gebhart/patrepeval huggingface dataset:
Reactivity of Biarylazacyclooctynones in Copper-Free Click Chemistry (2012)

The 1,3-dipolar cycloaddition of cyclooctynes with azides, also called "copper-free click chemistry", is a bioorthogonal reaction with widespread applications in biological discovery. The kinetics of this reaction are of paramount importance for studies of dynamic processes, particularly in living subjects. Here we performed a systematic analysis of the effects of strain and electronics on the reactivity of cyclooctynes with azides through both experimental measurements and computational studies using a density functional theory (DFT) distortion/interaction transition state model. In particular, we focused on biarylazacyclooctynone (BARAC) because it reacts with azides faster than any other reported cyclooctyne and its modular synthesis facilitated rapid access to analogues. We found that substituents on BARAC's aryl rings can alter the calculated transition state interaction energy of the cycloaddition through electronic effects or the calculated distortion energy through steric effects. Experimental data confirmed that electronic perturbation of BARAC's aryl rings has a modest effect on reaction rate, whereas steric hindrance in the transition state can significantly retard the reaction. Drawing on these results, we analyzed the relationship between alkyne bond angles, which we determined using X-ray crystallography, and reactivity, quantified by experimental second-order rate constants, for a range of cyclooctynes. Our results suggest a correlation between decreased alkyne bond angle and increased cyclooctyne reactivity. Finally, we obtained structural and computational data that revealed the relationship between the conformation of BARAC's central lactam and compound reactivity. Collectively, these results indicate that the distortion/interaction model combined with bond angle analysis will enable predictions of cyclooctyne reactivity and the rational design of new reagents for copper-free click chemistry.
MicroRNA regulation in mantle cell lymphoma (2007)

8056 Mantle Cell Lymphoma (MCL) represents only 5–10% of all non-Hodgkins lymphomas, making it an uncommon but difficult form of lymphoma to treat. It has the worst prognosis among the B cell lymphomas with median survival of three years. The genetic hallmark of MCL is a t(11;14) q32 translocation which results in ectopic and dysregulated expression of cyclin D1. Recent comparative genomic hybridization studies have identied Syk as another gene important in the pathogenesis of MCL. Previous studies have suggested that post transcriptional regulation of Cyclin D1 and Syk may be important the pathogenesis of in MCL. MicroRNAs are a new class of abundant small RNAs that play important regulatory roles at the post transcriptional level by binding to the 3’ untranslated region (UTR) of mRNAs blocking either their translation or initiating their degradation. There have been numerous reports of misregulation of microRNAs and their targets in human cancers. We hypothesized that altered microRNA regulation of cyclin D1 and/or Syk may be present in MCL. Based on bioinformatics, we identified 8 microRNAs and their putative docking sites in either Cyclin D1 and Syk. We then examined their integrity in MCL cell lines, and identified a mutation in the 3’UTR of Syk at the docking site of 1 mir-452* and a SNP in mir-458. Using a GFP reporter construct with the mutated Syk 3’UTR we demonstrated that this mutation resulted in altered microRNA function. We also show that mimics of the microRNA leads to down regulation of Syk protein. This data suggests that microRNA regulation of important genes in MCL may be compromised and play a role in the development and progression of this disease. No significant financial relationships to disclose.
A Bayesian View on Cryo-EM Structure Determination (2011)

Three-dimensional (3D) structure determination by single-particle analysis of cryo-electron microscopy (cryo-EM) images requires many parameters to be determined from extremely noisy data. This makes the method prone to overfitting, that is, when structures describe noise rather than signal, in particular near their resolution limit where noise levels are highest. Cryo-EM structures are typically filtered using ad hoc procedures to prevent overfitting, but the tuning of arbitrary parameters may lead to subjectivity in the results. I describe a Bayesian interpretation of cryo-EM structure determination, where smoothness in the reconstructed density is imposed through a Gaussian prior in the Fourier domain. The statistical framework dictates how data and prior knowledge should be combined, so that the optimal 3D linear filter is obtained without the need for arbitrariness and objective resolution estimates may be obtained. Application to experimental data indicates that the statistical approach yields more reliable structures than existing methods and is capable of detecting smaller classes in data sets that contain multiple different structures.
Computed tomography angiography vs 3 T black-blood cardiovascular magnetic resonance for identification of symptomatic carotid plaques (2014)

