gebhart/patrepeval huggingface dataset:
Rapid LC–MS Method for Accurate Molecular Weight Determination of Membrane and Hydrophobic Proteins (2018)

Therapeutic target characterization involves many components, including accurate molecular weight (MW) determination. Knowledge of the accurate MW allows one to detect the presence of post-translational modifications, proteolytic cleavages, and importantly, if the correct construct has been generated and purified. Denaturing liquid chromatography-mass spectrometry (LC-MS) can be an attractive method for obtaining this information. However, membrane protein LC-MS methodology has remained relatively under-explored and under-incorporated in comparison to methods for soluble proteins. Here, systematic investigation of multiple gradients and column chemistries has led to the development of a 5 min denaturing LC-MS method for acquiring membrane protein accurate MW measurements. Conditions were interrogated with membrane proteins, such as GPCRs and ion channels, as well as bispecific antibody constructs of variable sizes with the aim to provide the community with rapid LC-MS methods necessary to obtain chromatographic and accurate MW measurements in a medium- to high-throughput manner. The 5 min method detailed has successfully produced MW measurements for hydrophobic proteins with a wide MW range (17.5 to 105.3 kDa) and provided evidence that some constructs indeed contain unexpected modifications or sequence clipping. This rapid LC-MS method is also capable of baseline separating formylated and nonformylated aquaporinZ membrane protein.
Larger ACE 68 aspiration catheter increases first-pass efficacy of ADAPT technique (2018)

Use of the larger-bore ACE 68 aspiration catheter was associated with shorter groin puncture to reperfusion time, higher rate of successful reperfusion after the first ADAPT pass, and lower rate of stent-retriever rescue. Further, a first-pass effect was demonstrated in our ADAPT patient cohort.
An Integrated Design for Testability and Automatic Test Pattern Generation System: An Overview (1984)

A general overview on an Integrated Design for Testability and Automatic Test Pattern Generation System (IDAS) is given. The major components of IDAS include: heuristic controllability/observability (C/O) analysis, prediction of testing costs, tools for evaluation, display and improvement of testability, and C/O guided automatic test pattern generator. The IDAS system includes also the logic and concurrent fault simulator CADAT. A brief description of major components with a scenario how to use IDAS is given. Future research activities are discussed.
A fuzzy TOPSIS methodology to support outsourcing of logistics services (2006)

Purpose To present a multi‐attribute approach for the selection and ranking of the most suitable 3PL service provider. Design/methodology/approach The approach is based on the TOPSIS technique (Technique for Order Preference by Similarity to Ideal Solution) and the fuzzy set theory. Findings A quantitative methodology based on a structured framework, for the selection of the most appropriate 3PL service provider. Research limitations/implications Future research may attempt to compare the results of the methodology proposed with those of other Multi Attribute Group Decision Making methods. In particular, the selection tree could be developed in a multi‐tier hierarchy, trying to punctually address the relationships between the upper tier criteria and the lower level ones. With multi‐tier hierarchies, the performance of AHP could be compared with the one obtained with TOPSIS, not only with respect to “technical suitability” but also in terms of easiness to implement, shortcomings and general managerial viability. Practical implications From the application of the methodology to a real case, the approach proposed emerges as an appropriate tool, which makes it possible to easily and effectively rank alternatives. Conversely the most critical issue pointed out by the real case application is the preliminary “request of information” phase, which has to be given critical attention. The availability of a well structured body of knowledge about potential candidates emerged as the true discriminant for an effective analysis. Originality/value The originality of the paper is threefold: first, an original framework of criteria for the selection of the most suitable 3PL service provider is presented. Second, an original methodology based on a fuzzy TOPSIS approach is presented. Third, the practical implications and drawbacks are discussed by means of a real case application.
Renal oxygenases: differential contribution to vasoconstriction induced by ET-1 and ANG II (1997)

