gebhart/patrepeval huggingface dataset:
Recent Developments in the Medicinal Chemistry and Therapeutic Potential of Dihydroorotate Dehydrogenase (DHODH) Inhibitors (2011)

Dihydroorotate dehydrogenase (DHODH) is a flavin-dependent mitochondrial enzyme that catalyzes fourth reaction of pyrimidine de-novo synthesis. Pyrimidine bases are essential for cellular metabolism and cell growth, and are considered as important precursors used in DNA (thymine and cytosine), RNA (uracil and cytosine), glycoproteins and phospholipids biosynthesis. The significance of pyrimidines biosynthesis in DNA and RNA makes them ideal targets for pharmacological intervention. Inhibitors of DHODH have proven efficacy for the treatment of malaria, autoimmune diseases, cancer, rheumatoid arthritis and psoriasis. Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) represents an important target for the treatment of malaria. Many of the clinically relevant anti-tumor and immunosuppressive drugs target human dihydroorotate dehydrogenase (hDHODH), and the two most promising drugs of such kinds are brequinar (antitumor and immunosuppressive) and leflunomide (immunosuppressive). X-ray crystal structures of DHODH in complex with inhibitors reveal common binding region shared by each inhibitor. A number of compounds are identified by high-throughput screening (HTS) of chemical libraries and structure-based computational approaches as selective DHODH inhibitors. Based upon the understanding of molecular interaction of DHODH inhibitors with binding site, some of the common structural features are identified like ability of compounds to interact with ubiquinone (CoQ) binding site and substituents linked to a variety of heterocyclic and heteroaromatic rings responsible for H-bonding with binding site. These findings provide new approaches to design DHODH inhibitors and highlights DHODH as a target for chemotherapeutics. This review is mainly focused on the recent developments in the medicinal chemistry and therapeutic potential of DHODH inhibitors as a target for drug discovery.
Prioritized active learning for malicious URL detection using weighted text-based features (2017)

Data analytics is being increasingly used in cyber-security problems, and found to be useful in cases where data volumes and heterogeneity make it cumbersome for manual assessment by security experts. In practical cyber-security scenarios involving data-driven analytics, obtaining data with annotations (i.e. ground-truth labels) is a challenging and known limiting factor for many supervised security analytics task. Significant portions of the large datasets typically remain unlabelled, as the task of annotation is extensively manual and requires a huge amount of expert intervention. In this paper, we propose an effective active learning approach that can efficiently address this limitation in a practical cyber-security problem of Phishing categorization, whereby we use a human-machine collaborative approach to design a semi-supervised solution. An initial classifier is learnt on a small amount of the annotated data which in an iterative manner, is then gradually updated by shortlisting only relevant samples from the large pool of unlabelled data that are most likely to influence the classifier performance fast. Prioritized Active Learning shows a significant promise to achieve faster convergence in terms of the classification performance in a batch learning framework, and thus requiring even lesser effort for human annotation. An useful feature weight update technique combined with active learning shows promising classification performance for categorizing Phishing/malicious URLs without requiring a large amount of annotated training samples to be available during training. In experiments with several collections of PhishMonger's Targeted Brand dataset, the proposed method shows significant improvement over the baseline by as much as 12%.
Isolation rearing induces recognition memory deficits accompanied by cytoskeletal alterations in rat hippocampus (2006)

Social isolation from weaning affects hippocampal structure and function in the rat. The intrinsic dynamic instability of the cytoskeletal microtubular system is essential for neuronal development and organization. Accordingly, the present paper investigated the effects of social isolation on hippocampal levels of alpha-tubulin isoforms associated with microtubule dynamics, the dendritic marker MAP-2 and alterations in locomotor activity and recognition memory. Male Lister Hooded rats (postnatal day 25-28) were housed either in groups or singly (isolated animals) for 30 days. Locomotor activity in a novel arena and novel object recognition were monitored in activity boxes. The hippocampus was dissected out 18 h after the novel object recognition task. Levels of alpha-tubulin isoforms and MAP-2 were analysed using Western blots. The experiments were conducted in duplicate, using two batches of rats obtained from different suppliers. Isolated animals were hyperactive and showed recognition memory deficits in the novel object recognition task. These behavioural alterations were accompanied by specific alterations in hippocampal alpha-tubulin isoforms and decreased MAP-2 expression. The results confirm that rearing rats in isolation produces hyperactivity and cognitive deficits. The behavioural alterations were accompanied by hippocampal cytoskeletal changes consistent with microtubule stabilization, and by decreased MAP-2 expression. These findings are indicative of an abnormal development of synaptic connections and/or reductions in neuronal cell number. The developmental structural abnormalities in the hippocampus may contribute to the cognitive impairments which result from isolation rearing in rats.
Notes - Osmium Tetroxide-Catalyzed Periodate Oxidation of Olefinic Bonds (1956)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNotes - Osmium Tetroxide-Catalyzed Periodate Oxidation of Olefinic BondsR. Pappo, D. Allen, Jr., R. Lemieux, and W. JohnsonCite this: J. Org. Chem. 1956, 21, 4, 478–479Publication Date (Print):April 1, 1956Publication History Published online28 February 2003Published inissue 1 April 1956https://doi.org/10.1021/jo01110a606RIGHTS & PERMISSIONSArticle Views6879Altmetric-Citations552LEARN 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 InReddit PDF (281 KB) Get e-Alerts Get e-Alerts
Phased array antenna calibration and pattern prediction using mutual coupling measurements (1989)

