gebhart/patrepeval huggingface dataset:
Enhanced glial cell line-derived neurotrophic factor mRNA expression upon (?)-deprenyl and melatonin treatments (1998)

Glial cell line-derived neurotrophic factor (GDNF) has been shown to be a preferentially selective neurotrophic factor for dopamine (DA) neurons. In the present study, we have examined the distribution of GDNF mRNA expression in several major DA-containing cell body and terminal areas and the regulation of GDNF mRNA expression upon various pharmacological treatments. Results indicated that there is a relatively higher GDNF mRNA level in neurons of the nigrostriatal and mesolimbic dopaminergic pathways. Upon chronic 1-methyl-4-phenyl1,2,3,6-tetrahydropyridine (MPTP) treatment (30 mg/ kg, i.p., for 7 days), DA level was decreased, whereas GDNF mRNA expression was increased in the striatum, suggesting that more GDNF is synthesized and expressed to cope with the neurotoxin insult. Furthermore, among several DA neuron protective and/or therapeutic agents examined, both intrastriatal injections of (-)-deprenyl (1.25 microg and 2.5 microg) and melatonin (30 microg, 60 microg, and 120 microg) significantly enhanced GDNF mRNA expression in the striatum, whereas the same concentrations of (-)-deprenyl did not affect monoamine oxidase B (MAOB) activity, although it increased glutathione peroxidase (GPx) and/or superoxide dismutase (SOD) activities. Similarly, the same concentrations of melatonin did not alter SOD or GPx activities, except that the highest dose of melatonin (120 microg) increased lipid peroxidation in the striatum. Conversely, GM1 ganglioside injection (45 microg) lacked of an effect on GDNF mRNA expression. Together, these results suggest that both (-)-deprenyl and melatonin up-regulate GDNF gene expression at threshold doses lower than that needed for altering MAOB activity and/or the antioxidant enzyme systems, respectively. These results provide new information on the neuroprotective and therapeutic mechanisms of (-)-deprenyl and melatonin on DA neurons.
Neurotrophins, neuroprotection and the blood-brain barrier. (2002)

Small molecule drugs have not been effective neuroprotective agents in either the acute treatment of stroke or the chronic treatment of neurodegeneration. Thus, it is time to consider large molecule drugs such as recombinant neurotrophins. However, like many of the small molecules, neurotrophins do not cross the brain capillary endothelial wall, which forms the blood-brain barrier (BBB). Neurotrophins can be made transportable across the BBB by using chimeric peptide brain drug targeting technology, in which a neurotrophin is reformulated by fusion to a transport vector. The latter is a peptide or peptidomimetic monoclonal antibody that undergoes receptor-mediated transcytosis through the BBB, and acts as a 'molecular Trojan horse'. Neurotrophin chimeric peptides are highly neuroprotective following delayed intravenous administration, in both global and focal brain ischemia.
t(9;11)(p22;p15) in acute myeloid leukemia results in a fusion between NUP98 and the gene encoding transcriptional coactivators p52 and p75-lens epithelium-derived growth factor (LEDGF). (2000)

A t(9;11)(p22;p15) chromosomal translocation was identified in an adult patient with de novo acute myelogenous leukemia. Fluorescence in situ hybridization and Southern blot analysis mapped the 11p15 break-point to the NUP98 gene. Using 3' rapid amplification of cDNA ends, we have identified a chimeric mRNA that fused the NUP98 FXFG repeats in frame to the COOH-terminal portion of the gene encoding the transcriptional coactivators p52 and p75, also known as lens epithelium-derived growth factor (LEDGF). As expected, both NUP98-p52 and NUP98-p75 (LEDGF) chimeric mRNAs were detected by reverse transcription-PCR; however, the reciprocal p52/p75 (LEDGF)-NUP98 fusion mRNA was not detected. Our results demonstrate that this is the most 5' NUP98 fusion reported and reveal a previously unrecognized genetic target, the gene encoding p52/p75 (LEDGF).
New drug design with covalent modifiers (2016)

