gebhart/patrepeval huggingface dataset:
Modeling high-grade serous ovarian carcinogenesis from the fallopian tube (2011)

High-grade serous ovarian carcinoma (HGSOC) is a lethal disease for which improved screening and treatment strategies are urgently needed. Progress in these areas is impeded by our poor understanding of HGSOC pathogenesis. Most ovarian cancer research is based on the hypothesis that HGSOC arises from ovarian surface epithelial cells. However, recent studies suggest that &gt;50% of high-grade serous carcinomas involving the ovary likely arise from fallopian tube epithelium. Therefore, limiting HGSOC research to modeling based on ovarian surface epithelium alone is inadequate. To address the need for a fallopian tube–based model of HGSOC, we have developed a system for studying human fallopian tube secretory epithelial cell (FTSEC) transformation. Our model is based on ( i ) immortalization of FTSECs isolated from primary samples of normal, nondiseased human fallopian tubes, ( ii ) transformation of FTSECs with defined genetic elements, and ( iii ) xenograft-based tumorigenic assays. We use our model to show that FTSECs immortalized with human telomerase reverse transcriptase (hTERT) plus SV40 large T and small T antigens are transformed by either oncogenic Ras (H-Ras V12 ) or c-Myc expression, leading to increased proliferation, clonogenicity, and anchorage-independent growth. Additionally, we demonstrate that FTSECs remain susceptible to c-Myc–mediated transformation in the absence of viral oncoproteins, by replacing SV40 large T and small T antigens with sh-p53, mutant CDK4 (CDK4 R24C ), and sh-PP2A-B56γ. Importantly, all transformed FTSECs gave rise to high-grade Müllerian carcinomas that were grossly, histologically, immunophenotypically, and genomically similar to human HGSOC. With this model, we will now be able to assess the transformative effects of specific genetic alterations on FTSECs in order to characterize their respective roles in HGSOC development.
A contact method for the assessment of ultrasonic velocity and broadband attenuation in cortical and cancellous bone (1990)

A portable system using a direct contact for the measurement of ultrasonic velocity and broadband attenuation in bone is described (contact ultrasonic bone analyser, CUBA). Soft-tissue compensation is performed using an ultrasonic pulse-echo technique. CUBA has been successfully validated using reference materials, the precision of velocity and broadband attenuation measurements being typically 0.2% and 0.5% respectively. The clinical reproducibility has been assessed on the equine third metacarpal bone. The reproducibility of velocity measurement is typically 0.5% for cortical bone and 1% for cancellous bone. For broadband attenuation the reproducibility is typically 7% for cortical bone and 6% for cancellous bone. The lower reproducibility of the attenuation data is attributed to the high sensitivity to variations in the material properties of bone with small changes in transducer positioning. Coupling difficulties through an intact equine coat have been overcome and the system may now be assessed in the clinical environment, in both human and animal populations.
Structure of Testicular Angiotensin-converting Enzyme (1989)

Abstract The complete amino acid sequence of rabbit testicular angiotensin-converting enzyme has been deduced from the sequence of the corresponding cDNA clone. A protein of the expected molecular weight of 84,000 was translated in vitro from the mRNA encoded by this cDNA. All of the previously determined sequences of seven tryptic peptides from the enzyme are present in the deduced sequence, thus confirming the identity of the protein. From the deduced sequence it appears that the protein contains a signal peptide at the amino terminus and a hydrophobic anchoring domain near the carboxyl terminus. Northern analysis with oligonucleotide probes, whose sequences represented different regions of the cDNA, revealed not only the regions of extensive homology between the mRNAs encoding the testicular and the pulmonary isozymes but also a stretch of sequence near the 5' end unique to the testicular mRNA.
Safety, pharmacokinetics, and pharmacodynamics results from a phase I trial of BAY 86-9766 (RDEA119), a MEK inhibitor, in patients with advanced cancer. (2011)

