gebhart/patrepeval huggingface dataset:
Nanodroplet processing platform for deep and quantitative proteome profiling of 10–100 mammalian cells (2018)

Nanoscale or single-cell technologies are critical for biomedical applications. However, current mass spectrometry (MS)-based proteomic approaches require samples comprising a minimum of thousands of cells to provide in-depth profiling. Here, we report the development of a nanoPOTS (nanodroplet processing in one pot for trace samples) platform for small cell population proteomics analysis. NanoPOTS enhances the efficiency and recovery of sample processing by downscaling processing volumes to <200 nL to minimize surface losses. When combined with ultrasensitive liquid chromatography-MS, nanoPOTS allows identification of ~1500 to ~3000 proteins from ~10 to ~140 cells, respectively. By incorporating the Match Between Runs algorithm of MaxQuant, >3000 proteins are consistently identified from as few as 10 cells. Furthermore, we demonstrate quantification of ~2400 proteins from single human pancreatic islet thin sections from type 1 diabetic and control donors, illustrating the application of nanoPOTS for spatially resolved proteome measurements from clinical tissues.
Mutational analysis of the cleavage sequence of the human immunodeficiency virus type 1 envelope glycoprotein precursor gp160 (1989)

The envelope glycoproteins of the human immunodeficiency virus (HIV) type 1 are synthesized as a precursor molecule, gp160, which is cleaved to generate the two mature envelope glycoproteins, gp120 and gp41. The cleavage reaction, which is mediated by a host protease, occurs at a sequence highly conserved in retroviral envelope glycoprotein precursors. We have investigated the sequence requirements for this cleavage reaction by introducing four single-amino-acid changes into the glutamic acid-lysine-arginine sequence immediately amino terminal to the site of cleavage. We have also examined the effects of these mutations on the syncytium formation induced by HIV envelope glycoproteins. Our results indicate that a glutamic acid to glycine change at gp120 amino acid 516, a lysine to isoleucine change at amino acid 517, and an arginine to lysine change at amino acid 518 affect neither gp160 cleavage nor syncytium formation. The results obtained with the arginine to lysine change at amino acid 518 differ significantly from the results obtained with the same mutation at the envelope precursor cleavage site of a murine leukemia virus (E. O. Freed, and R. Risser, J. Virol. 61:2852-2856, 1987). An arginine to threonine mutation at gp120 amino acid 518, the terminal residue of gp120, abolishes both gp160 cleavage and syncytium formation. These findings demonstrate that despite its highly conserved nature, the basic pair of amino acids at the site of gp160 cleavage is not absolutely required for proper envelope glycoprotein processing. This report also supports the idea that cleavage of gp160 is required for activation of the HIV envelope fusion function.
Heterogeneous response of subsarcolemmal heart mitochondria to calcium (1986)

The Ca2+ -uptake capacity of two distinct populations of rat heart mitochondria was characterized by monitoring Ca2+ movements directly (using both 45Ca and dual-wavelength spectroscopy) and indirectly (monitoring effects of Ca2+ on respiration, enzyme release, and morphology). Interfibrillar mitochondria accumulated up to 930 nmol/mg protein, whereas the capacity of the subsarcolemmal mitochondria for Ca2+ uptake was limited to 620 nmol/mg protein. In both mitochondrial populations, uptake of the maximal amount of Ca2+ was accompanied by increased proton permeability and subsequent release of the accumulated Ca2+. Even when calcium was taken up and apparently retained by the subsarcolemmal mitochondria, resting respiratory rates increased. Morphological examination of these mitochondria revealed that, although the majority of mitochondria were in the aggregated, energized conformation, a considerable number were disrupted. These damaged mitochondria were probably responsible for the increased resting respiratory rates. No net release of calcium was observed, however, since the intact mitochondria could take up any calcium released by the damaged mitochondria. Morphological disruption of this subset of subsarcolemmal mitochondria was accompanied by release of not only cytochrome c but also of mitochondrial marker enzymes into the extramitochondrial milieu. In contrast, the interfibrillar mitochondria were relatively unaffected in terms of morphology and marker enzyme release, even when their capacity to retain calcium was exceeded.
Effect of 3 dietary phytogenic products on production performance and coccidiosis in challenged broiler chickens (2013)

