gebhart/patrepeval huggingface dataset:
Circuit analysis, logic simulation, and design verification for VLSI (1983)

In this paper, we consider computer-aided design techniques for VLSI. Specifically, the areas of circuit analysis, logic simulation and design verification are discussed with an emphasis on time domain techniques. Recently, researchers have concentrated on two general problem areas. One important problem discussed is the efficient, exact-time analysis of large-scale circuits. The other area is the unification of these techniques with logic simulation and design verification technique in so called multimode or multilevel systems.
Current and Future Pharmacologic Therapy of Exacerbations in Chronic Obstructive Pulmonary Disease and Asthma (2004)

Exacerbations are an important cause of the morbidity and mortality associated with asthma and chronic obstructive pulmonary disease. Newer therapies include long-acting beta(2)-agonists, which are more effective than short-acting bronchodilators. Inhaled corticosteroids and, in asthma, leukotriene receptor antagonists may have roles in the early phase of exacerbation as an alternative to or added to oral prednisolone. In the future, combinations of long-acting beta(2)-agonists and anticholinergic bronchodilators may offer additive clinical benefits. However, although the treatment and prevention of exacerbations of chronic obstructive pulmonary disease and asthma have been improved by using combinations of known therapies, further research addressing the underlying etiology as well as molecular and pathophysiologic mechanisms of exacerbation is needed to better target novel therapies to the appropriate patient populations and to develop new therapeutic strategies.
Synthetic Studies on Azadirachtin: An Efficient Asymmetric Synthesis of the Highly Functionalized Tricyclic Decalin Part of Azadirachtin (2000)

The detailed examination of intramolecular Diels - Alder reactions of several structurally related trienes led to construction of the desired tricyclic decalin moiety of azadirachtin with the α-hydroxyl groups at C1 and C3 as the oxygenated substituent at C8 in the naturally occurring form in good yields.
The inside scoop: Comparative genomics of two intranuclear bacteria, “Candidatus Berkiella cookevillensis” and “Candidatus Berkiella aquae” (2022)

"Candidatus Berkiella cookevillensis" (strain CC99) and "Candidatus Berkiella aquae" (strain HT99), belonging to the Coxiellaceae family, are gram-negative bacteria isolated from amoebae in biofilms present in human-constructed water systems. Both bacteria are obligately intracellular, requiring host cells for growth and replication. The intracellular bacteria-containing vacuoles of both bacteria closely associate with or enter the nuclei of their host cells. In this study, we analyzed the genome sequences of CC99 and HT99 to better understand their biology and intracellular lifestyles. The CC99 genome has a size of 2.9Mb (37.9% GC) and contains 2,651 protein-encoding genes (PEGs) while the HT99 genome has a size of 3.6Mb (39.4% GC) and contains 3,238 PEGs. Both bacteria encode high proportions of hypothetical proteins (CC99: 46.5%; HT99: 51.3%). The central metabolic pathways of both bacteria appear largely intact. Genes for enzymes involved in the glycolytic pathway, the non-oxidative branch of the phosphate pathway, the tricarboxylic acid pathway, and the respiratory chain were present. Both bacteria, however, are missing genes for the synthesis of several amino acids, suggesting reliance on their host for amino acids and intermediates. Genes for type I and type IV (dot/icm) secretion systems as well as type IV pili were identified in both bacteria. Moreover, both bacteria contain genes encoding large numbers of putative effector proteins, including several with eukaryotic-like domains such as, ankyrin repeats, tetratricopeptide repeats, and leucine-rich repeats, characteristic of other intracellular bacteria.
Ultrasound cardiac calcium assessment (2014)

Dear Editor ; We congratulate the authors Kalsch et al , for their interesting paper1 which demonstrates that aortic valve calcification (AVC) by CT builds on Framingham score for risk stratification of future cardiovascular events. These are important data for preventive strategies, obtained in a wide and prospective study of healthy asymptomatics.