A technique which utilized the inherent mutual coupling in an array to both calibrate and predict the radiation patterns of a phased-array antenna is investigated. The only restriction of the technique is that the ability to transmit and receive with pairs of the array elements is required. The theory associated with array mutual coupling and its relationship to both array calibration and array patterns is discussed. The design of a test bed phased-array antenna is covered. The mutual coupling technique (MCT) is used experimentally to calibrate the test array as well as to predict the array radiation patterns. It is shown that the results obtained by MCT are in good agreement with conventional far-field measurements.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Real-time reliable determination of binding kinetics of DNA hybridization using a multi-channel graphene biosensor (2017)

Reliable determination of binding kinetics and affinity of DNA hybridization and single-base mismatches plays an essential role in systems biology, personalized and precision medicine. The standard tools are optical-based sensors that are difficult to operate in low cost and to miniaturize for high-throughput measurement. Biosensors based on nanowire field-effect transistors have been developed, but reliable and cost-effective fabrication remains a challenge. Here, we demonstrate that a graphene single-crystal domain patterned into multiple channels can measure time- and concentration-dependent DNA hybridization kinetics and affinity reliably and sensitively, with a detection limit of 10 pM for DNA. It can distinguish single-base mutations quantitatively in real time. An analytical model is developed to estimate probe density, efficiency of hybridization and the maximum sensor response. The results suggest a promising future for cost-effective, high-throughput screening of drug candidates, genetic variations and disease biomarkers by using an integrated, miniaturized, all-electrical multiplexed, graphene-based DNA array.
Effects of Insulin on Cholesterol Synthesis in Type II Diabetes Patients (1995)

Our study demonstrates that in nonobese, normolipidemic, type II diabetic patients under poor metabolic control, an increased cholesterol synthesis is normalized by insulin therapy. Hyperinsulinemia in the presence of euglycemia acutely decreases the circulating levels of MVA, the immediate product of hydroxymethylglutaryl-CoA reductase activity and an index of whole-body cholesterol synthesis.
3D IC architecture for high density memories (2010)

Memory device scaling is facing increasing challenges due to the limited number of read and write cycles in flash memories, capacitor scaling limitations for DRAM cells, high lithography manufacturing costs, and low return-on-investment (ROI) from fab investments. Hence, emerging memories, based on new materials and concepts are being developed. However, material breakthroughs must be realized for these emerging memories to be successful before market introduction. Among potential candidates are phase-change and resistive memories. The scalability of ferroelectric and magnetic RAM is poor and unlikely to meet future scaling challenges. To overcome these challenges, low-cost and high-density memory cell stacking in 3-dimensional (3D) integrated circuits (ICs) is desirable. Unlike well-known 3D through-silicon-vias (TSV) a package-level technology the true 3D IC, or simply 3D IC, must be able to stack multi-memory layers sequentially on top of other device layers in a single chip at low cost using proven materials and devices. We propose such an approach and have developed the relevant technology to bring about this memory evolution.
Infliximab induced T lymphocyte apoptosis in Crohn's disease. (2005)

Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract of unknown origin. Therapies include immune modulating agents, biological therapies, and surgery. The activity and efficacy of the anti-tumor necrosis factor (TNF) therapies infliximab and etanercept have proved to be different: infliximab is effective to induce and maintain remission in refractory CD, while etanercept is not. This brief review considers the question of whether this disparity can be explained by the different structure of the proteins, their different binding affinities, or the subsequent effects on T lymphocytes.
Dental Implant Outcome after Primary Implantation into Double-Barreled Fibula Osteoseptocutaneous Free Flap–Reconstructed Mandible (2011)

Therapeutic, V.
Neutrophil Extracellular Traps protein composition is specific for patients with Lupus nephritis and includes methyl-oxidized αenolase (methionine sulfoxide 93) (2019)

