gebhart/patrepeval huggingface dataset:
Evidence of interactions between melanocortin and opioid systems in regulation of feeding (2001)

The aim of our experiments was to study the presumed functional relationship between the melanocortin and opioid systems in the regulation of food intake. We determined that a non-selective opioid receptor antagonist, naltrexone, at relatively low doses, decreases food intake induced by i.c.v. agouti-related protein (Agrp). We also observed that peripheral injection of naltrexone at a dose known to produce anorexigenic responses induced c-Fos immunoreactivity in significantly more arcuate nucleus alpha-MSH neurons than observed in control animals. The results of our study support the notion that the melanocortin and opioid systems interact in the regulation of food intake. Based on these data we speculate that opioid peptides suppress alpha-MSH-dependent satiety mechanisms; conversely, it is possible that the orexigenic action of Agrp is mediated via opioid dependent circuitry.
Apollo: scalable and coordinated scheduling for cloud-scale computing (2014)

Efficiently scheduling data-parallel computation jobs over cloud-scale computing clusters is critical for job performance, system throughput, and resource utilization. It is becoming even more challenging with growing cluster sizes and more complex workloads with diverse characteristics. This paper presents Apollo, a highly scalable and coordinated scheduling framework, which has been deployed on production clusters at Microsoft to schedule thousands of computations with millions of tasks efficiently and effectively on tens of thousands of machines daily. The framework performs scheduling decisions in a distributed manner, utilizing global cluster information via a loosely coordinated mechanism. Each scheduling decision considers future resource availability and optimizes various performance and system factors together in a single unified model. Apollo is robust, with means to cope with unexpected system dynamics, and can take advantage of idle system resources gracefully while supplying guaranteed resources when needed.
High Frequency of Epidermal Growth Factor Receptor Mutations with Complex Patterns in Non–Small Cell Lung Cancers Related to Gefitinib Responsiveness in Taiwan (2004)

Data from our study would predict a higher gefitinib response rate in lung adenocarcinoma patients in Chinese and, possibly, other East Asian populations. The tight association with adenocarcinoma and the high frequency of mutations raise the possibility that EGFR mutations play an important role in the tumorigenesis of adenocarcinoma of lung, especially in East Asians.
Interleukin 4 induces synthesis of IgE and IgG4 in human B cells (1989)

Interleukin (IL)4 has been shown to regulate the IgG subclasses and induce IgE production in splenic mouse B cells. Here we show that IL4 and phorbol 12-myristate 13-acetate (PMA) induce, on a per cell basis, very high IgE secretion in purified human B cells by using a mouse thymoma (EL4) co-culture method. In addition, a marked increase in the number of IgG4-producing cells was also observed. Furthermore, IL2 could synergize with IL4 and PMA in the production of IgE. By using limiting dilution analysis, a considerable increase in the precursor frequency for IgE was found when IL4 and PMA were added to cultures as compared to cultures with PMA only. This indicates that IL4 induces an isotype switch in human B cells.
The control of DNA synthesis in primary cultures of hepatocytes from adult and young rats: Interactions of extracellular matrix components, epidermal growth factor, and the cell cycle (1987)

Hepatocytes from adult and 4-week-old rats cultured on one of several extracellular matrix components were stimulated to replicate by epidermal growth factor (EGF). DNA synthesis was increased at 44-48 hr in adult hepatocytes and at 24, 48, and 72 hr in hepatocytes from young rats when EGF was added 2 hr after explantation. When EGF was added at 24 hr, maximal DNA synthesis of adult hepatocytes was observed at 48 hr, whereas that of 4-week-old hepatocytes was seen at 48 and 72 hr. Ten ng EGF per ml was the optimal concentration for maximal DNA synthesis in both adult and young cells. DNA synthesis decreased with increasing cell density, but this effect was less in hepatocytes from young than in those from adults. When hepatocytes were cultured on substrata consisting of individual extracellular matrix components, neither the time that adult cells needed to respond to EGF nor the time from stimulation by EGF to the peak of maximal DNA synthesis was altered in either adult or young cells. The optimal EGF concentration for maximal DNA synthesis and the cell density control of replication were also not altered by the substrata used. Substrata made from each of the extracellular matrix components studied enhanced DNA synthesis of adult and young hepatocytes stimulated by EGF in the following decreasing order: fibronectin, type IV collagen, type I collagen, and laminin. In both adult and young hepatocytes the enhancement of DNA synthesis was greatest when cultured on fibronectin. Thus the initiation and magnitude of DNA synthesis in primary cultures of rat hepatocytes were altered both by the age of the donor and the substratum on which the cells were explanted.
The Simultaneous Analysis of Proteins, Lipids, and Diterpenoid Resins Found in Cultural Objects. (2007)

