gebhart/patrepeval huggingface dataset:
The relationship of intramuscular nerve branching and synaptogenesis to motoneuron survival (1992)

The target has been considered for some time to play a major role in allowing neurons to survive the period of naturally occurring cell death. For the motoneurons that innervate the chick limb, evidence is presented that suggests access to target-derived trophic factor via intramuscular nerve branches and synapses may be important in regulating neuronal survival. Alterations in branching and synapse formation produced by activity blockade as well as by alteration of adhesion molecule function are shown to result in changes in motoneuron survival consistent with the proposed hypothesis. The relevance of these observations to the numerical-matching hypothesis of vertebrate neuronal cell death is also considered.
Tchad - Projet d'Appui aux Services Agricoles et aux Organisations de Producteurs : evaluation environnementale (2002)

The Agricultural Services and Producer Organizations Project will promote sustainable growth in agricultural production and capacity building for agricultural services; complemented by the provision of infrastructure investments. This environmental assessment identifies the potential negative impacts such as soil and water pollution; sedimentation and salinization during construction of water management schemes; groundwater over-abstraction in the absence of sound construction techniques for pastoral wells; and, other impacts, i.e., loss of flora and fauna resulting from the establishment of borrow pits during construction of small dams, or, increased use of pesticides leading to biodiversity degradation. Mitigation measures suggested: implementation of an environmental analysis for each subproject; compliance with the Pest Management Plan, which outlines the regular assessment of pesticide residues in irrigated agricultural production systems; establishment of strong collaboration between the project and the National Malaria Control Project; establishment of a dam unit within the Rural Engineering Department of the Ministry of Agriculture, responsible for advising producer organizations in the management of dams; and supervising such organizations in the development of operations and maintenance of environmental management plans, in addition to providing training and technical assistance to develop capacities.
Dysregulations in the PI3K pathway and targeted therapies for head and neck squamous cell carcinoma (2017)

The phosphoinositide 3-kinase (PI3K) signaling pathway is the most commonly mutated pathway in head and neck squamous cell carcinoma (HNSCC). There are several drugs targeting members of the PI3K signaling pathway in development for HNSCC. In this article, we review the genetic alterations reported in the pathway pertinent to HNSCC, various agents in development targeting various mediators of the pathway, results from clinical trials, and remaining challenges in the development of PI3K pathway inhibitors.
Dysregulated Toll-like receptor expression and signaling in bone marrow-derived macrophages at the onset of diabetes in the non-obese diabetic mouse (2006)

The expression, responsiveness and regulation of mouse Toll-like receptors (TLRs) in bone marrow-derived macrophages (BM-Ø) were investigated prior to and following the development of diabetes. Expression of TLR3 and TLR5 was significantly higher in newly diabetic non-obese diabetic (NOD) mice when compared with pre-diabetic and control strains of mice. The TLR3 ligand poly(I)poly(C) triggered up-regulation of its own receptor in NOR and pre-diabetic NOD, but TLR3 was already highly expressed in diabetic NOD mice. Expression levels of TLR3 correlated with poly(I)poly(C)-triggered IFN activity. LPS triggered down-regulation of TLR4 in pre-diabetic NOD, NOR and BALB/c, while levels of TLR4 remained consistently elevated in type 1 diabetic NOD and type 2 diabetic NZL mice. Dysregulation of TLR4 expression in the diabetic state correlated with increased nuclear factor kappa B (NF-kappaB) activation in response to the TLR4 ligand LPS and higher expression of IL-12p40, tumor necrosis factor alpha (TNFalpha), IL-6 and inducible nitric oxide synthase but lowered expression of IL-10. Exposure of bone marrow precursor cells from NOD mice to a hyperglycemic environment during differentiation into macrophages resulted in elevated levels of TLR2 and TLR4 and the cytokine TNFalpha. The results indicate that macrophage precursors are influenced by systemic changes in diabetes favoring altered TLR expression and sensitivity that may influence susceptibility to macrophage-mediated diabetes complications and explain inappropriate responses to infection in diabetes.
Delay modelling improvement for low voltage applications (1995)

