gebhart/patrepeval huggingface dataset:
An Alternative Enzymatic Route to the Ergogenic Ketone Body Ester (R)-3-Hydroxybutyl (R)-3-Hydroxybutyrate (2021)

Recent studies have highlighted the therapeutic and ergogenic potential of the ketone body ester, (R)-3-hydroxybutyl-(R)-3-hydroxybutyrate. In the present work, the enzymatic synthesis of this biological active compound is reported. The (R)-3-hydroxybutyl-(R)-3-hydroxybutyrate has been produced through the transesterification of racemic ethyl 3-hydroxybutyrate with (R)-1,3-butanediol by exploiting the selectivity of Candida antarctica lipase B (CAL-B). The needed (R)-1,3-butanediol was in turn obtained from the kinetic resolution of the racemate achieved by acetylation with vinyl acetate, also in this case, thanks to the enantioselectivity of the CAL-B used as catalyst. Finally, the stereochemical inversion of the unreacted (S) enantiomers of the ethyl 3-hydroxybutyate and 1,3-butanediol accomplished by known procedure allowed to increase the overall yield of the synthetic pathway by incorporating up to 70% of the starting racemic reagents into the final product.
CELEBRATING MORRIS (1984)

The Journal of the William Morris Society, New York and London, vol. V. no. 3, Summer 1983 William Morris: News from Nowhere and Selected Writings and Designs ed. Asa Briggs , Penguin, 1984, 320pp., 32 pp. ills, £2.50 William Morris by Peter Stansky , Oxford University Press, 1983, 96 pp., cloth £7.95, paperback £1.95 Morris and Company in Cambridge (Fitzwilliam Museum), Cambridge University Press, 1980, 127 pp., 81 ills, cloth £26, paperback £7.95 The Ideal Book, Essays on the Arts of the Book by William Morris ed. William S. Peterson , University of California Press, 1983, 176 pp., 33 col. ills, £36 William Morris Textiles by Linda Parry , London: Weidenfeld &amp; Nicolson, 1983, 192 pp., 104 ills, 174 colour pls, £20 The After‐Summer Seed ed. John Hollow , New York: The William Morris Society, 1982 The Juvenilia of William Morris ed. Florence S. Boos , New York: The William Morris Society, 1983 The Golden Chain: Essays on William Morris and Pre‐Raphaelitism ed. Carole G. Silver , New York: The William Morris Society, 1982 William Morris Today, London: Institute of Contemporary Arts, 1984, 160 pp., 148 ills, 10 colour pls, £6.95
Extended antibody-framework-to-antigen distance observed exclusively with broad HIV-1-neutralizing antibodies recognizing glycan-dense surfaces (2021)

Antibody-Framework-to-Antigen Distance (AFAD) - the distance between the body of an antibody and a protein antigen - is an important parameter governing antibody recognition. Here, we quantify AFAD for ~2,000 non-redundant antibody-protein-antigen complexes in the Protein Data Bank. AFADs showed a gaussian distribution with mean of 16.3 Å and standard deviation (σ) of 2.4 Å. Notably, antibody-antigen complexes with extended AFADs (>3σ) were exclusively human immunodeficiency virus-type 1 (HIV-1)-neutralizing antibodies. High correlation (R<sup>2</sup> = 0.8110) was observed between AFADs and glycan coverage, as assessed by molecular dynamics simulations of the HIV-1-envelope trimer. Especially long AFADs were observed for antibodies targeting the glycosylated trimer apex, and we tested the impact of introducing an apex-glycan hole (N160K); the cryo-EM structure of the glycan hole-targeting HIV-1-neutralizing antibody 2909 in complex with an N160K-envelope trimer revealed a substantially shorter AFAD. Overall, extended AFADs exclusively recognized densely glycosylated surfaces, with the introduction of a glycan hole enabling closer recognition.
Identification of biomarker sets for predicting the efficacy of sublingual immunotherapy against pollen-induced allergic rhinitis (2017)

