gebhart/patrepeval huggingface dataset:
Electrophysiologic Characterization of Dronedarone in Guinea Pig Ventricular Cells (2003)

The electrophysiological properties of dronedarone (SR33589), a noniodinated amiodarone-like agent, were studied on action potential (AP) and contraction of papillary muscle and on membrane ionic currents, Ca2+ transient, and shortening of ventricular cells of the guinea pig heart. In multicellular preparations, dronedarone (3, 10, and 30 microM) decreased maximum rate of rise of AP (dV/dt max) with a concentration- and frequency-dependent relationship; resting potential was not modified and AP amplitude was decreased only at 30 microM. The effects of dronedarone on AP durations (APDs) at different percentages of repolarization were not significantly changed, except for a slight decrease in APD30 and APD50 at the highest concentration. In isolated ventricular myocytes, dronedarone inhibited rapidly activating delayed-rectifier K+ current (I(Kr)) (median inhibitory concentration [IC50] </= 3 microM voltage-independent); slowly activating delayed-rectifier K+ current (I(Ks)) (IC50 approximately/= 10 microM voltage-dependent and time-, frequency-, or use-independent); and inward rectifier potassium current (I(K1)) (IC50 >/= 30 microM). Dronedarone blocked L-type Ca2+ current (I(Ca(L))) (IC50 = 0.18 +/- 0.018 microM at a stimulation frequency of 0.033 Hz) in a use- and frequency-dependent manner. Simultaneously to these electrophysiological effects, dronedarone reduced contraction amplitudes of papillary muscle and decreased Ca2+ transient and shortening of ventricular myocytes. The results show that dronedarone is a multichannel blocker because it decreases dV/dt max (I(Na)), I(Ca(L)), I(Kr), I(Ks), and I(K1). These effects are accompanied by a reduction in free intracellular calcium and contraction amplitudes. Dronedarone does not significantly change APD whatever the stimulation frequency. Our data demonstrate that the acute electrophysiological characteristics of dronedarone, despite absence of iodine in its molecular structure, are very similar to those of amiodarone in cardiac ventricle.
Synthesis and in vitro evaluation of 2,3-dimethoxy-5-(fluoroalkyl)-substituted benzamides: high-affinity ligands for CNS dopamine D2 receptors (1991)

A number of 2,3-dimethoxy-5-(fluoroalkyl)-N-[(1-ethyl-2- pyrrolidinyl)methyl]benzamides (with or without a 6-hydroxy group) were synthesized and evaluated as dopamine D2 receptor ligands. The parent acids were synthesized via the Claisen rearrangement of the appropriate O-allyl ethers, which were derived from o-vanillic acid or 2,3-dimethoxysalicylic acid. A decrease in reactivity was found to be characteristic of pentasubstituted benzoates, and difficulties were encountered with the introduction of fluorine onto the ethyl side chains. The (fluoroethyl)- and (fluoropropyl)salicylamides were 5 times more potent than the corresponding benzamides in inhibiting [3H]spiperone binding to the D2 receptor. These (fluoroalkyl)salicylamides are of potential value for in vivo positron emission tomography (PET) studies upon the basis of their relatively selective, high potency binding affinity for the D2 receptor.
Identification of a novel D6‐acyl‐group desaturase by targeted gene disruption in Physcomitrella patens (1998)

The moss Physcomitrella patens contains high levels of arachidonic acid. For its synthesis from linoleic acid by desaturation and elongation, novel delta 5- and delta 6-desaturases are required. To isolate one of these, PCR-based cloning was used, and resulted in the isolation of a full-length cDNA coding for a putatively new desaturase. The deduced amino acid sequence has three domains: a N-terminal segment of about 100 amino acids, with no similarity to any sequence in the data banks, followed by a cytochrome b5-related region and a C-terminal sequence with low similarity (27% identify) to acyl-lipid desaturases. To elucidate the function of this protein, we disrupted its gene by transforming P. patens with the corresponding linear genomic sequence, into which a positive selection marker had been inserted. The molecular analysis of five transformed lines showed that the selection cartridge had been inserted into the corresponding genomic locus of all five lines. The gene disruption resulted in a dramatic alteration of the fatty acid pattern in the knockout plants. The large increase in linoleic acid and the concomitant disappearance of gamma-linolenic and arachidonic acid in all knockout lines suggested that the new cDNA coded for a delta 6-desaturase. This was confirmed by expression of the cDNA in yeast and analysis of the resultant fatty acids by GC-MS. Only the transformed yeast cells were able to introduce a further double bond into the delta 6-position of unsaturated fatty acids. To our knowledge, this is the first report of a successful gene disruption in a multicellular plant resulting in a specific biochemical phenotype.
Learning domain-independent string transformation weights for high accuracy object identification (2002)

