gebhart/patrepeval huggingface dataset:
A high-throughput genetic screen identifies previously uncharacterized Borrelia burgdorferi genes important for resistance against reactive oxygen and nitrogen species (2017)

Borrelia burgdorferi, the causative agent of Lyme disease in humans, is exposed to reactive oxygen and nitrogen species (ROS and RNS) in both the tick vector and vertebrate reservoir hosts. B. burgdorferi contains a limited repertoire of canonical oxidative stress response genes, suggesting that novel gene functions may be important for protection of B. burgdorferi against ROS or RNS exposure. Here, we use transposon insertion sequencing (Tn-seq) to conduct an unbiased search for genes involved in resistance to nitric oxide, hydrogen peroxide, and tertiary-butyl hydroperoxide in vitro. The screens identified 66 genes whose disruption resulted in increased susceptibility to at least one of the stressors. These genes include previously characterized mediators of ROS and RNS resistance (including components of the nucleotide excision repair pathway and a subunit of a riboflavin transporter), as well as novel putative resistance candidates. DNA repair mutants were among the most sensitive to RNS in the Tn-seq screen, and survival assays with individual Tn mutants confirmed that the putative ribonuclease BB0839 is involved in resistance to nitric oxide. In contrast, mutants lacking predicted inner membrane proteins or transporters were among the most sensitive to ROS, and the contribution of three such membrane proteins (BB0017, BB0164, and BB0202) to ROS sensitivity was confirmed using individual Tn mutants and complemented strains. Further analysis showed that levels of intracellular manganese are significantly reduced in the Tn::bb0164 mutant, identifying a novel role for BB0164 in B. burgdorferi manganese homeostasis. Infection of C57BL/6 and gp91phox-/- mice with a mini-library of 39 Tn mutants showed that many of the genes identified in the in vitro screens are required for infectivity in mice. Collectively, our data provide insight into how B. burgdorferi responds to ROS and RNS and suggests that this response is relevant to the in vivo success of the organism.
Change of Ground State Configuration Induced by the Stark Shift of Surface States in Some bcc(001) Surfaces (1999)

Using density functional calculations, we found that the ground state configuration of some bcc(001) surfaces are field dependent because different configurations experience different Stark shifts of surface states. When the W(001) surface is positively biased, an external electric field stabilizes a $c(2\ifmmode\times\else\texttimes\fi{}2)$ array of surface vacancies, so that the ground state is no longer the well-established ``Debe-King'' model. Similar behavior is found for Mo(001), but not for Nb(001). The field-induced change of ground state provides a natural explanation for the anomalous behavior of W(001) inside field ion microscopes.
Data from Baseline Plasma Tumor Mutation Burden Predicts Response to Pembrolizumab-based Therapy in Patients with Metastatic Non–Small Cell Lung Cancer (2023)

