gebhart/patrepeval huggingface dataset:
Efficacy of prefrontal theta-burst stimulation in refractory depression: a randomized sham-controlled study (2014)

Theta-burst transcranial magnetic stimulation could modulate cortical excitability and has the potential to treat refractory depression. However, there has been a lack of large randomized studies of the antidepressant efficacy of different forms of theta-burst stimulation, such as intermittent and continuous theta-burst stimulation. A randomized sham-controlled study was conducted to investigate antidepressant efficacy of theta-burst stimulation and to compare efficacy among left-prefrontal intermittent theta-burst stimulation, right-prefrontal continuous theta-burst stimulation and a combination of them in patients showing different levels of antidepressant refractoriness. A group of 60 treatment-refractory patients with recurrent major depressive disorder were recruited and randomized to four groups (Group A: continuous theta-burst stimulation; Group B: intermittent theta-burst stimulation; Group C: a combination of continuous and intermittent theta-burst stimulation; and Group D: sham theta-burst stimulation; 15 patients were included in each group). After 2 weeks of theta-burst stimulation treatment, depression improved in all groups. Groups B and C had better antidepressant responses (as reflected by % decreases in depression score) than Groups A and D (P = 0.001, post hoc analysis: B > A, B > D, C > A, and C > D), even after controlling for age and refractoriness scores. The mean antidepressant effect was highest in Group C and followed by that in Group B. Additionally, a significant placebo effect was found in patients with low refractoriness; this disappeared in patients with moderate-to-high refractoriness. A significant correlation existed between refractoriness scores and treatment responses. Treatment refractoriness was a significant factor negatively predicting efficacy of theta-burst stimulation (P = 0.039). This randomized sham-controlled study demonstrated that active theta-burst stimulation is a well-tolerated form of repetitive transcranial magnetic stimulation and has good antidepressant efficacy, particularly in depressed subjects within a certain range of treatment refractoriness.
NLRX1 Modulates Immunometabolic Mechanisms Controlling the Host–Gut Microbiota Interactions during Inflammatory Bowel Disease (2018)

Interactions among the gut microbiome, dysregulated immune responses, and genetic factors contribute to the pathogenesis of inflammatory bowel disease (IBD). <i>Nlrx1</i><sup>-/-</sup> mice have exacerbated disease severity, colonic lesions, and increased inflammatory markers. Global transcriptomic analyses demonstrate enhanced mucosal antimicrobial defense response, chemokine and cytokine expression, and epithelial cell metabolism in colitic <i>Nlrx1</i><sup>-/-</sup> mice compared to wild-type (WT) mice. Cell-specificity studies using cre-lox mice demonstrate that the loss of NLRX1 in intestinal epithelial cells (IEC) recapitulate the increased sensitivity to DSS colitis observed in whole body <i>Nlrx1</i><sup>-/-</sup> mice. Further, organoid cultures of <i>Nlrx1</i><sup>-/-</sup> and WT epithelial cells confirm the altered patterns of proliferation, amino acid metabolism, and tight junction expression. These differences in IEC behavior can impact the composition of the microbiome. Microbiome analyses demonstrate that colitogenic bacterial taxa such as <i>Veillonella</i> and <i>Clostridiales</i> are increased in abundance in <i>Nlrx1</i><sup>-/-</sup> mice and in WT mice co-housed with <i>Nlrx1</i><sup>-/-</sup> mice. The transfer of an <i>Nlrx1</i><sup>-/-</sup>-associated gut microbiome through co-housing worsens disease in WT mice confirming the contributions of the microbiome to the <i>Nlrx1</i><sup>-/-</sup> phenotype. To validate NLRX1 effects on IEC metabolism mediate gut-microbiome interactions, restoration of WT glutamine metabolic profiles through either exogenous glutamine supplementation or administration of 6-diazo-5-oxo-l-norleucine abrogates differences in inflammation, microbiome, and overall disease severity in <i>Nlrx1</i><sup>-/-</sup> mice. The influence NLRX1 deficiency on SIRT1-mediated effects is identified to be an upstream controller of the <i>Nlrx1</i><sup>-/-</sup> phenotype in intestinal epithelial cell function and metabolism. The altered IEC function and metabolisms leads to changes in barrier permeability and microbiome interactions, in turn, promoting greater translocation and inflammation and resulting in an increased disease severity. In conclusion, NLRX1 is an immunoregulatory molecule and a candidate modulator of the interplay between mucosal inflammation, metabolism, and the gut microbiome during IBD.
Biochemical and pharmacological profile of a potent and selective nonpeptide antagonist of the neurotensin receptor. (1993)

