gebhart/patrepeval huggingface dataset:
A constitutive expression system for high‐throughput screening (2010)

Abstract To reduce the amount of consumables and number of pipetting steps in high‐throughput screening, a constitutive expression system was developed that comprises four different promoters of varying strength. The system was validated by the expression of different sucrose phosphorylase enzymes from Leuconostoc mesenteroides , Lactobacillus acidophilus and Bifidobacterium adolescentis in 96‐deep‐ and low‐well plates at three temperatures. Drastically improved soluble expression in mini‐cultures was observed for the enzymes from L. mesenteroides strains by reducing the promoter strength from strong to intermediate and by expressing the proteins at lower temperatures. In contrast, the enzymes from B. adolescentis and L. acidophilus were expressed most efficiently with a strong promoter. The constitutive expression of sucrose phosphorylases in low‐well plates resulted in a level of activity that is equal or even better than what was achieved by inducible expression. Therefore, our plasmid set with varying constitutive promoters will be an indispensable tool to optimize enzyme expression for high‐throughput screening.
The JC virus minimal core promoter is glial cell specific in vivo (1995)

The glial cell specificity of the human papovavirus JC (JCV), an etiologic agent for progressive multifocal leukoencephalopathy, is thought to be due to the presence of both positive and negative regulatory elements upstream of the TATA region within the JCV promoter. Here we report that the JCV minimal core promoter, containing only the TATA box and an 8-bp poly(T) region immediately upstream, is sufficient to initiate transcription of an attached gene in glial cells and functions as an autonomously active initiator. We further define the sequences required for this core promoter's glial cell specificity by appropriate substitution and point mutation analysis. Ectopic expression of Tst-1, a POU domain transcription factor that has been implicated in the regulation of oligodendrocyte development, leads to higher activation of the JCV minimal core promoter in Tst-1-deficient glial cells than in non-glial HeLa cells. These results suggest a requirement for a glial cell coactivator(s) for the optimum activation of the JCV minimal core promoter by Tst-1. A discrete affinity of Tst-1 for the JCV core promoter (Kd, 1.4 x 10(-8) M) is also shown to be optimal for its promoter strength. Mutations within the core promoter that maintain this affinity for Tst-1 show maintenance of promoter strength, whereas mutants carrying a change that results in an increased affinity for Tst-1 show reduced transcriptional activity. These results suggest that moderate affinity of Tst-1 for the JCV TATA region may allow the interaction of some glial cell-specific coactivator(s) along with the basal transcription machinery to direct glial cell-specific transcription from the JCV core promoter.
Coupled tendon-driven multijoint manipulator (2002)

A coupled tendon-driven manipulator called the CT arm is introduced, an its control is discussed. The CT arm has a specific tendon traction force transmission mechanism in which a pair of tendons for driving a joint are pulled from base actuators via pulleys mounted on the base-side joints. The mechanism makes the most of the coupled drive function of the tendon traction forces and thus can exhibit enormous payload capability. The CT arm is solidly structured and can be inexpensively manufactured because of its mechanical simplicity. A control algorithm which minimizes the square sum of the traction force of tendons while satisfying given restrictions is introduced. The validity of the control method is shown by computer simulation.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Kinetics of Fluorescence Quenching by Electron and H‐Atom Transfer (1970)

Abstract Fluorescence quenching rate constants, k q , ranging from 10 6 to 2 × 10 10 M −1 sec −1 , of more than 60 typical electron donor‐acceptor systems have been measured in de‐oxygenated acetonitrile and are shown to be correlated with the free enthalpy change, Δ G 23 , involved in the actual electron transfer process magnified image in the encounter complex and varying between + 5 and −60 kcal/mole. The correlation which is based on the mechanism of adiabatic outer‐sphere electron transfer requires Δ G ≠ 23 , the activation free enthalpy of this process to be a monotonous function of Δ G 23 and allows the calculation of rate constants of electron transfer quenching from spectroscopic and electrochemical data. A detailed study of some systems where the calculated quenching constants differ from the experimental ones by several orders of magnitude revealed that the quenching mechanism operative in these cases was hydrogen‐atom rather than electron transfer. The conditions under which these different mechanisms apply and their consequences are discussed.
First principles methods using CASTEP (2005)

