gebhart/patrepeval huggingface dataset:
Lipid composition of glucose‐stimulated pancreatic islets and insulin‐secreting tumor cells (1994)

The effect of glucose stimulation (25 mM for 5 min) on the phospholipid and neutral lipid composition of isolated pancreatic islets was studied to find out whether there is a change in the mass of potential lipid mediators or modulators of insulin secretion. For comparison, the lipid compositions of homogenates and subcellular fractions from RINm5F insulin-secreting tumor cells and of glucose-stimulated streptozotocin/nicotinamide-induced islet cell tumors were analyzed. After separation of the lipid extract into a neutral and an acidic fraction by anion-exchange chromatography, lipids were separated by high-performance thin-layer chromatography and quantitated by in situ densitometry of the cupric sulfate-charred bands. In glucose-stimulated islets, the molar percentages of phosphatidic acid (PA) and of phosphatidylinositol were significantly increased (3.1 vs. 4.7 mol% and 8.6 vs. 11.8 mol%), while those of all other phospholipids and neutral lipids, including 1,2-diacylglycerol, were not significantly changed. In stimulated islet cell tumors, an increase of PA was visible in the microsomal fraction, and there was an increase of lysophosphatidylcholine in the mitochondrial fraction. However, in both tumoral tissues, particularly in RINm5F cells, the lipid distribution pattern showed abnormalities which can be regarded as a loss of differentiation and which limit the usefulness of these tissues for the study of the physiological regulation of lipid metabolism during glucose stimulation. In conclusion, the data are in accordance with a role of PA early in stimulus-secretion coupling. The well-known stimulation of phospholipid synthesis in pancreatic islets during glucose-induced insulin secretion does not result in an increase in the total phospholipid mass.
SAFE: SPARQL Federation over RDF Data Cubes with Access Control (2017)

We validate the performance of the system with experiments over real-world datasets provided by three clinical organisations as well as legacy linked datasets. We show that SAFE enables granular graph-level access control over distributed clinical RDF data cubes and efficiently reduces the source selection and overall query execution time when compared with general-purpose SPARQL query federation engines in the targeted setting.
Neural stem/progenitor cells maintained in vitro under different culture conditions alter differentiation capacity of monocytes to generate dendritic cells (2017)

Cell therapy of the nervous system disorders using neural stem/progenitor cells (NSPCs) proved its efficacy in preclinical and pilot clinical studies. The mechanisms of the beneficial effects of NSPCs transplantation include replacement of damaged cells, paracrine activation of the regeneration, and immunomodulation. Detailed assessment of NSPCs-induced immunomodulation can contribute to better control of autoimmune reactions and inflammation in patients with neurodegenerative diseases. Interactions of NSPCs with dendritic cells (DCs), the key players in the induction of the immune system response to antigens are of particular interest. Here, we demonstrate that co-culturing of monocytes with NSPCs obtained and grown utilizing serum-containing medium instead of growth factor-containing serum-free medium, results in total suppression of monocyte differentiation into DCs. The effect is similar to the action of mesenchymal stem cells (MSCs). No significant effect on DCs maturation was observed. Cultures of NSPCs set up and maintained in serum-free medium have no influence on monocyte differentiation and DCs maturation. Therefore, the effects of NSPCs upon DC differentiation from monocytes strongly depend on culture conditions, whereas the molecular marker expression patterns are similar in both types of NSPCs cultures. In broader prospective, it means that cells with almost identical phenotypes can display opposite immunological properties depending upon culture conditions. It should be taken into account when developing NSPCs-based cell products for regenerative medicine.
Bispecific antibody-mediated redirection of NKG2D-CAR natural killer cells facilitates dual targeting and enhances antitumor activity (2021)

