gebhart/patrepeval huggingface dataset:
Anthrax toxin edema factor: a bacterial adenylate cyclase that increases cyclic AMP concentrations of eukaryotic cells. (1982)

Anthrax toxin is composed of three proteins: protective antigen (PA), lethal factor (LF), and edema factor (EF). These proteins individually cause no known physiological effects in animals but in pairs produce two toxic actions. Injection of PA with LF causes death of rats in 60 min, whereas PA with EF causes edema in the skin of rabbits and guinea pigs. The mechanisms of action of these proteins have not been determined. It is shown here that EF is an adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] produced by Bacillus anthracis in an inactive form. Activation occurs upon contact with a heat-stable eukaryotic cell material. The specific activity of the resulting adenylate cyclase nearly equals that of the most active known cyclase. In Chinese hamster ovary cells exposed to PA and EF, cAMP concentrations increase without a lag to values about 200-fold above normal, remain high in the continued presence of toxin, and decrease rapidly after its removal. The increase in cAMP is completely blocked by excess LF. It is suggested that PA interacts with cells to form a receptor system by which EF and perhaps LF gain access to the cytoplasm.
Les taux d'interet applicables aux microcredits (1997)

This paper outlines a method for estimating the interest rate that an microfinance institution (MFI) will need to realize on its loans, if it wants to fund its growth primarily with commercial funds at some point in the future. The model presented is simplified. However, it yields an approximation that should be useful for many MFIs, especially younger ones. Each component of the model is explained and then illustrated with the MicroFin (a young institution serving 1,000 active microloan customers) example.
Alteration of the tumorigenic and metastatic properties of neoplastic cells is associated with the process of calcium phosphate-mediated DNA transfection. (1987)

During the course of studies designed to assess the effect of human Ha-ras gene expression on the malignant behavior of transfected mouse tumor cells we noted that the process of Ca3(PO4)2-mediated DNA transfection was itself associated with profound alterations in tumorigenic or metastatic behavior. The cell line used as a recipient for these studies was a tumorigenic nonmetastatic CBA/J mouse mammary adenocarcinoma line called SP1. When cotransfected with plasmids containing the neo gene (pSV2neo) and the activated Ha-ras gene (pT24-c3), cells from the pooled (5-10 colonies) G418-resistant colonies gave rise to spontaneous lung metastases in 85% of mice after subcutaneous inoculation. However, we noted that 17% of control mice inoculated with G418-resistant pSV2neo-transfected SP1 cells also had lung metastases and that this number approached 100% as the inoculum comprised a greater pool size (50-100 colonies). When cell lines established from isolated pSV2neo-transfected colonies were examined, 3/16 were found to be metastatic. We also found that 3/16 clones grew slowly, or not at all, in CBA/J mice, whereas they grew readily in athymic (nude) mice. The increase in immunogenicity of two out of three of these latter clones was accompanied by expression of the class I H-2Dk major histocompatibility complex antigen that was not detectable in the parental SP1 cells. At least some of these results would appear to be due to exposure to Ca3(PO4)2 alone, as we found that it resulted in 5/20 (25%) clones manifesting metastatic properties. Our results suggest that heritable changes in malignant behavior of transfected tumor cells can be observed at high frequency subsequent to the process of Ca3(PO4)2-mediated DNA transfection, and these changes may be brought about in part by inherited disturbances in expression of recipient cell genes.
Selective Regulation of Lyn Tyrosine Kinase by CD45 in Immature B Cells (1995)

It has been well established that protein-tyrosine phosphatase CD45 is critically involved in the regulation of initial tyrosine phosphorylation and effector functions of T and B cells. However, the signaling pathway governed by CD45 is not completely understood. In B cells, it has not been unequivocally resolved as to which protein-tyrosine kinases (PTKs) associated with B cell antigen receptor are regulated by CD45 in intact cells. As a first step toward the elucidation of CD45-initiated signaling events, we have tried to identify physiological substrates for CD45 by analyzing PTK activity in CD45-deficient clones recently generated from the immature B cell line WEHI-231. The results clearly demonstrated that among PTKs examined (Lyn, Lck, and Syk), only Lyn kinase is dysregulated in the absence of CD45 such that without B cell antigen receptor ligation, Lyn is hyperphosphorylated and activated in CD45-negative clones. Thus, Lyn seems to be a selective in vivo substrate for CD45 in immature B cells.
Autophagy in human keratinocytes: an early step of the differentiation? (2010)

