gebhart/patrepeval huggingface dataset:
Improvement of the antimicrobial potency, pharmacokinetic and pharmacodynamic properties of albicidin by incorporation of nitrogen atoms (2021)

The worrisome development and spread of multidrug-resistant bacteria demands new antibacterial agents with strong bioactivities particularly against Gram-negative bacteria. Albicidins were recently structurally characterized as highly active antibacterial natural products from the bacterium <i>Xanthomonas albilineans</i>. Albicidin, which effectively targets the bacterial DNA-gyrase, is a lipophilic hexapeptide mostly consisting of <i>para</i> amino benzoic acid units and only one α-amino acid. In this study, we report on the design and synthesis of new albicidins, containing N-atoms on each of the 5 different phenyl rings. We systematically introduced N-atoms into the aromatic backbone to monitor intramolecular H-bonds and for one derivative correlated them with a significant enhancement of the antibacterial activity and activity spectrum, particularly also towards Gram-positive bacteria. In parallel we conducted DFT calculations to find the most stable conformation of each derivative. A drastic angle-change was observed for the lead compound and shows a preferred planarity through H-bonding with the introduced N-atom at the D-fragment of albicidin. Finally, we went to the next level and conducted the first <i>in vivo</i> experiments with an albicidin analogue. Our lead compound was evaluated in two different mouse experiments: In the first we show a promising PK profile and the absence of toxicity and in the second very good efficiency and reduction of the bacterial titre in an <i>E. coli</i> infection model with FQ-resistant clinically relevant strains. These results qualify albicidins as active antibacterial substances with the potential to be developed as a drug for treatment of infections caused by Gram-negative and Gram-positive bacteria.
Characterizing Complex Populations of Endogenous Adeno-Associated Viruses by Single-Genome Amplification (2022)

The isolation of adeno-associated virus (AAV) genomes from biomaterials at the molecular level has traditionally relied on polymerase chain reaction-based and cloning-based techniques. However, when applied to samples containing multiple species, traditional techniques for isolating viral genomes can amplify artificial recombinants and introduce polymerase misincorporation errors. In this study, we describe AAV single-genome amplification (AAV-SGA): a powerful technique to isolate, amplify, and sequence single AAV genomes from mammalian genomic DNA, which can then be used to construct vectors for gene therapy. We used AAV-SGA to precisely isolate 15 novel AAV genomes belonging to AAV clades A, D, and E and the Fringe outgroup. This technique also enables investigations of AAV population dynamics and recombination events to provide insights into virus-host interactions and virus biology. Using AAV-SGA, we identified regional heterogeneity within AAV populations from different lobes of the liver of a rhesus macaque and found evidence of frequent genomic recombination between AAV populations. This study highlights the strengths of AAV-SGA and demonstrates its capability to provide valuable insights into the biology and diversity of AAVs.
The complete time/temperature dependence of I-V drift in PCM devices (2016)

Phase-change memory (PCM) devices are expected to play a key role in future computing systems as both memory and computing elements. Hence, a comprehensive understanding of the change in the current/voltage (I-V) characteristics of these devices with time and temperature is of considerable importance. Here, we present a unified drift model able to predict the I-V characteristics at any instance in time and at any temperature. The model was validated on large sets of experimental data for an extensive range of time (10 orders of magnitude) and temperatures (180–400 K), different phase-change materials and a collection of 4k cells from a PCM chip.
Abstract 235: Preclinical activity of an antibody drug conjugate targeting tumor specificmuc1 structural peptide-glycotope (2019)

