gebhart/patrepeval huggingface dataset:
Design and Validation of FRESH, a Drug Discovery Paradigm Resting on Robust Chemical Synthesis (2015)

A method capable of identifying novel synthetic targets for small molecule lead optimization has been developed. The FRESH (FRagment-based Exploitation of modular Synthesis by vHTS) approach relies on a multistep synthetic route to a target series of compounds devised by a close collaboration between synthetic and computational chemists. It combines compound library generation, quantitative structure-acitvity relationship construction, fragment processing, virtual high throughput screening and display of results within the Pipeline Pilot framework. Outcomes enumerate tailored selection of novel synthetic targets with improved potency and optimized physical properties for an emerging compound series. To validate the application of FRESH, three retrospective case studies have been performed to pinpoint reported potent analogues. One prospective case study was performed to demonstrate that FRESH is able to capture additional potent analogues.
A fuzzy logics based scheduling for downlink OFDMA/SDMA systems with multimedia traffic (2010)

In this paper, we propose a fuzzy logics based scheduling (FLBS) scheme for downlink orthogonal frequency division multiple access (OFDMA)/space division multiple access (SDMA) systems with multimedia traffic. The challenge in the scheduling problem of OFDMA/SDMA systems with multimedia traffic is how to effectively utilize the scarce radio resource as well as maximize the system throughput and guarantee the quality of services (QoS) and fairness. Traditionally, the user information and the channel information are used to assist the scheduler to allocate the radio resource. However, these two information can not be simultaneously modeled on a mathematical function to provide a clear scheduling policy. By using fuzzy logics, the proposed FLBS scheme assigns an urgency value to user based on the user information and the channel information. According to the assigned urgency value, each user gets a suitable radio resource region to maximize the system throughput while guarantee QoS requirement and fairness. Simulation results show that, compared to the most recently proposed algorithms, the proposed scheduling algorithm can improve the packet drop ratio by more than 63 % and the fairness performance by more than 75 % when the traffic load is greater than 0.5.
0/1 Knapsack on Hardware: A Complete Solution (2007)

We present a memory efficient, practical, systolic, parallel architecture for the complete 0/1 knapsack dynamic programming problem, including backtracking. This problem was intentionally selected because its dynamic dependencies introduce difficulties in hardware implementation. The architecture uses a divide-and-conquer technique that results in a pseudo-linear memory requirement. This memory reduction comes in exchange for a factor of two slowdown due to redundant computation. The architecture uses TΘ(𝓃 + 𝒑(С + 𝑾 <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">max</sub> )) memory and the run time is Θ(𝓃С/𝒑 + 𝓃log(𝓃/𝒑)). The heart of the architecture is a systolic module to compute the optimal profit for any problem that fits in available hardware resources. We implemented the module using 64 processors on an Alpha Data coprocessor board using a Xilinx VirtexII FPGA(2001 technology). Our implementation showed a factor of 32 improvement on the total execution time over a sequential algorithm running on a 1.5GHz Xeon processor(2000 technology) and a factor of 16 improvement over a 3.2GHz Pentium 4(2004 technology) and a 64 bit 3.4GHz Pentium 4(2006 technology). We measured complete wall-clock time, including the time to download the problem to the board, but not the time to download the bit stream to the FPGA.
Botulinum Toxin in Poststroke Spasticity (2007)

Poststroke hemiparesis, together with abnormal muscle tone, is a major cause of morbidity and disability. Although most hemiparetic patients are able to reach different ambulatory levels with rehabilitation efforts, upper and lower limb spasticity can impede activities of daily living, personal hygiene, ambulation and, in some cases, functional improvement. The goals of spasticity management include increasing mobility and range of motion, attaining better hygiene, improving splint wear and other functional activities. Conservative measures, such as positioning, stretching and exercise are essential in spasticity management, but alone often are inadequate to effectively control it. Oral antispastic medications often provide limited effects with short duration and frequent unwanted systemic side effects, such as weakness, sedation and dry mouth. Therefore, neuromuscular blockade by local injections have become the first choice for the treatment of focal spasticity, particularly in stroke patients. Botulinum toxin (BTX), being one of the most potent biological toxins, acts by blocking neuromuscular transmission via inhibiting acetylcholine release. Currently, focal spasticity is being treated successfully with BTX via injecting in the spastic muscles. Two antigenically distinct serotypes of BTX are available on the market as type A and B. Clinical studies of BTX used for spastic hemiplegic patients are reviewed in this article in two major categories, upper and lower limb applications. This review addresses efficacy in terms of outcome measures, such as muscle tone reduction and functional outcome, as well as safety issues. Application modifications of dose, dilutions, site of injections and combination therapies with BTX injections are also discussed.
Assay of the von Willebrand factor (VWF) propeptide to identify patients with type 1 von Willebrand disease with decreased VWF survival (2006)