Studies have established that autophagy constitutes an efficient process to recycle cellular components and certain proteins. The phenomenon was demonstrated primarily in response to nutrient starvation, and there are increasing evidences that it is implied in differentiation. Keratinocyte differentiation was going along an activation of lysosomal enzymes and organelle clearance, and terminal steps are sometimes described as a specialized form of cell death leading to corneocytes. We examined whether initiation of the process in human keratinocyte HaCaT involves autophagy. The KSFM™ culture medium was substituted by M199, which contains a low glucose concentration but a high calcium level (known to induce differentiation). Metabolic stress reduced enhanced cell number in G(1) phase, without apoptotic features (ΔΨmt and membrane integrity are unchanged). Morphological changes were associated with a lower integrin ß1 expression and modifications of protein levels involved in keratinocyte differentiation (involucrin, keratin K10 and ΔNp63α). Whereas autophagic signalling was supported by SIRT1 and pAMPK (T172) increase according to time kinetic, which led to the disappearance of mTOR phosphorylated on S2448 residue. The significant Bcl-X(L) level reduction with stress promoted autophagy, by the release of Beclin-1, whereas ATG5-ATG12 and LC3-II that are involved in autophagosome formation were enhanced significantly. Then, the level of lysosomal protein cathepsin B rose to execute autophagy. Kinetic studies established that autophagy would constitute an early signalling process required for keratinocyte commitment in differentiation pathway.
Ox40 Costimulation Enhances the Development of T Cell Responses Induced by Dendritic Cells In Vivo (2002)

Dendritic cells (DCs) are bone marrow-derived APCs that display unique properties aimed at stimulating naive T cells. Several members of the TNF/TNFR families have been implicated in T cell functions. In this study, we examined the role that Ox40 costimulation might play on the ability of DCs to regulate CD4(+) and CD8(+) T cell responses in vivo. Administration of anti-mouse Ox40 mAb enhanced the Th response induced by immunization with Ag-pulsed DCs, and introduced a bias toward a Th1 immune response. However, anti-Ox40 treatment enhanced the production of Th2 cytokines in IFN-gamma(-/-) mice after immunization with Ag-pulsed DCs, suggesting that the production of IFN-gamma during the immune response could interfere with the development of Th2 lymphocytes induced by DCs. Coadministration of anti-Ox40 with DCs during Ag rechallenge enhanced both Th1 and Th2 responses induced during a primary immunization with DCs, and did not reverse an existing Th2 response. This suggests that Ox40 costimulation amplifies an ongoing immune response, regardless of Th differentiation potential. In an OVA-TCR class II-restricted adoptive transfer system, anti-Ox40 treatment greatly enhanced the level of cytokine secretion per Ag-specific CD4(+) T cell induced by immunization with DCs. In an OVA-TCR class I-restricted adoptive transfer system, administration of anti-Ox40 strongly enhanced expansion, IFN-gamma secretion, and cytotoxic activity of Ag-specific CD8(+) T cells induced by immunization with DCs. Thus, by enhancing immune responses induced by DCs in vivo, the Ox40 pathway might be a target for immune intervention in therapeutic settings that use DCs as Ag-delivery vehicles.
CD16+ monocytes in patients with cancer: spontaneous elevation and pharmacologic induction by recombinant human macrophage colony- stimulating factor (1995)

The small subset of circulating monocytes that express the maturation-associated CD16 antigen has recently been reported to be elevated in patients with bacterial sepsis. We now show that this novel CD16+ monocyte population is also spontaneously expanded in patients with cancer. We studied 14 patients with metastatic gastrointestinal carcinoma enrolled ina clinical trial of recombinant human macrophage colony-stimulating factor (rhMCSF) plus monoclonal antibody D612. We found that before any cytokine treatment, 12 of 14 patients constitutively displayed significant elevations in both the percentage and the absolute number of CD16+ monocytes, as compared with both normal subjects and ill patients with elevated monocyte counts but without malignancy. CD16+ monocytes accounted for 46% +/- 22% of total monocytes in the patients with cancer versus 5% +/- 3% for controls (P < .01). The increase was not attributable to infection or intercurrent illness and appeared to be associated with the underlying malignancy itself. A similar spontaneous elevation of CD16+ monocytes was observed in 35 of 44 additional patients diagnosed with a variety of other solid tumors. When patients with gastrointestinal carcinoma were treated with rhMCSF, there was a marked further increase in the percentage of CD16+ monocytes (to 83% +/- 11%), as well as in the absolute number of CD16+ cells and the level of CD16 antigen expression. In every case, the patients with cancer showed a greater CD16+ monocyte response than the maximal response obtained in normal volunteer subjects treated witha similar regimen of rhMCSF (n = 5, P < .001), suggesting that the presence of malignancy primed patients for enhanced responsiveness to rhMCSF. We hypothesize that spontaneous expansion of the CD16+ monocyte population may represent a novel biologic marker for a widespread and previously unsuspected host immune response to malignancy.
A new typhoid vaccine composed of the Vi capsular polysaccharide (1995)