&lt;div&gt;AbstractPurpose:&lt;p&gt;The role of plasma-based tumor mutation burden (pTMB) in predicting response to pembrolizumab-based first-line standard-of-care therapy for metastatic non–small cell lung cancer (mNSCLC) has not been explored.&lt;/p&gt;Experimental Design:&lt;p&gt;A 500-gene next-generation sequencing panel was used to assess pTMB. Sixty-six patients with newly diagnosed mNSCLC starting first-line pembrolizumab-based therapy, either alone or in combination with chemotherapy, were enrolled (Clinicaltrial.gov identifier: NCT03047616). Response was assessed using RECIST 1.1. Associations were made for patient characteristics, 6-month durable clinical benefit (DCB), progression-free survival (PFS), and overall survival (OS).&lt;/p&gt;Results:&lt;p&gt;Of 66 patients, 52 (78.8%) were pTMB-evaluable. Median pTMB was 16.8 mutations per megabase (mut/Mb; range, 1.9–52.5) and was significantly higher for patients achieving DCB compared with no durable benefit (21.3 mut/Mb vs. 12.4 mut/Mb, &lt;i&gt;P&lt;/i&gt; = 0.003). For patients with pTMB ≥ 16 mut/Mb, median PFS was 14.1 versus 4.7 months for patients with pTMB &lt; 16 mut/Mb [HR, 0.30 (0.16–0.60); &lt;i&gt;P&lt;/i&gt; &lt; 0.001]. Median OS for patients with pTMB ≥ 16 was not reached versus 8.8 months for patients with pTMB &lt; 16 mut/Mb [HR, 0.48 (0.22–1.03); &lt;i&gt;P&lt;/i&gt; = 0.061]. Mutations in &lt;i&gt;ERBB2&lt;/i&gt; exon 20, &lt;i&gt;STK11, KEAP1&lt;/i&gt;, or &lt;i&gt;PTEN&lt;/i&gt; were more common in patients with no DCB. A combination of pTMB ≥ 16 and absence of negative predictor mutations was associated with PFS [HR, 0.24 (0.11–0.49); &lt;i&gt;P&lt;/i&gt; &lt; 0.001] and OS [HR, 0.31 (0.13–0.74); &lt;i&gt;P&lt;/i&gt; = 0.009].&lt;/p&gt;Conclusions:&lt;p&gt;pTMB ≥ 16 mut/Mb is associated with improved PFS after first-line standard-of-care pembrolizumab-based therapy in mNSCLC. &lt;i&gt;STK11/KEAP1/PTEN&lt;/i&gt; and &lt;i&gt;ERBB2&lt;/i&gt; mutations may help identify pTMB-high patients unlikely to respond. These results should be validated in larger prospective studies.&lt;/p&gt;&lt;/div&gt;
A new approach to product structures for product families (2000)

info:eu-repo/semantics/published
Challenges in Cryptography (2021)

Cryptography as a field of study is exciting because it brings together beautiful mathematics and many cutting-edge areas of computer science and engineering to find solutions that touch all aspects of life in a digital era. In a single day at a cryptography conference, one can hear talks on election security and legislation on regulating encryption, new mathematical constructions that might yield more efficient encryption schemes, how to wirelessly hack a Tesla and drive away without the key, how Google secures communication between its data centers, and how to build a more private blockchain.
Phosphoprotein Stability in Clinical Tissue and Its Relevance for Reverse Phase Protein Microarray Technology (2011)

Phosphorylated proteins reflect the activity of specific cell signaling nodes in biological kinase protein networks. Cell signaling pathways can be either activated or deactivated depending on the phosphorylation state of the constituent proteins. The state of these kinase pathways reflects the in vivo activity of the cells and tissue at any given point in time. As such, cell signaling pathway information can be extrapolated to infer which phosphorylated proteins/pathways are driving an individual tumor's growth. Reverse phase protein microarrays (RPMAs) are a sensitive and precise platform that can be applied to the quantitative measurement of hundreds of phosphorylated signal proteins from a small sample of tissue. Pre-analytical variability originating from tissue procurement and preservation may cause significant variability and bias in downstream molecular analysis. Depending on the ex vivo delay time in tissue processing, and the manner of tissue handling, protein biomarkers such as signal pathway phosphoproteins will be elevated or suppressed in a manner that does not represent the biomarker levels at the time of excision. Consequently, assessment of the state of these kinase networks requires stabilization, or preservation, of the phosphoproteins immediately post-tissue procurement. We have employed RPMA analysis of phosphoproteins to study the factors influencing stability of phosphoproteins in tissue following procurement. Based on this analysis we have established tissue procurement guidelines for clinical research with an emphasis on quantifying phosphoproteins by RPMA.
Optimal Scheduling for Discounted Age Penalty Minimization in Multi-Loop\n Networked Control (2019)

Age-of-information (AoI) is a metric quantifying information freshness at the\nreceiver. Since AoI combines packet generation frequency, packet loss, and\ndelay into a single metric, it has received a lot of research attention as an\ninterface between communication network and application. In this work, we apply\nAoI to the problem of wireless scheduling for multi-loop networked control\nsystems (NCS), i.e., feedback control loops closed over a shared wireless\nnetwork. We model the scheduling problem as a Markov decision process (MDP)\nwith AoI as its observable states and derive a relation of control system error\nand AoI. We further derive a stationary scheduling policy to minimize control\nerror over an infinite horizon. We show that our scheduler outperforms the\nstate-of-the-art scheduling policies for NCS. To the best of our knowledge,\nthis is the first work proposing an AoI-based wireless scheduling policy that\nminimizes the control error over an infinite horizon for multi-loop NCS.\n
Abstract CN01-02: Maximizing the potential of bispecific antibodies for cancer drug development (2019)

