gebhart/patrepeval huggingface dataset:
In Vitro and In Vivo Profiles of ACH-702, an Isothiazoloquinolone, against Bacterial Pathogens (2011)

ACH-702, a novel isothiazoloquinolone (ITQ), was assessed for antibacterial activity against a panel of Gram-positive and Gram-negative clinical isolates and found to possess broad-spectrum activity, especially against antibiotic-resistant Gram-positive strains, including methicillin-resistant Staphylococcus aureus (MRSA). For Gram-negative bacteria, ACH-702 showed exceptional potency against Haemophilus influenzae, Moraxella catarrhalis, and a Neisseria sp. but was less active against members of the Enterobacteriaceae. Good antibacterial activity was also evident against several anaerobes as well as Legionella pneumophila and Mycoplasma pneumoniae. Excellent bactericidal activity was observed for ACH-702 against several bacterial pathogens in time-kill assays, and postantibiotic effects (PAEs) of >1 h were evident with both laboratory and clinical strains of staphylococci at 10 × MIC and similar in most cases to those observed for moxifloxacin at the same MIC multiple. In vivo efficacy was demonstrated against S. aureus with murine sepsis and thigh infection models, with decreases in the number of CFU/thigh equal to or greater than those observed after vancomycin treatment. Macromolecular synthesis assays showed specific dose-dependent inhibition of DNA replication in staphylococci, and biochemical analyses indicated potent dual inhibition of two essential DNA replication enzymes: DNA gyrase and topoisomerase IV. Additional biological data in support of an effective dual targeting mechanism of action include the following: low MIC values (≤0.25 μg/ml) against staphylococcal strains with single mutations in both gyrA and grlA (parC), retention of good antibacterial activity (MICs of ≤0.5 μg/ml) against staphylococcal strains with two mutations in both gyrA and grlA, and low frequencies for the selection of higher-level resistance (<10⁻¹⁰). These promising initial data support further study of isothiazoloquinolones as potential clinical candidates.
Digital biology and chemistry (2014)

This account examines developments in "digital" biology and chemistry within the context of microfluidics, from a personal perspective. Using microfluidics as a frame of reference, we identify two areas of research within digital biology and chemistry that are of special interest: (i) the study of systems that switch between discrete states in response to changes in chemical concentration of signals, and (ii) the study of single biological entities such as molecules or cells. In particular, microfluidics accelerates analysis of switching systems (i.e., those that exhibit a sharp change in output over a narrow range of input) by enabling monitoring of multiple reactions in parallel over a range of concentrations of signals. Conversely, such switching systems can be used to create new kinds of microfluidic detection systems that provide "analog-to-digital" signal conversion and logic. Microfluidic compartmentalization technologies for studying and isolating single entities can be used to reconstruct and understand cellular processes, study interactions between single biological entities, and examine the intrinsic heterogeneity of populations of molecules, cells, or organisms. Furthermore, compartmentalization of single cells or molecules in "digital" microfluidic experiments can induce switching in a range of reaction systems to enable sensitive detection of cells or biomolecules, such as with digital ELISA or digital PCR. This "digitizing" offers advantages in terms of robustness, assay design, and simplicity because quantitative information can be obtained with qualitative measurements. While digital formats have been shown to improve the robustness of existing chemistries, we anticipate that in the future they will enable new chemistries to be used for quantitative measurements, and that digital biology and chemistry will continue to provide further opportunities for measuring biomolecules, understanding natural systems more deeply, and advancing molecular and cellular analysis. Microfluidics will impact digital biology and chemistry and will also benefit from them if it becomes massively distributed.
ChemInform Abstract: TRAPPING FREE RADICALS FORMED IN THE REACTION OF OZONE WITH SIMPLE OLEFINS USING 2,6‐DI‐TERT‐BUTYL‐4‐CRESOL (BHT) (1985)

Abstract 2,6‐Di‐tert.‐butyl‐4‐kresol (I) kann freie Radikale, wie sie bei der Ozonolyse von Olefinen wie (II) erhalten werden, als Addukte abfangen.
Diacetylbis(N(4)-methylthiosemicarbazonato) Copper(II) (CuII(atsm)) Protects against Peroxynitrite-induced Nitrosative Damage and Prolongs Survival in Amyotrophic Lateral Sclerosis Mouse Model (2011)

