gebhart/patrepeval huggingface dataset:
Amino acid neighbours and detailed conformational analysis of cysteines in proteins (1999)

Here we present an investigation of the contacts that cysteines make with residues in their three-dimensional environment and a comprehensive analysis of the conformational features of 351 disulphide bridges in 131 non-homologous single-chain protein structures. Upstream half-cystines preferentially have downstream neighbours, whereas downstream half-cystines have mainly upstream neighbours. Non-disulphide bridged cysteines (free cysteines) have no preference for upstream or downstream neighbours. Free cysteines have more contacts to non-polar residues and fewer contacts to polar/charged residues than half-cystines, which correlates with our observation that free cysteines are more buried than half-cystines. Free cysteines prefer to be located in alpha-helices while no clear preference is observed for half-cystines. Histidine and methionine are preferentially seen nearby free cysteines. Tryptophan is found preferentially nearby half-cystines. We have merged sequential and spatial information, and highly interesting novel patterns have been discovered. The number of cysteines per protein is typically an even number, peaking at four. The number of residues separating two half-cystines is preferentially 11 and 16. Left-handed and right-handed disulphide bridges display different conformational parameters. Here we present side chain torsion angle information based on a 5-12 times larger number of disulphide bridges than has previously been published. Considering the importance of cysteines for maintaining the 3D-structural scaffold of proteins, it is essential to have as accurate information as possible concerning the packing and conformational preferences. The present work may provide key information for engineering the protein environment around cysteines.
PAR-2 Inhibition Reverses Experimental Pulmonary Hypertension (2012)

Our study identified a novel role of PAR-2 in vascular remodeling in the lung. Interference with this pathway may offer novel therapeutic options for the treatment of PH.
The MPEG-4 video standard verification model (1997)

The MPEG-4 standardization phase has the mandate to develop algorithms for audio-visual coding allowing for interactivity, high compression, and/or universal accessibility and portability of audio and video content. In addition to the conventional "frame"-based functionalities of the MPEG-1 and MPEG-2 standards, the MPEG-4 video coding algorithm will also support access and manipulation of "objects" within video scenes. The January 1996 MPEG Video Group meeting witnessed the definition of the first version of the MPEG-4 video verification model-a milestone in the development of the MPEG-4 standard. The primary intent of the video verification model is to provide a fully defined core video coding algorithm platform for the development of the standard. As such, the structure of the MPEG-4 video verification model already gives some indication about the tools and algorithms that will be provided by the final MPEG-4 standard. The paper describes the scope of the MPEG-4 video standard and outlines the structure of the MPEG-4 video verification model under development.
Sacral neuromodulation and intravesical botulinum toxin for refractory overactive bladder (2012)

Both intravesical BTX and SNM have been shown to be effective treatment options for OAB. Further research is needed to determine equivalence or if one therapy is superior and to identify the ideal patient population for each therapy.
Tissue-specific RNA interference in postimplantation mouse embryos with endoribonuclease-prepared short interfering RNA (2002)

RNA interference (RNAi) using double-stranded RNA has been used for the systematic analysis of gene function in invertebrate organisms. Here we have explored the use of short interfering RNA (siRNA) to knock down gene expression during the development of mammalian postimplantation embryos. The developing CNS system of embryonic day 10 mouse embryos was used as a model tissue. siRNA prepared by endoribonuclease digestion (esiRNA) was injected into the lumen of the neural tube at specific regions and delivered into neuroepithelial cells by directed electroporation. Injected and electroporated embryos were grown for 1 day in whole-embryo culture and the effects of RNAi were examined. esiRNA directed against beta-galactosidase (beta-gal), coelectroporated into neuroepithelial cells together with reporter plasmids expressing GFP and beta-gal, abolished expression of beta-gal but not GFP, showing the specificity of the esiRNA-mediated RNAi. To demonstrate RNAi of endogenous gene expression, we used heterozygous embryos of a knock-in mouse line expressing GFP from the Tis21 locus, a gene turned on in neuroepithelial cells that switch from proliferation to neurogenesis. GFP-directed esiRNA electroporated into neuroepithelial cells of such embryos blocked the GFP expression normally occurring on the onset of neurogenesis. Taken together, our data indicate that esiRNA delivered in a tissue-specific manner by topical injection followed by directed electroporation can efficiently silence endogenous gene expression in mammalian postimplantation embryos.
Three-dimensional multicriterion automatic segmentation of pulmonary nodules of helical computed tomography images (1999)