NETs constitute a network of DNA and proteins released by neutrophils in response to infectious and immunologic triggers. NET proteins are recognized as autoantigens in ANCA vasculitis; limited knowledge is available in other autoimmune pathologies. The composition of NETs produced ex vivo by resting and Phorbol-myristate acetate (PMA) stimulated neutrophils was analyzed by high-throughput Fusion Orbitrap technology in 16 patients with Systemic Lupus Erythematosus/Lupus nephritis (9 SLE/7 LN) and in 11 controls. Seven-hundred proteins were characterized and specific fingerprints discriminated LN from SLE. We focused on methyl-oxidized αenolase (methionine sulfoxide 93) that was markedly increased in NETs from LN and was localized in NET filaments in tight connection and outlying DNA. The isotype of anti-αenolase antibodies was IgG2 in LN and IgG4 in other autoimmune glomerulonephritis (Membranous Nephropathy, MN); serum anti-αenolase IgG2 were higher in LN than in SLE and absent in MN. The same IgG2 antibodies recognized 5 epitopes of the protein one containing methionine sulphoxide 93. In conclusion, specific NET protein fingerprints characterize different subsets of SLE; methyl-oxidized αenolase is over-expressed in LN. Circulating anti-αenolase IgG2 recognize the oxidized epitope and are high in serum of LN patients. Post-translational modified NET proteins contribute to autoimmunity in patients with LN.
Pregnancy Rates of Beef Heifers Bred Either on Puberal or Third Estrus (1987)

The objective of this study was to determine if pregnancy rates (PR) differed between beef heifers bred to fertile bulls on either their puberal (E1, n = 89) or third (E3, n = 67) estrus. Heifers were obtained from two lactations (Manhattan, L1; and Miles City, L2), and the experiment was conducted at Miles City. Heifers were assigned randomly within location to either E1 or E3. Heifers were fed to gain .56 kg.head-1 X d-1 and observed twice daily for estrus. After exhibiting first estrus (puberty) and breeding, each heifer in E1 was palpated rectally on d 6, 9 and 12 +/- 1 d (estrus = d 0) for the presence of a corpus luteum, and a venous blood sample was collected for assay of progesterone by radioimmunoassay. Heifers in E3 were palpated and bled on the same schedule as heifers in E1 after first estrus and after being bred to a fertile bull at third estrus. Pregnancy rates were determined by rectal palpation at approximately 38 d post-breeding. Location of origin did not affect (P greater than .10) weight at puberty or weight at breeding; however, heifers from L1 were younger (P less than .05) than heifers from L2 at puberty and breeding. Pregnancy rates were 57 and 78% for heifers in E1 and E3, respectively (P less than .05). Weight at breeding did not influence (P greater than .10) pregnancy rates. The probability of heifers in E1 becoming pregnant increased (P less than .05) with increasing age, while age was not a factor (P greater than .10) for heifers in E3. These results indicated that fertility of puberal estrus in beef heifers is lower than third estrus. Higher fertility of third estrus may be related to maturational changes associated with cycling activity.
Learning to Search Better Than Your Teacher (2015)

Methods for learning to search for structured prediction typically imitate a reference policy, with existing theoretical guarantees demonstrating low regret compared to that reference. This is unsatisfactory in many applications where the reference policy is suboptimal and the goal of learning is to improve upon it. Can learning to search work even when the reference is poor? We provide a new learning to search algorithm, LOLS, which does well relative to the reference policy, but additionally guarantees low regret compared to deviations from the learned policy: a local-optimality guarantee. Consequently, LOLS can improve upon the reference policy, unlike previous algorithms. This enables us to develop structured contextual bandits, a partial information structured prediction setting with many potential applications.
A review of optimization and quantification techniques for chemical exchange saturation transfer MRI toward sensitive in vivo imaging (2015)

Chemical exchange saturation transfer (CEST) MRI is a versatile imaging method that probes the chemical exchange between bulk water and exchangeable protons. CEST imaging indirectly detects dilute labile protons via bulk water signal changes following selective saturation of exchangeable protons, which offers substantial sensitivity enhancement and has sparked numerous biomedical applications. Over the past decade, CEST imaging techniques have rapidly evolved owing to contributions from multiple domains, including the development of CEST mathematical models, innovative contrast agent designs, sensitive data acquisition schemes, efficient field inhomogeneity correction algorithms, and quantitative CEST (qCEST) analysis. The CEST system that underlies the apparent CEST-weighted effect, however, is complex. The experimentally measurable CEST effect depends not only on parameters such as CEST agent concentration, pH and temperature, but also on relaxation rate, magnetic field strength and more importantly, experimental parameters including repetition time, RF irradiation amplitude and scheme, and image readout. Thorough understanding of the underlying CEST system using qCEST analysis may augment the diagnostic capability of conventional imaging. In this review, we provide a concise explanation of CEST acquisition methods and processing algorithms, including their advantages and limitations, for optimization and quantification of CEST MRI experiments.
The intracerebral distribution of BCNU delivered by surgically implanted biodegradable polymers (1992)

