gebhart/patrepeval huggingface dataset:
Effect of a neuroprotective drug, eliprodil on cardiac repolarisation: importance of the decreased repolarisation reserve in the development of proarrhythmic risk (2004)

The aim of this study was to analyse the effects of eliprodil, a noncardiac drug with neuroprotective properties, on the cardiac repolarisation under in vitro circumstances, under normal conditions and after the attenuation of the ‘repolarisation reserve’ by blocking the inward rectifier potassium current ( I K1 ) current with BaCl 2 . In canine right ventricular papillary muscle by applying the conventional microelectrode technique, under normal conditions, eliprodil (1 μ M ) produced a moderate reverse rate‐dependent prolongation of the action potential duration (7.4±1.5, 8.9±2.1 and 9.9±1.8% at cycle lengths of 300, 1000 and 5000 ms, respectively; n =9). This effect was augmented in preparations where I K1 was previously blocked by BaCl 2 (10 μ M ). BaCl 2 alone lengthened APD in a reverse frequency‐dependent manner (7.0±1.3, 14.2±1.6 and 28.1±2.1% at cycle lengths of 300, 1000 and 5000 ms, respectively; n =8). When eliprodil (1 μ M ) was administered to these preparations, the drug induced a marked further lengthening relative to the APD values measured after the administration of BaCl 2 (12.5±1.0, 17.6±1.5 and 20.5±0.9% at cycle lengths of 300, 1000 and 5000 ms, respectively; n =8). In the normal Langendorff‐perfused rabbit heart, eliprodil (1 μ M ) produced a significant QT c prolongation at 1 Hz stimulation frequency (12.7±1.8%, n =9). After the attenuation of the ‘repolarisation reserve’ by the I K1 blocker BaCl 2 (10 μ M ), the eliprodil‐evoked QT c prolongation was greatly enhanced (28.5±7.9%, n =6). In two out of six Langendorff preparations, this QT c lengthening degenerated into torsade de pointes ventricular tachycardia. Eliprodil significantly decreased the amplitude of rapid component of the delayed rectifier potassium current ( I Kr ), but slow component ( I Ks ), transient outward current ( I to ) and I K1 were not considerably affected by the drug when measured in dog ventricular myocytes by applying the whole‐cell configuration of the patch‐clamp technique. The results indicate that eliprodil, under normal conditions, moderately lengthens cardiac repolarisation by inhibition of I Kr . However, after the attenuation of the normal ‘repolarisation reserve’, this drug can induce marked QT interval prolongation, which may result in proarrhythmic action. British Journal of Pharmacology (2004) 143 , 152–158. doi: 10.1038/sj.bjp.0705901
Design and function of novel osteoblast‐adhesive peptides for chemical modification of biomaterials (1998)

Proactive, “next generation” dental/orthopedic biomaterials must be designed rationally to elicit specific, timely, and desirable responses from surrounding cells/tissues; for example, such biomaterials should support and enhance osteoblast adhesion (a crucial function for anchorage-dependent cells). In the past, integrin-binding peptides have been immobilized on substrates to partially control osteoblast adhesion; the present study focused on the design, synthesis, and bioactivity of the novel peptide sequence Lys-Arg-Ser-Arg that selectively enhances heparan sulfate-mediated osteoblast adhesion mechanisms. Osteoblast, but not endothelial cell or fibroblast, adhesion was enhanced significantly (p < 0.05) on substrates modified with Lys-Arg-Ser-Arg peptides, indicating that these peptides may be osteoblast- or bone cell specific. Blocking osteoblast cell-membrane receptors with various concentrations of soluble Arg-Gly-Asp-Ser peptides did not inhibit subsequent cell adhesion on substrates modified with Lys-Arg-Ser-Arg peptides, providing evidence that osteoblasts interact with Arg-Gly-Asp-Ser and with Lys-Arg-Ser-Arg peptides via distinct (i.e., integrin- and proteoglycan-mediated) mechanisms, each uniquely necessary for osteoblast adhesion. The present study constitutes an example of rational design/selection of bioactive peptides, confirms that osteoblast adhesion to substrates can be controlled selectively and significantly by immobilized peptides, and elucidates criteria and strategies for the design of proactive dental/orthopedic implant biomaterials. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 40, 371–377, 1998.
Review of massively parallel DNA sequencing technologies (2011)