Based on an explicit formulation of delays, an improved model for low voltage operation of CMOS inverter has been derived. Extrinsic and intrinsic effects, such as transistor current variation, input slew rate effects and mobility improvement at low field are considered. Explicit dependence of inverter delay on input controlling ramp is given with clear evidence of supply and threshold voltage influences. Validations are obtained by comparing the calculated and measured oscillation period evolution of ring oscillators, under supply voltage conditions varying from standard 5/spl nu/, to values as low as the highest threshold voltage of the process involved. The speed performance evolution and the limits to the reduction of supply voltage are clearly given in terms of threshold voltage values.
Robust Imitation of Diverse Behaviors (2017)

Deep generative models have recently shown great promise in imitation learning for motor control. Given enough data, even supervised approaches can do one-shot imitation learning; however, they are vulnerable to cascading failures when the agent trajectory diverges from the demonstrations. Compared to purely supervised methods, Generative Adversarial Imitation Learning (GAIL) can learn more robust controllers from fewer demonstrations, but is inherently mode-seeking and more difficult to train. In this paper, we show how to combine the favourable aspects of these two approaches. The base of our model is a new type of variational autoencoder on demonstration trajectories that learns semantic policy embeddings. We show that these embeddings can be learned on a 9 DoF Jaco robot arm in reaching tasks, and then smoothly interpolated with a resulting smooth interpolation of reaching behavior. Leveraging these policy representations, we develop a new version of GAIL that (1) is much more robust than the purely-supervised controller, especially with few demonstrations, and (2) avoids mode collapse, capturing many diverse behaviors when GAIL on its own does not. We demonstrate our approach on learning diverse gaits from demonstration on a 2D biped and a 62 DoF 3D humanoid in the MuJoCo physics environment.
7B2 facilitates the maturation of proPC2 in neuroendocrine cells and is required for the expression of enzymatic activity. (1995)

The prohormone convertase PC2, which is thought to mediate the proteolytic conversion of many peptide hormones, has recently been shown to interact with the neuroendocrine-specific polypeptide 7B2 in Xenopus intermediate lobe (Braks, J. A. M., and G. J. M. Martens. Cell. 78:263. 1994). In the present work we have stably transfected neuroendocrine cell lines with rat 7B2 constructs and found that overexpression of 27 kD 7B2 greatly facilitates the kinetics of maturation of proPC2, both in AtT-20/PC2 cells and in Rin5f cells. The half-life of conversion of proPC2 was reduced from 2.7 to 1.7 h in AtT-20/PC2 cells stably transfected with 27 kD 7B2 cDNA. The previously proposed "chaperone" domain was not sufficient for this facilitation event; however, a construct corresponding to the 21-kD 7B2 protein (which represents the naturally occurring maturation product) functioned well. A 7B2 construct in which maturation of 27 kD 7B2 to its 21-kD form was blocked was unable to facilitate maturation of proPC2. To correlate effects on PC2 maturation with the actual generation of PC2 enzymatic activity, a similar transfection of 21 kD 7B2 was performed using CHO cells previously amplified for the expression of proPC2. Enzymatic activity cleaving the fluorogenic substrate Cbz-Arg-Ser-Lys-Arg-AMC was highly correlated with the expression of immunoreactive 21 kD 7B2 in the conditioned medium; medium obtained from the parent cell line was completely inactive. Enzymatic activity was identified as PC2 on the basis of inhibition by the carboxy-terminal peptide of 7B2, which has previously been shown to represent a potent and specific PC2 inhibitor. Taken together, our in vivo results indicate that the interesting secretory protein 7B2 is a bifunctional molecule with an amino-terminal domain involved in proPC2 transport as well as activation.
An increase in spinal cord noradrenaline is a major contributor to the antihyperalgesic effect of antidepressants after peripheral nerve injury in the rat (2012)