We report a GC-MS method for the simultaneous analysis of proteins oil, and diterpenoid resins found in cultural objects. The method was initially designed for protein analysis of protenaceous paints and adhesives and involves acid hydrolysis as the first step. The amino acids in the protein hydrolysates, thus obtained, are treated with propan-l-ol/ hydrogen chloride and then pentafluoropropionic anhydride. The procedure was found also to yield the propyl esters of fatty acids derived from lipids and diterpenoid acids derived from natural resins, and thus allows the choice of a single method for the analysis of artists media which contain either oil s or proteins or mixtures of both proteins and oils or even resins. Thus natural mixtures such as egg yolk and also mixtures made by the artist such as animal glue/seed oil emulsions can be analysed. Coupled with FTIR analysis of paints and the staining of cross sections, to indicate layer structure the method can help to elucidate the paints and adhesives used by artists.
A CMOS-compatible Process for Fabricating Electrical Through-vias in Silicon (2006)

In the past, traditional CMOS scaling has been one of the principal levers to achieve increased system-level performance. Today, scaling is becoming increasingly difficult and less effective, and a range of new two- and three-dimensional silicon integration technologies are needed to support next-generation systems. A silicon-carrier system-on-package (SOP) is an advanced packaging solution, enabling interconnection between ICs and other devices at densities far beyond those of current first-level packaging. Silicon-carrier employs fine pitch Cu damascene wiring, high-density solder pads/joins and high-yielding electrical through-vias. A novel approach to fabricating robust though-vias in silicon is described. The key design feature enabling large-area, uniform arrays to be produced with high yield is the annular via shape. As compared to a standard cylindrical via shape, the annular via is easier to integrate into a standard CMOS copper back-end-of-the-line (BEOL) process flow. Two process flows are compared: the first having the conductor metal within the gap of the insulated annulus itself, the second having a conducting metal core enclosed within the inner wall of the annulus. For the first process flow, two annular conductors, plated copper and CVD tungsten, are compared in terms of ease of integration, yield and susceptibility to failure during thermal stressing. Large area (45 /spl times/ 48 mm) silicon carrier modules containing more than 51,000 electrically measurable through-vias are used to compare overall yield and robustness of each process. Results on deep thermal cycling, current carrying capacity and thermomechanical modeling are discussed. Wafer-level via testing is used to statistically distinguish between via chain opens caused by bond and assembly issues versus failures in the vias or integrated wiring structures. Through-via resistances on the order of /spl sim/10 m/spl Omega/ are typical, and through-via yields of 99.98% at module level have been demonstrated.
The Myosin I SH3 Domain and TEDS Rule Phosphorylation Site are Required for In Vivo Function (1998)

The class I myosins play important roles in controlling many different types of actin-based cell movements. Dictyostelium cells either lacking or overexpressing amoeboid myosin Is have significant defects in cortical activities such as pseudopod extension, cell migration, and macropinocytosis. The existence of Dictyostelium null mutants with strong phenotypic defects permits complementation analysis as a means of exploring important functional features of the myosin I heavy chain. Mutant Dictyostelium cells lacking two myosin Is exhibit profound defects in growth, endocytosis, and rearrangement of F-actin. Expression of the full-length myoB heavy chain in these cells fully rescues the double mutant defects. However, mutant forms of the myoB heavy chain in which a serine at the consensus phosphorylation site has been altered to an alanine or in which the C-terminal SH3 domain has been removed fail to complement the null phenotype. The wild-type and mutant forms of the myoB heavy chain appeared to be properly localized when they were expressed in the myosin I null mutants. These results suggest that the amoeboid myosin I consensus phosphorylation site and SH3 domains do not play a role in the localization of myosin I, but are absolutely required for in vivo function.
The Misty Land of Ideas and the Light of Dialogue: An Anthology of Contemporary Philosophy: Western & Islamic, Ali Paya (2018)