Type 1 von Willebrand disease (VWD) is characterized by a partial quantitative deficiency of von Willebrand factor (VWF). Few VWF gene mutations have been identified that cause dominant type 1 VWD. The decreased survival of VWF in plasma has recently been identified as a novel mechanism for type 1 VWD. We report 4 families with moderately severe type 1 VWD characterized by low plasma VWF:Ag and FVIII:C levels, proportionately low VWF:RCo, and dominant inheritance. A decreased survival of VWF in affected individuals was identified with VWF half-lives of 1 to 3 hours, whereas the half-life of VWF propeptide (VWFpp) was normal. DNA sequencing revealed a single (heterozygous) VWF mutation in affected individuals, S2179F in 2 families, and W1144G in 2 families, neither of which has been previously reported. We show that the ratio of steady-state plasma VWFpp to VWF:Ag can be used to identify patients with a shortened VWF half-life. An increased ratio distinguished affected from unaffected individuals in all families. A significantly increased VWFpp/VWF:Ag ratio together with reduced VWF:Ag may indicate the presence of a true genetic defect and decreased VWF survival phenotype. This phenotype may require an altered clinical therapeutic approach, and we propose to refer to this phenotype as type-1C VWD.
Observation of non-exponential decay in quantum tunneling (1997)

We report the observation of short-time deviation from exponential decay in tunneling of ultra-cold atoms from an accelerating periodic optical potential. We measure a'flat survival probability followed by a transition to exponential decay.
Placental nitrosative stress and in utero exposure to particulate matter (2015)

Background and aims A wide variety of adverse health effects on both fetuses and neonates have been ascribed to particulate matter (PM) air pollution. Recent evidence suggests that PM exposure results in increased oxidative and nitrosative stress. In the ENVIRONAGE birth cohort, we investigated the association of placental 3-nitrotyrosine (3-NT) with PM exposure during various time windows of pregnancy.
Preparation and Properties of Colloidal Core−Shell Rods with Adjustable Aspect Ratios (1998)

Colloidal boehmite (AlOOH) rods were used as cores for the preparation of rods with a silica shell. Via a three-step coating procedure silica rods with adjustable aspect ratios up to 20 were obtained by varying the amount of the added silica precursor tetraethoxysilane (TES). Silica rods are stable in various solvents such as water, ethanol, propanol, and dimethylformamide (DMF). Moreover, polymer-grafted silica rods can be dispersed in ethanol/toluene mixtures and cyclohexane. Incorporation of fluorescein isothiocyanate (FITC) in the silica shell enables the study of long-time self-diffusion processes in dispersions of rodlike particles with fluorescence recovery after photobleaching (FRAP). Fluorescent silica rods also may be used in direct imaging studies with confocal scanning laser fluorescence microscopy (CSLM).
Bacterial consortium proteomics under 4‐chlorosalicylate carbon‐limiting conditions (2009)

In this study, the stable consortium composed by Pseudomonas reinekei strain MT1 and Achromobacter xylosoxidans strain MT3 (cell numbers in proportion 9:1) was under investigation to reveal bacterial interactions that take place under severe nutrient-limiting conditions. The analysis of steady states in continuous cultures was carried out at the proteome, metabolic profile, and population dynamic levels. Carbon-limiting studies showed a higher metabolic versatility in the community through upregulation of parallel catabolic enzymes (salicylate 5-hydroxylase and 17-fold on 2-keto-4-pentenoate hydratase) indicating a possible alternative carbon routing in the upper degradation pathway highlighting the effect of minor proportions of strain MT3 over the major consortia component strain MT1 with a significant change in the expression levels of the enzymes of the mainly induced biodegradation pathway such as salicylate 1-hydroxylase and catechol 1,2-dioxygenase together with important changes in the outer membrane composition of P. reinekei MT1 under different culture conditions. The study has demonstrated the importance of the outer membrane as a sensing/response protective barrier caused by interspecies interactions highlighting the role of the major outer membrane proteins OprF and porin D in P. reinekei sp. MT1 under the culture conditions tested.
Predicting Legislative Roll Calls from Text (2011)

