gebhart/patrepeval huggingface dataset:
Sustained rescue of prefrontal circuit dysfunction by antidepressant-induced spine formation (2019)

The neurobiological mechanisms underlying the induction and remission of depressive episodes over time are not well understood. Through repeated longitudinal imaging of medial prefrontal microcircuits in the living brain, we found that prefrontal spinogenesis plays a critical role in sustaining specific antidepressant behavioral effects and maintaining long-term behavioral remission. Depression-related behavior was associated with targeted, branch-specific elimination of postsynaptic dendritic spines on prefrontal projection neurons. Antidepressant-dose ketamine reversed these effects by selectively rescuing eliminated spines and restoring coordinated activity in multicellular ensembles that predict motivated escape behavior. Prefrontal spinogenesis was required for the long-term maintenance of antidepressant effects on motivated escape behavior but not for their initial induction.
Inhibition of growth and metastatic progression of pancreatic carcinoma in hamster after somatostatin receptor subtype 2 (sst2) gene expression and administration of cytotoxic somatostatin analog AN-238 (2000)

The sst2 somatostatin receptor mediates the antiproliferative effects of somatostatin analogs. The present study demonstrates that stable expression of sst2 in the hamster pancreatic cancer cells PC-1 and PC-1.0 activates an autocrine negative loop leading to an in vitro inhibition of cell proliferation. In vivo studies conducted in Syrian golden hamsters after orthotopic implantation of PC-1.0 cells showed that both tumor growth and metastatic progression of allografts containing 100% of sst2-expressing cells were significantly inhibited for up to 20 days after implantation, as compared with control allografts that did not express sst2. A local antitumor bystander effect was observed after induction of mixed tumors containing a 1:3 ratio of sst2-expressing cells to control cells. Tumor volume and incidence of metastases of mixed tumors were significantly reduced at day 13 post implantation. This effect decreased with time as at day 20, growth of mixed tumors was similar to that of control tumors. After administration of the cytotoxic somatostatin conjugate AN-238 on day 13, antitumor bystander effect observed in mixed tumors was significantly extended to day 20. We also observed that in vitro invasiveness of sst2-expressing PC-1.0 cells was significantly reduced. Tyrosine dephosphorylation of E-cadherin may participate in restoring the E-cadherin function, reducing in turn pancreatic cancer cell motility and invasiveness. This dephosphorylation depends on the tyrosine phosphatase src homology 2-containing tyrosine phosphatase 1 (SHP-1) positively coupled to sst2 receptor. The inhibitory effect of sst2 gene expression on pancreatic cancer growth and invasion combined with chemotherapy with targeted cytotoxic somatostatin analog administration provides a rationale for a therapeutic approach to gene therapy based on in vivo sst2 gene transfer.
Targeting the Cytoprotective Chaperone, Clusterin, for Treatment of Advanced Cancer (2010)

Many strategies used to kill cancer cells induce stress-responses that activate survival pathways to promote emergence of a treatment resistant phenotype. Secretory clusterin (sCLU) is a stress-activated cytoprotective chaperone up-regulated by many varied anticancer therapies to confer treatment resistance when overexpressed. sCLU levels are increased in several treatment recurrent cancers including castrate resistant prostate cancer, and therefore sCLU has become an attractive target in cancer therapy. sCLU is not druggable with small molecule inhibitors, therefore nucleotide-based strategies to inhibit sCLU at the RNA level are appealing. Preclinical studies have shown that antisense oligonucleotide (ASO) or siRNA knockdown of sCLU have preclinical activity in combination with hormone- and chemotherapy. Phase I and II clinical trial data indicate that the second generation ASO, custirsen (OGX-011), has biologic and clinical activity, suppressing sCLU expression in prostate cancer tissues by more than 90%. A randomized study comparing docetaxel-custirsen to docetaxel alone in men with castrate resistant prostate cancer reported improved survival by 7 months from 16.9 to 23.8 months. Strong preclinical and clinical proof-of-principle data provide rationale for further study of sCLU inhibitors in randomized phase III trials, which are planned to begin in 2010.
Analysis of Ground Vibrations Caused by Open Pit Production Blasts ? A Case Study (2001)

