gebhart/patrepeval huggingface dataset:
AMG 102, an HGF/SF antagonist, in combination with anti-angiogenesis targeted therapies in adult patients with advanced solid tumors (2008)

3570 Background: AMG 102 is a novel, fully human monoclonal antibody that selectively targets hepatocyte growth factor/scatter factor (HGF/SF), the only ligand for the c-Met receptor, potentially inhibiting tumor cell proliferation, survival, and invasion. Bevacizumab and the small-molecule tyrosine kinase inhibitor motesanib diphosphate deter tumor angiogenesis by disrupting the VEGF pathway; in combination with AMG 102, they may have synergistic antitumor effects by targeting multiple signaling pathways. Methods: In an open-label Phase 1b study, 3 cohorts of 3–6 patients with advanced solid tumors received AMG 102 (3, 10, or 20 mg/kg) + bevacizumab 10 mg/kg every 2 weeks (Q2W); 2 patients received AMG 102 3 mg/kg IV Q2W + daily oral motesanib diphosphate 75 mg. Safety, tolerability, pharmacokinetics (PK), and tumor response (RECIST) were assessed. Results: Patient enrollment was complete in April 2007 with 14 patients (7 men, mean age 67). Prior treatment included radiotherapy (50%) and ≥ 3 lines of chemotherapy (71%). No dose-limiting toxicities were seen at any dosing levels. All patients reported treatment-related adverse events (AEs), most commonly nausea and fatigue. Serious treatment-related AEs included pulmonary embolism (PE) (n = 1) and hypotension (n = 1). Another case of PE was deemed not treatment-related. The PK profile of AMG 102 in combination with anti-angiogenic agents was similar to monotherapy. A decrease in the sum of tumor diameters and a best response of stable disease were seen in 8 of 10 evaluable patients. Stable disease persisted for > 12 months in a patient with carcinoid tumor (AMG 102 3 mg/kg + motesanib diphosphate) and > 9 months in a patient with endometrial cancer (AMG 102 10 mg/kg +bevacizumab). Levels of plasma HGF increased in all patients; the magnitude of increase appeared to be dose-dependent. Conclusions: AMG 102 in combination with anti-angiogenesis agents appeared to be well tolerated with an acceptable safety profile, and may inhibit tumor progression for some patients. Phase 2 evaluations of AMG 102 at 10–20 mg/kg are underway. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen Inc. Amgen Inc. Amgen Inc. Amgen Inc.
Total synthesis and development of bioactive natural products (2008)

The first total synthesis and development of a variety of bioactive natural products have been accomplished by using carbohydrates as a chiral source. In addition, practically useful intermediates have been created, analogs of natural products have been prepared, their structure-activity relationships studied, and the large-scale preparations of medicinally useful compounds established. The key target molecules have been the "Big Four" antibiotics (macrolides, aminoglycosides, beta-lactams and tetracyclines), pyranonaphthoquinone antibiotics, glycosidase inhibitors, and a side-chain of cephem antibiotics.
The Primary Immunodeficiencies (1995)

The primary immunodeficiency disorders reflect abnormalities in the development and maturation of cells of the immune system. These defects result in an increased susceptibility to infection; recurrent pyogenic infections occur with defects of humoral immunity, and opportunistic infections with defects of cell-mediated immunity. These two broad categories of illness correspond roughly to defects in the two principal types of immunocompetent cells, B lymphocytes and T lymphocytes. Defective development of B cells results in abnormalities in humoral immunity, whereas defects in the development of T cells cause problems with cellular immunity.When pathogens are taken up by macrophages or dendritic cells, . . .
EB66 cell line, a duck embryonic stem cell-derived substrate for the industrial production of therapeutic monoclonal antibodies with enhanced ADCC activity (2010)

