gebhart/patrepeval huggingface dataset:
Oxidized SOD1 alters proteasome activities in vitro and in the cortex of SOD1 overexpressing mice (2005)

Premature ageing, one of the characteristics of Down syndrome (DS), may involve oxidative stress and impairment of proteasome activity. Transgenic mice overexpressing the human copper/zinc superoxide dismutase (SOD1) gene are one of the first murine models for DS and it has been shown that SOD1 overexpression might be either deleterious or beneficial. Here, we show a reduction in proteasome activities in the cortex of SOD1 transgenic mice and an associated increase in the content of oxidized SOD1 protein. As we demonstrate that in vitro oxidized SOD can inhibit purified proteasome peptidase activities, modified SOD1 might be partially responsible for proteasome inhibition shown in SOD1 transgenic mice.
Analyzing communication latency using the Nectar communication processor (1992)

For multicomputer applications, the most important performance parameters of a network is the latency for short messages. In this paper we present an analysis of communication latency using measurement of the Nectar system. Nectar is a high-performance multicomputer built around a high-bandwidth crosspoint network. Nodes are connected to the Nectar network using network coprocessors that are primarily responsible the protocol processing, but that can also execute application code. This architecture allows us to analyze message latency both between workstations with an outboard protocol engine and between lightweight nodes with a minimal runtime system and a fast, simple network interface (the coprocessors). We study how much context switching, buffer management and protocol processing contribute to the communication latency and we discuss how the latency is influenced by the protocol implementation.
Quinolone Alkaloids, Diacylglycerol Acyltransferase Inhibitors from the Fruits ofEvodia rutaecarpa (2002)

From the diacylglycerol acyltransferase (DGAT) activity-guided fractionation, a new quinolone alkaloid, 1-methyl-2-tetradecyl-4(1H)-quinolone (1) was isolated from the fruits of Evodia rutaecarpa together with three known quinolone alkaloids, evocarpine (2), 1-methyl-2-[(4 Z,7 Z)-4,7-decadienyl]-4(1H)-quinolone (3) and 1-methyl-2-[(6 Z,9 Z)-6,9-pentadecadienyl]-4(1 H)-quinolone (4). They showed a dose-dependent DGAT inhibition with IC 50 values of 69.5 microM ( 1), 23.8 microM (2), 20.1 microM (3) and 13.5 mu (4).
Identification of an Active Sequence within the First Immunoglobulin Domain of Intercellular Cell Adhesion Molecule-1 (ICAM-1) That Interacts with Fibrinogen (1996)

Monocytic cells bind fibrinogen (fg) through integrin alphaMbeta2. fg-bound monocytic cells demonstrate an enhanced adhesion to endothelial cells, which is dependent on intercellular adhesion molecule-1 (ICAM-1). Our studies differentiate fg interactions with stimulated and resting endothelial cells, which are ICAM-1 dependent and independent, respectively. This report documents a direct interaction between fg and intact ICAM-1 and with a two-Ig domain form of ICAM-1. A small region within the first Ig domain of ICAM-1, ICAM-1-(8-21) (KVILPRGGSVLVTC), was identified to interact with fg in a specific and selective manner. ICAM-1-(8-21) bound to plasmin-derived fg fragments X, D100, and D80 but not to fragment E. Consistent with this finding, fg gamma-chain peptide, fg-gamma-117-133, blocked fg interaction with ICAM-1-(8-2 1. ICAM-1-(8-21) peptide and antibodies directed against ICAM-1-(8-21) also blocked the adhesion and binding of ICAM-1-bearing Raji cells with fg. ICAM-1-(8-21) and fg-gamma-117-133 are likely to be one of the contact pairs mediating fg-ICAM-1 interactions.
p145, a protein with associated tyrosine kinase activity in a human gastric carcinoma cell line. (1988)

A protein with an Mr of 145,000 (p145) was detected by antibodies to phosphotyrosine by Western blot (immunoblot) analysis. This protein was phosphorylated on tyrosine in a gastric carcinoma cell line. In cells that were metabolically labeled with 32Pi, this protein was phosphorylated on tyrosine and serine. p145 is a cysteine-rich transmembrane glycoprotein. The extracellular domain could be labeled by 125I under nonpermeating conditions and was cleaved by mild trypsin treatment of intact cells. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis under nonreducing conditions revealed a shift of p145 mobility to an apparent Mr of 190,000. After immunoprecipitation with phosphotyrosine antibodies, p145 displayed a strong associated protein kinase activity in vitro, becoming phosphorylated on tyrosine. There was no immunological cross-reaction between p145 and known tyrosine kinases. Both in vivo and in vitro tyrosine phosphorylations were unaffected by the addition of known growth factors. However, p145 was rapidly dephosphorylated in vivo when cells were exposed to low pH, a condition that is known to dissociate ligands from their receptors. These data suggest that p145 is associated with a protein tyrosine kinase activity which, in the tumor cell line studied, is activated by an as yet unidentified factor.
Lung image Ssgmentation using deep learning methods and convolutional neural networks (2016)

