gebhart/patrepeval huggingface dataset:
Biological and clinical significance of MMP-2, MMP-9, TIMP-1 and TIMP-2 in non-small cell lung cancer (2007)

Our main aim consists of investigating the clinical usefulness of gelatinases and their tissue inhibitors in non-small cell lung cancer (NSCLC). Thus, we have analysed in 111 NSCLCs, levels and activity of MMP-2, MMP-9, TIMP-1 and TIMP-2, by Enzymoimmunoassay and Gelatine zymography, respectively. Our data revealed higher MMP-2 net activity in the NSCLC population analyzed in this study, this parameter showing a significant association with the TNM stage of tumours (P=0.002). Moreover, MMP-9 levels were significantly associated with poor clinical evolution of patients (P=0.02). Also, disease-free survival time was higher for patients whose tumours showed TIMP-1 increased levels (P=0.04). Of interest, Cox multivariate analysis revealed that TIMP-1 levels can be considered as an independent prognostic factor in NSCLC. Relative Risk (RR) to tumour relapse was more than two times lower for patients showing high TIMP-1 levels (RR=0.420, P=0.041). Therefore, according to our results, we conclude that MMP-9 and TIMP-1 levels of synthesis could be useful for the selection of patients with potentially unfavourable clinical evolution in order to establish adjuvant therapy protocols. Among these parameters, TIMP-1 level evaluation emerges as the main factor to predict the clinical outcome of patients.
Storms Before the Storm: 1912–1914 (1995)

Residence in Switzerland and France was endured stoically by Russian émigrés. They had left their motherland involuntarily; and most of them regarded Geneva, Berne and Zurich as the least hateful of alternative bases. At first glance it is mystifying that they did not gravitate towards citadels of Europe’s contemporary avant-garde, such as Vienna. Why did they, in the main, avoid lengthy stays in centres of economic power such as London or Berlin? The main reason was that Switzerland’s constitution provided an unusual degree of civic tolerance. Russian revolutionaries attracted little attention from the authorities. The snowy winters were bitter-sweetly reminiscent of home. The mountains were strange, certainly, to inhabitants of the Russian empire unless they happened to come from the Caucasus. Yet all the émigrés, whatever their geographical origins, adored the Alps. Hill-walking was as popular among them as among Swiss townsfolk — in those days it was only a few aristocratic Britons who were mountaineering enthusiasts. Swiss orderliness could grate upon the sensibilities of Russians (although this was never Lenin’s reaction!), but in general earned its due esteem. The efficiency of libraries and postal services was a godsend to these bibliophile rebels. Russian socialists as Second International members also found the country well situated for communications with Central, Western and Southern Europe.
Mutational Analyses of the Metal Ion and Substrate Binding Sites of Phosphorylase Kinase .gamma. Subunit (1994)

Phosphorylase kinase (PhK) and truncated gamma subunit, denoted gamma 1-300, can phosphorylate seryl and tyrosyl residues dependent on the metal ion [Yuan, C.-J., Huang, C. F., & Graves, D. J. (1993) J. Biol. Chem. 268, 17683-17686]. Recombinant gamma 1-300 was used to explore its dual specificity and the location of the metal ion binding sites by using site-directed mutagenesis. Two approaches were taken to generate 26 mutants. First, on the basis of the crystal structure of cAMP-dependent protein kinase (cAPK), the invariant Asn155 and highly conserved Asp168-Phe169-Gly170 residues were mutated. Changes included production of N155H, D168E, D168N, F169R, G170V, G170I, G170L (less than 1% of enzymatic activities were found in these mutants), F169W, and G170A mutants. Second, charge to alanine and charge reversal scanning mutations were used to probe the metal ion binding sites. Two mutants, E111K and E154R, showed very different metal ion response compared to wild-type gamma and were further characterized. The mutants F169W, G170A, E111K, and E154R had 15%, 5%, 8%, and 25% specific activity relative to wild-type gamma, respectively. The folding pattern of wild-type and mutated enzyme forms of gamma was determined by photoacoustic infrared spectroscopy. Conformational disruptions were found in G170V, G170I, and G170L mutants, but the conformation of the rest of the mutants was similar to that of wild-type gamma, suggesting that the loss of enzymatic activities of these mutants was not because of incorrect refolding.(ABSTRACT TRUNCATED AT 250 WORDS)
Chronic Inflammatory Demyelinating Polyneuropathy (2009)

