gebhart/patrepeval huggingface dataset:
Synaptically Released and Exogenous ACh Activates Different Nicotinic Receptors to Enhance Evoked Glutamatergic Transmission in the Lateral Geniculate Nucleus (2005)

The effects of activation of nicotinic acetylcholine receptors (nAChRs) on glutamatergic transmission in the ventral lateral geniculate nucleus (LGNv) were examined in chick brain slices. Whole cell recordings showed that monosynaptic postsynaptic currents (PSCs) evoked in LGNv neurons by optic tract stimulation were blocked by glutamate receptor antagonists. Exogenously applied nicotine (0.5 microM), choline (1 mM), or acetylcholine (ACh, 100 microM) markedly increased (>3-fold) these evoked PSCs. Potentiation by ACh was dose-dependent and did not desensitize during a 5-min application. In a second set of experiments, the effect of releasing endogenous ACh by stimulating the lateral portion of the LGNv through a separate conditioning electrode before optic tract stimulation was examined. Conditioning stimulation trains increased PSCs by an average of 5.2-fold, an effect dependent on both the intensity and number of conditioning pulses. This increase in PSC amplitude was most likely caused by released ACh activating alpha6- and/or alpha3-containing nAChRs because it was blocked by 100 nM alpha-conotoxin MII, 100 nM dihydro-beta-erythroidine (DHbetaE), and 0.1-1.0 microM methyllycaconitine (MLA). In contrast, exogenously applied ACh increased PSC amplitude by activating a pharmacologically different population of nAChRs because this effect was inhibited by 100 nM alpha-bungarotoxin, 50 nM MLA, and a high concentration (30 microM) of DHbetaE, indicating that alpha7- and/or alpha8-containing receptors were involved. The results are consistent with a model whereby alpha6- and/or alpha3-containing nAChRs on retinal ganglion cell nerve terminals are located preferentially at cholinergic synapses, whereas alpha7- and/or alpha8-containing receptors are primarily extrasynaptic.
The Use of Transgenic Plants to Study the Regulation of Plant Carbohydrate Metabolism (1995)

Transgenic plants with decreased expression of specific enzymes provide a powerful new tool to investigate metabolic regulation. Their use is discussed in the context of theories of metabolic regulation. It is argued that an enzyme is a key site for regulation, in the strict sense, when (i) natural mechanisms exist to alter the activity of the enzyme in vivo ('regulatability'), and (ii) a change in the activity of the enzyme is able to lead to a change in flux through the pathway ('regulatory capacity'). Previous approaches to the study of regulation allow the identification of enzymes with high 'regulatability', but they do not provide consistent or valid criteria to assess their 'regulatory capacity'. They therefore do not distinguish between enzymes which actually control metabolic fluxes, and enzymes which just respond to changes initiated elsewhere in the pathway. They may also underestimate the contribution of enzymes that catalyse reversible reactions. In contrast, mutants and transgenic plants can be used to directly test the importance of different aspects of an enzyme's regulatory properties in vivo. Even more importantly, they provide a method to determine flux control coefficients which provide a quantitative measure of an enzyme's 'regulatory capacity'. Recent results are surnrnarised, and potential practical problems in measuring control coefficients are reviewed.
Experiments with a new boosting algorithm (1996)

Abstract. In an earlier paper, we introduced a new “boosting” algorithm called AdaBoost which, theoretically, can be used to significantly reduce the error of any learning algorithm that con-sistently generates classifiers whose performance is a little better than random guessing. We also introduced the related notion of a “pseudo-loss”which is a method for forcing a learning algorithm ofmulti-label concepts to concentrate on the labels that are hardest to discriminate. In this paper, we describe experiments we carried out to assess how well AdaBoost with and without pseudo-loss, performs on real learning problems. We performed two sets of experiments. The first set compared boosting to Breiman’s “bagging”method when used to aggregate various classifiers (including decision trees and single attribute-value tests). We compared the performance of the two methods on a collection of machine-learning benchmarks. In the second set of experiments, we studied in more detail the performance of boosting using a nearest-neighbor classifier on an OCR problem. 1
Expression of immunoreactive activin A protein in remodeling lesions associated with interstitial pulmonary fibrosis. (1996)