Monoclonal antibodies (mAbs) represent the fastest growing class of therapeutic proteins. The increasing demand for mAb manufacturing and the associated high production costs call for the pharmaceutical industry to improve its current production processes or develop more efficient alternative production platforms. The experimental control of IgG fucosylation to enhance antibody dependent cell cytotoxicity (ADCC) activity constitutes one of the promising strategies to improve the efficacy of monoclonal antibodies and to potentially reduce the therapeutic cost. We report here that the EB66 cell line derived from duck embryonic stem cells can be efficiently genetically engineered to produce mAbs at yields beyond a 1 g/L, as suspension cells grown in serum-free culture media. EB66 cells display additional attractive grown characteristics such as a very short population doubling time of 12 to 14 hours, a capacity to reach very high cell density (> 30 million cells/mL) and a unique metabolic profile resulting in low ammonium and lactate accumulation and low glutamine consumption, even at high cell densities. Furthermore, mAbs produced on EB66 cells display a naturally reduced fucose content resulting in strongly enhanced ADCC activity. The EB66 cells have therefore the potential to evolve as a novel cellular platform for the production of high potency therapeutic antibodies.
Emerging P2Y12 Receptor Antagonists: Role in Coronary Artery Disease (2010)

The use of oral antiplatelet therapy in reducing vascular events has been extensively studied. Currently available oral antiplatelet agents include aspirin and the thienopyridine P2Y12 receptor antagonists. These classes are combined frequently in the setting of acute coronary syndrome and percutaneous coronary intervention (PCI). Resistance to either or both of these agents is a major concern, as antiplatelet resistance has been linked to an increase in thrombotic events and worse clinical outcomes. As a result, there is a need for newer, more effective antiplatelet agents to address the limitations of currently available therapy. Prasugrel, a third generation thienopyridine, has been approved by both the FDA and European Commission. Two additional P2Y12 agents, ticagrelor and cangrelor are in advanced stages of development. The possible advantages of prasugrel over clopidogrel include a faster onset of action, reduced inter-patient variability and more potent platelet inhibition. Ticagrelor is an oral reversible P2Y12 antagonist with greater platelet inhibition compared with clopidogrel. Cangrelor is being developed as an intravenous P2Y12 antagonist with a very fast onset and offset, which may offer advantages particularly in the setting of coronary intervention. These emerging antiplatelet agents may offer advantages such as faster onset of action, greater potency and reversibility of platelet inhibition. This article summarizes the available clinical data on the upcoming P2Y12 antiplatelet agents in the treatment of coronary artery disease.
Genetic distance in the whole-genome perspective on Listeria monocytogenes strains F2-382 and NIHS-28 that show similar subtyping results (2014)

We show the relationship between the results of genome subtyping and whole-genome sequencing. It appears that the relationships among strains indicated by genome subtyping methods are in accord with the relationships indicated by whole-genome analysis. However, our results also indicate that the genetic distance between the closely related strains is greater than that between clonal strains. Our results demonstrate that subtyping methods using a part of the genome are reliable in assessing the genetic distance of the strains. Furthermore, the genetic differences in the same subtype strains may provide useful information to distinguish the bacterial strains.
Mapping of β‐adrenoceptor coupling domains to Gs‐protein by site‐specific synthetic peptides (1989)

Peptides corresponding to the known sequence of turkey erythrocyte beta 1-adrenergic receptor were synthesized and the effects on receptor-mediated cyclase activation were measured. Peptides corresponding to the first and second intracellular loops (T61-71 and T138-159) inhibited at micromolar concentrations the hormone-dependent cyclase activation in turkey erythrocyte membranes. In contrast, the peptide corresponding to the C-terminal part of the third intracellular loop (T284-295) increased the cyclase activity in a hormone-independent manner. Peptides T338-353 and T2-10 and a number of synthetic peptides unrelated to the beta-adrenoceptor had no effect.
Diffusion in Silicon and Germanium (1990)

Revue et realisation des etudes faites sur la diffusion dans Si et Ge. Description des mecanismes et les mathematiques de diffusion
Conceptual modelling of genomic information (2000)

This paper presents a collection of conceptual (i.e. implementation-independent) data models for genomic data. These conceptual models are amenable to (more or less direct) implementation on different computing platforms.
Immune parameters relevant to neural xenograft survival in the primate brain (2003)

