gebhart/patrepeval huggingface dataset:
Molecular cloning and complete sequence of prion protein cDNA from mouse brain infected with the scrapie agent. (1986)

The prion protein (PrP) is a scrapie-associated fibril protein that accumulates in the brains of hamsters and mice infected with the scrapie agent, and also in the brains of persons affected with kuru or Creutzfeldt-Jakob disease. It has been previously proposed that PrP could be either the primary transmissible agent of scrapie or a secondary component involved in the pathogenesis of scrapie. At present, the second possibility seems more likely, for the PrP-specific mRNA is present in both infected and uninfected brains. We have isolated and sequenced the complete PrP-specific cDNA from mRNA isolated from infected mouse brains. Comparison of the mouse PrP with the hamster PrP reveals a high homology in the amino acid sequence and the presence of a conserved octapeptide repeated four times, whose function is unknown at present. Structural features are discussed and compared with other proteins. Except for its homology with the hamster PrP, mouse PrP has no significant homology to any known protein sequence, including neurofilaments, neuropeptides, and amyloid proteins of Alzheimer disease. Some features of the PrP, however, are similar to structures found in aggregating proteins, such as the wheat glutenin, keratin, and collagen.
Indol-2-one Intermediates:  Mechanistic Evidence and Synthetic Utility. Total Syntheses of (±)-Flustramines A and C (2005)

A variety of 3,3-disubstituted 2-indolinones have been prepared by treatment of 3-bromo-3-alkyl-2-indolinones with dienophiles/nucleophiles in the presence of cesium carbonate. Application of this general strategy has facilitated the total syntheses of the reverse prenylated marine natural products (+/-)-flustramine A and (+/-)-flustramine C. [Structure: see text]
Characterization of an unusual cell type (CD4+ CD3-) expanded by helminth infection and related to the parasite stress response (1993)

Mice infected with the parasite Mesocestoides corti develop hypergammaglobulinemia, hepatomegaly, and splenomegaly. The immune response to M. corti infection is directed, in part, at molecules secreted by the organism. Two of these molecules have been shown to be hsp70 and hsp60 homologues. In this study it was found that incubation of splenocytes from infected animals with M. corti-secreted molecules or the isolated M. corti hsp70 results in the expansion of an unusual cell type with the morphology of large granular lymphocytes. The cell lines express Thy-1, CD4 (low), and CD45RB but lack TCR alpha beta, TCR gamma delta, CD3, CD8, and slg. The lack of a TCR suggested NK cells, but no cytolytic activity could be detected. In addition, the cell lines constitutively produce IL-6 and can be induced to express IL-2, but not IL-4, IL-5, or IFN-gamma. Given the phenotype of these cells, it is possible that they represent T lineage precursors or some type of effector cells. Notably, CD3- CD4+ cells appear to be expanded in the spleens and livers of M. corti-infected animals, suggesting an important role in infection. Moreover, the selective growth of this cell type with M. corti hsp70 suggests that the outgrowth and in vivo expansion of these cells may be related to the stress response of the parasite.
Heme Oxygenase-1 and the Ischemia-Reperfusion Injury in the Rat Heart (2003)

Carbon monoxide (CO) is a signaling gas produced intracellularly by heme oxygenase (HO) enzymes using heme as a substrate. During heme breakdown, HO-1 and HO-2 release CO, biliverdin, and Fe(2+). In this study, we investigated the effects of manipulation of the HO-1 system in an in vivo model of focal ischemia-reperfusion (FIR) in the rat heart. Male Wistar albino rats, under general anesthesia and artificial ventilation, underwent thoracotomy, the pericardium was opened, and a silk suture was placed around the left descending coronary artery; ischemia was induced by tightening the suture and was monitored for 30 min. Subsequently, the ligature was released to allow reperfusion lasting for 60 min. The first group of rats was sham operated and injected intraperitoneally (i.p.) with saline. The second group underwent FIR. The third group was treated ip 18 hr before FIR with hemin (4 mg/kg). The fourth group was pretreated ip 24 hr before FIR and 6 hr before hemin with zinc protoporphyrin IX (ZnPP-IX, 50 microg/kg). Specimens of the left ventricle were taken for determination of HO expression and activity, infarct size, malonyldialdehyde (MDA) production, and tissue calcium content. FIR led to a significant increase in the generation of MDA and notably raised tissue calcium levels. Induction of HO-1 by hemin significantly decreased infarct size, incidence of reperfusion arrhythmias, MDA generation, and calcium overload induced by FIR. These effects were prevented by the HO-1 inhibitor ZnPP-IX. The present experiments show that the concerted actions of CO, iron, and biliverdin/bilirubin modulate the FIR-induced myocardial injury.
Characterization of the interplay between DNA repair and CRISPR/Cas9-induced DNA lesions at an endogenous locus (2017)