Since the development of technologies that can determine the base-pair sequence of DNA, the ability to sequence genes has contributed much to science and medicine. However, it has remained a relatively costly and laborious process, hindering its use as a routine biomedical tool. Recent times are seeing rapid developments in this field, both in the availability of novel sequencing platforms, as well as supporting technologies involved in processes such as targeting and data analysis. This is leading to significant reductions in the cost of sequencing a human genome and the potential for its use as a routine biomedical tool. This review is a snapshot of this rapidly moving field examining the current state of the art, forthcoming developments and some of the issues still to be resolved prior to the use of new sequencing technologies in routine clinical diagnosis.
δ-Aminolevulinic Acid Dehydratase from Plasmodium falciparum (2004)

The heme biosynthetic pathway of the malaria parasite is a drug target and the import of host delta-aminolevulinate dehydratase (ALAD), the second enzyme of the pathway, from the red cell cytoplasm by the intra erythrocytic malaria parasite has been demonstrated earlier in this laboratory. In this study, ALAD encoded by the Plasmodium falciparum genome (PfALAD) has been cloned, the protein overexpressed in Escherichia coli, and then characterized. The mature recombinant enzyme (rPfALAD) is enzymatically active and behaves as an octamer with a subunit Mr of 46,000. The enzyme has an alkaline pH optimum of 8.0 to 9.0. rPfALAD does not require any metal ion for activity, although it is stimulated by 20-30% upon addition of Mg2+. The enzyme is inhibited by Zn2+ and succinylacetone. The presence of PfALAD in P. falciparum can be demonstrated by Western blot analysis and immunoelectron microscopy. The enzyme has been localized to the apicoplast of the malaria parasite. Homology modeling studies reveal that PfALAD is very similar to the enzyme species from Pseudomonas aeruginosa, but manifests features that are unique and different from plant ALADs as well as from those of the bacterium. It is concluded that PfALAD, while resembling plant ALADs in terms of its alkaline pH optimum and apicoplast localization, differs in its Mg2+ independence for catalytic activity or octamer stabilization. Expression levels of PfALAD in P. falciparum, based on Western blot analysis, immunoelectron microscopy, and EDTA-resistant enzyme activity assay reveals that it may account for about 10% of the total ALAD activity in the parasite, the rest being accounted for by the host enzyme imported by the parasite. It is proposed that the role of PfALAD may be confined to heme synthesis in the apicoplast that may not account for the total de novo heme biosynthesis in the parasite.
Multiple Independent Comb Shaping (MICS): Phase-only generation of optical pulse sequences (2009)

A simple technique for the synthesis of optical pulse sequences is described, where the input laser spectrum is viewed as a superposition of independent but interlaced combs assigned to different sub-pulses. The devised concept enables intuitive programming of complex multi-pulse waveforms via one-dimensional phase-only shaping. Using this approach, we perform self-referenced cross-correlation measurements of various optical waveforms and demonstrate the generation and coding of shaped pulse sequences.
Liver alcohol dehydrogenase and aldehyde dehydrogenase in the Japanese: isozyme variation and its possible role in alcohol intoxication. (1980)

Forty autopsy livers from Japanese individuals were studied concerning alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) isozymes using electrophoretic and enzyme assay methods. A remarkably high frequency (85%) was found for the atypical ADH phenotype. The gene frequencies of ADH22 and ADH32 were .625 and .05, respectively. The usual ALDH phenotype showed two major isozyme bands, a faster migrating (low Km for acetaldehyde) and a slower migrating isozyme (high Km for acetaldehyde). Fifty-two percent of the specimens had an unusual phenotype of ALDH, which showed only the slower migrating isozyme. The usual phenotype was inhibited about 20%--30% by disulfiram and the unusual type up to 90%. Such a high incidence in the Japanese of the unusual phenotype, which lacks in the low Km isozyme, suggests that the initial intoxicating symptoms after alcohol drinking in these subjects might be due to delayed oxidation of acetaldehyde rather than its higher-than-normal production by typical or atypical ADH.
Solving differential equations with unknown constitutive relations as recurrent neural networks (2017)

