gebhart/patrepeval huggingface dataset:
Differential Activation of c-Jun NH2-Terminal Kinase and p38 Pathways During FTY720-Induced Apoptosis of T Lymphocytes That Is Suppressed by the Extracellular Signal-Regulated Kinase Pathway (1999)

FTY720 is a novel immunosuppressive drug derived from a metabolite from Isaria sinclairii that is known to induce apoptosis of rat splenic T cells. In this study, we examined the intracellular signaling pathway triggered by FTY720. Treatment of human Jurkat T lymphocytes with FTY720-induced apoptosis characterized by DNA fragmentation. The same treatment induced activation of protein kinases such as c-Jun NH2-terminal kinase (JNK), p38/CSBP (CSAID-binding protein), and a novel 36-kDa myelin basic protein (MBP) kinase, but not extracellular signal-regulated kinase (ERK). Pretreatment of Jurkat cells with DEVD-CHO blocked FTY720-induced DNA fragmentation as well as the activation of p38/CSBP. However, DEVD-CHO treatment failed to inhibit FTY720-induced activation of JNK and the 36-kDa MBP kinase. We have also demonstrated that activation of the ERK signaling pathway completely suppressed the FTY720-induced apoptotic process including activation of caspase 3 and activation of JNK and the 36-kDa MBP kinase. Furthermore, transient expression of constitutively active mitogen-activated protein kinase/ERK kinase (MEK) protected the cells from FTY720-induced cell death. The effect of MEK was canceled by coexpression of a mitogen-activated protein kinase phosphatase, CL100. These results indicate that JNK and p38 pathways are differentially regulated during FTY720-induced apoptosis and that activation of ERK pathway alone is sufficient to cancel the FTY720-induced death signal.
ChemInform Abstract: Room Temperature Sonoelectrochemical Synthesis of Molybdenum Sulfide Fullerene‐Like Nanoparticles. (1999)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Inhibition of antibacterial activity of himastatin, a new antitumor antibiotic from Streptomyces hygroscopicus, by fatty acid sodium salts (1994)

Himastatin, a cyclohexadepsipeptide antibiotic, had in vivo antitumor activity against localized P388 leukemia and B16 melanoma but had no distal site antitumor activity. An in vitro Bacillus subtilis well-agar diffusion assay was employed to test the hypothesis that himastatin was enzymatically inactivated. The activity of himastatin against B. subtilis was inhibited when himastatin was mixed with mouse liver S9 fraction and microsomes. However, subsequent investigations demonstrated that the markedly decreased antibacterial activity was not enzymatic in nature but was related to the presence of certain fatty acid salts. Saturated fatty acid sodium salts with a carbon chain number of 8 or more reduced the antimicrobial activity of himastatin 50 to 100 times. If antibiotics such as ampicillin, bacitracin, chloramphenicol, and tunicamycin were used in place of himastatin, no meaningful reduction in antibacterial activity occurred. However, the antibacterial activity of the membrane-active peptide antibiotic polymyxin B, but not that of polymyxin E (colistin), was reduced in a manner similar to that of himastatin. Importantly, the activity of himastatin against HCT-116 colon adenocarcinoma cells in soft agar was markedly reduced in the presence of sodium palmitate as the reference fatty acid salt. The data indicate that himastatin may be trapped in micelles in vitro. It may be speculated that the lack of distal site antitumor activity resulted from similar complex formation between himastatin and lipids in vivo. The results also suggest that the cancer cytotoxic and antimicrobial effects of himastatin may result from interactions with the cell membrane.
Effect of ozone treatment on the electrical properties of (Ba0.7Sr0.3)TiO3 thin films (2005)

