gebhart/patrepeval huggingface dataset:
The Cognitive Efficacy of Atypical Antipsychotics in Schizophrenia (1998)

Cognitive dysfunction, a symptom of schizophrenia, has been recently identified as an important measure of outcome in the treatment of this disorder. Drug-mediated symptom improvement, the traditional measure of treatment success for schizophrenia, typically fails to associate with modifications of cognitive dysfunction, resulting in a failure of the patient to reintegrate into society. A paradigm shift is now required in the conceptualization of treatment success away from symptom decrement and towards treatments that improve cognitive function. Clozapine treatment has been shown to provide a significantly greater improvement in several domains of cognitive function, especially attention and verbal fluency, compared with conventional neuroleptics, whereas risperidone appears to have a beneficial effect on working memory. These results may be because of the normalization of dopamine function by clozapine and antagonism of 5HT2 receptors.
The tryphostin AG17 induces apoptosis and inhibition of cdk2 activity in a lymphoma cell line that overexpresses bcl-2. (1997)

Tyrphostins are low molecular weight compounds that specifically inhibit protein tyrosine kinases. We studied the effects of tyrphostins on OCI-Ly8, a cell line derived from a patient with immunoblastic lymphoma that carries the t(14;18) translocation and overexpresses the B-cell lymphoma/leukemia-2 gene (bcl-2). To test the possibility that tyrphostins induce apoptosis in these cells, overcoming the protection rendered by bcl-2, we screened 16 tyrphostins representing different families at a concentration of 0.5-50 microM. We found that AG17 was the most potent in this regard. Cell cycle analysis demonstrated that AG17 induces arrest at the G1 phase followed by apoptosis with general reduction of the intracellular level of tyrosine-phosphorylated proteins. To further elucidate the mechanism of action of AG17, we investigated its effect on some of the key proteins that regulate the cell cycle. Bcl-2 and cdk2 protein levels were not altered with AG17, whereas cdk2 kinase activity, as well as p21 and p16 protein levels, were reduced markedly. These results suggest that the target of AG17 is inactivation of cdk2. Because lymphoma cells with the t(14;18) translocation and bcl-2 overexpression are resistant to chemotherapy, novel drugs selectively able to induce apoptosis in these cells could offer a new approach to the treatment of lymphoma patients.
Shiga‐like Toxin Subunit B (SLTB)‐Enhanced Delivery of Chlorin e6 (Ce6) Improves Cell Killing (2005)

We used Shiga-like toxin B subunit (SLTB) to deliver the photosensitizer, chlorin e6 (Ce6), to Vero cells expressing the Gb3 receptor. Our aim was to provide an example of carrier-enhanced photodynamic cell killing with which to start a systematic consideration of photosensitizer delivery at the subcellular level. SLTB, in contrast to many other potential protein carriers, is delivered intracellularly to the Golgi apparatus and endoplasmic reticulum (ER). Ce6 was chosen both for its phototoxic properties and its potential for covalent conjugation with SLTB. Ce6-SLTB after cleanup contained < or =10% noncovalently bound Ce6. The noncovalent binding of porphyrins and chlorins to protein conjugates has been well documented, and hence the effective cleanup procedure is a significant accomplishment. We demonstrate that Ce6-SLTB enhances delivery of Ce6 to target cells as compared to free Ce6. In Vero cells, Ce6-SLTB was over an order of magnitude more photodynamically toxic than free Ce6. Moreover, we show that in the case of Ce6-SLTB, photosensitizer accumulation is in a combination of subcellular sites including mitochondria, Golgi apparatus, ER and plasma membrane. The occurrence in nature of diverse B subunit binding sites and the possibilities of varied intracellular delivery make optimized use of B subunit carriers attractive.
The Goldilocks Principle: Reading Children's Books with Explicit Memory Representations (2015)