All the current clinically approved covalent drugs were discovered by chance instead of systematic design. There is a promising and commendable effort towards high-throughput screening and the accurate discovery of new covalent inhibitors, which may address the problems of drug resistance and mutation. However, despite the current progression, there is still a need for more rational attention to improve the covalent warhead for improved receptor interaction and selectivity.
Thermal Conductance of an Individual Single-Wall Carbon Nanotube above Room Temperature (2005)

The thermal properties of a suspended metallic single-wall carbon nanotube (SWNT) are extracted from its high-bias (I−V) electrical characteristics over the 300−800 K temperature range, achieved by Joule self-heating. The thermal conductance is approximately 2.4 nW/K, and the thermal conductivity is nearly 3500 Wm-1K-1 at room temperature for a SWNT of length 2.6 μm and diameter 1.7 nm. A subtle decrease in thermal conductivity steeper than 1/T is observed at the upper end of the temperature range, which is attributed to second-order three-phonon scattering between two acoustic modes and one optical mode. We discuss sources of uncertainty and propose a simple analytical model for the SWNT thermal conductivity including length and temperature dependence.
Antisense Oligonucleotide Therapies (2014)

Many antisense oligonucleotides (ASOs) from several classes of molecules are currently in drug development. Despite over 20 years of pharmaceutical research, few ASOs have been marketed due to problems with clinical efficacy or preclinical toxicologic challenges. However, a number of recent developments have renewed interest in this class including the registration of mipomersen, the advent of successful screening strategies to eliminate more toxic molecules, and new understanding of the risks of off-target nucleotide binding and mitigation of potential off-target effects. Recent advances in backbone chemistries, conjugation to other moieties, and new delivery systems have allowed better tissue penetration, enhanced intracellular targeting, and less frequent dosing, resulting in fewer toxicities. While these new developments provide invigorated interest in these platforms, a few lingering challenges and preclinical/clinical toxicity issues remain to be completely resolved, including: (1) proinflammatory effects (vasculitis/inflammatory infiltrates); (2) nephrotoxicity and hepatotoxicity unrelated to lysosomal accumulation; and (3) thrombocytopenia. Recent investigative work by several laboratories have helped elucidate mechanisms for these issues, allowing a better understanding of the clinical relevance and implications of particular toxicities. It is important for toxicologists, pathologists, and regulatory reviewers to be familiar with new developments in the ASO field and their implications, as a greater number of new types of antisense molecules undergo preclinical toxicity testing.
IL‐6 Promotes the Proliferation and Immunosuppressive Function of Myeloid‐Derived Suppressor Cells via the MAPK Signaling Pathway in Bladder Cancer (2021)

Muscle-invasive bladder cancer (MIBC) is characterized by a highly complex immune environment, which is not well understood. Interleukin-6 (IL-6) is generated and secreted by multifarious types of cells, including tumor cells. This study was aimed at demonstrating that the levels of IL-6 and the number of myeloid-derived suppressor cells (MDSCs), with a positive correlation between them, increased in MIBC tissues, promoting MIBC cell proliferation, especially in patients with recurrence. In coculture analysis, MDSCs, with the stimulation of IL-6, could significantly lower the proliferation ability of CD4<sup>+</sup> or CD8<sup>+</sup> T lymphocytes. Further, this study demonstrated that IL-6 could upregulate the mitogen-activated protein kinase (MAPK) signaling pathway in MDSCs. The MAPK signaling inhibitor, aloesin, partially reversed the effects of IL-6 on MDSCs. These data suggested that IL-6 promoted MIBC progression by not only accelerating proliferation but also improving the immune suppression ability of MDSCs through activating the MAPK signaling pathway.
Dual PPARα/γ agonist saroglitazar improves liver histopathology and biochemistry in experimental NASH models (2017)

Saroglitazar, a dual PPARα/γ agonist with predominant PPARα activity, shows an overall improvement in NASH. The effects of saroglitazar appear better than pure PPARα agonist, fenofibrate and PPARγ agonist pioglitazone.
Uniformly curated signaling pathways reveal tissue-specific cross-talks and support drug target discovery (2010)

http://SignaLink.org.
DeepPrior++: Improving Fast and Accurate 3D Hand Pose Estimation (2017)