Thin films of (BaxSr1−x)TiO3 were deposited on Pt-coated Si substrates by chemical solution deposition. The films were postannealed under ozone atmosphere at various temperatures. Although there was no change observed in the microstructure after the anneal in ozone, the dielectric dispersion and the loss tangents were reduced for the films. It was also noticed that the leakage current reduced by almost two orders of magnitude after treatment with ozone. The ozone treatment was done at various temperatures between 250 and 450°C to find an optimum temperature with regard to the electrical properties. Films postannealed in ozone at 350°C for 30min showed a leakage reduction by almost three orders of magnitude. The leakage dependence on ozone postannealing is discussed on the basis of an interface-dominated (Schottky injection) and a bulk-dominated (point defect approach) charge transport process as the two limiting conduction mechanisms across thin films.
J054053 Molecular Dynamics on the Effect of Velocity on the Dynamic Contact Angle of Water on Platinum Surface (2011)

The dynamic contact angle and the behavior of the contact line of water on platinum surface were investigated by using molecular dynamics (MD). The simulations were performed for a system in which water was sheared between two parallel platinum plates moving in the opposite direction with each other. The 2D-particle-mesh-Ewald method for long range force correction was used in the simulation. The contact angle defined with the water-vapor interface position in the 2nd and 3rd nearest layers along the wall was measured for the moving velocities of the wall. It was shown that the receding contact was decreased as the wall velocity was increased. The advancing contact angle was increased with the wall velocity. While the receding contact line (interface in the first nearest layer) did not move for the wall, velocity difference was observed between the advancing contact line and the wall. The fluid velocity near the receding contact line in the first layer was equal with the wall velocity up to the contact line, which indicates that the water molecules in the first layer were locked to the wall. On the other hand, the fluid velocity near the advancing contact line was slowed down in the vicinity of the contact line.
Single Cell RNA Sequencing of Serial Tumor and Blood Biopsies from Lymphoma Patients on an in Situ Vaccination Clinical Trial (2018)

Abstract The critical determinants of effective antitumor immune responses, whether native or induced by therapy, remain poorly understood due to the complexity and plasticity of the immune system. To better profile and track these responses, we have employed the novel approach of performing single cell RNA sequencing for paired gene expression and immune repertoire analysis on tumor fine needle aspirates and peripheral blood of lymphoma patients undergoing immunotherapy on a clinical trial (NCT02927964). In this in situ vaccination study, patients with low-grade lymphoma received local low-dose radiation and intratumoral SD-101 (a TLR9 agonist) to one site of disease, with systemic ibrutinib (a BTK inhibitor) added in the second week of treatment. Tumor fine needle aspirates and peripheral blood samples were obtained prior to treatment, at one week (prior to ibrutinib initiation) and at six weeks after treatment start. Single cell preparations were processed using 10X Genomics' single cell RNA transcription and library preparation protocol, followed by sequencing on the Illumina platform. Cells were sequenced to an average depth of 50,000 reads/cell for gene expression libraries and 5000 reads/cell for TCR sequencing. Identification of variable genes, principal component and/or canonical correlation analysis, graph-based clustering and differential expression analysis of single-cell gene expression data was performed using the Seurat algorithm. Single-cell TCR repertoires were analyzed using TCR-specific analysis software. This data is being integrated with data from multiparameter flow cytometry and functional immune assays for these same patients, as well as with their clinical outcomes. Sequencing libraries have been prepared from 37 samples from 4 patients thus far. We have successfully generated single cell gene expression and TCR libraries from 3,000-10,000 cells from tumor fine needle aspirates and peripheral blood, with excellent sequencing quality metrics obtained. From detailed analyses of one patient's samples thus far, we have identified distinct immune populations in blood and tumor (Figure 1), including light-chain restricted B-cells, with good concordance with flow cytometry. Preliminary results show changes occurring in immune cell frequencies and phenotypes at the treated tumor site, at distant tumor sites and in the peripheral blood when samples from before and after treatment are compared. Sample collection, sequencing, and analysis are ongoing. Deep profiling of serial biopsies during immunotherapy using single cell RNA sequencing promises to illuminate underlying cellular dynamics, and paired with clinical outcome data, determinants of response. Ultimately, this may provide a roadmap for successful translation of single-cell genomics into the clinic for treatment monitoring and response prediction. Disclosures No relevant conflicts of interest to declare.
Optimal Multiple Surface Segmentation with Convex Priors in Irregularly Sampled Space. (2016)