A pen trial using 1,080 male Ross 308 broiler chicks (6 treatments with 6 replicates each) was conducted to examine the effects of 3 dietary phytogenic products on avian coccidiosis. The dietary treatments included (1) a negative control (NC), (2) a positive control (PC) without feed additive, (3) Narasin at 0.7 kg/t (COCC), (4) PHYT1 (oregano) at 2.0 kg/t, (5) PHYT2 (combination of Curcuma, saponins, and inulin) at 1.0 kg/t, and (6) PHYT3 (Quillaja) at 1.0 kg/t. Treatments 2 through 6 were challenged with a mixture of Eimeria acervulina, Eimeria maxima, and Eimeria tenella at d 15 via feed. Standard performance parameters and coccidial lesion scoring (d 22) were conducted. One week after coccidial challenge, chicks BW of the COCC treatment and the NC were higher than all other treatments. Body weights on d 39 were 2.47 (NC), 2.34 (PC), 2.51 (COCC), 2.35 (PHYT1), 2.39 (PHYT2), and 2.41 kg (PHYT3) with an SEM of 0.033. For the entire trial period, Narasin yielded a significantly better FCR in comparison with the PC and PHYT3. Overall mean lesion score was 0.54 (NC), 0.91 (PC), 0.50 (COCC), 0.81 (PHYT 1), 1.02 (PHYT 2), and 1.13 (PHYT 3) with an SEM of 0.122. It was concluded that all 3 phytogenic products were not effective at the used dosage in alleviating the negative effects observed in coccidiosis-challenged birds.
Optimization Design of Cascaded Classifiers (2005)

We present two optimization algorithms for the design of a cascade of classifiers, which is becoming a popular choice for many classification problems. Both algorithms represent each node classifier of a cascade using a high-level abstraction model and attempt to jointly optimize the setting of the thresholding parameters of all the node classifiers within the cascade. We applied both algorithms to optimize the famous Viola and Jones face detector and one of them in particular greatly improved the performance. We believe both algorithms can serve as a useful post-processing process for general cascaded classifier design.
Oral antioxidants counteract the negative effects of female aging on oocyte quantity and quality in the mouse (2002)

This study aims to compare the effect of early and late onset administration of oral antioxidants on number and quality of oocytes retrieved from aged mice after exogenous ovarian stimulation. Control hybrid females were fed a standard diet supplemented or not supplemented with pharmacological doses of vitamins C and E either from the first day of weaning or from the age of 32 weeks until they were autopsied at the age 40-42, 50-52, or 57-62 weeks after exogenous ovarian stimulation. Analysis of chromosomal distribution, DNA organization and cellular morphology was performed in ovulated cumulus-enclosed and -free oocytes, ovarian non-germinal vesicle oocytes enclosed by or free of mucous cumulus cells and in vitro-matured ovarian germinal-vesicle oocytes. Both early and late onset administration of oral antioxidants counteracted the negative effects of female aging on number of ovarian oocytes and total percentage of oocytes retrieved from oviducts and ovaries exhibiting a normal distribution of chromosomes in the metaphase-II plate and/or morphological traits of apoptosis. Although both early and late onset administration of oral antioxidants can counteract the negative effects of female aging on number and quality of oocytes, transference of these results to human beings should be made with caution because of the potential side effects of high doses of vitamins on reproductive function as well as many other undesirable systemic disorders.
Sequencing Knowledge for Construction Scheduling (1991)

This paper describes and formalizes knowledge utilized by skilled schedulers for sequencing construction activities. Although it is recognized that construction scheduling involves many tasks (activity identification, duration estimation, etc.), the focus here is limited to an understanding of a number of key activity sequencing principles. This paper provides a grammar or language that represents governing factors for construction activity sequencing. Four basic factors are identified and described in detail. The physical relationships that exist among the different building components is one of the factors. Another is the interaction of construction trades. Sequencing is also affected by the requirement of an interference‐free path for all the objects to be displaced around the job site at construction time. Code regulations are also relevant for determining the order of execution of certain activities. A discussion of the flexibility of these four different sequencing constraints and of their relation to time is also presented. Finally, a brief overview of a knowledge‐based prototype system that incorporates a few of the identified sequencing governing factors is provided.
Nonribosomal biosynthesis of peptide antibiotics (1990)