A 3-D multicriterion automatic segmentation algorithm is de- veloped to improve accuracy of delineation of pulmonary nodules on helical computed tomography (CT) images by removing their adjacent structures. The algorithm applies multiple gray-value thresholds to a nodule region of interest (ROI). At each threshold level, the nodule can- didate in the ROI is automatically detected by labeling 3-D connected components, followed by a 3-D morphologic opening operation. Once the nodule candidate is found, its two specific parameters, gradient strength of the nodule surface and a 3-D shape compactness factor, can be computed. The optimal threshold can be determined by analyzing these parameters. Our experiments with in vivo nodules demonstrate the feasibility of employing this algorithm to improve the accuracy of nodule delineation, especially for small nodules less than 1 cm in diameter. This discloses the potential of the algorithm for accurate characterizations of nodules (e.g., volume, change in volume over time) at an early stage, which can help to provide valuable guidance for further clinical manage- ment. © 1999 Society of Photo-Optical Instrumentation Engineers. (S0091-3286(99)00708-4)
Activation of a caspase-9-mediated apoptotic pathway by subcellular redistribution of the novel caspase recruitment domain protein TMS1. (2000)

Genetic and epigenetic alterations affecting proteins involved in apoptosis can contribute to the establishment and progression of cancer. Recently, our laboratory has isolated a novel gene, TMS1, that is aberrantly methylated and silenced in a significant proportion of human breast cancers. TMS1 contains a caspase recruitment domain (CARD), suggesting a role in caspase-mediated cell death. In the present study, we characterize the participation of TMS1 in apoptosis and examine the subcellular localization of the protein. Inducible expression of TMS1 inhibited cellular proliferation and induced DNA fragmentation in a time-dependent manner. These apoptotic events were blocked by the general caspase inhibitor, Z-VAD-fmk. The ability of TMS1 to trigger apoptosis was also suppressed by a dominant negative form of caspase-9 but not by a dominant negative form of caspase-8, indicating that TMS1 functions through activation of caspase-9. Unlike a number of other CARD-containing proteins, TMS1 did not activate nuclear factor kappaB-dependent transcription, consistent with a proapoptotic role for TMS1 in death signaling pathways. Timed localization studies revealed that TMS1-induced apoptosis was accompanied by the redistribution of TMS1 from the cytoplasm to perinuclear spherical structures. Whereas the apoptotic activity of TMS1 was blocked by caspase inhibition, the formation of TMS1-containing subcellular structures was not, suggesting that the redistribution of TMS1 precedes caspase activation. Both the proapoptotic activity of TMS1 and aggregate formation were dependent on the CARD. In summary, the data indicate that TMS1-induced apoptosis proceeds through a CARD-dependent aggregation step followed by activation of a caspase-9-mediated pathway.
In healthy volunteers responses to challenge with cholecystokinin tetrapeptide differ between administration during REM and delta sleep (2001)

