gebhart/patrepeval huggingface dataset:
Design and Quantitative Structure−Activity Relationship of 3-Amidinobenzyl-1H-indole-2-carboxamides as Potent, Nonchiral, and Selective Inhibitors of Blood Coagulation Factor Xa (2002)

A series of 138 nonchiral 3-amidinobenzyl-1H-indole-2-carboxamides and analogues as inhibitors of the blood coagulation enzyme factor Xa (fXa) were designed, synthesized, and investigated by X-ray structure analysis and 3D quantitative structure-activity relationship (QSAR) studies (CoMFA, CoMSIA) in order to identify important protein-ligand interactions responsible for biological affinity and selectivity. Several compounds from this series are highly potent and selective inhibitors of this important enzyme linking extrinsic and intrinsic coagulation pathways. To rationalize biological affinity and to provide guidelines for further design, all compounds were docked into the factor Xa binding site. Those docking studies were based on X-ray structures of factor Xa in complex with literature-known inhibitors. It was possible to validate those binding modes by four X-ray crystal structures of representative ligands in factor Xa, while one ligand was additionally crystallized in trypsin to rationalize requirements for selective factor Xa inhibition. The 3D-QSAR models based on a superposition rule derived from these docking studies were validated using conventional and cross-validated r(2) values using the leave-one-out method and repeated analyses using two randomly chosen cross-validation groups plus randomization of biological activities. This led to consistent and highly predictive 3D-QSAR models with good correlation coefficients for both CoMFA and CoMSIA, which were found to correspond to experimentally determined factor Xa binding site topology in terms of steric, electrostatic, and hydrophobic complementarity. Subsets selected as smaller training sets using 2D fingerprints and maximum dissimilarity methods resulted in 3D-QSAR models with remarkable correlation coefficients and a high predictive power. The final quantitative SAR information agrees with all experimental data for the binding topology and thus provides reasonable activity predictions for novel factor Xa inhibitors.
Analyzing the Structure and Evolution of Massive Telecom Graphs (2008)

With the ever-growing competition in telecommunications markets, operators have to increasingly rely on business intelligence to offer the right incentives to their customers. Existing approaches for telecom business intelligence have almost solely focused on the individual behavior of customers. In this paper, we use the call detail records of a mobile operator to construct call graphs, that is, graphs induced by people calling each other. We determine the structural properties of these graphs and also introduce the Treasure-Hunt model to describe the shape of mobile call graphs. Moreover, we determine how the structure of these call graphs evolve over time. Finally, since short messaging service (SMS) is becoming a preferred mode of communication among many sections of the society, we study the properties of the SMS graph. Our analysis indicates several interesting similarities and differences between the SMS graph and the corresponding call graph. We believe that our analysis techniques can allow telecom operators to better understand the social behavior of their customers and potentially provide major insights for designing effective incentives.
Model order selection for summation models (2002)

In this paper, we propose two model order selection procedures for a class of summation models. We exploit the special structure in the class of candidate models to provide a data dependent zipper bound on the model order. The proposed upper bound is also a consistent estimator of model order. Further, minimum descriptive length, AIC and maximum apriori when accompanied with the data dependent prior exhibit an improved rate of convergence to their asymptotic behaviour and an improved detection rate for finite SNR and finite data lengths. Asymptotic properties of the maximum likelihood parameters are used to derive the proposed methods. All simulations use the complex undamped exponential model.
Coherent Supercontinuum from a Silicon Nitride Waveguide (2015)

We show experimentally and theoretically that the coherence of a two-octave-spanning supercontinuum generated in a silicon nitride waveguide via 1-µm-pumping with ~100-fs pulses is fully coherent over most of its bandwidth.
Security and usability (2008)