In the discussion, the authors state that “detection of degenerative aortic valve disease by assessing the prevalence of AVC can easily be performed …
Effect of Prostaglandin Synthesis Inhibition and Sympathectomy on Ouabain-Induced Arrhythmia in Cats (1981)

The purpose of this study was to examine the importance of endogenous prostaglandins (PGs) and sympathectomy on the arrhythmogenic action of ouabain. Cats, anesthetized with dial-urethane, were infused intravenously with ouabain continuously. The dose of ouabain necessary to produce arrhythmia (AR), ventricular tachycardia (VT), and death was determined. Pretreatment with sulfinpyrazone at 100 mg kg-1 i.v. 1 h before glycoside infusion was used to inhibit PG synthesis. Removal of endogenous PGs with sulfinpyrazone reduced the cardiotoxic dose of ouabain. Sympathetic influences were removed by: (a) destroying sympathetic nerve terminals with 6-hydroxydopamine (6-OHDA); (b) depleting nerve terminal catecholamines with reserpine; or (c) preventing catecholamine release from the nerve terminal with bretylium. Reduction of sympathetic influences with reserpine or bretylium increased the cardiotoxic dose of ouabain; whereas removal of nerve terminals with 6-OHDA did not alter the toxic dose of ouabain from that found in control animals. When endogenous PG synthesis was inhibited with sulfinpyrazone the protective effects of reserpine and bretylium were eliminated. These results suggest that endogenous PGs protect against the arrhythmogenic action of ouabain, not only by interfering with catecholamine influences at the sympathetic nerve terminal, but also by a mechanism independent of sympathetic inhibition. Furthermore, the protective action of agents which diminishes the cardiotoxic action of ouabain by interfering with sympathetic influences is lost when endogenous PGs are removed. Finally, 6-OHDA, which destroys the sympathetic nerve terminals, removes both the arrhythmic influence of the catecholamine as well as the protective influence of the PG, resulting in no net change in the cardiotoxic dose of this glycoside.
Predicting natural language descriptions of smells (2018)

There has been recent progress in predicting whether common verbal descriptors such as “fishy”, “floral” or “fruity” apply to the smell of odorous molecules. However, the number of descriptors for which such a prediction is possible to date is very small compared to the large number of descriptors that have been suggested for the profiling of smells. We show here that the use of natural language semantic representations on a small set of general olfactory perceptual descriptors allows for the accurate inference of perceptual ratings for mono-molecular odorants over a large and potentially arbitrary set of descriptors . This is a noteworthy approach given that the prevailing view is that human’s capacity to identify or characterize odors by name is poor [1, 2, 3, 4, 5]. Our methods, when combined with a molecule-to-ratings model using chemoinformatic features, also allow for the zero-shot learning inference [6, 7] of perceptual ratings for arbitrary molecules . We successfully applied our semantics-based approach to predict perceptual ratings with an accuracy higher than 0.5 for up to 70 olfactory perceptual descriptors in a well-known dataset, a ten-fold increase in the number of descriptors from previous attempts. Moreover we accurately predict paradigm odors of four common families of molecules with an AUC of up to 0.75. Our approach solves the need for the consuming task of handcrafting domain specific sets of descriptors in olfaction and collecting ratings for large numbers of descriptors and odorants [8, 9, 10, 11] while establishing that the semantic distance between descriptors defines the equivalent of an odorwheel.
Super-Resolution Raman Spectroscopy by Digital Image Processing (2013)

We demonstrate the results of a strain (stress) evaluation obtained from Raman spectroscopy measurements with the super-resolution method (the so-called super-resolution Raman spectroscopy) for a Si substrate with a patterned SiN film (serving as a strained Si sample). To improve the spatial resolution of Raman spectroscopy, we used the super-resolution method and a high-numerical-aperture immersion lens. Additionally, we estimated the spatial resolution by an edge force model (EFM) calculation. One- and two-dimensional stress distributions in the Si substrate with the patterned SiN film were obtained by super-resolution Raman spectroscopy. The results from both super-resolution Raman spectroscopy and the EFM calculation were compared and were found to correlate well. The best spatial resolution, 70 nm, was achieved by super-resolution Raman measurements with an oil immersion lens. We conclude that super-resolution Raman spectroscopy is a useful method for evaluating stress in miniaturized state-of-the-art transistors, and we believe that the super-resolution method will soon be a requisite technique.
Investigation of pesticides on honey bee carbonic anhydrase inhibition (2020)