We develop several predictive models linking legislative sentiment to legislative text. Our models, which draw on ideas from ideal point estimation and topic models, predict voting patterns based on the contents of bills and infer the political leanings of legislators. With supervised topics, we provide an exploratory window into how the language of the law is correlated with political support. We also derive approximate posterior inference algorithms based on variational methods. Across 12 years of legislative data, we predict specific voting patterns with high accuracy. 1.
Identification of novel immunomodulatory tumor biology through comprehensive characterization of a metastases-specific epigenome in patients with metachronous primary and metastatic urothelial carcinoma (UC) tumor pairs. (2016)

452 Background: The Cancer Genome Atlas project identified a distinct cluster of hypermethylated muscle-invasive UC tumors in one third of patients. It is unknown if this epigenetic biology persists or changes in UC metastases. The present study aimed to identify uniquely hypermethylated regions in UC metastases compared to their matched primary tumors. Methods: UC patients with paired formalin fixed paraffin embedded tissue samples ( &gt; 75% tumor) from primary and metachronous metastatic tumors were identified. DNA methylation was analyzed on the Illumina HiSeq platform by double-enzyme reduced representation bisulfite sequencing (dRRBS). Results were analyzed by BS-seq within BSmooth open source software. Alignment and methylation estimation was done using Bismark open source software. CpG regions with coverage &lt; 2 in more than 66% of samples were removed to reduce false positive results. Differentially methylated regions (DMRs) in metastases compared to primary tumors were determined by paired t-test. Gene set enrichment analysis (GSEA) of the top 5% DMRs was performed utilizing multiple gene set collections including c7IMMUNO. A false discovery rate of &lt; 10% defined significant DMRs. Results: 15 UC primary/metachronous metastases pairs were analyzed. After filtering for low coverage, 1,781,762 loci remained for analysis. After merging loci within 2500 bp of each other, the top 5% DMRs resulted in 18,452 DMRs. GSEA including the c7IMMUNO gene set identified multiple previously undescribed hypermethylated genes modulating immune function through TGF-beta and Treg signaling including: TGFBR2, TGFBR3, SMAD1, SMAD3, SMAD4, BACH1, BACH2, and VDR all q &lt; 0.05. Conclusions: We identified numerous genes with immunomodulatory functions significantly hypermethylated in UC metastases compared to their matched primary tumors. Our findings provide rationale to examine epigenetic approaches as a means to improve clinical outcomes of UC patients treated with immunotherapy. Our small sample size limits definitive conclusions and warrants validation in independent data sets.
Building Graphs at a Large Scale: Union Find Shuffle (2021)

Large scale graph processing using distributed computing frameworks is becoming pervasive and efficient in the industry. In this work, we present a highly scalable and configurable distributed algorithm for building connected components, called Union Find Shuffle (UFS) with Path Compression. The scale and complexity of the algorithm are a function of the number of partitions into which the data is initially partitioned, and the size of the connected components. We discuss the complexity and the benchmarks compared to similar approaches. We also present current benchmarks of our production system, running on commodity out-of-the-box cloud Hadoop infrastructure, where the algorithm was deployed over a year ago, scaled to around 75 Billion nodes and 60 Billions linkages (and growing). We highlight the key aspects of our algorithm which enable seamless scaling and performance even in the presence of skewed data with large connected components in the size of 10 Billion nodes each.
La curiosidad del jurista persa y la reforma del recurso de casación contencioso-administrativo (2015)

La disposicion final tercera de la Ley Organica 7/2015, de 21 de julio, de modificacion de la LOPJ, reforma de manera radical el recurso de casacion contencioso-administrativo. Este estudio tiene por objeto determinar cual es, en rigor, el criterio de admision de los recursos que instaura la reforma, lo que no es sencillo tras una primera lectura de la norma. El legislador ha optado por adoptar un sistema de admision sustancialmente discrecional, lo que constituye una importante novedad en el diseno de los recursos de casacion en Espana.
Report from the field: results from an agricultural wireless sensor network (2004)

