gebhart/patrepeval huggingface dataset:
ANDROGENS DIRECTLY STIMULATE PROLIFERATION OF BONE CELLS IN VITRO (1989)

This report describes the first observation of a direct mitogenic effect of androgens on isolated osteoblastic cells in serum-free culture. [3H]thymidine incorporation into DNA and cell counts were used as measures of cell proliferation. The percentage of cells that stained for alkaline phosphatase was used as a measure of differentiation. Dihydrotestosterone (DHT) enhanced mouse osteoblastic cell proliferation in a dose dependent manner over a wide range of doses (10(-8) to 10(-11) molar), and was maximally active at 10(-9) M. DHT also stimulated proliferation in human osteoblast cell cultures and in cultures of the human osteosarcoma cell line, TE89. Testosterone, fluoxymesterone (a synthetic androgenic steroid) and methenolone (an anabolic steroid) were also mitogenic in the mouse bone cell system. The mitogenic effect of DHT on bone cells was inhibited by antiandrogens (hydroxyflutamide and cyproterone acetate) which compete for binding to the androgen receptor. In addition to effects on cell proliferation, DHT increased the percentage of alkaline phosphatase (ALP) positive cells in all three bone cell systems tested, and this effect was inhibited by antiandrogens. We conclude that androgens can stimulate human and murine osteoblastic cell proliferation in vitro, and induce expression of the osteoblast-line differentiation marker ALP, presumably by an androgen receptor mediated mechanism.
Biofunctionalized Silica Nanoparticles: Standards in Amyloid-β Oligomer-Based Diagnosis of Alzheimer’s Disease (2016)

Amyloid-β (Aβ) oligomers represent a promising biomarker for the early diagnosis of Alzheimer's disease (AD). However, state-of-the-art methods for immunodetection of Aβ oligomers in body fluids show a large variability and lack a reliable and stable standard that enables the reproducible quantitation of Aβ oligomers. At present, the only available standard applied in these assays is based on a random aggregation process of synthetic Aβ and has neither a defined size nor a known number of epitopes. In this report, we generated a highly stable standard in the size range of native Aβ oligomers that exposes a defined number of epitopes. The standard consists of a silica nanoparticle (SiNaP), which is functionalized with Aβ peptides on its surface (Aβ-SiNaP). The different steps of Aβ-SiNaP synthesis were followed by microscopic, spectroscopic and biochemical analyses. To investigate the performance of Aβ-SiNaPs as an appropriate standard in Aβ oligomer immunodetection, Aβ-SiNaPs were diluted in cerebrospinal fluid and quantified down to a concentration of 10 fM in the sFIDA (surface-based fluorescence intensity distribution analysis) assay. This detection limit corresponds to an Aβ concentration of 1.9 ng l-1 and lies in the sensitivity range of currently applied diagnostic tools based on Aβ oligomer quantitation. Thus, we developed a highly stable and well-characterized standard for the application in Aβ oligomer immunodetection assays that finally allows the reproducible quantitation of Aβ oligomers down to single molecule level and provides a fundamental improvement for the worldwide standardization process of diagnostic methods in AD research.
5-hydroxytryptophan Elevates Serum Melatonin (1983)

Daytime administration of 5-hydroxytryptophan to sheep elevated serum melatonin more than sevenfold within 2 hours. This suggests that administration of 5-hydroxytryptophan could be used as the basis of a clinical test of pineal function and that melatonin might mediate some clinical effects of 5-hydroxytryptophan.
The Emerging Role of Novel Therapies for the Treatment of Relapsed Myeloma (2007)

Despite advances in the first-line treatment of multiple myeloma, almost all patients eventually relapse, become chemoresistant, and die of the disease. Improved understanding of potential myeloma targets and molecular mechanisms of drug resistance, along with the development and clinical investigation of targeted antitumor agents, have led to new strategies for the treatment of relapsed myeloma. The proteasome inhibitor bortezomib, the immunomodulatory agent thalidomide, and the thalidomide derivative lenalidomide, are all recently approved treatment options for myeloma. Single-agent bortezomib has been shown to provide significantly greater efficacy than high-dose dexamethasone, and bortezomib has also been investigated in combination with other agents commonly used to treat myeloma, including thalidomide and lenalidomide, with high overall and complete response rates. The safety profile of bortezomib has been well characterized, and side effects have been shown to be generally predictable and manageable, including in high-risk and elderly patients and those with renal impairment. Thalidomide has been extensively studied alone and in combination in patients with relapsed myeloma, demonstrating substantial efficacy, and is therefore widely used in this setting. The toxicity profile is dose- and duration-linked, with lower doses appearing to be better tolerated. Lenalidomide plus dexamethasone has been shown to have significantly greater activity than dexamethasone alone in the relapsed setting, with impressive duration of disease control. Other combinations are also under investigation, with promising early results. Some aspects of the toxicity profile appear significantly reduced relative to thalidomide, although myelosuppression is increased. Other novel therapies at earlier stages of development are being studied and may provide further options in the treatment of relapsed myeloma. This review focuses on results from key phase II and III trials of bortezomib, thalidomide, and lenalidomide alone or in combination, and their emerging role in improving outcomes.
Bandwidth-efficient turbo trellis-coded modulation using punctured component codes (1998)

