gebhart/patrepeval huggingface dataset:
A highly precise and portable genome engineering method allows comparison of mutational effects across bacterial species (2016)

Currently available tools for multiplex bacterial genome engineering are optimized for a few laboratory model strains, demand extensive prior modification of the host strain, and lead to the accumulation of numerous off-target modifications. Building on prior development of multiplex automated genome engineering (MAGE), our work addresses these problems in a single framework. Using a dominant-negative mutant protein of the methyl-directed mismatch repair (MMR) system, we achieved a transient suppression of DNA repair in Escherichia coli, which is necessary for efficient oligonucleotide integration. By integrating all necessary components into a broad-host vector, we developed a new workflow we term pORTMAGE. It allows efficient modification of multiple loci, without any observable off-target mutagenesis and prior modification of the host genome. Because of the conserved nature of the bacterial MMR system, pORTMAGE simultaneously allows genome editing and mutant library generation in other biotechnologically and clinically relevant bacterial species. Finally, we applied pORTMAGE to study a set of antibiotic resistance-conferring mutations in Salmonella enterica and E. coli. Despite over 100 million y of divergence between the two species, mutational effects remained generally conserved. In sum, a single transformation of a pORTMAGE plasmid allows bacterial species of interest to become an efficient host for genome engineering. These advances pave the way toward biotechnological and therapeutic applications. Finally, pORTMAGE allows systematic comparison of mutational effects and epistasis across a wide range of bacterial species.
Protein Purification Protocols (2003)

The first edition of Protein Purification Protocols (1996), edited by Professor Shawn Doonan, rapidly became very successful. Professor Doonan achieved his aims of p- ducing a list of protocols that w
Replication of the Apparent Excess Heat Effect in a Light Water Potassium Carbonate Nickel Electrolytic Cell (1996)

Replication of experiments claiming to demonstrate excess heat production in light water-Ni-K2CO3 electrolytic cells was found to produce an apparent excess heat of 11 W maximum, for 60 W electrical power into the cell. Power gains range from 1.06 to 1.68. The cell was operated at four different dc current levels plus one pulsed current run at 1 Hz, 10% duty cycle. The 28 liter cell used in these verification tests was on loan from a private corporation whose own tests with similar cells are documented to produce 50 W steady excess heat for a continuous period exceeding hundreds of days. The apparent excess heat can not be readily explained either in terms of nonlinearity of the cell's thermal conductance at a low temperature differential or by thermoelectric heat pumping. However, the present data do admit efficient recombination of dissolved hydrogen-oxygen as an ordinary explanation. Calorimetry methods and heat balance calculations for the verification tests are described. Considering the large magnitude of benefit if this effect is found to be a genuine new energy source, a more thorough investigation of evolved heat in the nickel-hydrogen system in both electrolytic and gaseous loading cells remains warranted.
A unified rate-distortion analysis framework for transform coding (2001)

In our previous work, we have developed a rate-distortion (R-D) modeling framework for H.263 video coding by introducing the new concepts of characteristic rate curves and rate curve decomposition. In this paper, we further show it is a unified R-D analysis framework for all typical image/video transform coding systems, such as embedded zero-tree wavelet (EZW), set partitioning in hierarchical trees (SPIHT) and JPEG image coding; MPEG-2, H.263, and MPEG-4 video coding. Based on this framework, a unified R-D estimation and control algorithm is proposed for all typical transform coding systems. We have also provided a theoretical justification for the unique properties of the characteristic rate curves. A linear rate regulation scheme is designed to further improve the estimation accuracy and robustness, as well as to reduce the computational complexity of the R-D estimation algorithm. Our extensive experimental results show that with the proposed algorithm, we can accurately estimate the R-D functions and robustly control the output bit rate or picture quality of the image/video encoder.
Lipids, lipoproteins, triglyceride clearance, and cytokines in human immunodeficiency virus infection and the acquired immunodeficiency syndrome. (1992)