We introduce a new test of how well language models capture meaning in children's books. Unlike standard language modelling benchmarks, it distinguishes the task of predicting syntactic function words from that of predicting lower-frequency words, which carry greater semantic content. We compare a range of state-of-the-art models, each with a different way of encoding what has been previously read. We show that models which store explicit representations of long-term contexts outperform state-of-the-art neural language models at predicting semantic content words, although this advantage is not observed for syntactic function words. Interestingly, we find that the amount of text encoded in a single memory representation is highly influential to the performance: there is a sweet-spot, not too big and not too small, between single words and full sentences that allows the most meaningful information in a text to be effectively retained and recalled. Further, the attention over such window-based memories can be trained effectively through self-supervision. We then assess the generality of this principle by applying it to the CNN QA benchmark, which involves identifying named entities in paraphrased summaries of news articles, and achieve state-of-the-art performance.
Web Services (2003)

Webにおけるビジネスアプリケーション構築の基盤として注目を集めているWebサービスについて説明する。Webサービスは，プログラミング言語やプラットフォームに依存しないアプリケーション・コンポーネント統合を可能にする仕組みであり，急速に発展するビジネスの電子化，統合化の流れの中で生まれてきたものである。本稿では，Webサービスの生まれた背景と特徴に触れ，次にWebサービスの基本的な技術要素であるSOAP，WSDL，UDDIを説明する。さらに，Webサービスをソフトウエア部品の再利用という観点から議論する。最後に，Webサービスに関連する技術の最新動向について触れる。
The development of a tool to assess neonatal pain. (1993)

The objectives of this study were to (1) develop a behavioral assessment tool for the measurement of pain in the preterm and full-term neonate; (2) establish the construct and concurrent validity, interrater reliability, and internal consistency of the tool; and (3) examine the relationship between the pain scores and infant characteristics. Thirty-eight infants contributed to the 90 procedures videotaped for the study. The Neonatal Infant Pain Scale (NIPS) was used to score behavioral responses before, during, and after each intrusive procedure. The significant difference in NIPS scores over time indicates that the scale provides a measurement of intensity of infant responses to intrusive procedures. Concurrent validity was established by correlations, ranging from .53 to .84, between NIPS scores at each minute of observation and scores on the Visual Analogue Scale. Interrater reliability was high: Pearson correlations ranged from .92 to .97 across successive minutes of observation. The six component scores of the NIPS had high internal consistency: Cronbach's alphas were .95, .87, and .88 for before, during, and after the procedures, respectively. Although gestational age and five-minute Apgars were positively associated with NIPS scores over time, there was no association between these factors and responsiveness to pain, as measured by change in NIPS scores from before to during the procedure. Results are discussed in terms of the use of the NIPS in clinical trials and its clinical application in a neonatal intensive care unit.
Certified Professionals (2001)

Although negative selection in the thymus and induction of anergy in the periphery have been widely accepted as mechanisms for controlling autoreactivity, much less attention has been devoted to the role of suppressor T cells in mediating dominant immunologic self-tolerance. In 1995, Sakaguchi et al. 12 made the seminal observation that the transfer of CD4+ T cells which had been depleted of the minor subpopulation (10%) of cells that coexpressed the IL-2 receptor (IL-2R) α-chain (CD25) to nu/nu recipients induced organ-specific autoimmune disease in the majority of recipients. Cotransfer of CD4+CD25+ cells with the CD4+CD25− cells prevented the development of disease. The CD4+CD25+ population was also shown to be solely responsible for the prevention of autoimmunity observed after mice are thymectomized on the third day of life 3.

Rapid progress in the analysis of the regulatory function of the CD4+CD25+ T cell population was made by the development of in vitro model systems that mimicked the function of these cells in vivo 456. Although minor differences were observed in the results obtained by the different groups, it is widely accepted that these cells are both hyporesponsive and suppressive. Further studies demonstrated that the CD4+CD25+ T cells act through an APC-independent mechanism (7, and unpublished observations). Induction of suppressor activity requires that the CD4+ CD25+ cells be activated through their TCR, but once activated, they suppress T cell activation in an antigen-independent manner without a requirement for reactivation through their TCR. Therefore, we proposed 4 that CD4+ CD25+ cells represent a unique lineage of CD4+ T cells that function as “professional suppressor cells.” The publication in this issue of four papers dealing with different aspects of the function of CD4+CD25+ T cells clearly indicates that they have now received their “professional certification.”
Induction of human immunoglobulin secretion. I. Synergistic effect of B cell mitogen Cowan I plus T cell mitogens or factors. (1981)

