gebhart/patrepeval huggingface dataset:
Periodate Oxidized ATP (oATP) Reduces Hyperalgesia in Mice: Involvement of P2X7 Receptors and Implications for Therapy (2008)

Some inflammatory mediators play an important role not only in the pathogenesis of the inflammatory pain, but also in that of neuropathic and visceral pain. We previously showed the antihyperalgesic effect of oATP, the inhibitor of the P2X7 receptors for the pro-nociceptive ATP, in experimental inflammation. Here we show the antihyperalgesic effect of oATP in mouse models of neuropathic and visceral pain, other than in a model of arthritic pain mimicking rheumatoid arthritis in humans. We also show that mice lacking P2X7 receptors (KO) are resistant to hyperalgesic thermal stimuli following the induction of arthritic, neuropathic and visceral pain. Local (injection into the right hind paw) pre-treatment with oATP is able to prevent the successive induction of ATP-dependent hyperalgesia in wild type mice. In addition, KO mice are not insensitive to intraplantar treatment with ATP. Our data suggest that, even if oATP is able to inhibit purinoceptors different from P2X7, the latter are the more important involved in pain transmission.
Novel Probes Showing Specific Fluorescence Enhancement on Binding to a Hexahistidine Tag (2008)

The introduction of hexahistidine (His tag) is widely used as a tool for affinity purification of recombinant proteins, since the His tag binds selectively to nickel-nitrilotriacetic acid (Ni2+-NTA) complex. To develop efficient "turn-on" fluorescent probes for His-tagged proteins, we adopted a fluorophore displacement strategy, that is, we designed probes in which a hydroxycoumarin fluorophore is joined via a linker to a metal-NTA moiety, with which it forms a weak intramolecular complex, thereby quenching the fluorescence. In the presence of a His tag, with which the metal-NTA moiety binds strongly, the fluorophore is displaced, which results in a dramatic enhancement of fluorescence. We synthesized a series of hydroxycoumarins that were modified by various linkers with NTA (NTAC ligands), and investigated the chemical and photophysical properties of the free ligands and their metal complexes. From the viewpoint of fluorescence quenching, Ni2+ and Co2+ were the best metals. Fluorescence spectroscopy revealed a 1:1 binding stoichiometry for the Ni2+ and Co2+ complexes of NTACs in pH 7.4 aqueous buffer. As anticipated, these complexes showed weak intrinsic fluorescence, but addition of a His-tagged peptide (H-(His)6-Tyr-NH2; Tyr was included to allow convenient concentration measurement) in pH 7.4 aqueous buffer resulted in up to a 22-fold increase in the fluorescence quantum yield. We found that the Co2+ complexes showed superior properties. No fluorescence enhancement was seen in the presence of angiotensin I, which contains two nonadjacent histidine residues; this suggests that the probes are selective for the polyhistidine peptide.
THE PREPARATION OF TERMINALLY UNSATURATED PERFLUORO OLEFINS BY THE DECOMPOSITION OF THE SALTS OF PERFLUORO ACIDS (1951)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTHE PREPARATION OF TERMINALLY UNSATURATED PERFLUORO OLEFINS BY THE DECOMPOSITION OF THE SALTS OF PERFLUORO ACIDSLyle J. Hals, Thomas S. Reid, and George H. Smith Jr.Cite this: J. Am. Chem. Soc. 1951, 73, 8, 4054Publication Date (Print):August 1, 1951Publication History Published online1 May 2002Published inissue 1 August 1951https://pubs.acs.org/doi/10.1021/ja01152a547https://doi.org/10.1021/ja01152a547research-articleACS PublicationsRequest reuse permissionsArticle Views216Altmetric-Citations33LEARN 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-Alertsclose Get e-Alerts
Selective modification of alternative splicing by indole derivatives that target serine-arginine-rich protein splicing factors (2005)