This paper reports the results of a 6-month deployment of a 65-node multi-hop network in a vineyard setting. This deployment specifically looked to discover ways in which a farm setting could find a return on investment for deploying such a network. Our ongoing collaborations of over two years ultimately have included everyone from the vineyard owners to the technology developers. We have been able to find several areas where wireless sensor networks deliver valuable information and provide a return on investment.
Frequency of actionable cancer predisposing germline mutations in patients with lung cancers. (2018)

1504 Background: Most of the heritability for lung cancer, estimated at 18% in population studies, remains unexplained. Utilizing a tumor-normal screening, we determined the prevalence of clinically actionable germline cancer-susceptibility mutations in patients with lung cancer, and correlated findings with clinical, tumor associated, and family history characteristics Methods: Tumor/normal samples from lung cancer patients (pts) enrolled from 1/14 until 5/16 underwent sequencing analysis for 468 genes by MSK IMPACT [PMID: 28481359], with pathogenicity assessment for 76 cancer predisposition genes by ACMG guidelines. Selected patients with a strong family history of cancer, multiple primary tumors, or early age of diagnosis (≤50) were offered return of germline findings. As per IRB protocol, germline results were anonymized for all cases except those consenting to return of results. Frequencies of pathogenic/likely pathogenic (P/LP) germline mutations were compared to population databases. Results: 1118 pts consented to tumor-normal sequencing and 42 to return of germline findings; the median age of the two groups was 68 and 59 , respectively (p < 0.05). For the 42 pts receiving germline findings, 24% had early onset and 52% multiple cancer diagnosis, and 31% had P/LP mutations in 10 genes (3 BRCA2, 2 MEN1, 1 APC, 1 ATM, 1 BAP1, 1 BLM, 1 CHEK2, 1 FH, 1 FLCN, 1 RAD51D). Among 1118 pts, 8% had P/LP mutations in 16 genes (20 APC, 15 CHEK2, 13 MUTYH, 7 BRCA2, 6 BRCA1, 5 FH, 4 ATM, 4 FANCC, 4 RECQL4, 3 FANCA, 3 TP53, 2 RAD50, 2 RAD51C, 1 BRIP1, 1 NBN, 1 PMS2). 45% of the P/LP mutations of CHEK2, APC, MUTYH, BRCA1 were population “founder” mutations. There was no statistically significant increase in burden of these pathogenic variants in the lung cancer cases studied. The 31% prevalence of germline variants in pts enriched for family history of cancer was greater than the 8% prevalence in patients unselected for family history (p < 0.0002). Conclusions: Our preliminary findings demonstrate an increased prevalence of clinically actionable germline mutations in patients with lung cancer with either a family history of other cancers, early age at onset, or multiple cancer diagnosis, compared to unselected lung cancer patients.
Stimulation of the Extrusion of Protons and H<sup>+</sup>-ATPase Activities with the Decline in Pyrophosphatase Activity of the Tonoplast in Intact Mung Bean Roots under High-NaCl Stress and Its Relation to External Levels of Ca<sup>2+</sup> Ions (1992)

Extrusion of protons as a response to high-NaCl stress in intact mung bean roots was investigated at different external concentrations of Ca2+ ions ([Ca2+]ex). The extrusion of protons was gradually enhanced in the roots exposed to 100 mM NaCl, and high [Ca2+]ex diminished this enhancement of the extrusion. Vesicles of plasmalemma and tonoplast were prepared from the roots and the H+-translocating ATPase (H+-ATPase) activities associated with the two types of membrane and the H+-pyrophosphatase (H+-PPase) activity of the tonoplast were assayed. The plasmalemma ATPase was stimulated in parallel with dramatic increases in the intracellular concentration of Na+([Na+]in). High [Ca2+]ex prevented the increase in [Na+]in and diminished the stimulation of ATPase activity. The tonoplast ATPase showed a rapid response to salt stress and was similarly stimulated even at high [Ca2+]M. The activities of both ATPases were, however, insensitive to concentrations of Na+ ions up to 100 HIM. By contrast, H+-PPase activity of the tonoplast was severely inhibited with increasing [Na+]in under salt stress and recovered with high [Ca2+]ex. These findings suggest that high-NaCl stress increases the intracellular concentration of Na+ ions in mung bean roots, which inhibits the tonoplast H+-PPase, and the activity of the plasmalemma H+-ATPase is thereby stimulated and regulates the cytoplasmic pH.
Inhibition by Citrinin of Oxidase Activities in Nicotiana glutinosa Leaves Infected with Tobacco Mosaic Virus (1970)