The CRISPR-Cas9 system provides a versatile toolkit for genome engineering that can introduce various DNA lesions at specific genomic locations. However, a better understanding of the nature of these lesions and the repair pathways engaged is critical to realizing the full potential of this technology. Here we characterize the different lesions arising from each Cas9 variant and the resulting repair pathway engagement. We demonstrate that the presence and polarity of the overhang structure is a critical determinant of double-strand break repair pathway choice. Similarly, single nicks deriving from different Cas9 variants differentially activate repair: D10A but not N863A-induced nicks are repaired by homologous recombination. Finally, we demonstrate that homologous recombination is required for repairing lesions using double-stranded, but not single-stranded DNA as a template. This detailed characterization of repair pathway choice in response to CRISPR-Cas9 enables a more deterministic approach for designing research and therapeutic genome engineering strategies.
QoS control for random access wireless sensor networks (2004)

Herein, we present two new techniques that maintain QoS in a wireless sensor network even as sensors and base-stations die off. The first technique extends an earlier Gur game approach where QoS feedback is broadcasted to all sensors. The second technique provides QoS feedback to individual sensors as part of packet acknowledgements for random access protocols. The latter technique has the advantage of allowing sensors to operate in extremely low energy states when not transmitting data. While random access protocols exhibit low spectral efficiency, we contend that many cost-driven sensing applications are in practice not bandwidth limited. Through simulation, both strategies are shown to extend network life beyond the baseline Gur method. This work is especially applicable to remote, harsh environments where sensors die off at high rates and replenishment is not possible.
Herceptin<sup>®</sup> Alone or in Combination with Chemotherapy in the Treatment of HER2-Positive Metastatic Breast Cancer: Pivotal Trials (2001)

Large pivotal phase II and III clinical trials investigated the therapeutic efficacy and safety of the humanized anti-HER2 monoclonal antibody, Herceptin, alone and in combination with standard chemotherapy, respectively, in HER2-positive metastatic breast cancer. Eligible patients were HER2 2+ and 3+ overexpressors, as determined by immunohistochemistry (IHC). Herceptin was well tolerated in both trials. Single-agent second/third-line Herceptin produced durable tumor responses. First-line Herceptin in combination with chemotherapy, in particular paclitaxel, significantly improved time to disease progression, duration of response and time to treatment failure. Combination therapy also provided a significant 25% improvement in overall survival. These clinical benefits have led to the approval of Herceptin for clinical use in the USA and elsewhere. Greater efficacy was noted in IHC 3+ patients compared with the overall population in both trials. Retrospective fluorescent in situ hybridization (FISH) testing of patient-tumor HER2 status revealed similar clinical outcomes in IHC 3+ and FISH-positive patients, consistent with the reported high concordance between IHC and FISH. Responses in the single-agent Herceptin trial were seen exclusively in FISH-positive patients. Approximately a quarter of HER2 2+ patients test FISH positive and may therefore benefit from therapy. Numerous studies are underway or planned to evaluate other Herceptin combinations and regimens in the metastatic and adjuvant settings.
Conversion of CO2 into Formate by Homogeneously Catalyzed Hydrogenation in Water: Tuning Catalytic Activity and Water Solubility through the Acid–Base Equilibrium of the Ligand (2007)