We present a bandwidth-efficient channel coding scheme that has an overall structure similar to binary turbo codes, but employs trellis-coded modulation (TCM) codes (including multidimensional codes) as component codes. The combination of turbo codes with powerful bandwidth-efficient component codes leads to a straightforward encoder structure, and allows iterative decoding in analogy to the binary turbo decoder. However, certain special conditions may need to be met at the encoder, and the iterative decoder needs to be adapted to the decoding of the component TCM codes. The scheme has been investigated for 8-PSK, 16-QAM, and 64-QAM modulation schemes with varying overall bandwidth efficiencies. A simple code choice based on the minimal distance of the punctured component code has also been performed. The interset distances of the partitioning tree can be used to fix the number of coded and uncoded bits. We derive the symbol-by-symbol MAP component decoder operating in the log domain, and apply methods of reducing decoder complexity. Simulation results are presented and compare the scheme with traditional TCM as well as turbo codes with Gray mapping. The results show that the novel scheme is very powerful, yet of modest complexity since simple component codes are used.
The role of immune cells and inflammatory cytokines in Paget's disease and multiple myeloma (2005)

Summary: The osteoclast (OCL) is the primary cell involved in the pathogenesis of Paget's disease (PD) and the destructive bone process in multiple myeloma (MM). Both of these diseases are characterized by increased numbers of OCLs actively resorbing bone, but they differ in that bone formation is greatly increased in PD and is suppressed in MM. The marrow microenvironment plays a critical role in both disease processes, through the increased expression of inflammatory cytokines that enhance osteoclastogenesis and, in the case of MM, also suppress osteoblast (OBL) activity. In addition, the OCLs in PD are intrinsically abnormal, are markedly increased in number and size, and are hyper‐responsive to inflammatory cytokines and 1,25‐(OH) 2 D 3 . This article discusses the role of immune cells and inflammatory cytokines and chemokines in the increased OCL activity in PD and MM bone disease, as well as the potential role of interleukin‐3 in the suppression of OBL activity in MM.
A Framework for Multiple-Instance Learning (1997)

Multiple-instance learning is a variation on supervised learning, where the task is to learn a concept given positive and negative bags of instances. Each bag may contain many instances, but a bag is labeled positive even if only one of the instances in it falls within the concept. A bag is labeled negative only if all the instances in it are negative. We describe a new general framework, called Diverse Density, for solving multiple-instance learning problems. We apply this framework to learn a simple description of a person from a series of images (bags) containing that person, to a stock selection problem, and to the drug activity prediction problem. 1 Introduction One of the drawbacks of applying the supervised learning model is that it is not always possible for a teacher to provide labeled examples for training. Multiple-instance learning provides a new way of modeling the teacher&amp;apos;s weakness. Instead of receiving a set of instances which are labeled positive or negative, the lear...
Assessment of query execution performance using selected Business Intelligence tools and experimental agile oriented data modeling approach (2015)

The paper deals with the assessment of an experimental data modeling approach which is intended to support the agile oriented data modeling. The approach is based on the Anchor Data Modeling technique and is applied on a multidimensional data model. The assessed approach is expected to facilitate more effective execution of queries in the data mart environment. The emphasis is placed on the comparison of the query execution performance using database schemas, each built using traditional and the experimental approach. The tests are done in the environment of selected modern Business Intelligence tools, and using two test queries with varying output dataset sizes. The results show that the use of the database schema, created according to the experimental data modeling approach, had positive impact on the querying performance in several cases. The magnitude of impact on the querying performance, however, varied depending on each query's respective resulting dataset size.
Clinical Significance of Hepatitis C Virus Genotypes (2000)

On the basis of phylogenetic analysis of nucleotide sequences, multiple genotypes and subtypes of hepatitis C virus (HCV) have been identified. Characterization of these genetic groups is likely to facilitate and contribute to the development of an effective vaccine against infection with HCV. Differences among HCV genotypes in geographic distributions have provided investigators with an epidemiologic marker that can be used to trace the source of HCV infection in a given population. HCV genotype 1 may represent a more aggressive strain and one that is less likely to respond to interferon treatment than HCV genotype 2 or 3. However, these observations require confirmation before HCV genotyping can be used in clinical settings.
Two‐liquid flotation of fine oxide particles with 8‐hydroxyquinoline (1999)

