gebhart/patrepeval huggingface dataset:
Pilot study of intratumoral G100, toll-like receptor-4 (TLR4) agonist, therapy in patients with Merkel cell carcinoma (MCC). (2015)

3083 Background: MCC is an aggressive skin cancer with suboptimal therapeutic options. Despite persistent expression of Merkel cell polyomavirus (MCPyV) proteins in ~80% of cases, these tumors are able to evade host immunity. G100 consists of a specific formulation of glucopyranosyl lipid-A (GLA), a TLR4 agonist, and is capable of directly activating dendritic cells (DCs), T cells and other effector cells and stimulating anti-tumor responses in preclinical models. Intratumoral (IT) G100 may overcome immune suppression mechanisms prevalent in MCC tumors and lead to effective local and systemic anti-tumor responses. Methods: 10 MCC patients (pts) with accessible tumor will be enrolled for G100 treatment. Pts with loco-regional MCC (Cohort A) receive 1 cycle of G100 (5 mcg/day) IT on days 1, 8 followed by definitive surgery and/or radiation (RT) starting in week 4. Pts with metastatic disease (Cohort B) receive G100 (5 mcg/day) IT on days 1, 8 and 22 of a 6-week treatment cycle. For cycles 2-4, pts receive palliative RT to the injectable tumor on day 0 followed by G100 IT weekly for 6 doses. All pts have pre- and post-treatment tumor biopsies and blood samples collected for immune monitoring. Results: 8 pts have been enrolled to date (2 cohort A; 6 cohort B); all 8 pts have completed one or more cycles of G100. Treatment-related AEs have all been grade 1 (inflammation, pain and bruising at the injection site) or transient grade 2 (inflammation). 2/2 Cohort A pts with stage IIIB MCC are recurrence-free at 11+ and 4+ months; the first of whom had a pathologic CR after two G100 IT injections. Of 6 pts with stage IV MCC in Cohort B, 2 pts have SD after cycle 1 (one with 28% regression) and 4 pts had PD. MCPyV-specific CD8 and CD4 T cells have been isolated from tumors and peripheral blood, and correlative immune studies of frequency and functional status are in progress. Conclusions: In this pilot study in MCC pts, G100 has demonstrated acceptable safety and encouraging preliminary clinical efficacy. RT was recently added to cohort B and may further enhance immune and clinical responses by increasing the release of endogenous tumor antigens. G100 IT studies in other cancers and in combination with anti-PD-1 therapy are planned. Clinical trial information: NCT02035657.
Drosophila mutants in the 55 kDa regulatory subunit of protein phosphatase 2A show strongly reduced ability to dephosphorylate substrates of p34cdc2 (1994)

The 55 kDa regulatory subunit of Drosophila protein phosphatase 2A is located in the cytoplasm at all cell cycle stages, by the criterion of immunofluorescence. We are unable to detect significant change in protein phosphatase activity during the nuclear division cycle of syncytial embryos. However, cell cycle function of the enzyme is suggested by the mitotic defects exhibited by two Drosophila mutants, aar1 and twinsP, defective in the gene encoding the 55 kDa subunit. The reduced levels of the 55 kDa subunit correlate with the loss of protein phosphatase 2A-like, okadaic acid-sensitive phosphatase activity of brain extracts against caldesmon and histone H1 phosphorylated by p34cdc2/cyclin B kinase, but not against phosphorylase a. Thus the mitotic defects of aar1 and twinsP are likely to result from the lack of dephosphorylation of specific substrates by protein phosphatase 2A.
Recommendations for an educational programme to improve consumer knowledge of and attitudes towards nutritional information on food labels. (2001)