Abstract The CASTEP code for first principles electronic structure calculations will be described. A brief, non-technical overview will be given and some of the features and capabilities highlighted. Some features which are unique to CASTEP will be described and near-future development plans outlined.
Proliferative kinetics and differentiation of murine blast cell colonies in culture: Evidence for variable G0 periods and constant doubling rates of early pluripotent hemopoietic progenitors (1983)

Several investigators have described hemopoietic colonies expressing multi-lineage differentiation in culture. We recently identified a class of murine hemopoietic progenitors which form blast cell colonies with very high replating efficiencies. In order to clarify further the relationship between progenitors for blast cell colonies and progenitors for the multilineage hemopoietic colonies in culture, we carried out analyses of kinetic and differentiation properties of murine blast cell colonies. Serial observations of the development of blast cell colonies into multilineage (and single lineage) colonies in cultures of spleen cells obtained from 5-fluorouracil (5-FU)-treated mice confirmed the transitional nature of the murine blast cell colonies. The data also suggested that the early pluripotent progenitors are in G0 for variable periods, and that when triggered into cell cycle, they proliferate at relatively constant doubling rates during the early stages of differentiation. The notion that some of the pluripotent progenitors are in G0 was also supported by long-term thymidine suicide studies in which spleen cells were exposed to 3H-thymidine with high specific activity for 5 days in culture, washed, and assayed for surviving progenitors. Comparison of replating abilities of day-7 and day-16 blast cell colonies from normal as well as 5-FU-treated mice indicated that some of the day-7 blast cell colonies are derived from maturer populations of progenitors which are sensitive to 5-FU. In contrast, progenitors for the day-16 blast cell colonies are dormant in cell cycle and were not affected by 5-FU treatment. Previously we reported that progenitors for day-16 blast cell colonies have a significant capacity for self-renewal. These observations suggest the hypothesis that the capability for self-renewal is accompanied by long periods of G0, and that once commitment to differentiation takes place, then active cell division occurs.
Differential expression of central metabotropic glutamate receptor (mGluR) subtypes in a clinical model of post-surgical pain (2004)

Tissue damage during surgery can induce 'central sensitization' and the development of pain and hyperalgesia post-operatively. Metabotropic glutamate receptors (mGluRs) contribute to nociception, inflammatory pain and hyperalgesia. This study characterized the temporal expression of group I (mGluR(1), mGluR(5)) and II (mGluR(2), mGluR(3)) mGluRs in spinal cord following abdominal surgery. Lumbar spinal cord was recovered from adult sheep euthanased 5 h, 1, 2, 3 and 6 days after undergoing a midline laparotomy, and processed for mGluR mRNA (real-time PCR, in situ hybridization) and protein (Western blotting). mGluR(5) mRNA was up-regulated 5 h and 1 day post-surgery in laminae I-II of the spinal cord dorsal horn. mGluR(5) protein was increased 1 day post-surgery. A delayed induction of mGluR(2) and mGluR(3) mRNAs and mGluR(2/3) protein occurred in spinal cord 3 days after surgery. By 6 days, mGluR(2) mRNA levels had returned to normal, however, mGluR(3) mRNA and mGluR(2/3) protein remained elevated. No change was detected in mGluR(1). These results demonstrate that mGluRs are differentially regulated following surgery and support a link between mGluR-mediated activity and post-surgical pain.
Synergy Testing by Etest, Microdilution Checkerboard, and Time-Kill Methods for Pan-Drug-Resistant Acinetobacter baumannii (2010)