SAR566658 antibody drug conjugate (ADC) is a humanized DS6 (huDS6) antibody conjugated through a cleavable linker to the cytotoxic maytansinoid derivative DM4 that has been evaluated in the clinical setting. The purpose of our work was; 1) characterize the epitope targeted by anti DS6 on mucin1, 2) determine the prevalence of antigen expression in a patient population and 3) further explore preclinical activities of the ADC. Murine DS6 monoclonal antibody (muDS6) was generated from serous ovary adenocarcinoma immunization of immunocompetent mice. It specifically recognizes a MUC-1 tandem repeat domain in the context of cancer associated glycosylation. CA6-positive MUC-1 carries mucin-type O-linked glycans with α2,3-sialylated and β1,4-galactosylated termini, and antibody binding was abrogated by treating MUC-1 with specific glycosidases that remove either one of these glycan structures. However, the antibody did not bind to synthetic glycans modeled according to the major O-glycans of MUC-1. Our characterization of the peptide-glycotope leads us to conclude that tumor associated glycosylation is essential for the formation of the epitope on the peptide sequence of the MUC-1 tandem repeat domain. CA6 expression was evaluated by immunohistochemistry in paraffin embedded tumor tissue samples: 35.2% of breast cancer patients, 70,1% of ovarian cancer patients and 58,5% of bladder cancer patients have at least 30% of CA6 positive cells with an intensity of 2+/3+ in a multinational population-based study. In pre-clinical in vivo models, SAR566658 induced anti-tumor activity against CA6 positive tumor models of human pancreas, cervix and bladder cancer as well as and 3 Breast Patient-Derived Xenografts (PDX). Efficacy was correlated with MUC1-CA6 expression levels. In 3 additional models, SAR566658 showed anti-tumor activity that was more potent when compared to 3 conventional tubulin cytotoxic agents, docetaxel, vinorelbine and vinblastine.Citation Format: Marc Trombe, Anne Caron, Alexia Tellier, Chantal Carrez, Stephane Guérif, Severine Clavier, Nathalie Karst, Juhani Saarinen, Tero Satomaa, Virve Pitkänen, Olli Aitio, Annamari Heiskanen, Matteo Fassan, Jan Pinkas, Raffaele Baffa, Veronique Blanc, Celine Nicolazzi. Preclinical activity of an antibody drug conjugate targeting tumor specificmuc1 structural peptide-glycotope [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 235.
Telomere stability is frequently impaired in high-risk groups of patients with myelodysplastic syndromes. (1999)

Genomic instability induces an accumulation of genetic changes and may play a role in the pathogenesis of myelodysplastic syndromes (MDS). To clarify the possible association between genomic instability and clinical outcome in MDS patients, we compared telomere dynamics to the recently established International Prognostic Scoring System (IPSS) risk groups for MDS. We measured the terminal restriction fragments (TRFs) of 93 patients with MDS at the time of diagnosis, and telomerase activity was analyzed in 62 patients with MDS using the PCR-based telomeric repeat amplification protocol (TRAP) assay. A total of 53 of 93 MDS patients had TRFs within the age-matched normal range, and the remaining patients showed shortened TRFs (35 patients) or elongated TRFs (5 patients). MDS patients with shortened TRFs had a significantly low hemoglobin concentration (P = 0.04), a high percentage of marrow blasts (P = 0.02), and a high incidence of cytogenetic abnormalities (P < 0.05). The incidence of leukemic transformation was significantly high in patients with shortened TRF length (P < 0.05). In addition, patients with shortened TRF length were frequently seen in the IPSS high-risk group (P < 0.01). Most of the MDS patients had normal-to-low levels of telomerase activity, suggesting that changes in TRF length rather than telomerase activity may more accurately reflect the pathophysiology of MDS. MDS patients with shortened TRF length had a very poor prognosis (P < 0.01), suggesting that telomere dynamics may be linked to clinical outcome in MDS patients. Thus, an abnormal mechanism of telomere maintenance in subgroups of MDS patients may be an early indication of genomic instability. This study demonstrates that telomere stability is frequently impaired in a high-risk group of MDS patients and suggests that, in combination with the IPSS classification system, measurement of TRFs may be useful in the future to stratify MDS patients according to risk and manage the care of MDS patients.
Remodeling of Super-hydrophobic Surfaces (2016)