In the rat isolated perfused kidney, 5,8,11,14-eicosatetraynoic acid, an inhibitor of all pathways of arachidonic acid (AA) metabolism, diminished endothelin-1 (ET-1)- and angiotensin II (ANG II)-induced renal vasoconstriction by approximately 60-70%. We then examined the individual contribution of each oxygenase, cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P-450 (CYP) to the vasoconstrictor effects of ET-1 and ANG II. Inhibition of COX with indomethacin reduced by 30-40% the vasoconstrictor responses to ET-1 and ANG II. Inhibition of 12-LOX with baicalein and 5- and 12-LOX with 5,8,11-eicosatriynoic acid attenuated ANG II-induced renal vasoconstriction by approximately 40-60% but did not affect responses to ET-1. In contrast, 12,12-dibromododec-11-enoic acid (DBDD), an inhibitor of the CYP omega/omega 1-hydroxylase pathway, diminished ET-1-induced renal vasoconstriction by 30-40%, an effect reproduced by depletion of CYP enzymes with CoCl2. Neither DBDD nor CoCl2 affected renal vasoconstriction elicited by ANG II. ET-1 increased efflux of 19- and 20-hydroxyeicosatetraenoic acid, an effect reduced by DBDD. Thus products of the COX and CYP pathways contribute to the renal vasoconstrictor response to ET-1, whereas COX- and LOX-derived eicosanoids contribute to the response to ANG II, accounting for > or = 80% of the vasoactivity of the peptides.
Cycloaddition Chemistry on Silicon(001) Surfaces:  The Adsorption of Azo-<i>tert</i>-butane (1998)

The adsorption of azo-tert-butane on the Si(001) surface at 300 K has been investigated using X-ray photoelectron spectroscopy (XPS), Fourier transform infrared (FTIR) spectroscopy, scanning tunneling microscopy (STM), and ab initio computational chemistry methods. Although some cleavage of C−H bonds that prevents the formation of a completely ordered layer occurs at room temperature, adsorption onto a 130 K surface occurs molecularly with no bond cleavage. All of the experimental evidence shows that adsorption occurs through the interaction of the NN azo bond with a single SiSi dimer bond, in a manner similar to a [2 + 2] cycloaddition reaction. These results show that the use of [2 + 2] cycloaddition reactions to link organic substituents to the Si(001) surface is not limited to alkenes but can be extended to link compounds which have other types of unsaturated bonds to the Si(001) surface.
Both Boceprevir and GC376 efficaciously inhibit SARS-CoV-2 by targeting its main protease (2020)

COVID-19 was declared a pandemic on March 11 by WHO, due to its great threat to global public health. The coronavirus main protease (M<sup>pro</sup>, also called 3CLpro) is essential for processing and maturation of the viral polyprotein, therefore recognized as an attractive drug target. Here we show that a clinically approved anti-HCV drug, Boceprevir, and a pre-clinical inhibitor against feline infectious peritonitis (corona) virus (FIPV), GC376, both efficaciously inhibit SARS-CoV-2 in Vero cells by targeting M<sup>pro</sup>. Moreover, combined application of GC376 with Remdesivir, a nucleotide analogue that inhibits viral RNA dependent RNA polymerase (RdRp), results in sterilizing additive effect. Further structural analysis reveals binding of both inhibitors to the catalytically active side of SARS-CoV-2 protease M<sup>pro</sup> as main mechanism of inhibition. Our findings may provide critical information for the optimization and design of more potent inhibitors against the emerging SARS-CoV-2 virus.
A driver model for velocity tracking with look-ahead (2015)

Understanding the dynamics of the combined system of driver and vehicle opens up for improving the performance of powertrain controls. To this end, a new model structure is formulated for accelerator pedal behavior of human drivers. The structure is comprised of feedback and feedforward with preview of the reference. A system identification approach is developed for determining the parameters in the structure. Models are identified on data from experiments with different driver and vehicle combinations where the drivers are tracking the common FTP and US06 drive cycles. Experiments where the same individual drives different cycles show the driver adapting in response to how demanding the drive cycle is and individual driving styles are studied with another data set with different drivers on the same cycle. The results show that drivers have similar feedforward for a given vehicle while the look-ahead and feedback is variable based on drive cycle and driving style. The potential of using the driver model for prediction is demonstrated. For the first time, for longitudinal experiments, it is shown that the open loop frequency response for the driver cascaded with the vehicle is approximated by the so-called crossover model near the crossover frequency.
Terahertz emission mechanisms in InAsxP1−x (2008)

