gebhart/patrepeval huggingface dataset:
Total synthesis of echinocandins. I. Stereocontrolled syntheses of the constituent amino acids (1986)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTotal synthesis of echinocandins. I. Stereocontrolled syntheses of the constituent amino acidsNatsuko. Kurokawa and Yasufumi. OhfuneCite this: J. Am. Chem. Soc. 1986, 108, 19, 6041–6043Publication Date (Print):September 1, 1986Publication History Published online1 May 2002Published inissue 1 September 1986https://doi.org/10.1021/ja00279a064RIGHTS & PERMISSIONSArticle Views1078Altmetric-Citations87LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (436 KB) Get e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Eicosapentaenoic acid improves endothelial function and nitric oxide bioavailability in a manner that is enhanced in combination with a statin (2018)

The endothelium exerts many vasoprotective effects that are largely mediated by release of nitric oxide (NO). Endothelial dysfunction represents an early but reversible step in atherosclerosis and is characterized by a reduction in the bioavailability of NO. Previous studies have shown that eicosapentaenoic acid (EPA), an omega-3 fatty acid (O3FA), and statins individually improve endothelial cell function, but their effects in combination have not been tested. Through a series of in vitro experiments, this study evaluated the effects of a combined treatment of EPA and the active metabolite of atorvastatin (ATM) on endothelial cell function under conditions of oxidative stress. Specifically, the comparative and time-dependent effects of these agents on endothelial dysfunction were examined by measuring the levels of NO and peroxynitrite (ONOO<sup>-</sup>) released from human umbilical vein endothelial cells (HUVECs). The data suggest that combined treatment with EPA and ATM is beneficial to endothelial function and was unique to EPA and ATM since similar improvements could not be recapitulated by substituting another O3FA docosahexaenoic acid (DHA) or other TG-lowering agents such as fenofibrate, niacin, or gemfibrozil. Comparable beneficial effects were observed when HUVECs were pretreated with EPA and ATM before exposure to oxidative stress. Interestingly, the kinetics of EPA-based protection of endothelial function in response to oxidation were found to be significantly different than those of DHA. Lastly, the beneficial effects on endothelial function generated by combined treatment of EPA and ATM were reproduced when this study was expanded to an ex vivo model utilizing rat glomerular endothelial cells. Taken together, these findings suggest that a combined treatment of EPA and ATM can inhibit endothelial dysfunction that occurs in response to conditions such as hyperglycemia, oxidative stress, and dyslipidemia.
Ubiquitin‐dependent regulation of Foxp3 and Treg function (2015)

Regulatory T (Treg) cells are crucial enforcers of immune homeostasis. Their characteristic suppressive function largely arises from an equally unique pattern of gene expression. A complex network of factors and processes contribute to this 'signature' Treg gene expression landscape. Many of these alter the level and activity of the Treg-defining transcription factor Foxp3. As stable expression of Foxp3 is important for the ability of Treg cells to successfully prevent excessive or inappropriate immune activation, uncovering the mechanisms regulating Foxp3 level is required for the understanding and therapeutic exploitation of Tregs. While transcriptional regulation of the Foxp3 gene has been studied in depth, additional regulatory layers exist controlling the expression and activity of this key transcription factor. These include less-defined mechanisms active at the post-translational level. These pathways are just beginning to be elucidated. Here, we summarize emerging evidence for distinct, post-translationally active, ubiquitin-dependent pathways capable of controlling the activation and expression of Foxp3 and the function of Tregs. These pathways offer untapped opportunities for therapeutic fine-tuning of Tregs and their all-important restraint of the immune system.
Charge Effects and Transient Simulation of p-HEMT Meander Gate Switches (2006)

This paper presents a simulation of the transient behavior of a filtronic SP6T switch. By employing a non-linear switch model a representation of the switching dynamics is presented. The simulations predict that the changing control voltages has quickly attenuate the fundamental power, however harmonic performance is dependant on the total bias applied to the switch and hence relaxes to its steady state condition 0.15mus after the control voltages have settled. Within this paper we demonstrate the importance of understanding the behavior of the switch during transitions between equilibrium conditions with respect to the radiated spectral content
Localization of the Wilson’s disease protein product to mitochondria (1998)