An experimental study on the underlying mechanisms of structured super-hydrophobic surfaces was recently published [Butt, H.-J.; et al. How Water Advances on Superhydrophobic Surfaces. Phys. Rev. Lett. 2016, 116, 096101. DOI: 10.1103/PhysRevLett.116.096101]. After depositing small drops of water, Butt’s group inclined their surfaces to initiate movement. They examined the contact between the water and structured surfaces with confocal microscopy. They observed that drops were suspended atop the protruding features and movement of water was different at the advancing and receding edges. At the advancing edge, the water interface descended downward and draped itself across the features. At the receding edge, water jumped from one feature to the next. As Butt and co-workers did not test their data against any existing model, that is done in this paper. Here, a previously proposed model that employs linear averaging at the contact line was adapted to their surfaces in an attempt to estimate their contact and sliding angles. Predictions from the model generally agreed with their experimental measurements.
Sensitive Detection of Shiga Toxin 2 and Some of Its Variants in Environmental Samples by a Novel Immuno-PCR Assay (2011)

Shiga toxin-producing Escherichia coli (STEC) in the environment has been reported frequently. However, robust detection of STEC in environmental samples remains difficult because the numbers of bacteria in samples are often below the detection threshold of the method. We developed a novel and sensitive immuno-PCR (IPCR) assay for the detection of Shiga toxin 2 (Stx2) and Stx2 variants. The assay involves immunocapture of Stx2 at the B subunit and real-time PCR amplification of a DNA marker linked to a detection antibody recognizing the Stx2 A subunit. The qualitative detection limit of the assay is 0.1 pg/ml in phosphate-buffered saline (PBS), with a quantification range of 10 to 100,000 pg/ml. The IPCR method was 10,000-fold more sensitive than an analogue conventional enzyme-linked immunosorbent assay (ELISA) in PBS. Although the sensitivity of the IPCR for detection of Stx2 was affected by environmental sample matrices of feces, feral swine colons, soil, and water from watersheds, application of the IPCR assay to 23 enriched cultures of fecal, feral swine colon, soil, and watershed samples collected from the environment revealed that the IPCR detected Stx2 in all 15 samples that were shown to be STEC positive by real-time PCR and culture methods, demonstrating a 100% sensitivity and specificity. The modification of the sandwich IPCR we have described in this study will be a sensitive and specific screening method for evaluating the occurrence of STEC in the environment.
Electron Emission from Metal Surfaces by Ultrashort Pulses: Determination of the Carrier-Envelope Phase (2003)

The phase varphi of the field oscillations with respect to the peak of a laser pulse influences the light field evolution as the pulse length becomes comparable to the wave cycle and, hence, affects the interaction of intense few-cycle pulses with matter. We theoretically investigate photoelectron emission induced by an intense, few-cycle laser pulse from a metal surface (jellium) within the framework of time-dependent density functional theory and find a pronounced varphi dependence of the photocurrent. Our results reveal a promising route to measuring varphi of few-cycle light pulses (tau<6 fs at lambda=0.8 microm) at moderate intensity levels (I(p) approximately 10(12) W/cm(2)) using a solid-state device.
Detachable Strong Cation Exchange Monolith, Integrated with Capillary Zone Electrophoresis and Coupled with pH Gradient Elution, Produces Improved Sensitivity and Numbers of Peptide Identifications during Bottom-up Analysis of Complex Proteomes (2015)

A detachable sulfonate-silica hybrid strong cation-exchange monolith was synthesized in a fused silica capillary, and used for solid phase extraction with online pH gradient elution during capillary zone electrophoresis-tandem mass spectrometry (CZE-MS/MS) proteomic analysis. Tryptic digests were prepared in 50 mM formic acid and loaded onto the strong cation-exchange monolith. Fractions were eluted using a series of buffers with lower concentration but higher pH values than the 50 mM formic acid background electrolyte. This combination of elution and background electrolytes results in both sample stacking and formation of a dynamic pH junction and allows use of relatively large elution buffer volumes while maintaining reasonable peak efficiency and resolution. A series of five pH bumps were applied to elute E. coli tryptic peptides from the monolith, followed by analysis using CZE coupled to an LTQ-Orbitrap Velos mass spectrometer; 799 protein groups and 3381 peptides were identified from 50 ng of the digest in a 2.5 h analysis, which approaches the identification rate for this organism that was obtained with an Orbitrap Fusion. We attribute the improved numbers of peptide and protein identifications to the efficient fractionation by the online pH gradient elution, which decreased the complexity of the sample in each elution step and improved the signal intensity of low abundance peptides. We also performed a comparative analysis using a nanoACQUITY UltraPerformance LCH system. Similar numbers of protein and peptide identifications were produced by the two methods. Protein identifications showed significant overlap between the two methods, whereas peptide identifications were complementary.
Endosomal Organizationof CpG Constructs Correlateswith Enhanced Immune Activation (2020)