This study was designed to examine the sensitivity of different sleep stages to the pharmacological provocation of nocturnal panic attacks by cholecystokinin tetrapeptide (CCK-4). In a balanced cross-over design, healthy participants were challenged with identical doses of CCK-4 both during REM sleep and during delta sleep. In nine subjects, stimulation with 50 microg CCK-4 during REM sleep failed to elicit a full-blown panic awakening, while the same dose, administered during delta sleep, produced full-blown panic attacks in two participants. Similarly, stimulation of six subjects with 100 microg CCK-4 during REM sleep resulted in only one panic response, whereas four of nine subjects awoke experiencing a panic attack following stimulation with the identical dose during delta sleep. Severity of panic symptomatology, as measured by the self-rated Acute Panic Inventory, was also significantly increased when CCK-4 was administered during delta sleep. CCK-4 can be used as a challenge agent with an abrupt onset of action making it possible to provoke panic attacks precisely during a particular sleep stage. Sensitivity to the panicogenic effects of CCK-4 seems to be higher during delta sleep than REM sleep.
Improving Prediction of Ischemic Cardiovascular Disease in the General Population Using Apolipoprotein B (2006)

ApoB predicts ischemic cardiovascular events in both genders, and is better than low-density lipoprotein cholesterol in this respect. We suggest that prediction of future ischemic cardiovascular events could be improved by measuring apoB.
High-frequency distortion analysis of analog integrated circuits (1999)

An approach is presented for the analysis of the nonlinear behavior of analog integrated circuits. The approach is based on a variant of the Volterra series approach for frequency domain analysis of weakly nonlinear circuits with one input port, such as amplifiers, and with more than one input port, such as analog mixers and multipliers. By coupling numerical results with symbolic results, both obtained with this method, insight into the nonlinear operation of analog integrated circuits can be gained. For accurate distortion computations, the accuracy of the transistor models is critical. A MOS transistor model is discussed that allows us to explain the measured fourth-order nonlinear behavior of a 1 GHz CMOS upconverter. Further, the method is illustrated with several examples, including the analysis of an operational amplifier up to its gain-bandwidth product. This example has also been verified experimentally.
Large Area Electronics Using Printing Methods (2005)

After the demonstration of the first organic FET in 1986, a new era in the field of electronic began: the era of organic electronics. Although the reported performance of organic transistors is still considerably lower compared to that of silicon transistors, a new market is open for organic devices, where the excellent performance of silicon technology is not required. Several commercial applications for organic electronics have been suggested: organic RFID tags, electronic papers, imagers, sensors, organic LED drivers, etc. The main advantage of organic technologies over silicon technologies is the possibility of making low-cost, large area electronics. The main processes which allow patterning with suitable resolution on a large areas are printing methods. Here we will provide an overview of methods that can be useful in the low-cost production of large area electronics.
Recent advances in Gd-chelate based bimodal optical/MRI contrast agents (2015)

Research on bimodal contrast agents in general and optical/MRI contrast agents in particular has attracted increased attention from the scientific community in recent years. Whereas optical contrast agents reveal pathologies at the cellular or sub-cellular level, MRI contrast agents generally report physiological differences at the level of tissues and organs. The complementary information obtained from these two techniques allows for a more precise diagnosis. Furthermore the emergence of near-infrared luminophores accommodates the simultaneous detection of optical and MRI signals. The current multitude and diversity in molecular architectures mirrors the ever increasing interest in the field. In this review the developments between 2010 and mid-2014 are highlighted.
Deficiency of α-mannosidase in Angus cattle. An inherited lysosomal storage disease (1972)

A disease of Angus cattle previously known as pseudolipidosis has been shown to be an inherited lysosomal storage disease, in which an oligosaccharide containing mannose and glucosamine is the storage substance. Diseased animals have a near-absolute deficiency of the lysosomal enzyme, alpha-mannosidase, whereas heterozygotes have a partial deficiency of this enzyme. The condition is analogous to the human disease known as mannosidosis.
ChemInform Abstract: STUDIES ON THE REACTIVITY OF 2‐METHYL‐3‐PHENYL‐4(3H)‐QUINAZOLINONE (1980)

Abstract Die Titelverbindung (II) reagiert mit Paraformaldehyd und Piperidin zu der Mannichbase (I) und liefert mit Acrylnitril in Gegenwart von Na‐t‐butoxid in DMF durch Michael‐Addition das Derivat (III).
Submicron separation of microspheres via travelling surface acoustic waves (2014)