Abstract This Microreview focuses on the recently developed hydrogenation of CO 2 and hydrogen carbonate catalyzed by half‐sandwich complexes with 4,4′‐dihydroxy‐2,2′‐bipyridine (dhbp) and 4,7‐dihydroxy‐1,10‐phenanthroline (dhpt). An unprecedented high catalytic activity and reusability of the catalyst without waste generation were achieved by automatic tuning of the catalytic activity and water solubility of the catalyst through the acid–base equilibrium of the catalyst ligand. The oxyanion generated from the phenol hydroxy group played significant roles in the electronic effect and polarity. The catalyst design concept and the excellent properties of the ligands are expected to have significantly broader implications for the design of new homogeneous catalysts.(© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2007)
Chemistry of thienopyridines. III. Syntheses of the thieno[2,3-b]- and thieno[3,2-b]pyridine systems. Direct substitution into the former system (1969)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChemistry of thienopyridines. III. Syntheses of the thieno[2,3-b]- and thieno[3,2-b]pyridine systems. Direct substitution into the former systemLeRoy H. Klemm, Charles E. Klopfenstein, Reinhard Zell, David R. McCoy, and R. A. KlemmCite this: J. Org. Chem. 1969, 34, 2, 347–354Publication Date (Print):February 1, 1969Publication History Published online1 May 2002Published inissue 1 February 1969https://pubs.acs.org/doi/10.1021/jo01254a020https://doi.org/10.1021/jo01254a020research-articleACS PublicationsRequest reuse permissionsArticle Views452Altmetric-Citations74LEARN 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
PSKA: Usable and Secure Key Agreement Scheme for Body Area Networks (2009)

A body area network (BAN) is a wireless network of health monitoring sensors designed to deliver personalized healthcare. Securing intersensor communications within BANs is essential for preserving not only the privacy of health data, but also for ensuring safety of healthcare delivery. This paper presents physiological-signal-based key agreement (PSKA), a scheme for enabling secure intersensor communication within a BAN in a usable (plug-n-play, transparent) manner. PSKA allows neighboring nodes in a BAN to agree to a symmetric (shared) cryptographic key, in an authenticated manner, using physiological signals obtained from the subject. No initialization or predeployment is required; simply deploying sensors in a BAN is enough to make them communicate securely. Our analysis, prototyping, and comparison with the frequently used Diffie-Hellman key agreement protocol shows that PSKA is a viable intersensor key agreement protocol for BANs.
Natural Genetic Transformation: a Novel Tool for Efficient Genetic Engineering of the Dairy Bacterium Streptococcus thermophilus (2006)

Streptococcus thermophilus is widely used for the manufacture of yoghurt and Swiss or Italian-type cheeses. These products have a market value of approximately 40 billion dollars per year, making S. thermophilus a species that has major economic importance. Even though the fermentation properties of this bacterium have been gradually improved by classical methods, there is great potential for further improvement through genetic engineering. Due to the recent publication of three complete genome sequences, it is now possible to use a rational approach for designing S. thermophilus starter strains with improved properties. Progress in this field, however, is hampered by a lack of genetic tools. Therefore, we developed a system, based on natural transformation, which makes genetic manipulations in S. thermophilus easy, rapid, and highly efficient. The efficiency of this novel tool should make it possible to construct food-grade mutants of S. thermophilus, opening up exciting new possibilities that should benefit consumers as well as the dairy industry.
Macworld Networking Bible (1994)

An updated edition of this networking guide. The book is designed for managers of small to large Mac networks.
Leukaemia inhibitory factor retards the progression of atherosclerosis (2003)

LIF prevents progression of pre-formed atherosclerotic plaques, affecting lesion size and vascular reactivity. LIF treatment has differential effects within the artery wall, depending on the presence or absence of de-endothelialisation injury.
Lack of Interleukin-1β Decreases the Severity of Atherosclerosis in ApoE-Deficient Mice (2003)

The lack of IL-1beta decreases the severity of atherosclerosis in apoE deficient mice, possibly through increased expressions of VCAM-1 and monocyte chemotactic protein-1 in the aorta.
Molecular Cloning of cDNA Encoding the p70 (Ku) Lupus Autoantigen (1989)