Our results demonstrate that combining an NKAB antibody with effector cells expressing an activating NKAR receptor represents a powerful and versatile approach to simultaneously enhance tumor antigen-specific as well as NKG2D-CAR and natural NKG2D-mediated cytotoxicity, which may be particularly useful to target tumors with heterogeneous target antigen expression.
Introduction: law courts, contracts and rural society in Europe, 1200–1600 (2014)

Abstract Private contracts of many different kinds were at the heart of the rural economy in medieval and early modern Europe. This article considers some of the key issues involved in the study of those contracts, and of the institutions that facilitated their registration and enforcement. Drawing on examples from medieval England as well as the articles in this special issue of the journal, it is argued that complex and effective ‘public-order’ structures for contract registration and enforcement – principally various kinds of law court – were ubiquitous in European villages and small towns in this era.
Enhancement of Methyl Methanesulfonate-Induced Base Excision Repair in the Presence of Selenomethionine on p53-Dependent Pathway (2009)

Selenomethionine (SeMet) has been identified as a chemopreventive antioxidant to activate p53-mediated nucleotide excision repair. In this study, we examined whether p53-mediated base excision repair (BER) might be induced by SeMet. When methyl methanesulfonate, a BER-inducing agent, was treated in the cells, DNA damage was rapidly decreased in the presence of SeMet. In addition, our data showed that the removal of apurinic/apyrimidinic sites was significantly enhanced in the presence of SeMet. Furthermore, we observed that the expression of gadd45a, known to involve BER as one of the p53 downstream genes, was increased by SeMet in p53 wild-type RKO cells. Those results supported the proposal that BER activity might be dependent on wild-type p53 under the modulation of gadd45a expression in response to SeMet. We suggested that p53-dependent BER activity as a distinct mechanism of SeMet might play an important role to prevent cancer caused by various oxidative stresses.
pKa of adenine 2451 in the ribosomal peptidyl transferase center remains elusive (2001)

The universally conserved A2451 of 23S rRNA has been proposed to participate directly in the catalysis of peptide bond formation in the ribosomal peptidyl transferase center. An unusually high, near neutral, pKa of A2451 is a prerequisite for its action as a general acid-base catalyst. Increased reactivity of A2451 to dimethylsulfate (DMS) at pH 8.5 compared to pH 6.5 was taken as evidence that the pKa of this nucleotide falls within this pH range. Structural data suggested that the interaction between A2451 and G2447 in the ribosome is responsible for A2451 pKa perturbation. In contrast to expectation, our studies did not show pH dependence of A2451 dimethylsulfate modification in ribosomes of Thermus aquaticus and Mycobacterium smegmatis. Other rRNA regions, however, showed major alterations in DMS reactivity at pH 8.5 compared to pH 6.5, suggesting that conformational rearrangements in the structure of the large ribosomal subunit may occur upon the pH shift. The G2447U mutant of M. smegmatis was viable, indicating that the G2447-A2451 interaction is not critical for the ribosome function. We concluded that the proposed unusual pKa of A2451, if existing, may not be crucial for the ribosome activity and that the previously reported pH-dependent alterations in the DMS modification of A2451 do not necessarily reveal an unusual pKa of this nucleotide.
Effect of subinhibitory concentrations of imipenem and piperacillin on Pseudomonas aeruginosa toxA and exoS transcriptional expression (2019)

Subinhibitory concentrations (subMIC) of antibiotics, although not able to kill bacteria, can modify their physicochemical characteristics and may interfere with some bacterial functions. This study aimed to investigate the effect of subMIC of imipenem and piperacillin on the transcriptional expression of virulence-related genes <i>toxA</i> and <i>exoS</i> in <i>Pseudomonas auroginosa</i>. Five clinical isolates of <i>P. aeruginosa</i> were screened for the presence of <i>toxA</i> and <i>exoS</i> genes and MICs of imipenem and piperacillin were determined using broth macrodilution. The expression levels of <i>toxA</i> and <i>exoS</i> at subMIC concentrations of antibiotics were measured by real-time PCR. Our results showed that the expression of <i>toxA</i> decreased at all subinhibitory concentrations of imipenem, especially at concentrations 2, 4 and 8 mg/L (p < 0.05). Whereas, <i>exoS</i> expression was increased 4.1- to 7-fold at subinhibitory concentrations of imipenem. The increase of <i>toxA</i> expression was measured at concentrations 16, 4, 2, 0.25 and 0.125 mg/L of piperacillin. However, piperacillin had no significant influence on <i>exoS</i> expression (p > 0.05). Further studies will be required to assess whether subMIC of imipenem can improve the outcomes of severe and serious infections caused by <i>P. aeruginosa</i>.
Novel infrared polarimeter for the ESO CRIRES+ instrument (2014)