Abstract The two‐liquid flotation of fine oxide particles has been investigated using a chelating‐type collector of oxine and the isooctane‐water two‐liquids system. The recovery was enhanced in a certain pH range. The oil‐floatability during two‐liquid flotation was concerned with the oxine adsorption on the solids. In addition, solution‐chemical calculations indicated that the reactivity of the metal cation with oxine based upon a surface precipitation model was closely related to the adsorbability of oxine and, hence, to the oil‐floatability of the solids. Also, the possible conditions for collection by two‐liquid flotation were experimentally determined and were related to the solution‐chemical criterion.
Riluzole for relapse prevention following intravenous ketamine in treatment-resistant depression: a pilot randomized, placebo-controlled continuation trial (2009)

The N-methyl-D-aspartate (NMDA) glutamate receptor antagonist ketamine may have rapid, albeit transient, antidepressant properties. This study in patients with treatment-resistant major depression (TRD) aimed to (1) replicate the acute efficacy of single-dose intravenous (i.v.) ketamine; (2) test the efficacy of the glutamate-modulating agent riluzole in preventing post-ketamine relapse; and (3) examine whether pretreatment with lamotrigine would attenuate ketamine's psychotomimetic effects and enhance its antidepressant activity. Twenty-six medication-free patients received open-label i.v. ketamine (0.5 mg/kg over 40 min). Two hours prior to infusion, patients were randomized to lamotrigine (300 mg) or placebo. Seventeen patients (65%) met response criterion (50% reduction from baseline on the Montgomery-Asberg Depression Rating Scale) 24 h following ketamine. Lamotrigine failed to attenuate the mild, transient side-effects associated with ketamine and did not enhance its antidepressant effects. Fourteen patients (54%) met response criterion 72 h following ketamine and proceeded to participate in a 32-d, randomized, double-blind, placebo-controlled, flexible-dose continuation trial of riluzole (100-200 mg/d). The main outcome measure was time-to-relapse. An interim analysis found no significant differences in time-to-relapse between riluzole and placebo groups [log-rank chi(2) = 0.17, d.f. = 1, p = 0.68], with 80% of patients relapsing on riluzole vs. 50% on placebo. The trial was thus stopped for futility. This pilot study showed that a sub-anaesthetic dose of i.v. ketamine is well-tolerated in TRD, and may have rapid and sustained antidepressant properties. Riluzole did not prevent relapse in the first month following ketamine. Further investigation of relapse prevention strategies post-ketamine is necessary.
The involvement of T cell receptor peptide-specific regulatory CD4+ T cells in recovery from antigen-induced autoimmune disease. (1993)

Experimental allergic encephalomyelitis (EAE) is a prototype for CD4+ T cell-mediated autoimmune diseases. Immunization with myelin basic protein (MBP) in B10.PL mice results in EAE, and a majority of animals recover permanently from the disease. Most MBP-reactive encephalitogenic T cells recognize an immunodominant NH2-terminal peptide, Ac1-9, and predominantly use the T cell receptor (TCR) V beta 8.2 gene segment. Here we report that in mice recovering from MBP-induced EAE, peripheral T cells proliferate in response to a single immunodominant TCR peptide from the V beta 8.2 chain (amino acids 76-101), indicating natural priming during the course of the disease. Cloned T cells, specific for this TCR peptide, specifically downregulate proliferative responses to Ac1-9 in vivo and also protect mice from MBP-induced EAE. These regulatory T cells express CD4 molecules and recognize a dominant peptide from the TCR variable framework region of V beta 8.2, in the context of the major histocompatibility complex class II molecule, I-Au, and predominantly use the TCR V beta 14 gene segment. This is the first demonstration of the physiological induction of TCR peptide-specific CD4+ T cells that result from MBP immunization and that are revealed only during the recovery from disease. The downregulation of disease-causing T cells by TCR peptide-specific T cells offers a mechanism for antigen-specific, network-induced recovery from autoimmune disease.
Expression of Cellular Oncogenes in Human Malignancies (1984)