Synergistic effects of B cell mitogen Staphylococcus bacteria strain Cowan I (Cowan I) plus T cell mitogens in generating immunoglobulin-secreting cells (ISC) from human peripheral blood mononuclear cells (MNC) were investigated. ISC were assayed by reverse plaque-forming cells with protein A-coated red blood cells. Low concentrations of pokeweed mitogen (PWM) plus Cowan I gave superadditive effects on ISC induction, generating 3 to 10 times as many ISC as optimal amounts of either mitogen alone. The mitogens together and separately showed similar kinetics of ISC; synergy was observed at every day tested. Plaque-forming cells of IgM, IgG, and IgA classes all showed strong synergy, together routinely representing 20% of initial MNC. At day 7 of culture, over 80% of non-E-rosetting cells were ISC. Cell donors tested gave these strong responses even if they were low responders to either mitogen alone. Cowan I plus other T cell mitogens, PHA, Con A, and protein A, also provided good signals for B cell activation. Cowan I induced marked proliferation of purified B cells, but T cell-helper signals were required for differentiation to ISC. T cell-helper factor, induced by PWM or PHA, also showed synergistic effects with Cowan I in induction of ISC. Purified B cells did not respond to T cell-helper factor(s) alone to proliferate or differentiate to ISC. These results indicate that optimal ISC induction occurs with a B cell mitogen plus T cell signals acting synergistically.
Nogo-A, a Potent Inhibitor of Neurite Outgrowth and Regeneration (2000)

The lack of regrowth of injured neurons in the adult central nervous system (CNS) of higher vertebrates was accepted as a fact for many decades. In the last few years a very different view emerged; regeneration of lesioned fibre tracts in vivo could be induced experimentally, and molecules that are responsible for inhibition and repulsion of growing neurites have been defined. Mechanisms that link cellular phenomena like growth cone turning or growth cone collapse to intracellular changes in second messenger systems and cytoskeletal dynamics became unveiled. This article reviews recent developments in this field, focusing especially on one of the best characterised neurite out-growth inhibitory molecules found in CNS myelin that was recently cloned: Nogo-A. Nogo-A is a high molecular weight transmembrane protein and an antigen of the monoclonal antibody mAb IN-1 that was shown to promote long-distance regeneration and functional recovery in vivo when applied to spinal cord-injured adult rats. Nogo-A is expressed by oligodendrocytes in white matter of the CNS. With the molecular characterisation of this factor new possibilities open up to achieve structural and functional repair of the injured CNS.
Progress Of Erasable Phase-Change Materials (1989)

The current status of erasable phase-change recording materials is re-viewed. Using GeTeSn-based materials as examples, dynamic perform-ance data are presented along with discussions of the basic physical mechanisms determining media performance. For applications requiring limited number of cycles, phase-change materials have been developed to a very practical level.
Multiphoton Dissociation of Phenylsilane Upon Excitation at 212.5 NM (1996)

The photodissociation processes that follow the photolysis of phenylsilane with a narrow band laser at 212.5 nm were studied by observing photofragment fluorescence spectra in the 200 to 900 nm range. Emission from several excited states of Si atoms was detected together with emissions from the molecular fragments SiH(A 2 ∆) and C 2 (d 3 ∏ g ). Si and SiH emissions show a quadratic dependence with laser energy whereas dependence for C 2 emission is cubic, indicating the participation of two and three photon processes in the formation of the respective fragments. The emission spectra of the molecular fragments provides information about their internal energy content and allows discussion of the possible channels responsible for the appearance of those fragments.
Low-temperature unfolding of a mutant of phage T4 lysozyme. 2. Kinetic investigations (1989)

A disulfide-bridged variant of bacteriophage T4 lysozyme has been found to undergo a low- as well as high-temperature unfolding transition in guanidinium chloride [see Chen and Schellman (1989)]. The kinetics for this process have been followed for several temperatures, a range of guanidinium chloride concentrations, and a number of values of pH. Microscopic rate constants for protein unfolding and refolding were extracted from these data to explore the nature of the cold unfolding transition. The data were interpreted using transition-state theory. It was found that the Arrhenius energy is temperature dependent. The transition state is characterized by (1) a high energy and low entropy compared to the native state, (2) a heat capacity which is closer to the native state than to the unfolded state, and (3) a low exposure to solvent compared to the unfolded state, as judged by its interaction with guanidinium chloride. With increasing concentration of guanidinium chloride, the low-temperature unfolding rate increases strongly, and the refolding rate decreases very strongly.
Lenalidomide efficacy in activated B‐cell‐like subtype diffuse large B‐cell lymphoma is dependent upon IRF4 and cereblon expression (2012)