The task of object identification occurs when integrating information from multiple websites. The same data objects can exist in inconsistent text formats across sites, making it difficult to identify matching objects using exact text match. Previous methods of object identification have required manual construction of domain-specific string transformations or manual setting of general transformation parameter weights for recognizing format inconsistencies. This manual process can be time consuming and error-prone. We have developed an object identification system called Active Atlas [18], which applies a set of domain-independent string transformations to compare the objects' shared attributes in order to identify matching objects. In this paper, we discuss extensions to the Active Atlas system, which allow it to learn to tailor the weights of a set of general transformations to a specific application domain through limited user input. The experimental results demonstrate that this approach achieves higher accuracy and requires less user involvement than previous methods across various application domains.
Left Ventricular Septal and Left Ventricular Apical Pacing Chronically Maintain Cardiac Contractile Coordination, Pump Function and Efficiency (2009)

Acute and chronic LV apical and LV septal pacing maintain regional cardiac mechanics, contractility, relaxation, and efficiency near native levels, whereas RV apical or RV septal pacing diminish these variables. Acute LV apical and LV septal pacing tend to maintain or improve contractility and efficiency compared with biventricular pacing.
Using Web technologies in two MLS environments: a security analysis (2002)

Presents an analysis of the use of the HyperText Transfer Protocol (HTTP) and other Web technologies for multi-level secure (MLS) systems that are connected to single-level network environments (e.g. Internet-like and intranet-like environments). Multiple single-level networks may be connected to these MLS systems. This analysis considers two examples of MLS systems. Known HTTP and Web security vulnerabilities are considered in the context of multi-level operations planned for an MLS database server to be accessed by Web browser software and for an MLS infrastructure supporting Web browsing on multiple Webs that each have a different security sensitivity level. The analysis focuses on the transfer of information across security boundaries where the security classification of information on one side of the boundary differs from that of the other side (a high-to-low or low-to-high transfer of information). The transfer of information is initiated by the Web browser (a network client) and the bulk of information transferred is data returned from the Web server. The analysis also focuses on threats from the less secure side of the boundary, including the threats of insertion of malicious code (e.g. virus or Trojan horse code) and denial-of-service attacks. The applications are referred to as the "high-to-low" example and the "low-to-high" example, denoting the direction of primary information flow.
A simple and efficient connected components labeling algorithm (2003)

We describe a two-scan algorithm for labeling connected components in binary images in raster format. Unlike the classical two-scan approach, our algorithm processes equivalences during the first scan by merging equivalence classes as soon as a new equivalence is found. We show that this significantly improves the efficiency of the labeling process with respect to the classical approach. The data structure used to support the handling of equivalences is a 1D-array. This renders the more frequent operation of finding class identifiers very fast, while the less-frequent class-merging operation has a relatively high computational cost. Nonetheless, it is possible to reduce significantly the merging cost by two slight modifications to the algorithm's basic structure. The idea of merging equivalence classes is present also in Samet's general labeling algorithm. However when considering the case of binary images in raster format this algorithm is much more complex than the one we describe in this paper.
Integration of Gene Dosage and Gene Expression in Non-Small Cell Lung Cancer, Identification of HSP90 as Potential Target (2008)

We suggest that targeting HSP90 will have clinical impact for NSCLC patients.
Role of p38 Protein Kinase in the Ligand-independent Ubiquitination and Down-regulation of the IFNAR1 Chain of Type I Interferon Receptor (2011)