Submicron separation is the segregation of particles having a diameter difference of less than one micrometre. We present an acoustofluidic particle separator with submicron separation resolution to study the continuous, label-free, and contactless separation of polystyrene (PS) particles based on their acoustofluidic parameters such as size, density, compressibility and shape. In this work, the submicron separation of PS microspheres, having a marginal size difference, is achieved inside a polydimethylsiloxane (PDMS) microfluidic channel via travelling surface acoustic waves (TSAWs). The TSAWs of different frequencies (200, 192, 155, and 129 MHz), propagating normal to the fluid flow direction inside the PDMS microchannel, realized continuous separation of particles with a diameter difference as low as 200 nm. A theoretical framework based on the rigid and elastic theories is presented to support the experimental results.
Cellulose structure and biosynthesis: What is in store for the 21st century? (2003)

Abstract This article briefly summarizes historical developments in fundamental research related to the structure and biosynthesis of cellulose. Major advances concerning the structure of cellulose include the discovery of a new suballomorph of cellulose I, the lattice imaging of glucan chains showing no fringe micelle structure, parallel chain orientation in cellulose I, and the discovery of nematic ordered cellulose. Major advances in biosynthesis include the discovery of the terminal synthesizing complex, the isolation and purification of cellulose synthase, the in vitro synthesis of cellulose I, and synthetic cellulose assembly. This article focuses on recent advances in molecular biology with cellulose, including the cloning and sequencing of cellulose synthase genes from bacteria, cyanobacteria, and vascular plants; proof of the terminal synthesizing complex as the site of the catalytic subunit of cellulose synthase; cellulose and callose synthase expression during growth and development; and phylogenetic aspects of cellulose synthase evolution. This article concludes with thoughts about future uses for the accumulating genetic information on cellulose biosynthesis for textiles and forest products and discusses possibilities of new global resources for cellulose production. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 487–495, 2004
Atrial Fibrillation and Thromboembolism: A Decade of Progress in Stroke Prevention (1999)

Atrial fibrillation is associated with a sixfold increased risk for stroke. More than a dozen published randomized trials of anticoagulants or antiplatelet agents for stroke prevention provide solid evidence on which to base antithrombotic prophylaxis. Adjusted-dose warfarin reduces risk for stroke by about 60% compared with placebo, aspirin reduces this risk (primarily for nondisabling stroke) by about 20% compared with placebo, and warfarin reduces it by about 40% compared with aspirin. Warfarin provides maximal protection against stroke at international normalized ratios of 2.0 to 3.0. Risk stratification of patients with atrial fibrillation identifies those who potentially benefit most or least from anticoagulation; this is important because a substantial percentage of patients with atrial fibrillation have relatively low rates of stroke if they are given aspirin. Many elderly patients with recurrent intermittent atrial fibrillation experience high rates of stroke and benefit from anticoagulation. The value of precordial or transesophageal echocardiography in addition to clinical risk stratifiers for stratifying stroke risk is controversial. Altered hemostasis favoring thrombosis may contribute to formation of atrial appendage thrombus, but these conditions remain ill defined. The past decade has brought unprecedented progress toward understanding thromboembolism in patients with atrial fibrillation and has changed the clinical perspective of a prevalent cardiac arrhythmia into an important opportunity for stroke prevention. Making the most of this promise calls for appreciation of the epidemiology of atrial fibrillation and the concept of risk specificity in the face of diverse therapeutic options.
New Insights into Checkpoint Kinase 1 in the DNA Damage Response Signaling Network (2010)

