gebhart/patrepeval huggingface dataset:
Expression of APO‐1 (CD95), a member of the NGF/TNF receptor superfamily, in normal and neoplastic colon epithelium (1994)

APO-1 is a 48-kDa cell-membrane protein identical to the Fas antigen now designated CD95. It is a member of the NGF/TNF receptor superfamily. Anti-APO-1 monoclonal antibody induces apoptosis in a variety of cell types expressing this antigen. We immunohistochemically investigated APO-1 expression in normal colon mucosa, 20 adenomas, 258 colon carcinomas and 10 liver metastases and carried out in vitro studies using a panel of colon-carcinoma cell lines. Immunohistochemically, APO-1 was regularly expressed at the basolateral membrane of normal colon epithelia. In a minor fraction of colon adenomas and in 39.1% of colon carcinomas APO-1 expression was diminished and in 48.1% of carcinomas, predominantly of the non-mucinous type, APO-1 expression was completely abrogated. The normal level of APO-1 in carcinomas was correlated with the mucinous type. Reduced/lost APO-1 expression was more frequent in rectal carcinomas. Complete loss of APO-1 was more frequent in tumors that had already metastasized. APO-1 expression in liver metastases essentially corresponded to that of the primary tumors. Comparative analysis with data from previous studies revealed that the mode of APO-1 expression is correlated with that of HLA-A,B,C./beta 2m, HLA-DR, HLA-D-associated invariant chain and of the secretory component. Surface expression of APO-1 was heterogeneous in colon-carcinoma cell lines; SW480 expressed considerable amounts of APO-1 on all cells, while HT-29 constitutively did less so and only in a minority of cells. Surface density of APO-1 and the fraction of positive cells in HT-29 was enhanced by interferon-gamma (IFN-gamma) and, additively, by tumor necrosis factor-alpha (TNF-alpha), whereas in SW480 APO-1 expression was not modulated by these cytokines. We conclude that neoplastic transformation of colon epithelium often leads to a loss of the physiologic, high level of surface APO-1 by giving rise either to a stable lack of APO-1 or to an IFN-gamma/TNF-alpha-sensitive phenotype of inducible APO-1 expression.
8p12 Stem Cell Myeloproliferative Disorder: the FOP-Fibroblast Growth Factor Receptor 1 Fusion Protein of the t(6;8) Translocation Induces Cell Survival Mediated by Mitogen-Activated Protein Kinase and Phosphatidylinositol 3-Kinase/Akt/mTOR Pathways (2001)

The FOP-fibroblast growth factor receptor 1 (FGFR1) fusion protein is expressed as a consequence of a t(6;8) (q27;p12) translocation associated with a stem cell myeloproliferative disorder with lymphoma, myeloid hyperplasia and eosinophilia. In the present report, we show that the fusion of the leucine-rich N-terminal region of FOP to the catalytic domain of FGFR1 results in conversion of murine hematopoietic cell line Ba/F3 to factor-independent cell survival via an antiapoptotic effect. This survival effect is dependent upon the constitutive tyrosine phosphorylation of FOP-FGFR1. Phosphorylation of STAT1 and of STAT3, but not STAT5, is observed in cells expressing FOP-FGFR1. The survival function of FOP-FGFR1 is abrogated by mutation of the phospholipase C gamma binding site. Mitogen-activated protein kinase (MAPK) is also activated in FOP-FGFR1-expressing cells and confers cytokine-independent survival to hematopoietic cells. These results demonstrate that FOP-FGFR1 is capable of protecting cells from apoptosis by using the same effectors as the wild-type FGFR1. Furthermore, we show that FOP-FGFR1 phosphorylates phosphatidylinositol 3 (PI3)-kinase and AKT and that specific inhibitors of PI3-kinase impair its ability to promote cell survival. In addition, FOP-FGFR1-expressing cells show constitutive phosphorylation of the positive regulator of translation p70S6 kinase; this phosphorylation is inhibited by PI3-kinase and mTOR (mammalian target of rapamycin) inhibitors. These results indicate that translation control is important to mediate the cell survival effect induced by FOP-FGFR1. Finally, FOP-FGFR1 protects cells from apoptosis by survival signals including BCL2 overexpression and inactivation of caspase-9 activity. Elucidation of signaling events downstream of FOP-FGFR1 constitutive activation provides insight into the mechanism of leukemogenesis mediated by this oncogenic fusion protein.
Mice with type 2 and 3 Gaucher disease point mutations generated by a single insertion mutagenesis procedure (SIMP) (1998)