Optimal surface segmentation is widely used in numerous medical image segmentation applications. However, nodes in the graph based optimal surface segmentation method typically encode uniformly distributed orthogonal voxels of the volume. Thus the segmentation cannot attain an accuracy greater than a single unit voxel, i.e. the distance between two adjoining nodes in graph space. Segmentation accuracy higher than a unit voxel is achievable by exploiting partial volume information in the voxels which shall result in non-equidistant spacing between adjoining graph nodes. This paper reports a generalized graph based optimal multiple surface segmentation method with convex priors which segments the target surfaces in irregularly sampled space. The proposed method allows non-equidistant spacing between the adjoining graph nodes to achieve subvoxel accurate segmentation by utilizing the partial volume information in the voxels. The partial volume information in the voxels is exploited by computing a displacement field from the original volume data to identify the subvoxel accurate centers within each voxel resulting in non-equidistant spacing between the adjoining graph nodes. The smoothness of each surface modelled as a convex constraint governs the connectivity and regularity of the surface. We employ an edge-based graph representation to incorporate the necessary constraints and the globally optimal solution is obtained by computing a minimum s-t cut. The proposed method was validated on 25 optical coherence tomography image volumes of the retina and 10 intravascular multi-frame ultrasound image datasets for subvoxel and super resolution segmentation accuracy. In all cases, the approach yielded highly accurate results. Our approach can be readily extended to higher-dimensional segmentations.
A GIPC1-Palmitate Switch Modulates Dopamine Drd3 Receptor Trafficking and Signaling (2016)

Palmitoylation is involved in several neuropsychiatric and movement disorders for which a dysfunctional signaling of the dopamine D3 receptor (Drd3) is hypothesized. Computational modeling of Drd3's homologue, Drd2, has shed some light on the putative role of palmitoylation as a reversible switch for dopaminergic receptor signaling. Drd3 is presumed to be palmitoylated, based on sequence homology with Drd2, but the functional attributes afforded by Drd3 palmitoylation have not been studied. Since these receptors are major targets of antipsychotic and anti-Parkinsonian drugs, a better characterization of Drd3 signaling and posttranslational modifications, like palmitoylation, may improve the prospects for drug development. Using molecular dynamics simulations, we evaluated in silico how Drd3 palmitoylation could elicit significant remodeling of the C-terminal cytoplasmic domain to expose docking sites for signaling proteins. We tested this model in cellulo by using the interaction of Drd3 with the G-alpha interacting protein (GAIP) C terminus 1 (GIPC1) as a template. From a series of biochemical studies, live imaging, and analyses of mutant proteins, we propose that Drd3 palmitoylation acts as a molecular switch for Drd3-biased signaling via a GIPC1-dependent route, which is likely to affect the mode of action of antipsychotic drugs.
<title>Novel acousto-optic photonic switch</title> (1991)

An optical crossbar for single-mode fibers using acousto-optic (AO) interactions in a single acousto-optic device capable of rapid reconfiguration is presented.© (1991) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Politische Manifeste (2010)

Streift man mit einem geschichtlich interessierten Blick durch die Historie der letzten zweihundert Jahre, so stt man gar nicht einmal selten auf Ereignisse, die mit dem Wort "Manifest" in Verbindung gebracht werden.Denn Manifeste sind verlsslich zu historisch brisanten Daten anzutreffen.Dann, wenn es um gesellschaftlichen Umsturz, verbrecherischen Krieg oder gar drohende Vernichtung der Menschheit geht -man denke nur an das Kommunistische Manifest 1848, den Aufruf "An die Kulturwelt" 1914, den Appell anlsslich des Volksentscheids zur Frstenenteignung 1926, die Gttinger Erklrung 1957 oder "What we're fighting for" mitsamt der Reaktion aus Deutschland anlsslich des US-amerikanischen "Anti-Terrorkriegs" im Jahr 2002.Insoweit scheinen Manifeste bevorzugt in Phasen gesellschaftlicher Bewegung, politischen Konflikts, instabiler Verhltnisse aufzutauchen.Wie ausgiebige Beobachtung zeigt, "massieren sich die Manifeste quantita
Initial and Early Follow‐up Assessment of the Clinical Efficacy of a Multiparameter‐Programmable Puise Generator (1981)