Infection causes disturbances in lipid metabolism that may be mediated by cytokines. Therefore we studied plasma lipids, lipoproteins, triglyceride (TG) metabolism, and serum cytokines in three groups: patients with the acquired immunodeficiency syndrome (AIDS) without active secondary infection, patients with evidence of human immunodeficiency virus infection but without clinical AIDS (HIV+), and controls. Plasma TGs and FFA were increased in AIDS, while plasma cholesterol, high density lipoprotein (HDL) cholesterol, apolipoprotein-A-1 (Apo-A-1), low density lipoprotein (LDL) cholesterol, and Apo-B-100 levels were decreased. Increased TG levels in AIDS were primarily due to increases in very low density lipoprotein of normal composition; in addition, LDL and HDL were TG enriched. In HIV+, TGs and FFA were not increased, but total cholesterol, HDL cholesterol, Apo-A-1, and Apo-B-100 were significantly decreased. Interferon-alpha (IFN alpha) and C-reactive protein levels were increased in AIDS, but tumor necrosis factor and haptoglobin levels were not. There was a significant correlation between plasma TGs and IFN alpha levels (r = 0.477; P less than 0.01), but not between TGs and tumor necrosis factor, C-reactive protein, haptoglobin, or P-24 antigen. In addition, there was no relationship between circulating IFN alpha levels and plasma cholesterol, HDL cholesterol, Apo-A-1, LDL cholesterol, Apo-B-100, or FFA. TG clearance time and postheparin lipase were significantly decreased in AIDS and HIV+. There was a strong correlation between serum IFN alpha levels and TG clearance time in AIDS and HIV+ (r = 0.783; P less than 0.001). In summary, decreases in cholesterol and cholesterol containing lipoproteins (including HDL) in both AIDS and HIV+ precede the appearance of hypertriglyceridemia and are not related to IFN alpha or TG levels. Our data raise the possibility that with development of AIDS, subsequent increases in IFN alpha may contribute to increases in plasma TG levels in part by decreasing the clearance of TG.
Uses of Corona Discharges in the Semiconductor Industry (1987)

Corona discharges can be useful tools in the semiconductor industry. This paper describes published and previously unpublished applications of corona discharges in device manufacturing, in quality control of insulators, in failure analysis, and in understanding electrical properties of insulators. These uses include deposition of passivating glasses, decoration of defects in insulating thin films, and detection of very thin insulators. Applications of corona discharges in studying the physics of oxides and the kinetics of oxide growth are also reviewed. A description of previously unpublished uses of corona discharges for device evaluation and failure analysis is also presented, with emphasis on high voltage devices.
Nanopore Analysis of a Small 86‐Residue Protein (2007)

HPr is a small protein that must unfold to translocate the α-hemolysin pore (see image). Single amino acid substitutions can cause large changes to the translocation parameters. A conservative mutation is sufficient to alter the event profile; either the mutant must unfold differently or it must interact with the pore differently. A negatively charged mutant is driven through the pore, which facilitates unfolding.
A Comparative Oncology Study of Iniparib Defines Its Pharmacokinetic Profile and Biological Activity in a Naturally-Occurring Canine Cancer Model (2016)

Development of iniparib as an anti-cancer agent was hindered in part by lingering questions regarding its mechanism of action, the activity of its metabolites, and their potential accumulation in tumors. Due to strong similarities in metabolism of iniparib between humans and dogs, a veterinary clinical trial in pet dogs with spontaneous cancers was designed to answer specific questions pertaining to pharmacokinetic exposures and tolerability of iniparib. Dogs were treated with iniparib alone and in combination with carboplatin chemotherapy. Iniparib doses ranged between 10-70 mg/kg intravenously (IV). Plasma, tumor and normal tissue samples were collected before and at various time points scheduled after exposure for pharmacokinetic and biologic analysis. The primary endpoints included characterization of dose-limiting toxicities (DLT) and determination of the drug exposures that could be achieved in both normal and tumor tissues. Nineteen dogs were treated. DLT included fever, anorexia, diarrhea, neutropenia, and thrombocytopenia; most effects were attributable to carboplatin based on the timing of adverse event onset. The maximum tolerated dose (MTD) of iniparib was not identified. Moderate to high variability in plasma exposure was noted for iniparib and all metabolites between animals. When quantifiable, iniparib and metabolite plasma:tumor ratios were < 0.088 and <1.7, respectively. In this study, iniparib was well tolerated as a single agent and in combination with carboplatin over a range of doses. However, clinically relevant concentrations of the parent drug and selected metabolites were not detectable in canine tumor tissues at any studied dose, thus eliminating expectations for clinical responses in dogs or humans. Negative clinical trials in humans, and the uncertainties of its mechanism of action, ultimately led to the decision to stop clinical development of the drug. Nevertheless, the questions that can be asked and answered within the comparative oncology approach are evident from this successfully executed comparative clinical trial and exemplify the value of such studies in drug development.
Rotating-wave-plate Stokes polarimeter for differential group delay measurements of polarization-mode dispersion (1999)

We present a description and detailed uncertainty analysis of a polarization-mode dispersion (PMD) measurement system that uses the Jones matrix eigenanalysis measurement technique based on a rotating-wave-plate Stokes polarimeter. The uncertainty of the system is 3.2 fs (approximately 95% confidence interval) and is due primarily to PMD in the fiber leads of the measurement system.
Chapter 2: Source pigs (2009)