Online banking is one of the most sensitive tasks performed by general Internet users. Most traditional banks now offer online banking services, and strongly encourage customers to do online banking with 'peace of mind.' Although banks heavily advertise an apparent '100% online security guarantee,' typically the fine print makes this conditional on users fulfilling certain security requirements. We examine some of these requirements as set by major Canadian banks, in terms of security and usability. We opened personal checking accounts at the five largest Canadian banks, and one online-only bank. We found that many security requirements are too difficult for regular users to follow, and believe that some marketing-related messages about safety and security actually mislead users. We are also interested in what kind of computer systems people really use for online banking, and whether users satisfy common online banking requirements. Our survey of 123 technically advanced users from a university environment strongly supports our view of an emerging gap between banks' expectations (or at least what their written customer policy agreements imply) and users' actions related to security requirements of online banking. Our participants, being more security-aware than the general population, arguably makes our results best-case regarding what can be expected from regular users. Yet most participants failed to satisfy common security requirements, implying most online banking customers do not (or cannot) follow banks' stated end-user security requirements and guidelines. The survey also sheds light on the security settings of systems used for sensitive online transactions. This work is intended to spur a discussion on real-world system security and user responsibilities, in a scenario where everyday users are heavily encouraged to perform critical tasks over the Internet, despite the continuing absence of appropriate tools to do so.
An Omega(n^{1/3}) Lower Bound for Bilinear Group Based Private Information Retrieval. (2006)

A two server private information retrieval (PIR) scheme allows a user U to retrieve the i-th bit of an n-bit string x replicated between two servers while each server individually learns no information about i. The main parameter of interest in a PIR scheme is its communication complexity, namely the number of bits exchanged by the user and the servers. A large amount of effort has been invested by researchers over the last decade in search for efficient PIR schemes. A number of different schemes ((B. Chor. O. Goldreich. E. Kushilevitz. and M. Sudan, 1998), (A. Beimel and Y. Ishai, 2001) ,(D. Woodruff and S. Yekhanin, 2005)) have been proposed, however all of them ended up with the same communication complexity of O(n1/3). The best known lower bound to date is 5 log n by (S. Wehner and R. de Wolf, 2005) . The tremendous gap between upper and lower bounds is the focus of our paper. We show an Omega(n1/3) lower bound in a restricted model that nevertheless captures all known upper bound techniques. Our lower bound applies to bilinear group based PIR schemes. A bilinear PIR scheme is a one round PIR scheme, where user computes the dot product of servers' responses to obtain the desired value of the i-th bit. Every linear scheme can be turned into a bilinear one with an asymptotically negligible communication overhead. A group based PIR scheme is a PIR scheme that involves servers representing database by a function on a certain finite group G, and allows user to retrieve the value of this function at any group element using the natural secret sharing scheme based on G. Our proof relies on representation theory of finite groups
Direct identification of hydrophobins and their processing in Trichoderma using intact‐cell MALDI‐TOF MS (2007)

Intact-cell MS (ICMS) was applied for the direct detection of hydrophobins in various species and strains of Hypocrea/Trichoderma. In both mycelia and spores, dominating peaks were identified as hydrophobins by detecting mass shifts of 8 Da of reduced and unreduced forms, the analysis of knockout mutants, and comparison with protein databases. Strain-specific processing was observed in the case of Hypocrea jecorina (anamorph Trichoderma reesei). An analysis of 32 strains comprising 29 different species of Trichoderma and Hypocrea showed hydrophobin patterns that were specific at both at the species and isolate (subspecies) levels. The method therefore permits rapid and direct detection of hydrophobin class II compositions and may also provide a means to identify Trichoderma (and other fungal) species and strains from microgram amounts of biomass without prior cultivation.
Excess Bias Voltage Monitoring Circuit (2018)

An excess bias voltage monitoring circuit (EBVMC) for applications that use a single-photon avalanche diode (SPAD) is described in this paper. The circuit consists of a current controlled quenching circuit, comparators and digital logic gates for storing the results. The circuit is used to adjust the SPAD's reverse bias in order to eliminate the SPAD's excess bias voltage dependence. The power consumption of the circuit is 141μW and layout area is 160μm×75μm including a reference circuit.
Automatic laser welding and milling with in situ inline coherent imaging (2014)