Recent advances in pacemaker technology have produced noninvasively multiparameter‐programmable puise generators that have the potential for resolving complications that result from the pacing system and forproviding a mechanism whereby adjustments can be made for the specific needs of a patient without corapromising reliability and longevity. These applications were assessed by analyzing the initial indications, clinical efficacy, and reliability in 100 consecufive patients who received a multiparameter‐program‐mable puJse generator. Data analysis showed that 78% of the 100 patients had changes in rate programmed, 16% in pufse width, and 5% in sensitivity. Program‐mability was utilized for voJtage amplitude (one patient) but was not utilized for hysteresis and refractory period. Although progrtimming changes (rate and pulse width) generally could have been accomplished with simpler units, program‐mability for sensitivity made it possible to solve pacemaker problems in five patients and clearly eliminated the need for reoperation in two patients. The compact size of the multiparameter‐programmable pulse generator has allowed its use in patients in the pediatric age group, patients with a small frame, and patients with a major concern about cosmetic appearance. Programming sensitivity for proper sensing of the atrial signal allows use of the multiparameter‐programmable pulse generator as an atrial pacemaker. This was done in one pediatric patient who also benefited from suppression of atrial overdrive. There have been no episodes of spurious programming. Reliabitity has not been sacrificed by the increased complexity of this unit. If preimplant criteria for use of a multiparameter‐program‐mable puise generator are too sfrict, this may limit its potential therapeutic value because the need for its flexible characleristics is unpredictable.
Solution-Phase Parallel Synthesis of Carbamates as γ-Secretase Inhibitors (2007)

A novel methodology for parallel liquid-phase synthesis of carbamates suitable for the preparation of sterically hindered molecules is disclosed. The alcohols are converted to 4-nitrophenylcarbonates, followed by the reaction with amines. Side product 4-nitrophenol and the unreacted excess amines are scavenged by appropriately chosen cleanup resins, selected among Amberlyst A26 (hydroxide form) and macroporous sulfonic acid (MP-TsOH) or polystyrene isocyanate (PS-NCO) and polystyrene benzaldehyde (PS-PhCHO) resins. As a part of a medicinal chemistry program directed toward finding gamma-secretase inhibitors as prospective drug candidates for Alzheimer's disease, a 6 x 24 library of carbamates was prepared. Out of 144 library members, 133 had a purity for the targeted compound of 80% or better. The prepared compounds were assessed in the gamma-secretase inhibition assay and demonstrated activity with IC 50 values in the range from 1 microM to 5 nM, with the activity of 7 compounds being better than 10 nM.
<title>Advanced 4.7-GB DVD-RAM with a 4X data transfer rate</title> (2002)

We demonstrated the possibility of high data rate recording on a DVD-RAM disk which utilizes Ge-Sb-Te phase-change materials. To ensure high transfer rate overwriting on the DVD, quadruple speed (44Mbps) recording at a linear velocity of 16.4 m/s was tested using a Sn-added Ge-Sn-Sb-Te material as the recording layer. Double speed (22Mbps) recording on the present 4.7GB DVD-RAM at a linear velocity of 8.2 m/s was also tested. A CNR of more than 53 dB and an erasability of more than 30 dB were obtained at each double, triple and quadruple speeds. In addition, by recording via 8-16 random modulation signals, a jitter of 9 percent or less and a direct overwrite performance of 100,000 cycles were confirmed.
Lippmann and Dewey (2019)