The Ku (p70/p80) autoantigen consists of two phosphoproteins of molecular mass approximately 70,000 and 80,000 forming a macromolecular complex that binds DNA. Autoantibodies from a patient with systemic lupus erythematosus were used to isolate cDNA clones encoding the human approximately 70-kDa Ku antigen (p70) from a lambda gt11 expression library. The deduced amino acid sequence of p70 consisted of 609 amino acid residues and was confirmed by partial amino acid sequencing. The protein contains two acidic domains of 61 residues (31% Glu + Asp) and 19 residues (53% Glu + Asp) that are similar in size and charge to those found in a number of proteins involved in transcriptional activation. The 61-residue acidic region is rich in serine, raising the possibility that its charge might be modulated by phosphorylation. The predicted amino acid sequence also contains two regions with periodic repeats of either leucine alone, or leucine alternating with serine every seventh position. The latter repeat displays sequence and secondary structural similarities with the "leucine zipper" regions of the c-myc and v-myc oncogene products. The p70 antigen does not appear to have extensive sequence homology with the 80-kDa Ku autoantigen based on analysis of RNA blots and immunological criteria. A major antigenic determinant or determinants recognized by human autoantibodies is located near a leucine repeat on the carboxyl-terminal 190 amino acid residues of p70.
Subcutaneous lidocaine for treatment of neuropathic cancer pain (1991)

Three patients with terminal malignancy reporting ineffective analgesia using systemic and subsequently spinal opiates were treated with subcutaneous infusion of 10% lidocaine hydrochloride. During the infusion, reasonably stable blood concentrations were achieved and maintained using a subcutaneous infusion at varying dose rates over days to months with improvement of the pain complaints which continued to be refractory to conventional analgesics. Blood lidocaine levels obtained at regular intervals revealed effective concentrations between 2 and 5 micrograms/ml for each patient.
Effects of testosterone supplementation in the aging male. (1992)

Serum androgen levels decline with aging in normal males, such that a significant number of men over 60 yr of age will have a mean serum total testosterone (T) level near the low end of the normal adult range. It is not known whether lower T levels in older men have an effect on androgen-responsive organ systems, such as muscle, bone, bone marrow, and prostate, nor are there data to evaluate the relative benefits and risks of T supplementation in older men. We assessed the physiological and biochemical effects of T therapy in 13 healthy men, 57-76 yr old, who had low or borderline low serum T levels (< or = 13.9 nmol/L). Intramuscular testosterone enanthate (TE; 100 mg weekly) and placebo injections were given for 3 months each. Before treatment and at the end of both 3-month treatment regimens, lean body mass, body fat, biochemical parameters of bone turnover, hematological parameters, lipoprotein profiles, and prostate parameters [such as prostate-specific antigen (PSA)] were evaluated. Serum T levels rose in all subjects with TE treatment, such that the lowest level of T during a week's period was 19.7 +/- 0.7 nmol/L (mean +/- SE). After 3 months of TE treatment, lean body mass was significantly increased, and urinary hydroxyproline excretion was significantly depressed. With TE treatment, there was a significant increase in hematocrit, a decline in total cholesterol and low density lipoprotein cholesterol, and a sustained increase in serum PSA levels. Placebo treatment led to no significant changes in any of these parameters. We conclude that short term (3 months) TE supplementation to healthy older men who have serum T levels near or below the lower limit of normal for young adult men results in an increase in lean body mass and possibly a decline in bone resorption, as assessed by urinary hydroxyproline excretion, with some effect on serum lipoproteins, hematological parameters, and PSA. The sustained stimulation of PSA and the increase in hematocrit that occur with physiological TE supplementation suggest that older men should be screened carefully and followed periodically throughout T therapy.
Cytokines, growth factors and the loss of negative growth controls in the progression of human cutaneous malignant melanoma (1994)