The prevalence of alternative splicing as a target for alterations leading to human genetic disorders makes it highly relevant for therapy. Here we have used in vitro splicing reactions with different splicing reporter constructs to screen 4,000 chemical compounds for their ability to selectively inhibit spliceosome assembly and splicing. We discovered indole derivatives as potent inhibitors of the splicing reaction. Importantly, compounds of this family specifically inhibit exonic splicing enhancer (ESE)-dependent splicing, because they interact directly and selectively with members of the serine-arginine-rich protein family. Treatment of cells expressing reporter constructs with ESE sequences demonstrated that selected indole derivatives mediate inhibition of ESE usage in vivo and prevent early splicing events required for HIV replication. This discovery opens the exciting possibility of a causal pharmacological treatment of aberrant splicing in human genetic disorders and development of new antiviral therapeutic approaches.
Fabrication and Properties of Carbon Fibers (2009)

This paper reviews the research and development activities conducted over the past few decades on carbon fibers. The two most important precursors in the carbon fiber industry are polyacrylonitrile (PAN) and mesophase pitch (MP). The structure and composition of the precursor affect the properties of the resultant carbon fibers significantly. Although the essential processes for carbon fiber production are similar, different precursors require different processing conditions in order to achieve improved performance. The research efforts on process optimization are discussed in this review. The review also attempts to cover the research on other precursor materials developed mainly for the purpose of cost reduction.
Synthesis and Organocatalytic Ring-Opening Polymerization of Cyclic Esters Derived from l-Malic Acid (2010)

The synthesis of 3-(S)-[(benzyloxycarbonyl)methyl]-1,4-dioxane-2,5-dione (BMD) and 3,6-(S)-[di(benzyloxycarbonyl)methyl]-1,4-dioxane-2,5-dione (malide) from commercially available l-malic acid is reported. Ring-opening polymerization (ROP) studies of BMD are reported showing that the controlled ROP of this monomer is possible in the absence of transesterification side reactions, despite the presence of side-chain esters, using 1-(3,5-bis(trifluoromethyl)phenyl)-3-cyclohexylthiourea and (-)-sparteine to catalyze the polymerization. The ROP of malide with this system was ineffective. Investigation of the effect of initiating species revealed that the electronic nature of the alcohol had a greater effect on the ultimate molecular weight and hence initiator efficiency than steric considerations. Deprotection of the resultant poly(BMD) using H(2) and Pd/C resulted in hydrophilic poly(glycolic-co-malic acid)s (PGMAs) that were able to undergo autocatalytic degradation in dilute H(2)O solution such that complete degradation was observed within 6 days.
First acute haemodynamic study of soluble guanylate cyclase stimulator riociguat in pulmonary hypertension (2009)

Pulmonary hypertension (PH) is associated with impaired production of the vasodilator nitric oxide (NO). Riociguat (BAY 63-2521; Bayer Healthcare AG, Wuppertal, Germany) acts directly on soluble guanylate cyclase, stimulating the enzyme and increasing sensitivity to low NO levels. The present study evaluates riociguat safety, tolerability and efficacy in patients with moderate-to-severe PH (pulmonary arterial hypertension, distal chronic thromboembolic PH or PH with mild to moderate interstitial lung disease). The optimal tolerated dose was identified by incremental dosing in four patients with PH; pharmacodynamic and pharmacokinetic parameters were assessed following single-dose administration (2.5 mg or 1 mg) in 10 and five patients with PH, respectively. All subjects (n = 19) were analysed for safety and tolerability. Riociguat had a favourable safety profile at single doses < or =2.5 mg. It significantly improved pulmonary haemodynamic parameters and cardiac index in patients with PH in a dose-dependent manner, to a greater extent than inhaled NO. Although riociguat also had significant systemic effects and showed no pulmonary selectivity, mean systolic blood pressure remained >110 mmHg. The present report is the first to describe the use of riociguat in patients with pulmonary hypertension. The drug was well-tolerated and superior to nitric oxide in efficacy and duration. Riociguat, therefore, has potential as a novel therapy for pulmonary hypertension and warrants further investigation.
Hybrid Organic‐Inorganic Materials Derived from a Monosilylated Hoveyda‐Type Ligand as Recyclable Diene and Enyne Metathesis Catalysts. (2007)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
High Resolution Crystal Structure of a Human Tumor Necrosis Factor-α Mutant with Low Systemic Toxicity (1998)