Although new affordable high-power laser technologies enable many processing applications in science and industry, depth control remains a serious technical challenge. In this Letter we show that inline coherent imaging (ICI), with line rates up to 312 kHz and microsecond-duration capture times, is capable of directly measuring laser penetration depth, in a process as violent as kW-class keyhole welding. We exploit ICI's high speed, high dynamic range, and robustness to interference from other optical sources to achieve automatic, adaptive control of laser welding, as well as ablation, achieving 3D micron-scale sculpting in vastly different heterogeneous biological materials.
Rh-Catalyzed Cyclization of 3-Aryloxycarbonyldiazonaphthoquinones for the Synthesis of β-Phenylnaphthalene Lactones and Formal Synthesis of Pradimicinone (2015)

In this study, we developed a novel method for the synthesis of β-phenylnaphthalene lactones. The diazo-transfer reactions of 2-azido-1,3-dimethylimidazolinium chlorides to 3-aryloxycarbonyl-1-naphthols proceeded smoothly to give corresponding 3-aryloxycarbonyldiazonaphthoquinones in high yields. These intermediates were further transformed to β-phenylnaphthalene lactones through a Rh-catalyzed intramolecular formal C-H insertion reaction. This method of lactone formation was efficiently applied to the formal total synthesis of pradimicinone.
Engineering protein specificity: gene manipulation with semisynthetic nucleases (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEngineering protein specificity: gene manipulation with semisynthetic nucleasesDehua Pei and Peter G. SchultzCite this: J. Am. Chem. Soc. 1991, 113, 24, 9398–9400Publication Date (Print):November 1, 1991Publication History Published online1 May 2002Published inissue 1 November 1991https://pubs.acs.org/doi/10.1021/ja00024a072https://doi.org/10.1021/ja00024a072research-articleACS PublicationsRequest reuse permissionsArticle Views71Altmetric-Citations19LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
524. An Objective Measure of The Host Response Suggests Social Determinants, Rather than Pathobiology, as a Factor in Disparate Sepsis Outcomes Among Races (2022)

Abstract Background Sepsis is a common and costly condition encountered in United States hospitals and Emergency Departments (ED). Studies have shown that the incidence of sepsis and risk of sepsis morbidity and mortality increases with age. With increased efforts on early detection and process of care, in-hospital sepsis deaths have declined; however, racial disparities have been observed in sepsis-related outcomes. The objective of this study was to assess demographic, severity, and outcome differences among septic patients presenting to the ED self-reporting as White vs. Black, and evaluate the potential of an investigational cellular host response test in risk stratifying these subpopulations for risk of poor outcomes. Methods The IntelliSep test is an investigational in-vitro diagnostic that quantifies the state of immune activation by measuring the biophysical properties of leukocytes from a routine whole blood sample in under 10 minutes. The result is the IntelliSep Index (ISI), ranging between 0.1-10.0, stratified into three discrete interpretation bands of increasing disease severity risk: Green, Yellow, and Red. Adult patients presenting to the ED with signs or suspicion of infection were prospectively enrolled in four discrete but similar cohorts at multiple sites in the USA (Feb. 2016 – Apr. 2020). All patients had ISI performed and were followed by retrospective chart review for outcome information and sepsis adjudication. Treating clinicians did not have access to assay results, and only those determined to be septic were included in the final analysis. Results Of the 150 patients included in the analysis, 92 (61%) were White and 58 (39%) Black. No significant differences were observed in biological sex or severity of illness (Fig). Black subjects were significantly younger (mean difference 8.9 years; p &amp;lt; 0.001) compared to Whites. Independent of race, the ISI correlated with increasing likelihood of adverse sepsis-related outcomes. Biological sex and APACHE II scores by ISI Interpretation Band for White and Black Study subjects. Conclusion The ISI is an objective tool for the quantification of immune activation, and adequately risk-stratifies patients with sepsis for adverse outcomes, independent of race. This finding suggests that social determinants of health, rather than differences in immunobiology, contribute to racial disparities observed in sepsis-related outcomes. Disclosures Roya Sheybani, PhD, Cytovale: Employee|Cytovale: Stocks/Bonds Henry T. Tse, PhD, Cytovale: Stocks/Bonds Ajay M. Shah, PhD, Cytovale Inc: Board Member|Cytovale Inc: Ownership Interest|Cytovale Inc: Stocks/Bonds.
Analytical approach to I/Q imbalance in OFDM, CDMA and MC-CDMA based systems (2006)