Abstract In order to study the characteristics of ground vibrations caused by production blasts in an open pit gold mine and to evaluate the impact of the vibrations to buildings, a seismic survey was conducted at an open pit mine. Two monitoring lines with multiple seismic stations were surveyed. The first line had a length of 4,492 m and the second line runs approximately perpendicular to the first line with a length of 823 m. The seismographs recorded the particle acceleration, velocity, and displacement in longitudinal, transverse and vertical directions. The magnitudes of peak particle motions were calculated and compared with several established damage criteria used in mining and geotechnical/structure engineering. Empirical equations were established based on the field measurements. Analyses were also performed to exam the effects of geological structures on the attenuation of individual vibration components as well as the peak vector sum of the particle velocity.
Low Doses of the Glycine/NMDA Receptor Antagonist <i>R</i>‐(+)‐HA‐966 but not <scp>d</scp>‐Cycloserine Induce Paroxysmal Activity in Limbic Brain Regions of Kindled Rats (1994)

(+)-HA-966 [R-(+)-3-amino-1-hydroxypyrrolid-2-one], a functional antagonist at the glycine modulatory site on the N-methyl-D-aspartate (NMDA) receptor/ion channel complex, was evaluated in amygdala-kindled rats, a model of epilepsy recently shown to exhibit enhanced susceptibility to the adverse effects of competitive and non-competitive NMDA receptor antagonists. Since (+)-HA-966 displays weak partial agonistic effects at the glycine site (approximately 10% efficacy of glycine), D-cycloserine, a glycine ligand with much higher intrinsic activity, was evaluated in kindled rats for comparison. Following drug administration, electrographic activity was recorded from the basolateral amygdala (i.e. the focal site) as well as the ipsilateral piriform cortex, ventral hippocampus and nucleus accumbens. In addition to the evaluation of original recordings, power spectrum analysis was used to delineate drug effects. (+)-HA-966 (20-40 mg/kg i.p.) induced marked alterations in electrographic recordings, including increases in amplitude and isolated spiking, i.e. signs of paroxysmal activity. The severity or duration of fully kindled seizures was not changed by (+)-HA-966, but the drug dramatically increased the duration of immobilization and limbic seizure activity following a kindled motor seizure. In contrast to (+)-HA-966, D-cycloserine did not induce any electrographic changes, even when administered in much higher doses than (+)-HA-966. The changes in electrographic recordings seen after administration of (+)-HA-966 in kindled rats were almost absent in non-kindled rats, indicating that kindling had increased the sensitivity to the paroxysmal effects of the glycine/NMDA receptor ligand. The data indicate that functional glycine/NMDA antagonists with low intrinsic efficacy may bear the risk of proconvulsant activity.
A random variance model for detection of differential gene expression in small microarray experiments (2003)

ftp://linus.nci.nih.gov/pub/techreport/RVM_supplement.pdf
Downregulation of estrogen receptor alpha and beta expression in carcinogen-induced mammary gland tumors of rats. (2004)

This study represents that the decrease of expression of ER alpha and ER beta is associated with mammary carcinogenesis, and suggests that modulation of ER alpha and ER beta may be the target for the treatment of mammary gland tumors.
Learning to tokenize web domains (2011)

Domain Match is an Internet monetization product offered by web companies like Yahoo! The product offers display of ads and search results, when a user requests a webpage from a domain which is non-existent or does not have any content. This product earns significant amount of advertising revenue for major internet companies like Yahoo! Hence it is an important product receiving millions of queries per day. Domain Match (DM) works by tokenizing the input domains and sub-folders into keywords and then displaying ads and search results queried on the keywords. In this poster, we describe a machine learning based solution, which automatically learns to tokenize new domains, given a training dataset containing a set of domains and their tokenizations. We use positional frequency and parts of speech as features for scoring tokens. Tokens are scored combined using various scoring models. We compare two ways of training the models: a simple gain function based training and a large margin training. Experimental results are encouraging.
Age-related epigenetic drift in the pathogenesis of MDS and AML (2014)

