gebhart/patrepeval huggingface dataset:
Reaction and catalyst engineering to exploit kinetically controlled whole‐cell multistep biocatalysis for terminal FAME oxyfunctionalization (2014)

The oxyfunctionalization of unactivated C−H bonds can selectively and efficiently be catalyzed by oxygenase-containing whole-cell biocatalysts. Recombinant Escherichia coli W3110 containing the alkane monooxygenase AlkBGT and the outer membrane protein AlkL from Pseudomonas putida GPo1 have been shown to efficiently catalyze the terminal oxyfunctionalization of renewable fatty acid methyl esters yielding bifunctional products of interest for polymer synthesis. In this study, AlkBGTL-containing E. coli W3110 is shown to catalyze the multistep conversion of dodecanoic acid methyl ester (DAME) via terminal alcohol and aldehyde to the acid, exhibiting Michaelis-Menten-type kinetics for each reaction step. In two-liquid phase biotransformations, the product formation pattern was found to be controlled by DAME availability. Supplying DAME as bulk organic phase led to accumulation of the terminal alcohol as the predominant product. Limiting DAME availability via application of bis(2-ethylhexyl)phthalate (BEHP) as organic carrier solvent enabled almost exclusive acid accumulation. Furthermore, utilization of BEHP enhanced catalyst stability by reducing toxic effects of substrate and products. A further shift towards the overoxidized products was achieved by co-expression of the gene encoding the alcohol dehydrogenase AlkJ, which was shown to catalyze efficient and irreversible alcohol to aldehyde oxidation in vivo. With DAME as organic phase, the aldehyde accumulated as main product using resting cells containing AlkBGT, AlkL, as well as AlkJ. This study highlights the versatility of whole-cell biocatalysis for synthesis of industrially relevant bifunctional building blocks and demonstrates how integrated reaction and catalyst engineering can be implemented to control product formation patterns in biocatalytic multistep reactions.
Biologic-like In Vivo Efficacy with Small Molecule Inhibitors of TNFα Identified Using Scaffold Hopping and Structure-Based Drug Design Approaches (2020)

Scaffold hopping and structure-based drug design were employed to identify substituted 4-aminoquinolines and 4-aminonaphthyridines as potent, small molecule inhibitors of tumor necrosis factor alpha (TNFα). Structure-activity relationships in both the quinoline and naphthyridine series leading to the identification of compound <b>42</b> with excellent potency and pharmacokinetic profile are discussed. X-ray co-crystal structure analysis and ultracentrifugation experiments clearly demonstrate that these inhibitors distort the TNFα trimer upon binding, leading to aberrant signaling when the trimer binds to TNF receptor 1 (TNFR1). Pharmacokinetic-pharmacodynamic activity of compound <b>42</b> in a TNF-induced IL-6 mouse model and in vivo activity in a collagen antibody-induced arthritis model, where it showed biologic-like in vivo efficacy, will be discussed.
Hypertension in patients hospitalized with COVID-19 in Wuhan, China: A single-center retrospective observational study (2020)

Abstract Objectives It is unclear whether patients with hypertension are more likely to be infected with SARS-COV-2 than the general population and whether there is a difference in the severity of COVID-19 pneumonia in patients who have taken ACEI/ARB drugs to lower blood pressure compared to those who have not. Methods This observational study included data from all patients with clinically confirmed COVID-19 who were admitted to the Hankou Hospital, Wuhan, China between January 5 and March 8, 2020. Data were extracted from clinical and laboratory records. Follow-up was cutoff on March 8, 2020. Results A total of 274 patients, 75 with hypertension and 199 without hypertension, were included in the analysis. Patients with hypertension were older and were more likely to have pre-existing comorbidities, including chronic renal insufficiency, cardiovascular disease, diabetes mellitus, and cerebrovascular disease than patients without hypertension. Moreover, patients with hypertension tended to have higher positive COVID-19 PCR detection rates. Patients with hypertension who had previously taken ACEI/ARB drugs for antihypertensive treatment have an increased tendency to develop severe pneumonia after infection with SARS-COV-2 (P = 0.064). Conclusions COVID-19 patients with hypertension were significantly older and were more likely to have underlying comorbidities, including chronic renal insufficiency, cardiovascular disease, diabetes mellitus, and cerebrovascular disease. Patients with hypertension who had taken ACEI/ARB drugs for antihypertensive treatment have an increased tendency to develop severe pneumonia after infection with SARS-COV-2. In future studies, a larger sample size and multi-center clinical data will be needed to support our conclusions.
High performance Au–Cu alloy for enhanced visible-light water splitting driven by coinage metals (2016)