We describe the characteristics of SR 48692, a selective, nonpeptide antagonist of the neurotensin receptor. In vitro, this compound competitively inhibits 125I-labeled neurotensin binding to the high-affinity binding site present in brain tissue from various species with IC50 values of 0.99 +/- 0.14 nM (guinea pig), 4.0 +/- 0.4 nM (rat mesencephalic cells), 7.6 +/- 0.6 nM (COS-7 cells transfected with the cloned high-affinity rat brain receptor), 13.7 +/- 0.3 nM (newborn mouse brain), 17.8 +/- 0.9 nM (newborn human brain), 8.7 +/- 0.7 nM (adult human brain), and 30.3 +/- 1.5 nM (HT-29 cells). It also displaces 125I-labeled neurotensin from the low-affinity levocabastine-sensitive binding sites but at higher concentrations (34.8 +/- 8.3 nM for adult mouse brain and 82.0 +/- 7.4 nM for adult rat brain). In guinea pig striatal slices, SR 48692 blocks K(+)-evoked release of [3H]dopamine stimulated by neurotensin with a potency (IC50 = 0.46 +/- 0.02 nM) that correlates with its binding affinity. In a cell line derived from a human colon carcinoma (HT-29), SR 48692 competitively antagonizes neurotensin-induced intracellular Ca2+ mobilization with a pA2 (-log Kapp) values of 8.13 +/- 0.03, which is consistent with results obtained in binding studies. Moreover, SR 48692 is devoid of any intrinsic agonist activity. This compound is also active in vivo, since it reverses at low dose (80 micrograms/kg) the turning behavior induced by intrastriatal injection of neurotensin in mice with similar potency whatever the route of administration (i.p. or orally) and with a long duration of action (6 hr). Thus, being a potent and selective neurotensin receptor antagonist, SR 48692 may be considered as a powerful tool for investigating the role of neurotensin in physiological and pathological processes.
Effect of Interferon-τ on Prostaglandin Biosynthesis, Transport, and Signaling at the Time of Maternal Recognition of Pregnancy in Cattle: Evidence of Polycrine Actions of Prostaglandin E2 (2004)

Recognition and establishment of pregnancy involve several molecular and cellular interactions among the conceptus, uterus, and corpus luteum (CL). In ruminants, interferon-tau (IFNtau) of embryonic origin is recognized as the pregnancy recognition signal. Endometrial prostaglandin F(2alpha) (PGF(2alpha)) is the luteolysin, whereas PGE(2) is considered a luteoprotective or luteotrophic mediator at the time of establishment of pregnancy. The interplay between IFNtau and endometrial PGs production, transport, and signaling at the time of maternal recognition of pregnancy (MRP) is not well understood. We have studied the expression of enzymes involved in metabolism of PGE(2) and PGF(2alpha), cyclooxygenase-1 (COX-1) and COX-2, PG synthases (PGES and PGFS), PG 15-dehydrogenase, and PG transporter as well as PGE(2) (EP2 and EP3) and PGF(2alpha) receptors. IFNtau influences cell-specific expression of COX-2, PGFS, EP2, and EP3 in endometrium, myometrium, and CL in a spatio-temporal and tissue-specific manner, whereas it does not alter COX-1, PGES, PG 15-dehydrogenase, PG transporter, or PGF(2alpha) receptor expression in any of these tissues. In endometrium, IFNtau decreases PGFS in epithelial cells and increases EP2 in stroma. In myometrium, IFNtau decreases PGFS and increases EP2 in smooth muscle cells. In CL, IFNtau increases PGES and decreases EP3. Together, our results show that IFNtau directly or indirectly increases PGE(2) biosynthesis and EP2-associated signaling in endometrium, myometrium, and CL during MRP. Thus, PGE(2) may play pivotal roles in endometrial receptivity, myometrial quiescence, and luteal maintenance, indicating polycrine (endocrine, exocrine, paracrine, and autocrine) actions of PGE(2) at the time of MRP. Therefore, the establishment of pregnancy may depend not only on inhibition of endometrial PGF(2alpha), but also on increased PGE(2) production in cattle.
Small Interfering RNA–Directed Reversal of Urokinase Plasminogen Activator Demethylation Inhibits Prostate Tumor Growth and Metastasis (2007)