The needs and objectives of the various groups affected by nutritional labelling illustrate the complex and controversial nature of nutritional labelling and the problems in formulating a simple and easily understood system. Twenty homogeneous white middle-income suburbs were chosen at random from a total of 39 strata. The multistage cluster method of sampling was used to divide each suburb into smaller clusters. One area was chosen at random from each suburb. Twenty homes were then systematically selected to bring the total sample number of respondents to 400. White middle-income women completed a questionnaire analysing consumer attitudes towards and knowledge of nutritional labelling in order to identify the objectives needed for the formulation of an educational programme concerning the nutritional labelling of food containers. The results of the survey suggest that although white middle-income women (N = 388) lacked nutritional labelling knowledge (pass rate < 20%) they had a positive attitude towards nutritional labelling (mean 18.29 ± 4.8). As knowledge scores increased the following factors became more positive: attitudes towards nutritional labelling (R = 0.2905 P = 0.0000) nutritional education (c2 = 40.9273 P = 0.01) and the use of nutritional labelling in the purchase of food (r = 0.2230 P = 0.0258). The results of this survey suggest a definite need for a nutritional labelling education programme in South Africa. Although the subject group could be considered representative of the top end of the South African market a comprehensive needs assessment of the relevant target markets that make up South Africas diverse population should be undertaken for the formulation of a national nutritional education programme. (authors)
BLOOD LEVELS OF CRITICAL AMINO ACIDS IN VERY LOW BIRTHWEIGHT INFANTS ON A HIGH HUMAN MILK PROTEIN INTAKE (1982)

A method for a semi-industrial production of human milk subfractions (human milk protein and human milk fat isolates) is described. Four very low birthweight (VLBW) newborn were given a human milk protein isolate added to the mother's own fresh expressed milk in addition to sodium chloride up to 20 mEkv/liter. Growth followed the intrauterine growth curve. Urea levels did not increase in spite of providing a double-normal protein intake. There was no metabolic acidosis and the blood levels of free amino acids determined with a micro-method did not exceed those seen after a normal meal. The concentrated human milk protein product showed a considerable specific sIgA activity against E. coli 0-antigen. It seems possible to use similar "lacto-engineering"-techniques in order to satisfy the increased protein requirements of the VLBW infant, while providing the caloric requirements, without causing any visible disturbance of blood-homeostasis of urea, amino acids or base excess. The method could provide knowledge about the "human milk protein requirements" and a controlled study has been started.
Ibrutinib interferes with the cell-mediated anti-tumor activities of therapeutic CD20 antibodies: implications for combination therapy (2014)

The novel Bruton tyrosine kinase inhibitor ibrutinib and phosphatidyl-4-5-biphosphate 3-kinase-δ inhibitor idelalisib are promising drugs for the treatment of chronic lymphocytic leukemia and B-cell non-Hodgkin lymphoma, either alone or in combination with anti-CD20 antibodies. We investigated the possible positive or negative impact of these drugs on all known mechanisms of action of both type I and type II anti-CD20 antibodies. Pretreatment with ibrutinib for 1 hour did not increase direct cell death of cell lines or chronic lymphocytic leukemia samples mediated by anti-CD20 antibodies. Pre-treatment with ibrutinib did not inhibit complement activation or complement-mediated lysis. In contrast, ibrutinib strongly inhibited all cell-mediated mechanisms induced by anti-CD20 antibodies rituximab, ofatumumab or obinutuzumab, either in purified systems or whole blood assays. Activation of natural killer cells, and antibody-dependent cellular cytotoxicity by these cells, as well as phagocytosis by macrophages or neutrophils were inhibited by ibrutinib with a half maximal effective concentration of 0.3-3 μM. Analysis of anti-CD20 mediated activation of natural killer cells isolated from patients on continued oral ibrutinib treatment suggested that repeated drug dosing inhibits these cells in vivo. Finally we show that the phosphatidyl-4-5-biphosphate 3-kinase-δ inhibitor idelalisib similarly inhibited the immune cell-mediated mechanisms induced by anti-CD20 antibodies, although the effects of this drug at 10 μM were weaker than those observed with ibrutinib at the same concentration. We conclude that the design of combined treatment schedules of anti-CD20 antibodies with these kinase inhibitors should consider the multiple negative interactions between these two classes of drugs.
NT‐3 promotes growth of lesioned adult rat sensory axons ascending in the dorsal columns of the spinal cord (1999)