Peptide antibiotics are known to contain non-protein amino acids, D-amino acids, hydroxy acids, and other unusual constituents. In addition they may be modified by N-methylation and cyclization reactions. Their biosynthetic origin has been connected in many cases to an enzymatic system referred to as the 'thiotemplate multienzymic mechanism'. This mechanism includes the activation of the constituent residues as adenylates on the enzymic template, the acylation of specific template thiol groups, epimerization or N-methylation at this thioester stage, and polymerization in the sequence directed by the multienzymic structure with the aid of 4'-phosphopantetheine as a cofactor, including possible cyclization or terminal modification reactions. The reaction sequences leading to gramicidin S, tyrocidine, cyclosporine, bacitracin, polymyxin, actinomycin, enniatin, beauvericin, delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine and linear gramicidin are discussed. The structures of the multienzymes, their genetic organization, the biological functions of these peptides and results on related systems are discussed.
Implantation in Vivo and Retrieval of Artificial Structures Consisting of Rabbit and Human Urothelium and Human Bladder Muscle (1993)

The harvest of human bladder muscle and urothelial cells with subsequent growth may be useful for tissue replacement in genitourinary reconstruction. We previously reported the development of a system for the harvest, delivery and growth of rabbit urothelium in vivo using biodegradable polymers. We have now expanded and adapted this system for the harvest and in vivo implantation of human bladder urothelial and muscle cells. Synthetic polymer fibers of polyglycolic acid can serve as a scaffold and a delivery vehicle for the implantation of rabbit uroepithelial cells into athymic host animals. The polymers, which slowly degrade in vivo, allow the urothelial cells to survive at the implant site. We demonstrate that polyglycolic acid polymers support the proliferation of rabbit urothelial cells in situ and can serve as a maleable substrate for the creation of new urological structures that replace the degrading polymer fibers. We also show that human urothelial cells and bladder muscle cells, when implanted on polyglycolic acid fibers, from new urological structures in vivo composed of both cell types. The human cell-polymer xenografts can be recovered from host animals at extended times after implantation. These data suggest that feasibility of using polyglycolic acid polymers as substrates for the creation of human urothelial and muscle grafts for genitourinary reconstruction.
Alkali Metal Hydride Complexes: Well-Defined Molecular Species of Saline Hydrides* (2015)

The first examples of well-defined alkali metal hydride complexes have been synthesised and characterised in recent years, and their properties and underlying principles for their generation and stabilisation are emerging. This article gives an account of the hydrides of the alkali metals (Group 1 metals) and selected ‘-ate’ complexes containing hydrides and alkali metals, and reviews the chemistry of well-defined alkali metal hydride complexes including their syntheses, structures, and characteristics. The properties of the alkali metal hydrides LiH, NaH, KH, RbH, and CsH are dominated by their ionic NaCl structure. Stable, soluble, and well-defined LiH and NaH complexes have been obtained by metathesis and ß-hydride elimination reactions that require suitable ligands with some steric bulk and the ability to coordinate to several metal ions. These novel hydride complexes reward with higher reactivity and different properties compared with their parent ionic solids.
Administration of Low Doses of IL-2 Combined to Rapamycin Promotes Allogeneic Skin Graft Survival in Mice (2014)