Recent studies have shown that small interfering RNA (siRNA) silences genes at the transcriptional level in human cells. However, the therapeutic potential of siRNA-mediated transcriptional gene silencing remains unclear. Here, we show that siRNA targeted to the urokinase plasminogen activator (uPA) promoter induced epigenetic transcriptional silencing in human prostate cancer cells. This silencing resulted in a dramatic reduction of tumor cell invasion and angiogenesis in vitro. Furthermore, the results from a bioluminescence tumor/metastasis model showed that the silencing of uPA significantly inhibits prostate tumor growth and the incidence of lung metastasis. Our findings represent a potentially powerful new approach to not only epigenetic silencing of metastasis or growth-promoting genes as a cancer therapy, but also as a means to shed light on how aberrant de novo methylation during cancer progression might be targeted to specific sequences.
The AF-1 Domain of the Orphan Nuclear Receptor NOR-1 Mediates Trans-activation, Coactivator Recruitment, and Activation by the Purine Anti-metabolite 6-Mercaptopurine (2003)

NOR-1/NR4A3 is an "orphan member" of the nuclear hormone receptor superfamily. NOR-1 and its close relatives Nurr1 and Nur77 are members of the NR4A subgroup of nuclear receptors. Members of the NR4A subgroup are induced through multiple signal transduction pathways. They have been implicated in cell proliferation, differentiation, T-cell apoptosis, chondrosarcomas, neurological disorders, inflammation, and atherogenesis. However, the mechanism of transcriptional activation, coactivator recruitment, and agonist-mediated activation remain obscure. Hence, we examined the molecular basis of NOR-1-mediated activation. We observed that NOR-1 trans-activates gene expression in a cell- and target-specific manner; moreover, it operates in an activation function (AF)-1-dependent manner. The N-terminal AF-1 domain delimited to between amino acids 1 and 112, preferentially recruits the steroid receptor coactivator (SRC). Furthermore, SRC-2 modulates the activity of the AF-1 domain but not the C-terminal ligand binding domain (LBD). Homology modeling indicated that the NOR-1 LBD was substantially different from that of hRORbeta, a closely related AF-2-dependent receptor. In particular, the hydrophobic cleft characteristic of nuclear receptors was replaced with a very hydrophilic surface with a distinct topology. This observation may account for the inability of this nuclear receptor LBD to efficiently mediate cofactor recruitment and transcriptional activation. In contrast, the N-terminal AF-1 is necessary for cofactor recruitment and can independently conscript coactivators. Finally, we demonstrate that the purine anti-metabolite 6-mercaptopurine, a widely used antineoplastic and anti-inflammatory drug, activates NOR-1 in an AF-1-dependent manner. Additional 6-mercaptopurine analogs all efficiently activated NOR-1, suggesting that the signaling pathways that modulate proliferation via inhibition of de novo purine and/or nucleic acid biosynthesis are involved in the regulation NR4A activity. We hypothesize that the NR4A subgroup mediates the genotoxic stress response and suggest that this subgroup may function as sensors that respond to genotoxicity.
Solubilization of the low density lipoprotein receptor (1979)

The low density lipoprotein (LDL) receptor was solubilized from membranes of bovine adrenal cortex and cultured human cells by incubation with the nonionic detergent octyl-beta-D-glucoside. Receptor activity released into the 100,000 x g supernatant was assayed by a solid-phase procedure: an aliquot of the soluble extract was removed, the detergent was diluted below its critical micellar concentration, causing the receptor to precipitate as a lipid-protein aggregate; the precipitate was collected by centrifugation and incubated with (125)I-labeled LDL ((125)I-LDL); and the receptor-bound (125)I-LDL was separated from free (125)I-LDL by filtration. The (125)I-LDL binding site that was precipitated from the soluble extract of bovine adrenocortical membranes appeared to be the same as the functional LDL receptor of cultured bovine adrenocortical cells and human fibroblasts. It exhibited high affinity and specificity (affinity for LDL more than 200-fold greater than for acetylated LDL, methylated LDL, or high density lipoprotein), dependence on calcium, and susceptibility to destruction by Pronase. The amount of (125)I-LDL binding activity in solubilized membranes from cultured cells was proportional to the number of receptors on the surface of the intact cells. Thus, the number of solubilized receptors was 1/20th of normal in mutant fibroblasts from a subject with homozygous familial hypercholesterolemia and was 1/4th of normal in human epithelioid carcinoma A-431 cells when they were grown in the presence of 25-hydroxycholesterol plus cholesterol. While in the soluble form in the presence of octyl-beta-D-glucoside, the LDL receptor can be carried through several steps of purification.
H2S and COS Gas Exchange of Transgenic Potato Lines with Modified Expression Levels of Enzymes Involved in Sulphur Metabolism (2011)