We solve a system of ordinary differential equations with an unknown functional form of a sink (reaction rate) term. We assume that the measurements (time series) of state variables are partially available, and we use recurrent neural network to "learn" the reaction rate from this data. This is achieved by including a discretized ordinary differential equations as part of a recurrent neural network training problem. We extend TensorFlow's recurrent neural network architecture to create a simple but scalable and effective solver for the unknown functions, and apply it to a fedbatch bioreactor simulation problem. Use of techniques from recent deep learning literature enables training of functions with behavior manifesting over thousands of time steps. Our networks are structurally similar to recurrent neural networks, but differences in design and function require modifications to the conventional wisdom about training such networks.
A NOVEL DESIGN OF DUAL CIRCULARLY POLARIZED ANTENNA FED BY L-STRIP (2007)

A novel design of dual circularly polarized antenna is proposed. By etching cross slots on the patch, circular polarization (CP) is achieved. The patch is fed by two L-strips which provide wide impedance bandwidth and high isolation level. Polarization diversity between left-hand circular polarization (LHCP) and right-hand circular polarization (RHCP) is provided by switching the two ports and both LHCP and RHCP signals can be received simultaneously. The experimental results show that the 3 dB axial ratio CP bandwidth of the proposed design is increased two times, as compared to a referential CP antenna fed by L-strip. The details of experimental results for the proposed design are presented and discussed.
Monoclonal antibodies for carcinoembryonic antigen and related antigens as a model system: determination of affinities and specificities of monoclonal antibodies by using biotin-labeled antibodies and avidin as precipitating agent in a solution phase immunoassay. (1983)

A general method is described for the determination of affinity constants and antigen cross-reactivities of monoclonal antibodies. The method employs biotin-labeled antibody, radiolabeled antigen, and avidin as a precipitating agent in a homogeneous phase, competitive radioimmunoassay. This method eliminates incomplete or variable precipitation of antigen-antibody complexes often encountered in immunoassays in which monoclonal antibodies are employed. Using this assay system, we were able to rapidly determine the affinity constants for a number of monoclonal antibodies elicited to carcinoembryonic antigen (CEA). In the preceding paper it was shown that five of the monoclonal antibodies recognized distinct epitopes on CEA. In antigen-binding experiments with these five monoclonal antibodies, the percent of radiolabeled CEA bound in antibody excess ranged from 30 to 92%. The CEA cross-reacting antigens, normal cross-reacting antigen (NCA), and tumor-extracted, CEA-related antigen (TEX) were significantly bound by one, and to a lesser degree, by two of the five antibodies. Two antibodies did not bind significant amounts of NCA or TEX. In inhibition studies, the amount of unlabeled CEA leading to 50% inhibition of 125I-labeled CEA-binding was in the range of 3.7 to 760 ng per tube. The amount of TEX showing the same degree of inhibition was 23-fold greater than the amount of CEA for two antibodies and 351-fold greater than the amount of CEA for a third antibody. The affinity constants for CEA were in the range of 1.0 x 10(8) to 5.1 x 10(10) M-1. The affinity constants for NCA and TEX, determined for one of the antibodies, were three orders of magnitude lower in comparison to CEA. The heterogeneity of radiolabeled CEA as indicated by the low fraction bound by one of the monoclonal antibodies is shown to be most probably an artifact resulting from radioiodination damage. The application of the approach described in this report should eliminate the problems most commonly encountered in the determination of affinity constants for monoclonal antibodies or the use of monoclonal antibodies in competitive, homogeneous-phase immunoassays.
Distribution of the aquaporin CHIP in secretory and resorptive epithelia and capillary endothelia. (1993)