Typhoid is still prevalent in many parts of the world. We reviewed all published and unpublished studies of a newly licensed vaccine composed of the Vi capsular polysaccharide of<i>Salmonella typhi</i>, the causative agent of the disease, which had been licensed previously outside the United States. These included observational studies and double-blind randomized studies done in the United States, Europe, and the developing world in which children and adults unexposed to typhoid or those living in endemic areas were enrolled. A single dose of 25 μg of the purified polysaccharide was given by intramuscular injection. The vaccine was well tolerated, inducing only minor reactions in fewer than 10% of subjects. An antibody response occurred in about 90% of subjects and lasted about 3 years. Seroconversion was shown in children as young as 2 years. Protective efficacy was evaluated in two studies conducted in areas in which typhoid is endemic; the efficacy was 55% and 75%, respectively, in adults and in children older than 5 years. The Vi vaccine compares favorably with other typhoid vaccines in regard to safety, patient compliance, immunogenicity, and efficacy. Vi polysaccharide is a well-standardized antigen that is effective in a single parenteral dose, is safer than whole-cell vaccine, and may be used in children 2 years of age or older. (Arch Intern Med. 1995;155:2293-2299)
Microfluidic “jets” for generating steady-state gradients of soluble molecules on open surfaces (2006)

The ability to control the spatiotemporal microenvironment of cultured cells, such as cells in soluble gradients of signaling molecules, is critical for understanding the quantitative relationship between physicochemical signals and the induced biological responses. Existing methods for generating biomolecule gradients either offer little control, result in poor reproducibility, and/or place cells in potentially confounding or adverse conditions. Here the authors report the generation of soluble gradients by a system of microfluidic “jets” that inject picoliter amounts of fluid into an open pool with negligible exposure of the surface to flow. A stable, reproducible gradient can be formed in minutes.
Vulcan Binary transformation in a distributed environment (2001)

Distributed computing on the Internet presents new challenges and opportunities for tools that inspect and modify program binaries. The dynamic and heterogeneous nature of the Internet environment extends the traditional product development process by requiring program development tools like these, which were once used only internally, to work in live environments too. The concept of compilation process must be expanded along with the capabilities of the binary tools. This paper presents Vulcan , a second-generation technology that addresses many of these challenges. Vulcan provides both static and dynamic code modification and provides a framework for cross-component analysis and optimization. It provides system-level analysis for heterogeneous binaries across instruction sets. Vulcan works in the Win32 environment and can process x86, IA64, and MSIL binaries. Vulcan scales to large commercial applications and has been used to improve performance and reliability of Microsoft products in a production environment.
The Kinect as an interventional tracking system (2012)

This work explores the suitability of low-cost sensors for "serious" medical applications, such as tracking of interventional tools in the OR, for simulation, and for education. Although such tracking - i.e. the acquisition of pose data e.g. for ultrasound probes, tissue manipulation tools, needles, but also tissue, bone etc. - is well established, it relies mostly on external devices such as optical or electromagnetic trackers, both of which mandate the use of special markers or sensors attached to each single entity whose pose is to be recorded, and also require their calibration to the tracked entity, i.e. the determination of the geometric relationship between the marker's and the object's intrinsic coordinate frames. The Microsoft Kinect sensor is a recently introduced device for full-body tracking in the gaming market, but it was quickly hacked - due to its wide range of tightly integrated sensors (RGB camera, IR depth and greyscale camera, microphones, accelerometers, and basic actuation) - and used beyond this area. As its field of view and its accuracy are within reasonable usability limits, we describe a medical needle-tracking system for interventional applications based on the Kinect sensor, standard biopsy needles, and no necessary attachments, thus saving both cost and time. Its twin cameras are used as a stereo pair to detect needle-shaped objects, reconstruct their pose in four degrees of freedom, and provide information about the most likely candidate.
rheb, a growth factor- and synaptic activity-regulated gene, encodes a novel Ras-related protein. (1994)