Chronic inflammatory demyelinating polyneuropathy typically presents with both proximal and distal weakness, areflexia, and distal sensory findings. This chapter emphasizes the importance of differential diagnosis and work up. Treatment options are also described.
p53 Activates the CD95 (APO-1/Fas) Gene in Response to DNA Damage by Anticancer Drugs (1998)

Chemotherapeutic drugs cause DNA damage and kill cancer cells mainly by apoptosis. p53 mediates apoptosis after DNA damage. To explore the pathway of p53-dependent cell death, we investigated if p53-dependent apoptosis after DNA damage is mediated by the CD95 (APO-1/Fas) receptor/ligand system. We investigated hepatoma, gastric cancer, colon cancer, and breast cancer cell lines upon treatment with different anticancer agents known to act via p53 accumulation. Cisplatin, mitomycin, methotrexate, mitoxantrone, doxorubicin, and bleomycin at concentrations present in the sera of patients during therapy led to an upregulation of both CD95 receptor and CD95 ligand. Induction of the CD95 ligand occurred in p53 wild-type (wt), p53 mutant (mt), and p53 deficient (p53(-/-)) cell lines and at wt and mt conformation of temperature-sensitive p53 mutants. In contrast, upregulation of the CD95 receptor was observed only in cells with wt p53, not in cells with mt or without any p53. Restitution of inducible wt p53 function restored the ability of p53(-/-) Hep3B cells to upregulate the CD95 receptor in response to anticancer drugs. This rendered the cells sensitive to CD95-mediated apoptosis. In an attempt to understand how CD95 expression is regulated by p53, we identified a p53-responsive element within the first intron of the CD95 gene, as well as three putative elements within the promoter. The intronic element conferred transcriptional activation by p53 and cooperated with p53-responsive elements in the promoter of the CD95 gene. wt p53 bound to and transactivated the CD95 gene, whereas mt p53 failed to induce apoptosis via activation of the CD95 gene. These observations provide a mechanistic explanation for the ability of p53 to contribute to tumor progression and to resistance of cancer cells to chemotherapy.
Electronic Cigarettes: A Short Review (2013)

Marketed since 2004 as an alternative to nicotine delivery and advertised as a valid means to smoking cessation, the electronic (e)-cigarette has been the subject of much controversy but very little experimental study. This review provides a brief summary of the current knowledge of this product. Propylene glycol and glycerol, the main ingredients of the fluid that is vaporized, have proved to be harmless in the fog machines of the entertainment industry. However, in the case of the e-cigarette fluid, the composition is not properly labeled: additives like nicotine and flavors vary between and within brands and contamination with various chemicals has been detected. The short-term toxicity seems low, but the long-term toxicity is unknown. The usefulness of the e-cigarette in smoking cessation has still to be clinically established.
CRC handbook of polymer-liquid interaction parameter s and solubility parameters (1990)

PART I: INTRODUCTION. Definitions and Relationships. Citation of References. Solvents and Nonsolvents. Ordering of Entries in Part III. Glossary of Symbols. PART II: MAJOR ENTRIES. Acrylic. polyAcrylonitrile. Alkyd. polyAmide. Bisphenol A-Epichlorohydrin Epoxy. Bisphenol A polySulfone. polyButadiene. polyButadiene-Acrylonitrile. Butyl (polyIsobutylene-Isoprene). polyn-Butyl Acrylate. polyn-BUTYL Methacrylate. Cellulose Acetate. Cellulose Nitrate. polyChloroprene. polyChlorostyrene. polyChlorotrifluoroethylene. Coal. poly 2,6-Dimethyl-1,4-Phenylene Oxide. polyDimethylsiloxane. Epoxy. polyEthyl Acrylate. Ethyl Cellulose. polyEthylene. polyEthylene Oxide. polyEthylene-Propylene. Ethylene Terephthalate. polyEthylene-Vinyl Acetate. polyEthyl Methacrylate. Hydroxypropyl Cellulose. polyIsobutylene. polyIsoprene. polyMethyl Acrylate. polyMethyl Methacrylate. polyPropylene. Silicone. polyStyrene. polyStyrene-Acrylonitrile. polyStyrene-Butadiene. polyStyrene-Divinylbenzene. polyTetrafluoroethylene. polyVinyl Acetate. polyVinyl Acetate-Vinyl Alcohol. polyVinyl Acetate-Vinyl Chloride. polyVinyl Acetate-Vinyl Chloride-Vinyl Alcohol. polyVinyl Alcohol. polyVinyl Chloride. polyVinyl Chloride-Plasticizer. polyVinyl Methyl Ether. PART III: FULL ALPHABETICAL LISTING. BIBLIOGRAPHY.
In Vitro Antibodies: Strategies for Production and Application (1992)