3007 Background: BAY 86-9766 is a highly selective, allosteric inhibitor of MEK1/2. A phase I dose-escalation trial was conducted to determine the maximum tolerated dose (MTD), pharmacokinetics (PK) and pharmacodynamics (PD) in patients with advanced metastatic or locally recurrent solid tumors. Methods: Sixty-nine patients received doses from 2-160 mg once daily (QD) or 50-80 mg twice daily (BID). Tumor types included 22 colorectal (CRC), 8 melanoma, 5 prostate, 5 NSCLC, 5 pancreatic, 3 adrenal, 3 cholangiocarcinoma, 2 breast and 16 other. Patients were given a single oral dose on Day 1, were off drug for 7 days, and then began a 28-day course of daily continuous dosing. If benefiting, dosing continued in 28-day courses with tumor response and PD assessed every 2 courses. Safety was assessed by adverse events (AEs), clinical laboratory tests, vital signs, ECGs, ECHO/MUGA scans and physical exams. PK was collected each course. PD assessments included circulating tumor cells, leukocyte phosphorylated ERK (pERK) and leukocyte released tumor necrosis factor alpha (TNFα). Biopsies from 12 of 20 MTD patients were genotyped, of which 8 were assessed for changes in Ki67, pERK, and phosphorylated AKT. Results: The MTD was 100 mg/day. At this dose, the most common treatment-related AEs were rash, diarrhea, nausea, vomiting, fatigue, and peripheral edema. Central nervous system AEs occurred predominantly at doses of 100-160 mg/day. Group mean Cmax and AUC0-24 values increased linearly with dose. At doses of 60 mg QD, 100 mg QD and 50 mg BID, a significant suppression of leukocyte pERK and TNFα was seen through 24 hours post dose. Tumor pERK showed significant reduction from baseline in 75% of the samples. Initial mutational analysis revealed 0% NRAS, 0% PTEN, 8% PIK3CA, 17% KRAS, 17% BRAF, and 17% KRAS/PIK3CA. Stable disease (≥ 4 courses) was achieved in 10 patients and 1 patient with CRC who was KRAS-wild type had a confirmed partial response. Conclusions: BAY 86-9766 was generally well tolerated at doses ≤ 100 mg daily with rash being the most common treatment-related AE. At the MTD, significant inhibition of tumor pERK was observed in a variety of disease types and genetic backgrounds.
Mutational events in mouse myeloma cells. (1981)

Cultured mouse myeloma cells frequently generate variants in immunoglobulin expression and structure. In this paper the authors will review the phenotypes of the variants which have been identified and discuss the mechanisms which may be responsible for the somatic instability of the immunoglobulin genes in mouse myeloma cells.
Extending UDDI with Context-Aware Features Based on Semantic Service Descriptions (2003)

The web has evolved from the HTML-based repositories of text and images towards the current web services and semantic web developments. Web services are believed to help the integration of diverse applications while the semantic web promises to increase the &amp;quot;intelligence&amp;quot; of the web, enabling richer discovery, data integration, navigation and automation of tasks. A natural next step would be the combination of these developments, resulting in semantic web services. Another trend we observe is the development of next generation networks, such as GPRS and UMTS, which provide a richer environment as they will have access to information about the user&amp;apos;s, location, preferences and changing environment. With the aid of this information, service providers will be able to develop services that adapt to the user&amp;apos;s context. However, current web services technologies, based on WSDL and UDDI, do not provide a means for context-aware service discovery. In this paper we present the design and implementation of an enhanced UDDI server, capable of storage, matching and retrieval of semantically rich service profiles that contain contextual information. We also present a tool that facilitates the creation, publication and discovery of such service profiles.
Asymmetric synthesis and properties of the enantiomers of the antibacterial agent 7-(3-aminopyrrolidin-1-yl)-1-(2,4-difluorophenyl)-1,4-dihydro-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid hydrochloride (1988)

Compound 1 [7-(3-aminopyrrolidin-1-yl)-1-(2,4-difluorophenyl)-1,4-dihydro-6-f luoro-4-oxo-1,8-naphthyridine-3-carboxylic acid hydrochloride] is a potent member of the quinolonecarboxylic acid class of antibacterial agents and is currently undergoing clinical evaluation. We have developed efficient asymmetric syntheses of the enantiomers of this agent. The S-(+) enantiomer 1a is 1-2 log2 dilutions more active than the R-(-) enantiomer 1b against aerobic bacteria and 1-2 or more log2 dilutions more active against anaerobic bacteria in vitro. The enantiomer 1a shows significantly better in vivo activity in a Pseudomonas aeruginosa mouse protection model compared to racemic 1. Coupled with the improved solubility profile of 1a relative to racemic material, these features may be of practical significance from a clinical standpoint.
Alcod idss: Assisting the Australian stock market surveillance team's review process (1996)