Phosphorylation-dependent ubiquitination and degradation of the IFNAR1 chain of type I interferon (IFN) receptor is a robust and specific mechanism that limits the magnitude and duration of IFNα/β signaling. Besides the ligand-inducible IFNAR1 degradation, the existence of an "inside-out" signaling that accelerates IFNAR1 turnover in the cells undergoing the endoplasmic reticulum (ER) stress and activated unfolded protein responses has been recently described. The latter pathway does not require either presence of ligands (IFNα/β) or catalytic activity of Janus kinases (JAK). Instead, this pathway relies on activation of the PKR-like ER kinase (PERK) and ensuing specific priming phosphorylation of IFNAR1. Here, we describe studies that identify the stress activated p38 protein kinase as an important regulator of IFNAR1 that acts downstream of PERK. Results of the experiments using pharmacologic p38 kinase inhibitors, RNA interference approach, and cells from p38α knock-out mice suggest that p38 kinase activity is required for priming phosphorylation of IFNAR1 in cells undergoing unfolded protein response. We further demonstrate an important role of p38 kinase in the ligand-independent stimulation of IFNAR1 ubiquitination and degradation and ensuing attenuation of IFNα/β signaling and anti-viral defenses. We discuss the distinct importance of p38 kinase in regulating the overall responses to type I IFN in cells that have been already exposed to IFNα/β versus those cells that are yet to encounter these cytokines.
Feature-Based Lucas–Kanade and Active Appearance Models (2015)

Lucas-Kanade and active appearance models are among the most commonly used methods for image alignment and facial fitting, respectively. They both utilize nonlinear gradient descent, which is usually applied on intensity values. In this paper, we propose the employment of highly descriptive, densely sampled image features for both problems. We show that the strategy of warping the multichannel dense feature image at each iteration is more beneficial than extracting features after warping the intensity image at each iteration. Motivated by this observation, we demonstrate robust and accurate alignment and fitting performance using a variety of powerful feature descriptors. Especially with the employment of histograms of oriented gradient and scale-invariant feature transform features, our method significantly outperforms the current state-of-the-art results on in-the-wild databases.
Automatic Segmentation and Quantitative Analysis of the Articular Cartilages From Magnetic Resonance Images of the Knee (2009)

In this paper, we present a segmentation scheme that automatically and accurately segments all the cartilages from magnetic resonance (MR) images of nonpathological knees. Our scheme involves the automatic segmentation of the bones using a three-dimensional active shape model, the extraction of the expected bone-cartilage interface (BCI), and cartilage segmentation from the BCI using a deformable model that utilizes localization, patient specific tissue estimation and a model of the thickness variation. The accuracy of this scheme was experimentally validated using leave one out experiments on a database of fat suppressed spoiled gradient recall MR images. The scheme was compared to three state of the art approaches, tissue classification, a modified semi-automatic watershed algorithm and nonrigid registration (B-spline based free form deformation). Our scheme obtained an average Dice similarity coefficient (DSC) of (0.83, 0.83, 0.85) for the (patellar, tibial, femoral) cartilages, while (0.82, 0.81, 0.86) was obtained with a tissue classifier and (0.73, 0.79, 0.76) was obtained with nonrigid registration. The average DSC obtained for all the cartilages using a semi-automatic watershed algorithm (0.90) was slightly higher than our approach (0.89), however unlike this approach we segment each cartilage as a separate object. The effectiveness of our approach for quantitative analysis was evaluated using volume and thickness measures with a median volume difference error of (5.92, 4.65, 5.69) and absolute Laplacian thickness difference of (0.13, 0.24, 0.12) mm.
Analysis of PDZ Domain-Ligand Interactions Using Carboxyl-terminal Phage Display (2000)

PDZ domains mediate protein-protein interactions at specialized subcellular sites, such as epithelial cell tight junctions and neuronal post-synaptic densities. Because most PDZ domains bind extreme carboxyl-terminal sequences, the phage display method has not been amenable to the study of PDZ domain binding specificities. For the first time, we demonstrate the functional display of a peptide library fused to the carboxyl terminus of the M13 major coat protein. We used this library to analyze carboxyl-terminal peptide recognition by two PDZ domains. For each PDZ domain, the library provided specific ligands with sub-micromolar binding affinities. Synthetic peptides and homology modeling were used to dissect and rationalize the binding interactions. Our results establish carboxyl-terminal phage display as a powerful new method for mapping PDZ domain binding specificity.
DU-176b, an oral, direct Factor Xa antagonist. (2007)