The approaches to the production of antibodies (Ab) using the techniques of genetic engineering and expression are reviewed. Genetic engineering facilitates the production of proteins tailormade for an intended use. Bacterial and mammalian expression systems are commonly used for the production of Ab and Ab-like molecules. While genomic or cDNA cloning can be used to obtain the relevant variable regions, PCR-based cloning approaches facilitate the acquisition of additional binding specificities. Large numbers of different chimeric Abs with murine variable regions joined to constant regions from human and other species have been expressed and found to exhibit the expected binding specificities and effector functions. These molecules have been used to study the structural basis of effector functions such as complement activation and Fc receptor binding, and potentially they may be used as therapeutic agents. Carbohydrate has been shown to influence both variable and constant region function. Single-chain Abs and fusion proteins with Ab binding specificities joined to nonimmunoglobulin sequences provide a source of Ab-like molecules with novel properties, and genetically engineered Ab-like molecules provide a source of useful antigens. Combinatorial libraries produced in bacteriophage present an alternative to hybridomas for the production of Abs with desired combining specificities. Issues of the immunogenicity of the recombinant molecules are addressed.
Selective amino acid substitutions of a subdominant Epstein-Barr virus LMP2-derived epitope increase HLA/peptide complex stability and immunogenicity: implications for immunotherapy of Epstein-Barr virus-associated malignancies (1999)

The latent membrane protein 2 is an immunogenic antigen expressed in Epstein-Barr virus (EBV)-associated tumors and consequently it may represent a target for specific cytotoxic T lymphocyte (CTL)-based immunotherapies. However, the efficacy of such a therapy is limited by the poor immunogenicity of the protein that induces weak CTL responses directed to the CLGGLLTMV (CLG) epitope only in the minority of EBV-seropositive donors. We have now demonstrated that selective peptide stimulation of peripheral blood lymphocytes induced CLG-specific CTL in all donors, suggesting that this epitope can be a suitable target for specific immunotherapies. We found that the CLG peptide has a low affinity for HLA-A*0201 and does not produce stable complexes, both factors that are likely to determine the strength of CTL responses to this epitope. Therefore, we synthesized and tested CLG analogues carrying single or combined amino acid substitutions to increase HLA/peptide stability. Among the analogues tested we identified two peptides which, compared to the natural epitope, showed higher affinity for HLA-A*0201 molecules, and produced stable complexes. These peptides demonstrated a potent, specific stimulatory capacity and could be used for selective CTL-based therapies.
Bone marrow stem cells regenerate infarcted myocardium (2003)