Durable responses with lenalidomide monotherapy have been reported in patients with non-Hodgkin lymphoma. In relapsed/refractory diffuse large B-cell lymphoma (DLBCL), higher responses were observed in the activated B-cell-like (ABC) subtype than in the germinal centre B-cell-like subtype. Herein, the molecular mechanisms involved in the differential efficacy of lenalidomide in DLBCL subtypes were investigated. Using DLBCL cell lines, lenalidomide treatment was found to preferentially suppress proliferation of ABC-DLBCL cells in vitro and delay tumour growth in a human tumour xenograft model, with minimal effect on non-ABC-DLBCL cells. This tumouricidal effect was associated with downregulation of interferon regulatory factor 4 (IRF4), a hallmark of ABC-DLBCL cells. IRF4 inhibition by lenalidomide induced downregulation of B-cell receptor (BCR)-dependent NF-κB. Whereas IRF4-specific small, interfering RNA mimicked the effects of lenalidomide reducing NF-κB activation, IRF4 overexpression enhanced NF-κB activation and conferred resistance to lenalidomide. These findings indicate the crucial role of IRF4 inhibition in lenalidomide efficacy in ABC cells. Furthermore, lenalidomide-induced IRF4 downregulation required the expression of cereblon, a molecular target of lenalidomide. Taken together, these findings suggest that lenalidomide has direct antitumour activity against DLBCL cells, preferentially ABC-DLBCL cells, by blocking IRF4 expression and the BCR-NF-κB signalling pathway in a cereblon-dependent manner.
Reducing shading on GPUs using quad-fragment merging (2010)

Current GPUs perform a significant amount of redundant shading when surfaces are tessellated into small triangles. We address this inefficiency by augmenting the GPU pipeline to gather and merge rasterized fragments from adjacent triangles in a mesh. This approach has minimal impact on output image quality, is amenable to implementation in fixed-function hardware, and, when rendering pixel-sized triangles, requires only a small amount of buffering to reduce overall pipeline shading work by a factor of eight. We find that a fragment-shading pipeline with this optimization is competitive with the REYES pipeline approach of shading at micropolygon vertices and, in cases of complex occlusion, can perform up to two times less shading work.
Decreased expression of the memory marker CD26 on both CD4+ and CD8+ T lymphocytes of HIV-infected subjects. (1993)

Using a novel anti-CD26 (or anti-dipeptidyl peptidase IV) monoclonal antibody, we showed that the absolute numbers and the proportions of T4 and T8 cells expressing CD26 were significantly lower in HIV-infected persons than in controls. The absolute number of CD26+ T4 cells decreased according to disease progression, whereas the number of CD26+ T8 cells was low throughout all clinical stages. These trends were similar in CD26 dim and bright positive T-cell subsets. In both controls and HIV-positive subjects, the CD26 bright positive T cells were restricted to the CD45RO+ subset and preferentially co-expressed CD25 but largely lacked HLA-DR and CD38. Recall antigen-responsive cells from seronegative individuals were shown to co-express CD26 and CD45RO. The deficient CD26 expression on T8 cells from HIV-infected subjects could be normally upregulated after in vitro stimulation. In contrast to decreased T-cell-bound CD26, the enzymatic activity of plasma CD26/dipeptidyl peptidase IV was unchanged in HIV-infected patients compared with controls. We conclude that HIV infection leads to a deficient in vivo co-expression of CD26 bright and CD45RO on T cells. We speculate that this deficiency might play a part in the decrease of immunological memory during HIV infection.
Spatial Distribution of Phosphate Species in Mature and Newly Generated Mammalian Bone by Hyperspectral Raman Imaging (1999)