The CRIRES infrared spectrograph at the European Southern Observatory (ESO) Very Large Telescope (VLT) facility will soon receive an upgrade. This upgrade will include the addition of a module for performing highresolution spectropolarimetry. The polarimetry module will incorporate a novel infrared beamsplitter based on polarization gratings (PGs). The beamsplitter produces a pair of infrared output beams, with opposite circular polarizations, which are then fed into the spectrograph. Visible light passes through the module virtually unaltered and is then available for use by the CRIRES adaptive optics system. We present the design of the polarimetry module and measurements of PG behavior in the 1 to 2.7 μm wavelength range.
The amyloid cascade hypothesis: are we poised for success or failure? (2016)

The first description of Alzheimer's disease (AD) was made in 1907 by Alois Alzheimer (Allgemeine Zeitschrift fur Psyciatrie und Psychisch-Gerichtliche Medizin 64, 3, 1907), although other contemporary physicians had made similar, and rather more complete, assessments of the neuropathological changes present in the AD brain (Fischer, Monatsschr Psychiat Neurol 22, 17, 1907). Our knowledge of AD has increased dramatically and continues to accelerate. This year is 25 years after the publication of a series of papers that, in various ways, articulated the amyloid cascade hypothesis (ACH) for AD (Beyreuther and Masters, Brain Pathol 1, 241-251, 1991; Hardy and Allsop, Trends Pharmacol Sci 12, 383-388, 1991; Selkoe, Neuron 6, 487-498, 1991; Hardy and Higgins, Science 256, 184-185, 1992). This review will cover some familiar territory, but we shall also place the ACH into a wider context, compare it with other hypotheses for AD, explore the evolution of the hypothesis to encompass new findings, and determine, irrespective of the merits of the hypothesis itself, whether it has been useful for the research field, both in academia and in industry. Finally, we shall review how the ACH has led to a number of therapeutic approaches, all of which have, to date, failed to reach their primary efficacy end-points in clinical trials and reflect upon what the future may hold. We review the amyloid cascade hypothesis (ACH) and compare it with other hypotheses that have been posited to explain the initiation and progression Alzheimer's disease. We document the data that support the ACH, and also reflect upon its deficiencies. We list the recent clinical failures of amyloidocentric drugs and anticipate the results that new therapeutic approaches may deliver. This article is part of the 60th Anniversary special issue.
Electron energy filtering by a nonplanar potential to enhance the thermoelectric power factor in bulk materials (2013)

We present a detailed theory on electron energy filtering by the nonplanar potential introduced by dispersed nanoparticles or impurities in bulk materials for enhancement of the thermoelectric power factor. When electrons with energies below a certain cut-off energy are prevented from participating in conduction through the material, the Seebeck coefficient and thus the thermoelectric power factor can be drastically enhanced. Instead of using planar heterostructures which require elaborate epitaxial techniques, we study embedded nanoparticles or impurities so that the conservation of lateral momentum limiting electron transport at heterointerfaces is no longer a limiting factor. Based on the Boltzmann transport equations under the relaxation time approximation, the optimal cut-off energy level that maximizes the power factor is calculated to be a few ${k}_{B}T$ above the Fermi level, and is a function of the scattering parameter, Fermi level, and temperature. The maximized power factor enhancement is quantified as a function of those parameters. The electronic thermal conductivity and Lorenz number are also shown to be suppressed by the electron filtering to further enhance the thermoelectric figure of merit. We find that the power factor of PbTe at 300 K could be enhanced by more than 120$%$ when the cut-off energy level is 0.2 eV or higher and the carrier density higher than $5\ifmmode\times\else\texttimes\fi{}{10}^{19}$ cm${}^{\ensuremath{-}3}$. Finally we propose the use of distributed resonant scatterings to partially realize the nonplanar electron filtering in bulk materials.
Data‐driven docking: HADDOCK's adventures in CAPRI (2005)