Neuronal activity results in long term cellular changes that underlie normal brain development and synaptic plasticity. To examine the molecular basis of activity-dependent plasticity, we have used differential cloning techniques to identify genes that are rapidly induced in brain neurons by synaptic activity. Here we describe an inducible novel member of the Ras family of small GTP-binding proteins we have termed Rheb. rheb mRNA is rapidly and transiently induced in hippocampal granule cells by seizures and by NMDA-dependent synaptic activity in the long term potentiation paradigm. The predicted amino acid sequence of Rheb is most closely homologous to yeast Ras1 and human Rap2. The putative GTP binding regions are highly conserved. A bacterial fusion protein of Rheb binds GTP and exhibits intrinsic GTPase activity. Like Ha-Ras, the carboxylterminal sequence encodes a CAAX box that is predicted to signal post-translational farnesylation and to target Rheb to specific membranes. rheb mRNA is expressed at comparatively high levels in normal adult cortex as well as a number of peripheral tissues, including lung and intestine. In the developing brain, rheb mRNA is expressed at relatively high levels in embryonic day 19 cortical plate, and expression remains at stable levels throughout the remainder of prenatal and postnatal development. Its close homology with ras and its rapid inducibility by receptor-dependent synaptic activity suggest that rheb may play an important role in long term activity-dependent neuronal responses.
Reproductive disorders in boars infected experi-mentally with Japanese encephalitis virus (1977)

雄豚において,日本脳炎ウイルスの人工感染試験を行い,精液性状及び生殖器の変化を観察して次の結果を得た。1)日本脳炎ウイルスに対する抗体陰性の7~8ヵ月齢の雄豚5頭に,マウス脳3代継代の本ウイルス野外株106.5~109.0TCID50/mlを含むウイルス液1mlを頸部皮下に接種した結果,全頭が2~3日後にウイルス血症を呈し,半日~5日間39.5~41.2°Cの熱を持続した。このうち2頭においては,それぞれ接種の翌日及び3日目から17日目まで採取した精液中にウイルスが証明された。2)比較的長時間高熱を持続した豚では,その間交尾欲が減退し採精不能となった。いずれの豚も解熱後は精子活力の軽度の低下がみられ,精子数の減少は2頭において観察された。しかし,奇形精子出現率が高いものは1頭のみであった。3)ウイルス接種後23~146日目に解剖された豚の生殖器は,肉眼的には精索,総鞘膜及び精巣上体縁の固有鞘膜表面に繊維素の沈着がみられ,2頭は軽度の陰嚢水腫を呈した。組織学的には,総鞘膜,固有鞘膜及び精巣上体間質に軽度~中等度の炎症性変化が観察された。また一部の精細管において,精子形成が阻害されていることが認められた。4)以上の成績から,日本脳炎ウイルスの感染により雄豚の造精機能障害が発生することを認めた。
Analysis of Gene Transcription in Bovine Nuclear Transfer Embryos Reconstructed with Granulosa Cell Nuclei1 (2000)

The low efficiency of animal production using somatic cell nuclear transfer procedures is considered to be the result of an incomplete reprogramming of the donor somatic cell nucleus, which leads to a lack of, or abnormal expression of developmentally important genes. However, our current understanding of the process of somatic cell nuclear reprogramming and its effect on gene expression is limited. In this study, we compare the transcription patterns of six developmentally important genes, Oct4, IL6, FGF2, FGF4, FGFr2, and gp130 in single in vitro fertilized (IVF) and nuclear transfer embryos reconstructed using granulosa cells for the donor nuclei. Similar patterns of transcription were detected for Oct4, FGF2, and gp130 in IVF and nuclear transfer embryos during the preimplantation stages of development. However, a number of morula- and blastocyst-stage embryos derived from nuclear transfer procedures showed abnormal transcription of IL6, FGF4, and FGFr2. Previous studies have demonstrated that these three genes play an important role in implantation, early postimplantation development, or both in the mouse. Therefore, the aberrant transcription patterns detected in nuclear transfer embryos may lead to a reduction in embryo viability.
C5a induction of human interleukin 1. Synergistic effect with endotoxin or interferon-gamma. (1987)