Antidepressants are often used for the treatment of neuropathic pain. Clinical studies suggest that the efficacy of serotonin (5-HT) and noradrenaline (NA) reuptake inhibitors (SNRIs) for neuropathic pain is greater than that of selective 5-HT reuptake inhibitors (SSRIs). In the present study, we determined the efficacy and mechanisms involved in the antihyperalgesic effects of milnacipran, an SNRI, compared with paroxetine, an SSRI, and maprotiline, a selective NA reuptake inhibitor, using a rat model of neuropathic pain. Male Sprague-Dawley rats underwent spinal nerve ligation (SNL), and the withdrawal threshold to paw pressure was measured. Intraperitoneal injection of milnacipran (3-30mg/kg) produced a dose-dependent antihyperalgesic effect. The effect was reversed by intrathecal injection of the α(2)-adrenoceptor antagonist idazoxan (30μg), but not by various 5-HT receptor antagonists. Paroxetine produced an antihyperalgesic effect only at the highest dose tested (10mg/kg). This effect was reversed by intrathecal injection of both idazoxan and ondansetron (30μg), a 5-HT3 receptor antagonist. Maprotiline produced an antihyperalgesic effect (10 and 30mg/kg), and the effect was reversed by intrathecal idazoxan. In microdialysis studies, NA and 5-HT concentrations in the spinal dorsal horn were increased after injection of either milnacipran or paroxetine, and only NA was increased after maprotiline. Furthermore, the NA content in the spinal cord of SNL rats was greater than that in normal animals. These findings suggest that an increase in NA in the spinal cord plays an important role in the antihyperalgesic effects of not only NA reuptake inhibitors but also SSRIs.
Biliverdin reductase is a transporter of haem into the nucleus and is essential for regulation ofHO-1gene expression by haematin (2008)

hBVR (human biliverdin reductase) is an enzyme that reduces biliverdin (the product of haem oxygenases HO-1 and HO-2 activity) to the antioxidant bilirubin. It also functions as a kinase and as a transcription factor in the MAPK (mitogen-activated protein kinase) signalling cascade. Fluorescence correlation spectroscopy was used to investigate the mobility of hBVR in living cells and its function in the nuclear transport of haematin for induction of HO-1. In transiently transfected HeLa cells only kinase-competent hBVR translocates to the nucleus. A reduced mobility in the nucleus of haematin-treated cells suggests formation of an hBVR-haematin complex and its further association with large nuclear components. The binding of haematin is specific, with the formation of a 1:1 molar complex, and the C-terminal 7-residue fragment KYCCSRK(296) of hBVR contributes to the binding. The following data suggest formation of dynamic complexes of hBVR-haematin with chromatin: (i) the reduction of hBVR mobility in the presence of haematin is greater in heterochromatic regions than in euchromatic domains and (ii) hBVR mobility is not retarded by haematin in nuclear lysates that contain only soluble factors. Moreover, hBVR kinase activity is stimulated in the presence of double-stranded DNA fragments corresponding to HO-1 antioxidant and HREs (hypoxia response elements), as well as by haematin. Experiments with nuclear localization, export signal mutants and si-hBVR [siRNA (small interfering RNA) specific to hBVR] indicate that nuclear localization of hBVR is required for induction of HO-1 by haematin. Because gene regulation is energy-dependent and haematin regulates gene expression, our data suggest that hBVR functions as an essential component of the regulatory mechanisms for haem-responsive transcriptional activation.
Direct electrical detection of antigen–antibody binding on diamond and silicon substrates using electrical impedance spectroscopy (2007)

The integration of biological molecules with semiconducting materials such as silicon and diamond has great potential for the development of new types of bioelectronic devices, such as biosensors and bioactuators. We have investigated the electrical properties of the antibody-antigen modified diamond and silicon surfaces using electrical impedance spectroscopy (EIS). Frequency dependent measurements at the open-circuit potential show: (a) significant changes in impedance at frequency >10(4) Hz when the surface immobilized IgG was exposed to anti-IgG, and (b) only little or no change when exposed to anti-IgM. Mott-Schottky measurements at high frequency (200 kHz) show that the impedance is dominated by the space charge layer of the semiconducting substrates. Silicon surfaces modified in a similar manner to the diamond surface are compared; n-type and p-type samples show complementary behavior, as expected for a field effect. We also show it is possible to directly observe antigen-antibody interaction at a fixed frequency in real time, and with no additional labeling.
A New Gene with Sequence and Structural Similarity to the Gene Encoding Human Lysyl Oxidase (1995)