Human CD4(+) CD25(+) FoxP3(+) regulatory T cells (Tregs) prevent allogeneic graft rejection by inhibiting T cell activation, as has been shown in mouse models. Recently, low-dose IL-2 administration was shown to specifically activate Tregs but not pathogenic conventional T cells, leading to resolution of type 1 diabetes in nonobese diabetic mice. We therefore tested the ability of low-dose IL-2 to prevent allogeneic skin graft rejection. We found that while IL-2 alone was inefficient in preventing rejection, combined with rapamycin, IL-2 treatment promoted skin graft survival both in minor disparate and semi-allogeneic skin graft combinations. Tregs are activated by this combined treatment while conventional CD4(+) cell expansion and activation are markedly inhibited. Co-administration of anti-CD25 antibodies dramatically reduces the effect of the IL-2/rapamycin treatment, strongly supporting a central role for Treg activation. Thus, we provide the first preclinical data showing that low-dose IL-2 combined with rapamycin can significantly delay transplant rejection in mice. These findings may form the rational for clinical evaluation of this novel approach for the prevention of transplant rejection.
The Role of Body-on-a-Chip Devices in Drug and Toxicity Studies (2011)

High-quality, in vitro screening tools are essential in identifying promising compounds during drug development. Tests with currently used cell-based assays provide an indication of a compound's potential therapeutic benefits to the target tissue, but not to the whole body. Data obtained with animal models often cannot be extrapolated to humans. Multicompartment microfluidic-based devices, particularly those that are physical representations of physiologically based pharmacokinetic (PBPK) models, may contribute to improving the drug development process. These scaled-down devices, termed micro cell culture analogs (μCCAs) or body-on-a-chip devices, can simulate multitissue interactions under near-physiological fluid flow conditions and with realistic tissue-to-tissue size ratios. Because the device can be used with both animal and human cells, it can facilitate cross-species extrapolation. Used in conjunction with PBPK models, the devices permit an estimation of effective concentrations that can be used for studies with animal models or predict the human response. The devices also provide a means for relatively high-throughput screening of drug combinations and, when utilized with a patient's tissue sample, an opportunity for individualized medicine. Here we review efforts made toward the development of microfabricated cell culture systems and give examples that demonstrate their potential use in drug development, such as identifying synergistic drug interactions as well as simulating multiorgan metabolic interactions. In addition to their use in drug development, the devices also can be used to estimate the toxicity of chemicals as occupational hazards and environmental contaminants.
Factors associated with the blood pressures of children born to women who were hypertensive during pregnancy. (1985)

At age 7.5 years the supine blood pressures of 216 children born to women who had been hypertensive during pregnancy were recorded. No associations were found between the blood pressures of the children and their mothers. The blood pressures of children whose mothers received methyldopa during pregnancy did not differ from those of children whose mothers had no specific treatment. Four boys whose mothers had taken methyldopa for more than 150 days had significantly lower systolic and diastolic pressures than those in whom the treatment had been of shorter duration. Significant findings from multiple regression analyses were: positive associations between boys' systolic and diastolic pressures and current weight, and diastolic pressure and maternal weight; negative associations between boys' systolic and diastolic pressures and birthweight; and a positive association between girls' systolic pressure and current weight.
Interfacial characteristics of a carbon nanotube–polystyrene composite system (2001)

The performance of a composite material system is critically controlled by the interfacial characteristics of the reinforcement and the matrix material. Here we report a study on the interfacial characteristics of a carbon nanotube (CNT)-reinforced polystyrene (PS) composite system through molecular mechanics simulations and elasticity calculations. In the absence of atomic bonding between the reinforcement and the matrix material, it is found that the nonbond interactions consists of electrostatic and van der Waals interaction, deformation induced by these forces, as well as stress/deformation arising from mismatch in the coefficients of thermal expansion. All of these contribute to the interfacial stress transfer ability, the critical parameter controlling material performance. Results of a CNT pullout simulation suggests that the interfacial shear stress of the CNT–PS system is about 160 MPa, significantly higher than most carbon fiber reinforced polymer composite systems.
Impala: A Modern, Open-Source SQL Engine for Hadoop. (2015)

Cloudera Impala is a modern, open-source MPP SQL en-gine architected from the ground up for the Hadoop data processing environment. Impala provides low latency and high concurrency for BI/analytic read-mostly queries on Hadoop, not delivered by batch frameworks such as Apache Hive. This paper presents Impala from a user’s perspective, gives an overview of its architecture and main components and briefly demonstrates its superior performance compared against other popular SQL-on-Hadoop systems. 1.
Efficacy and safety of epratuzumab in patients with moderate/severe flaring systemic lupus erythematosus: results from two randomized, double-blind, placebo-controlled, multicentre studies (ALLEVIATE) and follow-up (2013)