Amyotrophic lateral sclerosis (ALS) is a progressive paralyzing disease characterized by tissue oxidative damage and motor neuron degeneration. This study investigated the in vivo effect of diacetylbis(N(4)-methylthiosemicarbazonato) copper(II) (CuII(atsm)), which is an orally bioavailable, blood-brain barrier-permeable complex. In vitro the compound inhibits the action of peroxynitrite on Cu,Zn-superoxide dismutase (SOD1) and subsequent nitration of cellular proteins. Oral treatment of transgenic SOD1G93A mice with CuII(atsm) at presymptomatic and symptomatic ages was performed. The mice were examined for improvement in lifespan and motor function, as well as histological and biochemical changes to key disease markers. Systemic treatment of SOD1G93A mice significantly delayed onset of paralysis and prolonged lifespan, even when administered to symptomatic animals. Consistent with the properties of this compound, treated mice had reduced protein nitration and carbonylation, as well as increased antioxidant activity in spinal cord. Treatment also significantly preserved motor neurons and attenuated astrocyte and microglial activation in mice. Furthermore, CuII(atsm) prevented the accumulation of abnormally phosphorylated and fragmented TAR DNA-binding protein-43 (TDP-43) in spinal cord, a protein pivotal to the development of ALS. CuII(atsm) therefore represents a potential new class of neuroprotective agents targeting multiple major disease pathways of motor neurons with therapeutic potential for ALS.
Changes in the Law of Contract (1961)

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Robot handling of flat textile materials (1997)

The authors present a robotic system incorporating vision and force/torque sensing for handling flat textile materials and describe the results of experiments to measure the accuracy and reliability of the system for a variety of representative handling tasks for textile materials.
Nuclear magnetic resonance spectroscopy for studying the development and detection of the grain weevil,<i>Sitophilus granarius</i>(L.) (Coleoptera: Curculionidae), within wheat kernels (1984)

Abstract A novel non-destructive method was devised for studying the development of insects hidden within individual wheat grains using a standard nuclear magnetic resonance (NMR) spectrometer. The development of Sitophilus granarius (L.) at 25°C and 70% RH was studied from egg-laying to emergence by NMR, X-radiography and weighing. The results of the three methods correlated quite well. Neither the NMR nor the X-radiation appeared to harm the insects. The NMR method did not usually detect the insects until they were in the third larval instars, but after that the areas of the two NMR peaks observed with each infested grain followed a pattern which was readily interpreted in terms of the insect development. The major NMR peak was found to be due almost wholly to water and the minor peak to lipid, and the size of the major peak obtained with adults was close to that expected on the basis of their water content. The movement of some of the insects within the grains was observed for short periods and appeared to be characteristic of each developmental stage. Preliminary work with a less sophisticated NMR machine showed that it is possible in a single scan to detect ten grains infested with S. granarius larvae in a batch of 500 grains, but further work is required to see whether single eggs can be detected. The results obtained in this study were sufficiently encouraging for a wide variety of other areas to be suggested in which use of NMR might help to solve some entomological problems.
Understanding gut microbiota in elderly's health will enable intervention through probiotics (2014)

Today, advances in the public health system of most countries have managed to extend notably life expectancy, however, elderly's health remain as a very serious concern. The lifelong stimulation of innate and adaptive immune systems leads to immunosenescence and, as result, to a low ability to produce immunoglobulins against pathogens but also to a low-grade chronic inflammatory state (inflammaging) that is linked to most age-related health problems, such as dementia, Alzheimer or atherosclerosis. This inflammatory state could make the host more sensitive to intestinal microbes, or vice versa, as changes in the gut microbiota composition are related to the progression of diseases and frailty in the elderly population. It was considered that gut microbiota changed during aging, with an increase of Bacteroidetes vs. Firmicutes proportion and a reduction of bifidobacterial counts, however recent studies reported a great inter-individual variation among elderly and a significant relationship between gut microbiota, diet and institution or community living. Intervention studies of probiotics and prebiotics in elderly are not very abundant, but most cases showed that Bifidobacterium populations can efficiently be stimulated with a concomitant decrease of Enterobacteria. Furthermore, also some studies demonstrated that probiotics decreased the synthesis of pro-inflammatory cytokines which are upregulated in the elderly, such as interleukin (IL)-8, IL-6 or tumour necrosis factor ?, among others, and they increased the levels of activated lymphocytes, natural killer cells, phagocytic activity and even showed a greater response to influenza vaccination. This suggests that direct manipulation of the gut microbiota may improve adaptive immune response and reduce inflammatory secretions, therefore compensating immunosenescence effects, however, there are no records of their effect on clinical symptoms or risk for disease. Those facts reveal that this is an open research field with very good scientific perspectives and above all they could bring likely improvements in the wellbeing of our seniors.
Synthesis of .alpha.- and .gamma.-alkyl-substituted phosphinothricins: potent new inhibitors of glutamine synthetase (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of .alpha.- and .gamma.-alkyl-substituted phosphinothricins: potent new inhibitors of glutamine synthetaseEugene W. Logusch, Daniel M. Walker, John F. McDonald, Gregory C. Leo, and John E. FranzCite this: J. Org. Chem. 1988, 53, 17, 4069–4074Publication Date (Print):August 1, 1988Publication History Published online1 May 2002Published inissue 1 August 1988https://pubs.acs.org/doi/10.1021/jo00252a034https://doi.org/10.1021/jo00252a034research-articleACS PublicationsRequest reuse permissionsArticle Views520Altmetric-Citations76LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Theoretical investigation of the signal-to-noise ratio for different fluorescence lifetime imaging techniques (2002)