Carbonic anhydrase (CA, EC 4.2.1.1) plays crucial physiological roles in many different organisms, such as in pH regulation, ion transport, and metabolic processes. CA was isolated from the European bee <i>Apis mellifera</i> (AmCA) spermatheca and inhibitory effects of pesticides belonging to various classes, such as carbamates, thiophosphates, and pyrethroids, were investigated herein. The inhibitory effects of methomyl, oxamyl, deltamethrin, cypermethrin, dichlorodiphenyltrichloroethane (DDT) and diazinon on AmCA were analysed. These pesticides showed effective <i>in vitro</i> inhibition of the enzyme, at sub-micromolar levels. The IC<sub>50</sub> values for these pesticides ranged between of 0.0023 and 0.0385 μM. The CA inhibition mechanism with these compounds is unknown at the moment, but most of them contain ester functionalities which may be hydrolysed by the enzyme with the formation of intermediates that can either react with amino acid residues or bid to the zinc ion from the active site.
Linear Assembly of a Human Y Centromere (2017)

The human genome reference sequence remains incomplete due to the challenge of assembling long tracts of near-identical tandem repeats-in centromeric regions. To address this, we have implemented a nanopore sequencing strategy to generate high quality reads that span hundreds of kilobases of highly repetitive DNAs. Here, we use this advance to produce a sequence assembly and characterization of the centromeric region of a human Y chromosome.
Abstract 1190: The Complement Component C5a is Present in Human Unstable Coronary Lesions in Vivo and Induces the Expression of MMP-9 in Human Macrophages via Nf-kappaB Activation In Vitro (2007)

Background. The complement component C5a formed during activation of the complement cascade exerts chemotactic and proinflammatory effects. We have recently shown that serum levels of C5a predict cardiovascular risk in patients with advanced atherosclerosis. However, it is not known whether C5a may play an active role in the onset of acute coronary events. Methods and Results. Immunohistochemical analysis of human coronary plaques obtained by atherectomy demonstrated the presence of C5a in macrophage rich areas and the necrotic core. Unstable plaques (n=9) showed significantly higher staining for C5a than stable coronary lesions (n=10; p&lt;0.05). Double-labeling studies demonstrated colocalization of C5a and MMP-9. When human monocyte derived macrophages were stimulated in vitro with rhC5a, MMP-9 mRNA levels were increase 6-fold. In addition, MMP-9 antigen as detected by ELISA and MMP-9 activity as detected by a specific activity assay significantly increased after stimulation with rhC5a. Nuclear shift assay revealed that rhC5a stimulated NF-κB DNA binding and the NF-κB inhibitor 6-amino-4-phenoxyphenethylaminoquinazoline blocked the up-regulation of MMP-9 by rhC5a. Conclusion. C5a is increased in unstable coronary plaques, colocalizes with MMP-9 and induces the expression of MMP-9 in human macrophages via NF-κB activation. Taken this observations together, activation of the complement cascade and formation of C5a may be involved in the onset of acute coronary events.
The Annals of Loch Cé. Reproduced at the Ordnance Survey, Dublin. Vol. i. Pp. [2,] lix, 655. 1939 [1940]. 15s. Vol. ii. Pp. [2, 8,] 690. 1939 [1940]. 15J. Dublin: Stationery Office (Coimisiún Láimhscríbhinní na hÉireann, Reflex facsimiles, III.) - The Annals of Loch Cé. By Rev. Paul Walsh. In IERec., series 5, lvi. 113-22. Sept. 1940. (1941)