Gaucher disease is caused by mutations in the gene encoding the lysosomal enzyme glucocerebrosidase (GC). Three clinical types of Gaucher disease have been defined according to the presence (type 2 and 3) or absence (type 1) of central nervous system disease and severity of clinical manifestations. The clinical course of the disease correlates with the mutation carried by the GC gene. To produce mice with point mutations that correspond to the clinical types of Gaucher disease, we have devised a highly efficient one-step mutagenesis method-the single insertion mutagenesis procedure (SIMP)-to introduce human disease mutations into the mouse GC gene. By using SIMP, mice were generated carrying either the very severe RecNciI mutation that can cause type 2 disease or the less severe L444P mutation associated with type 3 disease. Mice homozygous for the RecNciI mutation had little GC enzyme activity and accumulated glucosylceramide in brain and liver. In contrast, the mice homozygous for the L444P mutation had higher levels of GC activity and no detectable accumulation of glucosylceramide in brain and liver. Surprisingly, both point mutation mice died within 48 hr of birth, apparently of a compromised epidermal permeability barrier caused by defective glucosylceramide metabolism in the epidermis.
Thrombelastography Today: Practicability and Analytical Power (2007)

Today, rotational thrombelastography as a further development of the classical thrombelastography is increasingly applied to assess haemostasis and to predict complications of coagulation. Due to the improved robustness of the method, RoTEM® analyses are now also performed outside specialised coagulation laboratories and applied in emergency settings. Since coagulation testing,particularly when performed with different activators, is very sensitive to artifacts due to variations in the proportion to anticoagulants, temperature and concentration of activators, meticulous quality control is indispensable. For this reason, the German Federal Chamber of Physicians has issued rigorous validity ranges for the classic coagulation tests, such as the prothrombin time (PT/INR)or the activated partial thromboplastin time (aPTT) for variation coefficient acceptance, which are audited 4 times a year by external quality control circles. At present,no comparable quality assurance setup exists for whole blood coagulation testing. Thus, knowledge of the analytical limits, restrictions and caveats of this method is central for critical interpretation of the results and reliable clinical application. This review gives an outline of the practicability and accuracy of the RoTEM methodology and illustrates some pitfalls for the use in detecting and predicting disturbances of haemostasis in a case report.
Energy-Optimal Scheduling with Dynamic Channel Acquisition in Wireless Downlinks (2009)

We consider a wireless base station serving L users through L time-varying channels. It is well known that opportunistic scheduling algorithms with full channel state information (CSI) can stabilize the system with any data rates within the capacity region. However, such opportunistic scheduling algorithms may not be energy efficient when the cost of channel acquisition is high and traffic rates are low. In particular, under the low traffic rate regime, it may be sufficient and more energy efficient to transmit data with no CSI, i.e., to transmit data blindly, since no power for channel acquisition is consumed. In general, we show strategies that probe channels in every slot or never probe channels in any slot are not necessarily optimal, and we must consider mixed strategies. We derive a unified scheduling algorithm that dynamically chooses to transmit data with full or no CSI based on queue backlog and channel statistics. Our methodology is general and can be naturally extended to include timing overhead due to channel acquisition, and to treat systems that allow any subset of channels to be measured. Through Lyapunov analysis, we show that the unified algorithm is throughput-optimal and stabilizes the downlink with optimal power consumption, balancing well between channel-aware and channel-blind transmission modes.
Characterization of a Plant Scaffold Attachment Region in a DNA Fragment That Normalizes Transgene Expression in Tobacco (1992)

Peter Breyne, Marc Van Montagu, Ann Depicker, Godelieve Gheysen, Characterization of a Plant Scaffold Attachment Region in a DNA Fragment That Normalizes Transgene Expression in Tobacco, The Plant Cell, Vol. 4, No. 4 (Apr., 1992), pp. 463-471
Anti-Selective Epoxidation of Methyl α-Methylene-β-tert-butyldimethylsilyloxycarboxylate Esters. Evidence for Stereospecific Oxygen Atom Transfer in a Nucleophilic Epoxidation Process (2009)