The expression of activin A, one of the transforming growth factor-beta supergene family, was studied in various pulmonary conditions associated with interstitial pulmonary fibrosis (3 cases with diffuse alveolar damage, 6 cases with idiopathic pulmonary fibrosis, and 1 case with pulmonary fibrosis associated with rheumatoid arthritis) using immunohistochemical techniques on paraffin-embedded sections. Controls consisted of 10 cases with normal pulmonary parenchyma, and 2 cases with primary pulmonary hypertension and 1 case with secondary pulmonary hypertension were also studied. The lung specimens from normal parenchyma weakly expressed immunoreactive activin A on the bronchiolar epithelium. In marked contrast, all of the specimens from cases with diffuse alveolar damage and interstitial pulmonary fibrosis demonstrated strong expression of activin A on metaplastic epithelium, hyperplastic smooth muscle cells, desquamated cells, and alveolar macrophages. Pulmonary arteries from patients with primary or secondary pulmonary hypertension showed abundant immunoreactive activin A on smooth muscle cells. These findings suggest a potential role for this growth factor, activin A, in the pathogenesis of pulmonary tissue remodeling associated with interstitial pulmonary fibrosis.
Evolution Toward Simpler, Less Risky Multilateral Wells (2001)

Abstract This paper discusses a paradigm shift in multilateral technology. The new focus is away from increasingly complex completion installations and toward simple yet highly functional multilateral completions. This paper reviews the TAML multilateral classification system, then traces Level 3 multilateral completion technology from original to current configurations. This latest iteration retains simplicity while adding full reentry functionality into both the main bore and lateral completions. The discussion then addresses pre-engineered Level 6 multilateral solutions that, by definition, uniquely embrace simplicity while providing optimal functionality. Following this discussion, case studies from Venezuela, Nigeria, and the United States illustrate installation procedures, operational issues, resulting efficiencies and economies, and opportunities to further improve the technologies.
Results From 2 Randomized, Double-Blind, Placebo-Controlled Studies of the Novel NK1 Receptor Antagonist Casopitant in Patients With Major Depressive Disorder (2011)

Clinical study results for neurokinin (NK) receptor antagonists in the treatment of depression have been mixed, with Phase III studies failing to fulfill the early promise demonstrated in Phase II studies. Casopitant, a selective NK1 antagonist that achieves nearly complete receptor occupancy was studied in 2 randomized, placebo-controlled, double-blind, Phase II trials in depressed outpatients to test the hypothesis that nearly complete NK1 receptor occupancy is required to achieve antidepressant efficacy. Study 092 used an interactive voice response system to recruit depressed patients with baseline Hamilton Depression (17-item, HAMD17) total scores higher than 24 who were randomized to fixed-dose casopitant 30 mg/d, 80 mg/d, or placebo for 8 weeks (n = 356). Study 096 required Carroll Depression Scale-Revised self-assessment scores of higher than 24 for randomization to casopitant 120 mg/d, paroxetine 30 mg/d (both reached via forced titration), or placebo for 8 weeks (n = 362). In study 092, casopitant 80 mg but not 30 mg achieved statistically significant improvement versus placebo on the primary outcome measure, week 8 last observation carried forward change from baseline HAMD17 (difference = -2.7; 95% confidence interval, -5.1 to -0.4, P = 0.023). In study 096, neither casopitant nor paroxetine achieved statistical separation from placebo at end point on HAMD17 (casopitant difference = -1.7; 95% CI, -3.8 to 0.4, P = 0.282). Casopitant and paroxetine were generally well tolerated in most patients. These studies suggest that NK1 antagonists that have nearly complete receptor occupancy may be effective in the treatment of depression.
Visual SLAM for autonomous ground vehicles (2011)