Cicchetti F, Fodor W, Deacon TW, van Horne C, Rollins S, Burton W, Costantini LC, Isacson O. Immune parameters relevant to neural xenograft survival in the primate brain. Xenotransplantation 2003: 10: 41–49. © Blackwell Munksgaard, 2003 The lack of supply and access to human tissue has prompted the development of xenotransplantation as a potential clinical modality for neural cell transplantation. The goal of the present study was to achieve a better understanding of the immune factors involved in neural xenograft rejection in primates. Initially, we quantified complement mediated cell lysis of porcine fetal neurons by primate serum and demonstrated that anti‐C5 antibody treatment inhibited cell death. We then developed an immunosuppression protocol that included in vivo anti‐C5 monoclonal antibody treatment, triple drug therapy (cyclosporine, methylprednisolone, azathioprine) and donor tissue derived from CD59 or H‐transferase transgenic pigs and applied it to pig‐to‐primate neural cell transplant models. Pre‐formed αGal, induced αGal and primate anti‐mouse antibody (PAMA) titers were monitored to assess the immune response. Four primates were transplanted. The three CD59 neural cell recipients showed an induced anti‐αGal response, whereas the H‐transferase neural cell recipient exhibited consistently low anti‐αGal titers. Two of these recipients contained surviving grafts as detected by immunohistochemistry using selected neural markers. Graft survival correlated with high dose cyclosporine treatment, complete complement blockade and the absence of an induced PAMA response to the murine anti‐C5 monoclonal antibodies.
An update to 21-hydroxylase deficient congenital adrenal hyperplasia (2009)

Congenital adrenal hyperplasia (CAH) due to deficiency of the enzyme 21-hydroxylase (21-OH) is distinguished in classical (C-CAH) and non-classical form (NC-CAH), and it is also one of the most common autosomal recessive inherited disorders in humans. The prevalence of C-CAH is between 1:10,000 and 1:15,000 among the live neonates of North America and Europe while the NC-CAH occurs in approximately 0.2% of the general white population. The highest incidence of CAH (1:282 and 1:2141, respectively) has been evaluated in Yupik Eskimos in Alaska and in the populations of the island La Reunion (France), while the lower was detected in New Zealand newborns (0.3%). Nowadays, it has been established that except for the adrenal cortex in CAH cases, the adrenal medulla was also affected. In human 21-OH deficient adrenal gland it has been discovered that not only the chromaffin cells formed extensive neurites, expanding between adrenocortical cells, but also that the adrenal androgens promote outgrowth, whereas glucocorticoids preserve neuroendocrine cells. It seems that normal cortisol secretion by the adrenal cortex is necessary for adrenomedullary organogenesis. The synthesis of 21-OH is controlled by the active CYP21A2 gene located at a distance of 30 kb from a highly homologous pseudogene designated CYP21A1P.
Semipolar (202¯1) GaN and InGaN quantum wells on sapphire substrates (2014)

Here, we demonstrate a process to produce planar semipolar (202¯1) GaN templates on sapphire substrates. We obtain (202¯1) oriented GaN by inclined c-plane sidewall growth from etched sapphire, resulting in single crystal material with on-axis x-ray diffraction linewidth below 200 arc sec. The surface, composed of (101¯1) and (101¯0) facets, is planarized by the chemical-mechanical polishing of full 2 in. wafers, with a final surface root mean square roughness of &amp;lt;0.5 nm. We then analyze facet formation and roughening mechanisms on the (202¯1) surface and establish a growth condition in N2 carrier gas to maintain a planar surface for further device layer growth. Finally, the capability of these semipolar (202¯1) GaN templates to produce high quality device structures is verified by the growth and characterization of InGaN/GaN multiple quantum well structures. It is expected that the methods shown here can enable the benefits of using semipolar orientations in a scalable and practical process and can be readily extended to achieve devices on surfaces using any orientation of semipolar GaN on sapphire.
Delineation of Borrelia burgdorferi Sensu Stricto, Borrelia garinii sp. nov., and Group VS461 Associated with Lyme Borreliosis (1992)