DeepPrior [18] is a simple approach based on Deep Learning that predicts the joint 3D locations of a hand given a depth map. Since its publication early 2015, it has been outperformed by several impressive works. Here we show that with simple improvements: adding ResNet layers, data augmentation, and better initial hand localization, we achieve better or similar performance than more sophisticated recent methods on the three main benchmarks (NYU, ICVL, MSRA) while keeping the simplicity of the original method. Our new implementation is available at https://github.com/moberweger/deep-prior-pp.
High IL-6 Serum Levels are Associated with Septic Shock and Mortality in Septic Patients with Severe Leukopenia due to Hematological Malignancies (1995)

The serum levels of immunoreactive interleukin-6 (IL-6) and tumor necrosis factor (TNF) were analyzed in 14 leukopenic patients with documented sepsis, at 60 min (T0), 24 h (T1), and one week (T3) after the onset of sepsis syndrome. Sera from 10 leukopenic patients without sepsis (controls) were also tested. All septic patients had high IL-6 levels at T0. These levels persisted only in the seven patients who died of septic shock, presenting a 30-fold increase (p<0.001) as compared to the survivors and the controls. At T3, 7 survivors had recovered from sepsis and showed low IL-6 serum levels. The TNF serum concentration always <30 pg/ml in both the subjects and in the controls. The C-reactive protein (CRP) and clinical parameters appeared to be less specifically associated with shock and mortality than IL-6.
The structure of self-assembled monolayers of alkylsiloxanes on silicon: a comparison of results from ellipsometry and low-angle x-ray reflectivity (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe structure of self-assembled monolayers of alkylsiloxanes on silicon: a comparison of results from ellipsometry and low-angle x-ray reflectivityStephen R. Wasserman, George M. Whitesides, Ian M. Tidswell, Ben M. Ocko, Peter S. Pershan, and John D. AxeCite this: J. Am. Chem. Soc. 1989, 111, 15, 5852–5861Publication Date (Print):July 1, 1989Publication History Published online1 May 2002Published inissue 1 July 1989https://pubs.acs.org/doi/10.1021/ja00197a054https://doi.org/10.1021/ja00197a054research-articleACS PublicationsRequest reuse permissionsArticle Views2435Altmetric-Citations363LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
A Single Nucleotide Polymorphism in the FOXP3 Gene Associated with Behçet's Disease in an Iranian Population (2015)

Therefore, the SNP rs3761548 in the FOXP3 gene appears to contribute to the risk of Behçet's disease among the north-western Iranian population.
Manganese-Based Superoxide Dismutase Mimics Modify Both Acute and Long-Term Outcome Severity in a Drosophila melanogaster Model of Classic Galactosemia (2013)

Our results confirm oxidative stress as a mediator of acute galactose sensitivity in GALT-null Drosophila larvae and demonstrate for the first time that oxidative stress may also contribute to galactose-independent adult outcomes in GALT deficiency. Finally, our results demonstrate for the first time that both MnTnBuOE-2-PyP(5+) and MnTE-2-PyP(5+) are bioavailable and effective when administered through an oral route in a D. melanogaster model of classic galactosemia.
A role for the gut microbiota in energy harvesting? (2010)

The amount of energy that is stored in the body depends on the balance between energy intake and expenditure: when energy intake exceeds expenditure, excess energy is stored as fat, which leads to weight gain and eventually obesity. A number of factors are associated with the obesity epidemic that is spreading worldwide, such as individual genetic predisposition, diet and lifestyle. Recently, the community of microbes colonising the gastrointestinal tract, the gut microbiota, has been recognised as one such factor.1–3 Studies on mice maintained under germ-free conditions have shown that the gut microbiota promotes increased adiposity by enhancing energy extraction from food and modulating host genes that regulate fat storage.1