Pan-drug-resistant (PDR) Acinetobacter baumannii is an important nosocomial pathogen that poses therapeutic challenges. Tigecycline alone or in combination with agents such as colestimethate, imipenem, and/or amikacin is being used clinically to treat PDR A. baumannii infections. The purpose of this study was to compare in vitro susceptibility testing by epsilometric (Etest) methods and the checkerboard (CB) method with testing by time-kill analysis. PDR A. baumannii clinical strains representing eight unique pulsed-field gel electrophoresis clones selected from a total of 32 isolates were tested in vitro with tigecycline, colestimethate, imipenem, and amikacin in single- and two-drug combinations by using two different methods of Etest (with a fixed ratio method [method 1] and with the incorporation of the active drug in medium [method 2]) and by using CB. The three-drug combination of imipenem, tigecycline, and amikacin was also tested by CB. These results were compared to time-kill results. Synergy was consistently detected with the imipenem plus colestimethate and tigecycline plus imipenem combinations. The Etest method with active drug incorporated into the agar allowed us to detect synergy even in the presence of the active drug and was more comparable to CB and time-kill tests. Synergy was detected with the three-drug combination of imipenem, tigecycline, and amikacin by both CB and time-kill methods among several tested clones. These findings indicate the utility of synergy testing to predict activity of specific antibiotic combinations against PDR A. baumannii.
Soft drug design: General principles and recent applications (2000)

Soft drug design represents a new approach aimed to design safer drugs with an increased therapeutic index by integrating metabolism considerations into the drug design process. Soft drugs are new therapeutic agents that undergo predictable metabolism to inactive metabolites after exerting their therapeutic effect. Hence, they are obtained by building into the molecule, in addition to the activity, the most desired way in which the molecule is to be deactivated and detoxified. In an attempt to systematize and summarize the related work done in a number of laboratories, including ours, the present review presents an overview of the general soft drug design principles and provides a variety of specific examples to illustrate the concepts. A number of already marketed drugs, such as esmolol, remifentanil, or loteprednol etabonate, resulted from the successful application of such design principles. Many other promising drug candidates are currently under investigation in a variety of fields including possible soft antimicrobials, anticholinergics, corticosteroids, beta-blockers, analgetics, ACE inhibitors, antiarrhythmics, and others. Whenever possible, pharmacokinetic and pharmacodynamic properties are briefly summarized and compared to those of other compounds used in the same field.
Alarm correlation (1993)

The authors discuss the development of an alarm correlation model and a corresponding software support system that allow efficient specification of alarm correlation by the domain experts themselves. Emphasis is placed on the end-user orientation of IMPACT, the intelligent management platform for alarm correlation tasks which implements the proposed model. The desire was to lower the barrier between the network management application development process and the end user of the application, the network management personnel. IMPACT is a step towards this goal. The proposed alarm correlation model was used for three purposes: intelligent alarm filtering, alarm generalization and fault diagnosis.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Longevity Regulation inSaccharomyces cerevisiae: Linking Metabolism, Genome Stability, and Heterochromatin (2003)

When it was first proposed that the budding yeast Saccharomyces cerevisiae might serve as a model for human aging in 1959, the suggestion was met with considerable skepticism. Although yeast had proved a valuable model for understanding basic cellular processes in humans, it was difficult to accept that such a simple unicellular organism could provide information about human aging, one of the most complex of biological phenomena. While it is true that causes of aging are likely to be multifarious, there is a growing realization that all eukaryotes possess surprisingly conserved longevity pathways that govern the pace of aging. This realization has come, in part, from studies of S. cerevisiae, which has emerged as a highly informative and respected model for the study of life span regulation. Genomic instability has been identified as a major cause of aging, and over a dozen longevity genes have now been identified that suppress it. Here we present the key discoveries in the yeast-aging field, regarding both the replicative and chronological measures of life span in this organism. We discuss the implications of these findings not only for mammalian longevity but also for other key aspects of cell biology, including cell survival, the relationship between chromatin structure and genome stability, and the effect of internal and external environments on cellular defense pathways. We focus on the regulation of replicative life span, since recent findings have shed considerable light on the mechanisms controlling this process. We also present the specific methods used to study aging and longevity regulation in S. cerevisiae.
An Integrated Built-In Test and Repair Approach for Memories with 2D Redundancy (2007)