The existence of water-selective channels has been postulated to explain the high water permeability of erythrocytes and certain epithelial cells. The aquaporin CHIP (channel-forming integral membrane protein of 28 kDa), a molecular water channel, is abundant in erythrocytes and water-permeable segments of the nephron. To determine whether CHIP may mediate transmembrane water movement in other water-permeable epithelia, membranes of multiple organs were studied by immunoblotting, immunohistochemistry, and immunoelectron microscopy using affinity-purified anti-CHIP IgG. The apical membrane of the choroid plexus epithelium was densely stained, implying a role for CHIP in the secretion of cerebrospinal fluid. In the eye, CHIP was abundant in apical and basolateral domains of ciliary epithelium, the site of aqueous humor secretion, and also in lens epithelium and corneal endothelium. CHIP was detected in membranes of hepatic bile ducts and water-resorptive epithelium of gall bladder, suggesting a role in bile secretion and concentration. CHIP was not detected in glandular epithelium of mammary, salivary, or lacrimal glands, suggesting the existence of other water-channel isoforms. CHIP was also not detected within the epithelium of the gastrointestinal mucosa. CHIP was abundant in membranes of intestinal lacteals and continuous capillaries in diverse tissues, including cardiac and skeletal muscle, thus providing a molecular explanation for the known water permeability of certain lymphatics and capillary beds. These studies underscore the hypothesis that CHIP plays a major role in transcellular water movement throughout the body.
Synthesis and Biological Evaluation of New Quinoxaline Derivatives as Antioxidant and Anti‐Inflammatory Agents (2011)

We report the synthesis, anti-inflammatory, and antioxidant activities of novel quinoxaline and quinoxaline 1,4-di-N-oxide derivatives. Microwave-assisted methods have been used to optimize reaction times and to improve yields. The tested compounds presented important scavenging activities and promising in vitro inhibition of soybean lipoxygenase (LOX). Two of the best LOX inhibitors (compounds 7b and 8f) were evaluated as in vivo anti-inflammatory agents using the carrageenin-induced edema model. One of them (compound 7b) showed important in vivo anti-inflammatory effect (41%) similar to that of indomethacin (47%) used as the reference drug.
New antiplatelet drugs (1997)

Many clinical trials and pathologic analyses have clearly demonstrated a central role for platelets in the pathophysiology of major cardiovascular disorders, including unstable angina pectoris, acute myocardial infarction (MI), transient ischaemia, and stroke following thrombolytic therapy [1,2]. A meta-analysis of 25 randomised trials of various antiplatelet agents that included 29,000 patients revealed a highly significant decrease in non-fatal MI, stroke, total cardiovascular death, and overall mortality in patients treated with antiplatelet agents compared with placebo [3]. These data have triggered intense efforts over the past 10 years in studying the role of the platelet in cardiovascular disorders, and in developing more potent and selective antiplatelet agents. This discussion summarises recent advances in the development and evaluation of these newer agents with particular emphasis on antagonists of the glycoprotein (GP) IIb/IIIa receptor, since this protein plays a key role in the final common pathway of platelet aggregation.
Informatics in Radiology: Use of CouchDB for Document-based Storage of DICOM Objects (2012)