Culture independent analyses of the composition of the gut microbiota have revealed that obese individuals harboured a varied proportion of two prevailing phyla, Firmicutes and Bacteroidetes, in comparison to lean subjects.4 Furthermore, the obese metagenome, which is the set of all genes present in the genomes of gut microbes, was enriched in gene functions associated with carbohydrate and lipid metabolism.5 Both in animal and human studies, obesity has been linked to a different composition of the gut microbiota. However, results from different studies are not concordant as to the contribution of specific components of the gut microbiota to the pathogenesis of obesity …
Total synthesis of (±)-cephalotaxine (1990)

H. Ishibashi, M. Okano, H. Tamaki, K. Maruyama, T. Yakura and M. Ikeda, J. Chem. Soc., Chem. Commun., 1990, 1436 DOI: 10.1039/C39900001436
Photoluminescence characterisations of a dynamic aging process of organic–inorganic CH3NH3PbBr3perovskite (2016)

After unprecedented development of organic-inorganic lead halide perovskite solar cells over the past few years, one of the biggest barriers towards their commercialization is the stability of the perovskite material. It is thus important to understand the interaction between the perovskite material and oxygen and/or humidity and the associated degradation process in order to improve device and encapsulation design for better durability. Here we characterize the dynamic aging process in vapour-assisted deposited (VASP) CH3NH3PbBr3 perovskite thin films using advanced optical techniques, such as time-resolved photoluminescence and fluorescence lifetime imaging microscopy (FLIM). Our investigation reveals that the perovskite grains grow spontaneously and the larger grains are formed at room temperature in the presence of moisture and oxygen. This crystallization process leads to a higher density of defects and a shorter carrier lifetime, specifically in the larger grains. Excitation-intensity-dependent steady-state photoluminescence shows both N2 stored and aged perovskite exhibit a super-linear increase of photoluminescence intensity with increasing excitation intensity; and the larger slope in aged sample suggests a larger density of defects is generated, consistent with time-resolved PL measurements.
Tomography of dispersive media (2000)

When waves propagate through layered structures, the phase velocity is frequency dependent (dispersive). If one wants to reconstruct the velocity variations in this medium, conventional traveltime-based tomographic methods cannot be used, since each frequency component has a different traveltime. A tomographic method is presented for reconstructing the phase velocity of guided waves in laterally varying media. The dispersive character of guided waves is explicitly accounted for by using a phase-based error criterium instead of "picked" traveltimes. Phase velocity and source waveform can be reconstructed to within a few percent, and the algorithm is shown to be robust in the presence of interference noise. When applied to seismic field data, the reconstructed phase velocity field correlates well with the topography of the area.
Homology between hydroxybutyryl and hydroxyacyl coenzyme A dehydrogenase enzymes from Clostridium acetobutylicum fermentation and vertebrate fatty acid beta-oxidation pathways (1989)

The enzymes NAD-dependent beta-hydroxybutyryl coenzyme A dehydrogenase (BHBD) and 3-hydroxyacetyl coenzyme A (3-hydroxyacyl-CoA) dehydrogenase are part of the central fermentation pathways for butyrate and butanol production in the gram-positive anaerobic bacterium Clostridium acetobutylicum and for the beta oxidation of fatty acids in eucaryotes, respectively. The C. acetobutylicum hbd gene encoding a bacterial BHBD was cloned, expressed, and sequenced in Escherichia coli. The deduced primary amino acid sequence of the C. acetobutylicum BHBD showed 45.9% similarity with the equivalent mitochondrial fatty acid beta-oxidation enzyme and 38.4% similarity with the 3-hydroxyacyl-CoA dehydrogenase part of the bifunctional enoyl-CoA hydratase:3-hydroxyacyl-CoA dehydrogenase from rat peroxisomes. The pig mitochondrial 3-hydroxyacyl-CoA dehydrogenase showed 31.7% similarity with the 3-hydroxyacyl-CoA dehydrogenase part of the bifunctional enzyme from rat peroxisomes. The phylogenetic relationship between these enzymes supports a common evolutionary origin for the fatty acid beta-oxidation pathways of vertebrate mitochondria and peroxisomes and the bacterial fermentation pathway.
Regulation of linkages between the erythrocyte membrane and its skeleton by 2,3-diphosphoglycerate (1993)

