gebhart/patrepeval huggingface dataset:
Tissue microarray analysis of hepatocyte growth factor/Met pathway components reveals a role for Met, matriptase, and hepatocyte growth factor activator inhibitor 1 in the progression of node-negative breast cancer. (2003)

Numerous studies have demonstrated that overexpression of Met, the hepatocyte growth factor(HGF) receptor, plays an important role in tumorigenesis. Met activation can either occur through ligand-independent or -dependent mechanisms, both of which are mediated by a series of proteases and modulators. We studied the protein expression of several components of the HGF/Met pathway on a cohort of 330 node-negative breast carcinomas using a tissue microarray annotated with 30-year, disease-specific patient follow-up data. We examined HGF, matriptase (an activator of HGF expressed on mammary epithelial cell surfaces), HAI-I (the cognate inhibitor of matriptase), and the Met receptor itself. Our studies demonstrate tight correlation between the expression of HGF, matriptase, and Met in breast carcinoma. High-level expression of Met, matriptase, and HAI-I were associated with poor patient outcome. Met and HAI-I showed independent prognostic value when compared with traditional breast markers in a multivariate analysis. Intriguingly, antibodies against the intracellular but not the extracellular domain of Met were prognostic, suggesting that overexpression of the cytoplasmic-tail of Met, perhaps through cleavage or truncating mutation, may play an important role in breast cancer progression.
NONOates–Polyethylenimine Hydrogel for Controlled Nitric Oxide Release and Cell Proliferation Modulation (2011)

In recent years, numerous research activities have been devoted to the controlled release of nitric oxide (NO) due to its potential as a restenosis inhibitor which inhibits the proliferation of vascular smooth muscle cells, the apoptosis of vascular endothelial cells, and aggregation of platelets. This work has demonstrated the development of a novel NO-conjugated gel system comprising of thermosensitive Pluronic F127, branched polyethylenimine (BPEI), and diazeniumdiolates (NONOates). Synthesis of conjugated Pluronic-BPEI-NONOates involved coupling of activated F127 to BPEI followed by the installation of NONOates at the secondary amine sites of branched PEI backbone under high pressure. NO-conjugated gel system, F127-BPEI-NONOates, reduced the initial burst of NO release and prolonged NO release. Furthermore, F127-BPEI-NONOates polymer coated on cell culture dish displayed much higher increase of endothelial cell proliferation and reduction of smooth muscle cell proliferation than that exhibited by non-NO releasing control. Such an NO-releasing device can operate locally and has a great potential in several biomedical applications due to high biocompatibility imparted by the conjugated F127.
Optimizing the radiation pattern of sparse periodic linear arrays (1996)

We have developed a method for designing sparse periodic arrays. Grating lobes in the two-way radiation pattern are avoided by using different element spacings on transmission and reception. The transmit and receive aperture functions are selected such that the convolution of the aperture functions produces a desired effective aperture. A desired effective aperture is simply an aperture with an appropriate width, element spacing, and shape such that the Fourier transform of this function gives the desired two-way radiation pattern. If a synthetic aperture approach is used, an exact solution to the problem is possible. However, for conventional imaging, often only an approximation of the desired effective aperture can be found. Different strategies for obtaining these approximate solutions are described. The radiation pattern of a sparse array designed using the effective aperture concept is compared experimentally with the radiation patterns of a dense array, and sparse arrays with periodic and random element spacing. We show that the number of elements in a 128-element linear array can be reduced by at least four times with little degradation of the beam forming properties of the array.
Complete proton and carbon nuclear magnetic resonance spectral assignments of some morphinan‐6‐one alkaloids by two‐dimensional NMR techniques (1993)

Abstract The 1 H (400 MHz) and carbon 13 C (100 MHz) NMR peak assignments of two oxymorphone alkaloids including the free base and the hydrochloride (HCl) salt and four oxycodone alkaloids including the free base, the HCl salt, the N ‐oxide and the methyl iodide quaternary salt were assigned using a variety of two‐dimensional NMR techniques. Proton coupling constants provide evidence that the cyclohexanone (D) and the piperidine (E) rings adopt slightly distorted chair conformations. Nuclear Overhauser enhancement difference experiments indicate that the conformation of the N ‐methyl group is equatorial and the O ‐methyl group prefers a cis orientation relative to C‐2. The minor component observed in aqueous 1 H and 13 C NMR spectra of each HCl salt and the N ‐oxide is produced by the reaction of the alkaloid with water at the C‐6 carbonyl, forming a gem ‐diol, and is not due to the presence of the axial isomer. The first complete solution and solid conformational analyses of oxycodone N ‐oxide by NMR and x‐ray crystallography have been investigated. The data indicate that the C‐14‐OH proton is intramolecularly hydrogen bonded to the NO oxygen.
DNA repair genes are selectively mutated in diffuse large B cell lymphomas (2013)