Growing requirements set upon communications transceivers lead to high sensitivity to non-idealities of analog front-end components. Mismatches in the amplitudes and phases of the I and Q signal branches is one of the major concerns resulting in insufficient rejection of the image frequency band. This paper presents a novel analytical model of I/Q imbalance in OFDM, CDMA and MC-CDMA based communications systems. According to the obtained results, I/Q imbalance effects depend heavily on the applied spreading code class and cell load in case of CDMA and MC-CDMA, which should be taken into account in the system and receiver design. Outcomes of the theoretical studies are verified by extensive system simulations.
On the tradeoffs between path computation efficiency and information abstraction in optical mesh networks (2004)

Distributed, IP-based control architecture has been proposed for switched optical mesh networks, as a means to automate operations, enhance interoperability and facilitate the deployment of new applications. While distributed control in general enhances scalability and flexibility, it also offers challenges to path computation, especially for shared mesh restored paths, because of the summarization of link state information disseminated by the routing protocol. This paper discusses the tradeoffs between the path computation efficiency and the abstraction level of link state information. Several heuristic algorithms for computing shared mesh restored paths are described, which require different levels of abstraction and summarization of link resource sharing information. The performance of these algorithms is compared in term of the efficiency of network capacity utilization, the computation complexity, and the amount of required network information. We show that with appropriately aggregated link state information the proposed path computation algorithms are able to utilize the network resource very efficiently.
Combined effects of progesterone and SOCS3 DNA methylation on T2DM: a case–control study (2021)

The independent and combined effects of progesterone and SOCS3 methylation on T2DM were found among men and postmenopausal women, suggesting that ensuring low levels of progesterone and high methylation of SOCS3 could reduce the prevalence of T2DM. Trial registration The Chinese Clinical Trial registration: The Henan Rural Cohort Study, ChiCTR-OOC-15006699. Registered 06 July 2015, http://www.chictr.org.cn/showproj.aspx?proj=11375.
Arginine-Specific Gingipains from Porphyromonas gingivalis Stimulate Production of Hepatocyte Growth Factor (Scatter Factor) through Protease-Activated Receptors in Human Gingival Fibroblasts in Culture (2005)

Cystein proteinases (gingipains) from Porphyromonas gingivalis cleave a broad range of in-host proteins and are considered to be key virulence factors in the onset and development of adult periodontitis and host defense evasion. In periodontitis, an inflammatory disease triggered by bacterial infection, the production of hepatocyte growth factor (HGF) is induced not only by various factors derived from the host, such as inflammatory cytokines, but also by bacterial components. In this study we examined the possible enhanced production of HGF produced by human gingival fibroblasts upon stimulation with gingipains. Arginine-specific gingipain (Rgp) caused a marked production of HGF into the supernatant, the induction of HGF expression on the cell surface, and the up-regulation of HGF mRNA expression in a dose-dependent and an enzymatic activity-dependent manner. Because it has been reported that Rgp activated protease-activated receptors (PARs), we examined whether the induction of HGF triggered by Rgps on human gingival fibroblasts occurred through PARs. An RNA interference assay targeted to PAR-1 and PAR-2 mRNA revealed that gingipains-induced secretion of HGF was significantly inhibited by RNA interference targeted to PAR-1 and PAR-2. In addition, the Rgps-mediated HGF induction was completely inhibited by the inhibition of phospholipase C and was clearly inhibited by RNA interference targeted to p65, which is an NF-kappaB component. These results suggest that Rgps activated human gingival fibroblasts to secrete HGF in the inflamed sites and the mechanism(s) involved may actively participate in both inflammatory and reparative processes in periodontal diseases.
Potency of CRISPR-Cas Antifungals Is Enhanced by Co-targeting DNA Repair and Growth Regulatory Machinery at the Genetic Level (2023)