We studied 48 Borrelia isolates that were associated with Lyme borreliosis or were isolated from ticks and identified three DNA relatedness groups by using the S1 nuclease method. The three DNA groups (genospecies) were associated with specific rRNA gene restriction patterns, protein electrophoresis patterns, and patterns of reactivity with murine monoclonal antibodies. Genospecies I corresponded to Borrelia burgdorferi sensu stricto since it contained the type strain of this species (strain ATCC 35210); this genospecies included 28 isolates from Europe and the United States. Genospecies II was named Borrelia garinii sp. nov. and included 13 isolates from Europe and Japan. Genospecies III (group VS461) included seven isolates from Europe and Japan.
MHC Class II Presentation of gp100 Epitopes in Melanoma Cells Requires the Function of Conventional Endosomes and Is Influenced by Melanosomes (2008)

Many human solid tumors express MHC class II (MHC-II) molecules, and proteins normally localized to melanosomes give rise to MHC-II-restricted epitopes in melanoma. However, the pathways by which this response occurs have not been defined. We analyzed the processing of one such epitope, gp100(44-59), derived from gp100/Pmel17. In melanomas that have down-regulated components of the melanosomal pathway, but constitutively express HLA-DR*0401, the majority of gp100 is sorted to LAMP-1(high)/MHC-II(+) late endosomes. Using mutant gp100 molecules with altered intracellular trafficking, we demonstrate that endosomal localization is necessary for gp100(44-59) presentation. By depletion of the AP-2 adaptor protein using small interfering RNA, we demonstrate that gp100 protein internalized from the plasma membrane to such endosomes is a major source for gp100(44-59) epitope production. The gp100 trapped in early endosomes gives rise to epitopes that are indistinguishable from those produced in late endosomes but their production is less sensitive to inhibition of lysosomal proteases. In melanomas containing melanosomes, gp100 is underrepresented in late endosomes, and accumulates in stage II melanosomes devoid of MHC-II molecules. The gp100(44-59) presentation is dramatically reduced, and processing occurs entirely in early endosomes or stage I melanosomes. This occurrence suggests that melanosomes are inefficient Ag-processing compartments. Thus, melanoma de-differentiation may be accompanied by increased presentation of MHC-II restricted epitopes from gp100 and other melanosome-localized proteins, leading to enhanced immune recognition.
Hepatitis B virus proteins eliciting protective immunity. (1987)

The immune response to current hepatitis B vaccines appears to be qualitatively different from the response elicited during recovery from natural infection. Such disparate responses can probably be explained by the absence or under-representation of preS- and the nucleoprotein core-specific determinants in the vaccines. The incorporation of these determinants into future vaccines may improve their efficacy.
Bioartificial materials based on collagen: 1. Collagen cross-linking with gaseous glutaraldehyde (1996)

The effect of exposure time of thin films of soluble collagen to glutaraldehyde (GTA) vapour was studied at 37 degrees C, and was evaluated by examining the thermal and biological stability and the swelling ratio. It was found that the collagen films treated with GTA vapour for 18 h showed the highest denaturation temperature, the lowest swelling ratio, and an enhanced proteolytic stability. This study shows that soluble collagen can be effectively cross-linked with GTA vapour and that the degree of cross-linking can be controlled by varying the exposure time.
Immunohistochemical Localization of the Nucleosome-Binding Protein HMGN3 in Mouse Brain (2002)

HMGN3 (Trip7) is a member of the high-mobility group N (HMGN) nucleosome-binding protein family, which binds specifically to nucleosomes, reduces the compactness of the chromatin fiber, and enhances transcription from chromatin templates. By Western blotting and Northern blotting analysis, we showed that HMGN3 is expressed in a tissue-specific manner, with the strongest expression in mouse brain. Here we analyzed the expression of HMGN3 in various regions of the mouse brain by histological techniques. Enhanced expression of HMGN3 was observed in the lateral olfactory tract, anterior commissure, corpus callosum, internal capsule, fornix, stria medullans, optic tract, and axon bundles. The expression patterns of HMGN3 in the mouse brain was significantly different from that of the related protein HMGN2 and was very similar to that of the glial fibrillary acidic protein (GFAP). We suggest that HMGN3 might play a role in astrocyte function.
Extraction of acetonitrile from aqueous mixtures. 2. Ternary liquid equilibriums (1979)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTExtraction of acetonitrile from aqueous mixtures. 2. Ternary liquid equilibriumsD. Subba Rao, K. Venkateswara Rao, A. Ravi Prasad, and C. ChiranjiviCite this: J. Chem. Eng. Data 1979, 24, 3, 241–244Publication Date (Print):July 1, 1979Publication History Published online1 May 2002Published inissue 1 July 1979https://pubs.acs.org/doi/10.1021/je60082a014https://doi.org/10.1021/je60082a014research-articleACS PublicationsRequest reuse permissionsArticle Views610Altmetric-Citations27LEARN 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
Atrial natriuretic peptide (ANP) is a high‐affinity substrate for rat insulin‐degrading enzyme (1991)