A Au-Cu alloy strategy is, for the first time, demonstrated to be effective in enhancing visible-light photocatalytic H2 evolution via promoting metal interband transitions. Au3Cu/SrTiO3, in which oxidation of Cu was successfully restrained, showed the highest visible-light H2 evolution activity.
On-demand media streaming over the internet (2004)

We propose a new model for on-demand media streaming centered around the peer-to-peer (P2P) paradigm. The proposed P2P model can support a large number of clients with a low overall system cost. The P2P model allows for peers to share some of their resources with the system and in return, they get some incentives or rewards. We describe how to realize (or deploy) the proposed model. In addition, we present a new dispersion algorithm (for disseminating the media files into the system) and a searching algorithm (for locating peers with the required objects). We demonstrate the potential of the P2P model as an infrastructure for a large-scale on-demand media streaming service through an extensive simulation study on large, Internet-like, topologies. Starting with a limited streaming capacity (hence, low cost), the simulation shows that the capacity is rapidly increased and many clients can be served even if they come according to different arrival patterns such as constant rate arrivals, flash crowd arrivals, and Poisson arrivals.
Defining Rehabilitation (2005)

As recently as the early 1980s, academic commentators were writing about rehabilitation as an approach towards offenders that had had its day. In the wake of the well-documented collapse of the 'rehabilitative ideal' (Allen, 1959), critics and supporters alike seemed to converge on the idea that rehabilitation as a penal strategy would soon be a thing of the past (e.g. Bottomley, 1980; Bottoms, 1980a; Allen, 1981). This conclusion was powerfully re-stated a decade later by American criminologists Feeley and Simon (1992, 1994), whose 'new penology' thesis seemed to confirm the death of rehabilitation in Western penal systems.KeywordsCorrectional ModelRestorative JusticeCriminal RecordCriminal ConvictionOxford English DictionaryThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Simple dynamic polarisation mode dispersion compensator (1999)

A new optical polarisation mode dispersion compensator is proposed which is based on the dynamic maximisation of the degree of polarisation. It requires no variable differential group delay and has been experimentally validated.
Ultra-long Distance Distributed Intrusion Detecting System Assisted With In-line Amplification (2017)

An ultra-long distance distributed intrusion detecting system assisted with power amplification and sensitivity enhancement is proposed and demonstrated. First, through introducing multiple bidirectional amplifiers into the unbalanced Mach-Zehnder/Sagnac interferometer-based fiber sensing link, the sensing distance is remarkably extended, and second, the signal-to-noise ratio of this sensing system is significantly improved from less than 2 to 6-8 dB by coating the sensing fiber with organic silicone polymer. Furthermore, the high-order downtrend fitting function is adopted to implement the intrusion locating of ultralong distance sensing; the zero-padding fast Fourier transform algorithm and multiple-averaging method are jointly utilized for the improvement of the locating accuracy. Experimentally, a proof-of-concept distributed intrusion detecting system is constructed with the employment of bidirectional amplification. In particular, the ultra-long sensing distance up to 226.337 km is implemented, which is the reported longest distributed sensing system to the best of our knowledge.
Importance of Size, Sulfation, and Anticoagulant Activity in the Potentiation of Acidic Fibroblast Growth Factor by Heparin (1989)

