the basis of these recent advances in knowledge, the author outlines possible therapeutic approaches that may enable more effective CNS regeneration to be accomplished in the future.
Role of Platelet-Endothelial Cell Adhesion Molecule (PECAM) in Platelet Adhesion/Aggregation Over Injured but Not Denuded Endothelium In Vivo and Ex Vivo (1996)

PECAM is an important modulator of platelet adhesion/aggregation at sites of minor endothelial damage in brain arterioles. The data are consistent with the hypothesis that PECAM sites on the endothelium are involved and may be exposed by the injury to promote adhesion/aggregation. Since the endothelial cell layer is intact at these sites, mechanisms such as this offer important alternatives to the more commonly studied pathways of platelet activation, which require exposure of collagen and are not applicable in this model.
HPLC Purification of In Vitro Transcribed Long RNA (2012)

In vitro transcription of DNA with phage RNA polymerases is currently the most efficient method to produce long sequence-specific RNA. While the reaction can yield large quantities of RNA, it contains impurities due to various unwanted activities of the polymerases. Here, we described an easily performed HPLC purification that removes multiple contaminants from in vitro transcribed RNA and is scalable. The purified RNA is translated at much greater levels, especially in primary cells and in vivo. HPLC purification of RNA containing modified nucleosides that suppress RNA-mediated activation of innate immune sensors leads to a non-immunogenic RNA with superior translational capacity.
Cytokine and immuno-gene therapy for solid tumors. (2005)

Despite recent progress in our understanding of cancer biology and in many areas of cancer treatment, the success rate for cancer therapy remains dismal. Immunotherapy for cancer has long been an exciting field for many cancer researchers due to the possibility to mobilize the body's own immune system to eradicate cancer not only locally but also systemically. Since its initial discovery, cytokine-based immunotherapy has been vigorously and extensively investigated for cancer treatment due to the perception of it as a relatively easily purifiable, injectable form of cancer treatment agent. However, so far most cytokine-based therapy trials have fallen short of expectations. One of main obstacles is the difficulty to achieve therapeutically relevant dosage in patients without generating excessive normal tissue toxicity. The emergence of novel gene therapy approach to deliver therapeutic cytokine to tumors locally generated great excitement since it has the potential of generating sustained high local concentration of immunostimulatory cytokine without raising the systemic levels of the cytokines, which is responsible for most of the observed toxicity. In this review, we will attempt to provide an overview of the field and discuss some of the problems associated with cytokine-based immuno-gene therapy and potential solutions.
Assessment of the economic impact of porcine reproductive and respiratory syndrome on swine production in the United States (2005)

PRRS imposes a substantial financial burden on US swine producers and causes approximately dollar 560.32 million in losses each year. By comparison, prior to eradication, annual losses attributable to classical swine fever (hog cholera) and pseudorabies were estimated at dollar 364.09 million and dollar 36.27 million, respectively (adjusted on the basis of year 2004 dollars). Current PRRS control strategies are not predictably successful; thus, PRRS-associated losses will continue into the future. Research to improve our understanding of ecologic and epidemiologic characteristics of the PRRS virus and technologic advances (vaccines and diagnostic tests) to prevent clinical effects are warranted.
New conceptual electromagnetic induction fluid heating system using resonant PWM inverter with auto-tuning PID controller (2002)

A new concept of a novel prototype electromagnetic induction fluid heating appliance using series capacitor-compensated load resonant high-frequency inverter with a phase-shifted PWM and power factor correction schemes. Its operating characteristics in steady-state are illustrated and evaluated using the computer simulation and experimental results. From a practical point of view, a promising cost effective application of this electromagnetic induction fluid heating appliance is proposed, which is more suitable for industrial, chemical and consumer pipeline systems.
Identification of NVP-BKM120 as a Potent, Selective, Orally Bioavailable Class I PI3 Kinase Inhibitor for Treating Cancer (2011)