This paper presents results of the first,&#13;\nexploratory stage of research and developments on&#13;\nsegmentation of lungs in X-Ray chest images (Chest&#13;\nRadiographs) using Deep Learning methods and&#13;\nEncoder-Decoder Convolutional Neural Networks (EDCNN).&#13;\nComputational experiments were conducted using&#13;\nGPU Nvidia TITAN X equipped with 3072 CUDA Cores&#13;\nand 12Gb of GDDR5 memory. Comparison of resultant&#13;\nsegmentation accuracy with manual segmentation using&#13;\nDice's score has revealed that the average accuracy&#13;\nachieves 0.962 with the minimum and maximum Dice's&#13;\nscore values of 0.926, 0.974 respectively, and standard&#13;\ndeviation of 0.008. The study was performed in the&#13;\ncontext of large-scale screening of population for lung&#13;\nand heart diseases as well as development of&#13;\ncomputational services for international portal on lung&#13;\ntuberculosis. The results obtained with this study allow&#13;\nconcluding that ED-CNN networks may be considered as&#13;\na promising tool for automatic lung segmentation in&#13;\nlarge-scale projects.
Genitourinary malignancies in organ transplant recipients. (1994)

The current recommendations for management of patients with pre-existing neoplasms before transplantation is a function of the cure rate achieved with the available therapeutic modalities and the risk of recurrence following initiation of immunosuppression. Recurrences after transplantation, as well as de novo malignancies, although unpredictable in many cases, have been identified as arising in certain individuals at risk and are a result of multifactorial etiologies. These etiologies include oncogenic effects of immunosuppressive agents or their broken-down metabolites, depressed immunity, dampened immune response, and activation of oncogenic viruses (herpes group, EBV), carcinogens, congenital predilection, and dormant residual cancers of high malignant potentials. Better understanding of the interplay of these factors and longer follow-up of transplant recipients receiving contemporary immunosuppressive agents are needed in order to diminish the likelihood of tumor recurrence/development in this population. Judicious application of current information obtained from the transplant registries, better understanding of immunosuppressive agents and their long-term oncogenic effects, and careful and conscientious allocation of cadaveric organs are advised.
THE B CHROMOSOME OF CORN (1978)

INTRODUCTION ........ ........ . . . . .. . . . . ...... ... 5 PROCESSES CONTROLLED BY THE B CHROMOSOME ........ . .. .. ....... ... 8 Nondisjunction 8 Preferential Fertilization , . . . . . . . . . . . . . . . . . , . . . . . . . . . . . . . . . ... . . . . . . . . . . . . . . . . ,. . . . . . . . . . . . ....... 11 Recombination 12 MOLECULAR AND CELLULAR BIOLOGY . . . . . 13 RELATIONSHIP TO ABNORMAL CHROMOSOME 10 IS APPLICATION OF B CHROMOSOME NONDISJUNCTION TO GENETIC STUDIES 16 Chromosome Mapping 16 Transfer of A Chromosome Segments Between Lines .. 16 Gene Dosage and Gene Imprinling Studies 17 SUMMARY ..... . . . . .. ......... ... . ....... 18
CME Article: Long-Lasting Reduction of Blood Pressure by Electroacupuncture in Patients with Hypertension: Randomized Controlled Trial (2015)