Methyl alpha-methylene-beta-tert-butyldimethylsilyloxycarboxylate esters are found to undergo diastereoselective epoxidation in the presence of potassium tert-butoxide-tert-butyl hydroperoxide to form anti products. In an effort to better understand mechanistic details of the transformation and the basis of diastereoselectivities observed, we studied the epoxidation of substrates with alpha-methylene groups containing (trans) deuterium labels and discovered that oxygen-atom transfer proceeds with > or = 95% stereospecificity in all cases examined. These and other experiments suggest that the mechanism of epoxidation is not distinguishable from a concerted process.
Multiplex fluorometric assessment of nutrient limitation as a strategy for enhanced lipid enrichment and harvesting of Neochloris oleoabundans (2012)

Detailed in this study are the results of fluorometric assays used to assess the impact of gradual nutrient limitation versus punctuated nitrate limitation on the lipid content and morphology of Neochloris oleoabundans cells in batch culture. Punctuated nitrate limitation was imposed during pre-log, log, late-log, stationary, and senescent growth phases, and the cells were analyzed by bulk fluorescence emission, flow cytometry, and hyperspectral fluorescence imaging. In addition to intrinsic spectroscopic signatures provided by scatter and endogenous fluorescence, Nile Red staining was employed to monitor relative changes in lipid concentration. Analysis of the fluorescence images and temporal data sets was performed using multivariate curve resolution and fitting to logistic growth models to extract parameters of interest. The spectral components independently isolated from the image and temporal data sets showed close agreement with one another, especially relating to chlorophylls and Nile Red in polar and neutral lipid fractions, respectively. The fastest accumulation and highest total neutral lipid per cell and per chlorophyll were obtained with punctuated nitrate limitation during log phase growth on day 4 of culture. The presence of unbound chlorophyll in the resulting lipid bodies supports a membrane recycling TAG accumulation mechanism mediated by chloropolast-ER lipid exchange. Furthermore, an increase in cell size, indicated by forward scatter, was also found to correlate with increased neutral lipid, providing a size selection mechanism for passive harvest of algal cells at peak lipid enrichment.
Narrow-band, tunable, semiconductor-laser-based source for deep-UV absorption spectroscopy (1997)

Tunable, narrow-bandwidth (<200-MHz), ~215-nm radiation was produced by frequency quadrupling the ~860-nm output of a high-power, pulsed GaAlAs tapered amplifier seeded by an external-cavity diode laser. Pulsing the amplifier increased the 860 nm?215 nm conversion efficiency by 2 orders of magnitude with respect to cw operation. Detection of nitric oxide and sulfur dioxide by high-resolution absorption spectroscopy was demonstrated.
Digital Predistortion for Power Amplifiers Using Separable Functions (2010)

This paper is concerned with digital predistortion for linearization of RF high power amplifiers (HPAs). It has two objectives. First, we establish a theoretical framework for a generic predistorter system, and show that if a postdistorter exists, then it is also a predistorter, and therefore, the predistorter and postdistorter are equivalent. This justifies the indirect learning methods for a large class of HPAs. Second, we establish a systematic and general structure for a predistorter that is capable of compensating nonlinearity for a large variety of HPAs. This systematic structure is derived using approximation by separable functions, and avoids selection of predistorters based on the assumption of HPA models traditionally done in the literature.
Tissue Processing of Nitrite in Hypoxia (2008)