Abstract Landmark advances in the engineering and development of bispecific antibodies (bsAbs) are enabling unprecedented versatility in therapeutic antibody concepts. Currently more than 20 different commercialized technology platforms are available for bsAb creation and development, two bsAbs are marketed, of which one in cancer, and over 85 are in clinical development. A defining bsAb feature is their potential for novel functionalities — that is, activities that do not exist in mixtures of the parental or reference antibodies. These so-called obligate bsAb have high potential for the development of novel and differentiating cancer drugs. Bispecific T cell engagers (bs-TCE) are a prominent class of obligate bsAb for targeted cancer immunotherapy. Classical bs-TCE designs consist of a tumor antigen-binding domain combined with a binding domain against the CD3 T-cell receptor-signaling complex. Irrespective of the bispecific antibody format used, CD3-based bs-TCEs have a number of disadvantages, which in part are explained by the fact that they activate all T-cells irrespective of lineage, which associates with serious adverse events as a result of exaggerated T cell activation and cytokine release in some patients, and limited efficacy due to T suppressor cell activation in others. The development of bs-TCEs with increased tumor selectivity to widen the therapeutic window has high potential. The engagement of γδ T cells, and Vγ9Vδ2-T cells in particular, is in this context of particular interest. This γδ T cell subset has been shown to display powerful innate anti-tumor immune effector activity with an ability to infiltrate human tumors in which its abundance has been shown to positively correlate with patient survival. The potential of bsTCEs designed to engage Vγ9Vδ2-T cells as an approach for the development of novel cancer immunotherapies will be discussed. Citation Format: Paul W H I Parren. Maximizing the potential of bispecific antibodies for cancer drug development [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr CN01-02. doi:10.1158/1535-7163.TARG-19-CN01-02
Mechanisms of charge transfer at the chemically derivatized interface: the Ni/[NiII(CN)FeII/III(CN)5]2-/1- system as an electrocatalyst (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMechanisms of charge transfer at the chemically derivatized interface: the Ni/[NiII(CN)FeII/III(CN)5]2-/1- system as an electrocatalystBrian D. Humphrey, Sujit. Sinha, and Andrew B. BocarslyCite this: J. Phys. Chem. 1987, 91, 3, 586–593Publication Date (Print):January 1, 1987Publication History Published online1 May 2002Published inissue 1 January 1987https://pubs.acs.org/doi/10.1021/j100287a020https://doi.org/10.1021/j100287a020research-articleACS PublicationsRequest reuse permissionsArticle Views282Altmetric-Citations129LEARN 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 options Get e-Alerts
From Rust to Quantum Biology: The Role of Iron in Retina Physiopathology (2020)

Iron is essential for cell survival and function. It is a transition metal, that could change its oxidation state from Fe<sup>2+</sup> to Fe<sup>3+</sup> involving an electron transfer, the key of vital functions but also organ dysfunctions. The goal of this review is to illustrate the primordial role of iron and local iron homeostasis in retinal physiology and vision, as well as the pathological consequences of iron excess in animal models of retinal degeneration and in human retinal diseases. We summarize evidence of the potential therapeutic effect of iron chelation in retinal diseases and especially the interest of transferrin, a ubiquitous endogenous iron-binding protein, having the ability to treat or delay degenerative retinal diseases.
Slow ventricular tachycardia presenting with acute liver failure (2017)

Diagnosis of VT can be challenging if occurring at unexpected slow heart rates. Analysis of pacemaker recordings could help to make the diagnosis of slow VT.
Trifluoroethanol Stabilizes a Helix‐Turn‐Helix Motif in Equine Infectious‐Anemia‐Virus Trans ‐Activator Protein (1994)