The Misty Land of Ideas and the Light of Dialogue is an edited collection of essays in comparative philosophy which presents the reader with an engaging dialogue between the famous philosophers of the Western and Islamic philosophical traditions. The philosophers discussed in the book are all pivotal figures of the Eastern and Western intellectual and spiritual heritage.
Investigations of Reactions between Chiral Molybdenum Imido Alkylidene Complexes and Ethylene:  Observation of Unsolvated Base-Free Methylene Complexes, Metalacyclobutane and Metalacyclopentane Complexes, and Molybdenum(IV) Olefin Complexes (2004)

In this paper we explore reactions between 13CH213CH2 and the imido alkylidene complexes, Mo(NAr)(CHCMe2Ph)[(S)-Biphen] (3a; NAr = N-2,6-i-Pr2C6H3), Mo(NArCl)(CHCMe3)[(S)-Biphen] (3b; NArCl = N-2,6-Cl2C6H3), Mo(NAd)(CHCMe2Ph)[(S)-Biphen] (3c; NAd = N-1-adamantyl), Mo(NAr)(CHCMe2Ph)[(R)-Benz2Bitet] (3d), and Mo(NArCl)(CHCMe2Ph)[(R)-Benz2Bitet] (3e). (See text for a description of Biphen and Benz2Bitet.) Under a variety of conditions and for various combinations of imido, alkylidene, and diolate ligands, we have observed α-substituted molybdacyclobutanes Mo(NR)(*CH2*CH2CHCMe2Ph)[diolate] (*C = 13C), unsubstituted molybdacyclobutanes Mo(NR)(*CH2*CH2*CH2)[diolate], olefin complexes Mo(NR)(*CH2CHR)[diolate] (R = H or CMe2Ph), molybdacyclopentane complexes Mo(NR)(*CH2*CH2*CH2*CH2)[diolate], and base-free methylene complexes Mo(NR)(*CH2)[diolate]. We also have crystallographically characterized a molybdenum ethylene complex derived from a biphenolate complex, Mo(N-2,6-Cl2C6H3)(CH2CH2)[rac-Biphen](Et2O).
Mechanisms of antiepileptic drug resistance (2003)

Purpose of review The present review considers new developments in the study and our understanding of resistance to treatment with antiepileptic drugs in epilepsy. Recent findings Studies suggest that mechanisms of resistance to drug treatment that operate in other diseases may also be relevant in human and animal drug-resistant epilepsy. Immunohistochemical and molecular genetic data show that there is overexpression of a number of genes and proteins that mediate nonspecific resistance to drug treatment. In particular, there is upregulation of P-glycoprotein and multidrug resistance-associated proteins 1 and 2. These proteins appear to be expressed in cerebral parenchymal cell populations that do not normally do so. Work in animal models suggests that these proteins are able to reduce the local concentration of antiepileptic drugs. Although these proteins are therefore good candidates for mediators of drug resistance, there is still limited proof that they are functionally important in human drug-resistant epilepsy. Summary Careful attention needs to be given to the identification and confirmation of the practical importance of mechanisms postulated to underlie drug resistance in human epilepsy. If certain mechanisms are shown to be involved, then new therapeutic options for drug-resistant human epilepsy may be forthcoming.
Cross-lingual experiments with phone recognition (1993)