The regeneration capacity of spinal cord axons is severely limited. Recently, much attention has focused on promoting regeneration of descending spinal cord pathways, but little is known about the regenerative capacity of ascending axons. Here we have assessed the ability of neurotrophic factors to promote regeneration of sensory neurons whose central axons ascend in the dorsal columns. The dorsal columns of adult rats were crushed and either brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), neurotrophin-3 (NT-3) or a vehicle solution was delivered continuously to the lesion site for 4 weeks. Transganglionic labelling with cholera toxin beta subunit (CTB) was used to selectively label large myelinated Abeta fibres. In lesioned rats treated with vehicle, CTB-labelled fibres were observed ascending in the gracile fasciculus, but these stopped abruptly at the lesion site, with no evidence of sprouting or growth into lesioned tissue. No CTB-labelled terminals were observed in the gracile nucleus, indicating that the lesion successfully severed all ascending dorsal column axons. Treatment with BDNF did not promote axonal regeneration. In GDNF-treated rats fibres grew around cavities in caudal degenerated tissue but did not approach the lesion epicentre. NT-3, in contrast, had a striking effect on promoting growth of lesioned dorsal column axons with an abundance of fibre sprouting apparent at the lesion site, and many fibres extending into and beyond the lesion epicentre. Quantification of fibre growth confirmed that only in NT-3-treated rats did fibres grow into the crush site and beyond. No evidence of terminal staining in the gracile nucleus was apparent following any treatment. Thus, although NT-3 promotes extensive growth of lesioned axons, other factors may be required for complete regeneration of these long ascending projections back to the dorsal column nuclei. The intrathecal delivery of NT-3 or other neurotrophic molecules has obvious advantages in clinical applications, as we show for the first time that dorsal column axonal regeneration can be achieved without the use of graft implantation or nerve lesions.
Thromboxane as a Measure of Cutaneous Vascular Damage Following Irradiation (1994)

The present study was designed to evaluate the role of thromboxane in radiation-induced cutaneous injury and to use the quantitation of cutaneous thromboxane B2 as an indicator of vascular alteration and tissue viability in canine skin. Ten adult intact male dogs underwent epithermal neutron irradiation with or without boron neutron capture. Skin biopsies were obtained from (1) within, (2) the edge of, and (3) outside the radiation field at 5, 8, 11, 14, 21, and 90 days after irradiation. Clinical changes at each sampling time were assigned a numerical score. One-half of each biopsy was assigned a numerical score based on histologic changes. Thromboxane B2 was measured from the second half by enzyme immunoabsorbent assay. Thromboxane B2 concentration paralleled the response of clinical and histologic score over time, indicating the value of thromboxane measurement for evaluation of skin changes secondary to irradiation.
Power Electronics: Converters, Applications and Design (1989)

Partial table of contents: Overview of Power Semiconductor Switches. Computer Simulation of Power Electronic Converters and Systems. GENERIC POWER ELECTRONIC CIRCUITS. dc--dc Switch-Mode Converters. Resonant Converters: Zero-Voltage and/or Zero-Current Switchings. POWER SUPPLY APPLICATIONS. Power Conditioners and Uninterruptible Power Supplies. MOTOR DRIVE APPLICATIONS. dc Motor Drives. Induction Motor Drives. Synchronous Motor Drives. OTHER APPLICATIONS. Residential and Industrial Applications. Optimizing the Utility Interface with Power Electronic Systems. SEMICONDUCTOR DEVICES. Basic Semiconductor Physics. Power Diodes. Power MOSFETs. Thyristors. Emerging Devices and Circuits. PRACTICAL CONVERTER DESIGN CONSIDERATIONS. Snubber Circuits. Gate and Base Drive Circuits. Design of Magnetic Components. Index.
T-cell antigen CD28 interacts with the lipid kinase phosphatidylinositol 3-kinase by a cytoplasmic Tyr(P)-Met-Xaa-Met motif. (1994)