Daiichi Sankyo Inc (formerly Daiichi Seiyaku Co Ltd) is developing DU-176b, a direct, orally active Factor Xa inhibitor, as an anticoagulant for the potential treatment of cardiovascular indications, including venous and arterial thrombosis. By January 2005, phase II studies had begun in the US and Europe, and by March 2006, phase II studies had begun in Japan. Phase II trials for the prevention of thromboembolism were ongoing in mid 2007.
Adenovirus type 5 virions can be assembled in vivo in the absence of detectable polypeptide IX (1981)

Mutant dl313 is an adenovirus type 5 deletion mutant which lacks 2,307 base pairs, including the 5' portion of the polypeptide IX gene. Mutant virions did not contain detectable levels of this polypeptide. They were substantially more thermolabile than wild-type particles and did not produce hexon nonomers upon pyridine disruption.
The effector functions of immunoglobulins: implications for therapy. (1995)

The effector functions of immunoglobulins of the G class (IgGs) are essential for their effective use in therapy. The functions that operate following complex formation with cognate antigen involve binding to C1q (to mediate complement fixation) and the Fc receptors, Fc gamma RI, II and III. Another class of functions that is independent of antigen binding encompasses the transfer of antibodies across the placenta and maintaining the levels in the serum. All effector functions of IgGs are conferred by sequences in the Fc region of antibodies, and this review discusses the localisation of the functions to specific amino acid residues. Such knowledge is of use for the further improvement of IgCs for therapy.
Human Tumor Necrosis Factor Receptor p75/80 (CD120b) Gene Structure and Promoter Characterization (1996)

Tumor necrosis factor receptor p75 (TNF-R p75) is a 75-kDa type I transmembrane protein expressed predominantly on cells of hematopoietic lineage. TNF-R p75 belongs to the TNF receptor superfamily characterized by cysteine-rich extracellular regions composed of three to six disulfide-linked domains. In the present report we have characterized, for the first time, the complete gene structure for human TNF-R p75, which spans approximately 43 kbp. The gene consists of 10 exons (ranging from 34 base pairs to 2.5 kilobase pairs) and nine introns (343 base pairs to 19 kilobase pairs). Consensus elements for transcription factors involved in T cell development and activation were noted in the 5'-flanking region including T cell factor-1, Ikaros, AP-1, CK-2, interleukin-6 receptor E (IL-6RE), ISRE, GAS, NF-kappaB, and Sp1. The unusual (GATA)n and (GAA)(GGA) repeats found within intron 1 may prove useful for further genome analysis within the 1p36 chromosomal locus. Characterization of the human TNF-R p75 gene structure will permit further assessment of its involvement in normal hematopoietic cell development and function, autoimmune disease, and nonrandom translocations in hematopoietic malignancies.
Basal components of the transcription apparatus (RNA polymerase II, TATA ‐binding protein) contain activation domains: Is the repetitive c‐terminal domain (CTD) of RNA polymerase II a “Portable Enhance Domain”? (1994)

Regions rich in serine, threonine, and proline residues can be found in transcriptional activation domains, as well as in the N-terminal parts of mammalian TATA-binding proteins, where they are interrupted by polyglutamine stretches. Likewise, the C-terminal domain of the largest subunit of RNA polymerase II contains multiple repeats of the consensus heptapeptide sequence YSPTSPS. To test directly for possible activation functions, we fused the GAL4 DNA-binding domain to the N-terminal domain of human TBP or subdomains of it, and to the C-terminal domain (CTD) of mouse RNA polymerase II or synthetic polymers of a CTD consensus repeat. We found that these chimeric proteins were able to activate transcription when bound to a GAL4 site in front of the TATA box, a function characteristic of transcription factors. However, while subdomains of TBP functioned only from a position close to the TATA box ("promoter" position), multiple repeats of the CTD consensus sequence were also able to mediate transcriptional activation from a remote ("enhancer") position. Our findings suggest that a region of TBP that is unique to mammals functionally cooperates with "proximal" activation domains of promoter-bound transcription factors. They also imply that the C-terminal domain of RNA polymerase II includes a function that is otherwise confined to remote activation domains of enhancer-bound transcription factors. We suggest that the CTD of RNA polymerase II contains a "portable" remote activation domain that may also facilitate chromatin opening within the transcription unit.
A new structuring technique for polymer integrated circuits (2002)