The terahertz emission mechanisms from the surface of bulk InAsxP1−x crystals have been examined. The dominant terahertz emission mechanism from InAsxP1−x for low-fluence optical excitation is the photo-Dember effect for As compositions of 78% and greater while the surface field effect is dominant for As compositions of 50% and lower for the measured transport properties. The observed terahertz emission magnitude from the photo-Dember effect increased with As composition due to decreasing absorption depth. The observed terahertz emission magnitude from the surface field effect decreased with increasing As composition and was lower than modeled values due to the lower high-field mobility in the depletion region in those samples.
Attitude and position control using real-time color tracking (1997)

A variety of sensors and positioning methods have been developed over the years. Most methods rely on active sensors (such as sonars or lasers) which have range and power restrictions, or rely on computationally complex (and often slow) methods such as recovering position from stereo or optical flow. This paper describes a system that can determine a robot&apos;s position and orientation, in all six degrees of freedom, relative to a simple passive target. The system can determine its position relative to the target from a single image frame, and process the image and calculate the position faster than a camera&apos;s frame rate (60Hz). It uses a standard, uncalibrated color video camera as its sensor. The system runs on an inexpensive microprocessor (a Motorola 68332) leaving many cycles left over. By careful design of the target and the vision processing hardware and software, we are able to selectively perceive only the relevant parts of the target, greatly simplifying and speeding all the nec...
Probing the Proteolytic Stability of β‐Peptides Containing α‐Fluoro‐ and α‐Hydroxy‐β‐Amino Acids (2004)

One of the benefits of beta-peptides as potential candidates for biological applications is their stability against common peptidases. Attempts have been made to rationalize this stability by altering the electron availability of a given amide carbonyl bond through the introduction of polar substituents at the alpha-position of a single beta-amino acid. Such beta-amino acids (beta-homoglycine, beta-homoalanine), containing one or two fluorine atoms or a hydroxy group in the alpha-position, were prepared in enantiopure form. A versatile method for preparing these alpha-fluoro-beta-amino acids by the homologation of appropriate alpha-amino acids and C-OH->C-F or C=O-->CF(2) substitution with DAST, is described. Consequently, a series of beta-peptides possessing an electronically modified residue at the N terminus or embedded within the chain was synthesized, and their proteolytic stability was investigated against a selection of enzymes. All ten beta-peptides tested were resilient to proteolysis. Introducing a polar, sterically undemanding group, into the alpha-position of beta-amino acids in a beta-peptide chain does not appear to facilitate localized or general enzymatic degradation.
Intravenous Thrombolysis for Acute Ischemic Stroke Within 3 Hours Versus Between 3 and 4.5 Hours of Symptom Onset (2015)

Data from randomized clinical trials have supported the safety and efficacy of intravenous tissue-type plasminogen activator (IV tPA) for acute ischemic stroke when administered within 3 hours of symptom onset, and regulatory approvals for this indication have been in place for almost 20 years. However, recent clinical trials have provided evidence that IV tPA may be safe and effective in selected patients up to 4.5 hours after symptom onset, thereby increasing the proportion of patients that may be eligible for treatment. Although professional organizations in the United States and many regulatory agencies internationally have supported this expanded time window for IV tPA, the US Food and Drug Administration has declined to approve this expanded indication and so this use of IV tPA has remained off-label in the United States. Here we review the current evidence for IV tPA in the standard and the expanded time windows and the data on current clinical practice in the United States as it relates to IV tPA treatment for acute stroke within 3 to 4.5 hours of symptom onset.
Mode control of Ti-diffused LiNbO_3 slab optical waveguide (1977)

The investigations were carried out on optical waveguides obtained by thermal diffusion of Ti into LiNbO(3) single crystals. In the Ti-diffused LiNbO(3) slab waveguides, the relationships of the refractive index profile (index change at the surface, diffusion depth) to various diffusion conditions were examined. Conditions were found to fabricate the waveguides of the required number of modes (TE modes) and effective indices for the wavelength of a He-Ne laser (0.6328 microm) and a GaAs-GaAIAs double heterostructure laser (DH laser) (0.8730 microm). The slab waveguides of the required number of modes and effective indices could be obtained by adjusting only the thickness of evaporated Ti film.
Cyr61 increases migration and MMP-13 expression via αvβ3 integrin, FAK, ERK and AP-1-dependent pathway in human chondrosarcoma cells (2009)