A cytosolic protein specifically binding to and degrading atrial natriuretic peptide (ANP) was purified from rat brain homogenate. Based on partial amino acid sequences and enzymatic properties, this protein with an apparent molecular mass of 112 kDa has been identified as the rat insulin-degrading enzyme (IDE). In addition to the known substrates, insulin and transforming-growth-factor alpha IDE binds also with high affinity (apparent Kd 60 nM) to ANP. Competition studies with structural variants of ANP demonstrate that both the C terminus and the disulfide loop of the molecule are essential for high-affinity binding. The data suggest that IDE might be involved in the cellular processing and/or metabolic clearance of ANP.
Molecular Mechanisms and Treatment Options for Muscle Wasting Diseases (2011)

Loss of muscle mass can be the consequence of pathological changes, as observed in muscular dystrophies; or it can be secondary to cachexia-inducing diseases that cause muscle atrophy, such as cancer, heart disease, or chronic obstructive pulmonary disease; or it can be a consequence of aging or simple disuse. Although muscular dystrophies are rare, muscle loss affects millions of people worldwide. We discuss the molecular mechanisms involved in muscular dystrophy and in muscle atrophy and present current strategies aimed at ameliorating these diseases. Finally, we discuss whether lessons learned from studying muscular dystrophies will also be helpful for halting muscle loss secondary to nondystrophic diseases and whether strategies to halt muscle atrophy have potential for the treatment of muscular dystrophies.
Mismatches of Minor Histocompatibility Antigens between HLA-Identical Donors and Recipients and the Development of Graft-Versus-Host Disease after Bone Marrow Transplantation (1996)

A mismatch of minor histocompatibility antigen HA-1 can cause GVHD in adult recipients of allogeneic bone marrow from HLA-identical donors. Prospective HA-1 typing may improve donor selection and identify recipients who are at high risk for GVHD.
Multiple Endocrine Neoplasia Type 2: 2007 Update (2007)

MEN-2 provides a unique model for early prevention and cure of cancer and for stratified roles of mutation-based diagnosis of carriers.
Radiation filters and emitters for the NIR based on periodically structured metal surfaces (2000)

Abstract The spectrally selective optical properties of wavelength selective radiation emitters and filters based on periodically microstructured metal surfaces were investigated. Metal surfaces were structured by the use of a holographic mask and subsequent etching processes. Due to the microstructure, thermally excited surface plasmons couple to electromagnetic radiation. Therefore a structured tungsten surface can act as a selective radiation emitter. The calculation of the absorptance by a rigorous diffraction theory allows the prediction of the emissivity of such structures. The angle dependent emissivity of tungsten gratings with periods of 1.4 μm and 2.0 μm was measured. A peak emissivity of 70% at a wavelength of 1.6 μm was achieved. Band pass filters for the near infrared spectral range based on perforated metal films were investigated theoretically and experimentally. Filters with a grating period of 2.0 μm were produced. A peak transmittance of 80% at a wavelength 2.9 μm was achieved. The optical properties of the diffractive elements described partly show a strong angle dependence
Vignette (2012)

Vignette is an interactive system that facilitates texture creation in pen-and-ink illustrations. Unlike existing systems, Vignette preserves illustrators' workflow and style: users draw a fraction of a texture and use gestures to automatically fill regions with the texture. We currently support both 1D and 2D synthesis with stitching. Our system also has interactive refinement and editing capabilities to provide a higher level texture control, which helps artists achieve their desired vision. A user study with professional artists shows that Vignette makes the process of illustration more enjoyable and that first time users can create rich textures from scratch within minutes.