Wilson's disease (WND) is an inherited disorder of copper homeostasis characterized by abnormal accumulation of copper in several tissues, particularly in the liver, brain, and kidney. The disease-associated gene encodes a copper-transporting P-type ATPase, the WND protein, the subcellular location of which could be regulated by copper. We demonstrate that the WND protein is present in cells in two forms, the 160-kDa and the 140-kDa products. The 160-kDa product was earlier shown to be targeted to trans-Golgi network. The 140-kDa product identified herein is located in mitochondria as evidenced by the immunofluorescent staining of HepG2 cells with specific mitochondria markers and polyclonal antibody directed against the C terminus of the WND molecule. The mitochondrial location for the 140-kDa WND product was confirmed by membrane fractionation and by analysis of purified human mitochondria. The antibody raised against a repetitive sequence in the N-terminal portion of the WND molecule detects an additional 16-kDa protein, suggesting that the 140-kDa product was formed after proteolytic cleavage of the full-length WND protein at the N terminus. Thus, the WND protein is a P-type ATPase with an unusual subcellular localization. The mitochondria targeting of the WND protein suggests its important role for copper-dependent processes taking place in this organelle.
Metal-on-metal hip joint tribology (2006)

The basic tribological features of metal-on-metal total hip replacements have been reviewed to facilitate an understanding of the engineering science underpinning the renaissance of these hard-on-hard joints. Metal-on-polymer hip replacements operate in the boundary lubrication regime, thus leading to the design guidance to reduce the femoral head diameter as much as is feasible to minimize frictional torque and volumetric wear. This explains why the gold-standard implant of this form from the past half-century had a diameter of only 22.225 mm (7/8 in). Metal-on-metal implants can operate in the mild mixed lubrication regime in which much of the applied load is supported by elastohydrodynamic films. Correct tribological design leads to remarkably low steady state wear rates. Promotion of the most effective elastohydrodynamic films calls for the largest possible head diameters and the smallest clearances that can reasonably be adopted, consistent with fine surface finishes, good sphericity and minimal structural elastic deformation of the cup on its foundations. This guidance, which is opposite in form to that developed for metal-on-polymer joints, is equally valid for solid (monolithic) metallic heads on metallic femoral stems and surface replacement femoral shells. Laboratory measurements of friction and wear in metal-on-metal joints have confirmed their potential to achieve a very mild form of mixed lubrication. The key lies in the generation of effective elastohydrodynamic lubricating films of adequate thickness compared with the composite roughness of the head and cup. The calculation of the film thickness is by no means easy, but the full procedure is outlined and the use of an empirical formula that displays good agreement with calculations based upon the full numerical solutions is explained. The representation of the lambda ratio, lambda, embracing both film thickness and composite roughness, is described.
DNA sequencing by delayed extraction-matrix-assisted laser desorption/ionization time of flight mass spectrometry. (1996)

Matrix-assisted laser desorption/ionization (MALDI) time of flight mass spectrometry was used to detect and order DNA fragments generated by Sanger dideoxy cycle sequencing. This was accomplished by improving the sensitivity and resolution of the MALDI method using a delayed ion extraction technique (DE-MALDI). The cycle sequencing chemistry was optimized to produce as much as 100 fmol of each specific dideoxy terminated fragment, generated from extension of a 13-base primer annealed on 40- and 50-base templates. Analysis of the resultant sequencing mixture by DE-MALDI identified the appropriate termination products. The technique provides a new non-gel-based method to sequence DNA which may ultimately have considerable speed advantages over traditional methodologies.
LIM domain recognition of a tyrosine-containing tight turn. (1994)

Endocytosis of cell surface receptors requires sequence "codes" consisting of tight turn structures with an essential Tyr or Phe residue. To determine mechanisms through which cells recognize this information, we utilized exon 16 of the human insulin receptor in the two-hybrid system to isolate a novel 455-amino acid cytoplasmic protein that contains two LIM domains within its carboxyl terminus. Mutational analyses indicate that one of the Cys-rich Zn2+ binding LIM domains specifically recognizes active but not inactive endocytic codes contained in exon 16. These findings suggest that LIM domain structures in proteins provide molecular recognition of Tyr-containing tight turn structures.
Inhaled glucocorticoids in asthma : mechanisms and clinical actions (1997)