Abstract During the 1920s, Walter Lippmann expressed his growing doubts about the epistemic capacities of the journalistically informed mass public, and John Dewey published three responses to these doubts—none of which grappled with the interpretive problems that Lippmann saw as the barrier to an adequate understanding of modern society. Rather than lamenting the mass public’s lack of knowledge, as Dewey did, Lippmann was mainly worried about the inevitably biased stereotypes by means of which journalists and their readers winnow down overabundant knowledge into coherent interpretations. Dewey’s hopes for a new form of journalism, his faith in ordinary people’s knowledge of the problems afflicting them, and his ideas for a new social science failed to confront this problem of interpretation. However, Lippmann’s own solution, early in the debate, was an epistocracy of statisticians, which also failed to confront the interpretive problem he had identified. The debate ended, then, with neither engagement nor resolution.
Genetic variation in soluble epoxide hydrolase (EPHX2) and risk of coronary heart disease: The Atherosclerosis Risk in Communities (ARIC) study (2020)

Endothelial dysfunction contributes to the development of coronary heart disease (CHD). Soluble epoxide hydrolase metabolizes epoxyeicosatrienoic acids in the vasculature and regulates endothelial function. We sought to determine whether genetic variation in soluble epoxide hydrolase (EPHX2) was associated with the risk of CHD. We genotyped 2065 Atherosclerosis Risk in Communities study participants (1085 incident CHD cases, 980 non-cases) for 10 previously identified polymorphisms in EPHX2. Using a case–cohort design, associations between incident CHD risk and both non-synonymous EPHX2 polymorphisms and phase-reconstructed haplotypes were evaluated using proportional hazards regression. Individuals carrying the K55R polymorphism variant allele demonstrated higher apparent soluble epoxide hydrolase activity in vivo. Presence of the K55R variant allele was significantly more common among Caucasian CHD cases when compared with non-cases (20.8% versus 15.3%, respectively, P = 0.012), and was associated with significantly higher risk of incident CHD (adjusted hazard rate ratio 1.45, 95% confidence interval 1.05–2.01, P = 0.026). A significant association between the K55R variant allele and risk of CHD was not observed in African-Americans. The distribution of reconstructed haplotypes were significantly different in Caucasian cases when compared with non-cases (P = 0.021). Significant differences in haplotype distribution were not observed in African-Americans (P = 0.315). Genetic variation in EPHX2 was significantly associated with risk of incident CHD in Caucasians, implicating EPHX2 as a potential cardiovascular disease-susceptibility gene.
Guidelines for cardiac pacing and cardiac resynchronization therapy: The Task Force for Cardiac Pacing and Cardiac Resynchronization Therapy of the European Society of Cardiology. Developed in Collaboration with the European Heart Rhythm Association (2007)

The ESC Guidelines represent the views of the ESC and were arrived at after careful consideration of the available evidence at the time they were written. Health professionals are encouraged to take them fully into account when exercising their clinical judgement. The guidelines do not, however, override the individual responsibility of health professionals to make appropriate decisions in the circumstances of the individual patients, in consultation with that patient, and where appropriate and necessary the patient's guardian or carer. It is also the health professional's responsibility to verify the rules and regulations applicable to drugs and devices at the time of prescription.
OTFS-Based Multiple-Access in High Doppler and Delay Spread Wireless Channels (2018)

We propose a multiple-access (MA) method in the uplink of a orthogonal time frequency space modulation-based wireless communication system where the channel has high Doppler and delay spread. Each user terminal (UT) is allocated delay-Doppler (DD) resource blocks which are spaced at equal intervals in the DD domain. This limits the corresponding time-frequency (TF) transmit signal to a sub-domain of the entire TF domain. By allocating non-overlapping portions to the TF transmit signal of different UTs, multi-user interference (MUI) is avoided. The proposed MA method is analytically shown to be MUI free and therefore has a significantly higher sum spectral efficiency when compared to other methods proposed in literature which utilize guard bands in the DD domain to reduce MUI.