In addition to reducing hemoglobin-O2 affinity, 2,3-diphosphoglycerate (DPG) is known to modulate the mechanical properties of the erythrocyte membrane. By fluorescence spectroscopy and differential scanning calorimetry, we demonstrate that DPG binds the cytoplasmic domain of erythrocyte membrane band 3 in two stages characterized by apparent KD values of approximately approximately 2 and 12 mM. DPG was also shown to perturb the stability of ankyrin, protein 4.1, and protein 4.2 in situ and to directly bind to protein 4.1. In studies of membrane-skeleton interactions, DPG was observed to inhibit the fast and slow phases of ankyrin binding to band 3 and to reduce both the number of ankyrin sites and affinity of ankyrin for each class of site. The inhibition was biphasic, similar to the band 3-DPG binding isotherm; however, at physiological DPG concentrations a reduction in only 15% of the ankyrin sites was observed. In contrast, inhibition of protein 4.1 binding to the membrane reached 65% at physiological DPG concentrations (approximately approximately 5.9 mM); at more elevated concentrations, blockade was nearly quantitative, affecting glycophorin and band 3 sites alike. Taken together with previous observations, these data suggest that DPG's effect on O2 delivery may extend beyond its well recognized impact on hemoglobin-O2 affinity.
Rapid and Continuous Hydrothermal Crystallization of Metal Oxide Particles in Supercritical Water (1992)

Hydrolysis of 10 metal salt aqueous solutions of 6 metal oxides was conducted in supercritical water. Continuous and rapid production of metal oxide fine particles was achieved by mixing a metal salt aqueous solution with preheated water fed from another line. The reaction time required was less than 2 min. Particle size, morphology, and crystal structure of the obtained metal (hydrous) oxides were examined. Particle size (20 to 600 nm) was different among the systems but the size range was relatively narrow in all the cases.
Localization of the human pim oncogene (PIM) to a region of chromosome 6 involved in translocations in acute leukemias. (1986)

The human homolog, hpim, of the murine pim-1 gene, which is activated in murine T-cell lymphomas by insertion of retrovirus proviral genomes in the pim-1 region, has been molecularly cloned; the cloned probe has been used to map the hpim locus to human chromosome region 6p21 by somatic cell hybrid analysis and chromosomal in situ hybridization. The hpim gene is expressed as a 3.2-kilobase mRNA in various human cell lines of hematopoietic lineage, most dramatically in the K562 erythroleukemia cell line, which contains a cytogenetically demonstrable rearrangement in the 6p21 region. A characteristic chromosome anomaly, a reciprocal translocation t(6;9)(p21;q33), has been described in myeloid leukemias and could involve the hpim gene.
Comparison of On-Chip and Off-Chip Microfluidic Kinase Assay Formats (2004)

Kinases represent an important class of targets for pharmaceutical drug development. Microfluidic devices capable of running kinase assays with either an on-chip or an off-chip enzymatic reaction have been developed. For the on-chip assay, reagent addition, mixing, enzymatic reaction, and electrophoretic separation and detection of substrate and product all take place in the channels of the microfluidic chip. For the off-chip assay, the reaction takes place in a microtiter plate, whereas the electrophoretic separation and detection of substrate and product take place in the channels of the chip. To probe differences between the on-chip and off-chip assays, a panel of commercially available kinase inhibitors was assayed at 10 microM against cyclic AMP-dependent protein kinase A, glycogen synthase kinase 3beta, mitogen- and stress-activated protein kinase, and Akt1 using both the off-chip and on-chip assays. Good correlation was observed between inhibition measured by the two methods, with most of the differences in measured inhibition being attributed to compound solubility and enzyme concentration effects. Microfluidic devices represent an attractive platform for kinase assays due to high data quality and the possibility of on-chip assay integration, leading to reagent and labor savings.