Sublingual immunotherapy (SLIT) is effective against allergic rhinitis, although a substantial proportion of individuals is refractory. Herein, we describe a predictive modality to reliably identify SLIT non-responders (NRs). We conducted a 2-year clinical study in 193 adult patients with Japanese cedar pollinosis, with biweekly administration of 2000 Japanese allergy units of cedar pollen extract as the maintenance dose. After identifying high-responder (HR) patients with improved severity scores and NR patients with unchanged or exacerbated symptoms, differences in 33 HR and 34 NR patients were evaluated in terms of peripheral blood cellular profiles by flow cytometry and serum factors by ELISA and cytokine bead array, both pre- and post-SLIT. Improved clinical responses were seen in 72% of the treated patients. Pre-therapy IL-12p70 and post-therapy IgG1 serum levels were significantly different between HR and NR patients, although these parameters alone failed to distinguish NR from HR patients. However, the analysis of serum parameters in the pre-therapy samples with the Adaptive Boosting (AdaBoost) algorithm distinguished NR patients with high probability within the training data set. Cluster analysis revealed a positive correlation between serum Th1/Th2 cytokines and other cytokines/chemokines in HR patients after SLIT. Thus, processing of pre-therapy serum parameters with AdaBoost and cluster analysis can be reliably used to develop a prediction method for HR/NR patients.
Biochemical, Biophysical, and Mutational Analyses of Subunit Interactions of the Human Cytomegalovirus Nuclear Egress Complex (2009)

Nuclear egress, the trafficking of herpesvirus nucleocapsids from the nucleus to the cytoplasm, involves two conserved viral proteins that form a complex at the nuclear envelope, referred to as the nuclear egress complex. In human cytomegalovirus, these two proteins are called UL50 and UL53. To study UL50 and UL53 in molecular detail, these proteins were expressed in bacteria and purified. To obtain highly expressed, pure proteins, it was necessary to truncate both constructs based on sequence conservation and predicted secondary structural elements. Size exclusion chromatography and analytical ultracentrifugation studies indicated that the truncated form of UL50 is a monomer in solution, that the truncated form of UL53 is a homodimer, and that, when mixed, the two proteins form a heterodimer. To identify residues of UL53 crucial for homodimerization and for heterodimerization with UL50, we constructed and expressed mutant forms of UL53 containing alanine substitutions in a predicted helix. Isothermal titration calorimetry was used to measure the binding affinities of the UL53 mutants to UL50. UL53 residues, the replacement of which reduced binding to UL50, form a surface on one face of the predicted helix. Moreover, most of the substitutions that reduce UL53-UL50 interactions also reduced homodimerization. Substitutions that reduced the interaction between UL50 and UL53 in vitro also reduced colocalization of full-length UL50 and UL53 at the nuclear rim in transfected cells. These results demonstrate direct protein-protein interactions between these proteins that are likely to be mediated by a helix, and they have implications for understanding nuclear egress and for drug discovery.
Data from PROgesterone Therapy for Endometrial Cancer Prevention in Obese Women (PROTEC) Trial: A Feasibility Study (2023)

&lt;div&gt;Abstract&lt;p&gt;Obesity is the major etiologic driver for endometrial cancer. The levonorgestrel intrauterine system (LNG-IUS) reduces the risk of endometrial cancer and its precursor, atypical hyperplasia. We assessed feasibility and uptake of the LNG-IUS for primary prevention of endometrial cancer in high-risk women and its impact on endometrial tissue biomarkers. Women with class-III obesity [body mass index (BMI) &gt; 40 kg/m&lt;sup&gt;2&lt;/sup&gt;] and histologically normal endometrium were invited to participate in a clinical trial of the LNG-IUS for endometrial protection. Recruitment, successful LNG-IUS insertion, and adherence to trial procedures were recorded. We measured impact of the LNG-IUS on circulating biomarkers of endometrial cancer risk, endometrial proliferation (Ki-67, pAKT, PTEN), endometrial hormone receptor status [estrogen receptor and progesterone receptor (PR)], mental wellbeing, and menstrual function. At 6 months, women chose to keep their LNG-IUS or have it removed. In total, 103 women were approached, 54 were offered a participant information sheet, 35 agreed to participate, and 25 received a LNG-IUS. Their median age and BMI were 54 years [interquartile range (IQR) 52–57] and 47 kg/m&lt;sup&gt;2&lt;/sup&gt; (IQR 44–51), respectively. Three women (3/35, 9%) were ineligible due to atypical hyperplasia/endometrial cancer on their baseline biopsy. The LNG-IUS was well tolerated and had a positive overall effect on bleeding patterns and mental wellbeing. The LNG-IUS was associated with endometrial morphologic change, reduced Ki-67, and PR expression, but circulating biomarkers of endometrial cancer risk were unchanged. All but one woman (96%) kept her LNG-IUS. The LNG-IUS appears to be acceptable to some women with class-III obesity for primary prevention of endometrial cancer, which could provide a strategy for a prevention trial.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Prevention Relevance:&lt;/b&gt; Novel strategies are urgently needed to prevent the rise in endometrial cancer diagnoses predicted by escalating obesity rates. Here, we show that women with class III obesity are willing to engage in risk reduction with a levonorgestrel intrauterine system, which could provide a strategy for an endometrial cancer prevention trial.&lt;/p&gt;&lt;/div&gt;
232 Incinerated Ash Treatment Result By Stoker Furnace + Surface Melting Furnace : Verfication for the System with 2-Stage(Normal and Catalytic) Bag Filter (2005)