Bb-CMR is superior to MDCTA at identifying symptomatic carotid plaques, while MDCTA offers high specificity at the cost of low sensitivity. Results were only slightly improved over bb-CMR alone when combining both techniques.
Microprocessor Controlled, Variable Intensity, Variable Timing, Rainfall Simulator (1986)

The South Australian Department of Agriculture has completed the construction of a rainfall simulator. Its main features include excellent uniformity of water distribution on the target area, ease of operation in the field and repeatability of various and variable rainfall intensities. These attributes are necessary for field measurements of infiltration, the effects of surface management systems and some soil erodibility factor determinations. This paper discusses the criteria used in the initial design, problems and the final design, especially the achievement of uniformity of water distribution patterns.
Effect of a calcitonin gene‐related peptide antagonist (CGRP8–37) on skin vasodilatation and oedema induced by stimulation of the rat saphenous nerve (1993)

1. The effect of the calcitonin gene-related peptide antagonist (CGRP8-37, 400 nmol kg-1, i.v.) on the increased blood flow induced by calcitonin gene related peptide (CGRP), vasodilator prostaglandins, and topical capsaicin was measured with a laser Doppler blood flow meter in rat abdominal skin. 2. The saphenous nerve was electrically stimulated and the effect of CGRP8-37 (400 nmol kg-1, i.v.) on the increased blood flow (measured by laser Doppler flowmetry) and oedema formation (measured by the extravascular accumulation of [125I]-albumin) was investigated in the rat hind paw. 3. CGRP8-37 (400 nmol kg-1, i.v.) had no effect on basal cutaneous blood flow at uninjected sites and sites injected with Tyrode buffer, but acted selectively to inhibit the increased blood flow induced by intradermal CGRP (10 pmol/site, P < 0.05), but not that induced by prostaglandin E2 (PGE2, 300 pmol/site) or carba-prostacyclin (cPGI2, 100 pmol/site). 4. Capsaicin (0.1-33 mM), applied topically, acted in a dose-related manner to increase blood flow. CGRP8-37 (400 nmol kg-1, i.v.) almost totally inhibited blood flow induced by capsaicin (10 mM; P < 0.05) but did not significantly inhibit blood flow induced by a higher dose of capsaicin (33 mM). 5. The increased blood flow induced by short stimulation of the saphenous nerve (10 V, 1 ms, 2 Hz for 30 s) was inhibited by 76%, 5 min after i.v. CGRP8-37 (400 nmol kg-1, i.v., P < 0.05). 6. A longer (5 min) electrical stimulation of the saphenous nerve caused oedema formation, in addition to increased blood flow. The oedema formation was significantly inhibited by CGRP8-37 (400 nmol kg-1,i.v., P<0.05).7. The results suggest that the potent microvascular vasodilator neuropeptide, CGRP, is responsible for the increased blood flow observed after short stimulation of the saphenous nerve and that endogenous CGRP contributes in a pro-inflammatory manner to neurogenic oedema formation in the rat hind paw.
Ultra-narrow-linewidth Al_2O_3:Er^3+ lasers with a wavelength-insensitive waveguide design on a wafer-scale silicon nitride platform (2017)