<b>Background:</b> Acupuncture at specific acupoints has experimentally been found to reduce chronically elevated blood pressure. <b>Objective:</b> To examine effectiveness of electroacupuncture (EA) at select acupoints to reduce systolic blood pressure (SBP) and diastolic blood pressures (DBP) in hypertensive patients. <b>Design:</b> Two-arm parallel study. <b>Patients:</b> Sixty-five hypertensive patients not receiving medication were assigned randomly to one of the two acupuncture intervention (33 versus 32 patients). <b>Intervention:</b> Patients were assessed with 24-hour ambulatory blood pressure monitoring. They were treated with 30-minutes of EA at PC 5-6+ST 36-37 or LI 6-7+GB 37-39 once weekly for 8 weeks. Four acupuncturists provided single-blinded treatment. <b>Main outcome measures:</b> Primary outcomes measuring effectiveness of EA were peak and average SBP and DBP. Secondary outcomes examined underlying mechanisms of acupuncture with plasma norepinephrine, renin, and aldosterone before and after 8 weeks of treatment. Outcomes were obtained by double-blinded evaluation. <b>Results:</b> After 8 weeks, 33 patients treated with EA at PC 5-6+ST 36-37 had decreased peak and average SBP and DBP, compared with 32 patients treated with EA at LI 6-7+GB 37-39 control acupoints. Changes in blood pressures significantly differed between the two patient groups. In 14 patients, a long-lasting blood pressure-lowering acupuncture effect was observed for an additional 4 weeks of EA at PC 5-6+ST 36-37. After treatment, the plasma concentration of norepinephrine, which was initially elevated, was decreased by 41%; likewise, renin was decreased by 67% and aldosterone by 22%. <b>Conclusions:</b> EA at select acupoints reduces blood pressure. Sympathetic and renin-aldosterone systems were likely related to the long-lasting EA actions.
Decarboxylative elimination of enol triflates as a general synthesis of acetylenes (1999)

I. Fleming and C. Ramarao, Chem. Commun., 1999, 1113 DOI: 10.1039/A901921I
Phytochemicals from traditional medicinal plants used in the treatment of diarrhoea: modes of action and effects on intestinal function (2006)

Medicinal plants have been used as traditional treatments for numerous human diseases for thousands of years. Diarrhoeal diseases continue to be a major cause of morbidity and mortality throughout the world and there is renewed interest in the discovery of novel compounds that can be used to fight these diseases. Numerous studies have validated the traditional use of antidiarrhoeal medicinal plants by investigating the biological activity of extracts of such plants, which have antispasmodic effects, delay intestinal transit, suppress gut motility, stimulate water adsorption or reduce electrolyte secretion. Of the numerous phytochemicals (such as alkaloids, tannins, flavonoids and terpenes) present in active extracts, tannins and flavonoids are thought to be responsible for antidiarrhoeal activity by increasing colonic water and electrolyte reabsorption. Others act by inhibiting intestinal motility. As some of the active ingredients are potentially toxic, there is a need to evaluate the safety of plant preparations. A few clinical trials have evaluated the safety and tolerability of traditional and herbal medicine preparations used to treat diarrhoea and generally indicate that minimal side effects are observed. However, with the increased popularity of plant-derived and herbal medicines in Western society, the benefits and potential dangers of these medicines must be considered.
Effects of White Blood Cells on the In Vitro Penetration of Zona‐free Hamster Eggs by Human Spermatozoa (1985)

The presence of white blood cells in semen has been associated with male infertility. Previous studies indicate that pyospermia occurs in conjunction with decreases in sperm motility, number of normal sperm forms, and penetration rates in the zona-free hamster egg sperm penetration assay. We have evaluated the relationship of seminal white blood cells and sperm function, as reflected in the zona-free hamster egg penetration assay, and have investigated the possible mode of action of the white cells. Egg penetration rates decreased when white blood cells from fertile or potentially fertile donors were added to their sperm suspensions prior to preincubation and at insemination in the in vitro assay. Zona-free hamster egg penetration assay results were also inhibited when the supernatant from white blood cells incubated in Biggers, Whitten, and Whittingham (BWW) medium overnight were introduced to sperm-oocyte suspensions at insemination. Conversely, egg penetration rates were enhanced in samples from hypofertile individuals when white blood cell concentrations in the semen or WBC/sperm ratios were reduced, either by physical removal or as a result of antibiotic therapy. The physical presence of leukocytes, and possibly, the extracellular release of lysosomal enzymes may be responsible for the inhibitory effects in vitro. Although the mechanism(s) by which white blood cells interfere with the fertilizing capacity of spermatozoa are not clear, it is quite obvious that their presence in the in vitro environment is undesirable and can mask an individual's actual fertilizing potential.
BCG lmmunotherapy of Malignant Melanoma (1974)