We present a new technique for structuring polymeric interconnects and drain/source contacts of organic field-effect transistors in polymer integrated circuits. Our method is based on the selective electrochemical polymerisation of conductive polymers (e.g. PEDOT) on electrodes partially covered with a patterned insulating layer and the subsequent transfer of the polymeric structure to a flexible plastic substrate. Lateral resolutions of 10 /spl mu/m have already been obtained. The process is simple, does not require costly techniques like photolithography or vacuum deposition and it has the prospect of being applicable in reel-to-reel industrial processes.
Reduction and dissolution of manganese(III) and manganese(IV) oxides by organics: 2. Survey of the reactivity of organics (1984)

Reduction and dissolution of manganese(III, IV) oxide suspensions by 27 aromatic and nonaromatic compounds resembling natural organics were examined in order to understand the solubilization reaction in nature. At pH 7.2, 10⁻³ M formate, fumarate, glycerol, lactate, malonate, phthalate, propanol, propionaldehyde, propionate, and sorbitol did not dissolve appreciable amounts of oxide after&#13;\n3 h of reaction. The following organics did dissolve manganese oxides under these conditions and are listed in order of decreasing reactivity: 3-methoxycatechol ~ catechol 3,4-dihydroxybenzoic acid ~ ascorbate &gt; 4-nitrocatechol &gt; thiosalicylate &gt; hydroquinone &gt; 2,5-dihydroxybenzoic acid &gt; syringic acid &gt; o-methoxyphenol &gt; vanillic acid &gt; orcinol - 3,5-dihydroxybenzoic acid &gt; resorcinol &gt; oxalate ~ pyruvate - salicylate. Relative reactivities of organic substrates are discussed in terms of surface complex formation prior to electron transfer. Dissolution of manganese oxides by marine fulvic acid was enhanced by illumination, verifying that the reaction is photocatalyzed.
Dynamic changes in gene expression during in vitro differentiation of mouse embryonic stem cells. (1995)

The expression pattern of protein tyrosine kinases (PTK) and phosphatases (PTP) was determined during the first eight days of in vitro differentiation of mouse embryonic stem (ES) cells. DNA fingerprinting of catalytic domains amplified from cDNA revealed dynamic changes in expression of previously described genes. A novel PTP is expressed in undifferentiated ES cells, and is down-regulated during in vitro differentiation.
Tunnel-induced photon emission in semiconductors using an STM (1992)

The need for higher resolution in the study of semiconductor nanometer structures has led to the development of sharper probes for imaging of the geometrical structures, all the way down to the atomic level as in scanning tunnelling microscopy (STM). Simultaneously there is a pressing need for a possibility to make spectroscopic investigations of the electronic properties of such nm-structures, especially for the excitations of individual nm-features. In this paper we describe results from investigations of spectral analysis of photons emitted as a consequence of tunnel-injection of minority carriers in semiconductor bulk or quantum-well (QW) samples. We denote this technique scanning tunnelling luminescence (STL). Two different types of STL-experiments will be described: One where electrons are injected from states having energies close to the Fermi-level of a metal STM-tip into the conduction-band of p-type InP where they recombine, partly radiatively, as minority carriers. In the other type of experiment we employ a tip of a large band-gap semiconductor, p-type GaP, to which electrons tunnel from an n-type InP/GaInAs/InP QW sample. We report the first observation of such minority carrier injection where the sharply defined carrier (hole) energy distribution of the emitting tip is employed for almost mono-energetic injection and, again for the first time, on the observation at higher bias levels of how electrons are being injected from the InP surface into the tip where they recombine radiatively with the emission spectrum having the characteristic energy distribution of the tip material.