Different transgenic potato lines were generated for improving the nutritional value of tubers by an advanced perception of their sulphur metabolism. So far no data exist about possible implications for plant health and stress resistance. Metabolite analysis revealed that modifications of enzymes involved in sulphur metabolism were necessarily not reflected in distinctly altered thiol contents. The release of H2S by plants is putatively involved in pathogen resistance, because of its fungi-toxic mode of action. The emission of H2S was determined in 16 potato lines with modified expression level in ATP sulphurylase (ATPS), serine acetyltransferase (SAT), O-acetylserine(thiol)lyase (OASTL), homoserine kinase (HSK) and threonine synthase activities. The emission significantly increased by factor 7 in one of the ATPS antisense lines and by factor 8 in one of the OASTL antisense lines. A strong increase in H2S emissions was observed in transgenic plants based on the potato cultivar White Lady, which expressed the Escherichia coli SAT. In addition, the exchange of COS was determined in relation to genetic modifications. Generally, plants act as a sink for COS, but all transgenic lines expressing the E. coli HSK and one of the ATPS antisense lines emitted COS indicating to strong changes in the metabolism of these plants. Such alterations in the gas exchange of transgenic potato plants will most likely also affect their resistance against biotic and abiotic stress.
Efficacy of small‐molecule glycogen synthase kinase‐3 inhibitors in the postnatal rat model of tau hyperphosphorylation (2007)

Selective small-molecule inhibitors of GSK-3 reduce tau phosphorylation in vivo. These findings corroborate earlier suggestions that GSK-3beta may be an attractive target for disease-modification in AD and related conditions where tau phosphorylation is believed to contribute to disease pathogenesis.
Algorithm 368: Numerical inversion of Laplace transforms [D5] (1970)

article Free Access Share on Algorithm 368: Numerical inversion of Laplace transforms [D5] Author: Harald Stehfest J. W. Goethe Univ., W. Germany J. W. Goethe Univ., W. GermanyView Profile Authors Info & Claims Communications of the ACMVolume 13Issue 1Jan. 1970pp 47–49https://doi.org/10.1145/361953.361969Published:01 January 1970Publication History 2,425citation6,117DownloadsMetricsTotal Citations2,425Total Downloads6,117Last 12 Months653Last 6 weeks146 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
High-power Er:Yb fiber laser with very high numerical aperture pump-cladding waveguide (2003)

One watt of laser power at 1535 nm has been generated from an Er:Yb codoped double-clad fiber structure, in which the inner cladding was suspended in air by a large number of thin silica webs. The acceptance numerical aperture (NA) of the inner cladding has been measured over a range of wavelengths, for lengths from 1 up to 100 m. For fiber lengths of ∼40 m, the NA at the pump diode wavelength was 0.88.
Anti–PD-1/PD-L1 therapy of human cancer: past, present, and future (2015)

Major progress has been made toward our understanding of the programmed death-1/programmed death ligand-1 (PD-1/PD-L1) pathway (referred to as the PD pathway). mAbs are already being used to block the PD pathway to treat human cancers (anti-PD therapy), especially advanced solid tumors. This therapy is based on principles that were discovered through basic research more than a decade ago, but the great potential of this pathway to treat a broad spectrum of advanced human cancers is just now becoming apparent. In this Review, we will briefly review the history and development of anti-PD therapy, from the original benchwork to the most up-to-date clinical results. We will then focus the discussion on three basic principles that define this unique therapeutic approach and highlight how anti-PD therapy is distinct from other immunotherapeutic approaches, namely tumor site immune modulation, targeting tumor-induced immune defects, and repairing ongoing (rather than generating de novo) tumor immunity. We believe that these fundamental principles set the standard for future immunotherapies and will guide our efforts to develop more efficacious and less toxic immune therapeutics to treat human cancers.
Novel One-Step Route for Synthesizing CdS/Polystyrene Nanocomposite Hollow Spheres (2004)