A human tumor necrosis factor-alpha (TNF-alpha) mutant (M3S) with low systemic toxicity in vivo was designed, and its structures in two different crystal packings were determined crystallographically at 1.8 and 2.15-A resolution, respectively, to explain altered biological activities of the mutant. M3S contains four changes: a hydrophilic substitution of L29S, two hydrophobic substitutions of S52I and Y56F, and a deletion of the N-terminal seven amino acids that is disordered in the structure of wild-type TNF-alpha. Compared with wild-type TNF-alpha, it exhibits 11- and 71-fold lower binding affinities for the human TNF-R55 and TNF-R75 receptors, respectively, and in vitro cytotoxic effect and in vivo systemic toxicity of M3S are 20 and 10 times lower, respectively. However, in a transplanted solid tumor mouse model, M3S suppresses tumor growth more efficiently than wild-type TNF-alpha. M3S is highly resistant to proteolysis by trypsin, and it exhibits increased thermal stability and a prolonged half-life in vivo. The L29S mutation causes substantial restructuring of the loop containing residues 29-36 into a rigid segment as a consequence of induced formation of intra- and intersubunit interactions, explaining the altered receptor binding affinity and thermal stability. A mass spectrometric analysis identified major proteolytic cleavage sites located on this loop, and thus the increased resistance of M3S to the proteolysis is consistent with the increased rigidity of the loop. The S52I and Y56F mutations do not induce a noticeable conformational change. The side chain of Phe56 projects into a hydrophobic cavity, while Ile52 is exposed to the bulk solvent. Ile52 should be involved in hydrophobic interactions with the receptors, since a mutant containing the same mutations as in M3S except for the L29S mutation exhibits an increased receptor binding affinity. The low systemic toxicity of M3S appears to be the effect of the reduced and selective binding affinities for the TNF receptors, and the superior tumor-suppression of M3S appears to be the effect of its weak but longer antitumoral activity in vivo compared with wild-type TNF-alpha. It is also expected that the 1.8-A resolution structure will serve as an accurate model for explaining the structure-function relationship of wild-type TNF-alpha and many TNF-alpha mutants reported previously and for the design of new TNF-alpha mutants.
Interleukin 1 protects hair follicles from cytarabine (ARA‐C)‐induced toxicity in vivo and in vitro (1992)

ImuVert, a biologic response modifier, and interleukin 1 (IL 1) have been shown to protect the young rat from alopecia induced by cytarabine (ARA-C). In the present study the inhibition by ARA-C of DNA synthesis in hair follicles (HFs) and the protective effect of ImuVert and IL 1 were investigated in vivo and in vitro. Both ImuVert and IL 1 were equally effective in protecting rats from ARA-C-induced alopecia. DNA synthesis in HFs isolated from ARA-C-treated animals was 10-20% of untreated controls. Follicles isolated from animals given either ImuVert or IL 1 before ARA-C exhibited normal DNA synthesis. In vitro, the incubation of normal rat HF with ARA-C resulted in 80% inhibition of [3H]-thymidine uptake. Preincubation of the follicles for 1 hr with IL 1 before the addition of ARA-C completely blocked the inhibition. Preincubation with imuVert, however, was less effective in blocking the inhibition from ARA-C.
Anticytokine Therapy in Rheumatoid Arthritis (1997)

Only a few years ago, little was known about the role of cytokines in rheumatoid arthritis. The original view of the cytokine milieu in the inflamed joint as a melange of factors from various cells was clarified by two observations.1 First, in inflammation of rheumatoid arthritis, cytokines from macrophages and fibroblasts dominate, and second, the cytokine profile within the macrophage and fibroblast reflects a hierarchy, with interleukin-1 and tumor necrosis factor α (TNF-α) assuming particular importance. Anticytokine therapy for rheumatoid arthritis has now reached the clinic, and the report in this issue of the Journal by Moreland et al.2 adds . . .
Voice Recognition Algorithms using Mel Frequency Cepstral Coefficient (MFCC) and Dynamic Time Warping (DTW) Techniques (2010)