This
Letter describes how the endosomal organization of immunostimulatory
nanoconstructs can tune the in vitro activation of
macrophages. Nanoconstructs composed of gold nanoparticles conjugated
with unmethylated cytosine-phosphate-guanine (CpG) oligonucleotides
have distinct endosomal distributions depending on the surface curvature.
Mixed-curvature constructs produce a relatively high percentage of
hollow endosomes, where constructs accumulated primarily along the
interior edges. These constructs achieved a higher level of toll-like
receptor (TLR) 9 activation along with the enhanced secretion of proinflammatory
cytokines and chemokines compared to constant-curvature constructs
that aggregated mostly in the center of the endosomes. Our results
underscore the importance of intraendosomal interactions in regulating
immune responses and targeted delivery.
Role of Hepatic Arterial Blood Flow and Hepatic Nerves on Renal Circulation and Function (1965)

HORN, MOTOKAZU M.D.; AUSTEN, W. GERALD M.D.; MCDERMOTT, WILLIAM V. JR. M.D. Author Information
A Statistical Machine Learning Model to Predict Equivalent Circulation Density ECD while Drilling, Based on Principal Components Analysis PCA (2021)

Abstract Mathematical equations, based on conservation of mass and momentum, are used to determine the ECD at different depths in the wellbore. However, such equations do not consider important factors that have a influence on the ECD such as: (i) bottom hole temperature, (ii) pipe rotation and eccentricity, and (iii) wellbore roughness. Thus, discrepancy between the calculated ECDs and actual ones has been reported in the literature. This paper aims to explore how artificial intelligence (AI) and machine learning (ML) could provide real-time accurate prediction of the ECD, to have more insight and management of wellbore downhole conditions. For this purpose, a supervised ML algorithm, support vector machine (SVM), based on principal components analysis (PCA), was developed. Actual field data of Well-1 including drilling surface parameters and ECDs, measured by downhole sensors, were collected to develop a classical SVM model. The dataset was split with an 80/20 training-testing data ratio. Sensitivity analysis with different SVM parameters such as regularization parameter C, gamma, kernel type (linear, radial basis function "RBF") was performed. The performance of the model was assessed in terms of root mean square error (RMSE) and coefficient of determination (R2). Afterward, PCA was applied to the dataset of Well-1 to develop an SVM model using the transformed dataset in PCA space. The performance of the model while using different numbers of principal components was evaluated. The results showed that the classical SVM with the linear kernel predicted the ECD with RMSE of 0.53 and R2 of 0.97 in the training set, while RMSE and R2 were 0.56 and 0.97 respectively in the testing set. The PCA-based SVM model, with the linear kernel and four principal components (93.53% variation of the dataset), predicted the ECD with RMSE 0.79 and R2 of 0.95 in the testing set.
Studies of the chemoenzymatic modification of cellulosic pulps by the laccase-TEMPO system (2011)