The T-cell antigen CD28 provides a costimulatory signal that is required for T-cell proliferation. T-cell receptor zeta/CD3 engagement without CD28 ligation leads to a state of nonresponsiveness/anergy, thereby implicating CD28 in the control of peripheral tolerance to foreign antigens or tumors. A key unresolved question has concerned the mechanism by which CD28 generates intracellular signals. Phosphatidylinositol 3-kinase (PI 3-kinase) is a lipid kinase with Src-homology 2 (SH2) domain(s) that binds to the platelet-derived growth factor receptor (PDGF-R), an interaction that is essential for signaling by growth factor. In this study, we demonstrate that CD28 binds to PI 3-kinase by means of a Y(P)MXM motif within its cytoplasmic tail. CD28-associated PI 3-kinase was detected by lipid kinase and HPLC analysis as well as by reconstitution experiments with baculoviral-expressed p85 subunit of PI 3-kinase. CD28 bound directly to the p85 subunit without the need for the associated p110 subunit. Site-directed mutagenesis and peptide competition analysis using Y(P)-MXM-containing peptides showed that PI 3-kinase bound to a Y(P)MXM motif within the CD28 cytoplasmic tail (residues 191-194). Mutation of the Y191 within the motif resulted in a complete loss of binding, while mutation of M194 caused partial loss of binding. Binding analysis showed that the CD28 Y(P)-MXM motif bound to the p85 C- and N-terminal SH2 domains with an affinity comparable to that observed for PDGF-R and insulin receptor substrate 1. In terms of signaling, CD28 ligation induced a dramatic increase in the recruitment and association of PI 3-kinase with the receptor. CD28 is likely to use PI 3-kinase as the second signal leading to T-cell proliferation, an event with implications for anergy and peripheral T-cell tolerance.
A Framework for Identification and Resolution of Interoperability Mismatches in COTS-Based Systems (2007)

Software systems today are frequently composed from prefabricated commercial components that provide complex functionality and engage in complex interactions. Such projects that utilize multiple commercial-off-the-shelf (COTS) products often confront interoperability conflicts resulting in budget and schedule overruns. These conflicts occur because of the incompatible assumptions made by developers of these products. Identification of such conflicts and planning strategies to resolve them is critical for developing such systems under budget and schedule constraints. In this paper we present an attribute-based framework that can be used to perform automated interoperability assessment to filter out COTS product combinations whose integration will not be feasible within the project constraints. Our framework is built upon standard definitions of both COTS components and connectors and is intended for use by architects and developers during the design phase of a software system. Our preliminary experience in using the framework indicates an increase in interoperability assessment productivity by 50% and accuracy by 20%.
Real-time face detection/identification for surveillance system (2008)

Face processing is one among the popular problems of detection and recognition. In surveillance system application, the massive data of video is analyzed by complex algorithms that must consider the real-time constraints. In this paper we propose a face processing framework as a component-based architecture for dealing with face online processing. Face detection and classification algorithms are realized based on a Haar-like features and support vector machine (SVM) respectively as a way to efficiently extract a face image and enhance face recognition rates with robustness on different orientation Experimental results are presented with discussion.
Studies on a species-specific epitope in murine, ovine and bovine prion protein (1993)

Transmissible spongiform encephalopathies are fatal neurodegenerative disorders which are linked to abnormal isoforms of the prion protein (PrP), which is expressed in different cells of various mammalian species. Susceptibility to disease and reduced transmission rates upon the first passage to another species are thought to be a result of functional and biochemical differences of the PrP as a consequence of amino acid sequence among species. In 1985 an epidemic of bovine spongiform encephalopathy (BSE) started after accidental transmission of scrapie by feeding infected sheep and goat meat and bone meal products to cattle. In this report we present data demonstrating species-specific epitopes in bovine, ovine and murine PrP that are based on amino acid substitutions at positions 108 and 110. Rabbit antisera to synthetic peptides representing amino acid sequence 108 to 123 of PrP of cattle, sheep and mice reacted strongly with modified PrP of the homologous host but not, or only poorly, with PrP of heterogeneous origin. Cross-reactivity was observed, however, with antisera to bovine and ovine peptide sequences 102 to 117, thus stressing the importance of the location of the amino acid substitution in synthetic peptides used for immunization. Based on these data, BSE PrP and ovine and murine scrapie PrP can be distinguished from each other, and these differences might help elucidate the species barrier effect.
Increased Endoplasmic Reticulum Stress in Atherosclerotic Plaques Associated With Acute Coronary Syndrome (2007)

A cute coronary syndrome (ACS) represents a series of indications of sudden cardiac ischemia that involve a variety of causes, including acute myocardial infarction and unstable angina. 1 ACS usually is associated with thrombus formation in the coronary artery or coronary artery vasospasm, resulting in myocardial ischemia. 2 Thrombus formation may involve platelet adhesion and degranulation on damaged or dysfunctional endothelium overlying the intact or ruptured atherosclerotic plaque, as well as microthrombi. therosclerotic plaque rupture represents a series of deleterious events linked to the breakdown of the fibrous cap. This process may occur as a result of the increased secretion of matrix metalloproteinases by lesion resident macrophages or enhanced apoptotic cell death within the fibrous cap. However, viable smooth muscle cells (SMCs) within the fibrous cap synthesize interstitial collagen fibers that enhance the structural integrity of the plaque and prevent its rupture.
Activation of oxytocin-containing neurons of the paraventricular nucleus (PVN) following generalized seizures (1996)