ALCOD is a cooperative multiagent intelligent decision support system to assist stock market surveillance teams to classify alerted noncompliant events transacted on the exchange. ALCOD facilitates the review of the classifications. The system combines heuristic, approximate, and causal reasoning and is centered around a relational database, which is used as a control blackboard.
New hydroxyethylamine HIV protease inhibitors that suppress viral replication (1992)

The synthesis of analogues of AcSerLeuAsn[Phe-HEA-Pro]IleValOMe (1, JG-365; where HEA stands for the hydroxyethylamine unit 2), a tight-binding inhibitor of HIVP, are reported. Systematic modification of the P3 and P3' regions of the inhibitors has led to smaller HIVP inhibitors that inhibit viral replication in HIV-infected and SIV-infected cell cultures. Six aliphatic and/or aromatic derivatives were prepared by replacing residues in the P3 regions of BocLeuAsn[Phe-HEA-Pro]IleValOMe. Aromatic side chains at P3 gave better inhibitors than aliphatic side chains. The better inhibitors in this series contained a beta-naphthylalanine or a biphenyl unit at P3. A second series of HIVP inhibitors were obtained by converting the P3 group into acyl groups. CbzAsn[Phe-HEA-Pro]IlePheOMe and Qua-Asn-[Phe-HEA-Pro]-Ile-Phe-OMe (where Qua = quinolin-2-ylcarbonyl) are potent HIVP inhibitors with Ki values equal to 1.0 and 0.1 nM, respectively. The inhibition constants were determined by using the continuous fluorometric assay developed by Toth and Marshall. The activities of the protease inhibitors for inhibition of SIV replication were determined in vitro using CEM x 174 cells. Inhibition of HIV infection was determined essentially as reported by Pauwels and co-workers. The anti-HIV assay was carried out in culture using CEM cells (a CD4+ lymphocyte line) infected with virus strain HTLV-IIIb with a multiplicity of infection of 0.1. Several analogues inhibited the cytopathic effect at concentrations of 0.1-0.8 microgram/mL. These results establish that good inhibitors of HIV protease that inhibit viral replication in infected lymphocytes in in vitro cell assays can be obtained from JG-365 when the AcSerLeu unit is replaced by aromatic acyl derivatives.
A family of clostridial and streptococcal ligand‐binding proteins with conserved C‐terminal repeat sequences (1991)

Analysis of the derived amino acid sequences of toxins A and B from Clostridium difficile has identified an extraordinarily large number of repeat amino acid units in the C-terminal regions of the proteins. Nearly one third of each of the proteins consist of repeating units which appear, at least in the case of toxin A, to be responsible for carbohydrate binding. Similar repeat units are also found in the C-terminal region of four glucosyltransferases from Streptococcus mutans and Streptococcus downei, and in four lytic enzymes from Streptococcus pneumoniae and its bacteriophages (HB-3, Cp-1 and Cp-9). In each case the repeats constitute the ligand-binding portion of the respective enzymes. A glucan-binding protein from S. mutans, which lacks enzymatic activity, has similar repeats spanning almost the entire molecule. This family of ligand-binding proteins appears to be of modular design, with one module consisting of a repetitive ligand-binding domain located in the C-terminal region and the other module(s) providing enzymatic functions.
Linkage, recombination and mapping (1981)

So far we have seen that some traits of the laboratory mouse exhibit segregation in conformity with Mendel’s principle of segregation of alleles and that some sets of two traits exhibit assortment in conformity with Mendel’s principle of random assortment of non-alleles. In this chapter, we shall deal with an experiment in which the first principle holds but the second does not. Instead of random or independent assortment of non-alleles, we shall be led to infer, as many others have done since 1910, when Morgan perceived the phenomenon, that there can be non-random or dependent assortment of non-alleles. This phenomenon is called genetic linkage or, simply, linkage.
Inhibition of O2- generation by dexamethasone is mimicked by lipocortin I in alveolar macrophages. (1989)