Citrinin, which was isolated from cultures of Penicillium sp. AK-019, inhibited local lesion formation on detached leaves of Nicotiana glutinosa infected with tobacco mosaic virus (TMV). Peroxidase and polyphenoloxidase activities in infected leaves decreased with the prolonged times of treatments with 100ppm citrinin. Five hour's treatment with citrinin inhibited peroxidase activity, but did not so much polyphenoloxidase. Both oxidase activities increased simultaneously with lesion appearance. Citrinin reduced most of the oxidase activities at early infection stages, reaching a maximum 48 hours after inoculation, then the rate of inhibition decreased. Both oxidase activities in infected leaves were recovered by the addition of 250ppm Fecitrate or 100ppm CuSO4 with citrinin. Inhibition by citrinin of local lesions formation and the oxidases activities is discussed.
Impressão molecular de polifenóis em partículas de polímero sensíveis a estímulos (2016)

Polifenóis como o frans-resveratrol, catequina, ácido elágico, ete, apresentam aplicações importantes na indústria farmacêutica, cosmética ou em medicina devido às suas propriedades antioxidantes. Estes compostos estSo presentes em diversas fontes vegetais e existe um elevado interesse no desenvolvimento de técnicas e processos de extracção, purificação e concentração que permitam a sua utilização de forma eficiente. Por outro lado, muitos polifenóis (ex. resveratrol) têm baixa bndisponibilidade por administração oral devido a múltiplos factores como a fraca solubilidade em melo aquoso e a sua elevada taxa de metabolizaçâo e excreção pelo organismo. Desta forma, é também vantajoso o desenvolvimento de veículos para a sua retenção e libertação controlada. A técnica de impressão molecular tem como objectivo criar numa rede de polímero cavidades com tamanho molecular que apresentem elevada afinidade e especificidade com uma molécula alvo (T). Idealmente, o material molecularmente impresso deve ser capaz de reconhecer essa molécula em sucessivos ciclos de retençSo/Iibertaçao.
Stabilizing and destabilizing effects of intercalators on DNA triplexes (1997)

Oligonucleotide-directed triplex formation attracts much attention due to its potential usefulness in diagnostic and biotechnological applications. Among other aspects, the research embraces numerous studies probing the influence of intercalating ligands on triplex stability. The effect of the intercalator on triplex formation and stability is known to depend on nucleotide sequence, type of intercalator and solution conditions. The present work is aimed at determining the average number of intercalated ethidium bromide (EtBr) and acridine orange (AO) molecules leading to the most effective stabilization of triplexes. First, fluorescing complexes of intramolecular parallel (recombinant) triplex 5'-d(CATGCTAACT)-L-d(AGTTAGCATG)-L-d(CATGCTAACT)-3' (parARB) and classical antiparallel 5'-(dA)10-L-(dT)10-L-(dT)10-3'(antiATT) (L = -pO(CH2CH2O)3p-) with EtBr and AO were characterized, binding constants were obtained and compared to those for homologous DNA duplexes. Then the total EtBr and AO concentrations corresponding to an average of one, two or three intercalated molecules per oligonucleotide were estimated. Thermal denaturation of parARB and antiATT complexes with an average of one, two or three bound molecules was carried out, thermodynamic parameters of the triplex-to-duplex and duplex-to-open-strand transitions were evaluated using a three-state model. The ability of EtBr and AO to stabilize or destabilize both parallel (recombinant) and classical antiparallel triplexes was found to depend strongly on the concentration of bound intercalator. The triplexes were shown to be stabilized by intercalation of the first and second EtBr or AO molecules, while binding of the third intercalator molecule to 10 nucleotide long triplex resulted in significant triplex destabilization.