The myelodysplastic syndrome (MDS) is a clonal hematologic disorder that frequently evolves to acute myeloid leukemia (AML). Its pathogenesis remains unclear, but mutations in epigenetic modifiers are common and the disease often responds to DNA methylation inhibitors. We analyzed DNA methylation in the bone marrow and spleen in two mouse models of MDS/AML, the NUP98-HOXD13 (NHD13) mouse and the RUNX1 mutant mouse model. Methylation array analysis showed an average of 512/3445 (14.9%) genes hypermethylated in NHD13 MDS, and 331 (9.6%) genes hypermethylated in RUNX1 MDS. Thirty-two percent of genes in common between the two models (2/3 NHD13 mice and 2/3 RUNX1 mice) were also hypermethylated in at least two of 19 human MDS samples. Detailed analysis of 41 genes in mice showed progressive drift in DNA methylation from young to old normal bone marrow and spleen; to MDS, where we detected accelerated age-related methylation; and finally to AML, which markedly extends DNA methylation abnormalities. Most of these genes showed similar patterns in human MDS and AML. Repeat element hypomethylation was rare in MDS but marked the transition to AML in some cases. Our data show consistency in patterns of aberrant DNA methylation in human and mouse MDS and suggest that epigenetically, MDS displays an accelerated aging phenotype.
Peroxisome Proliferator-Activated Receptors and Acute Lung Injury (2007)

Peroxisome proliferator-activated receptors are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily. PPARs regulate several metabolic pathways by binding to sequence-specific PPAR response elements in the promoter region of target genes, including lipid biosynthesis and glucose metabolism. Recently, PPARs and their respective ligands have been implicated as regulators of cellular inflammatory and immune responses. These molecules are thought to exert anti-inflammatory effects by negatively regulating the expression of proinflammatory genes. Several studies have demonstrated that PPAR ligands possess anti-inflammatory properties and that these properties may prove helpful in the treatment of inflammatory diseases of the lung. This review will outline the anti-inflammatory effects of PPARs and PPAR ligands and discuss their potential therapeutic effects in animal models of inflammatory lung disease.
[Autologous cartilage cell transplantation. The goal is pain relief and restored joint function]. (1995)

Chondral and osteochondral damage is a common result of trauma to the joints. The capacity of cartilage to heal such damage is poor, and repetitive wear on joint surfaces that do not heal results in impaired joint function, which can culminate in full blown arthrosis. Thus, it is important to improve our knowledge of cartilage regenerative potential, and develop methods to forestall progression to arthrosis by promoting the early healing of cartilage damage. Autologous cartilage cell transplantation may be a mean of healing cartilage damage. A method of cultivating autologous chondrocytes for transplantation in the treatment of isolated damage to articular cartilage of the knee is presented in the article.
Isolation and identification of fresh tumor-derived endothelial cells from a murine RIF-1 fibrosarcoma. (1994)

Tumor vasculature is anatomically heterogeneous and distinct from the vasculature found in normal mature tissues. Examination of the differences between tumor and normal vasculature is critical to the future design of therapeutic modalities which either target tumor vasculature or potentially enable more efficient delivery of tumor cytotoxic agents. Such efforts to date have been hampered due to the inability to isolate live endothelial cells from solid tumors. We report here the isolation of fresh, noncultured endothelial cells from a C3H/HeJ RIF-1 murine fibrosarcoma through the use of fluorescence-activated cell sorting based on antibody staining for angiotensin-converting enzyme with further characterization by uptake and metabolism of acetylated low-density lipoprotein, factor VIII staining, and electron microscopy.
Identification of SR1078, a Synthetic Agonist for the Orphan Nuclear Receptors RORα and RORγ (2010)

The retinoic acid receptor-related receptors (RORs) are members of the nuclear receptor (NR) superfamily of transcription factors. Several NRs are still characterized as orphan receptors because ligands have not yet been identified for these proteins. Here, we describe the identification of a synthetic RORα/RORγ ligand, SR1078. SR1078 modulates the conformation of RORγ in a biochemical assay and activates RORα and RORγ driven transcription. Furthermore, SR1078 stimulates expression of endogenous ROR target genes in HepG2 cells that express both RORα and RORγ. Pharmacokinetic studies indicate that SR1078 displays reasonable exposure following injection into mice, and consistent with SR1078 functioning as a RORα/RORγ agonist, expression of two ROR target genes, glucose-6-phosphatase and fibroblast growth factor 21, were stimulated in the liver. Thus, we have identified the first synthetic RORα/γ agonist, and this compound can be utilized as a chemical tool to probe the function of these receptors both in vitro and in vivo.
2×2 adiabatic 3-dB coupler on silicon-on-insulator rib waveguides (2013)