Simultaneous Localization and Mapping (SLAM) and Visual SLAM (V-SLAM) in particular have been an active area of research lately. In V-SLAM the main focus is most often laid on the localization part of the problem allowing for a drift free motion estimate. To this end, a sparse set of landmarks is tracked and their position is estimated. However, this set of landmarks (rendering the map) is often too sparse for tasks in autonomous driving such as navigation, path planning, obstacle avoidance etc. Some methods keep the raw measurements for past robot poses to address the sparsity problem often resulting in a pose only SLAM akin to laser scanner SLAM. For the stereo case, this is however impractical due to the high noise of stereo reconstructed point clouds. In this paper we propose a dense stereo V-SLAM algorithm that estimates a dense 3D map representation which is more accurate than raw stereo measurements. Thereto, we run a sparse V SLAM system, take the resulting pose estimates to compute a locally dense representation from dense stereo correspondences. This dense representation is expressed in local coordinate systems which are tracked as part of the SLAM estimate. This allows the dense part to be continuously updated. Our system is driven by visual odometry priors to achieve high robustness when tracking landmarks. Moreover, the sparse part of the SLAM system uses recently published sub mapping techniques to achieve constant runtime complexity most of the time. The improved accuracy over raw stereo measurements is shown in a Monte Carlo simulation. Finally, we demonstrate the feasibility of our method by presenting outdoor experiments of a car like robot.
A few billion lines of code later (2010)

How Coverity built a bug-finding tool, and a business, around the unlimited supply of bugs in software systems.
Safety and efficacy of denileukin diftitox in patients with steroid-refractory acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation (2004)

Denileukin diftitox (Ontak), a recombinant protein composed of human interleukin 2 (IL-2) fused to diphtheria toxin, has selective cytotoxicity against activated lymphocytes expressing the high-affinity IL-2 receptor. We conducted a phase 1 study of denileukin diftitox in 30 patients with steroid refractory acute graft-versus-host disease (GVHD). Seven patients received 9 microg/kg intravenously on days 1 and 15; 18 received 9 microg/kg intravenously on days 1, 3, 5, 15, 17, and 19; and 5 received 9 microg/kg intravenously on days 1 to 5 and 15 to 19. Hepatic transaminase elevation was the dose-limiting toxicity (DLT), and dose level 2 was the maximum tolerated dose (MTD). Overall, 71% of patients responded with complete resolution (12 of 24; 50%) or partial resolution (5 of 24; 21%) of GVHD. Eight of 24 patients (33%) are alive at 6.3 to 24.6 months (median, 7.2 months). Denileukin diftitox is tolerable and has promising activity in steroid-refractory acute GVHD.
Easily Prepared Azopyridines As Potent and Recyclable Reagents for Facile Esterification Reactions. An Efficient Modified Mitsunobu Reaction (2008)

The 2,2'-, 3,3'-, and 4,4'-azopyridines (azpy) and their alkyl pyridinium ionic liquids were studied as a new class of electron-deficient reagents for Mitsunobu esterification reactions. Among these compounds, 4,4'-azopyridine was found to be the most suitable one for esterification and thioesterification reactions. This new reagent promises to provide general and complementary solutions for separation problems in Mitsunobu reactions without restricting the reaction scope and facilitates the isolation of its hydrazine byproduct. The pyridine hydrazine byproduct can be simply recycled to its azopyridine by an oxidation reaction.
Structured Deferral: Synchronization via Procrastination (2013)

Developers often take a proactive approach to software design, especially those from cultures valuing industriousness over procrastination. Lazy approaches, however, have proven their value, with examples including reference counting, garbage collection, and lazy evaluation. This structured deferral takes the form of synchronization via procrastination, specifically reference counting, hazard pointers, and RCU (read-copy-update).
Hyaluronan and Homeostasis: A Balancing Act (2002)

The investigation of the functions of hyaluronan, which began with its discovery in the 1930s (1), has evolved slowly. Re-examination of the fascinating and complex biology of hyaluronan is now occurring both as a result of increasing awareness of the key and complex role played by components of the extracellular matrix in the regulation of developmental, physiological, and disease processes and of the relatively recent cloning of many new hyaladherins, synthases, and hyaluronidases. During the coming decades, unraveling the hyaluronan enigma will undoubtedly uncover paradigms that shift our understanding for its roles in the regulation of cell homeostasis and matrix biology.
A common TCR β-chain expressed by CD8+ intestinal mucosa T cells in ulcerative colitis (1996)