CdS/polystyrene nanocomposite hollow spheres with diameters between 240 and 500 nm were synthesized under ambient conditions by a novel microemulsion method in which the polymerization of styrene and the formation of CdS nanoparticles were initiated by gamma-irradiation. The product was characterized by transmission electron microscopy (TEM), field-emission scanning electron microscopy (FESEM), X-ray powder diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, and thermogravimetric analysis (TGA), which show the walls of the hollow spheres are porous and composed of polystyrene containing homogeneously dispersed CdS nanoparticles. The quantum-confined effect of the CdS/polystyrene nanocomposite hollow spheres is confirmed by the ultraviolet-visible (UV-vis) and photoluminescent (PL) spectra. We propose that the walls of these nanocomposite hollow spheres originate from the simultaneous synthesis of polystyrene and CdS nanoparticles at the interface of microemulsion droplets. This novel method is expected to produce various inorganic/polymer nanocomposite hollow spheres with potential applications in the fields of materials science and biotechnology.
Temporal phase-unwrapping algorithm for automated interferogram analysis (1993)

A new algorithm is proposed for unwrapping interferometric phase maps. Existing algorithms search the two-dimensional spatial domain for 2π discontinuities: only one phase map is required, but phase errors can propagate outward from regions of high noise, corrupting the rest of the image. An alternative approach based on one-dimensional unwrapping along the time axis is proposed. It is applicable to an important subclass of interferometry applications, in which a sequence of incremental phase maps can be obtained leading up to the final phase-difference map of interest. A particular example is quasi-static deformation analysis. The main advantages are (i) it is inherently simple, (ii) phase errors are constrained within the high-noise regions, and (iii) phase maps containing global discontinuities are unwrapped correctly, provided the positions of the discontinuities remain fixed with time. The possibility of real-time phase unwrapping is also discussed.
Matrilysin(MMP-7) Is a Novel Broadly Expressed Tumor Antigen Recognized by Antigen-Specific T Cells (2008)

Our study describes the identification of a novel broadly expressed T-cell epitope derived from the MMP-7 protein that represents an interesting candidate to be applied in immunotherapies of human malignancies targeting both tumor cells and neovascularization.
High ambient-contrast-ratio display using tandem reflective liquid crystal display and organic light-emitting device (2005)

A high ambient-contrast-ratio (A-CR) and large aperture-ratio display is conceptually demonstrated and experimentally validated by stacking a normally black reflective liquid crystal display (NB-RLCD) and an organic light-emitting device (OLED). Such a tandem device can be switched between the NB-RLCD mode and the OLED mode under bright and dark ambient light, respectively. The normally black characteristic of the RLCD also helps to boost the A-CR under OLED-mode operation. To obtain a better image quality in the RLCD mode, a bumpy and transmissive structure is used to eliminate the specular reflection and to increase the viewing angle performance that results in CR>2:1 over 55 degrees viewing cone. Besides, such a structure can also increase the external quantum efficiency of the OLED by 49.4%. In our experiments, regardless of the ambient intensity the A-CR is kept higher than 100:1.
The Role of Thymus-Expressed Chemokine and Its Receptor CCR9 on Lymphocytes in the Regional Specialization of the Mucosal Immune System (2000)

Chemokines play an important role in the migration of leukocytes at sites of inflammation, and some constitutively expressed chemokines may direct lymphocyte trafficking within lymphoid organs and peripheral tissues. Thymus-expressed chemokine (TECK or Ckbeta-15/CCL25), which signals through the chemokine receptor CCR9, is constitutively expressed in the thymus and small intestine but not colon, and chemoattracts a small fraction of PBLs that coexpress the integrin alpha(4)beta(7). Here we show that TECK is expressed in the human small bowel but not colon by endothelial cells and a subset of cells in intestinal crypts and lamina propria. CCR9 is expressed in the majority of freshly isolated small bowel lamina propria mononuclear cells (LPMC) and at significantly higher levels compared with colonic LPMC or PBL. TECK was selectively chemotactic for small bowel but not colonic LPMC in vitro. The TECK-induced chemotaxis was sensitive to pertussis toxin and partially inhibited by Abs to CCR9. TECK attracts predominantly the T cell fraction of small bowel LPMC, whereas sorted CD3(+)CCR9(+) and CD3(+)CCR9(-) lymphocytes produce similar Th1 or Th2 cytokines at the single cell level. Collectively, our data suggest that the selective expression of TECK in the small bowel underlie the homing of CCR9(+) intestinal memory T cells to the small bowel rather than to the colon. This regional specialization implies a segregation of small intestinal from colonic immune responses.