Abstract Fungal pathogens are virulent and resistant to antibiotic treatment. Due to their adaptability, specificity, and efficiency, CRISPR-Cas systems can be harnessed for neutralizing these fungal pathogens. However, the conventional design of CRISPR-Cas antimicrobials, based on induction of DNA double-strand-breaks (DSBs), is potentially less effective in fungi due to robust eukaryotic DNA repair machinery. Here, we report a novel design principle to formulate more effective CRISPR-Cas antifungals by co-targeting essential genes with DNA repair defensive genes that remove the fungi’s ability to repair the DSB sites of essential genes. By evaluating this design on the model fungus Saccharomyces cerevisiae , we demonstrated that essential and defensive gene co-targeting is more effective than either essential or defensive gene targeting alone. The top-performing CRISPR-Cas antifungals performed as effectively as the antibiotic Geneticin. Fast growth kinetics of S. cerevisiae induced resistance to CRISPR-Cas antifungals where genetic mutations mostly occurred in defensive genes and guide RNA sequences. Significance The emergence of virulent, resistant, and rapidly evolving fungal pathogens poses a significant threat to public health, agriculture, and the environment. Targeting cellular processes with standard small-molecule intervention may be effective but requires long development times and is prone to antibiotic resistance. To overcome the current limitation of antibiotic development and treatment, this study harnesses CRISPR-Cas systems as antifungals by capitalizing on their adaptability, specificity, and efficiency in target design. Simultaneous co-targeting of both essential and defensive genes is shown to be a novel design principle for formulating effective CRISPR-Cas antimicrobials that can be rapidly tuned to adapt to inevitable escapee events.
Wound Closure in Nonidiopathic Scoliosis: Does Closure Matter? (2015)

Level III-therapeutic.
Kisspeptin-10 Is a Potent Stimulator of LH and Increases Pulse Frequency in Men (2011)

Kisspeptin-10 boluses potently evoke LH secretion in men, and continuous infusion increases testosterone, LH pulse frequency, and pulse size. Kisspeptin analogues have therapeutic potential as regulators of LH and thus testosterone secretion.
Potent inhibition of respiratory syncytial virus replication using a 2-5A-antisense chimera targeted to signals within the virus genomic RNA (1998)

The 2-5A system is a recognized mechanistic component of the antiviral action of interferon. Interferon-induced 2-5A synthetase generates 2-5A, which, in turn, activates the latent constitutive RNase L that degrades viral RNA. Chemical conjugation of 2-5A to an antisense oligonucleotide can target the 2-5A-dependent RNase L to the antisense-specified RNA and effect its selective destruction. Such a 2-5A-antisense chimera (NIH351) has been developed that targets a consensus sequence within the respiratory syncytial virus (RSV) genomic RNA. NIH351 was 50- to 90-fold more potent against RSV strain A2 than was ribavirin, the presently approved drug for clinical management of RSV infection. It was similarly active against a variety of RSV strains of both A and B subgroups and possessed a cell culture selectivity index comparable to ribavirin. In addition, the anti-RSV activity of NIH351 was shown to be virus-specific and a result of a true antisense effect, because a scrambled nucleotide sequence in the antisense domain of NIH351 caused a significant decrease in antiviral activity. The 2-5A system's RNase L was implicated in the mechanism of action of NIH351 because a congener with a disabled 2-5A moiety was of greatly reduced anti-RSV effectiveness. These findings represent an innovative approach to the control of RSV replication.