We demonstrated 2&times;2 broadband adiabatic 3-dB couplers based on silicon rib waveguides. Functioning as 50/50 optical power splitters, these devices can be used in optoelectronic applications. Fabricated using siliconon-insulator technology, we demonstrated the performance of the adiabatic 3-dB couplers by integrating two couplers into an unbalanced Mach-Zehnder Interferometer (MZI). Measurements of the MZI were made over a 100 nm wavelength range. Extinction ratios in excess of 33.4 dB were obtained over the wavelength range from 1520 nm to 1600 nm, for light injected into Input Port1 and measured at Output Port2, i.e., the cross port response.
Protection of Essential Oil of Fresh Ginger against Cerebral Ischemia Reperfusion Injury (2007)

Objective To study the protection of essential oil of fresh ginger against cerebral ischemical reperfusion injury (CIRI).Methods Mouse CIRI models were established by ligating bilateral common carotid artery. The activity of Na+, K+-ATPase, Ca2+-ATPase and superoxide dismutase (SOD) and content of malondialdehyde (MDA) were detected by chemical colorimetric assay.Results As compared with sham operation group, the activity of Na+, K+-ATPase and Ca2+-ATPase in model control group decreased significantly (P0.01), but there was no obvious change in activity of SOD and content of MDA. Volatile oil of fresh ginger could increase the activity of Na+, K+-ATPase, Ca2+-ATPase and SOD and decrease the content of MDA significantly (P0.05 or P0.01).Conclusion Essential oil of fresh ginger has protective effect against CIRI by enhancing the activity of ATPase and resisting oxidation.
Fibroblast Growth Factor 23 and Klotho: Physiology and Pathophysiology of an Endocrine Network of Mineral Metabolism (2013)

The metabolically active and perpetually remodeling calcium phosphate-based endoskeleton in terrestrial vertebrates sets the demands on whole-organism calcium and phosphate homeostasis that involves multiple organs in terms of mineral flux and endocrine cross talk. The fibroblast growth factor (FGF)-Klotho endocrine networks epitomize the complexity of systems biology, and specifically, the FGF23-αKlotho axis highlights the concept of the skeleton holding the master switch of homeostasis rather than a passive target organ as hitherto conceived. Other than serving as a coreceptor for FGF23, αKlotho circulates as an endocrine substance with a multitude of effects. This review covers recent data on the physiological regulation and function of the complex FGF23-αKlotho network. Chronic kidney disease is a common pathophysiological state in which FGF23-αKlotho, a multiorgan endocrine network, is deranged in a self-amplifying vortex resulting in organ dysfunction of the utmost severity that contributes to its morbidity and mortality.
Reflection-Impulsivity and the Performance of Fifth-Grade Children on Two Art Tasks (1989)

The purpose of this study was to compare the performance of reflective (slowaccurate) and impulsive (fast-inaccurate) children on two distinctly different drawing tasks. A total of 56 fifth-grade children were administered the Matching Familiar Figures Test (MFFT) to determine their degree of reflection-impulsivity. Subjects completed an imaginary and a realistic drawing which were evaluated by three judges on creative and formal artistic properties. Analysis of variance indicated significant main effects for both the imaginary and realistic drawing activities. Regression analysis revealed that reflectives performed better than impulsives on the imaginary drawing activity on formal artistic criteria. However, reflection-impulsivity was not significantly related to performance on the realistic drawing activity. This study confirms the earlier research which revealed that reflectives perform better on certain tasks than impulsives.
Discovery of New Biocatalysts for the Glycosylation of Terpenoid Scaffolds (2008)