We report ultra-narrow-linewidth erbium-doped aluminum oxide (Al<sub>2</sub>O<sub>3</sub>:Er<sup>3+</sup>) distributed feedback (DFB) lasers with a wavelength-insensitive silicon-compatible waveguide design. The waveguide consists of five silicon nitride (SiN<sub>x</sub>) segments buried under silicon dioxide (SiO<sub>2</sub>) with a layer Al<sub>2</sub>O<sub>3</sub>:Er<sup>3+</sup> deposited on top. This design has a high confinement factor (> 85%) and a near perfect (> 98%) intensity overlap for an octave-spanning range across near infra-red wavelengths (950-2000 nm). We compare the performance of DFB lasers in discrete quarter phase shifted (QPS) cavity and distributed phase shifted (DPS) cavity. Using QPS-DFB configuration, we obtain maximum output powers of 0.41 mW, 0.76 mW, and 0.47 mW at widely spaced wavelengths within both the C and L bands of the erbium gain spectrum (1536 nm, 1566 nm, and 1596 nm). In a DPS cavity, we achieve an order of magnitude improvement in maximum output power (5.43 mW) and a side mode suppression ratio (SMSR) of > 59.4 dB at an emission wavelength of 1565 nm. We observe an ultra-narrow linewidth of ΔνDPS = 5.3 ± 0.3 kHz for the DPS-DFB laser, as compared to ΔνQPS = 30.4 ± 1.1 kHz for the QPS-DFB laser, measured by a recirculating self-heterodyne delayed interferometer (R-SHDI).
Overview of Antibody Phage-Display Technology and Its Applications (2003)

The generation of new drugs has long involved the screening of hundreds of thousands of components with well defined in vitro tests, seeking compounds to mimic as closely as possible the desired in vivo activity of the new drug. New library methodologies offer many alternative routes that are at least as powerful as traditional approaches by combining the generation of billions of components with a fast screening or selection procedure to identify the most interesting lead candidates. One of the most widely used library methodologies is based on the use of filamentous phage (1), a virus that lives on Escherichia coli. Phage display has proven to be a powerful technique for the interrogation of libraries containing millions or even billions of different peptides or proteins. One of the most successful applications of phage display has been the isolation of monoclonal antibodies using large phage antibody libraries (2,3). This chapter reviews the progress made in this rapidly developing field and discusses a broad range of applications, including the use of large phage Ab libraries to discover novel therapeutic targets and methods for selection of biologically active ligands. Finally, it addresses the potential of combining phage display with complementary methods to increase the scope and range of applications of this technology.
Emerging topic detection on Twitter based on temporal and social terms evaluation (2010)

Twitter is a user-generated content system that allows its users to share short text messages, called tweets, for a variety of purposes, including daily conversations, URLs sharing and information news. Considering its world-wide distributed network of users of any age and social condition, it represents a low level news flashes portal that, in its impressive short response time, has the principal advantage.In this paper we recognize this primary role of Twitter and we propose a novel topic detection technique that permits to retrieve in real-time the most emergent topics expressed by the community. First, we extract the contents (set of terms) of the tweets and model the term life cycle according to a novel aging theory intended to mine the emerging ones. A term can be defined as emerging if it frequently occurs in the specified time interval and it was relatively rare in the past. Moreover, considering that the importance of a content also depends on its source, we analyze the social relationships in the network with the well-known Page Rank algorithm in order to determine the authority of the users. Finally, we leverage a navigable topic graph which connects the emerging terms with other semantically related keywords, allowing the detection of the emerging topics, under user-specified time constraints. We provide different case studies which show the validity of the proposed approach.
Continuous-Infusion Floxuridine and Alpha Interferon in Metastatic Renal Cancer: A National Biotherapy Study Group Phase II Study (1999)

Eighteen patients with advanced renal cancer were treated with 0.15 mg/kg/day floxuridine by continuous intravenous infusion for 14 days with 3 million IU/m2/day alpha interferon subcutaneously three times weekly. Treatment cycles were repeated every 28 days. Floxuridine dosages were escalated to a maximum of 0.2 mg/kg/day and alpha interferon dosages were escalated to a maximum of 6 million IU/m2/day depending on patient tolerability. A total of 49 treatment courses were administered with a median of 2.7 courses per patient. Of 14 assessable patients, there were no complete or partial responses. Eight patients (57%) had stabilization of disease. The median survival for patients with stable disease was 20.9 months and for all 18 patients was 7.2 months. Grades 3 and 4 toxicities included diarrhea (44%), nausea/vomiting (28%), mucositis (11%), fever (22%), and fatigue (50%). Dose-limiting toxicities were primarily gastrointestinal symptoms. There were no treatment-related deaths. This combination in the dose schedule used did not result in any significant objective tumor response but was associated with considerable toxicity.
The Structure and Function of Ficolins, MBLs and MASPs (2008)