We have isolated a number of recombinant clones from a human skin fibroblast cDNA library that contain extensive sequence homology to several coding domains within the human lysyl oxidase mRNA. Using one of these lysyl oxidase-like cDNAs, we obtained several overlapping genomic DNA recombinants. Restriction mapping and DNA sequence analysis revealed that the complete sequence of the lysyl oxidase-like mRNA was encoded by seven exons distributed throughout 25 kilobases of genomic DNA. Exons 2-6 encoded the region of greatest homology to lysyl oxidase. The size of these five exons, moreover, was exactly the same as the size of the corresponding exons within the lysyl oxidase gene. Northern blot analysis also revealed the concomitant appearance of lysyl oxidase and lysyl oxidase-like mRNA in several human tissues. It appears therefore that the genes encoding lysyl oxidase and a lysyl oxidase-like protein share a common evolutionary origin and may also be functionally related.
Structural and functional impairment of endocytic pathways by retinitis pigmentosa mutant rhodopsin-arrestin complexes (2004)

Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous degenerative eye disease. Mutations at Arg135 of rhodopsin are associated with a severe form of autosomal dominant RP. This report presents evidence that Arg135 mutant rhodopsins (e.g., R135L, R135G, and R135W) are hyperphosphorylated and bind with high affinity to visual arrestin. Mutant rhodopsin recruits the cytosolic arrestin to the plasma membrane, and the rhodopsin-arrestin complex is internalized into the endocytic pathway. Furthermore, the rhodopsin-arrestin complexes alter the morphology of endosomal compartments and severely damage receptor-mediated endocytic functions. The biochemical and cellular defects of Arg135 mutant rhodopsins are distinct from those previously described for class I and class II RP mutations, and, hence, we propose that they be named class III. Impaired endocytic activity may underlie the pathogenesis of RP caused by class III rhodopsin mutations.
<title>Multiparameter process metrology using scatterometry</title> (1995)

Scatterometry, the analysis of light scaattered by diffraction from periodic structures, is shown to be a versatile metrology technique applicable to a number of processes involved in microelectronic manufacturing. Contemporary inspection technologies such as scanning force microscopy (SFM) and scanning electron microscopy (SEM), apart from being slow and possibly destructive, in general cannot be used in-situ. Scatterometry, on the other hand, is rapid, nondestructive, inexpensive, and has the potential for use in-situ. In the production of a sub-micron microelectronic device, a typical series of process steps could involve the deposition of a poly-Si layer on oxide, followed by the application of an anti-reflection coating (ARC) and resist layer. After the resist is exposed and developed there are four dimensions which will affect further wafer processing: the linewidth of the resist, the resist thickness, and the ARC and poly-Si thicknesses. By varying the angle of incidence and continuously monitoring the diffracted power in any diffraction order, a scatter 'signature' may be obtained. We have demonstrated that there is sufficient information in one signature to determine all these dimensions at once, even when the linewidth dimensions are as small as 0.25 micrometers and the poly-Si thickness is on the order to 2500 angstrom. Results from determining these dimensions on a 25 wafer study show excellent agreement between the scatterometry measurements and measurements made with other metrology instruments (SEM and ellipsometer). For example, there is a 22.6 nm average difference between SEM and scatterometry measurements of 0.25 micrometers nominal linewidths. In addition, the repeatability (1(sigma) ) of this technique is shown to be sub-nanometer for all of the parameters measured (linewidth, resist height, ARC thickness, and poly thickness).
Phase 1 study of polyethylene glycol formulation of interferon α-2B (Schering 54031) in Philadelphia chromosome–positive chronic myelogenous leukemia (2001)

Interferon alpha (IFN-alpha) therapy improves prognosis in Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML). Polyethylene glycol (PEG) attached to IFN-alpha prolongs its half-life and may offer better therapy. The aims of this phase 1 study were to define the maximal tolerated dose (MTD), dose-limiting toxicities (DLTs), and response with PEG IFN-alpha-2b. Twenty-seven adults with Ph(+) CML in chronic or accelerated phases, in whom IFN-alpha treatment had failed, were studied. Patients had hematologic (9 patients) or cytogenetic resistance (12 patients) or intolerance to IFN-alpha (6 patients). PEG IFN-alpha-2b was given as a weekly subcutaneous injection starting at 0.75 microg/kg weekly and escalating to 1.5, 3, 4.5, 6, 7.5, and 9.0 microg/kg. The MTD was defined at 7.5 to 9 microg/kg; DLT included severe fatigue, neurotoxicity, liver function abnormalities, and myelosuppression. Longer administration of PEG IFN-alpha-2b resulted in chronic side effects not observed earlier, which defined the MTD and DLT. The proposed phase 2 dose of PEG IFN-alpha-2b was 6 microg/kg weekly. Among 19 patients with active disease, 7 (37%) achieved complete hematologic response (CHR); 2 (11%) had a cytogenetic response (complete). Among 8 patients treated in CHR, 7 (87%) improved cytogenetic response to complete (4 patients) or partial (3 patients). All 6 patients intolerant to IFN-alpha tolerated PEG IFN-alpha-2b; 4 improved their cytogenetic response. The results show that PEG IFN-alpha-2b is easier to deliver (once weekly), better tolerated, and perhaps more effective than IFN-alpha.
Molecular Cloning and Characterization of Two Isoforms of Saccharomyces cerevisiae Acyl-CoA:Sterol Acyltransferase (1996)