Cysteine-rich 61 (Cyr61), from the CCN gene family, is a secreted and matrix-associated protein, which is involved in many cellular activities such as growth and differentiation. However, the effect of Cyr61 on migration activity in human chondrosarcoma cells is mostly unknown. Here, we found that Cyr61 increased the migration and expression of matrix metalloproteinase (MMP)-13 in human chondrosarcoma cells (JJ012 cells). RGD peptide, alphavbeta3 monoclonal antibody and mitogen-activated protein kinase (MEK) inhibitors (PD98059 and U0126) but not RAD peptide inhibited the Cyr61-induced increase of the migration and MMP-13 upregulation of chondrosarcoma cells. Cyr61 stimulation increased the phosphorylation of focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK). In addition, activator protein-1 (AP-1) decoy oligodeoxynucleotide also suppressed the MMP-13 messenger RNA and enzyme activity enhanced by Cyr61. Moreover, Cyr61 increased the binding of c-Fos and c-Jun to the AP-1 element on the MMP-13 promoter. Taken together, our results indicated that Cyr61 enhances the migration of chondrosarcoma cells by increasing MMP-13 expression through the alphavbeta3 integrin receptor, FAK, ERK, c-Fos/c-Jun and AP-1 signal transduction pathway.
Solving SAT and MaxSAT with a Quantum Annealer: Foundations, Encodings, and Preliminary Results (2018)

Quantum annealers (QAs) are specialized quantum computers that minimize objective functions over discrete variables by physically exploiting quantum effects. Current QA platforms allow for the optimization of quadratic objectives defined over binary variables (qubits), also known as Ising problems. In the last decade, QA systems as implemented by D-Wave have scaled with Moore-like growth. Current architectures provide 2048 sparsely-connected qubits, and continued exponential growth is anticipated, together with increased connectivity. We explore the feasibility of such architectures for solving SAT and MaxSAT problems as QA systems scale. We develop techniques for effectively encoding SAT -and, with some limitations, MaxSAT- into Ising problems compatible with sparse QA architectures. We provide the theoretical foundations for this mapping, and present encoding techniques that combine offline Satisfiability and Optimization Modulo Theories with on-the-fly placement and routing. Preliminary empirical tests on a current generation 2048-qubit D-Wave system support the feasibility of the approach for certain SAT and MaxSAT problems.
The Immunomodulatory Drug Glatiramer Acetate is Also an Effective Antimicrobial Agent that Kills Gram-negative Bacteria (2017)

Classic drug development strategies have failed to meet the urgent clinical needs in treating infections with Gram-negative bacteria. Repurposing drugs can lead to timely availability of new antibiotics, accelerated by existing safety profiles. Glatiramer acetate (GA) is a widely used and safe formulation for treatment of multiple sclerosis. It contains a large diversity of essentially isomeric polypeptides with the cationic and amphiphilic character of many antimicrobial peptides (AMP). Here, we report that GA is antibacterial, targeting Gram-negative organisms with higher activity towards Pseudomonas aeruginosa than the naturally-occurring AMP LL-37 in human plasma. As judged from flow cytometric assays, bacterial killing by GA occurred within minutes. Laboratory strains of Escherichia coli and P. aeruginosa were killed by a process of condensing intracellular contents. Efficient killing by GA was also demonstrated in Acinetobacter baumannii clinical isolates and approximately 50% of clinical isolates of P. aeruginosa from chronic airway infection in CF patients. By contrast, the Gram-positive Staphylococcus aureus cells appeared to be protected from GA by an increased formation of nm-scale particulates. Our data identify GA as an attractive drug repurposing candidate to treat infections with Gram-negative bacteria.
Recognition Algorithm for Topographic Features (2007)

This research describes development of recognition algorithm for topographic features such as impact craters, wrinkle ridges, and grabens on Digital Terrain Models of SELENE (SELenological and Engineering Explorer). Because SELENE provides massive volumes of lunar data, its data sets require semi-automatic labor saving analysis. We try to recognize circular and linear topographic features with General Hough Transform. Although the transform is one of the most popular techniques, this should be optimized for our targeted features. Experimental results of this algorithm show that typical craters and topographic lineaments can be extracted.
Retrieving Biological Activity from LukF-PV Mutants Combined with Different S Components Implies Compatibility between the Stem Domains of These Staphylococcal Bicomponent Leucotoxins (2002)