Phosphoinositide-3-kinases (PI3Ks) are important oncology targets due to the deregulation of this signaling pathway in a wide variety of human cancers. Herein we describe the structure guided optimization of a series of 2-morpholino, 4-substituted, 6-heterocyclic pyrimidines where the pharmacokinetic properties were improved by modulating the electronics of the 6-position heterocycle, and the overall druglike properties were fine-tuned further by modification of the 4-position substituent. The resulting 2,4-bismorpholino 6-heterocyclic pyrimidines are potent class I PI3K inhibitors showing mechanism modulation in PI3K dependent cell lines and in vivo efficacy in tumor xenograft models with PI3K pathway deregulation (A2780 ovarian and U87MG glioma). These efforts culminated in the discovery of 15 (NVP-BKM120), currently in Phase II clinical trials for the treatment of cancer.
Follicular NHL: From Antibodies and Vaccines to Graft-versus-Lymphoma Effects (2007)

Monoclonal antibody therapy with rituximab in combination with standard chemotherapy has improved the survival of patients with advanced-stage follicular lymphoma (FL). A series of next-generation anti-CD20 antibodies may be less immunogenic and have even greater antitumor activity through augmented interactions with host effector mechanisms responsible for tumor cell kill. Additional approaches with patient-specific immunoglobulin idiotype vaccines; novel monoclonal antibodies binding to biologically active cell-surface antigen are also demonstrating early clinical activity. Antibodies targeting radioisotopes, toxins or drugs are also slowly entering clinical trials and practice. Last, allogeneic stem cell transplantation following reduced-intensity conditioning provides graft-versus-tumor immune responses that may be able to control FL and allow this risky but potentially curative treatment option to older patents or those with comorbidities.
Chemical Constituents and Insecticidal Activities of the Essential Oil from Amomum tsaoko against Two Stored-Product Insects (2014)

The aim of this research was to determine the chemical constituents and toxicities of the essential oil derived from Amomum tsaoko Crevost et Lemarie fruits against Tribolium castaneum (Herbst) and Lasioderma serricorne (Fabricius). Essential oil of A. tsaoko was obtained from hydrodistillation and was investigated by gas chromatography-mass spectrometry (GC-MS). GC-MS analysis of the essential oil resulted in the identification of 43 components, of which eucalyptol (23.87%), limonene (22.77%), 2-isopropyltoluene (6.66%) and undecane (5.74%) were the major components. With a further isolation, two active constituents were obtained from the essential oil and identified as eucalyptol and limonene. The essential oil and the two isolated compounds exhibited potential insecticidal activities against two storedproduct insects. Limonene showed pronounced contact toxicity against both insect species (LD50 = 14.97 μg/adult for T. castaneum; 13.66 μg/adult for L. serricorne) and was more toxic than eucalyptol (LD50 = 18.83 μg/adult for T. castaneum; 15.58 μg/adult for L. serricorne). The essential oil acting against the two species of insects showed LD50 values of 16.52 and 6.14 μg/adult, respectively. Eucalyptol also possessed strong fumigant toxicity against both insect species (LC50 = 5.47 mg/L air for T. castaneum; 5.18 mg/L air for L. serricorne) and was more toxic than limonene (LC50 = 6.21 mg/L air for T. castaneum; 14.07 mg/L air for L. serricorne), while the crude essential oil acting against the two species of insects showed LC50 values of 5.85 and 8.70 mg/L air, respectively. These results suggested that the essential oil of A. tsaoko and the two compounds may be used in grain storage to combat insect pests.
环孢素A治疗肾小球疾病的应用共识 (2007)

环孢素A(Cyclosporin A,CsA)为11个氨基酸组成的环形多肽,是从土壤霉菌中分离出来的一种强效、选择性的免疫抑制剂.CsA广泛用于器官移植及免疫性疾病的治疗,近年来已被用于治疗难治性肾病综合征和其他肾脏疾病。
Plasmid DNA size does not affect the physicochemical properties of lipoplexes but modulates gene transfer efficiency (1999)