The DNA damage response (DDR) represents a complex network of multiple signaling pathways involving cell cycle checkpoints, DNA repair, transcriptional programs, and apoptosis, through which cells maintain genomic integrity following various endogenous (metabolic) or environmental stresses. In cancer treatment, the DDR occurs in response to various genotoxic insults by diverse cytotoxic agents and radiation, representing an important mechanism limiting chemotherapeutic and radiotherapeutic efficacy. This has prompted the development of agents targeting DDR signaling pathways, particularly checkpoint kinase 1 (Chk1), which contributes to all currently defined cell cycle checkpoints, including G1/S, intra-S-phase, G2/M, and the mitotic spindle checkpoint. Although numerous agents have been developed with the primary goal of enhancing the activity of DNA-damaging agents or radiation, the therapeutic outcome of this strategy remains to be determined. Recently, new insights into DDR signaling pathways support the notion that Chk1 represents a core component central to the entire DDR, including direct involvement in DNA repair and apoptotic events in addition to checkpoint regulation. Together, these new insights into the role of Chk1 in the DDR machinery could provide an opportunity for novel approaches to the development of Chk1 inhibitor strategies.
Additivity of mutational effects in proteins (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAdditivity of mutational effects in proteinsJames A. WellsCite this: Biochemistry 1990, 29, 37, 8509–8517Publication Date (Print):September 18, 1990Publication History Published online1 May 2002Published inissue 18 September 1990https://doi.org/10.1021/bi00489a001RIGHTS & PERMISSIONSArticle Views1702Altmetric-Citations478LEARN 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 (2 MB) Get e-Alerts Get e-Alerts
Identification of novel NRF2-regulated genes by ChIP-Seq: influence on retinoid X receptor alpha (2012)

Cellular oxidative and electrophilic stress triggers a protective response in mammals regulated by NRF2 (nuclear factor (erythroid-derived) 2-like; NFE2L2) binding to deoxyribonucleic acidregulatory sequences near stress-responsive genes. Studies using Nrf2-deficient mice suggest that hundreds of genes may be regulated by NRF2. To identify human NRF2-regulated genes, we conducted chromatin immunoprecipitation (ChIP)-sequencing experiments in lymphoid cells treated with the dietary isothiocyanate, sulforaphane (SFN) and carried out follow-up biological experiments on candidates. We found 242 high confidence, NRF2-bound genomic regions and 96% of these regions contained NRF2regulatory sequence motifs. The majority of binding sites were near potential novel members of the NRF2 pathway. Validation of selected candidate genes using parallel ChIP techniques and in NRF2-silenced cell lines indicated that the expression of about two-thirds of the candidates are likely to be directly NRF2-dependent including retinoid X receptor alpha (RXRA). NRF2 regulation of RXRA has implications for response to retinoid treatments and adipogenesis. In mouse, 3T3-L1 cells' SFN treatment affected Rxra expression early in adipogenesis, and knockdown of Nrf2-delayed Rxra expression, both leading to impaired adipogenesis.
Identification and characterization of murine caspase-14, a new member of the caspase family. (1998)

We report here the identification and characterization of a new member of the mouse caspase family, named caspase-14. Northern blot analysis of mRNA from various tissues with caspase-14-specific probe showed a major transcript size of approximately 2.4 kb and variant transcripts of 2.0 kb and 1.5 kb. The major transcript is detected mainly in the liver and to a lesser extent in the brain and kidney. Caspase-14 cDNA encodes a 257-amino acid-long protein that has significant homology to other members of the caspase family. Like other caspases, caspase-14 has a conserved active site, pentapeptide QACRG. However, it lacks an NH2-terminal prodomain or a caspase recruitment domain, suggesting that it could be a downstream caspase that depends on other initiator caspases for activation. Consistent with this, procaspase-14 can be processed in vitro by the death receptor-associated caspase-8 and caspase-10 but not other caspases, and in vivo after stimulation of cells with anti-Fas agonist antibody or Tumor Necrosis Factor-Related Apoptosis Inducing Ligand. Furthermore, procaspase-14 can be cleaved by granzyme B. These observations suggest that caspase-14 may play a role in death receptor and granzyme B-induced apoptosis.
A Simple Synthetic Approach to Allylated Aromatics via the Suzuki-Miyaura Cross-Coupling Reaction (2005)

The Pd-catalyzed cross-coupling reaction of aromatic iodides and bromides with allylboronic acid esters (2a,b) in the presence of CsF gave allylated aromatics.