In this review we focus on the structure and function of mannose-binding lectin (MBL) and ficolins and their interactions with MBL-associated serine proteases (MASPs) to initiate activation of the lectin pathway of complement. Work carried out by Jinhua Lu and Steffen Thiel in 1990, in Ken Reid's gr...
Truncation of the extended carboxyl-terminal domain increases the expression and regulatory activity of the avian beta-adrenergic receptor (1991)

A series of mutant avian beta-adrenergic receptors with progressively truncated carboxyl termini have been expressed in insect and mammalian cells. Removal of 18-124 amino acid residues caused multiple phenotypic changes in the receptor. Membranes from cells that expressed the truncated receptors displayed elevated basal (2- to 3-fold) and agonist-stimulated adenylylcyclase activities. Adenylylcyclase activity in these membranes also displayed greater stimulation in response to partial agonists. Activity was also markedly stimulated by beta-adrenergic ligands that are usually considered to be antagonists (alprenolol, greater than 4-fold; propranolol, approximately 2-fold). Wild type receptor did not mediate a response to these classical antagonists. After purification and reconstitution with Gs, the truncated receptors did not appear to be more active than the wild type. Guanine nucleotides modulated the affinity of agonist for the truncated receptors, whereas the affinity of agonist for the wild type receptor was not altered by guanine nucleotides. The truncated receptors were solubilized from the membrane more efficiently and were more susceptible to amino-terminal proteolysis than was the wild type protein. These results suggest interaction of the carboxyl terminus of the avian beta-adrenergic receptor with cellular regulatory or structural elements.
Effects of Diet and Exercise in Men and Postmenopausal Women with Low Levels of HDL Cholesterol and High Levels of LDL Cholesterol (1998)

The NCEP Step 2 diet failed to lower LDL cholesterol levels in men or women with high-risk lipoprotein levels who did not engage in aerobic exercise. This finding highlights the importance of physical activity in the treatment of elevated LDL cholesterol levels.
Thiazole and oxazole peptides: biosynthesis and molecular machinery (1999)

R. Sinha Roy, A. M. Gehring, J. C. Milne, P. J. Belshaw and C. T. Walsh, Nat. Prod. Rep., 1999, 16, 249 DOI: 10.1039/A806930A
Community structure in social and biological networks (2002)

A number of recent studies have focused on the statistical properties of networked systems such as social networks and the Worldwide Web. Researchers have concentrated particularly on a few properties that seem to be common to many networks: the small-world property, power-law degree distributions, and network transitivity. In this article, we highlight another property that is found in many networks, the property of community structure, in which network nodes are joined together in tightly knit groups, between which there are only looser connections. We propose a method for detecting such communities, built around the idea of using centrality indices to find community boundaries. We test our method on computer-generated and real-world graphs whose community structure is already known and find that the method detects this known structure with high sensitivity and reliability. We also apply the method to two networks whose community structure is not well known--a collaboration network and a food web--and find that it detects significant and informative community divisions in both cases.
Modern technologies for improving cleaning and disinfection of environmental surfaces in hospitals (2016)