We have shown previously that given high-resolution structures of the unbound molecules, structure determination of protein complexes is possible by including biochemical and/or biophysical data as highly ambiguous distance restraints in a docking approach. We applied this method, implemented in the HADDOCK (High Ambiguity Driven DOCKing) package (Dominguez et al., J Am Chem Soc 2003;125:1731-1737), to the targets in the fourth and fifth rounds of CAPRI. Here we describe our results and analyze them in detail. Special attention is given to the role of flexibility in our docking method and the way in which this improves the docking results. We describe extensions to our approach that were developed as a direct result of our participation in CAPRI. In addition to experimental information, we also included interface residue predictions from PPISP (Protein-Protein Interaction Site Predictor; Zhou and Shan, Proteins 2001;44:336-343), a neural network method. Using HADDOCK we were able to generate acceptable structures for 6 of the 8 targets, and to submit at least 1 acceptable structure for 5 of them. Of these 5 submissions, 3 were of medium quality (Targets 10, 11, and 15) and 2 of high quality (Targets 13 and 14). In all cases, predictions were obtained containing at least 40% of the correct epitope at the interface for both ligand and receptor simultaneously.
Spontaneous Posterior Segment Vascular Disease Phenotype of a Mouse Model,<i>rnv3</i>, Is Dependent on the<i>Crb1<sup>rd8</sup></i>Allele (2018)

Purpose: To determine the molecular basis of lesion development in a murine model of spontaneous retinal vascularization, rnv3 (retinal vascularization 3, aka JR5558). Methods: Disease progression of rnv3 was examined in longitudinal studies by clinical evaluation, electroretinography (ERG) and light microscopy analyses. The chromosomal position for the recessive rnv3 mutation was determined by DNA pooling and genome-wide linkage analysis. The causative mutation was discovered by comparison of whole exome sequences of rnv3 mutant and wild-type (WT) controls. In order to confirm the causative mutation, transcription activator-like effector nuclease (TALEN)-mediated oligonucleotide directed repair (ODR) was utilized to correct the mutant allele. Phenotypic correction was assessed by fundus imaging and optical coherence tomography of live mice. Results: rnv3 exhibits early-onset, multifocal depigmented retinal lesions observable by fundus examination starting at 18 days of age. The retinal lesions are associated with fluorescein leakage around 25 days of age, with peak leakage at about 4 weeks of age. ERG responses deteriorate as rnv3 mutants age, concomitant with progressive photoreceptor disruption and loss that is observable by histology. Genetic analysis localized rnv3 to mouse chromosome (Chr) 1. By high throughput sequencing of a whole exome capture library of a rnv3/rnv3 mutant and subsequent sequence analysis, a single base deletion (del) in the Crb1 [crumbs family member 1] gene, which was previously reported to cause retinal degeneration 8, was identified. The TALEN-mediated ODR rescued the posterior segment vascularization phenotype; heterozygous Crb1rd8+em1Boc/Crb1rd8 and homozygous Crb1rd8+em1Boc/Crb1rd8+em1Boc mice showed a normal retinal phenotype. Additionally, six novel disruptions of Crb1 that were generated through aberrant non-homologous end joining induced by TALEN exhibited variable levels of vascularization, suggesting allelic effects. Conclusions: The rnv3 model and the models of six novel disruptions of Crb1 are all reliable, novel mouse models for the study of both early and late events associated with posterior segment vascularization and can also be used to test the effects of pharmacological targets for treating human ocular vascular disorders. Further study of these models may provide a greater understanding about how different Crb1 alleles result in aberrant angiogenesis.
Soft-Iterative Channel Estimation: Methods and Performance Analysis (2007)