An efficient on-chip infrastructure for memory test and repair is crucial to enhance yield and availability of SoCs. Therefore embedded memories are commonly equipped with spare rows and columns (2D redundancy). To avoid the storage of large failure bitmaps needed by classical algorithms for offline repair analysis, existing heuristics for built-in repair analysis (BIRA) either follow very simple search strategies or restrict the search to smaller local bitmaps. Exact BIRA algorithms work with sub analyzers for each possible repair combination. While a parallel implementation suffers from a high hardware overhead, a serial implementation leads to high test times. The integrated built-in test and repair approach proposed in this paper interleaves test and repair analysis and supports an exact solution without failure bitmap. The basic search procedure is combined with an efficient technique to continuously reduce the problem complexity and keep the test and analysis time low.
Field-Flow Fractionation: Analysis of Macromolecular, Colloidal, and Particulate Materials (1993)

Field-flow fractionation (FFF) is a family of flexible elution techniques capable of simultaneous separation and measurement. Its sample domain extends across a broad macromolecular-colloidal-particulate continuum from about 1 nanometer to more than 100 micrometers and incorporates both simple and complex macromaterials of biological, biomedical, industrial, and environmental relevance. Complex materials are separated into components to simplify measurement. Component properties measurable by FFF include mass, size, density, charge, diffusivity, and thickness of adsorbed layers. When characterization by these properties is inadequate, other measurement tools can be readily coupled to FFF, either off-line or on-line, by virtue of its flow-elution operation. This article describes the principles and major subtechniques of the FFF family along with application of its measurement and separative capabilities.
Charge Reduction in Electrosprays:  Slender Nanojets as Intermediates (2006)

Molecular dynamics simulations were used to study charge reduction in electrosprayed liquids through the formation of slender nanojet intermediates. The dynamics of shape relaxation and disintegration were followed as a function of charge in cylindrical water nanojets containing protonated diglycine molecules. Depending on the overall charge, simulations showed three basic scenarios for nanojet evolution. Moderately charged nanojets reduced to spheres, whereas nanojets charged close to the Rayleigh limit divided into two offspring droplets. Due to the large Coulomb interaction between ions, highly charged nanojets suffered repeated fission until the resulting droplets were charged below the Rayleigh limit. We demonstrated the role of surface fluctuations and Maxwell stress distributions in the disintegration process. The relaxation dynamics of the moderately charged systems to spherical geometry followed a damped oscillator behavior. Compared to neutral water jets, the presence of charges in subcritical nanojets resulted in a stiffer system with longer relaxation times to spherical geometry. Interparticle forces acting between the separating offspring droplets in nanojet breakup were also determined. Due to the increased role of fluctuations in nanojets, the Rayleigh limit was shown to overestimate the maximum charge on stable systems indicating higher nanodroplet production efficiency than one would expect from macroscopic theories alone.
Partial Storage Optimization and Load Control Strategy of Cloud Data Centers (2015)

We present a novel approach to solve the cloud storage issues and provide a fast load balancing algorithm. Our approach is based on partitioning and concurrent dual direction download of the files from multiple cloud nodes. Partitions of the files are saved on the cloud rather than the full files, which provide a good optimization to the cloud storage usage. Only partial replication is used in this algorithm to ensure the reliability and availability of the data. Our focus is to improve the performance and optimize the storage usage by providing the DaaS on the cloud. This algorithm solves the problem of having to fully replicate large data sets, which uses up a lot of precious space on the cloud nodes. Reducing the space needed will help in reducing the cost of providing such space. Moreover, performance is also increased since multiple cloud servers will collaborate to provide the data to the cloud clients in a faster manner.
Graphene Oxide, Highly Reduced Graphene Oxide, and Graphene: Versatile Building Blocks for Carbon‐Based Materials (2010)