Bicomponent leucotoxins, such as Panton-Valentine leucocidin, are composed of two classes of proteins, a class S protein such as LukS-PV, which bears the cell membrane binding function, and a class F protein such as LukF-PV, which interacts to form a bipartite hexameric pore. These leucotoxins induce cell activation, linked to a Ca(2+) influx, and pore formation as two consecutive and independently inhibitable events. Knowledge of the LukF-PV monomer structure has indicated that the stem domain is folded into three antiparallel beta-strands in the water-soluble form and has to refold into a transmembrane beta-hairpin during pore formation. To investigate the requirements for the cooperative assembly of the stems of the S and F components to produce biological activity, we introduced multiple deletions or single point mutations into the stem domains of LukF-PV and HlgB. While the binding of the mutated proteins was weakly dependent on these changes, Ca(2+) influx and pore formation were affected differently, confirming that they are independent events. Ca(2+) entry into human polymorphonuclear cells requires oligomerization and may follow the formation of a prepore. The activity of some of the LukF-PV mutants, carrying the shorter deletions, was actually improved. This demonstrated that a crucial event in the action of these toxins is the transition of the prefolded stem into the extended beta-hairpins and that this step may be facilitated by small deletions that remove some of the interactions stabilizing the folded structure.
<i>Chlamydia pneumoniae</i>immunoglobulin A reactivation and airway inflammation in acute asthma (2002)

Infection with Chlamydia pneumoniae can trigger acute asthma and is associated with severe chronic asthma. The aim of the present study was to examine the relationship between airway inflammation and serological response to C. pneumoniae in acute severe asthma. Subjects (n=54) were recruited within 4 h of presentation to the emergency department with an acute exacerbation of asthma. Clinical history taking, sputum induction (0.9% saline), spirometry and acute and convalescent serology for C. pneumoniae immunoglobulins A and G were performed. At presentation, 47% of subjects had antibodies directed against C. pneumoniae, and 38% (20) demonstrated an increase in C. pneumoniae antibody levels, with 15 demonstrating a rise in immunoglobulin A concentration. C. pneumoniae responders exhibited significantly higher sputum neutrophil levels (4.6 x 10(6) cells x mL(-1)) compared to nonresponders (1.2 x 10(6) cells x mL(-1), p=0.02) and elevated sputum eosinophil cationic protein concentration (3,981 versus 1,122 ng x mL(-1), p=0.02). An acute antibody response to Chlamydia pneumoniae is common in exacerbations of asthma. The serological features suggest that Chlamydia pneumoniae reactivation may trigger neutrophilic airway inflammation in acute asthma.
Fine granularity scalability in MPEG-4 for streaming video (2000)

This paper describes the bitplane coding technique to achieve fine granularity scalability (FGS) in MPEG-4. It reports its coding efficiency results and discusses a few improvement methods.
The sensitivity analysis on torsional stresses and life expenditure of turbine-generator shaft (2002)

This paper explores sensitivities of torsional stresses to design parameters of turbine-generator shafts. The sensitivity guideline is as a new concept to reduce the high torsional torque to which the turbine-generator shafts might be subjected during high speed switching of network faults. In this context, investigations have been conducted on a large turbine-generator model and its life expenditure is calculated.
The Second Persona (2020)

The Vidal description is more nearly a kind of journalism than a kind of criticism, but its thrust is clearly illustrative of the distinction the reader have become accustomed to making—the distinction between the man and the image, between reality and illusion. In the classical theories of rhetoric the implied auditor-this second persona-is but cursorily treated. More recently the readers have learned that the second persona may be favorably or unfavorably disposed toward the thesis of the discourse, or he may have a neutral attitude toward it. The expectation that a verbal token of ideology can be taken as implying an auditor who shares that ideology is something more than a hypothesis about a relationship. It rather should be viewed as expressing a vector of influence. Regarding the communism-as-cancer metaphor, it could make considerable difference to critical analysis whether a preoccupation with or morbid fear of cancer had any psychopathological significance, whether such a fear had been identified by psychiatrists.