This initial efficacy and safety profile of epratuzumab supports its continued development for SLE treatment.
A rendering algorithm for visualizing 3D scalar fields (1988)

This paper presents a ray tracing algorithm for rendering 3D scalar fields. An illumination model is developed in which the field is characterized as a varying density emittter with a single level of scattering. This model is equivalent to a particle system in which the particles are sufficiently small. Along each ray cast from the eye, the field is expressed as a function of the ray parameter. The algorithm computes properties of the field along the ray such as the attenuated intensity, the peak density, and the center of gravity, etc., These are mapped into HSV color space to produce an image for visualization.Images produced in this manner are perceived as a varying density 'cloud' where color highlights the computed attributes. The application of this technique is demonstrated for visualizing a three dimensional seismic data set.
Quantitative expression of Toll‐like receptor‐2, ‐4, and ‐9 in dendritic cells generated from blasts of patients with acute myeloid leukemia (2008)

Microbial ligands like ODNs and LPS constitute promising adjuvants for enhancing (AML-) DC vaccines.
Modified-Peptide Inhibitors of Amyloid β-Peptide Polymerization (1999)

Cellular toxicity resulting from nucleation-dependent polymerization of amyloid beta-peptide (Abeta) is considered to be a major and possibly the primary component of Alzheimer's disease (AD). Inhibition of Abeta polymerization has thus been identified as a target for the development of therapeutic agents for the treatment of AD. The intrinsic affinity of Abeta for itself suggested that Abeta-specific interactions could be adapted to the development of compounds that would bind to Abeta and prevent it from polymerizing. Abeta-derived peptides of fifteen residues were found to be inhibitory of Abeta polymerization. The activity of these peptides was subsequently enhanced through modification of their amino termini with specific organic reagents. Additional series of compounds prepared to probe structural requirements for activity allowed reduction of the size of the inhibitors and optimization of the Abeta-derived peptide portion to afford a lead compound, cholyl-Leu-Val-Phe-Phe-Ala-OH (PPI-368), with potent polymerization inhibitory activity but limited biochemical stability. The corresponding all-D-amino acyl analogue peptide acid (PPI-433) and amide (PPI-457) retained inhibitory activity and were both stable in monkey cerebrospinal fluid for 24 h.
New Antifolates: Pharmacology and Clinical Applications (1996)

Many new antifolate compounds with unique clinical properties are currently in clinical development. Some of these agents have been rationally designed to circumvent known mechanisms of resistance to methotrexate, the most useful and extensively studied antifolate in clinical practice. Resistance to methotrexate can result from decreased active transport into cells, decreased polyglutamation resulting in enhanced drug efflux from cells, mutations in dihydrofolate reductase which reduce drug binding affinity, and increased expression of dihydrofolate reductase due to gene amplification or increased translational efficiency. As a consequence, the newer antifolates may differ from methotrexate because of increased lipid solubility, improved cellular uptake or increased ability to undergo polyglutamation. Several of these newer agents also uniquely target specific folate-dependent enzymes such as thymidylate synthase or glycinamide ribonucleotide transformylase. Antifolates currently in clinical development include trimetrexate, edatrexate, piritrexim, ZD1694, lometrexol, AG337, LY231514 and 1843U89. This report summarizes the basic pharmacology and potential clinical applications of these promising new agents.
PhaseIandIImetabolism andMRP2‐mediated export of bosentan in aMDCKII‐OATP1B1‐CYP3A4‐UGT1A1‐MRP2quadruple‐transfected cell line (2013)

These in vitro data indicate that bosentan is a substrate of UGT1A1. Moreover, the efflux transporter MRP2 mediates export of bosentan and most likely also of bosentan glucuronide in the cell system. Taken together, cell lines simultaneously expressing transport proteins and metabolizing enzymes represent additional useful tools for the investigation of the interplay of transport and metabolism of drugs.