Interleukin-1 (IL-1) is a potent cytokine which possesses the ability to mediate systemic acute phase responses as well as local tissue inflammation. In these studies, we have examined the ability of C5a and C5a des Arg to induce IL-1 production in vitro. Human C5a and C5a des Arg were purified to homogeneity and were found to stimulate IL-1 release from freshly obtained human mononuclear cells into the extracellular medium. Only 2 hr of exposure to the purified complement components were necessary in order to stimulate IL-1 production. The minimal concentration of C5a required was 25 ng/ml, whereas 125 ng/ml of C5a des Arg induced comparable amounts of IL-1. This dose relationship was maintained at higher concentrations (150 ng/ml vs 750 ng/ml, respectively). That the effect was due to the anaphylatoxins themselves, and not endotoxin contamination, was shown by negative Limulus amebocyte lysate tests and employing preincubation of C5a/C5a des Arg with polymyxin B. The latter blocked a wide dose range of endotoxin-stimulated IL-1 production. However, when endotoxin was added to C5a or C5a des Arg, significant synergism in the stimulation of IL-1 production was observed, occurring at various concentrations of either agent. A similar synergism with C5a/C5a des Arg was seen with interferon-gamma. In these studies, IL-1 production was measured by bioassay employing cloned D . 10 . G4 . 1 murine T cells and by radioimmunoassay for human IL-1 beta; using C5a/C5a des Arg as stimulants, there was a high degree of correlation (r = 0.82) between the two assays. Since traumatic, infectious, and inflammatory diseases may result in the simultaneous appearance of these stimuli, the synergism described herein is likely to be clinically relevant.
An Analysis of the Sensitivity of Proteogenomic Mapping of Somatic Mutations and Novel Splicing Events in Cancer (2015)

Improvements in mass spectrometry (MS)-based peptide sequencing provide a new opportunity to determine whether polymorphisms, mutations, and splice variants identified in cancer cells are translated. Herein, we apply a proteogenomic data integration tool (QUILTS) to illustrate protein variant discovery using whole genome, whole transcriptome, and global proteome datasets generated from a pair of luminal and basal-like breast-cancer-patient-derived xenografts (PDX). The sensitivity of proteogenomic analysis for singe nucleotide variant (SNV) expression and novel splice junction (NSJ) detection was probed using multiple MS/MS sample process replicates defined here as an independent tandem MS experiment using identical sample material. Despite analysis of over 30 sample process replicates, only about 10% of SNVs (somatic and germline) detected by both DNA and RNA sequencing were observed as peptides. An even smaller proportion of peptides corresponding to NSJ observed by RNA sequencing were detected (<0.1%). Peptides mapping to DNA-detected SNVs without a detectable mRNA transcript were also observed, suggesting that transcriptome coverage was incomplete (∼80%). In contrast to germline variants, somatic variants were less likely to be detected at the peptide level in the basal-like tumor than in the luminal tumor, raising the possibility of differential translation or protein degradation effects. In conclusion, this large-scale proteogenomic integration allowed us to determine the degree to which mutations are translated and identify gaps in sequence coverage, thereby benchmarking current technology and progress toward whole cancer proteome and transcriptome analysis.
SiGe-free strained Si on insulator by wafer bonding and layer transfer (2003)

SiGe-free strained Si on insulator substrates were fabricated by wafer bonding and hydrogen-induced layer transfer of strained Si grown on bulk relaxed Si0.68Ge0.32 graded layers. Raman spectroscopy shows that the 49-nm thick strained Si on insulator structure maintains a 1.15% tensile strain even after SiGe layer removal. The strain in the structure is thermally stable during 1000 °C anneals for at least 3 min, while more extreme thermal treatments at 1100 °C cause slight film relaxation. The fabrication of epitaxially defined, thin strained Si layers directly on a buried insulator forms an ideal platform for future generations of Si-based microelectronics.
Ray–tracing of multiresolution B–Spline volumes (1995)

This paper describes a wavelet–based ray–tracing algorithm that carries out high quality images. Our appoach takes advantage of the multiresolution representation of the volume data and the self–similarity of the basis functions. The results are flexible high order approximations of the low albedo rendering equation. We propose accurate integration and evaluation schemes for shading and intensity computation. This paper also describes the calculation of error bounds of the intensity integration. The theory and its implementation are discussed and shaded images are presented.