The Annals of Loch Cé. Reproduced at the Ordnance Survey, Dublin. Vol. i. Pp. [2,] lix, 655. 1939 [1940]. 15s. Vol. ii. Pp. [2, 8,] 690. 1939 [1940]. 15J. Dublin: Stationery Office (Coimisiún Láimhscríbhinní na hÉireann, Reflex facsimiles, III.) - The Annals of Loch Cé. By Rev. Paul Walsh. In IERec., series 5, lvi. 113-22. Sept. 1940. - Volume 2 Issue 7
Optimization of the split-spectrum amplitude-decorrelation angiography algorithm on a spectral optical coherence tomography system (2015)

An erratum is presented to include conflict of interest disclosures that were unintentionally left out of our recent Letter [Opt. Lett.40, 2305 (2015)10.1364/OL.40.002305OPLEDP0146-9592].
<title>The Los Alamos Free-Electron Laser Oscillator Experiment: Plans And Present Status</title> (1984)

Plans have been made to modify the Los Almos free-electron laser amplifier experiment to allow its use as an oscillator at 10.6 microns. Several major changes were required, all of which have now been completed. The necessity for these changes is discussed as are the details of their fulfillment. In some cases we have progressed to the point where we can report on the performance of the new systems. The present status is described.
A double‐blind placebo‐controlled clinical trial of recombinant human brain‐derived neurotrophic factor (rhBDNF) in diabetic polyneuropathy (2001)

A randomized, double-blind, placebo-controlled study of brain-derived neurotrophic factor (rhBDNF) was conducted in 30 patients with insulin-treated diabetes mellitus, with obligatory abnormalities of sural nerve conduction studies and vibration perception threshold (VPT) at the great toe on recruitment. Nine patients received placebo, 11 rhBDNF (25 microg/ kg) and 10 rhBDNF (100 microg/kg) s.c. daily for 3 months, and were assessed at days 0, 8, 15, 29, 43, 57 and 85 with nerve conduction and quantitative sensory and autonomic tests including VPT, thermal and light touch thresholds, and cutaneous axon-reflexes. No statistically significant differences were found among the 3 treatment groups between baseline and day 85 values. To examine possible reasons for lack of effect, post hoc analysis was performed. In the subset of patients with abnormal but detectable cool detection threshold (CDT) at baseline, there was improvement of CDT at day 85 when compared to baseline in the treated (p < 0.02) but not placebo group. Further, from days 43 to 85, in the treated group but not the placebo group, CDT was indistinguishable from a group of matched normal subjects (p > 0.05). Skin biopsies failed to show evidence of structural change; assessment of innervation of hair follicles, which is partly dependent on BDNF, was not possible because of the marked loss of this end-organ in diabetic neuropathic skin. The only side effects of rhBDNF were infrequent non-painful injection-site skin reactions and increased gut motility at the higher dose. We conclude that further preclinical studies are warranted before any future clinical trials to see if rhBDNF improves CDT and constipation in diabetics.
An analysis of in vitro T cell responsiveness in lepromatous leprosy. (1985)

In lepromatous leprosy, there is extensive replication of Mycobacterium leprae (M. leprae) within dermal macrophages. This lack of microbial resistance has been attributed to a defective cell-mediated immune response to M. leprae antigens. We have examined the in vitro response of T cells to M. leprae to determine if hyporesponsiveness could be reversed. The study included 40 unselected patients from New York and from Colombia, most with the severe lepromatous form of the disease. We first noted that lepromatous leprosy patients were of two types: those unable to respond, as assessed by T cell proliferation and immune (gamma) interferon (IFN-gamma) release, and a second group, exhibiting low but detectable responses relative to tuberculoid controls. When the effect of exogenous recombinant interleukin-2 (IL-2) on the response to M. leprae antigens was compared in the two groups, many of the low responders, but not the nonresponders, showed enhanced proliferation and IFN-gamma release. To evaluate a possible suppressive effect of monocytes, these cells were eliminated with a cell-specific monoclonal antibody and complement. Depletion of monocytes often expanded preexisting weak responses but did not reverse the anergy of the M. leprae nonresponders. The enhancement was not M. leprae-specific, since it was also observed when bacillus Calmette-Guerin was the antigenic stimulus for proliferation and IFN-gamma production. Removal of the suppressor T cell subset, with OKT8 antibody and complement, also did not restore responses in nonresponder patients. We conclude that a sizable number of lepromatous leprosy patients exhibit a low degree of responsiveness to M. leprae and that the responses can be enhanced in vitro with IL-2 or with monocyte depletion. Nonresponsiveness, however, cannot be reversed. Since currently available assays measure the function of previously sensitized T cells, suppressor mechanisms may yet contribute to defective cell-mediated immunity by impairing the initial sensitization to M. leprae antigens.
Laminin and fibronectin in cell adhesion: enhanced adhesion of cells from regenerating liver to laminin. (1981)