Various systems are developed, and have been put to practical use in the ash processing and the flue gas processing. Our company gets the operation results of two years in the facility with the system that processes flue gas with 2-stage (normal and catalytic) bug filter and melts the dry ash. The mass balance and the amount of a total exhaust dioxins for each ton of municipal solid waste were calculated with the report of the operation results in this research, and the superiority was verified.
Preparation and characterization of Thioflavin T doped silica nanoparticles (2009)

Fluorescent silica nanoparticles with diameters of about 300 nm were synthesized based on Stöber´s method, using Thioflavin T as fluorescent co-reagent. The particles were characterized via transmission electron microscopy and fluorimetry measurements. Fluorescence intensity of the sols was ten times higher than that of the ethanol phase solutions of Thioflavin T. Release of dye molecules in stable alcosols was investigated by measuring UV-Vis absorbance spectrum of the supernatant. To try an alternative route, we investigated accumulation of dye molecules in native silica particles. No release effect was detected, and slow accumulation was observed. Water contact angles of the particles were assessed from analyzing the Langmuir films, and were found to be 18\r , very similar to native silica particles. Langmuir-Blodgett films of the particles were deposited on a glass substrate and were examined via UV-Vis spectrophotometry, fluorimetry and scanning electron microscopy. Presence of the film was revealed; the particles formed a continuous, well-packed monolayer.
Characterization of the inherent error in a spherically-biased corneal topography system in mapping a radially aspheric surface. (1994)

The EyeSys Corneal Analysis System does not accurately measure the instantaneous radii of curvature of an ellipsoid. Misalignment error is small compared to the inherent error due to a spherically-biased reconstruction.
Synthesis and herbicidal activity of new benzenesulfonylureas (1999)

A series of benzenesulfonylurea derivatives possessing a branched hydroxymethyl moiety as an ortho-substituent were synthesized and found to have interesting herbicidal activity under submerged paddy conditions.
Cell selectivity and interaction with model membranes of Val/Arg‐rich peptides (2011)

Antimicrobial peptides are major components of the innate self-defence system and a large number of peptides have been designed to study the mechanism of action. In the present study, a small combinatorial library was designed to study whether the biological activity of Val/Arg-rich peptides is associated with targeted cell membranes. The peptides were produced by segregating hydrophilic residues on the polar side and hydrophobic residues on the opposite side. The peptides displayed strong antimicrobial activity against Gram-negative and Gram-positive bacteria, but weak haemolysis even at a concentration of 256 µM. CD spectra showed that the peptides formed α-helical-rich structure in the presence of negatively charged membranes. The tryptophan fluorescence and quenching experiments indicated that the peptides bound preferentially to negatively charged phospholipids over zwitterionic phospholipids, which corresponds well with the biological activity data. In the in vivo experiment, the peptide G6 decreased the bacterial counts in the mouse peritoneum and increased survival after 7 days. Overall, a high binding affinity with negatively charged phospholipids correlated closely with the cell selectivity of the peptides and some peptides in this study may be likely candidates for the development of antibacterial agents.
Optical fiber refractometers based on localized surface plasmon resonance (LSPR) and lossy mode resonance (LMR) (2014)

An optical fiber device showing simultaneously two optical phenomena, localized surface plasmon resonance (LSPR) and lossy mode resonance (LMR), is presented here for the first time. It consists of a fragment of stripped optical fiber coated with a polymeric film that includes gold nanoparticles. The absorption peaks related to both phenomena were captured during the deposition of the coating, showing a different evolution. In addition, the behavior of both phenomena to variations of the surrounding medium refractive index (SMRI) was monitored, studying the different responses of LSPR and LMR.
Influence of gas rarefaction on the lateral resolution achievable by thermocapillary patterning (2011)