Heparin was previously reported to potentiate the mitogenic activity of endothelial cell mitogens in a crude extract of bovine hypothalami (Thornton, S. C., Mueller, S. N., and Levine, E. M. (1983) Science 222, 623-625). We and others (Gospodarowicz, D., and Cheng, J. (1986) J. Cell. Physiol. 128, 475-484) have reported that the growth stimulatory effects of acidic fibroblast growth factor (aFGF) are potentiated in a similar manner. We have used these observations as the basis of an assay to characterize the importance of size, sulfation, and anticoagulant activity of heparin in mediating this effect. Partial nitrous acid depolymerization of heparin from porcine intestinal mucosa resulted in a mixture of heparin fragments, containing oligosaccharides ranging from disaccharides to polysaccharides of about 40 monosaccharides in length. This mixture was fractionated by ion exchange chromatography and gel permeation chromatography to obtain size-homogeneous oligosaccharides with different degrees of sulfation. Assay of these heparin-derived saccharides in the presence of a suboptimal concentration of aFGF revealed that a minimum chain length and a certain degree of sulfation is required in order to potentiate the action of aFGF. Low sulfate oligosaccharides (4-16 units) were unable to potentiate aFGF, whereas medium sulfate fractions of octadecasaccharides and larger were able to moderately potentiate aFGF. The potentiation of aFGF by the high sulfate fraction correlated with the saccharide size: 12 or more monosaccharide units were necessary to achieve potentiation equivalent to whole heparin, octa- and decasaccharides were mildly stimulatory, and hexasaccharides were without effect. In the absence of aFGF, intact heparin as well as all the oligosaccharides examined, inhibited the proliferation of capillary endothelial cells to approximately the same degree, between 20 and 50% inhibition. When a tetradecasaccharide was separated into a binding and a nonbinding fraction on matrix-bound antithrombin III, no difference was seen for these fractions in the endothelial cell proliferation assay. These results indicate that both size and sulfation of a heparin-derived oligosaccharide contribute to its ability to interact with aFGF and/or endothelial cells and that this interaction is independent of anticoagulant activity. In addition, our findings suggest that the inhibitory and potentiating effects of heparin on capillary endothelial cells have different structural requirements.
Interaction of metal ions with nucleic acids. Interaction of copper(II) with pyrimidine nucleosides and their derivatives. (1979)

1. In aqueous and non-aqueous solutions, copper(II) interacts with the N-3 of cytidine but not with the carbonyl group oxygens of pyrimidine nucleosides. 2. In aqueous solution, copper(II) interacts with the phosphate group and ribose of pyrimidine nucleotides, and additionally with N-3 of 5'-CMP. 3. Broadening of resonance signals of the H-5 proton of 5'-UMP and C-5 of 5'-UMP and 5'-TMP results probably from the interaction between metal ion and the phosphate group situated in direct vicinity of the above atoms. 4. In the copper(II)-pyrimidine nucleotide complexes in solid state, copper is coordinated with the phosphate group, and in 5'-CMP additionally with the pyrimidine moiety of the nucleotide.
Regulated Intramembrane Proteolysis: Signaling Pathways and Biological Functions (2011)

Intramembrane cleavage of transmembrane proteins is a fundamental cellular process. Several enzymes capable of releasing domains of integral membrane proteins have been described. Transmembrane protein proteolytic cleavage is regulated and involved not only in degrading membrane spanning segments but also in generating messengers that elicit biological responses. This review examines the role of the released functional protein domain in signaling mechanisms regulating an array of cellular and physiological processes.
Construction of phosphorylatable chimeric monoclonal antibody CC49. (1998)

Phosphorylation sites were introduced into chimeric monoclonal antibody CC49 (MAb-chCC49) by inserting synthetic fragments encoding two and six phosphorylation sites into an expression vector, pdHL7. The phosphorylation sites were created by using the predicted consensus sequences for phosphorylation by the cAMP-dependent protein kinase to the carboxyl terminus of the heavy chain constant region of the MAb-chCC49. The resultant modified antibodies (MAb-chCC49K1 and MAb-chCC49-6P) were expressed in NS0 cells and purified. The MAb-chCC49K1 protein contains two phosphorylation sites per heavy chain whereas the MAb-chCC49-6P protein contains six sites per heavy chain. Both MAb-chCC49K1 and MAb-chCC49-6P proteins can be phosphorylated by the catalytic subunit of cAMP-dependent protein kinase with [gamma-32P]ATP to high specific activity. The 32P-labeled MAb-chCC49K1 and MAb-chCC49-6P proteins bind to cells expressing TAG-72 antigens. The introduction of phosphorylation sites into a monoclonal antibody provides a reagent for the diagnosis and treatment of cancer. The use of multiple phosphorylation sites provides antibodies with very high specific radioactivity and demonstrates that cassettes of phosphorylation sites can be introduced into proteins without altering their functional activity.
Common fixed point theorems for four weakly compatible mappings using CLRg property (2016)

The aim of this paper is to prove common fixed point theorems for weakly compatible maps in fuzzy metric spaces using the CLRg property, which generalizes the results of A.F. Roldan-Lopez-de-Hierro, W. Sintunavarat [17], and Manish Jain et al. [8].
Observation of switching behaviors in post-breakdown conduction in NiSi-gated stacks (2009)