The solution structure of the 75-amino-acid trans-activator (Tat) protein of the equine infectious-anemia virus in trifluoroethanol-containing solution was determined by two-dimensional and three-dimensional nuclear magnetic resonance spectroscopy, resulting in a total of 838 nuclear-Over-hauser-enhancement distance restraints, and restrained molecular-dynamics simulations. In contrast to the recently determined structure of this protein in trifluoroethanol-free pH 6.3 solution, the hydrophobic core and the adjacent basic RNA-binding region of the protein showed well-defined alpha-helical secondary structure in trifluoroethanol-containing solution. The helical regions comprise those parts of the molecule whose helix-forming tendencies were noted earlier in trifluoroethanol-free solution. Two helices (Gln38-Arg43 and Asp48-Ala64) are connected by a tight type-II turn centered at the strictly conserved Gly46 leading to a helix-turn-helix motif in the core and basic region of the protein. A third helix (Thr9-Asn13) is located in the less well defined N-terminal part of the protein. These observations may support the notion that the protein adopts a helical structure in the RNA-binding region on complex formation. Although the secondary-structure elements become better defined in trifluoroethanol-containing solution, the opposite is true for the hydrophobically stabilized tertiary structure. This adds a caveat to studies of protein structures in trifluoroethanol-containing solution in general.
Structural insights into cis element recognition of non-polyadenylated RNAs by the Nab3-RRM (2010)

Transcription termination of non-polyadenylated RNAs in Saccharomyces cerevisiae occurs through the action of the Nrd1-Nab3-Sen1 complex. Part of the decision to terminate via this pathway occurs via direct recognition of sequences within the nascent transcript by RNA recognition motifs (RRMs) within Nrd1 and Nab3. Here we present the 1.6 Å structure of Nab3-RRM bound to its UCUU recognition sequence. The crystal structure reveals clear density for a UCU trinucleotide and a fourth putative U binding site. Nab3-RRM establishes a clear preference for the central cytidine of the UCUU motif, which forms pseudo-base pairing interactions primarily through hydrogen bonds to main chain atoms and one serine hydroxyl group. Specificity for the flanking uridines is less defined; however, binding experiments confirm that these residues are also important for high affinity binding. Comparison of the Nab3-RRM to other structures of RRMs bound to polypyrimidine RNAs showed that this mode of recognition is similar to what is observed for the polypyrimidine-tract binding RRMs, and that the serine residue involved in pseudo-base pairing is only found in RRMs that bind to polypyrimidine RNAs that contain a cytosine base, suggesting a possible mechanism for discriminating between cytosine and uracil bases in RRMs that bind to polypyrimidine-containing RNA.
Parallel analysis of sporadic primary ovarian carcinomas by spectral karyotyping, comparative genomic hybridization, and expression microarrays. (2002)

Analysis of ovarian carcinomas has shown that karyotypes are often highly abnormal and cannot be identified with certainty by conventional cytogenetic methods. In this study, 17 tumors derived from 13 patients were analyzed by a combination of spectral karyotyping (SKY), comparative genomic hybridization (CGH), and expression microarrays. Within the study group, a total of 396 chromosomal rearrangements could be identified by SKY and CGH analysis. When the distribution of aberrations was normalized with respect to relative genomic length, chromosomes 3, 8, 11, 17, and 21 had the highest frequencies. Parallel microarray expression studies of 1718 human cDNAs were used to analyze expression profiles and to determine whether correlating gene expression with chromosomal rearrangement would identify smaller subsets of differentially expressed genes. Within the entire set of samples, microarray expression analysis grouped together poorly differentiated tumors irrespective of histological subtype. For three patients, a comparison between genomic alterations and gene expression pattern was performed on samples of primary and metastatic tumors. Their common origin was demonstrated by the close relationship of both the SKY and CGH karyotypes and the observed profiles of gene expression. In agreement with the pattern of genomic imbalance observed for chromosome 3 in ovarian cancer, the relative expression profile with respect to a normal ovary exhibited a contiguous pattern of reduced expression of genes mapping to the 3p25.5-3p21.31 and increased expression of genes from 3q13.33-3q28. This study demonstrates that SKY, CGH, and microarray analysis can in combination identify significantly smaller subsets of differentially expressed genes for future studies.
In Vivo Pharmacology of L-159,913, A New Highly Potent and Selective Nonpeptide Angiotensin II Receptor Antagonist (1995)