Digital processing of speech signal and voice recognition algorithm is very important for fast and accurate automatic voice recognition technology. The voice is a signal of infinite information. A direct analysis and synthesizing the complex voice signal is due to too much information contained in the signal. Therefore the digital signal processes such as Feature Extraction and Feature Matching are introduced to represent the voice signal. Several methods such as Liner Predictive Predictive Coding (LPC), Hidden Markov Model (HMM), Artificial Neural Network (ANN) and etc are evaluated with a view to identify a straight forward and effective method for voice signal. The extraction and matching process is implemented right after the Pre Processing or filtering signal is performed. The non-parametric method for modelling the human auditory perception system, Mel Frequency Cepstral Coefficients (MFCCs) are utilize as extraction techniques. The non linear sequence alignment known as Dynamic Time Warping (DTW) introduced by Sakoe Chiba has been used as features matching techniques. Since it's obvious that the voice signal tends to have different temporal rate, the alignment is important to produce the better performance.This paper present the viability of MFCC to extract features and DTW to compare the test patterns.
Lawyer Role, Agency Law, and the Characterization Officer of the Court (2000)

The law of agency has governed American lawyers since before the Revolution, but recent scholarship about legal ethics and professional role almost entirely ignores it. Most commentators would concede that attorneys are agents, but would quickly add that the lawyer is also an "officer of the court" who has obligations to seek justice. However, analysis of the phrase "officer of the court" reveals that it has surprisingly little content; it is mostly rhetoric, caused by self-love and self-promotion. What little content it has points to a role of the attorney as agent whose obligations to the court are almost identical to those owed by non-lawyers and almost entirely consistent with duties to clients. By largely ignoring agency law, and failing to throughly examine the attorney's role as an "officer of the court," commentators have mistakenly grounded wide ranging arguments that lawyers must seek "justice" because they are officers of the court who have a special obligation to seek justice. Lawyers do perform a screening or gate-keeping function for the courts, society, and clients. Allegations or responses that are without foundation may not be made. Courts, therefore, have some-assurance that complaints and defenses have some merit. However, non-lawyers are also prohibited from making claims or asserting defenses that are without merit, thus, lawyers do not have a special, or unique gate-keeping role. This article will demonstrate that agency law provides a sound framework for examining even the most vexing ethical and role issues. In particular, the role issues at the junction of zealous advocate and "officer of the court" are explored. In Part I, the concept "officer of the court" is examined to determine its content. The attempt by prominent commentators to ground a substantive duty to seek justice in the lawyer's role as an "officer of the court" is noted and then critically examined from a historical and modern perspective. The 19th century writers David Hoffman, and George Sharswood, considered the father of legal ethics, are scrutinized. Then, attorney as an "officer of the court" in medieval England, the Roman Empire, and Greece is briefly discussed. In Part II, agency law and the role of the lawyer as agent will be discussed. A short historical excursion to ancient Greece, Rome, and England will be taken to show the role of the lawyer as agent in those societies. We will discover that common to all three societies is a role in which an individual assists a party in legal proceedings at the party's direction. Finally, Part III, examines agency law to determine if it can provide content to the label "officer of the court." Also discussed in Part III is whether the lawyer's role within our adversary system should ever include a substantive duty to the court to seek justice that is inconsistent with the duty of client loyalty.
Field trials and testing of the OctArm continuum manipulator (2006)

This paper describes the results of field trials and associated testing of the OctArm series of multi-section continuous backbone "continuum" robots. This novel series of manipulators has recently (Spring 2005) undergone a series of trials including open-air and in-water field tests. Outcomes of the trials, in which the manipulators demonstrated the ability for adaptive and novel manipulation in challenging environments, are described. Implications for the deployment of continuum robots in a variety of applications are discussed
Nonlinear optical properties of photoresists for projection lithography (1996)