Subcellular Actions of GlucocorticoidsGlucocorticoid Receptor Structure and Function, Roger L. Miesfeld and John W. BloomNegative Transcriptional Regulation by the Glucocorticoid Receptor Is Responsible for the Anti-Inflammatory Activity of Glucocorticoids, Michael Karin and Fahri SaatciogluGlucocorticoids Attenuate Induction of Two Primary Response Immediate Early Genes Prostaglandin Synthase 2 and Inducible Nitric Oxide Synthase, Whose Products Mediate Paracrine Cell Communication, Harvey Herschman, Rebecca Gilbert, Srinivasa Reddy,Bradley Fletcher, Weiln Xie, Jeffrey Smith, and Dean KujubuGlucocorticoids and Apoptosis of Hematopoietic Cells: Transcriptional and Posttranscriptional Control, E. Brad ThompsonLymphocyte Activation: The Interplay and Synergy of Immunosuppressants, Isabella Graef, Neil Clipstone, Steffan N. Ho, Luika A. Timmerman, Jeffrey Northrop, and Gerald R. CrabtreeEffects on Airway Mucosa and SubmucosaAirway Ultrastructure in Asthma, Lauri A. Laitinen and Annika LaitinenSputum Indices of Inflammation in Asthma, Frederick E. Hargreave, Emilio Pizzichini, Marcia Pizzichini, Ann Efthimiadis, Jerry Dolovich, and Paul M. O'ByrneTissue Remodeling and Fibroblast Heterogeneity in Asthma and Other Chronic Airways Inflammatory Diseases, Jack Gauldie, Patricia J. Sime, Guy M. Tremblay, Diane Torry, Manel Jordana, and Bengt SarnstrandAirway Microcirculation, Epithelium, and Glucocorticoids, Carl G. A. PerssonInhibition of Inflammatory Cell Recruitment by Glucocorticoids: Cytokines as Primary Targets, Robert P. Schleimer, Lisa A. Beck, Lisa A. Schweibert, Cristiana Stellato, Kelly Davenpeck, and Bruce S. BochnerAirway Lymphocytes, Stephen R. Durham, Chris J. Corrigan, Douglas S. Robinson, Quatayba Hamid, and A. B. KayEffects of Corticosteroids on Basophils and Mast Cells, Judah A. DenburgGlucocorticoid Effects on Human Eosinophils, Gerald J. Gleich, Loren W. Hunt, Bruce S. Bochner, and Robert P. SchleimerCytokines and Growth Factors in Asthma, Stephen J. Lane, David J. Cousins, Ana R. Sousa, Dontcho Z. Staynov, and Tak H. LeeGlucocorticoid Activity and Selectivity at the Airway LevelBasis of Airway Selectivity of Inhaled Glucocorticoids, Ralph Brattsand and Bengt I. AxelssonGlucocorticoid Pharmacokinetics: Principles and Clinical Applications, Staffan Edsb?cker and Stanley J. SzeflerDeterminants of Dose and Response to Inhaled Therapeutic Agents in Asthma, Gerald C. SmaldoneClinical AspectsA Comparison of Inhaled Versus Oral Corticosteroids as Maintenance Therapy in Asthma, William W. BusseInhaled Corticosteroids in Asthma: Importance of Early Intervention, Paul M. O'ByrneRole of Glucocorticoids in the Therapy of Acute Asthma, E. R. McFadden, Jr.Corticosteroids in the Treatment of Allergic Rhinitis, Peter H. HowarthEfficacy and Safety of Inhaled Corticosteroids in Children, S?ren E. PedersenEffects of Inhaled Steroid Therapy for Asthma of Skeletal Metabolism, John H. Too
Study on respiration monitoring method using near-infrared multiple slit-lights projection (2006)

