gebhart/patrepeval huggingface dataset:
Direct effects of metformin in the endometrium: a hypothetical mechanism for the treatment of women with PCOS and endometrial carcinoma (2014)

Although a number of in vitro studies have demonstrated the antiproliferative, anti-invasive, and antimetastatic effects of metformin in multiple cancer cell types, its cellular and molecular mechanisms of anti-cancer action in the endometrium of women with polycystic ovary syndrome (PCOS) have not yet been fully elucidated. Organic cation transporters (OCTs) and multidrug and toxin extrusion proteins (MATEs) are known to be involved in metformin uptake and excretion in cells. In this article, we discuss the novel therapeutic possibilities for early-stage endometrial carcinoma (EC) in women with PCOS focusing on metformin, which might have a direct effect in the endometrium through the OCTs and MATEs. We then review the molecular mechanism(s) of the action of metformin in the endometrium and highlight possible mechanistic insights into the inhibition of cell proliferation and tumor growth and, ultimately, the reversal of early-stage EC into normal endometria in women with PCOS.
Treatment of bulimia with bupropion: a multicenter controlled trial. (1988)

In a placebo-controlled, double-blind study of the unique antidepressant agent bupropion in the treatment of nondepressed subjects with bulimia (bupropion group, N = 55; placebo group, N = 26), we found the drug significantly superior to placebo in reducing episodes of binge eating and purging. In general, side effects with bupropion were minimal. However, four subjects experienced grand mal seizures during treatment with bupropion, a frequency of seizures far higher than observed in previous studies with this drug. Pending a satisfactory explanation for the occurrence of these seizures, we recommend that bupropion not be administered alone to bulimic patients.
A suite of novel promoters and terminators for plant biotechnology (2003)

The gene regulation signals from subterranean clover stunt virus (SCSV) were investigated for their expression in dicot plants. The SCSV genome has at least eight circular DNA molecules. Each circular DNA component contains a promoter element, a single open reading frame and a terminator. The promoters from seven of the segments were examined for their strength and tissue specificity in transgenic tobacco (Nicotiana tabacum L.), potato (Solanum tuberosum L.) and cotton (Gossypium hirsutum L.) using a GUS reporter gene assay system. While the promoters of many of the segments were poorly expressed, promoters derived from segments 4 and 7 were shown to direct high levels of expression in various plant tissues and organs. The segment 1 promoter directs predominantly callus-specific expression and, when used to control a selectable marker gene, facilitated the transformation of all three species (tobacco, potato and cotton). From the results, a suite of plant expression vectors (pPLEX) derived from the SCSV genome were constructed and used here to produce herbicide- and insect-resistant cotton, demonstrating their utility in the expression of foreign genes in dicot crop species and their potential for use in agricultural biotechnology.
Reevaluating the CD8 T-Cell Response to Herpes Simplex Virus Type 1: Involvement of CD8 T Cells Reactive to Subdominant Epitopes (2008)

In C57BL/6 (B6) mice, most herpes simplex virus (HSV)-specific CD8 T cells recognize a strongly immunodominant epitope on glycoprotein B (gB498) and can inhibit HSV type 1 (HSV-1) reactivation from latency in trigeminal ganglia (TG). However, half of the CD8 T cells retained in latently infected TG of B6 mice are not gB498 specific and have been largely ignored. The following observations from our current study indicate that these gB498-nonspecific CD8 T cells are HSV specific and may contribute to the control of HSV-1 latency. First, following corneal infection, OVA257-specific OT-1 CD8 T cells do not infiltrate the infected TG unless mice are simultaneously immunized with OVA257 peptide, and then they are not retained. Second, 30% of CD8 T cells in acutely infected TG that produce gamma interferon in response to HSV-1 stimulation directly ex vivo are gB498 nonspecific, and these cells maintain an activation phenotype during viral latency. Finally, gB498-nonspecific CD8 T cells are expanded in ex vivo cultures of latently infected TG and inhibit HSV-1 reactivation from latency in the absence of gB498-specific CD8 T cells. We conclude that many of the CD8 T cells that infiltrate and are retained in infected TG are HSV specific and potentially contribute to maintenance of HSV-1 latency. Identification of the viral proteins recognized by these cells will contribute to a better understanding of the dynamics of HSV-1 latency.
Molecular Pathways: JAK/STAT Pathway: Mutations, Inhibitors, and Resistance (2013)