Optical beams are self-focused and self-trapped upon initiating crosslinking in photoresists. This nonlinear optical phenomenon is apparent only for low average optical intensities and produces index of refraction changes as large as 0.04. We propose using the self-focusing and self-trapping phenomenon in projection photolithography to enhance the resolution and depth of focus.
Bi-specific splice-switching PMO oligonucleotides conjugated via a single peptide active in a mouse model of Duchenne muscular dystrophy (2014)

The potential for therapeutic application of splice-switching oligonucleotides (SSOs) to modulate pre-mRNA splicing is increasingly evident in a number of diseases. However, the primary drawback of this approach is poor cell and in vivo oligonucleotide uptake efficacy. Biological activities can be significantly enhanced through the use of synthetically conjugated cationic cell penetrating peptides (CPPs). Studies to date have focused on the delivery of a single SSO conjugated to a CPP, but here we describe the conjugation of two phosphorodiamidate morpholino oligonucleotide (PMO) SSOs to a single CPP for simultaneous delivery and pre-mRNA targeting of two separate genes, exon 23 of the Dmd gene and exon 5 of the Acvr2b gene, in a mouse model of Duchenne muscular dystrophy. Conjugations of PMOs to a single CPP were carried out through an amide bond in one case and through a triazole linkage ('click chemistry') in the other. The most active bi-specific CPP-PMOs demonstrated comparable exon skipping levels for both pre-mRNA targets when compared to individual CPP-PMO conjugates both in cell culture and in vivo in the mdx mouse model. Thus, two SSOs with different target sequences conjugated to a single CPP are biologically effective and potentially suitable for future therapeutic exploitation.
Shedding of porcine reproductive and respiratory syndrome virus in mammary gland secretions of sows (2001)

Naïve sows inoculated late in gestation shed PRRS virus in mammary secretions. Previous vaccination appeared to prevent shedding during the subsequent lactation. Results for samples obtained from sows in commercial herds suggested that virus shedding in mammary gland secretions of such sows is uncommon.
An Authentication and Authorization Architecture for Jini Services (2000)

class KeyPairGenerator { static KeyPairGenerator getInstance(String, String); void initialize(AlgorithmParameterSpec); final KeyPair genKeyPair(); ... } First, the instance is created by calling getInstance(), then it has to be initialized with some parameter which the algorithm needs and at least the key pair can be created by calling genKeyPair(). KeyPair is only a container class that stores the private and public key. 4.5.5 Usage of the Diffie Hellman Key Agreement Algorithm As mentioned above, the architecture suggests a default algorithm. The key agreement algorithm suggestion is the Diffie Hellmann key agreement algorithm (DH) which uses Diffie Hellman key pairs (DH). The parameters needed to generate the keys exponent and modulus are pregenerated, public and taken from Suns Diffie Hellman example program. DH is a one phase protocol, so that the doPhase() method has only to be called once with true as argument because the first phase is the last phase.
Intelligent artifact classification for ambulatory physiological signals (2010)

Connected health represents an increasingly important model for health-care delivery. The concept is heavily reliant on technology and in particular remote physiological monitoring. One of the principal challenges is the maintenance of high quality data streams which must be collected with minimally intrusive, inexpensive sensor systems operating in difficult conditions. Ambulatory monitoring represents one of the most challenging signal acquisition challenges of all in that data is collected as the patient engages in normal activities of everyday living. Data thus collected suffers from considerable corruption as a result of artifact, much of it induced by motion and this has a bearing on its utility for diagnostic purposes. We propose a model for ambulatory signal recording in which the data collected is accompanied by labeling indicating the quality of the collected signal. As motion is such an important source of artifact we demonstrate the concept in this case with a quality of signal measure derived from motion sensing technology viz. accelerometers. We further demonstrate how different types of artifact might be tagged to inform artifact reduction signal processing elements during subsequent signal analysis. This is demonstrated through the use of multiple accelerometers which allow the algorithm to distinguish between disturbance of the sensor relative to the underlying tissue and movement of this tissue. A brain monitoring experiment utilizing EEG and fNIRS is used to illustrate the concept.