The development of clinically frank malignant melanomas in humans is thought to evolve over decades in a stepwise process of progression. By analogy with certain other adult cancers, eg, colorectal carcinomas, alterations in expression or function of a number of different suppressor genes might be expected to be involved in this process. This could lead to loss of expression of a number of different negative growth controls. Evidence is reviewed implicating the presence of putative suppressor genes for the melanocytic lineage located on chromosomes 9p21, 6q, and 1p. In addition, there is evidence suggesting a contribution for the p53 and NF1 tumor-suppressor genes, and the nm23 metastasis-suppressor gene, in melanoma development or progression. Additional possible suppressor genes include those encoding manganese superoxide dismutase, and possibly c-kit. An accumulation of such alterations may be responsible for the progressive loss of responsiveness to several independent growth inhibitors for melanocytes or early stage melanomas, including interleukin-6, transforming growth factor-beta, and oncostatin M. They may also be responsible for some aspects of the production of direct acting autocrine growth factors or production of angiogenesis stimulating factors, or both, by melanoma cells. The acquisition of resistance to several growth inhibitors and the multiplicity of putative suppressor gene alterations (combined with the production of multiple autocrine and paracrine growth factors) may be necessary for the evolution of nondividing single melanocytes resident in the epidermis into highly proliferative and metastatic melanomas capable of growing multicellularly in ectopic organ sites.
Isolation and Maintenance of Primate Embryonic Stem Cells (2003)

Primate embryonic stem (ES) cells are derived from preimplantation embryos and are capable of prolonged undifferentiated proliferation in culture. Under particular conditions, these cells differentiate into derivatives of endoderm, mesoderm, ectoderm, and trophoblast (1,2). In mammals, many developmental events are studied using mouse embryos or ES cells, but some aspects of development differ significantly between humans and mice, such as the timing of embryonic genome expression (3), fetal membrane and placental structure and development (4–6), and the formation of an embryonic disc instead of an egg cylinder (7,8). These and other features of human development are better studied using a primate model.
Gene Expression in Fibroblasts and Fibrosis (2002)

Structural remodeling of the ventricular wall is a key determinant of clinical outcome in heart disease. Such remodeling involves the production and destruction of extracellular matrix proteins, cell proliferation and migration, and apoptotic and necrotic cell death. Cardiac fibroblasts are crucially involved in these processes, producing growth factors and cytokines that act as autocrine and paracrine factors, as well as extracellular matrix proteins and proteinases. Recent studies have shown that the interactions between cardiac fibroblasts and cardiomyocytes are essential for the progression of cardiac remodeling. This review addresses the functional role played by cardiac fibroblasts and the molecular mechanisms that govern their activity during cardiac hypertrophy and remodeling. A particular focus is the recent progress toward our understanding of the transcriptional regulatory mechanisms involved.
Crystal growth and characterization of CsSr1–xEux I3 high light yield scintillators (2010)

Abstract In this work, we report on single crystal growth and characterizations of a new scintillation material: CsSr 1– x Eu x I 3 (0 ≤ x ≤ 1). Single crystals of CsSr 0.99 Eu 0.01 I 3 , CsSr 0.92 Eu 0.08 I 3 and CsEuI 3 were grown via the Vertical Gradient Freeze method. The crystals exhibit good crystal quality, high light yield, and excellent energy resolution. Initial results show that the scintillation light yield of our CsSr 0.92 Eu 0.08 I 3 crystal is ∼65,000 ph/MeV with 5.9% energy resolution at 662 keV. (© 2011 WILEY‐VCH Verlag GmbH &amp; Co. KGaA, Weinheim)
Antiplatelet and antithrombotic efficacy of DMP 728, a novel platelet GPIIb/IIIa receptor antagonist. (1994)

Acute intravenous DMP 728 administration (0.001 to 1.0 mg/kg) has dose-dependent antiplatelet and antithrombotic effects in different arterial thrombosis models. These data suggest that DMP 728, a low-molecular-weight GPIIb/IIIa receptor antagonist, may have therapeutic potential as an effective antithrombotic agent in coronary and peripheral artery thromboembolic disorders.
The decline in paediatric malaria admissions on the coast of Kenya (2007)

This study provides evidence of a changing disease burden on the Kenyan coast and that the most parsimonious explanation is an expansion in the coverage of interventions such as the use of insecticide-treated nets and the availability of anti-malarial medicines. While specific attribution to intervention coverage cannot be computed what is clear is that this area of Kenya is experiencing a malaria epidemiological transition.