Molten polymer nanofilms subject to a large transverse thermal gradient can undergo a thermocapillary instability leading to the growth of nanopillar arrays on the cooler side. The array pitch can be estimated from the fastest growing wavelength from linear stability analysis. Here we quantify the influence of gas rarefaction on thermal conduction for cases in which the gas layer thickness above the film approaches dimensions of the molecular mean free path. For experimentally relevant parameters, rarefaction increases the pitch by as much as 65%, an important consideration for noncontact three-dimensional structure formation by thermocapillary lithography.
Supplementary Figure 4 from Src Mediates Cigarette Smoke–Induced Resistance to Tyrosine Kinase Inhibitors in NSCLC Cells (2023)

&lt;p&gt;PDF file - 1448K, Phosphorylation of Y845-EGFR does not control the CS-driven aberrant EGFR activation, nor the subsequent TKI resistance. A. Serum starved NIH-3T3 cells stably over expressing either WT or Y845F MT EGFR were incubated (or not) with 1microM AG1478 for 30' and then treated, or not (-), with EGF or CS, as before for additional 30'. EGFR was IPed from the total cell lysates and IBed for total receptor and for auto-phosphorylation on Y1173.&lt;/p&gt;
P4‐403: Extended‐release (ER) memantine capsule (28 mg, once daily): A multiple‐dose, open‐label study evaluating steady‐state pharmacokinetics in healthy volunteers (2008)

Memantine is a moderate-affinity, uncompetitive antagonist of N-methyl-D-aspartate (NMDA) receptors, indicated for the treatment of moderate to severe Alzheimer's disease (AD). Approved memantine administration is 10 mg twice daily (20 mg/day), in the form of an immediate-release (IR) tablet or solution. In this study, we investigated the safety, tolerability, and pharmacokinetics of an extended-release (ER) memantine capsule (28 mg) in healthy volunteers. In this Phase I, single-center, open-label study, 16 men and 8 women received a single daily oral dose of memantine ER for 29 days, as follows: 7 mg (days 1–3), 14 mg (days 4–9), 21 mg (days 10–15), and 28 mg (days 16–29). Safety and tolerability were assessed throughout the study, for each individual who received at least one dose of the drug. Blood samples were obtained on days 1, 27, 28, and 29, and analyzed for memantine using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). There were no serious adverse events (AEs) or deaths. Four participants discontinued the study: one due to an AE (somnolence), one due to a protocol violation, and two withdrew consent. Treatment-emergent AEs (TEAEs) were all mild in severity and in most cases judged possibly related to study drug. The most common TEAEs were headache, somnolence, and dizziness. One subject had a reversible increase in aspartate and alanine aminotransferases after discontinuation of study drug. None had a potentially clinically significant (PCS) change in vital signs from screening to endpoint, or a PCS change during the treatment, relative to predose values. The absorption rate of memantine from the ER capsule was relatively slow, with a median Tmax of 12 hours. Mean Cmax and Cmin were 127.1 ± 21.1 ng/mL and 102.5 ± 16.5 ng/mL, respectively. Mean elimination half-life was 55.7 ± 9.5 h and AUC0–τ was 2726 ± 430 ng/mL. Memantine ER capsule administration was safe and well-tolerated. The relatively small difference between Cmax and Cmin suggests small fluctuations in plasma levels during the steady-state dosing interval.
Open Source Bayesian Models. 1. Application to ADME/Tox and Drug Discovery Datasets (2015)

On the order of hundreds of absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox) models have been described in the literature in the past decade which are more often than not inaccessible to anyone but their authors. Public accessibility is also an issue with computational models for bioactivity, and the ability to share such models still remains a major challenge limiting drug discovery. We describe the creation of a reference implementation of a Bayesian model-building software module, which we have released as an open source component that is now included in the Chemistry Development Kit (CDK) project, as well as implemented in the CDD Vault and in several mobile apps. We use this implementation to build an array of Bayesian models for ADME/Tox, in vitro and in vivo bioactivity, and other physicochemical properties. We show that these models possess cross-validation receiver operator curve values comparable to those generated previously in prior publications using alternative tools. We have now described how the implementation of Bayesian models with FCFP6 descriptors generated in the CDD Vault enables the rapid production of robust machine learning models from public data or the user's own datasets. The current study sets the stage for generating models in proprietary software (such as CDD) and exporting these models in a format that could be run in open source software using CDK components. This work also demonstrates that we can enable biocomputation across distributed private or public datasets to enhance drug discovery.
Network-assisted device-decided channel selection and power control for multi-pair device-to-device (D2D) communications in heterogeneous networks (2014)