Clinical applications of gene therapy mainly depend on the development of efficient gene transfer vectors. Large DNA molecules can only be transfected into cells by using synthetic vectors such as cationic lipids and polymers. The present investigation was therefore designed to explore the physicochemical properties of cationic lipid-DNA particles, with plasmids ranging from 900 to 52 500 bp. The colloidal stability of the lipoplexes formed by complexing lipopolyamine micelles with plasmid DNA of various lengths, depending on the charge ratio, resulted in the formation of three domains, respectively corresponding to negatively, neutrally and positively charged lipoplexes. Lipoplex morphology and structure were determined by the physicochemical characteristics of the DNA and of the cationic lipid. Thus, the lamellar spacing of the structure was determined by the cationic lipid and its spherical morphology by the DNA. The main result of this study was that the morphological and structural features of the lipopolyamine-DNA complexes did not depend on plasmid DNA length. On the other hand, their gene transfer capacity was affected by the size of plasmid DNA molecules which were sandwiched between the lipid bilayers. The most effective lipopolyamine-DNA complexes for gene transfer were those containing the shortest plasmid DNA.
Bandwidth and modal noise effects in fused-head-end multimode fiber passive components (1989)

Passive multimode fiber components, particularly 1-to-2 splitters/couplers, manufactured using the fused-head-end technique, are tested under network conditions. The mode power transfer matrix and its effects on the network are discussed. The modification of the pulse mode spectrum in the splitter is analyzed by studying the pulsewidth variation and the transmitted pulse power for components at the near and far end of a long length of fiber. The modal noise generated in such passive fiber components is determined, and the modal noise ratio (MNR) and the modal noise susceptibility (MNS) are introduced as figures of merit characterizing modal noise sources and multimode fiber passive components, respectively.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Genotype of metabolic enzymes and the benefit of tamoxifen in postmenopausal breast cancer patients (2005)

Abstract Background Tamoxifen is widely used as endocrine therapy for oestrogen-receptor-positive breast cancer. However, many of these patients experience recurrence despite tamoxifen therapy by incompletely understood mechanisms. In the present report we propose that tamoxifen resistance may be due to differences in activity of metabolic enzymes as a result of genetic polymorphism. Cytochrome P450 2D6 ( CYP2D6 ) and sulfotransferase 1A1 ( SULT1A1 ) are polymorphic and are involved in the metabolism of tamoxifen. The CYP2D6*4 and SULT1A1*2 genotypes result in decreased enzyme activity. We therefore investigated the genotypes of CYP2D6 and SULT1A1 in 226 breast cancer patients participating in a trial of adjuvant tamoxifen treatment in order to validate the benefit from the therapy. Methods The patients were genotyped using PCR followed by cleavage with restriction enzymes. Results Carriers of the CYP2D6*4 allele demonstrated a decreased risk of recurrence when treated with tamoxifen (relative risk = 0.28, 95% confidence interval = 0.11–0.74, P = 0.0089). A similar pattern was seen among the SULT1A1*1 homozygotes (relative risk = 0.48, 95% confidence interval = 0.21–1.12, P = 0.074). The combination of CYP2D6*4 and/or SULT1A1*1/*1 genotypes comprised 60% of the patients and showed a 62% decreased risk of distant recurrence with tamoxifen (relative risk = 0.38, 95% confidence interval = 0.19–0.74, P = 0.0041). Conclusion The present study suggests that genotype of metabolic enzymes might be useful as a guide for adjuvant endocrine treatment of postmenopausal breast cancer patients. However, results are in contradiction to prior hypotheses and the present sample size is relatively small. Findings therefore need to be confirmed in a larger cohort.
The Mode of Plastic Deformation of &beta; Ti&ndash;V Alloys (1982)

Deformation modes of quenched β Ti–16∼27%V alloys are investigated in compressive and tensile tests as a function of crystallographic orientation and deformation temperature. The {332} twinning takes place in the low vanadium content alloys. By analysing the twinning systems appearing in compressive and tensile tests, the polarization of twinning shear is confirmed to occur in the {332} twinning. The {332} twinning is suppressed by aging or oxygen addition. It is suggested that the formation of the {332} twinning is due to the instability of the β phase of Ti–V alloys containing some interstitial impurity atoms. On the other hand, deformation occurs by slip in the alloys with high content of V. These alloys exhibit an asymmetry of both the yield stress and the slip plane, the degree of asymmetry being larger at 77 K than at 300 K.
The Design of the POSTGRES Storage System (1987)