For NiSi FUSI gate transistors, switching behaviors have been observed after breakdown (BD) under certain favorable conditions. The conductive BD path can be ¿switched-off¿ if a reverse bias, as opposed to the stressing voltage, is applied, a condition required for observing SET and RESET conduction in switching material systems. Using the percolation model of BD of gate dielectric systems, we explain this switching behavior as a result of passivation of oxygen-deficient BD path. First ionized oxygen atoms are removed from the BD path upon BD, and are driven by e-field and ¿stored¿ in the NiSi gate. Then, upon applying a threshold reverse bias, they are driven back to the nanoscale BD path and due to the presence of a Joule heating in the highly resistive BD path, they rebond/passivate the Si dangling bonds in the oxygen-deficient BD path. This means that BD transistor can be ¿repaired¿ electrically by a reverse threshold voltage to expend its lifetime.
Reactivation of the silenced and imprinted alleles of ARHI is associated with increased histone H3 acetylation and decreased histone H3 lysine 9 methylation (2003)

ARHI has been identified as a maternally imprinted tumor suppressor gene that maps to chromosome 1p31 and whose expression is markedly down-regulated in breast cancer. To explore possible mechanisms that could silence ARHI expression, we have tested the importance of DNA methylation, histone acetylation and histone methylation in regulating ARHI expression. We found that treatment with CpG demethylating agents and/or histone deacetylase inhibitors could reactivate both the silenced and the imprinted alleles of this tumor suppressor gene. Reactivation of ARHI expression by these reagents is related to the methylation status of the CpG islands in the ARHI promoter, especially CpG island II. Chromatin immunoprecipitation assays revealed that histone H3 lysine 9/18 acetylation levels associated with ARHI in normal cells were significantly higher than those in breast cancer cell lines that lacked ARHI expression. Treatment with a CpG demethylating agent and/or histone deacetylase inhibitor could increase ARHI expression in breast cancer cells, with a corresponding increase in histone H3 lysine 9/18 acetylation and decrease in histone H3 lysine 9 methylation.
Study of precise optical modulation using Mach-Zehnder interferometers for advanced modulation formats (2007)

We investigated impact of parasitic phase modulation at Mach-Zehnder modulators on advanced modulation formats, such as quadrature-amplitude-modulation. Phase error due to imbalance in a modulator can be compensated by using an optical frequency-shift-keying modulator. (2 pages)
[Antimicrobial activity of the epicarp of the fruits of Paulownia fortunei and Paulownia tomentosa]. (1982)

One antimicrobial substance was obtained from the epicarp of the fruits of Paulownia fortunei and Paulownia tomentosa. Other parts of the fruits and leaves had no detectable antimicrobial activity. The substance was active in vitro for Staphylococcus aureus and Bacillus subtilis while it had lower activity for Saccharomyces carlsbergensis and the lowest was for Escherichia coli. The active material was extracted with organic solvents (ether, ethanol and acetone). The activity "in vitro" was demonstrated by the method of dilution in nutrient agar media. The active substance looked as a resin and was insoluble in water at neutral or acid pH. It was very soluble in strong alkaline pH solution.
Enzymatic Properties of Human Cytosolic Phospholipase A2γ (2002)

The enzymatic properties of cytosolic phospholipase A(2)gamma (cPLA(2)gamma), an isoform of 85-kDa group IV cPLA(2)alpha (cPLA(2)alpha) were studied in vitro and when the enzyme was expressed in cells. cPLA(2)gamma expressed in Sf9 cells is associated with membrane. Membranes isolated from [(3)H]arachidonic acid-labeled Sf9 cells expressing cPLA(2)gamma, constitutively release [(3)H]arachidonic acid. The membrane-associated activity is inhibited by the group IV PLA(2) inhibitor methylarachidonyl fluorophosphonate, but not effectively by the group VI PLA(2) inhibitor (E)-6-(bromomethylene)-3-(1-naphthalenyl)-2H-tetrahydropyran-2-one. cPLA(2)gamma has higher lysophospholipase activity than PLA(2) activity. Purified His-cPLA(2)gamma does not exhibit phospholipase A(1) activity, but sequentially hydrolyzes fatty acid from the sn-2 and sn-1 positions of phosphatidylcholine. cPLA(2)gamma overexpressed in HEK293 cells is constitutively active in isolated membranes, releasing large amounts of oleic, arachidonic, palmitic, and stearic acids; however, basal fatty acid release from intact cells is not increased. cPLA(2)gamma overexpressed in lung fibroblasts from cPLA(2)alpha-deficient mice is activated by mouse serum resulting in release of arachidonic, oleic, and palmitic acids, whereas overexpression of cPLA(2)alpha results primarily in arachidonic acid release.
Determination of cholesterol in human serum by an enzymatic method with the application of daos reagent (2000)