An islet xenotransplantation product includes live cells from a non-human source, in this study, a pig source. A live product cannot be subjected to conventional disinfection, and therefore the source pig must be depleted of infectious agents that can transmit to the recipient and cause disease. Among other requirements, regulatory guidances specify that donor animals fulfill the designated pathogen-free (DPF) status. Donor pigs fulfilling DPF status are generally bred and maintained in biosecure facilities, where they are shielded from the outside by filtered air, disinfected water, and irradiated food that is certified free of any mammalian protein. All materials are autoclaved upon entry, and personnel enter by shower-in/shower-out, and are wearing special clothes. The operation of such facilities is in compliance with Current Good Manufacturing Practices. To ensure DPF status, pigs are brought into such facilities via Cesarean section, and the source pigs are kept as a closed herd. The DPF status cannot be realized for endogenous viruses, such as porcine endogenous retrovirus. Therefore, regulatory authorities require patient monitoring after xenotransplantation. Considering the infectious pathogen status and necessary regulatory compliance, it is recommended that organ procurement be conducted at the animal facility and that cell manufacturing facilities be located nearby. To enable assessment of as-yet unknown pathogens long after xenotransplantation, regulatory guidances mandate archiving donor materials for at least 50 yr. As this is essentially a public health issue, governmental institutions are urged to be responsible for the archive.
Corin Is Present in the Normal Human Heart, Kidney, and Blood, with Pro–B-Type Natriuretic Peptide Processing in the Circulation (2010)

Our results support the concept that proBNP(1-108) may be processed outside of the heart in the circulation where the proprotein convertase is present. Moreover, sex may impact this process, since corin concentrations are higher in men. These findings may have important physiologic and pathophysiologic implications for the proBNP/corin system in the human.
Environmental Sound Recognition and Classification (2011)

Describes getting information out of soundtracks and environmental recordings.
Recent advances in the medicinal chemistry of antisense oligonucleotides. (2000)

The therapeutic index of an antisense oligonucleotide is determined by its nucleotide sequence and the type of chemical modification. In the last decade, a great deal of effort has been devoted to the development of a second generation of novel antisense oligonucleotide analogs with improved properties compared to the uniformly phosphorothioate-modified oligonucleotides of the first generation. In this review, the advances in the medicinal chemistry of antisense oligonucleotides of the last 2 years will be discussed with emphasis on modifications of the phosphate backbone, heterocyclic bases, carbohydrate moiety and pendent groups for improved delivery. Understanding the basic rules by which a certain modification influences the mechanism of antisense action, binding affinity, metabolic stability, cellular uptake, toxicity and bioavailability of an oligonucleotide, will have a profound impact on the further development of antisense therapeutics.
Establishment of Novel Embryonic Stem Cell Lines Derived from the Common Marmoset ( Callithrix jacchus ) (2005)

The successful establishment of human embryonic stem cell (hESC) lines has inaugurated a new era in regenerative medicine by facilitating the transplantation of differentiated ESCs to specific organs. However, problems with the safety and efficacy of hESC therapy in vivo remain to be resolved. Preclinical studies using animal model systems, including nonhuman primates, are essential to evaluate the safety and efficacy of hESC therapies. Previously, we demonstrated that common marmosets are suitable laboratory animal models for preclinical studies of hematopoietic stem cell therapies. As this animal model is also applicable to preclinical trials of ESC therapies, we have established novel common marmoset ESC (CMESC) lines. To obtain marmoset embryos, we developed a new embryo collection system, in which blastocysts can be obtained every 3 weeks from each marmoset pair. The inner cell mass was isolated by immunosurgery and plated on a mouse embryonic feeder layer. Some of the CMESC lines were cultured continuously for more than 1 year. These CMESC lines showed alkaline phosphatase activity and expressed stage-specific embryonic antigen (SSEA)-3, SSEA-4, TRA-1-60, and TRA-1-81. On the other hand, SSEA-1 was not detected. Furthermore, our novel CMESCs are pluripotent, as evidenced by in vivo teratoma formation in immunodeficient mice and in vitro differentiation experiments. Our established CMESC lines and the common marmoset provide an excellent experimental model system for understanding differentiation mechanisms, as well as the development of regenerative therapies using hESCs.
Role of resistance and exchange vessels in local microvascular control of skeletal muscle oxygenation in the dog. (1976)