Picture archiving and communication systems traditionally have depended on schema-based Structured Query Language (SQL) databases for imaging data management. To optimize database size and performance, many such systems store a reduced set of Digital Imaging and Communications in Medicine (DICOM) metadata, discarding informational content that might be needed in the future. As an alternative to traditional database systems, document-based key-value stores recently have gained popularity. These systems store documents containing key-value pairs that facilitate data searches without predefined schemas. Document-based key-value stores are especially suited to archive DICOM objects because DICOM metadata are highly heterogeneous collections of tag-value pairs conveying specific information about imaging modalities, acquisition protocols, and vendor-supported postprocessing options. The authors used an open-source document-based database management system (Apache CouchDB) to create and test two such databases; CouchDB was selected for its overall ease of use, capability for managing attachments, and reliance on HTTP and Representational State Transfer standards for accessing and retrieving data. A large database was created first in which the DICOM metadata from 5880 anonymized magnetic resonance imaging studies (1,949,753 images) were loaded by using a Ruby script. To provide the usual DICOM query functionality, several predefined "views" (standard queries) were created by using JavaScript. For performance comparison, the same queries were executed in both the CouchDB database and a SQL-based DICOM archive. The capabilities of CouchDB for attachment management and database replication were separately assessed in tests of a similar, smaller database. Results showed that CouchDB allowed efficient storage and interrogation of all DICOM objects; with the use of information retrieval algorithms such as map-reduce, all the DICOM metadata stored in the large database were searchable with only a minimal increase in retrieval time over that with the traditional database management system. Results also indicated possible uses for document-based databases in data mining applications such as dose monitoring, quality assurance, and protocol optimization.
Synthesis of Optically Pure Arylsilylcarbinols and Their Use as Chiral Auxiliaries in Oxacarbenium Ion Reactions (2003)

A family of arylsilylcarbinols was synthesized and investigated as chiral auxiliaries for oxacarbenium ion reactions. The optically pure arylsilylcarbinols were prepared using Noyori's transfer hydrogenation catalyst 11. The transfer hydrogenation shows very good enantioselectivities and turnover efficiency for the aryl silyl ketones and is the method of choice for preparing these optically pure alcohols. The diastereoselective addition of allyltrimethylsilane to an in situ generated oxacarbenium ion was explored using Marko's conditions. The selectivity for a representative aliphatic aldehyde was very good, but the selectivity was significantly reduced with unsaturated and aromatic aldehydes. The range of selectivities with different auxiliaries was narrow, and the most practical auxiliary is the phenylsilylcarbinol 2.
Plasma placenta growth factor levels in midtrimester pregnancies (2001)

Our results show that plasma placenta growth factor levels are decreased before preeclampsia is clinically evident. The data suggest that placenta growth factor may be useful to determine the relative risk of developing preeclampsia and intrauterine growth restriction.
The Design of a Thermoelectric Generator and Its Medical Applications (2019)

Growing energy demands are driving people to generate power in every possible way. New energy sources are needed to plug the energy gap. There is a growing interest in distributed energy generation due to its remarkable advantages such as flexibility, reliability, adaptability and minimal transmission losses. Thermoelectric generators (TEGs) are one such distributed power source that relies on thermal energy for electricity generation. The current review focusses on the design and optimization of TEGs to maximize the power output from the available thermal sources. The basic principle of thermoelectricity generation and suitable architecture for specific applications are explained with an overview of materials and manufacturing processes. Various cooling techniques to dissipate heat from the cold side and their influence on overall efficiency are reviewed in this work. Applications of TEGs for powering biomedical sensors have been discussed in detail. Recent advancements in TEGs for various implantable devices and their power requirements are evaluated. The exploitation of TEGs to generate power for wearable sensors has been presented, along with published experimental data. It is envisioned that this study will provide profound knowledge on TEG design for specific applications, which will be helpful for future endeavours.
Spatially Confined Chemistry:  Fabrication of Ge Quantum Dot Arrays (1996)

We report a technique for investigating nucleation and growth confined to nanometer scale surfaces. Lithographic and etching processes were used to create arrays of 100 and 150 nm holes through a thin SiO2 layer onto Si(100). Ge dots were nucleated and grown to a few nanometers in diameter within the patterned wells. Transmission electron and atomic force microscopic analyses revealed the presence of 0−1 Ge quantum dots in each of the 100 nm wells and 2−4 dots in the 150 nm wells. For the latter case, size−distance correlations indicated the effective radius of the diffusion field around a growing Ge particle was much larger than for growth on an infinite surface.
Widespread signatures of local mRNA folding structure selection in four Dengue virus serotypes (2015)

The fact that many of the positions with significant folding related signals are conserved among different Dengue variants suggests that a better understanding of the mRNA structures in the corresponding regions may promote the development of prospective anti- Dengue vaccination strategies. The comparative genomics approach described here can be employed in the future for detecting functional regions in other pathogens with very high mutations rates.