A sensitive and specific enzymatic method has been developed for the determination of the total and free cholesterol in human serum based on the application of the newly-synthesized N-ethyl-N-(2-hydroxy-3-sulfopropyl)-3,5-dimethoxyaniline, (DAOS) Trinder's reagent. Using the proposed method, cholesterol could be determined in the concentration range of 0.15 mmol/L with a relative standard deviation of up to 1.1%. In order to find the optimal experimental conditions for the application of the DAOS reagent, the influence of its concentration on the linearity of the method, the influence of pH, as well as the influence of the activities of cholesterolesterase and cholesteroloxidase were examined. The obtained results of the determination of the total and free cholesterol were compared to the results obtained by the application of the most frequently employed enzymatic method in clinical practice, based on phenol as a reagent. The sensitivity of the method was 0.070 A/mmol/L, the limit of detection DL=0.03 mmol/L and the limit of quantification QL=0.09 mmol/L of cholesterol.
Lipoxygenase‐mediated generation of lipid peroxides enhances ferroptosis induced by erastin and RSL3 (2017)

In cancer cells the small compounds erastin and RSL3 promote a novel type of cell death called ferroptosis, which requires iron-dependent accumulation of lipid reactive oxygen species. Here we assessed the contribution of lipid peroxidation activity of lipoxygenases (LOX) to ferroptosis in oncogenic Ras-expressing cancer cells. Several 12/15-LOX inhibitors prevented cell death induced by erastin and RSL3. Furthermore, siRNA-mediated silencing of ALOX15 significantly decreased both erastin-induced and RSL3-induced ferroptotic cell death, whereas exogenous overexpression of ALOX15 enhanced the effect of these compounds. Immunofluorescence analyses revealed that the ALOX15 protein consistently localizes to cell membrane during the course of ferroptosis. Importantly, treatments of cells with ALOX15-activating compounds accelerated cell death at low, but not high doses of erastin and RSL3. These observations suggest that tumor ferroptosis is promoted by LOX-catalyzed lipid hydroperoxide generation in cellular membranes.
Evaluation of Hyperbaric Spinal Ropivacaine in Lower Limb and Hip Surgery: A Comparison with Hyperbaric Bupivacaine (2013)

Objectives: In this clinical study hyperbaric ropivacaine in spinal anaesthesia for lower limb and hip surgery was evaluated and results obtained were compared with those using hyperbaric bupivacaine. Methodology: Two hundred patients scheduled for lower limb and hip surgery were randomly divided into two groups of 100 patients each. These patients received a spinal injection of either 3ml (15mg) of 0.5% hyperbaric ropivacaine or 3ml (15mg) of 0.5% hyperbaric bupivacaine using 25G Quincke type spinal needle. The parameters studied were - onset and total duration of sensory block, onset and total duration of motor block, quality of intraoperative anaesthesia, hemodynamic alterations, and any intraoperative and postoperative complications. Results: The mean onset of sensory block (6±1.3min vs. 3±1.1min; p value<0.05) and motor block (13±1.6min vs. 9±1.3min; p value< 0.05) was significantly slower in ropivacaine group as compared to bupivacaine group. The total duration of sensory block was significantly shorter in ropivacaine group (160±12.9min) than in bupivacaine group (260±16.1min; p value <0.05). The mean duration of motor block was also shorter in ropivacaine group compared to bupivacaine group (126±9.2min vs. 174±12.6min; p value<0.05). Conclusion: The quality of anaesthesia was excellent in both the groups. In conclusion , a solution of ropivacaine (hyperbaric) can be used for spinal anaesthesia and is comparable with hyperbaric bupivacaine in terms of quality of block, but has shorter recovery profile.
α-Thioalkylation<i>via</i>Aldehydes and Thiols (1987)

Procedures for thioalkylation at carbon and at nitrogen are classified into six major types. These are discussed in relation to the principal substrates. In each area the most significant results are considered and commonly used methods of thioalkylation are exemplified. A brief account of some applications of thioalkylation in synthesis is presented. 1. Introduction 2. Terminology 3. Scope 4. Thioalkylation Routes 5. Mechanisms of Thioalkylation 6. Thioalkylation at Carbon 7. Thioalkylation at Nitrogen 8. Applications of Thioalkylation 9. Conclusions