Heart disease is the leading cause of death in the United States for both men and women. Nearly 50% of all cardiovascular deaths result from coronary artery disease. Occlusion of the left coronary artery leads to ischemia, infarction, necrosis of the affected myocardial tissue followed by scar formation and loss of function. Although myocytes in the surviving myocardium undergo hypertrophy and cell division occurs in the border area of the dead tissue, myocardial infarcts do not regenerate and eventually result in the death of the individual. Numerous attempts have been made to repair damaged myocardium in animal models and in humans. Bone marrow stem cells (BMSC) retain the ability throughout adult life to self-renew and differentiate into cells of all blood lineages. These adult BMSC have recently been shown to have the capacity to differentiate into multiple specific cell types in tissues other than bone marrow. Our research is focused on the capacity of BMSC to form new cardiac myocytes and coronary vessels following an induced myocardial infarct in adult mice. In this paper we will review the data we have previously published from studies on the regenerative capacity of BMSC in acute ischemic myocardial injury. In one experiment donor BMSC were injected directly into the healthy myocardium adjacent to the injured area of the left ventricle. In the second experiment, mice were treated with cytokines to mobilize their BMSC into the circulation on the theory that the stem cells would traffic to the myocardial infarct. In both experimental protocols, the BMSC gave rise to new cardiac myocytes and coronary blood vessels. This BMSC-derived myocardial regeneration resulted in improved cardiac function and survival.
Stable expression of rat cytochrome P-450IIB1 cDNA in Chinese hamster cells (V79) and metabolic activation of aflatoxin B1. (1988)

V79 Chinese hamster fibroblasts are widely used for mutagenicity testing but have the serious limitation that they do not express cytochromes P-450, which are needed for the activation of many promutagens to mutagenic metabolites. A full-length cDNA clone encoding the monooxygenase cytochrome P-450IIB1 under control of the simian virus 40 early promoter was constructed and cointroduced with the selection marker neomycin phosphotransferase (conferring resistance to G418) into V79 Chinese hamster cells. G418-resistant cells were selected, established as cell lines, and tested for cytochrome P-450IIB1 expression and enzymatic activity. Two cell lines (SD1 and SD3) were found that stably produce cytochrome P-450IIB1. Although purified cytochromes P-450 possess monooxygenase activity only after reconstitution with cytochrome P-450 reductase and phospholipid, the gene product of the construct exhibited this activity. This implies that the gene product is intracellularly localized in a way that allows access to the required components. If compared with V79 cells, the mutation rate for the hypoxanthine phosphoribosyltransferase (HPRT) locus in SD1 cells is markedly increased when exposed to aflatoxin B1, which is activated by this enzyme.
Comparison of vasoconstrictors for functional endoscopic sinus surgery in children (1992)

Three different vasoconstricting agents were evaluated during functional endoscopic sinus surgery (FESS) in 57 children. Oxymetazoline hydrochloride 0.05%, phenylephrine hydrochloride 0.25%, or cocaine 4% was applied to the nasal mucosa in a prospective, randomized, double-blind fashion. Heart rate and blood pressure changes were recorded 5 and 10 minutes after application of the study vasoconstrictor to each nostril. The surgeon's subjective impressions of bleeding and visualization were recorded for each side of the nose, as were total blood loss and anesthesia time. Although all three vasoconstrictors were tolerated well by the children, there was a suggestion that heart rate decreased more at 5 minutes with phenylephrine than with oxymetazoline or cocaine (P = .08) and that blood pressure increased more at 10 minutes with phenylephrine than with oxymetazoline or cocaine (P = .1). No arrhythmias were noted. Subjective scoring for bleeding showed that children receiving oxymetazoline were less likely to receive scores of "more" bleeding than usual (3/38 vs. 10/34 for phenylephrine and 10/35 for cocaine, P less than .02). Subjective scoring for visualization showed that children receiving oxymetazoline were also less likely to receive scores of "worse" visualization than usual (3/38 vs. 12/38 for phenylephrine and 9/35 for cocaine, P less than .01). There was no difference in surgical bleeding or visualization between children receiving phenylephrine and children receiving cocaine. In our institution, 0.05% oxymetazoline is the preferred vasoconstrictor for FESS in children.
Gene cassette knock-in in mammalian cells and zygotes by enhanced MMEJ (2016)

Our results provide a technical platform for high-throughput knock-in.
Biological Responses to Materials (2001)

▪ Abstract All materials intended for application in humans as biomaterials, medical devices, or prostheses undergo tissue responses when implanted into living tissue. This review first describes fundamental aspects of tissue responses to materials, which are commonly described as the tissue response continuum. These actions involve fundamental aspects of tissue responses including injury, inflammatory and wound healing responses, foreign body reactions, and fibrous encapsulation of the biomaterial, medical device, or prosthesis. The second part of this review describes the in vivo evaluation of tissue responses to biomaterials, medical devices, and prostheses to determine intended performance characteristics and safety or biocompatibility considerations. While fundamental aspects of tissue responses to materials are important from research and development perspectives, the in vivo evaluation of tissue responses to these materials is important for performance, safety, and regulatory reasons.
[Epidermal growth factor receptor mutation detection methods: a general review]. (2013)