Abstract The chemoenzymatic modification of cellulosic pulps by the laccase-mediator system (LMS) consisting of laccase (EC 1.10.3.2) and the 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO) has been investigated. The reaction proceeds under mild aqueous conditions (sodium citrate buffer pH 6, 30°C) and introduces primarily aldehyde groups into cellulose so that carboxyl groups amount to one-third to one-fifth of the carbonyl groups only. LMS treatment caused uniform oxidation of the material, also in the high-molecular weight area, which is a non-typical behavior compared to other chemical oxidations of cellulose. Treatment of the pulp only with TEMPO or only with laccase caused no changes whatsoever, whereas treatment with the TEMPO-derived oxoammonium ion (in the absence of laccase) introduced carbonyl groups into the pulp, but no carboxyls. This chemoenzymatic approach was compared to the well-known chemical approach by means of TEMPO and hypohalite. Both approaches yielded comparable distributions of functional groups at the low oxidation degrees studied, indicating a similar reaction mechanism with the TEMPO-derived oxoammonium ion being the actual oxidant. The laccase is able to generate this oxoammonium ion, which in turn oxidized the 6-hydroxymethyl group into the corresponding aldehyde.
Norms as a basis for governing sociotechnical systems (2013)

We understand a sociotechnical system as a multistakeholder cyber-physical system. We introduce governance as the administration of such a system by the stakeholders themselves. In this regard, governance is a peer-to-peer notion and contrasts with traditional management, which is a top-down hierarchical notion. Traditionally, there is no computational support for governance and it is achieved through out-of-band interactions among system administrators. Not surprisingly, traditional approaches simply do not scale up to large sociotechnical systems. We develop an approach for governance based on a computational representation of norms in organizations. Our approach is motivated by the Ocean Observatory Initiative, a thirty-year $400 million project, which supports a variety of resources dealing with monitoring and studying the world's oceans. These resources include autonomous underwater vehicles, ocean gliders, buoys, and other instrumentation as well as more traditional computational resources. Our approach has the benefit of directly reflecting stakeholder needs and assuring stakeholders of the correctness of the resulting governance decisions while yielding adaptive resource allocation in the face of changes in both stakeholder needs and physical circumstances.
Systematic evaluation of underlying defects in DNA repair as an approach to case-only assessment of familial prostate cancer (2015)

Risk assessment for prostate cancer is challenging due to its genetic heterogeneity. In this study, our goal was to develop an operational framework to select and evaluate gene variants that may contribute to familial prostate cancer risk. Drawing on orthogonal sources, we developed a candidate list of genes relevant to prostate cancer, then analyzed germline exomes from 12 case-only prostate cancer patients from high-risk families to identify patterns of protein-damaging gene variants. We described an average of 5 potentially disruptive variants in each individual and annotated them in the context of public databases representing human variation. Novel damaging variants were found in several genes of relevance to prostate cancer. Almost all patients had variants associated with defects in DNA damage response. Many also had variants linked to androgen signaling. Treatment of primary T-lymphocytes from these prostate cancer patients versus controls with DNA damaging agents showed elevated levels of the DNA double strand break (DSB) marker γH2AX (p < 0.05), supporting the idea of an underlying defect in DNA repair. This work suggests the value of focusing on underlying defects in DNA damage in familial prostate cancer risk assessment and demonstrates an operational framework for exome sequencing in case-only prostate cancer genetic evaluation.
Action of fibroblast growth factor-2 on the intervertebral disc (2008)

FGF2 is anti-anabolic in bovine spine disc cells, revealing the potential of FGF2 antagonists as unique biologic treatments for both prevention and reversal of IVD degeneration.
Electronic origins and consequences of pyramidalization of asymmetric alkenes in ground and triplet excited states (1983)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTElectronic origins and consequences of pyramidalization of asymmetric alkenes in ground and triplet excited statesK. N. Houk, Nelson G. Rondan, Frank K. Brown, William L. Jorgensen, Jeffry D. Madura, and David C. SpellmeyerCite this: J. Am. Chem. Soc. 1983, 105, 19, 5980–5988Publication Date (Print):September 1, 1983Publication History Published online1 May 2002Published inissue 1 September 1983https://pubs.acs.org/doi/10.1021/ja00357a004https://doi.org/10.1021/ja00357a004research-articleACS PublicationsRequest reuse permissionsArticle Views374Altmetric-Citations81LEARN 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-Alertsclose Get e-Alerts