Abstract : This paper presents the design of the storage system for the POSTGRES data base system under construction at Berkeley. It is novel in several ways. First, the storage manager supports transaction management but does so without using a conventional write ahead log (WAL). In fact, there is no code to run at recovery time, and consequently recovery from crashes is essentially instantaneous. Second, the storage manager allows a user to optionally keep the entire past history of data base objects by closely integrating an archival storage system to which historical records are spooled. Lastly, the storage manager is consciously constructed as a collection of asynchronous processes. Hence, a large monolithic body of code is avoided and opportunities for parallelism can be exploited. The paper concludes with a analysis of the storage system which suggests that it is performance competitive with WAL systems in many situations.
Therapeutic vaccines against IgE-mediated allergies (2008)

Therapeutic vaccines targeting various self-molecules is an emerging field of vaccine development that is studied extensively in areas such as birth control, cancer, allergy and autoimmunity. Promising results have come from a number of animal studies and several vaccines are in advanced clinical trials. However, no vaccine is currently on the market. This review will focus on the progress in the development of vaccines against IgE-mediated allergies. Targets under investigation are the IgE molecule itself and several Th2 cytokines, that is, IL-4, -5, -13, -33, -18 and thymic stromal lymphopoietin. This review will also discuss new methods to enhance the immunogenicity of the vaccines and how this can contribute to more rapid progress in the field.
SDA9280 D／A电路：在数学处理彩色电视机中的应用 (2000)

本文首先介绍了数字信号的特点，对Ｄ／Ａ（数字／模拟）转换电路的工作原理做了较为详细的说明，同时对ＳＤＡ９２８０集成电路进行了较为系统的分析，对ＳＤＡ９２８０在数字处理彩色电视机中的应用作了说明。
A dominant-negative receptor for type beta transforming growth factors created by deletion of the kinase domain (1993)

To prove the postulated role of type beta transforming growth factors (TGF beta) in cardiac development and other events, specific inhibitors of TGF beta signal transduction are needed. We truncated the type II TGF beta receptor cDNA (delta kT beta RII), to delete the predicted serine/threonine kinase cytoplasmic domain. delta kT beta RII was co-transfected into neonatal cardiac myocytes, together with reporter constructs for two cardiac-restricted genes that are regulated antithetically by TGF beta. delta kT beta RII impaired activation of the skeletal alpha-actin promoter by TGF beta 1, -2, and -3 and, conversely, impaired TGF beta inhibition of alpha-myosin heavy chain transcription. Thus, a kinase-defective T beta RII blocks signaling by all three mammalian TGF beta isoforms, and can disrupt both positive and negative control of transcription by TGF beta.
Rapid Bergman Cyclization of 1,2-Diethynylheteroarenes (1998)

The synthesis and cyclization of acyclic quinoxaline, pyridine, and pyrimidine enediynes (1−3) are described. These compounds were prepared using palladium(0) coupling of trimethylsilyl acetylene to o-dihalo- or o-halotriflic heteroarenes. All compounds were prepared in modest to good yields. The enediynes prepared were shown to undergo Bergman cyclization. Kinetics over a minimum of 3 half-lives were used to construct Arrhenius plots. Pyrimidine 3 was found to have an activation energy of 16.1 kcal/mol. Cyclization of the closest known aromatic analogue, o-diethynylbenzene (15), has Ea = 25.1 kcal/mol (Grissom, J. W.; Calkins, T. L.; McMillen, H. A.; Jiang, Y. J. Org. Chem. 1994, 59, 5833−5835). Pyridine 2 and quinoxaline 1 gave activation energies of 21.5 and 33.6 kcal/mol, respectively. The results illustrate that heteroarenes can be used to activate Bergman cyclization. We expect these compounds to play an important role in furthering the understanding of Bergman cyclization and in aiding the development of new biologically significant enediynes.