The present study was designed to characterize the in vivo pharmacology of L-159,913 (4-[[2'-(N-benzoylsulfamoyl)biphenyl-4-yl]-5butyl-2,4-dihydr o-2- [2-(trifluoromethyl)phenyl]-3H-1,2,4-triazol-3-one); a potent All receptor antagonist. In normotensive rats, dogs, rhesus monkeys, and chimpanzees, L-159,913 inhibited All-induced elevations in blood pressure. In conscious rats, the relative potencies (ED50) were 0.51 mg/kg i.v. and 0.72 mg/kg p.o. Duration of action with single i.v. or p.o. doses exceeded 6 hr in rats. L-159,913 was 3 times less potent than losartan in rats and equipotent to losartan in monkeys. All induced elevation of plasma aldosterone in rats was also inhibited by L-159,913. L-159,913 was antihypertensive in high renin hypertensive rats (aortic coarctation). The maximum hypotensive response to an acute dose of L-159,913 (10 mg/kg, po) was equal to that of enalaprilat (0.3 mg/kg, iv) in this renin dependent animal model. In conscious normotensive dogs, L-159,913 had a moderate diuretic, natriuretic and kaliuretic response with no effect on glomerular filtration rate, effective renal plasma flow or filtration fraction, suggesting a tubular site of action. L-159,913 is a selective and potent All receptor antagonist with good oral activity, long duration of action and antihypertensive efficacy.
Nonlinear Frequency Generation of High-Power Polarisation Vortices in Optical Fibers (2010)

We exploit stimulated-Raman-scattering to generate polarisation-vortices over 3-Stokes-shifts (40-THz) with a specially-designed optical fiber. This illustrates the possibility of generating these beams, of immense recent interest, at any wavelength that nonlinear processes in glass allow.
Stability and Low-Frequency Noise in InAs NW Parallel-Array Thin-Film Transistors (2013)

In this letter, we present the dc characteristics, stability, and low-frequency noise (LFN) measurements, for n-type indium arsenide nanowire (NW) parallel-array thin-film transistors (TFTs) with a global back gate. These devices perform with mobilities ranging from 200-1200 cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> V <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-1</sup> s <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-1</sup> and produce a threshold voltage shift less than 0.25 V after 10 000 <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">s</i> of stress. The resulting LFN measurements indicate that the 1/ <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">f</i> noise can be modeled by the number fluctuation model, at low drain currents, which can provide an essential guideline for the device design considerations of NW TFTs.
Efficiency Enhancement in Organic Photovoltaic Cells: Consequences of Optimizing Series Resistance (2009)

Abstract Here, means to enhance power conversion efficiency (PCE or η ) in bulk‐heterojunction (BHJ) organic photovoltaic (OPV) cells by optimizing the series resistance ( R s )—also known as the cell internal resistance—are studied. It is shown that current state‐of‐the‐art BHJ OPVs are approaching the limit for which efficiency can be improved via R s reduction alone. This evaluation addresses OPVs based on a poly(3‐hexylthiophene):6,6‐phenyl C 61 ‐butyric acid methyl ester (P3HT:PCBM) active layer, as well as future high‐efficiency OPVs ( η &gt; 10%). A diode‐based modeling approach is used to assess changes in R s . Given that typical published P3HT:PCBM test cells have relatively small areas (∼0.1 cm 2 ), the analysis is extended to consider efficiency losses for larger area cells and shows that the transparent anode conductivity is then the dominant materials parameter affecting R s efficiency losses. A model is developed that uses cell sizes and anode conductivities to predict current–voltage response as a function of resistive losses. The results show that the losses due to R s remain minimal until relatively large cell areas (&gt;0.1 cm 2 ) are employed. Finally, R s effects on a projected high‐efficiency OPV scenario are assessed, based on the goal of cell efficiencies &gt;10%. Here, R s optimization effects remain modest; however, there are now more pronounced losses due to cell size, and it is shown how these losses can be mitigated by using higher conductivity anodes.