Experts agree that careful cleaning and disinfection of environmental surfaces are essential elements of effective infection prevention programs. However, traditional manual cleaning and disinfection practices in hospitals are often suboptimal. This is often due in part to a variety of personnel issues that many Environmental Services departments encounter. Failure to follow manufacturer’s recommendations for disinfectant use and lack of antimicrobial activity of some disinfectants against healthcare-associated pathogens may also affect the efficacy of disinfection practices. Improved hydrogen peroxide-based liquid surface disinfectants and a combination product containing peracetic acid and hydrogen peroxide are effective alternatives to disinfectants currently in widespread use, and electrolyzed water (hypochlorous acid) and cold atmospheric pressure plasma show potential for use in hospitals. Creating “self-disinfecting” surfaces by coating medical equipment with metals such as copper or silver, or applying liquid compounds that have persistent antimicrobial activity surfaces are additional strategies that require further investigation. Newer “no-touch” (automated) decontamination technologies include aerosol and vaporized hydrogen peroxide, mobile devices that emit continuous ultraviolet (UV-C) light, a pulsed-xenon UV light system, and use of high-intensity narrow-spectrum (405 nm) light. These “no-touch” technologies have been shown to reduce bacterial contamination of surfaces. A micro-condensation hydrogen peroxide system has been associated in multiple studies with reductions in healthcare-associated colonization or infection, while there is more limited evidence of infection reduction by the pulsed-xenon system. A recently completed prospective, randomized controlled trial of continuous UV-C light should help determine the extent to which this technology can reduce healthcare-associated colonization and infections. In conclusion, continued efforts to improve traditional manual disinfection of surfaces are needed. In addition, Environmental Services departments should consider the use of newer disinfectants and no-touch decontamination technologies to improve disinfection of surfaces in healthcare.
Coupling effects in high-resistivity SIMOX substrates for VHF and microwave applications (2002)

The use of high-resistivity SIMOX substrates has been proposed to enable the integration of low-loss adapted lines for MMIC applications in SOI CMOS technology. In this work we investigate the impact of the substrate resistivity on another important substrate coupling effect: the intrinsic load impedance of active transistors in amplifier configuration, which conditions the device maximum stable frequency. Related device and line modelling aspects are also discussed.
Motion estimation based on time-sequentially sampled imagery (1995)

Determining the parameters of motion within a time-varying scene is an important problem in such fields as computer vision, motion compensated video coding, and tracking. Most motion estimation algorithms operate on image data that has been sampled in both space and time. However, very little work has been done to investigate the impact of the underlying sampling strategy on the motion estimation problem. The authors investigate motion estimation with time-sequentially sampled image data. They consider both centroid-displacement-based and Fourier-based approaches to motion estimation with this type of data. For comparision, they also examine the performance of these estimators with conventional, frame-instantaneously sampled data. The motion estimators are developed and evaluated in the context of the tracking problem. In particular, they present extensive numerical results showing the performance of the motion estimators in a simulated tracking environment within which the assumptions underlying the development of the estimators are violated. These results suggest empirical rules for choosing parameter values for the estimators.
Self-Assembled Monolayers of Alkanethiolates Presenting Tri(propylene sulfoxide) Groups Resist the Adsorption of Protein (1996)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTSelf-Assembled Monolayers of Alkanethiolates Presenting Tri(propylene sulfoxide) Groups Resist the Adsorption of ProteinLi Deng, Milan Mrksich, and George M. WhitesidesView Author Information Department of Chemistry, Harvard University Cambridge, Massachusetts 02138 Cite this: J. Am. Chem. Soc. 1996, 118, 21, 5136–5137Publication Date (Web):May 29, 1996Publication History Received13 February 1996Published online29 May 1996Published inissue 1 January 1996https://pubs.acs.org/doi/10.1021/ja960461dhttps://doi.org/10.1021/ja960461drapid-communicationACS PublicationsCopyright © 1996 American Chemical SocietyRequest reuse permissionsArticle Views1058Altmetric-Citations109LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (2)»Supporting Information Supporting Information SUBJECTS:Adsorption,Alcohols,Alkyls,Oxides,Peptides and proteins Get e-Alerts
Influence of structure on the isomerization of dialkylaminoalkylbenzotriazoles (1990)

Abstract The N‐1 to N‐2 substituent isomerization in a series of 4‐methyl and 4,7‐dimethyl‐ N ‐(α‐morpholinoalkyl)benzotriazoles and in 1,5‐bis(morpholinomethyl)benzo [1,2‐ d :4,5‐ d ′] bistriazole was studied and the influence of the structure on this process was evaluated.