The human intestine contains two populations of anatomically distinct T cells, intraepithelial lymphocytes and lamina propria lymphocytes (LPLs), both of which preferentially use the TCR-alpha beta. Recent studies of TCR alpha- and beta-chain usage by intestinal intraepithelial lymphocytes, which are predominantly CD8+ T cells, have demonstrated that these cells are oligoclonal in normal intestine. This report examined the TCR beta-chains expressed by purified CD4+ and CD8+ T cells from normal colonic lamina propria and from the intestinal mucosa of patients with active ulcerative colitis (UC). The selective expansion of CD8+ T cell clones, and to a lesser extent CD4+ T cell clones, was observed among both normal LPLs and mucosal T cells in UC. These expanded LPL clones from normal donors were all distinct, but the mucosal T cells isolated from five of nine patients with UC contained CD8+ T cells expressing related V beta 3-J beta 1.6 TCRs. These observations provide evidence for an Ag-specific mucosal T cell response in UC. Further studies will be required to identify this Ag and address whether the T cell response to it plays a primary role in initiating the disease or is secondary to the inflammatory response.
From light scattering to the microstructure of thin-film multilayers (1993)

It is shown how light scattering provides a powerful tool for thin-film characterization. The introduction of a roughness isotropy degree permits the extraction of structural parameters of the stacks. Replication functions and residual roughnesses are given for TiO(2), SiO(2), and Ta(2)O(5) materials produced by ion-assisted deposition and ion plating. Additional confirmation is given by measurements of scattering versus wavelength. The sensitivity of design to material and substrate effects is studied. At low-loss levels, surface and bulk phenomena are discussed together. Microstructure is characterized in the frequency bandwidth given by experiment.
Annealing effect on the electrical properties of heavily C-doped p+GaAs (1991)

The carrier concentration in heavily carbon-doped p+-GaAs epilayers (about 1.3×1020 cm−3) is decreased together with the mobility by annealing at temperatures of 700 °C or higher but not at temperatures of 600 °C or lower. In comparatively lightly C-doped p+ epilayers (about 3.5×1019 cm−3), the carrier concentration is not decreased by annealing at temperatures from 500 to 850 °C. The deep photoluminescence peak at a wavelength of around 1080 nm accompanied by a hump at around 1420 nm are found only in heavily C-doped epilayers; the wavelength of this peak is very close to that of the Ga vacancy −the C donor center. The photoluminescence intensity is increased by the annealing at 850 °C but not at 600 °C. The thermal behaviors of the deep photoluminescence levels can well explain those of carrier concentration and mobility if we consider the photoluminescence levels to be the index for the compensation centers.
Frequency, Spectrum, and Nonzero Fitness Costs of Resistance to Myxopyronin in Staphylococcus aureus (2012)

The antibiotic myxopyronin (Myx) functions by inhibiting bacterial RNA polymerase (RNAP). The binding site on RNAP for Myx-the RNAP "switch region SW1/SW2 subregion"-is different from the binding site on RNAP for the RNAP inhibitor currently used in broad-spectrum antibacterial therapy, rifampin (Rif). Here, we report the frequency, spectrum, and fitness costs of Myx resistance in Staphylococcus aureus. The resistance rate for Myx is 4 × 10(-8) to 7 × 10(-8) per generation, which is equal within error to the resistance rate for Rif (3 × 10(-8) to 10 × 10(-8) per generation). Substitutions conferring Myx resistance were obtained in the RNAP β subunit [six substitutions: V1080(1275)I, V1080(1275)L, E1084(1279)K, D1101(1296)E, S1127(1322)L, and S1127(1322)P] and the RNAP β' subunit [five substitutions: K334(345)N, T925(917)K, T925(917)R, G1172(1354)C, and G1172(1354)D] (residues numbered as in Staphylococcus aureus RNAP and, in parentheses, as in Escherichia coli RNAP). Sites of substitutions conferring Myx resistance map to the RNAP switch region SW1/SW2 subregion and do not overlap the binding site on RNAP for Rif, and, correspondingly, Myx-resistant mutants exhibit no cross-resistance to Rif. All substitutions conferring Myx resistance exhibit significant fitness costs (4 to 15% per generation). In contrast, at least three substitutions conferring Rif resistance exhibit no fitness costs (≤0% per generation). The observation that all Myx-resistant mutants have significant fitness costs whereas at least three Rif-resistant mutants have no fitness costs, together with the previously established inverse correlation between fitness cost and clinical prevalence, suggests that Myx resistance is likely to have lower clinical prevalence than Rif resistance.
Editorial Notes Vol.7(2) (2013)