Over the past 7 years, 151 patients with malignant melanoma have been treated with BCG immunotherapy alone or as an adjunct to surgical therapy. Direct injection of metastatic melanoma lesions limited to skin resulted in 90% regression of injected lesions and 17% regression of uninjected lesions in immunocompetent patients. Approximately 25% of these patients remained free of disease for 1 to 6 years. Direct injections of BCG into nodules of patients with subcutaneous or visceral metastases resulted in a lower incidence of local control and no long term survivors. Attempts to improve the results of immunotherapy in these patients by palliative surgical resection of large metastatic lesions to lower tumor burden followed by BCG immunotherapy significantly improved the results although many patients still developed recurrent disease. Early results of a clinical trial combining BCG immunotherapy with regional lymphadenectomy in patients with melanoma metastatic to lymph nodes have been encouraging and promising. Further controlled clinical trials are necessary to elucidate the role of BCG in immunotherapy. However, since BCG is but one of a number of potential immunologic adjuvants, even more effective immunotherapy will be possible as further knowledge of the interactions of cellular and humoral immunity is acquired.
Molecular Biology of the Pore-forming Cytolysins fromStaphylococcus aureus,α- andγ-Hemolysins and Leukocidin (1997)

Staphylococcus aureus is an important opportunistic pathogen. It produces a variety of extracellular proteins, which may play important roles in infections by this bacterium. Staphylococcal alpha-toxin is a pore-forming 33-kDa polypeptide. In the first part of this article, we will refer to the roles of cell membranes in the pore formation by alpha-toxin as well as the molecular dissection of alpha-toxin for understanding its pore-forming nature. Staphylococcal gamma-hemolysin and leukocidin are bi-component cytolysins, which have different cell specificities towards erythrocytes and leukocytes, respectively. We have found that these bi-component cytolysins share a common component. In the second part of this article, we will refer to the current status of knowledge of molecular cloning of the genes coding for gamma-hemolysin and leukocidin, molecular domains of the toxins which decide the cell specificities, and mode of action of these bi-component toxins.
The Story of An American Soldier (1994)

In lieu of an abstract, below is the essay's first paragraph.\n"Only a couple of dozen nails to go, and sure enough old Herm, right on time, waddled around the comer of his beat-up neglected house heading towards us. My brother-in-law, Scott, and I knew we would be unable to finish fixing my front porch steps without a visit from my waning but curious neighbor. Even at nine o'clock in the morning, Herm figured it was not too early to spit out a war story, or a chopped up explanation about what we were doing wrong."
Gene transfer to mammalian cells using genetically targeted filamentous bacteriophage (1999)

We have genetically modified filamentous bacteriophage to deliver genes to mammalian cells. In previous studies we showed that noncovalently attached fibroblast growth factor (FGF2) can target bacteriophage to COS-1 cells, resulting in receptor-mediated transduction with a reporter gene. Thus, bacteriophage, which normally lack tropism for mammalian cells, can be adapted for mammalian cell gene transfer. To determine the potential of using phage-mediated gene transfer as a novel display phage screening strategy, we transfected COS-1 cells with phage that were engineered to display FGF2 on their surface coat as a fusion to the minor coat protein, pIII. Immunoblot and ELISA analysis confirmed the presence of FGF2 on the phage coat. Significant transduction was obtained in COS-1 cells with the targeted FGF2-phage compared with the nontargeted parent phage. Specificity was demonstrated by successful inhibition of transduction in the presence of excess free FGF2. Having demonstrated mammalian cell transduction by phage displaying a known gene targeting ligand, it is now feasible to apply phage-mediated transduction as a screen for discovering novel ligands.
The PDZ protein discs‐large (DLG): the ‘Jekyll and Hyde’ of the epithelial polarity proteins (2012)

Discs-large (DLG) is a multi-PDZ domain-containing protein that belongs to the family of molecular scaffolding proteins known as membrane guanylate kinases or MAGUKs. DLG is a component of the Scribble polarity complex and genetic analyses of DLG in Drosophila have identified a role for the protein in several key biological processes including the regulation of apico-basal polarity of epithelial cells, as well as other polarity processes such as asymmetric cell division and cell invasion. Disturbance of DLG function leads to uncontrolled epithelial cell proliferation and neoplastic transformation, thereby defining DLG as a potential tumour suppressor. However, whether mammalian homologues of DLG (DLG1, DLG2, DLG3 and DLG4) also possess tumour suppressor functions is not known. In this minireview, we focus on the biological functions of DLG1 in human epithelial cells and on how the function of this MAGUK relates to its intracellular location. We examine some of the evidence that implies that DLG has both tumour suppressor and, paradoxically, oncogenic functions depending upon the precise cellular context.
Differences in the Ligand Specificity between CD1d‐Restricted T Cells with Limited and Diverse T‐Cell Receptor Repertoire (2000)