Esterification of cholesterol by acyl-CoA:cholesterol acyltransferase (ACAT) is a key element in maintaining cholesterol homeostasis in cells of higher animals. In the budding yeast, Saccharomyces cerevisiae, accumulation of ergosteryl esters accompanies entry into stationary phase and sporulation. We have determined that two genes in yeast, SAT1 and SAT2, encode isozymes of acyl-CoA:sterol acyltransferase (ASAT) which are functionally related to ACAT. The SAT1 isozyme is the major catalytic isoform, accounting for at least 65-75% of total ASAT activity. Targeted deletions of one or both genes do not compromise mitotic cell growth or spore germination. However, diploids that are homozygous for a SAT1 null mutation exhibit significantly reduced sporulation efficiency. Furthermore, a larger fraction of the sporulating diploids arrest after the first meiotic division. Human ACAT expressed in sat1 sat2 mutant cells can catalyze esterification of cholesterol and, to a lesser extent, ergosterol in vitro, but restores ergosteryl oleate formation in vivo to only approximately 8% of that catalyzed by yeast ASAT in wild-type cells.
Fumarates improve psoriasis and multiple sclerosis by inducing type II dendritic cells (2011)

Fumarates improve multiple sclerosis (MS) and psoriasis, two diseases in which both IL-12 and IL-23 promote pathogenic T helper (Th) cell differentiation. However, both diseases show opposing responses to most established therapies. First, we show in humans that fumarate treatment induces IL-4-producing Th2 cells in vivo and generates type II dendritic cells (DCs) that produce IL-10 instead of IL-12 and IL-23. In mice, fumarates also generate type II DCs that induce IL-4-producing Th2 cells in vitro and in vivo and protect mice from experimental autoimmune encephalomyelitis. Type II DCs result from fumarate-induced glutathione (GSH) depletion, followed by increased hemoxygenase-1 (HO-1) expression and impaired STAT1 phosphorylation. Induced HO-1 is cleaved, whereupon the N-terminal fragment of HO-1 translocates into the nucleus and interacts with AP-1 and NF-κB sites of the IL-23p19 promoter. This interaction prevents IL-23p19 transcription without affecting IL-12p35, whereas STAT1 inactivation prevents IL-12p35 transcription without affecting IL-23p19. As a consequence, GSH depletion by small molecules such as fumarates induces type II DCs in mice and in humans that ameliorate inflammatory autoimmune diseases. This therapeutic approach improves Th1- and Th17-mediated autoimmune diseases such as psoriasis and MS by interfering with IL-12 and IL-23 production.
Enhanced Adaptive Loop Filter for Motion Compensated Frame (2011)

We propose an adaptive loop filter to remove the redundancy between current and motion compensated frames so that the residual signal is minimized, thus coding efficiency increases. The loop filter coefficients and offset are optimized for each frame or a set of blocks to minimize the total energy of the residual signal resulting from motion estimation and compensation. The optimized loop filter with offset is applied for the set of blocks where the filtering process gives coding gain based upon rate-distortion cost. The proposed loop filter is used for the motion compensated frame whereas the conventional adaptive interpolation filter (AIF) is applied to the reference frames to interpolate the subpixel values. Another conventional scheme adaptive loop filter (ALF), is used after deblocking filtering to enhance quality of reconstructed frames, not to minimize energy of residual signal. The proposed loop filter can be used in combination with the AIF and ALF. Experimental results show that proposed algorithm provides the averaged bit reduction of 8% compared to conventional H.264/AVC scheme. When the proposed scheme is combined with AIF and ALF, the coding gain increases even further.