DOI: http://dx.doi.org/10.3329/jbt.v7i2.16449 Journal of Business and Technology Vol.7(2) 2012
Nuclear Localization and Shuttling of Herpes Simplex Virus Tegument Protein VP13/14 (2001)

The herpes simplex virus type 1 gene UL47 encodes the tegument proteins referred to collectively as VP13/14, which are believed to be differentially modified forms of the same protein. Here we show that the major product of the UL47 gene during transient expression is VP14, suggesting that some feature of virus infection is required to produce VP13. We have tagged VP13/14 with green fluorescent protein and have demonstrated that the protein is targeted efficiently to the nucleus, where it often localizes in numerous punctate domains. Furthermore, we show that removal of the N-terminal 127 residues of the protein abrogates nuclear accumulation, and we have identified a 14-amino-acid peptide from this region that is sufficient to function as a nuclear targeting signal and transport a heterologous protein to the nucleus. This short peptide contains two runs of four arginine residues, suggesting that the VP13/14 nuclear localization signal may behave in a manner similar to that of the arginine-rich nuclear localization signals of the retrovirus transactivator proteins Tat, Rev, and Rex. In addition, by using heterokaryon assays, we show that VP13/14 is capable of shuttling between the nucleus and cytoplasm of the cell, a property that may be attributed to three leucine-rich stretches in the C-terminal half of the protein that again bear similarity to the nuclear export signals of Rev and Rex. This is the first demonstration of a tegument protein that is specifically targeted to the nucleus, a feature which may be relevant both during virus entry, when VP13/14 enters the cell as a component of the tegument, and at later times, when large amounts of newly synthesized VP13/14 are present within the cell.
Tirofiban and Activated Protein C Synergistically Inhibit the Instant Blood Mediated Inflammatory Reaction (IBMIR) from Allogeneic Islet Cells Exposure to Human Blood (2009)

Instant blood mediated inflammatory reaction (IBMIR) occurs when islets are exposed to blood and manifests clinically as portal vein thrombosis and graft failure. The aim of this study was to determine the impact of recombinant human activated protein C (rhAPC) and platelet inhibition on IBMIR in order to develop a better targeted treatment for this condition. Five thousand human islet cell equivalents (IEQ) were mixed in a PVC loop system with 7 mL of ABO compatible human blood and incubated with rhAPC, either alone or in combination with tirofiban. Admixing human islets and blood caused rapid clot formation, consumption of platelets, leukocytes, fibrinogen, coagulation factors and raised d-dimers. Islets were encased in a fibrin and platelet clot heavily infiltrated with neutrophils. Tirofiban monotherapy was ineffective, whereas rhAPC monotherapy prevented IBMIR in a dose-dependent manner, preserving islet integrity while maintaining platelet and leukocyte counts, fibrinogen and coagulation factor levels, and reducing d-dimer formation. The combination of tirofiban and low-dose rhAPC inhibited IBMIR synergistically with an efficacy equal to high dose rhAPC. Tirofiban and rhAPC worked synergistically to preserve islets, suggesting that co-inhibition of the platelet and coagulation pathways' contribution to thrombin generation is required for the optimal anti-IBMIR effect.
Functional Screening of Serine Protease Inhibitors in the Medical Leech Hirudo medicinalis Monitored by Intensity Fading MALDI-TOF MS (2005)

The blood-feeding invertebrates are a rich biological source of drugs and lead compounds to treat cardiovascular diseases because they have evolved highly efficient mechanisms to feed on their hosts by blocking blood coagulation. In this work, we focused our attention on the leech Hirudo medicinalis. We performed, by "intensity fading" MALDI-TOF mass spectrometry, a comprehensive detection and functional analysis of pre-existent peptides and small proteins with the capability of binding to trypsin-like proteases related to blood coagulation. Combining "intensity fading MS" and off-line LC prefractionation allowed us to detect more than 75 molecules present in the leech extract that interact specifically with a trypsin-like protease over a sample profile of nearly 2,000 different peptides/proteins in the 2-20-kDa range. Moreover we resolved 232 individual components from the complex mixture, 13 of which have high sequence homology with previously described serine protease inhibitors. Our findings indicate that such extracts are much more complex than expected. Additionally, intensity fading MS, when complemented with LC separation strategies, seems to be a useful tool to investigate complex biological samples, establishing a new bridge between profiling, functional peptidomics, and subsequent drug discovery.