The device-to-device (D2D) communications can improve the spectrum efficiency with low power and effectively offload the traffic from the macro-eNB. However, the macro/femto/D2D heterogeneous networks face a complicated three-tier interference issue. The completely centralized resource management is not applicable in such three-tier heterogeneous networks. Therefore, we propose a network-assisted device-decided (NADD) scheme to jointly select the channels and adjust the transmission power for D2D devices. In the NADD method, the macro-eNB broadcasts resource allocation instruction to D2D devices. According to the resource allocation instruction and the device's communication quality, D2D devices autonomously and dynamically select the suitable channels and adjust the transmission power. Simulation results show that NADD scheme can significantly improve the total throughput and ensure the link reliability of macrocell users, comparing to both the fixed power scheme and the network-decided (ND) power control scheme.
Increased alanine dehydrogenase activity during dormancy inMycobacterium smegmatis (1998)

The aerobic fast-growing Mycobacterium smegmatis has, like its slow-growing pathogenic counterpart M. tuberculosis, the capability to adapt to anaerobiosis by shifting down to a drug resistant dormant state. Here, we report the identification of the first enzyme, L-alanine dehydrogenase, whose specific activity is increased during dormancy development in M. smegmatis. This mycobacterial enzyme activity was previously identified as the 40-kDa antigen in M. tuberculosis and shows a preference for the reductive amination of pyruvate to alanine at physiological pH. The determination of the temporal profile of alanine dehydrogenase activity during dormancy development showed that the activity stayed at a low baseline level during the initial aerobic exponential growth phase (0.7 mU mg-1 min-1). After termination of aerobic growth, alanine dehydrogenase activity increased rapidly 5-fold. As oxygen becomes more and more limiting, the enzyme activity declined until it reached a level about two-third that of the peak value. The strong induction immediately after deflection from aerobic growth suggests that alanine might be required for the adaptation from aerobic growth to anaerobic dormancy. As alanine synthesis is coupled to NADH oxidation, we propose that the induction of alanine dehydrogenase activity might also support the maintenance of the NAD pool when oxygen as a terminal electron acceptor becomes limiting.
Induction of systemic and therapeutic antitumor immunity using intratumoral injection of dendritic cells genetically modified to express interleukin 12. (1999)

Bone marrow-derived dendritic cells (BM-DCs) retrovirally transduced with genes encoding murine interleukin (IL)-12 stably expressed bioactive IL-12 protein at high levels. Intratumoral injection with IL-12 gene-modified BM-DCs resulted in regression of day 7 established weakly immunogenic tumors (MCA205, B16, and D122). This antitumor effect was substantially better than that of IL-12-transduced syngeneic fibroblasts or nontransduced BM-DCs. Furthermore, intratumoral injection with IL-12-transduced dendritic cells (DCs) induced specific TH1-type responses to the tumor in regional lymph nodes and spleen at levels greater than those of IL-12-transduced fibroblasts or nontransduced BM-DCs. Trafficking studies confirmed that intratumorally injected IL-12-transduced DCs, but not fibroblasts, could migrate to the draining lymph node to the same extent as nontransduced BM-DCs. This strategy designed to deliver genetically modified DCs to tumor sites is associated with systemic and therapeutic antitumor immunity and is an alternative approach to those that use delivery of DCs loaded with tumor antigen. These results support the clinical application of IL-12 gene-modified DCs in patients with cancer.
[Antifungal medical plants in a complex treatment of generalized parodontosis complicated with candidosis]. (2005)

There is a wide spectrum of Antifungoid medical plants. An Antifungoid effect is as usual combined with an antibacterial and anti-inflammatory one. It enables to use such medications in a comlex treatment of generalized parodontosis complicated with candidosis. Besides, plant medications have not virtually any adverse effect and produce no allergenic reactions.