Using Monte-Carlo methods, we have investigated the signal- to-noise ratio obtainable for different fluorescence lifetime imaging methods. Quantum noise limited performance and mono-exponential decays were assumed. We have also investigated the importance of parameter choice and implementation for the different methods. In addition, our simulations were in many cases compared with analytical theoretical investigations. The results from the simulations proved to be in good agreement with the theoretical results. It was found that all the investigated lifetime imaging methods have the potential to produce a high signal-to-noise ratio, but careful attention must be paid to implementation method and parameter choice in order to get optimal results.
Imprinted DLK1 is a putative tumor suppressor gene and inactivated by epimutation at the region upstream of GTL2 in human renal cell carcinoma (2006)

A common deletion at chromosomal arm 14q32 in human renal cell carcinoma (RCC) prompted us to explore a tumor suppressor gene (TSG) in this region. We report that imprinted DLK1 at 14q32, a regulator of adipocyte differentiation, is a candidate TSG in RCCs. DLK1 expression was lost in 39 out of 50 (78%) primary RCC tissues, whereas expression of DLK1 was maintained in every normal kidney tissue examined. DLK1 was expressed in only one of 15 (7%) RCC-derived cell lines. In order to see the biological significance of DLK1 inactivation in RCCs, we tested the effect of restoration of DLK1 in RCC cell lines, using a recombinant retrovirus containing the gene. Reintroduction of DLK1 into DLK1-null RCC cell lines markedly increased anchorage-independent cell death, anoikis and suppressed tumor growth in nude mice. We then investigated the underlying mechanisms for DLK1 inactivation in RCCs. We found loss of heterozygosity at this region in 12 out of 50 RCC tissues (24%). To explore the role of epigenetic regulation of DLK1 inactivation in RCCs, we conducted methylation analysis of the upstream region and the gene body of DLK1. We could not find a differentially methylated region in either the upstream region or the gene body of DLK1. However, we found that gain of methylation upstream of GTL2, a reciprocal imprinted gene for DLK1, is a critical epigenetic alteration for the inactivation of DLK1 in RCCs. The present data have shown that gain of methylation upstream of the untranslated GTL2 leads to pathological downregulation of DLK1 in RCCs.
X-band MMIC switch with 70 dB isolation and 0.5 dB insertion loss (2002)

A single-pole, single-throw reflective MMIC switch with 0.5 dB insertion loss and 70 dB isolation over X-band has been demonstrated. A fabrication process that was optimized to achieve the best performance for switch FETs produced this exceptional device. The FET OFF capacitance was reduced by a factor of 1.6 by selectively recessing into the backside of the wafer underneath the FETs to within 1 /spl mu/m of the top surface. The FET ON resistance remained the same. The reduced FET OFF capacitance allowed the use of larger periphery FETs to obtain the improved performance. The Ron-Coff product of this device is 30% lower than previously reported results.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Liberal Youth, Modern Exuberance, and Calamity: Aspirations for Modern Nationhood in Paraguay, 1858-1870 (2015)

This article follows the sojourns of five Paraguayan youths sent by their government to study in Europe and be trained as lettered officials there. It subsequently explores the tensions that they faced upon returning to Paraguay and serving as publicists for the Francisco Solano Lopez regime in the years immediately preceding the Triple Alliance War (1864-1870)—the largest international conflict in the history of South America. The article finds that the young men, filled up with the exuberance of the cultural liberalism of the age, crafted an image of a modernizing liberal republic for their country and its autocratic regime as promoted to much of the rest of Latin America and the North Atlantic world. It further alters the historical understanding of pre-war Paraguay from as, often thought, a hermit state steeling itself against the onslaught of modern economic and political forces, to rather a state that was anxious to engage those forces on its own terms. And, upon doing so, the article encourages a rethinking of the general depiction of the war itself.
Evidence and liberty (2009)