We describe the principle of the respiration monitoring by the multiple slit light irradiation and the configuration of the respiration monitoring system. In the developed system, the fiber grating vision sensor known as an active type high-speed three-dimensional sensor was applied to satisfy the non-contact and non-restraint respiration monitoring. The fiber grating vision sensor is composed of a multiple slit light projector and a CCD camera, and these are placed above the sleeping person oriented in a lengthwise direction of the bed. And the multiple slit light projector projects the slit light array on the body surface of sleeping person. In this paper, the algorithm for monitoring and analyzing of the respiration status of the sleeping person is proposed. And, the result of the preliminary experiment performed to verify the effectiveness of developed system is described. As results of preliminary experiment through the simultaneous measurements with the developed system and a spirometer, it is confirmed that respiratory waveforms obtained by this system reflect the changes of volume occurring with respiratory movement of the examinee.
Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites (2020)

The outbreak of coronavirus disease (COVID-19) caused by SARS-CoV-2 virus continually lead to worldwide human infections and deaths. Currently, there is no specific viral protein-targeted therapeutics. Viral nucleocapsid protein is a potential antiviral drug target, serving multiple critical functions during the viral life cycle. However, the structural information of SARS-CoV-2 nucleocapsid protein remains unclear. Herein, we have determined the 2.7 Å crystal structure of the N-terminal RNA binding domain of SARS-CoV-2 nucleocapsid protein. Although the overall structure is similar as other reported coronavirus nucleocapsid protein N-terminal domain, the surface electrostatic potential characteristics between them are distinct. Further comparison with mild virus type HCoV-OC43 equivalent domain demonstrates a unique potential RNA binding pocket alongside the <i>β</i>-sheet core. Complemented by <i>in vitro</i> binding studies, our data provide several atomic resolution features of SARS-CoV-2 nucleocapsid protein N-terminal domain, guiding the design of novel antiviral agents specific targeting to SARS-CoV-2.
PARTICLE SIZE ANALYSIS OF BEER SOLIDS USING A COULTER COUNTER (1984)

An improved method of operation has been developed which enables the Coulter Counter to be employed effectively for the determination of particle size distribution in beer. Possible areas of application are outlined.
Early N-Terminal Changes and Caspase-6 Cleavage of Tau in Alzheimer's Disease (2004)

Alzheimer's disease (AD) is a progressive amnestic dementia that involves post-translational hyperphosphorylation, enzymatic cleavage, and conformational alterations of the microtubule-associated protein tau. The truncation state of tau influences many of its pathologic characteristics, including its ability to assume AD-related conformations and to assemble into filaments. Cleavage also appears to be an important marker in AD progression. Although C-terminal truncation of tau at D421 has recently been attributed to the apoptotic enzyme caspase-3, N-terminal processing of the protein remains mostly uncharacterized. Here, we report immunohistochemical staining in a cohort of 35 cases ranging from noncognitively impaired to early AD with a panel of three N-terminal anti-tau antibodies: Tau-12, 5A6, and 9G3-pY18. Of these three, the phosphorylation-independent epitope of 5A6 was the earliest to emerge in the pathological lesions of tau, followed by the appearance of the Tau-12 epitope. The unmasking of the Tau-12 epitope in more mature 5A6-positive tangles was not correlated with tau phosphorylation at tyrosine 18 (9G3-pY18). Still, later in the course of tangle evolution, the extreme N terminus of tau was lost, correlating temporally with the appearance of a C-terminal caspase-truncated epitope lacking residues 422-441. In addition, caspase-6 cleaved the N terminus of tau in vitro, preventing immunoreactivity with both Tau-12 and 5A6. Mass spectrometry confirmed that the in vitro caspase-6 truncation site is D13, a semicanonical and hitherto undescribed caspase cleavage site in tau. Collectively, these results suggest a role for caspase-6 and N-terminal truncation of tau during neurofibrillary tangle evolution and the progression of Alzheimer's disease.
Branched-chain amino acids in liver diseases (2013)

Branched chain amino acids (BCAAs) have been shown to affect gene expression, protein metabolism, apoptosis and regeneration of hepatocytes, and insulin resistance. They have also been shown to inhibit the proliferation of liver cancer cells in vitro, and are essential for lymphocyte proliferation and dendritic cell maturation. In patients with advanced chronic liver disease, BCAA concentrations are low, whereas the concentrations of aromatic amino acids such as phenylalanine and tyrosine are high, conditions that may be closely associated with hepatic encephalopathy and the prognosis of these patients. Based on these basic observations, patients with advanced chronic liver disease have been treated clinically with BCAA-rich medicines, with positive effects.
The effect of vascular changes on the photoplethysmographic signal at different hand elevations (2015)