Although nitrite (NO(2)(-)) and nitrate (NO(3)(-)) have been considered traditionally inert byproducts of nitric oxide (NO) metabolism, recent studies indicate that NO(2)(-) represents an important source of NO for processes ranging from angiogenesis through hypoxic vasodilation to ischemic organ protection. Despite intense investigation, the mechanisms through which NO(2)(-) exerts its physiological/pharmacological effects remain incompletely understood. We sought to systematically investigate the fate of NO(2)(-) in hypoxia from cellular uptake in vitro to tissue utilization in vivo using the Wistar rat as a mammalian model. We find that most tissues (except erythrocytes) produce free NO at rates that are maximal under hypoxia and that correlate robustly with each tissue's capacity for mitochondrial oxygen consumption. By comparing the kinetics of NO release before and after ferricyanide addition in tissue homogenates to mathematical models of NO(2)(-) reduction/NO scavenging, we show that the amount of nitrosylated products formed greatly exceeds what can be accounted for by NO trapping. This difference suggests that such products are formed directly from NO(2)(-), without passing through the intermediacy of free NO. Inhibitor and subcellular fractionation studies indicate that NO(2)(-) reductase activity involves multiple redundant enzymatic systems (i.e. heme, iron-sulfur cluster, and molybdenum-based reductases) distributed throughout different cellular compartments and acting in concert to elicit NO signaling. These observations hint at conserved roles for the NO(2)(-)-NO pool in cellular processes such as oxygen-sensing and oxygen-dependent modulation of intermediary metabolism.
Intrinsically Motivated Reinforcement Learning (2005)

Psychologists call behavior intrinsically motivated when it is engaged in for its own sake rather than as a step toward solving a specific problem of clear practical value. But what we learn during intrinsically motivated behavior is essential for our development as competent autonomous entities able to efficiently solve a wide range of practical problems as they arise. In this paper we present initial results from a computational study of intrinsically motivated reinforcement learning aimed at allowing artificial agents to construct and extend hierarchies of reusable skills that are needed for competent autonomy.
A Recombinant Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Complex Stabilized by an Intermolecular Disulfide Bond between the gp120 and gp41 Subunits Is an Antigenic Mimic of the Trimeric Virion-Associated Structure (2000)

The few antibodies that can potently neutralize human immunodeficiency virus type 1 (HIV-1) recognize the limited number of envelope glycoprotein epitopes exposed on infectious virions. These native envelope glycoprotein complexes comprise three gp120 subunits noncovalently and weakly associated with three gp41 moieties. The individual subunits induce neutralizing antibodies inefficiently but raise many nonneutralizing antibodies. Consequently, recombinant envelope glycoproteins do not elicit strong antiviral antibody responses, particularly against primary HIV-1 isolates. To try to develop recombinant proteins that are better antigenic mimics of the native envelope glycoprotein complex, we have introduced a disulfide bond between the C-terminal region of gp120 and the immunodominant segment of the gp41 ectodomain. The resulting gp140 protein is processed efficiently, producing a properly folded envelope glycoprotein complex. The association of gp120 with gp41 is now stabilized by the supplementary intermolecular disulfide bond, which forms with approximately 50% efficiency. The gp140 protein has antigenic properties which resemble those of the virion-associated complex. This type of gp140 protein may be worth evaluating for immunogenicity as a component of a multivalent HIV-1 vaccine.
Intraarterial Occlusion by Radiofrequency (1994)

Arterial occlusion using radiofrequency energy was performed. The length of the noninsulated part of the guidewire was 10 mm and the duration of radiofrequency supply was 20 s. Animal experiments were carried out in 17 canine arteries; 4 out of 6 arteries less than 2.3 mm in diameter were completely occluded during the 20 s radiofrequency supply. A clinical application was also successfully performed without any complications. Arterial occlusion with radiofrequency can be applied to vessels less than about 2 mm in diameter.
Yeast mitochondrial ADP/ATP carriers are monomeric in detergents (2006)

Mitochondrial carriers are believed widely to be homodimers both in the inner membrane of the organelle and in detergents. The dimensions and molecular masses of the detergent and protein-detergent micelles were measured for yeast ADP/ATP carriers in a range of different detergents. The radius of the carrier at the midpoint of the membrane, its average radius, its Stokes' radius, its molecular mass, and its excluded volume were determined. These parameters are consistent with the known structural model of the bovine ADP/ATP carrier and they demonstrate that the yeast mitochondrial ADP/ATP carriers are monomeric in detergents. Therefore, models of substrate transport have to be considered in which the carrier operates as a monomer rather than as a dimer.
Las nuevas pantallas planas (1999)

La Sociedad de la Informacion del siglo XXI estara sustentada por la proliferacion de dispositivos de presentacion de alta calidad. Cada vez que se presenta una estampa o decorado que pretende aparentar un aire futurista, invariablemente surge todo tipo de visualizadores pantallas murales, cuadros animados, ambientes virtuales- como parte integrante del escenario.
Disruption of the protein C inhibitor gene results in impaired spermatogenesis and male infertility (2000)