Glucocorticoids inhibit superoxide (O2-) generation by phagocytes through a mechanism that remains unclear. We investigated this effect by using dexamethasone on guinea pig alveolar macrophages. O2- generation was induced either by the calcium ionophore A23187, a potent stimulus of phospholipase A2, or by the protein kinase C activator, phorbol myristate acetate (PMA). Dexamethasone inhibited O2- generation initiated by A23187 by 50-55%. This inhibition required: (a) more than 45 min incubation and was maximal after 2 h; (b) glucocorticoid receptor occupancy; and (c) protein synthesis. The inhibitory effect of dexamethasone could not be explained by an interaction with the respiratory burst enzyme NADPH oxidase since O2- generation was only weakly affected upon PMA stimulation. Lipocortin I, a glucocorticoid inducible and phospholipase A2 inhibitory protein, inhibited O2- generation initiated by A23187 but failed to modulate the respiratory burst activated by PMA. These results were obtained with lipocortin I purified from mouse lungs, human blood mononuclear cells, and with human recombinant lipocortin I. We propose that lipocortin I is capable of inhibiting the activation of NADPH oxidase only when membrane signal transduction involves phospholipase A2. By mimicking the effect of dexamethasone, lipocortin I may extend its potential anti-inflammatory action to the partial control of the formation of oxygen reactive species by phagocytes.
Telomere dysfunction causes alveolar stem cell failure (2015)

Telomere syndromes have their most common manifestation in lung disease that is recognized as idiopathic pulmonary fibrosis and emphysema. In both conditions, there is loss of alveolar integrity, but the underlying mechanisms are not known. We tested the capacity of alveolar epithelial and stromal cells from mice with short telomeres to support alveolar organoid colony formation and found that type 2 alveolar epithelial cells (AEC2s), the stem cell-containing population, were limiting. When telomere dysfunction was induced in adult AEC2s by conditional deletion of the shelterin component telomeric repeat-binding factor 2, cells survived but remained dormant and showed all the hallmarks of cellular senescence. Telomere dysfunction in AEC2s triggered an immune response, and this was associated with AEC2-derived up-regulation of cytokine signaling pathways that are known to provoke inflammation in the lung. Mice uniformly died after challenge with bleomycin, underscoring an essential role for telomere function in AEC2s for alveolar repair. Our data show that alveoloar progenitor senescence is sufficient to recapitulate the regenerative defects, inflammatory responses, and susceptibility to injury that are characteristic of telomere-mediated lung disease. They suggest alveolar stem cell failure is a driver of telomere-mediated lung disease and that efforts to reverse it may be clinically beneficial.
Determinants of Inapparent and Symptomatic Dengue Infection in a Prospective Study of Primary School Children in Kamphaeng Phet, Thailand (2011)

Our findings point to an important aspect of virus-host interactions at either a population or individual level possibly due to an effect of heterotypic cross-reactive immunity to reduce dengue disease severity. These findings have important implications for future dengue vaccines.
The Ketogenic Diet as a Treatment Paradigm for Diverse Neurological Disorders (2012)

Dietary and metabolic therapies have been attempted in a wide variety of neurological diseases, including epilepsy, headache, neurotrauma, Alzheimer disease, Parkinson disease, sleep disorders, brain cancer, autism, pain, and multiple sclerosis. The impetus for using various diets to treat - or at least ameliorate symptoms of - these disorders stems from both a lack of effectiveness of pharmacological therapies, and also the intrinsic appeal of implementing a more "natural" treatment. The enormous spectrum of pathophysiological mechanisms underlying the aforementioned diseases would suggest a degree of complexity that cannot be impacted universally by any single dietary treatment. Yet, it is conceivable that alterations in certain dietary constituents could affect the course and impact the outcome of these brain disorders. Further, it is possible that a final common neurometabolic pathway might be influenced by a variety of dietary interventions. The most notable example of a dietary treatment with proven efficacy against a neurological condition is the high-fat, low-carbohydrate ketogenic diet (KD) used in patients with medically intractable epilepsy. While the mechanisms through which the KD works remain unclear, there is now compelling evidence that its efficacy is likely related to the normalization of aberrant energy metabolism. The concept that many neurological conditions are linked pathophysiologically to energy dysregulation could well provide a common research and experimental therapeutics platform, from which the course of several neurological diseases could be favorably influenced by dietary means. Here we provide an overview of studies using the KD in a wide panoply of neurologic disorders in which neuroprotection is an essential component.
Administration of Interleukin-10 at the Time of Priming ProtectsCorynebacterium parvum-Primed Mice against LPS- and TNF-α-Induced Lethality (1996)