The local concentration and distribution of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) within normal brain tissue were studied following surgical implantation of biodegradable polymer containing BCNU in New Zealand White rabbits. Cylindrical discs of poly(bis(p-carboxyphenoxy)-propane:sebacic acid) copolymer in a 20:80 formulation were made containing [3H]-inulin or [3H]-BCNU labeled in the methylene hydrogens of the chloroethyl groups. These were implanted in the brains of 56 New Zealand White rabbits. The animals were sacrificed 3, 7, 14, or 21 days later and the brains were rapidly removed, frozen, and prepared for quantitative autoradiography. Autoradiographs from coronal sections bisecting the polymer were analyzed to determine both the proportion of the brain section exposed to the tracer and the local drug concentrations as a function of distance from the polymer. Tritiated BCNU was also injected directly into the brains of eight additional rabbits, and local brain concentrations were studied over time. The results of this study demonstrate that approximately 50% of the area of the brain sections was exposed to radiolabeled compound 3 days after BCNU-polymer implantation, 15% at 7 days, and less than 10% at 14 and 21 days. Polymer discs containing 600 micrograms BCNU generated 6 mM concentrations of BCNU in brain tissue 10 mm from the polymer at 3 and 7 days. Pharmacological studies demonstrated that approximately 25% of the tritium label was associated with intact BCNU 3 days following polymer implantation. Radiolabeled inulin delivered by polymer remained dispersed throughout the ipsilateral hemisphere for 14 days. Direct injection of [3H]-BCNU into brain parenchyma resulted in widely distributed tracer at 1 and 3 hours with rapid disappearance thereafter. It is concluded that local delivery of BCNU to brain tissue with this polymeric drug delivery system results in sustained high local concentrations of BCNU which may be of value in the treatment of patients with brain tumors.
SUPPORTING EFFICIENT, EVIDENCE‐CENTERED ITEM DEVELOPMENT FOR THE GRE VERBAL MEASURE (2007)

ABSTRACT This paper explores alternative approaches for facilitating efficient, evidence‐centered item development for a new type of verbal reasoning item developed for use on the GRE® General Test. Results obtained in two separate studies are reported. The first study documented the development and validation of a fully automated approach for locating the types of stimulus materials needed to support more efficient generation of the studied item type. The validation results confirmed that the proposed filtering technique can help item writers increase the percentage of acceptable stimulus paragraphs located per unit time interval from the current level of about 10% to nearly 30%. The second study documented the development and validation of a set of task models designed to help item writers generate new items that are optimally constructed to provide high‐quality evidence about targeted skills. The proposed models were validated by considering the percentage of difficulty variance accounted for by the specified item classifications. That amount ranged from slightly more than 30% for items designed to test vocabulary skills to slightly more than 40% for items designed to test additional verbal reasoning skills, such as generating near and far inferences and understanding complex oppositional reasoning.
El carácter laboral de la prestación de servicios a través de plataformas digitales: el caso de Glovo. Comentario de la Sentencia del Tribunal Superior de Justicia de Cataluña de 21 de febrero de 2020 (2020)

espanolLa principal cuestion que se plantea en aquellos supuestos en que se prestan servicios a traves de plataformas digitales no es otra que la de determinar la calificacion juridica que debe otorgarse a la relacion existente entre la empresa, titular de la plataforma, y los prestadores de servicios a traves de la misma. En estos momentos ya empezamos a disponer de un amplio bagaje de doctrina judicial, aunque todavia no de jurisprudencia del Tribunal Supremo, que de un modo recurrente han tenido que pronunciarse sobre la naturaleza juridica de la prestacion de servicios que se desarrolla a traves de las plataformas digitales. En este contexto se incardina, precisamente, la STSJ de Cataluna de 21 de febrero de 2020 que revocando una sentencia de instancia que negaba el caracter laboral de una prestacion de servicios desarrollada a traves de la plataforma digital conocida como Glovo concluye que la misma si merece esta calificacion. EnglishThe main issue which is raised in those cases in which services are provided through digital platforms is none other than that of determining the legal description that should be granted to the relationship existing between the company, the owner of the platform, and those who provide their services through it. We are already beginning to have a vast judicial doctrine - although not yet with jurisprudence of the Supreme Court - which has recurrently had to give its opinion on the legal nature of the provision of services developed through digital platforms. This context includes, precisely, the Ruling of the High Court (STSJ) of Catalonia of 21 February 2020 which, reversing a first instance ruling which denied the labour character of a provision of services developed through the digital platform known as Glovo, concludes that the same does deserve to be described as a labour relationship