Due to the complex nature of generalized limbic seizures, marked disturbances in physiological homeostasis occur. Accompanying the motor manifestations which characteristically are associated with generalized limbic seizures, alterations in neuroendocrine, behavioral, and autonomic functions may be observed. The paraventricular nucleus (PVN) of the hypothalamus is known to play a significant role in such neuronal responses to stressful stimuli; however, the effect of seizures on hypothalamic neurons is unknown. We have used the immunocytochemical detection of the Fos protein to anatomically identify neurons in the PVN which are activated following generalized limbic seizures. To induce seizures, rats received intraperitoneal injections of kainic acid or were kindled from the entorhinal cortex. We have demonstrated that elicitation of generalized limbic seizures induces a dramatic number of neurons in the PVN to express the Fos protein. Numerous Fos-immunolabeled neurons were identified in both the parvicellular and magnocellular component of the PVN. In the latter, this study clearly reveals a preferential and selective activation of oxytocin-containing neurons, and it extends and supports the hypothesis that oxytocin plays a role in the body's response to specific stress paradigms. Data suggest that an activation of the oxytocin neuronal system may be part of the adaptive mechanism that enables the hypothalamus to modulate and maintain an adequate response to stressors (e.g., generalized seizures) to regain homeostasis.
Incidence of Unilateral Fertilizations after Low Dose Deep Intrauterine Insemination in Spontaneously Ovulating Sows under Field Conditions (2006)

A new procedure for non-surgical deep intrauterine insemination (DUI) in unrestrained sows hormonally induced to ovulate, has been reported. In comparison with standard artificial insemination (AI), with this procedure, the sperm numbers inseminated can be reduced 20-fold without reducing the reproductive performance of these hormonally treated sows. The present study evaluated, using two experiments, the reproductive performance applying 20-fold different sperm numbers per AI dose using DUI or standard AI in spontaneously ovulating sows, under field conditions. In experiment 1, AI was applied to crossbred sows at 12, 24 and 36 h after onset of spontaneous oestrus using one of the following two regimes: (i) DUI (treatment) with 0.15 x 10(9) fresh boar spermatozoa in 5 ml of Beltsville thawing solution (BTS) extender (n = 95), and (ii) standard cervical AI (control) with 2.85 x 10(9) fresh spermatozoa in 95 ml of BTS extender (n = 95). The farrowing rates of the two groups of sows were statistically similar (NS). However, a decrease (p < 0.002) in litter size and the total number of pigs born alive was observed in sows inseminated with the DUI procedure. In experiment 2, 42 post-weaned oestrus sows were inseminated following the same design described for experiment 1 during spontaneous oestrus. On day 6 after onset of oestrus, the proximal segment of the uterine horns of the sows were flushed under surgery to retrieve eventual embryos and evaluate the success of fertilization per cornua (e.g. occurrence of effective uni- vs bilateral sperm transport rendering uni- or bilateral, complete or partial fertilization). Retrieved embryos were assessed for cleavage and number of accessory spermatozoa. Although identical overall pregnancy rates were achieved in both insemination groups, the percentage of sows with partial bilateral fertilization and unilateral fertilization was markedly higher (p < 0.05) in the DUI group (35%) compared with the control (standard AI) group (5%), with a consequent lower (p < 0.001) percentage of viable early embryos after DUI. The number of accessory spermatozoa in the zona pellucida of the embryos was highly variable, but higher (p < 0.001) in control animals than in DUI-AI. No accessory spermatozoa were found in oocytes retrieved from sows depicting unilateral fertilization. In conclusion, DUI in spontaneously ovulating sows with 0.15 x 10(9) spermatozoa renders similar farrowing rates but a lower litter size compared with use of standard AI with a 20-fold higher sperm dose. The lower litter size ought to be related to a decreased distribution of spermatozoa after DUI leading to a higher incidence of partial bilateral and unilateral fertilization.