Research on speaker-independent continuous phone recognition for both French and English is presented. The phone accuracy is assessed on the BREF corpus for French, and on the Wall Street Journal (WSJ) and TIMIT corpora for English. Cross-language differences concerning language properties are presented. It is found that French is easier to recognize at the phone level (the phone error for BREF is 23.6% vs. 30.1% for WSJ), but harder to recognize at the lexical level due to the larger number of homophones. Experiments with signal analysis indicate that a 4 kHz signal bandwidth is sufficient for French, whereas 8 kHz is needed for English. Phone recognition is a powerful technique for language, sex, and speaker identification. With 2 s of speech, the language can be identified with better than 99% accuracy. Sex-identification for BREF and WSJ is error-free. Speaker identification accuracies of 98.2% on TIMIT (462 speakers) and 99.1% on BREF (57 speakers) were obtained with one utterance per speaker. 100% accuracies were obtained with two utterances per speaker.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Two Novel IL-1 Family Members, IL-1δ and IL-1ε, Function as an Antagonist and Agonist of NF-κB Activation Through the Orphan IL-1 Receptor-Related Protein 2 (2001)

IL-1 is of utmost importance in the host response to immunological challenges. We identified and functionally characterized two novel IL-1 ligands termed IL-1delta and IL-1epsilon. Northern blot analyses show that these IL-1s are highly abundant in embryonic tissue and tissues containing epithelial cells (i.e., skin, lung, and stomach). In extension, quantitative real-time PCR revealed that of human skin-derived cells, only keratinocytes but not fibroblasts, endothelial cells, or melanocytes express IL-1delta and epsilon. Levels of keratinocyte IL-1delta are approximately 10-fold higher than those of IL-1epsilon. In vitro stimulation of keratinocytes with IL-1beta/TNF-alpha significantly up-regulates the expression of IL-1epsilon mRNA, and to a lesser extent of IL-1delta mRNA. In NF-kappaB-luciferase reporter assays, we demonstrated that IL-1delta and epsilon proteins do not initiate a functional response via classical IL-1R pairs, which confer responsiveness to IL-1alpha and beta or IL-18. However, IL-1epsilon activates NF-kappaB through the orphan IL-1R-related protein 2 (IL-1Rrp2), whereas IL-1delta, which shows striking homology to IL-1 receptor antagonist, specifically and potently inhibits this IL-1epsilon response. In lesional psoriasis skin, characterized by chronic cutaneous inflammation, the mRNA expression of both IL-1 ligands as well as IL-1Rrp2 are increased relative to normal healthy skin. In total, IL-1delta and epsilon and IL-1Rrp2 may constitute an independent signaling system, analogous to IL-1alphabeta/receptor agonist and IL-1R1, that is present in epithelial barriers of our body and takes part in local inflammatory responses.
Two genes, pemK and pemI, responsible for stable maintenance of resistance plasmid R100 (1988)

Plasmid R100 was found to have two genes, designated pemK and pemI, that were responsible for its stable inheritance during cell division. They are located near the region that is essential for autonomous replication. Under conditions that inhibit replication of R100 derivatives, the plasmid containing these pem genes gave only a few segregants in viable cells and increased the number of nonviable cells in the population, suggesting that a product from the pem region stabilized the plasmid by killing plasmid-free segregants. Inactivation of one of the two translational open reading frames in the pem region caused the loss of the killing function, and thus, the open reading frame is a gene designated pemK, which encodes the killing factor. The coexistence of the pem+ plasmid with a high-copy-number plasmid carrying the other open reading frame inhibited stabilization, and thus, the second open reading frame is a gene designated pemI, which encodes the inhibitor which might control the killing function of pemK. It is likely that the two open reading frames were transcribed from a promoter. There were no significant homologies in DNA sequences between the pem gene of R100 and the genes previously shown to be responsible for the stable inheritance of the other plasmids.
Complete amino acid sequence of rat brain hexokinase, deduced from the cloned cDNA, and proposed structure of a mammalian hexokinase. (1989)

The complete amino acid sequence for the type I isozyme of hexokinase from rat brain has been deduced from the nucleotide sequence of cloned cDNA. The nucleotide sequence of 91 bases in the 5' untranslated region as well as that of the entire 3' untranslated region preceding the poly(A) sequence have also been determined. The N- and C-terminal halves of brain hexokinase show extensive sequence similarity to each other and to yeast hexokinase. These results provide direct support for the proposal that the mammalian hexokinases of approximately 100 kDa have evolved by a process of duplication and fusion of a gene encoding an ancestral hexokinase similar to the yeast enzyme of approximately 50 kDa. Taking this similarity in sequence to indicate basic similarity in structure between the N- and C-terminal regions of brain hexokinase and the yeast enzyme, a proposed structure for the mammalian hexokinase has been developed by fusing two molecules of yeast hexokinase, whose structure has previously been determined by x-ray crystallographic studies. Various features of the model are shown to be consistent with experimental observations bearing on the structure of the brain enzyme.
Epratuzumab, a Humanized Monoclonal Antibody Targeting CD22 (2003)