<para xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> In this paper, we propose a soft-iterative approach for the estimation of block-fading channels based on multiblock (MB) processing. Coded transmission over fading channels is usually performed by interleaving the code word over a large time interval and arranging it into data packets (or blocks) that include also pilot symbols to allow the estimation of the time-varying channel. In this paper, we propose to exploit this block-based structure, and also the inherent latency of soft-iterative receivers due to data interleaving, to improve the channel estimate accuracy. Within the observed frame of blocks, the MB approach uses the invariance of some multipath features, such as delays and mean powers, to estimate the covariance matrix of the channel vector and to identify the corresponding channel subspace. Here, the MB method is extended to incorporate soft information, which is available in iterative receiver structures. The performance of this soft-iterative method is derived in terms of mean square error of the estimate by using a general framework that applies also to other soft-based methods in the literature. A performance comparison is carried out among these estimation methods, both analytically and by numerical simulations, showing the benefits of the proposed approach on the turbo equalizer convergence. </para>
Developmental and behavioral effects of toe clipping on neonatal and preweanling mice with and without vapocoolant anesthesia. (2014)

Toe clipping is used to identify and genotype preweanling mice, but the procedure generates concerns relevant to pain and distress. The few pertinent studies available evaluated mice between postnatal days (PND) 3 and 7, advocate the use of toe clipping in mice PND 7 or younger, and identify handling as the most distressing aspect of the procedure. Because both toe and tail clipping may be necessary in older mice to obtain sufficient DNA for genotyping, we surmised that performing these procedures concurrently to minimize handling would be beneficial. We also examined reflex development until PND 21 and adult behavior at 8 to 10 wk of age in mice toe clipped at PND 7 or 17 and the benefits of using topical vapocoolant anesthesia. C57BL/6J pups at PND 7 and 17 were assigned to 1 of 4 groups: 1) clipping of digit 3 of contralateral fore- and hindpaws; 2) toe clipping after topical vapocoolant anesthesia; 3) unclipped, unsprayed controls; and, 4) unclipped and vapocoolant-sprayed. Compared with unanesthetized pups, those sprayed with vapocoolant vocalized and struggled more when handled and had more bleeding, erythema, and swelling, which persisted for as long as 12 h after toe clipping. Reflex development, anxiety, locomotion, and motor coordination were not different among groups or with regard to the age of toe clipping. No tissue reaction was noted microscopically in paws collected at 10 wk of age. We conclude that the use of vapocoolant cannot be recommended due to its harmful effects and that toe clipping at PND 7 or 17 does not significantly affect the long-term welfare of mice.
Exciton chirality method and its application to configurational and conformational studies of natural products (1972)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTExciton chirality method and its application to configurational and conformational studies of natural productsNobuyuki Harada and Koji NakanishiCite this: Acc. Chem. Res. 1972, 5, 8, 257–263Publication Date (Print):August 1, 1972Publication History Published online1 May 2002Published inissue 1 August 1972https://pubs.acs.org/doi/10.1021/ar50056a001https://doi.org/10.1021/ar50056a001research-articleACS PublicationsRequest reuse permissionsArticle Views2454Altmetric-Citations428LEARN 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-Alertsclose Get e-Alerts
Thermal diffusivity and chaos in metals without quasiparticles (2017)

The authors study the Fermi surface in ``strange'' metals, where there are no well defined quasiparticle excitations. They show that in holographic models, the thermal conductivity is related solely to the gravitational metric near the horizon.