The synthesis of terpenoid glycosides typically uses a chemical strategy since few biocatalysts have been identified that recognise these scaffolds. In this study, a platform of 107 recombinant glycosyltransferases (GTs), comprising the multigene family of small molecule GTs of Arabidopsis thaliana have been screened against a range of model terpenoid acceptors to identify those enzymes with high activity. Twenty-seven GTs are shown to glycosylate a diversity of mono-, sesqui- and diterpenes, such as geraniol, perillyl alcohol, artemisinic acid and retinoic acid. Certain enzymes showing substantial sequence similarity recognise terpenoids containing a primary alcohol, irrespective of the linear or cyclical structure of the scaffold; other GTs glycosylate scaffolds containing secondary and tertiary alcohols; the carboxyl group of other terpenoids also represents a feature that is recognized by GTs previously known to form glucose esters with many different compounds. These data underpin the rapid prediction of potential biocatalysts from GT sequence information. To explore the potential of GTs as biocatalysts, their use for the production of terpenoid glycosides was investigated by using a microbial-based whole-cell biotransformation system capable of regenerating the cofactor, UDP-glucose. A high cell density fermentation system was shown to produce several hundred milligrams of a model terpenoid, geranyl-glucoside. The activities of the GTs are discussed in relation to their substrate recognition and their utility in biotransformations as a complement or alternative to chemical synthesis.
Differential Presynaptic Localization of Metabotropic Glutamate Receptor Subtypes in the Rat Hippocampus (1997)

Neurotransmission in the hippocampus is modulated variously through presynaptic metabotropic glutamate receptors (mGluRs). To establish the precise localization of presynaptic mGluRs in the rat hippocampus, we used subtype-specific antibodies for eight mGluRs (mGluR1–mGluR8) for immunohistochemistry combined with lesioning of the three major hippocampal pathways: the perforant path, mossy fiber, and Schaffer collateral. Immunoreactivity for group II (mGluR2) and group III (mGluR4a, mGluR7a, mGluR7b, and mGluR8) mGluRs was predominantly localized to presynaptic elements, whereas that for group I mGluRs (mGluR1 and mGluR5) was localized to postsynaptic elements. The medial perforant path was strongly immunoreactive for mGluR2 and mGluR7a throughout the hippocampus, and the lateral perforant path was prominently immunoreactive for mGluR8 in the dentate gyrus and CA3 area. The mossy fiber was labeled for mGluR2, mGluR7a, and mGluR7b, whereas the Schaffer collateral was labeled only for mGluR7a. Electron microscopy further revealed the spatial segregation of group II and group III mGluRs within presynaptic elements. Immunolabeling for the group III receptors was predominantly observed in presynaptic active zones of asymmetrical and symmetrical synapses, whereas that for the group II receptor (mGluR2) was found in preterminal rather than terminal portions of axons. Target cell-specific segregation of receptors, first reported for mGluR7a (Shigemoto et al., 1996), was also apparent for the other group III mGluRs, suggesting that transmitter release is differentially regulated by 2-amino-4-phosphonobutyrate-sensitive mGluRs in individual synapses on single axons according to the identity of postsynaptic neurons.
CD8 T cells from major histocompatibility complex class II‐deficient mice respond vigorously to class II molecules in a primary mixed lymphocyte reaction (1997)

Mature CD4+ and CD8+ T cells are restricted by major histocompatibility complex (MHC) class II and class I molecules, respectively. In a primary mixed lymphocyte reaction (MLR), CD8+ T cells from C57BL/6 (B6) mice can respond to allo-class I molecules, but not allo-class II molecules. However, a significant fraction of CD8+ T cells from C57BL/6 class II-deficient (B6Aalpha-) mice violate this rule by responding vigorously in a MLR to class II molecules. The frequency of responding cells is approximately 50% of that of B6 CD8+ T cells responding to B6bm1 allo-class I molecules. This response requires neither appropriate co-receptor, i.e. CD4, nor exogenous lymphokines, indicating that interactions between the T cell receptors (TCR) and class II molecules are remarkably efficient. Since these CD8+ T cells are positively selected by class I molecules in the thymus of class II-deficient mice, these CD8+ T cells should interact with both classes of MHC molecules. The absence of thymic negative selection by class II molecules may result in the production of these CD8+ T cells. The data imply that a substantial fraction of CD4+CD8+ double-positive thymocytes in wild-type mice interacts with both classes of MHC molecules prior to thymic selection.