Purpose: Epratuzumab is a novel humanized antihuman CD22 IgG1 antibody that has recently shown promising clinical activity, both as a single agent and in combination with rituximab, in patients with non-Hodgkin’s lymphomas (NHL). In an attempt to better understand the mode of action of epratuzumab, the antibody was tested in vitro in a variety of cell-based assays similar to those used to evaluate the biological activity of other therapeutic monoclonal antibodies, including rituximab. In this report, we present epratuzumab activities as they relate to binding, signaling, and internalization of the receptor CD22.

Methods: Chinese hamster ovary-expressed CD22 extracellular domain was used to measure epratuzumab affinity on Biacore. CD22 receptor density and internalization rate were measured indirectly using a monovalently labeled, noncompeting (with epratuzumab) anti-CD22 antibody on Burkitt lymphoma cell lines, primary B cells derived from fresh tonsils, and B cells separated from peripheral blood samples obtained from patients with chronic lymphocytic leukemia or healthy volunteers. Epratuzumab-induced CD22 phosphorylation was measured by immunoprecipitation/Western blot and compared with that induced by anti-IgM stimulation.

Results: Epratuzumab binds to CD22-extracellular domain, with an affinity of K D = 0.7 nm. Binding of epratuzumab to B cell lines, or primary B cells from healthy individuals and patients with NHL, results in rapid internalization of the CD22/antibody complex. Internalization appears to be faster at early time points in cell lines than in primary B cells and NHL patient-derived B cells, but the maximum internalization reached is comparable for all B cell populations after several hours of treatment and appears to reach saturation at antibody concentrations of 1–5 μg/ml. Finally, epratuzumab binding results in modest but significant CD22 phosphorylation.

Conclusions: Epratuzumab represents an excellent anti-CD22 ligating agent, highly efficacious in inducing CD22 internalization, and can induce phosphorylation. Although we cannot unequivocally demonstrate here that epratuzumab-induced internalization and signaling of CD22 directly contribute to its therapeutic efficacy, these properties are the fundamental characteristics of the target CD22 and its interaction with epratuzumab. Similar results were observed when epratuzumab was tested in vitro on Burkitt B cell lines as well as on primary normal B cells and neoplastic B cells separated from fresh peripheral blood samples from patients with chronic lymphocytic leukemia.
The role of tumour necrosis factor‐α in acquired immunodeficiency syndrome (1990)

Tumour necrosis factor-alpha (TNF) is a primary mediator in the pathogenesis of infection, tissue injury and inflammation. It is synthesised by various activated, phagocytic and non-phagocytic cells, and a wide variety of infectious or inflammatory stimulae are capable of triggering TNF biosynthesis. Recent studies indicate that overproduction of TNF in septicaemia is a critical step in triggering septic shock and multiple organ damage. Intravenous administration of recombinant human TNF induced the same types of derangement in cardiovascular homatologic, inflammatory and metabolic homeostasis that are found with endotoxic or septic shock. Chronic TNF production causes a potentially lethal syndrome of cachexia, anaemia, and protein and lipid wasting. Several investigators have recently demonstrated elevated levels of serum TNF in patients with acquired immunodeficiency syndrome (AIDS), these levels being closely correlated with the severity of the disease. This review discusses the role of TNF in the pathophysiology of AIDS and of several disorders associated with the latter. In addition, it discusses the interactions between TNF and several agents used in AIDS therapy, and suggests the use of TNF-antagonists in combination as a therapeutic regimen for AIDS patients.
New developments in the pathology of malignant lymphoma. A review of the literature published from January–April 2016 (2016)

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