Hyperspectral Raman images of mineral components of trabecular and cortical bone at 3 μm spatial resolution are presented. Contrast is generated from Raman spectra acquired over the 600-1400 cm-1 Raman shift range. Factor analysis on the ensemble of Raman spectra is used to generate descriptors of mineral components. In trabecular bone independent phosphate (PO4-3) and monohydrogen phosphate (HPO4-2) factors are observed. Phosphate and monohydrogen phosphate gradients extend from trabecular packets into the interior of a rod. The gradients are sharply defined in newly regenerated bone. There, HPO4-2 content maximizes near a trabecular packet and decreases to a minimum value over as little as a 20 μm distance. Incomplete mineralization is clearly visible. In cortical bone, factor analysis yields only a single mineral factor containing both PO4-3 and HPO4-2 signatures and this implies uniform distribution of these ions in the region imaged. Uniform PO4-3 and HPO4-2 distribution is verified by spectral band integration. © 1999 Society of Photo-Optical Instrumentation Engineers.
TLR-Activated B Cells Suppress T Cell-Mediated Autoimmunity (2008)

TLR sense microbial infections, and control activation of immune responses. Dendritic cells, macrophages, and B lymphocytes express TLR and the TLR-signaling adaptor protein MyD88. The impact of TLR-activated B cells on T cell-mediated inflammation is unknown. In this study, we have used mice carrying B cell-restricted deficiencies in MyD88 or in distinct TLR to examine the impact of TLR-activated B cells on a T cell-mediated autoimmune disease, experimental autoimmune encephalomyelitis (EAE). We demonstrate that TLR-signaling in B cells suppresses inflammatory T cell responses (both Th1 and Th17), and stimulates recovery from EAE. Only certain TLR are required on B cells for resolution of EAE, and these are dispensable for disease initiation, indicating that a category of TLR agonists preferentially triggers a suppressive function in B cells and thereby limits autoimmune disease. The TLR agonists controlling the regulatory function of B cells are provided by components of Mycobacterium tuberculosis present in the adjuvant. Thus, MyD88 signaling in B cells antagonizes MyD88 signaling in other cells, which drives differentiation of Th17 cells and is required for induction of EAE. Altogether, our data indicate that B cells link recognition of microbial products via TLR to suppression of a T cell-mediated autoimmune disease.
Glycosyl Fluorides Can Function as Substrates for Nucleotide Phosphosugar-dependent Glycosyltransferases (1999)

alpha-Galactosyl fluoride is shown to function as a substrate, in place of uridine-5'-diphosphogalactose, for the alpha-galactosyltransferase from Neisseria meningitidis. The reaction only occurs in the presence of catalytic quantities of uridine 5'-diphosphate. In the presence of galactosyl acceptors, the expected oligosaccharide product is formed in essentially quantitative yields, reaction having been performed on multi-milligram scales. In the absence of a suitable acceptor, the enzyme synthesizes uridine-5'-diphosphogalactose, as demonstrated through a coupled assay in which uridine-5'-diphosphogalactose is converted to uridine-5'-diphosphoglucuronic acid with conversion of NAD to NADH. These glycosyl fluoride substrates therefore offer the potential of an inexpensive alternative donor substrate in the synthesis of oligosaccharides as well a means of generating steady state concentrations of nucleotide diphosphate sugars for in situ use by other enzymes. Further, they should prove valuable as mechanistic probes.
Localization of the HU Protein on the Escherichia coli Nucleoid (1978)

We recently described the isolation and characterization of a low-molecular-weight DNA-binding protein, HU, from Escherichia coli (Rouvière-Yaniv and Gros 1975). In some of its properties, as well as in its amino acid composition, this protein resembles the eukaryotic histone H2B. Like histones, this protein is highly conserved in prokaryotes. Closely related proteins showing immunological cross-reactivity with the anti-HU serum were isolated from several strains of blue-green algae (Haselkorn and Rouvière-Yaniv 1976; Rouvière-Yaniv et al. 1977) as well as from Bacillus subtilis (J. Rouvière-Yaniv and F. Le Hegarat, unpubl.). Analysis of the N-terminal portions of both E. coli HU (B. Laine et al., unpubl.) and algal HU (A. Aitken et al., unpubl.) showed a high degree of sequence conservation between these two proteins. Among the first 25 amino acids, ten residues are identical, six are conservative changes, and three can be related by a single base change in the DNA sequence...