Cellular oncogenes have been implicated in the induction of malignant transformation in some model systems in vitro and may be related to malignancies in vivo in some vertebrate species. This article describes a study of the expression of 15 cellular oncogenes in fresh human tumors from 54 patients, representing 20 different tumor types. More than one cellular oncogene was transcriptionally active in all of the tumors examined. In 14 patients it was possible to study normal and malignant tissue from the same organ. In many of these patients, the transcriptional activity of certain oncogenes was greater in the malignant than the normal tissue. The cellular fes (feline sarcoma) oncogene, not previously known to be transcribed in mammalian tissue, was found to be active in lung and hematopoietic malignancies.
Monolithic rare-earth doped sol-gel tapered rib waveguide laser (2008)

We report the design, fabrication, and characterization of a monolithic tapered rib waveguide laser made of Nd doped silica hafnia sol-gel. The laser has a 604nm thick guiding layer. CW pumping was coupled in via a grating which also coupled out the lasing signal output, while reflection gratings supported the feedback. A lasing threshold of 20mW and an output power of 2.45mW were measured in a 3cm long device.
Exploiting mitochondrial targeting signal(s), TPP and bis-TPP, for eradicating cancer stem cells (CSCs) (2018)

Tri-phenyl-phosphonium (TPP) is a non-toxic chemical moiety that functionally behaves as a mitochondrial targeting signal (MTS) in living cells. Here, we explored the hypothesis that TPP-related compounds could be utilized to inhibit mitochondria in cancer stem cells (CSCs). We randomly selected 9 TPP-related compounds for screening, using an ATP depletion assay. Based on this approach, five compounds were identified as "positive hits"; two had no detectable effect on ATP production. Remarkably, this represents a >50% hit rate. We validated that the five positive hit compounds all inhibited oxygen consumption rates (OCR), using the Seahorse XFe96 metabolic flux analyzer. Interestingly, these TPP-related compounds were non-toxic and had little or no effect on ATP production in normal human fibroblasts, but selectively targeted adherent "bulk" cancer cells. Finally, these positive hit compounds also inhibited the propagation of CSCs in suspension, as measured functionally using the 3D mammosphere assay. Therefore, these TPP-related compounds successfully inhibited anchorage-independent growth, which is normally associated with a metastatic phenotype. Interestingly, the most effective molecule that we identified contained two TPP moieties (i.e., bis-TPP). More specifically, 2-butene-1,4-bis-TPP potently and selectively inhibited CSC propagation, with an IC-50 < 500 nM. Thus, we conclude that the use of bis-TPP, a "dimeric" mitochondrial targeting signal, may be a promising new approach for the chemical eradication of CSCs. Future studies on the efficacy of 2-butene-1,4-bis-TPP and its derivatives are warranted. In summary, we show that TPP-related compounds provide a novel chemical strategy for effectively killing both i) "bulk" cancer cells and ii) CSCs, while specifically minimizing or avoiding off-target side-effects in normal cells. These results provide the necessary evidence that "normal" mitochondria and "malignant" mitochondria are truly biochemically distinct, removing a significant barrier to therapeutically targeting cancer metabolism.
The Human Microbiome in Multiple Sclerosis: Pathogenic or Protective Constituents? (2010)

The human microbiome is comprised of commensal and pathogenic microorganisms, which exert diverse effects in close proximity to the site of intection as well as in remote tissues through immune-mediated mechanisms. Multiple infectious agents have been implicated in the pathogenesis of multiple sclerosis (MS) with variable findings depending on the agent, techniques, and disease phenotype. Herein, the contributions of individual infectious agents to MS and their effects on the immune and nervous systems are reviewed, focusing on herpes viruses, coronaviruses, retroviruses, and synchronic infections. While infectious agents are often assumed to be pathogenic, their effects might also be beneficial to the host in the long-term, depending on age and the type of immunogen/pathogen exposure, as proposed by the hygiene hypothesis. The human microbiome has potential impact on future diagnostic and therapeutic issues in MS.
Genomic structure and chromosomal mapping of the murine CD40 gene (1992)

The B cell-associated surface molecule, CD40, is likely to play a central role in the expansion of Ag-stimulated B cells, and their interaction with activated Th cells. In our study we have isolated genomic clones of murine CD40 from a mouse liver genomic DNA library. Comparison with the murine CD40 cDNA sequence revealed the presence of nine exons that together contain the entire murine CD40 coding region, and span approximately 16.3 kb of genomic DNA. The intron/exon structure of the CD40 gene resembles that of the low affinity nerve growth factor receptor gene, a close homolog of both human and murine CD40. In both cases the functional domains of the receptor molecules are separated onto different exons throughout the genes. Southern blot analysis demonstrated that murine CD40 is a single copy gene that maps in the distal region of mouse chromosome 2.
Herbicide safeners - commercial products and tools for agrochemical research (2001)

J. Davies, Pestic. Outlook, 2001, 12, 10 DOI: 10.1039/B100799H