DNA repair mechanisms are fundamental for B cell development, which relies on the somatic diversification of the immunoglobulin genes by V(D)J recombination, somatic hypermutation, and class switch recombination. Their failure is postulated to promote genomic instability and malignant transformation in B cells. By performing targeted sequencing of 73 key DNA repair genes in 29 B cell lymphoma samples, somatic and germline mutations were identified in various DNA repair pathways, mainly in diffuse large B cell lymphomas (DLBCLs). Mutations in mismatch repair genes (EXO1, MSH2, and MSH6) were associated with microsatellite instability, increased number of somatic insertions/deletions, and altered mutation signatures in tumors. Somatic mutations in nonhomologous end-joining (NHEJ) genes (DCLRE1C/ARTEMIS, PRKDC/DNA-PKcs, XRCC5/KU80, and XRCC6/KU70) were identified in four DLBCL tumors and cytogenetic analyses revealed that translocations involving the immunoglobulin-heavy chain locus occurred exclusively in NHEJ-mutated samples. The novel mutation targets, CHEK2 and PARP1, were further screened in expanded DLBCL cohorts, and somatic as well as novel and rare germline mutations were identified in 8 and 5% of analyzed tumors, respectively. By correlating defects in a subset of DNA damage response and repair genes with genomic instability events in tumors, we propose that these genes play a role in DLBCL lymphomagenesis.
Characterization and immunohistochemical localization of alpha 2-macroglobulin receptor (low-density lipoprotein receptor-related protein) in human brain. (1992)

Proteinase inhibitors have been implicated in brain development and in degenerative processes such as Alzheimer's disease. Low-density lipoprotein receptor-related protein (LRP) is a multifunctional cell-surface receptor that binds activated forms of the proteinase inhibitor, alpha 2-macroglobulin (alpha 2M) and apolipoprotein E. Solubilized plasma membranes of human cerebral cortical gray matter were subjected to affinity chromatography on alpha 2M-methylamine-sepharose. A single receptor was purified; this protein was LRP as determined by molecular mass, peptide structure, and immunoreactivity with monoclonal and polyclonal antibodies. In adult human brain, LRP immunoreactivity was abundant on neuronal cell bodies and proximal processes. Other cells within the neuropil, including glia and microvascular cells (endothelium and pericytes), were immunonegative. Weak LRP immunoreactivity was identified in a perivascular pattern corresponding to the location of astrocytic foot processes. The distribution of LRP in the central nervous system is consistent with the potential function of this receptor in the regulation of proteinase activity, cytokine activity, and cholesterol metabolism.
Protein sequence classification using feature hashing (2012)

Recent advances in next-generation sequencing technologies have resulted in an exponential increase in the rate at which protein sequence data are being acquired. The k-gram feature representation, commonly used for protein sequence classification, usually results in prohibitively high dimensional input spaces, for large values of k. Applying data mining algorithms to these input spaces may be intractable due to the large number of dimensions. Hence, using dimensionality reduction techniques can be crucial for the performance and the complexity of the learning algorithms. In this paper, we study the applicability of feature hashing to protein sequence classification, where the original high-dimensional space is "reduced" by hashing the features into a low-dimensional space, using a hash function, i.e., by mapping features into hash keys, where multiple features can be mapped (at random) to the same hash key, and "aggregating" their counts. We compare feature hashing with the "bag of k-grams" approach. Our results show that feature hashing is an effective approach to reducing dimensionality on protein sequence classification tasks.
The role of an astrocytic NADPH oxidase in the neurotoxicity of amyloid beta peptides (2005)