Isolated graphene, a nanometer-thick two-dimensional analog of fullerenes and carbon nanotubes, has recently sparked great excitement in the scientific community given its excellent mechanical and electronic properties. Particularly attractive is the availability of bulk quantities of graphene as both colloidal dispersions and powders, which enables the facile fabrication of many carbon-based materials. The fact that such large amounts of graphene are most easily produced via the reduction of graphene oxide--oxygenated graphene sheets covered with epoxy, hydroxyl, and carboxyl groups--offers tremendous opportunities for access to functionalized graphene-based materials. Both graphene oxide and graphene can be processed into a wide variety of novel materials with distinctly different morphological features, where the carbonaceous nanosheets can serve as either the sole component, as in papers and thin films, or as fillers in polymer and/or inorganic nanocomposites. This Review summarizes techniques for preparing such advanced materials via stable graphene oxide, highly reduced graphene oxide, and graphene dispersions in aqueous and organic media. The excellent mechanical and electronic properties of the resulting materials are highlighted with a forward outlook on their applications.
In Vivo Characterization of the Murine Intranasal Model for Assessing the Immunogenicity of AttenuatedSalmonella entericaSerovar Typhi Strains as Live Mucosal Vaccines and as Live Vectors (2000)

Attenuated Salmonella enterica serovar Typhi live vector vaccine strains are highly immunogenic in mice following intranasal but not orogastric inoculation. To elucidate the relationship between organs within which vaccine organisms are found and the induction of specific serum immunoglobulin G (IgG) antibodies, we examined the in vivo distribution of serovar Typhi vaccine strain CVD 908-htrA following intranasal administration. Vaccine organisms were cultured from the nasal lymphoid tissue (NALT), lungs, and Peyer's patches 2 min after intranasal inoculation. Vaccine organisms persisted longer in NALT than in other organs. By decreasing the volume of intranasal inoculum containing 10(9) CFU (from a single 30- or 10-microl dose to four 2.5-microl doses given over the course of 1 h), we were able to significantly reduce the number of vaccine organisms isolated from the lungs (P < 0.05) without reducing the number of vaccine organisms in NALT. Reducing the number of vaccine organisms in the lungs resulted in a significant decrease in the serum tetanus antitoxin response elicited by CVD 908-htrA expressing tetanus toxin fragment C under the control of the redox-responsive nir15 promoter. In contrast, a similar construct expressing tetanus toxin fragment C under control of the constitutive lpp promoter stimulated a strong serum IgG tetanus antitoxin response with both inoculation regimens. The data suggest that following intranasal inoculation, NALT is a sufficient inductive site for elicitation of an immune response against both the live vector and heterologous antigen and, as occurs following oral inoculation of humans, attenuated serovar Typhi vaccine organisms elicit serum IgG responses.
Neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes have a pentameric quaternary structure (1991)

We have determined the subunit stoichiometry of chicken neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes by quantitation of the amount of radioactivity in individual subunits of [35S] methionine-labeled receptors. The chicken neuronal nicotinic acetylcholine receptor appears to be a pentamer of two alpha 4 acetylcholine-binding subunits and three beta 2 structural subunits. We also show that these expressed receptors bind L-[3H]nicotine with high affinity, are transported to the surface of the oocyte outer membrane, and cosediment on sucrose gradients with acetylcholine receptors isolated from chicken brain. Using this unique and generally applicable method of determining subunit stoichiometry of receptors expressed in oocytes, we obtained the expected (alpha 1) 2 beta 1 gamma delta stoichiometry for muscle-type acetylcholine receptors assembled from coexpression of either Torpedo alpha 1 or human alpha 1 subunits, with Torpedo beta 1, gamma, and delta subunits.