Laminin, a basement membrane glycoprotein isolated from cultures of mouse endodermal cells and rat yolk sac carcinoma cells, promoted the attachment of liver cells obtained from regenerating mouse liver. Cells from normal mouse liver attached readily to dishes coated with fibronectin but attached poorly to surfaces coated with laminin. Both proteins efficiently promoted the attachment of cells from livers undergoing regeneration. After regeneration, the attachment to laminin returned to the low levels found in animals not subjected to partial hepatectomy but attachment to fibronectin remained high. Immunofluorescent staining of sections of normal liver with antilaminin revealed the presence of laminin in or adjacent to the walls of the bile ducts and blood vessels. After induction of regeneration by partial hepatectomy, increased amounts of laminin appeared in the sinusoidal areas. After carbon tetrachloride poisoning, staining for laminin was especially pronounced in the necrotic and postnecrotic areas around the central veins. This additional expression of laminin was transient. It reached a maximum around 5--6 days after the injury and then gradually disappeared. These findings show that laminin is an adhesive protein. The increase of laminin in regenerating liver and the adhesiveness of cells from such livers to laminin suggest a role for laminin in the maintenance of a proper tissue organization during liver regeneration.
3‐Silylated Cyclohexa‐1,4‐dienes as Precursors for Gaseous Hydrosilanes: The B(C6F5)3‐Catalyzed Transfer Hydrosilylation of Alkenes (2013)

Set Me3SiH free! The strong Lewis acid B(C6F5)3 catalyzes the release of hydrosilanes from 3-silylated cyclohexa-1,4-dienes with concomitant formation of benzene. Subsequent B(C6F5)3-catalyzed SiH bond activation allows for alkene hydrosilylation (see scheme). The net reaction is an ionic transfer hydrosilylation. The new technique is particularly attractive in the case of otherwise gaseous, highly flammable hydrosilanes. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Allosteric interactions prime androgen receptor dimerization and activation (2022)

The androgen receptor (AR) is a nuclear receptor that governs gene expression programs required for prostate development and male phenotype maintenance. Advanced prostate cancers display AR hyperactivation and transcriptome expansion, in part, through AR amplification and interaction with oncoprotein cofactors. Despite its biological importance, how AR domains and cofactors cooperate to bind DNA has remained elusive. Using single-particle cryo-electron microscopy, we isolated three conformations of AR bound to DNA, showing that AR forms a non-obligate dimer, with the buried dimer interface utilized by ancestral steroid receptors repurposed to facilitate cooperative DNA binding. We identify novel allosteric surfaces which are compromised in androgen insensitivity syndrome and reinforced by AR's oncoprotein cofactor, ERG, and by DNA-binding motifs. Finally, we present evidence that this plastic dimer interface may have been adopted for transactivation at the expense of DNA binding. Our work highlights how fine-tuning AR's cooperative interactions translate to consequences in development and disease.
An optical tap based on the twin waveguide laser-amplifier with asymmetric flared output waveguides (1992)

An optical tap based on the twin waveguide laser-amplifier with asymmetric flared output waveguides is presented. The new optical tap exhibits gain, allows the tap channel gain to be electrically controlled over a dynamic range of 30 dB, without greatly affecting the through channel gain and is optically broadband. The general features of the optical tap can be understood from coupled mode theory.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>