Evidence and liberty are two great ideas in British history. One consequence of both ideas is experimental criminology, which applies research designs developed in Britain to matters of liberty affecting the entire world. The promise of experimental criminology is to generate better evidence about how to increase liberty. The crucial challenge to experimental criminology is the means by which research results, even when accepted as true, may be translated into widespread practice. Two models for applying experimental research are possible. One is `bottom—up discretion', in which crime victims, police, judges and probation officers and others take experimental results into account when making their decisions one case at a time. Another model is `top—down guidance', in which either Ministers or an independent evidence-assessment agency like `NICE'—the National Institute of Health and Clinical Excellence—appoint committees of practitioners and researchers to develop succinct operational guidance based upon systematic reviews of experimental evidence. Bottom—up discretion will grow steadily from the sheer persistence of criminologists and practitioners doing experiments. Liberty could be advanced much faster by top—down guidance, however, if government chose to invest in `prospective meta-analysis' a method of multi-site randomized trials that would assess generalizability of policy effects as well as their magnitude and cost-effectiveness.
Measurement of bilirubin and its monoconjugates and diconjugates in human serum by alkaline methanolysis and high-performance liquid chromatography. (1980)

No accurate methods are available for specific determination of unconjugated and conjugated bilirubin. Using a novel approach, we now have developed such an assay which permits direct individual measurement of bilirubin and its isomeric monoconjugates and diconjugates in serum. The monosugar and disugar conjugates are quantitatively converted to the corresponding methyl esters, which are readily extractable into chloroform. These monomethyl and dimethyl esters and unconjugated bilirubin are then separated by HPLC and detected spectrophotometrically in the effluent. Use of an internal standard and calibration of the method with crystalline reference bilirubin and bilirubin methyl esters permit direct measurement of the individual pigment fractions in the sample. The acuracy of this procedure was verified by a radioisotope dilution method. In sera of 22 healthy adults and six patients with Gilbert syndrome, only unconjugated bilirubin was detected. In 42 serum samples of jaundiced patients with hepatobiliary disease, unconjugated and all conjugated bilirubin fractions were increased, with the monoconjugates generally predominating. The total concentration of bilirubin and its carbohydrate conjugates, as determined by the new method, was considerably lower than the TB obtained with conventional diazo procedures. Contrariwise, both the new method and the diazo procedures gave comparable resuts when normal serum enriched with purified bilirubin glucuronides was assayed. Our findings thus indicate that unidentified, diazo-positive compounds distinct from bilirubin and its ester conjugates are present in pathlogical serum samples. The reported asssay is expectd to serve as a reference method for measurement of bilirubin and its carbohydrate conjugates in serum and to find general application in the study of bilirubin metabolism.
Efficient fully adaptive wormhole routing in n-dimensional meshes (2002)

An efficient fully adaptive wormhole routing algorithm for n-dimensional meshes is developed. The routing algorithm provides full adaptivity at a cost of one additional virtual channel per physical channel irrespective of the number of dimensions of the network. The algorithm is based on dividing the network graph into two acyclic graphs that contain all of the physical channels in the system. Virtual channels are classified as either waiting or nonwaiting channels. Busy channels that a message waits for to become available are classified as waiting channels, otherwise they are classified as nonwaiting channels. Thus, a message considers nonwaiting channels first to reach its destination. If all non-waiting channels are busy, the message considers waiting channels. Messages acquire waiting channels in two phases. In each phase, waiting channels belonging to one acyclic network graph are traversed. This 2-phase routing algorithm could be either minimal or nonminimal. However, we concentrate on minimal routing. It is demonstrated that this adaptive routing algorithm can utilize the virtual paths (channels) between any two nodes more efficiently than any of the present algorithms with the same hardware requirement.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
A MAC address based authentication system applicable to campus-scale network (2013)

The authors have been developing a Web based network user authentication system “Opengate”. In the system, a user is required to type his/her password through the Web page before connecting to the Internet. Recently, types of terminal devices have been diverse, while the number of devices has been increasing. Some devices require full-time connectivity, some are not easy to type passwords smoothly, and some do not have Web functions. In this paper, the authors propose an alternate authentication system “OpengateM”, which is applicable to campus-scale networks where the users want to use various types of mobile devices. The proposed system inspects packets at the gateway, and opens the firewall when the source MAC address in the packet is found in the management database. The firewall is closed when the packet having the address is not captured for a while. User devices can be registered, expired and confirmed semi-automatically. By this implementation, the system can work even in the network having many users and devices and can maintain convenience, high device compatibility, and sufficient performance.
The evaluation of error probabilities for intersymbol and cochannel interference (1991)

An efficient series that can be used to calculate the probability of error in a binary symmetric channel with intersymbol interference and additive noise is derived. The series is derived by representing the noise complementary probability distribution function by an exact or approximate Fourier series. Bounds on the accuracy of the estimate are derived for Gaussian noise. Examples show that only a small numerical effort may be required to compute error probabilities of interest using the series. Applications to both finite and infinite intersymbol interference systems are discussed. A similar technique is used to derive series representations for the probability of error of additive noise channels with cochannel interference or with combined intersymbol and cochannel interferences. The accuracy of the results is bounded for Gaussian noise.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>