The natural killer (NK) T-lymphocyte population consists of two subsets utilizing a diverse and restricted T-cell receptor (TCR) repertoire, respectively. Both populations have been shown to include autoreactive cells. NKT cells carrying restricted Valpha14(AV14S1)Jalpha281/Vbeta8.2(BV8S2A1 ) TCR have been shown to recognize alpha-galactosylceramide (alphaGalCer) presented in the context of murine CD1d. In this study we screened a set of murine CD1d-autoreactive T-cell hybridomas with diverse TCR for their reactivity with several glycosylated variants of ceramide, including alphaGalCer. These hybridomas showed a different pattern of reactivity to CD1d-expressing antigen-presenting cells (APC) and were not reactive with any of the tested variants of ceramide. A second set of hybridomas had been selected for expression of Valpha14 and Vbeta8.2 TCR chains. These cells responded to alphaGalCer presented on CD1d, but were only weakly reactive to syngeneic splenocytes or CD1d-transfected cells. Their fine specificity in the response to glycosylation variants of ceramide demonstrated a homogenous reactivity pattern, including reactivity to alpha-galactosylsphingosine, the variant of alphaGalCer with truncated fatty acyl chain. These findings underline the differences in ligand specificity between the two subsets of CD1d-restricted NKT cells, and demonstrate a similarity in reactivity among the hybridomas using the Valpha14-Jalpha281/Vbeta8.2 TCR.
Multiplexed protein maps link subcellular organization to cellular states (2018)

Obtaining highly multiplexed protein measurements across multiple length scales has enormous potential for biomedicine. Here, we measured, by iterative indirect immunofluorescence imaging (4i), 40-plex protein readouts from biological samples at high-throughput from the millimeter to the nanometer scale. This approach simultaneously captures properties apparent at the population, cellular, and subcellular levels, including microenvironment, cell shape, and cell cycle state. It also captures the detailed morphology of organelles, cytoskeletal structures, nuclear subcompartments, and the fate of signaling receptors in thousands of single cells in situ. We used computer vision and systems biology approaches to achieve unsupervised comprehensive quantification of protein subcompartmentalization within various multicellular, cellular, and pharmacological contexts. Thus, highly multiplexed subcellular protein maps can be used to identify functionally relevant single-cell states.
Safety and efficacy of panitumumab monotherapy in patients with metastatic colorectal cancer (mCRC) (2005)

3520 Background: Panitumumab (formerly ABX-EGF) is a fully human monoclonal antibody that binds with high affinity to the epidermal growth factor receptor (EGFr). This ongoing phase 2 study is evaluating the safety and efficacy of panitumumab monotherapy in patients (pts) with mCRC who have failed standard chemotherapy. Here we present mature unaudited data from the ongoing study. Methods: Pts with mCRC who failed therapy with a fluoropyrimidine (± leucovorin) and either irinotecan or oxaliplatin, or both, were eligible for this study. Cohort A included pts with EGFr staining of 2+ or 3+ in ≥ 10% tumor cells; cohort B included pts with EGFr staining of the sum of 1+, 2+ and 3+ in ≥ 10% of tumor cells, but with the sum of 2+ and 3+ in < 10% of tumor cells. Panitumumab was given IV at 2.5 mg/kg once weekly in 8-wk cycles. Pts continued receiving treatment until disease progression or unacceptable toxicity occurred. Endpoints included tumor response (RECIST), time to disease progression, survival, and safety. Results: Enrollment is complete, with treatment ongoing. In total, 148 pts were treated (82 men/66 women; ECOG status of 1 [n = 111] or 0 [n = 37]; mean age 59 yrs [range 21 - 88 yrs]). Efficacy results are shown in the table. The 4 most frequently reported grade (gr) 3 or 4 treatment-related adverse events (AEs) were rash NOS (5 pts), fatigue (4 pts), vomiting NOS (2 pts), nausea (1 pt), and pruritus (1 pt). Skin toxicity-related AEs were reported for 141 pts (95%; 5% gr 3 and no gr 4). One infusion-related gr 3 AE, which did not require dose modification, was reported; no other infusion-related AE has been reported to date. No human anti-human antibodies were observed in 145 pts tested. Conclusions: These mature data confirm previously reported safety and response findings (Hecht et al, 2004) and provide encouraging survival data in pts with mCRC who have failed multiple lines of standard chemotherapy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen, Genentech, Pfizer, Sanofi Amgen Amgen, Bristol-Myers Squibb, Genentech, Novartis, Pfizer, Roche Amgen, Eli Lilly, Pfizer, Roche Amgen