Amyloid beta peptide (Abeta) accumulates in the CNS in Alzheimer's disease. Both the full peptide (1-42) or the 25-35 fragment are toxic to neurons in culture. We have used fluorescence imaging technology to explore the mechanism of neurotoxicity in mixed asytrocyte/neuronal cultures prepared from rat or mouse cortex or hippocampus, and have found that Abeta acts preferentially on astrocytes but causes neuronal death. Abeta causes sporadic transient increases in [Ca2+]c in astrocytes, associated with a calcium dependent increased generation of reactive oxygen species (ROS) and glutathione depletion. This caused a slow dissipation of mitochondrial potential on which abrupt calcium dependent transient depolarizations were superimposed. The mitochondrial depolarization was reversed by mitochondrial substrates glutamate, pyruvate or methyl succinate, and by NADPH oxidase (NOX) inhibitors, suggesting that it reflects oxidative damage to metabolic pathways upstream of mitochondrial complex I. The Abeta induced increase in ROS and the mitochondrial depolarization were absent in cells cultured from transgenic mice lacking the NOX component, gp91phox. Neuronal death after 24 h of Abeta exposure was dramatically reduced both by NOX inhibitors and in gp91phox knockout mice. Thus, by raising [Ca2+]c in astrocytes, Abeta activates NOX, generating oxidative stress that is transmitted to neurons, causing neuronal death.
Hyperthermic effects on the human metastatic liver: a TEM study. (1998)

Using ultrastructural analysis, we studied the effects of hyperthermic treatment of one case of human liver metastasis from colon carcinoma. The results indicate that the main hyperthermic response involves the neoplastic and the histiocytic cell population. The drastic decrease in metastatic cells was accompanied by the appearance of cell fragments and apoptotic bodies. Consequently, the histiocytic component (Kupffer cells) showed increased frequency, indicating an activated state. The data are consistent with a direct action of the heat on tumor cells with subsequent activation of Kupffer cells.
Self-managing technology in IBM DB2 universal database (2001)

As the cost of both hardware and software falls due to technological advancements and economies of scale, the cost of ownership for database applications is increasingly dominated by the cost of people to manage them. Databases are growing rapidly in scale and complexity, while skilled database administrators (DBAs) are becoming rarer and more expensive. The scope of responsibility of DBAs is indeed daunting. This paper describes the self-managing technology in IBM DB2 Universal Database to illustrate how self-managing technology can enhance the usability of enterprise middleware and reduce the total cost of ownership (TCO).
Spoken Discourse in the TESOL Classroom (1993)

Anne Burns describes a recent project undertaken by the National Center for English Language Teaching and Research at Macquarie University and two groups of AMEP teachers from New South Wales and South Australia. The project looked at the nature of spoken discourse and its implications for teaching.
Ionic effects on the behavior of thermoresponsive PEO–PNIPAAm block copolymers (2014)

ABSTRACT The temperature‐dependent aggregation and recovery of the copolymer poly(ethylene oxide) 22 ‐ b‐ poly( N ‐isopropylacrylamide) 29 with a C 12 end‐cap in aqueous solutions of salts and acids are investigated. Salt solutions affected the critical aggregation temperature of the copolymer in a manner predictable according to the Hofmeister series, with the kosmotropic adipic ion lowering the critical aggregation temperature and the chaotropic iodide raising it. Also, both salts and acids increased the size of copolymer aggregates formed with heating, due to the electrostatic shielding of aggregated structures provided by the electrolytes. Additionally, the presence of ionic additives caused a thermohysteretic increase in the size of copolymer aggregates with temperature cycling. The transitions of polymer structure with increasing temperature were surprisingly sharp with the C 12 end‐cap present, and particularly broad in samples in which the end cap had been cleaved. This observation suggested that the hydrophobic end group was responsible for imparting some degree of order to the polymer at low temperatures, which allowed for rapid reconfiguration with increasing temperature. Finally, in addition to the transitions expected from the least critical solution temperature behavior of the polymer blocks, we have observed an unexpected additional transition which we attribute to the contraction of the poly(ethylene oxide) chains of the copolymer aggregates at higher temperatures. This work illustrates the importance of considering the environment and composition of thermoresponsive block copolymers in certain applications, particularly in solutions with even modest electrolyte concentrations (1–10 mM), as it can have a profound effect on transition temperatures and morphology. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2014 , 52 , 507–516
Adaptive Control Design of Neural Fuzzy System for NARMA-L2 Model (2006)

An adaptive neural control method is presented for the nonlinear discrete-time systems with the NARMA-L2 model. The neural fuzzy system is integrated with the approximate model-based control method to handle the nonlinear complexity, where the multiple fuzzy CMAC (MFCMAC) network is used to compensate the approximate NARMA model of the nonaffine nonlinear system. The weights of neural networks are modified by a novel adaptive algorithm, which guarantee the stability of the neural system without the persistent excitation requirement. The stability of the closed-loop system is proved with the Lyapunov method. Simulation results show that the method is effective.
Fluorescence Resonance Energy Transfer–Based Analysis of cAMP Dynamics in Live Neonatal Rat Cardiac Myocytes Reveals Distinct Functions of Compartmentalized Phosphodiesterases (2004)

Cardiac myocytes have provided a key paradigm for the concept of the compartmentalized cAMP generation sensed by AKAP-anchored PKA. Phosphodiesterases (PDEs) provide the sole route for degrading cAMP in cells and are thus poised to regulate intracellular cAMP gradients. PDE3 and PDE4 represent the major cAMP degrading activities in rat ventriculocytes. By performing real-time imaging of cAMP in situ, we establish the hierarchy of these PDEs in controlling cAMP levels in basal conditions and on stimulation with a beta-adrenergic receptor agonist. PDE4, rather than PDE3, appears to be responsible for modulating the amplitude and duration of the cAMP response to beta-agonists. PDE3 and PDE4 localize to distinct compartments and this may underpin their different functional roles. Our findings indicate the importance of distinctly localized PDE isoenzymes in determining compartmentalized cAMP signaling.
Fondaparinux‐associated heparin‐induced thrombocytopenia (2013)

The risk of fondaparinux-associated HIT, although low is real, which along with documented cases of fondaparinux failure mandate its cautious use in the management of HIT.
Dimethyl fumarate: A fumaric acid ester under investigation for treatment of relapsing-remitting multiple sclerosis (2012)

Dimethyl fumarate is an investigational drug being studied for the treatment of relapsing-remitting multiple sclerosis (RRMS).
(Trad.), Les Paradoxes du délire : Schreber, Wittgenstein et l'esprit schizophrénique (2010)

Cet ouvrage est un essai sur la philosophie et sur la folie comme proche parente de la philosophie, et sur la philosophie comme une espece de la folie. Etre fou, tant dans la pratique clinique que dans l'imagination de tout un chacun, est considere comme un etat de l'esprit ou l'on croit des choses fausses et ou l'on en percoit d'autres qui n'existent pas. Mais bien des schizophenes n'agissent pas comme s'ils prenaient leurs delires pour la realite. Dans un travail d'une penetration et d'une sensibilite exceptionnelles, Louis Sass fait voler en eclats les conceptions recues du delire, en mettant en regard les notes autobiographiques d'un schizophrene paranoide - le celebre Daniel Paul Schreber - avec les ecrits du philosophe (ou de l'antiphilosophe) Ludwig Wittgenstein.
Acute infection and macrophage subversion by Mycobacterium tuberculosis require a specialized secretion system (2003)

Although many bacterial pathogens use specialized secretion systems for virulence, no such systems have been described for Mycobacterium tuberculosis, a major pathogen of humans that proliferates in host macrophages. In a screen to identify genes required for virulence of M. tuberculosis, we have discovered three components and two substrates of the first Sec-independent secretion pathway described in M. tuberculosis, which we designate the Snm pathway. Here we demonstrate that the proteins Snm1, -2, and -4 are required for the secretion of ESAT-6 and CFP-10, small proteins previously identified as major T cell antigens. Snm2, a member of the AAA ATPase family, interacts with substrates and with Snm1, another AAA ATPase. We show that M. tuberculosis mutants lacking either the Snm system or these substrates exhibit defects in bacterial growth during the acute phase of a mouse infection and are attenuated for virulence. Strikingly, snm mutants fail to replicate in cultured macrophages and to inhibit macrophage inflammatory responses, two well established activities of wild-type M. tuberculosis bacilli. Thus, the Snm secretion pathway works to subvert normal macrophage responses and is a major determinant of M. tuberculosis virulence.
The cloning of plant E2F, a retinoblastoma-binding protein, reveals unique and conserved features with animal G1/S regulators (1999)

Association of the retinoblastoma (Rb) protein with E2F transcription factors is central to cell cycle-specific gene expression and growth in animal cells. Whether Rb-E2F complexes are also involved in plant cell growth and differentiation is still unknown since E2F proteins have not yet been identified in plants. Here we report the isolation and characterisation of a wheat E2F (TmE2F) cDNA clone. Interestingly, the overall domain organisation of plant E2F is related to the human E2F-1/2/3 subset but its primary sequence is slightly more related to the E2F-4/5 subset. TmE2F-Rb binding depends on residues, located at the C-terminus, which are different from those of animal E2Fs. However, the acidic or hydrophobic nature of certain residues is maintained, strongly suggesting that they may have a crucial role in E2F activities. Plant E2F is expressed in proliferating cultured cells and in differentiated tissues and is up-regulated early in S phase. Our studies reinforce the idea that G(1)/S regulators in plants are unrelated to those of yeast cells but similar to those of animal cells and provide new tools to analyse the links between cell cycle regulators, plant growth and developmental signals.
DLP-based 3D metrology by structured light or projected fringe technology for life sciences and industrial metrology (2009)

Since the mid-eighties, a fundamental idea for achieving measuring accuracy in projected fringe technology was to consider the projected fringe pattern as an interferogram and evaluate it on the basis of advanced algorithms widely used for phase measuring in real-time interferometry. A fundamental requirement for obtaining a sufficiently high degree of measuring accuracy with this so-called "phase measuring projected fringe technology" is that the projected fringes, analogous to interference fringes, must have a cos<sup>2</sup>-shaped intensity distribution. Until the mid-nineties, this requirement for the projected fringe pattern measurement technology presented a basic handicap for its wide application in 3D metrology. This situation changed abruptly, when in the nineties Texas Instruments introduced to the market advanced digital light projection on the basis of micro mirror based projection systems, socalled DLP technology, which also facilitated the generation and projection of cos<sup>2</sup>-shaped intensity and/or fringe patterns. With this DLP technology, which from its original approach was actually oriented towards completely different applications such as multimedia projection, Texas Instruments boosted phase-measuring fringe projection in optical 3D metrology to a worldwide breakthrough both for medical as well as industrial applications. A subject matter of the lecture will be to present the fundamental principles and the resulting advantages of optical 3D metrology based on phase-measuring fringe projection using DLP technology. Further will be presented and discussed applications of the measurement technology in medical engineering and industrial metrology.
Oxidative stress and enzymatic antioxidant mechanisms in essential hypertension (2001)

The objective was to evaluate the oxidative status, the extent of lipid and DNA oxidation and the activity of enzymatic antioxidants in essential hypertensive patients out of antihypertensive treatment. Forty-one essential hypertensive subjects (mean age 48 yr, 24 males, SBP 160±18 mmHg, DBP 97±12 mmHg), and 10 normotensive controls were included. According 24h ABP hypertensives were grouped in those with isolated clinic hypertension (ISCH) and true hypertensives (HTN). In whole blood and in lymphocites, oxidative stress status (GSSG/GSH), lipid-perodixation product (malondialdehyde), DNA-damage (8-oxo-2'-deoxyguanosine only in lymphocites) and the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (Gpx) were measured in absence of antihypertensive treatment. All hypertensive subjects shown a significative increase in the GSSG/GSH index as well as in the levels of malondialdehyde or 8-oxo-2'-deoxyguanosine. Subjects with ISCH shown higher GSSG/GSH, malondialdehyde and 8-oxo-2'-deoxyguanosine than the controls did, but lower than those observed in HTN. A decreased activity of the three enzymatic systems, SOD, CAT and Gpx measured were observed in all hypertensive subjects, both ISCH and HTN. Conclusion: Essential hypertension is associated with greater than normal oxidative stress partially related to ambulatory BP levels. Furthermore an imbalance in anti-oxidant status was present in hypertensive subjects.
Der Schlüssel zum Schloß II. Hansch‐Analyse, 3D‐QSAR undDe novo‐Design (1994)

Abstract Die Auffindung neuer Leitstrukturen und ihre gezielte Optimierung sind mehr denn je Kriterien für eine erfolgreiche Arzneimittelforschung. Computergestützte Methoden, wie Hansch‐Analyse, 3D‐QSAR und De novo ‐Design leisten dazu einen wichtigen Beitrag.