The effects of reduction in perfusion pressure, arterial hypoxia, muscle contraction, and adrenergic stimulation on the hindlimb muscle circulation were studied. Under normal conditions (venous PO2 greater than or equal to 40 mm Hg), oxygen delivery to the muscle was maintained mainly by large increases in the capillary exchange capacity and the oxygen extraction ratio in accord with tissue demand following the application of the above stresses. The participation of the resistance vessels under these conditions was minimal. The prevailing venous oxygen tension then was reduced by several means and the response of vascular resistance and capillary exchange capacity to the same stresses was reexamined. At the lower prevailing venous PO2, the sensitivity of the resistance vessels to metabolic and hemodynamic disturbances was greatly increased. Consequently, blood flow autoregulation, functional hyperemia, and hypoxic hyperemia were more intense when venous oxygen tension was low. In contrast, the contribution of exchange capacity was diminished, probably owing to the fact that most of the capillaries already are open at low venous PO2. These data suggest that the locus of local microvascular control of muscle oxygenation shifts from the normally more sensitive precapillary sphincters to the proximal flow-controlling arterioles as the prevailing venous oxygen tension falls. Yet, although the relative contribution of the resistance and exchange vessels to intrinsic regulation of tissue oxygenation is related to the prevailing venous oxygen tension, the two compensatory mechanisms operating in concert maintain tissue PO2 above the critical level over a wide range of stresses.
Current status and future directions in lipid management: emphasizing low-density lipoproteins, high-density lipoproteins, and triglycerides as targets for therapy (2010)

Current lipid management guidelines are focused on decreasing low-density lipoprotein (LDL-C) levels as the primary target for reducing coronary heart disease (CHD) risk. Yet, many recent studies suggest that low levels of high-density lipoprotein (HDL-C) are a major independent risk factor for cardiovascular diseases. According to several clinical trials, a 1% increase in HDL-C is associated with a 0.7%-3% decrease in CHD events. The direct link between high levels of triglycerides (TG) and CHD, on the other hand, is less well defined. A large reduction in TG is needed to show a difference in CHD events, especially in men. Evidence for a shift in lipid management toward targeting both LDL-C and HDL-C as primary targets for therapy is presented. Currently, the 3-hydroxy-3-methylgutaryl coenzyme A reductase inhibitors (HMG-CoA reductase inhibitors) have proven to significantly decrease LDL-C levels, reduce CHD morbidity/mortality and improve overall survival. However, improvement of survival with statins may be due to other pleiotropic effects beyond LDL-C lowering. Fibric acid derivatives and niacin are primarily used to increase HDL-C levels, although with side effects. Future therapies targeting HDL-C may have profound results on reducing CHD morbidity and mortality. This article highlights existing and future targets in lipid management and is based on available clinical data. There is an urgent need for new treatments using a combination of drugs targeting both LDL-C and HDL-C. Such treatments are expected to have a superior outcome for dyslipidemia therapy, along with TG management.
Techniques for frame synchronization on unknown frequency selective channels (2002)

For burst oriented data transmission over frequency selective fading channels, the problem of optimum frame synchronization is discussed. A new criterion for frame synchronization accuracy is derived. In the following, we propose new algorithms that allow to estimate the frame start of a data packet transmitted over a noisy unknown dispersive fading channel. The algorithms are classified in data-aided and non-data aided algorithms. All techniques are successively derived from the ML criterion taking into account less and less information. Frame synchronization may be improved basing the frame start estimate on multiple frames. Solutions working under the constraint of clock inaccuracies are presented. The algorithms are compared using simulation. It is shown that a combination of power-ramp up and data-aided synchronization is best suited for asynchronous transmission. With minor modification, the algorithms may be used for multicarrier modulation as well.
Inflammatory Cells and Cancer (2001)

It is well established that cancer is a progressive disease, occurring in a series of well-defined steps, typically arising as a consequence of activating mutations (oncogenes) or deactivating mutations (tumor suppressor genes) in proliferating cells. From studies exploiting cultured tumor cells,
Transmit antennae space-time block coding for generalized OFDM in the presence of unknown multipath (2001)

Transmit antenna diversity has been exploited to develop high-performance space-time coders and simple maximum-likelihood decoders for transmissions over flat fading channels. Relying on block precoding, this paper develops generalized space-time coded multicarrier transceivers appropriate for wireless propagation over frequency-selective multipath channels. Multicarrier precoding maps the frequency-selective channel into a set of flat fading subchannels, whereas space-time encoding/decoding facilitates equalization and achieves performance gains by exploiting the diversity available with multiple transmit antennas. When channel state information is unknown at the receiver, it is acquired blindly based on a deterministic variant of the constant-modulus algorithm that exploits the structure of space-time block codes. To benchmark performance, the Cramer-Rao bound of the channel estimates is also derived. System performance is evaluated both analytically and with simulations.
Hadoop: The Definitive Guide (2009)

Discover how Apache Hadoop can unleash the power of your data. This comprehensive resource shows you how to build and maintain reliable, scalable, distributed systems with the Hadoop framework -- an open source implementation of MapReduce, the algorithm on which Google built its empire. Programmers will find details for analyzing datasets of any size, and administrators will learn how to set up and run Hadoop clusters. This revised edition covers recent changes to Hadoop, including new features such as Hive, Sqoop, and Avro. It also provides illuminating case studies that illustrate how Hado