In order to further understand the contribution of venous and arterial effects to the photoplethysmographic (PPG) signal, recordings were made from 20 healthy volunteer subjects during an exercise in which the right hand was raised and lowered with reference to heart level. Red (R) and infrared (IR) PPG signals were obtained from the right index finger using a custom-made PPG processing system. Laser Doppler flowmetry (LDF) signals were also recorded from an adjacent fingertip. The signals were compared with simultaneous PPG signals obtained from the left index finger. On lowering the hand to 50 cm below heart level, both ac and dc PPG amplitudes from the finger decreased (e.g. 18.70 and 63.15% decrease in infrared dc and ac signals respectively). The decrease in dc amplitude most likely corresponded to increased venous volume, while the decrease in ac PPG amplitude was due to regulatory adjustments on the arterial side in response to venous distension. Conversely, ac and dc PPG amplitudes increased on raising the arm above heart level. Morphological changes in the ac PPG signal are thought to be due to vascular resistance changes, predominately venous, as the hand position is changed.
Low-Molecular-Weight Heparins (2005)

Deep venous thrombosis is a common but underdiagnosed medical condition. The epidemiologic features, economic impact, morbidity, and mortality of venous thromboembolism make it imperative that the podiatric physician be familiar with its pathogenesis as well as its pharmacologic treatment. Medical literature rooted in clinical evidence has demonstrated that low-molecular-weight heparins are safe and effective for the prevention and treatment of venous thromboembolism. The primary purpose of this article is to review the pharmacologic characteristics of low-molecular-weight heparins. Dosing recommendations for low-molecular-weight heparins as they apply to the prevention of deep venous thrombosis are presented. Finally, a dosing criteria chart is presented to assist the podiatric physician in prescribing and evaluating low-molecular-weight heparins as a therapeutic class.
Mycobacteria precipitate an SLE-like syndrome in diabetes-prone NOD mice. (1994)

Non-obese diabetic (NOD) mice spontaneously develop organ-specific autoimmunity and are widely used as a model for diabetes. Aged NOD mice also exhibit some features of non-organ-specific autoimmune rheumatic disease such as anti-nuclear antibodies and late-onset haemolytic anaemia. Here, we report that a single dose of 2.6 x 10(7) heat-killed bacillus Calmette-Guérin (BCG) i.v. in 8-week-old NOD mice prevented diabetes but precipitated a syndrome similar to systemic lupus erythematosus (SLE). Treated mice developed haemolytic anaemia, anti-DNA and anti-Sm anti-nuclear autoantibodies and an increased severity of sialadenitis. Perivascular lymphocytic infiltration in the kidneys and glomerular immune complex deposition were also found. The action of BCG appeared to be mediated by an adjuvant-like activity as treated mice showed a substantial increase in reticuloendothelial cell function and enhanced antigen presentation capacity.
Finding good peers in peer-to-peer networks (2002)

As computing and communication capabilities have continued to increase, more and more activity is taking place at the edges of the network, typically in homes or on workers desktops. This trend has been demonstrated by the increasing popularity and usability of "peer-to-peer" systems, such as Napster and Gnutella. Unfortunately, this popularity has quickly shown the limitations of these systems, particularly in terms of scale. Because the networks form in an ad-hoc manner, they typically make inefficient use of resources. We propose a mechanism, using only local knowledge, to improve the overall performance of peer-to-peer networks based on interests. Peers monitor which other peers frequently respond successfully to their requests for information. When a peer is discovered to frequently provide good results, the peer attempts to move closer to it in the network by creating a new connection with that peer. This leads to clusters of peers with similar interests, and in turn allows us to limit the depth of searches required to find good results. We have implemented our algorithm in the context of a distributed encyclopedia-style information-sharing application which is built on top of the Gnutella network. In our testing environment, we have shown the ability to greatly reduce the amount of communication resources required to find the desired articles in the encyclopedia.