Protein C inhibitor (PCI) is a nonspecific, heparin-binding serpin (serine protease inhibitor) that inactivates many plasmatic and extravascular serine proteases by forming stable 1:1 complexes. Proteases inhibited by PCI include the anticoagulant activated protein C, the plasminogen activator urokinase, and the sperm protease acrosin. In humans PCI circulates as a plasma protein but is also present at high concentrations in organs of the male reproductive tract. The biological role of PCI has not been defined so far. However, the colocalization of high concentrations of PCI together with several of its target proteases in the male reproductive tract suggests a role of PCI in reproduction. We generated mice lacking PCI by homologous recombination. Here we show that PCI(-/-) mice are apparently healthy but that males of this genotype are infertile. Infertility was apparently caused by abnormal spermatogenesis due to destruction of the Sertoli cell barrier, perhaps due to unopposed proteolytic activity. The resulting sperm are malformed and are morphologically similar to abnormal sperm seen in some cases of human male infertility. This animal model might therefore be useful for analyzing the molecular bases of these human conditions.
Enhancement of a multianalyte serum biomarker panel to identify lymph node metastases in non‐small cell lung cancer with circulating autoantibody biomarkers (2010)

We recently reported the development of a multianalyte serum algorithm to identify nodal status in non-small cell lung cancer (NSCLC) patients facing an anatomic resection with curative intent. This study aims to enhance the overall performance characteristics of this test by adding autoantibody biomarkers identified through immunoproteomic discovery. More specifically, we used sera from 20 NSCLC patients to probe 2-D immunoblots of HCC827 lysates for tumor-associated autoantigens. Relevant differences in immunoreactivity associated with pathological nodal status were then identified via tandem mass spectrometry. Identified autoantigens were then developed into Luminex immunobead assays alongside a series of autoantigen targets relevant to early-disease detection. These assays were then used to measure circulating autoantibody levels in the identical cohort of NSCLC patients used in our original study. This strategy identified 11 autoantigens found primarily in patients with disease progression to the locoregional lymph nodes. Custom Luminex-based "direct-capture" assays (25 total; including autoantibody targets relevant to early-disease detection) were assembled to measure autoantibody levels in sera from 107 NSCLC patients. Multivariate classification algorithms were then used to identify the optimal combination of biomarkers when considered collectively with our original 6-analyte serum panel. The new algorithm resulting from this analysis consists of TNF-α, TNF-RI, MIP-1α and autoantibodies against Ubiquilin-1, hydroxysteroid-(17-β)-dehydrogenase, and triosephosphate isomerase. The inclusion of autoantibody biomarkers provided a dramatic improvement in the overall test performance characteristics, relative to the original test panel, including an 11% improvement in the classification efficiency.
Pharmacokinetic/pharmacodynamic modelling of 2-acetyl-4(5)-tetrahydroxybutyl imidazole-induced peripheral lymphocyte sequestration through increasing lymphoid sphingosine 1-phosphate (2010)

2-Acetyl-4(5)-tetrahydroxybutyl imidazole (THI) has been shown to reduce rodent peripheral blood lymphocytes through increasing lymphoid sphingosine 1-phosphate (S1P) by inhibiting S1P lyase. The objective of this study was to characterize the relationship between systemic THI exposure, splenic S1P concentrations, and lymphopenia in rats. Following the oral administration of 10 and 100 mg kg(-1) THI to male rats, THI was rapidly absorbed and reached a plasma peak level at 1 h post-dosing. Splenic S1P increased and reached the peak level at 24 h. Blood lymphocyte count decreased as the splenic S1P level increased. THI plasma concentration was linked to splenic S1P concentration using an indirect model incorporated with a four-step signal transduction model. In turn, the S1P level was directly coupled with blood lymphocyte number. The integrated model simultaneously captured the splenic S1P and blood lymphocyte responses. This pharmacokinetic-biomarker-pharmacodynamic model resolved the remarkable discrepancy between plasma THI concentration and the pharmacological response and quantitatively described the relationship of THI exposure, S1P, and lymphopenic response.