Several laboratories have described the protective effects of interleukin-10 (IL-10) in mouse models of lethal endotoxemia. In most of these experiments, protection was observed in normal mice that were given a lethal dose of LPS. However, we failed to observe protection with IL-10 in LPS-challenged mice that had been primed with Corynebacterium parvum (Proprionibacterium acnes). We have extended our studies with IL-10 in C. parvum-primed mice and in some cases have observed protection that appears to depend on the strength of the sensitization to C. parvum. When IL-10 was administered to mice at the time of priming, it was particularly effective in blocking sensitization, as evidenced by the inability of treated mice to mount a strong inflammatory cytokine response when subsequently challenged with LPS. Following such treatment with IL-10, C. parvum-primed mice were also protected from a subsequent lethal challenge with rMuTNF-alpha. In addition, the mice were protected against LPS- and TNF-alpha-induced lethality with a single dose of an anti-TNF-alpha or anti-IFN-gamma mAb given at the time of priming. Our results suggest that TNF-alpha and IFN-gamma are produced early after priming with C. parvum and are at least partly responsible for the enhanced sensitivity of the mice to LPS and TNF-alpha. IL-10 affords protection to the mice because of its ability to block the C. parvum-induced TNF-alpha and IFN-gamma responses.
Synthesis of Proposed Oxidation−Cyclization−Methylation Intermediates of the Coumarin Antibiotic Biosynthetic Pathway (2003)

[structure: see text] A chemoenzymatic synthesis was described to prepare proposed oxidation-cyclization-methylation intermediates of the coumarin antibiotic biosynthetic pathway. The successful synthesis of these fragile molecules relies heavily on mild enzymatic deprotection and efficient enzymatic kinetic resolution to minimize epimerization, decomposition, multiple orthogonal protections, and retro aldol reactions often encountered in their chemical synthesis.
Surface electronic scattering in d-wave superconductors (1999)

Theoretical model of a rough surface in a d-wave superconductor is studied for the general case of arbitrary strength of electron scattering by an impurity layer covering the surface. Boundary conditions for quasiclassical Eilenberger equations are derived at the interface between the impurity layer and the d-wave superconductor. The model is applied to the selfconsisrent calculation of the surface density of states and the critical current in d-wave Josephson junctions
Zirconium-labeled monoclonal antibodies and their distribution in tumor-bearing nude mice. (1997)

This method is well suited for labeling MAbs with Zr isotopes. Using 89Zr, the biodistribution of the radioimmunoconjugate can easily be visualized with a PET camera.
CODEX: a robust and secure secret distribution system (2004)

CODEX (COrnell Data Exchange) stores secrets for subsequent access by authorized clients. It also is a vehicle for exploring the generality of a relatively new approach to building distributed services that are both fault-tolerant and attack-tolerant. Elements of that approach include: embracing the asynchronous (rather than synchronous) model of computation, use of Byzantine quorum systems for storing state, and employing proactive secret sharing with threshold cryptography for implementing confidentiality and authentication of service responses. Besides explaining the CODEX protocols, experiments to measure their performance are discussed.
Characterization of major recognition sequences for a herpes simplex virus type 1 origin-binding protein (1988)

To investigate early initiation events in the replication of herpes simplex virus type 1, we analyzed interactions of proteins from infected cell extracts with the small origin of herpes simplex virus type 1 (oris1). Using the mobility shift assay, we detected two origin-specific binding interactions. We characterized the more prominent interaction on both strands of the DNA duplex with DNase I protection and methylation interference assays. Protein binding protects 17 bases of DNA on each strand from DNase I. These sequences are located at the left end of the central palindrome and are shifted four bases relative to one another. On the basis of the DNase protection pattern, we believe this protein to be related to the origin-binding protein defined by Elias et al. (P. Elias, M.E. O'Donnell, E.S. Mocarski, and I.R. Lehman, Proc. Natl. Acad. Sci. 83:6322-6326, 1986). Our DNase I footprint shows both strong and weak areas of protection. The regions strongly protected from DNase I align with the essential contact residues identified by interference footprinting. Methylation interference defines a small binding domain of 8 base pairs: 5'-GTTCGCAC-3'/3'-CAAGCGTG-5'. This recognition sequence contains two inverted 5'-GT(T/G)CG-3' repeats which share a 2-base overlap; thus, the origin-binding protein probably binds to the inverted repeats as a dimer.
Treatment of Angina Pectoris by Electrical Stimulation of Carotid-Sinus Nerves (1970)

Epstein, S E; Beiser, G D; Goldstein, R E; Redwood, D; Rosing, D R; Glick, G; Wechsler, A S; Stampfer, M; Cohen, L S; Reis, R L; Braunwald, N S; Graunwald, E Author Information