表皮生长因子受体(epidermal growth factor receptor,EGFR)基因位于人的第7号染色体,长度约为200 kb,由28个外显子组成.EGFR基因编码的蛋白主要由细胞外的配体结合结构域、跨膜的疏水结构域以及细胞内的酪氨酸激酶结构域三个部分组成,在肿瘤的增殖、抑制凋亡、去分化、侵袭和转移、血管生成等关键特性中发挥着重要的作用[1]。
Indianapolis v. Edmond: Roadblock to Fourth Amendment Erosion of Individual Security (2002)

The text of the Fourth Amendment states:The right of the people to be secure in their persons, houses, papers, and effects, against unreasonable searches and seizures, shall not be violated, and no Warrants shall issue, but upon probable cause, supported by Oath or affirmation, and particularly describing the place to be searched, and the persons or things to be seized.,Generally, under the guidance of the Fourth Amendment, every search or seizure by a government agent must be reasonable.The Supreme Court interpreted this requirement to mean that an arrest or search must be based on probable cause and executed pursuant to a warrant.' Courts have created a number of exceptions to the warrant and probable cause requirements of the Fourth Amendment, such as investigatory detentions, seizures of items in plain view, warrantless arrests, inventory searches, administrative searches, border patrol searches, vehicle searches, and special needs searches. 3 However, in balancing these exceptions, the Court has traditionally required some level of individualized suspicion to justify government intrusion on an individual's privacy. 4 In the absence of individualized suspicion or probable cause of wrongdoing, a search or seizure is ordinarily unreasonable. 5 One area in which courts have upheld suspicionless searches is that of the roving police checkpoint. 6 In the context of such roadblocks, the Court has tradition-*
A Randomized Trial of Intensive Lipid-Lowering Therapy in Calcific Aortic Stenosis (2005)

Intensive lipid-lowering therapy does not halt the progression of calcific aortic stenosis or induce its regression. This study cannot exclude a small reduction in the rate of disease progression or a significant reduction in major clinical end points. Long-term, large-scale, randomized, controlled trials are needed to establish the role of statin therapy in patients with calcific aortic stenosis.
Gas6, the ligand of Axl tyrosine kinase receptor, has mitogenic and survival activities for serum starved NIH3T3 fibroblasts. (1996)

Reversible growth arrest has been characterised for enhanced expression of a set of genes called gas (growth arrest specific). gas6 product (Gas6) is a secreted protein that was identified as the ligand for the tyrosine kinase receptor Axl. Here we report that Gas6 is able to induce cell cycle division entry in serum starved NIH3T3 cells. This mitogenic activity of Gas6 strictly correlates with its ability to interact with NIH3T3 endogenous Axl receptor since it can be abolished by soluble Axl extracellular domain and activates both Axl intrinsic kinase activity and the downstream MAPK pathway. Moreover when ectopic Axl overexpression is performed by microinjection in serum starved NIH3T3 cells, addition of a non mitogenic level of Gas6 induces selective entry into S phase in Axl overexpressing cells. Interestingly, Axl overexpression per se is not able to induce S phase entry. Finally we present evidences indicating that Gas6 is able to protect serum starved NIH3T3 cells from cell death by apoptosis as induced by complete growth factor depletion. The reported survival activity seems to be independent of Gas6 mitogenic activity, thus implicating a double and separable activity for Gas6 during growth arrest.
Protein folding (1972)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTProtein foldingI. D. KuntzCite this: J. Am. Chem. Soc. 1972, 94, 11, 4009–4012Publication Date (Print):May 1, 1972Publication History Published online1 May 2002Published inissue 1 May 1972https://pubs.acs.org/doi/10.1021/ja00766a060https://doi.org/10.1021/ja00766a060research-articleACS PublicationsRequest reuse permissionsArticle Views454Altmetric-Citations163LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts