gebhart/patrepeval huggingface dataset:
Acamprosate Enhances N‐Methyl‐D‐Apartate Receptor‐Mediated Neurotransmission But Inhibits Presynaptic GABAB Receptors in Nucleus Accumbens Neurons (1998)

Acamprosate (calcium acetylhomotaurine) is used therapeutically in Europe to reduce relapse in weaned alcoholics. However, the mechanisms of acamprosate action in the central nervous system are still obscure, although early studies suggested an action on GABA receptors. The nucleus accumbens (NAcc) is a brain region thought to underlie ethanol reinforcement. Recent studies from our laboratory have demonstrated that ethanol inhibits both N-methyl-D-aspartate (NMDA) and non-NMDA types of glutamatergic synaptic transmission in the NAcc. In the present study, we used voltage- and current-clamp intracellular recording of NAcc core neurons in a slice preparation to examine acamprosate actions on resting membrane properties and pharmacologically isolated synaptic responses. We isolated NMDA and non-NMDA receptor-mediated excitatory postsynaptic potentials or currents (EPSP/Cs) with 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and DL-2-amino-5-phosphonovalerate (d-APV), respectively. Bicuculline was also included to block GABA(A) receptors. Superfusion of acamprosate (5, 50, and 300 microM) did not alter the resting membrane properties of NAcc neurons. However, 300 microM acamprosate significantly increased the NMDA receptor-mediated components of EPSP/Cs (NMDA-EPSP/Cs) with recovery on washout. In contrast, 300 microM acamprosate had no significant effect on the non-NMDA receptor component of the EPSP/Cs (non-NMDA-EPSP/Cs). To test acamprosate actions on the GABA system, we superfused 60 microM d-APV and 20 microM CNQX to block glutamatergic transmission and evoked monosynaptic GABA(A) receptor-mediated synaptic responses within the NAcc. Acamprosate (300 microM) did not change these monosynaptic GABA(A)-IPSCs. We also used a paired-pulse paradigm to test whether acamprosate could act on presynaptic GABA(B) autoreceptors, in the presence of d-APV and CNQX to block glutamatergic transmission. Like 0.5 microM CGP 34358 (a GABA[B] receptor blocker), acamprosate significantly decreased the paired-pulse inhibition (PPI) of GABA(A)-IPSCs at short interstimulus intervals (ISIs). Thus, acamprosate may concomitantly enhance NMDA-EPSP/Cs while blocking presynaptic GABA(B) receptor-mediated inhibition of GABA release. These results suggest that acamprosate's clinical efficacy in preventing relapse in weaned alcoholics could derive from its interactions with both the glutamatergic and GABAergic systems in the NAcc.
Complete L‐Alanine Scan of Neuropeptide Y Reveals Ligands Binding to Y1 and Y2 Receptors with Distinguished Conformations (1994)

The synthesis of more than fifty 36-residue oligopeptide analogs of neuropeptide Y (NPY) and their affinity to human Y1 and Y2 receptors is described. Each amino acid of the natural sequence was replaced by L-alanine, the four alanine residues at position 12, 14, 18 and 23 were replaced by glycine. Additional residues were exchanged to closely related ones in order to characterize the prerequisites for binding. A combination of automated single and multiple peptide synthesis using fluoren-9-ylmethoxycarbonyl/tert-butoxy strategy was applied. The purified peptides were characterized by electrospray mass spectrometry, analytical HPLC and amino acid analysis. Binding was investigated by displacement of 125I-labelled neuropeptide Y from human neuroblastoma cell lines SK-N-MC and SMS-KAN. Whereas Pro2 and the integrity of the neuropeptide Y loop is important for the binding to the Y1 receptor, exchanges within the C-terminal helix affect the affinity to the Y2 receptor. The C-terminal pentapeptide amide is important for both receptors and probably represents the binding site. However, Arg33 and Arg35 may not be exchanged by L-alanine in the Y1 system, whereas Arg35 and Tyr36 are the most susceptible residues in the Y2 system. In order to distinguish between conformational effects and direct hormone/receptor interaction via the side chains of neuropeptide Y, circular dichroic studies of the alanine-containing peptides were performed and structure affinity relationships are discussed. Comparing the affinities of the neuropeptide Y analogs to Y1 and Y2 receptors significant differences were found for the two binding sites, which suggests a different active conformation of neuropeptide Y at the two subtypes of receptors. Using molecular dynamics calculations, two distinct conformations were identified which are in good agreement with the data obtained by structure/affinity investigations.
Plasma-induced alignment of carbon nanotubes (2000)

Uniform films of well-aligned carbon nanotubes have been grown using microwave plasma-enhanced chemical vapor deposition. It is shown that nanotubes can be grown on contoured surfaces and aligned in a direction always perpendicular to the local substrate surface. The alignment is primarily induced by the electrical self-bias field imposed on the substrate surface from the plasma environment. It is found that switching the plasma source off effectively turns the alignment mechanism off, leading to a smooth transition between the plasma-grown straight nanotubes and the thermally grown “curly” nanotubes. The nanotubes grow at a surprisingly high rate of ∼100 nm/s in our plasma process, which may be important for large-scale commercial production of nanotubes.
Connective tissue and its heritable disorders : molecular, genetic, and medical aspects (1993)

Partial table of contents: Principles of Medical Genetics Morphology of Connective Tissue Structure of the Skin and Tendon Structure of Cartilage Structure of Bone Collagen: Protein Elastin Proteoglycans and Glycoproteins Keratin Bone Extracellular Matrix Degradation The Ehlers-Danlos Syndrome Pseudoxanthoma Elasticum The Marfan Syndrome Disorders of Copper Transport: Menkes' Disease and the Occipital Horn Syndrome Prolidase Deficiency Osteopetrosis and the Heritable Forms of Rickets Alacaptonuria Fibrodyxplasia Ossificans Progressiva Disorders of Lysosomal Enzymes Chondrodysplasis Disorders of Keratinization.
Skeletal muscle repair by adult human mesenchymal stem cells from synovial membrane (2003)

We have demonstrated previously that adult human synovial membrane-derived mesenchymal stem cells (hSM-MSCs) have myogenic potential in vitro (De Bari, C., F. Dell'Accio, P. Tylzanowski, and F.P. Luyten. 2001. Arthritis Rheum. 44:1928-1942). In the present study, we have characterized their myogenic differentiation in a nude mouse model of skeletal muscle regeneration and provide proof of principle of their potential use for muscle repair in the mdx mouse model of Duchenne muscular dystrophy. When implanted into regenerating nude mouse muscle, hSM-MSCs contributed to myofibers and to long term persisting functional satellite cells. No nuclear fusion hybrids were observed between donor human cells and host mouse muscle cells. Myogenic differentiation proceeded through a molecular cascade resembling embryonic muscle development. Differentiation was sensitive to environmental cues, since hSM-MSCs injected into the bloodstream engrafted in several tissues, but acquired the muscle phenotype only within skeletal muscle. When administered into dystrophic muscles of immunosuppressed mdx mice, hSM-MSCs restored sarcolemmal expression of dystrophin, reduced central nucleation, and rescued the expression of mouse mechano growth factor.
Interactions between the retinoid X receptor and a conserved region of the TATA-binding protein mediate hormone-dependent transactivation. (1995)

The retinoid X receptor (RXR) participates in a wide array of hormonal signaling pathways, either as a homodimer or as a heterodimer, with other members of the steroid and thyroid hormone receptor superfamily. In this report the ligand-dependent transactivation function of RXR has been characterized, and the ability of RXR to interact with components of the basal transcription machinery has been examined. In vivo and in vitro experiments indicate the RXR ligand-binding domain makes a direct, specific, and ligand-dependent contact with a highly conserved region of the TATA-binding protein. The ability of mutations that reduce ligand-dependent transcription by RXR to disrupt the RXR-TATA-binding protein interaction in vivo and in vitro suggests that RXR makes direct contact with the basal transcription machinery to achieve activation.
Digital Signal Processing Issues in the Context of Binaural and Transaural Stereophony (1995)

cote interne IRCAM: Jot95d
HeatProbe: a Thermal-based Power Meter System for Tracking Per-user Power Consumption (2011)

Abstract. This paper proposes HeatProbe, a per-user power meter system that uses thermal imaging to track the power consumption of individual users in a shared space. The per-user power consumption data produced by this system is helpful in designing personalized feedback to promote power-saving behavior.
Multiple Mechanisms of Phase Variation of PorA in Neisseria meningitidis (2000)

Previously, we reported that PorA expression in Neisseria meningitidis is modulated by variation in the length of the homopolymeric tract of guanidine residues between the -35 and -10 regions of the promoter or by deletion of porA. To reveal additional mechanisms of variation in PorA expression, the meningococcal isolates from 41 patients and 19 carriers were studied. In addition, at least 3 meningococcal isolates from different body parts of each of 11 patients were analyzed. Sequence analysis of the porA promoter showed that the spacer between the -35 and -10 regions varies in length between 14 and 24 bp. PorA expression was observed in strains with a porA promoter spacer of 16 to 24 bp. All but one strain with a porA promoter spacer of 16 to 20 bp and undetectable PorA expression have a homopolymeric tract of 8 or 6 instead of 7 adenine residues in the porA coding region. The other PorA-negative strain had a single-base-pair deletion in the coding region. The highest level of PorA expression was observed in strains with a promoter spacer of 17 or 18 bp. PorA expression was reduced twofold in strains with a porA promoter spacer of 16 or 19 bp. Strains with a 16-bp promoter spacer with substitutions in the polyguanidine tract displayed increased levels of PorA expression compared to strains with a homopolymeric tract of guanidine residues in the porA promoter. In conclusion, meningococci display multiple mechanisms for varying PorA expression.
Cetuximab and irinotecan as third line therapy in patients with advanced colorectal cancer after failure of irinotecan, oxaliplatin and 5-fluorouracil (2007)

Cetuximab (Erbitux) in combination with irinotecan is the most promising combination in heavily pretreated patients with advanced colorectal cancer. Efficacy of this combination was confirmed in the pivotal BOND I study. The aim of the present study was to evaluate efficacy and toxicity of a combination regimen of cetuximab and irinotecan but in contrast to the BOND I study all patients had previously received 5-FU, oxaliplatin and irinotecan and all had progressed during or shortly after completion of treatment. Before January 2005 salvage therapy with cetuximab and irinotecan was not used in Denmark. The Danish government had initiated a national programme for patients with advanced cancer and according to this programme the National Board of Health may approve and finance experimental treatment. From January 2005 to September 2005, 65 consecutive patients were treated with cetuximab (weekly) and irinotecan (each 2 or 3 weeks) at three university hospitals. Median age was 57 years (23-78), and median performance status was 1 (0-3). Response rate was 20%, median TTP was 5.5 months and median OS was 10.4 months. Response and survival was significantly correlated with severity of skin toxicity. Toxicity grade 3 was rare (skin toxicity 8%, diarrhoea 10%, nausea 3%, vomiting 3%, fatigue 8%). Salvage therapy with cetuximab and irinotecan is effective in patients pretreated with irinotecan, and oxaliplatin and in a general population the results from the BOND I study was confirmed.
Deliberate imposture: a challenge for automatic speaker verification systems. (1999)

We describe a speaker tracking and detection system, for Switchboard conversations, that uses a two-speaker and silence hidden Markov model (HMM) with a minimum state duration constraint and Gaussian mixture model (GMM) state distributions adapted from a single gender- and handset-independent imposter model distribution. Speaker tracking is used to segment speakers for detection, which is carried out by averaging frame scores of the Viterbi path and HNORM’ing via a novel parameter interpolation extension of HNORM for use with files of arbitrary lengths. Use of duration statistics augmenting the acoustic scores is also introduced via a nonlinear combination function. Results are reported on the NIST 1998 Multispeaker development evaluation dataset.
Development and a Practical Synthesis of the JAK2 Inhibitor LY2784544 (2011)

The route selection and process research and development of a practical synthesis for JAK2 inhibitor LY2784544 is described. The first-generation synthesis route, similar to that used in discovery for derivatization of a benzylic amine moiety, was 14 overall steps and possessed several steps that required extensive development for large-scale production. Route selection considerations led to a modified synthesis that utilized a novel vanadium-catalyzed carbon–carbon bond-forming arylation reaction for incorporation of the key benzylic morpholine moiety. A protecting group used to mask an amino pyrazole unit was modified from PMB to tert-butyl, resulting in a dramatic reduction in the overall length of the route. These two major changes resulted in an eight-step synthesis, which was six steps shorter than the first-generation synthesis. In the pilot plant, the new synthesis was scaled to produce >100 kg of LY2784544 in high yield and purity under GMP conditions. The overall development including the vanadium-catalyzed C–C bond-forming methodology, a ketone reductive deoxygenation, and a palladium-catalyzed amination is described.
The structure of Bombyx mori silk fibroin membrane swollen by water studied with ESR, 13C‐NMR, and FT‐IR spectroscopies (1990)

Abstract Structure of Bombyx mori silk fibroin membrane insolubilized with methanol, especially in the swollen state, is studied by means of spin‐label ESR, 13 C‐NMR, and FT‐IR (ATR method) spectroscopies. FT‐IR data indicate that the conformational transition from random coil to antiparallel β‐sheet occurs at the surface of the membrane upon immersion into 80% aqueous methanol. High resolution 13 C‐NMR observation of the membrane swollen in water shows that, the random coil portion whose segmental motion is very fast remains in the inner part of the swollen membrane. The fraction of this portion decreases with increasing methanol treatment time in the sample preparation. The heterogeneous structure of the swollen membrane was clarified from the complicated ESR spectra of the spin‐labeled silk fibroin membranes. The ESR spectra were analyzed quantitatively and the fractions of the fast, slow, and very slow motions of the spin‐label site (tyrosine side chain) were determined. A model is proposed for the heterogeneous structure of the swollen silk fibroin membrane.
Erythrocyte and polymorphonuclear cell transit time and concentration in human pulmonary capillaries (1994)

Pulmonary capillary transit times were examined in patients who required lung resection by use of 99mTc-labeled macroaggregates (99Tc-MAA) and chromium-labeled erythrocytes (51Cr-RBC) to measure regional blood flow and volume in the resected lung. Cell flow (cells.ml-1.s-1) to each resected lung sample was determined by multiplying the number of polymorphonuclear leukocytes (PMN) per milliliter of circulating blood by the blood flow to that sample. Capillary blood volume was obtained by multiplying the morphometrically determined fraction of pulmonary blood in capillaries by the total 51Cr-RBC volume in each sample. Cell concentrations (cells/ml) in capillary blood were calculated morphometrically, and capillary transit times were obtained by dividing cell concentration by cell flow. The results show that PMN transit times were 60-100 times longer than the RBC transit times, with a 22% overlap between their distributions. We conclude that PMN are concentrated with respect to RBC in pulmonary capillary blood because of differences in their transit times and that these long transit times provide an opportunity for PMN-endothelial interactions.
Dasatinib (BMS-354825) targets an earlier progenitor population than imatinib in primary CML but does not eliminate the quiescent fraction (2006)

Dasatinib (BMS-354825), a novel dual SRC/BCR-ABL kinase inhibitor, exhibits greater potency than imatinib mesylate (IM) and inhibits the majority of kinase mutations in IM-resistant chronic myeloid leukemia (CML). We have previously demonstrated that IM reversibly blocks proliferation but does not induce apoptosis of primitive CML cells. Here, we have attempted to overcome this resistance with dasatinib. Primitive IM-resistant CML cells showed only single-copy BCR-ABL but expressed significantly higher BCR-ABL transcript levels and BCR-ABL protein compared with more mature CML cells (P = .031). In addition, CrKL phosphorylation was higher in the primitive CD34(+)CD38(-) than in the total CD34(+) population (P = .002). In total CD34(+) CML cells, IM inhibited phosphorylation of CrKL at 16 but not 72 hours, consistent with enrichment of an IM-resistant primitive population. CD34(+)CD38(-) CML cells proved resistant to IM-induced inhibition of CrKL phosphorylation and apoptosis, whereas dasatinib led to significant inhibition of CrKL phosphorylation. Kinase domain mutations were not detectable in either IM or dasatinib-resistant primitive CML cells. These data confirm that dasatinib is more effective than IM within the CML stem cell compartment; however, the most primitive quiescent CML cells appear to be inherently resistant to both drugs.
c-myc inhibition of MyoD and myogenin-initiated myogenic differentiation. (1991)

In vertebrate development, a prominent feature of several cell lineages is the coupling of cell cycle regulation with terminal differentiation. We have investigated the basis of this relationship in the skeletal muscle lineage by studying the effects of the proliferation-associated regulator, c-myc, on the differentiation of MyoD-initiated myoblasts. Transient cotransfection assays in NIH 3T3 cells using MyoD and c-myc expression vectors demonstrated c-myc suppression of MyoD-initiated differentiation. A stable cell system was also developed in which MyoD expression was constitutive, while myc levels could be elevated conditionally. Induction of this conditional c-myc suppressed myogenesis effectively, even in the presence of MyoD. c-myc suppression also prevented up-regulation of a relative of MyoD, myogenin, which is normally expressed at the onset of differentiation in all muscle cell lines examined and may be essential for differentiation. Additional experiments tested whether failure to differentiate in the presence of myc could be overcome by providing myogenin ectopically. Cotransfection of c-myc with myogenin, MyoD, or a mixture of myogenin and MyoD showed that neither myogenin alone nor myogenin plus MyoD together could bypass the c-myc block. The effects of c-myc were further dissected by showing that c-myc can inhibit differentiation independently of Id, a negative regulator of muscle differentiation. These results lead us to propose that c-myc and Id constitute independent negative regulators of muscle differentiation, while myogenin and any of the other three related myogenic factors (MyoD, Myf-5, and MRF4/herculin/Myf-6) act as positive regulators.
Detection ofMycobacterium aviumsubsp.paratuberculosisin Infected Tissues by New Species-Specific Immunohistological Procedures (1998)

We have previously described the cloning and sequencing of a gene portion coding for the terminal part of a 34-kDa protein of Mycobacterium avium subsp. paratuberculosis, the etiological agent of Johne's disease (P. Gilot, M. De Kesel, L. Machtelinckx, M. Coene, and C. Cocito, J. Bacteriol. 175:4930-4935, 1993). The recombinant polypeptide (a362) carries species-specific B-cell epitopes which do not cross-react with other mycobacterial pathogens (M. De Kesel, P. Gilot, M.-C. Misonne, M. Coene, and C. Cocito, J. Clin. Microbiol. 31:947-954, 1993). The present work describes the preparation of polyclonal and monoclonal antibodies directed against a362 and the use of these immunoglobulins for histopathological diagnosis of Johne's disease. The new immunohistological procedures herewith detailed proved to be able to identify M. avium subsp. paratuberculosis antigens in the intestinal tissues and lymph nodes of cattle affected by either the paucibacillary or pluribacillary form of the disease. They yielded negative responses not only with healthy animals but also with those affected by tuberculosis (Mycobacterium bovis). Both immunohistological procedures proved to be as sensitive as or more sensitive than Ziehl-Neelsen staining and, in addition, to be endowed with species specificity.
Intracellular pH of bovine sperm increases during capacitation (1995)

The effect of heparin-induced capacitation on the intracellular pH (pHi) of individual bovine sperm was determined with image analysis. Sperm were loaded with the acetoxymethyl ester of the pH sensitive fluorescent indicator, 2',7'-bis(carboxyethyl)-5(6)-carboxy-fluorescein (BCECF). The pHi of 5303 sperm was evaluated from a total of five bulls at .5, 2, 3, 4, and 5 h of incubation. The pHi did not differ between the sperm head and mid-piece (P > 0.05). An increase in sperm head pHi was seen in heparin-treated sperm at 3, 4, and 5 h of incubation relative to sperm incubated without heparin (control, P < 0.05). At 5 h of incubation, the pHi in heparin-treated sperm was 6.92 +/- 0.07, while control-treated sperm pHi was 6.70 +/- 0.03. Initially a normal frequency distribution was seen for sperm pHi in both heparin- and control-treated sperm. As the incubation progressed, the frequency distribution began to skew towards higher pHi in both samples but was more dispersed for the heparin-treated sperm. Following an NH4Cl-induced alkaline load, the pHi of both control- and heparin-treated sperm recovered toward the resting pHi with a half-time of recovery of 1.5-1.7 min. The recovery of sperm pHi was not due to leakage of NH4+ into sperm because recovery also occurred with trimethylamine. The instantaneous velocity of the pHi recovery (v(i)) was dependent on pHi and decreased as pHi decreased. Capacitation by heparin was associated with an 81% decrease in v(i) at a pHi of 7.00, but there was no effect of capacitation on the proton buffering power of the sperm, which was 87 +/- 8 mM/pH unit. Results demonstrate that both the regulation of pHi and resting pHi were altered during capacitation of bovine sperm by heparin.