Aberrant activation of the JAK/STAT pathway has been reported in a variety of disease states, including inflammatory conditions, hematologic malignancies, and solid tumors. For instance, a large proportion of patients with myeloproliferative neoplasms (MPN) carry the acquired gain-of-function JAK2 V617F somatic mutation. This knowledge has dramatically improved our understanding of the pathogenesis of MPNs and has facilitated the development of therapeutics capable of suppressing the constitutive activation of the JAK/STAT pathway, now recognized as a common underlying biologic abnormality in MPNs. Ruxolitinib is an oral JAK1 and JAK2 inhibitor that has recently been approved for the treatment of myelofibrosis and has been tested against other hematologic malignancies. A series of agents with different specificities against different members of the JAK family of proteins is currently undergoing evaluation in clinical trials for patients with MPNs, lymphoma, and solid tumors such as breast or pancreatic cancer. Despite the significant clinical activity exhibited by these agents in myelofibrosis, some patients fail to respond or progress during JAK kinase inhibitor therapy. Recent reports have shed light into the mechanisms of resistance to JAK inhibitor therapy. Several approaches hold promise to overcome such resistance.
Modular Universal Scalable Ion-trap Quantum Computer (MUSIQC) (2011)

Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter Facebook Reddit LinkedIn Tools Icon Tools Reprints and Permissions Cite Icon Cite Search Site Citation Jungsang Kim, Peter Maunz, Taehyun Kim, Jeffrey Hussman, Rachel Noek, Abhijit Mehta, Christopher Monroe; Modular Universal Scalable Ion‐trap Quantum Computer (MUSIQC). AIP Conf. Proc. 14 October 2011; 1363 (1): 190–193. https://doi.org/10.1063/1.3630178 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAIP Publishing PortfolioAIP Conference Proceedings Search Advanced Search |Citation Search
An Integrated Microreactor System for Self‐Optimization of a Heck Reaction: From Micro‐ to Mesoscale Flow Systems (2010)

Set it and forget it: The combination of feedback control and continuous-flow operations in microreactors (see picture) enables online and fully automated reaction optimization. A Heck reaction demonstrates the potential for rapid multivariable reaction optimization while requiring a minimal amount of material. Optimal conditions are quickly scaled-up by a factor of 50. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Cyanoacrylate Temporary Tarsorrhaphy in the Management of Corneal Epithelial Defects (1991)

Cyanoacrylate tarsorrhaphy is an easily administered, painless technique for the temporary management of corneal epithelial defects. We have used the technique in 17 patients to treat persistent epithelial defects and exposure keratitis, as well as following epikeratophakia, allowing the tarsorrhaphy to remain in place for 1 to 15 days (mean, 5.7 days). Eleven of the 17 patients required only one application of cyanoacrylate; five had additional cyanoacrylate applied at the time of the original tarsorrhaphy to produce more extensive lid closure; and one required additional cyanoacrylate on day 3 to produce more extensive lid apposition.
Technology-assisted dietary assessment (2008)

Dietary intake provides valuable insights for mounting intervention programs for prevention of disease. With growing concern for adolescent obesity, the need to accurately measure diet becomes imperative. Assessment among adolescents is problematic as this group has irregular eating patterns and have less enthusiasm for recording food intake. Preliminary studies among adolescents suggest that innovative use of technology may improve the accuracy of diet information from young people. In this paper, we propose a novel food record method using a mobile device that will provide an accurate account of daily food and nutrient intake among adolescents. Our approach includes the use of image analysis tools for identification and quantification of food consumption. Images obtained before and after food is consumed can be used to estimate the diet of an individual. In this paper we describe our initial results and indicate the potential of the proposed system.
Immobilized MICA Could Expand Human Vδ1 γδ T Cells In Vitro that Displayed Major Histocompatibility Complex Class I Chain‐Related A‐Dependent Cytotoxicity to Human Epithelial Carcinomas (2003)

Human major histocompatibility complex class I chain-related A (MICA) is a human leucocyte antigen-related polymorphic molecule, which is expressed on many kinds of epithelial tumours and can be recognized by the Vdelta1 subset of gammadelta T cells. In the present study, monoclonal antibodies (MoAbs) were produced in mice immunized with recombinant MICA (rMICA)*008. It was found that MICA was expressed on ovarian and colonic tumour tissues and could be detected by these anti-MICA MoAbs. The immobilized rMICA could induce the proliferation of human ovarian epithelial carcinoma- or colonic carcinoma-derived gammadelta T cells of the Vdelta1 phenotype in vitro. These Vdelta1 T cells displayed a strong, broad-range cytolytic activity towards tumour cell lines positive for MICA. The efficiency of this cytolytic activity depended greatly on the level of MICA expressed on the cell surface and could be inhibited by anti-MICA MoAbs. Therefore, MICA may play an important role in immune responses against epithelial tumours and function as a stimulating factor for the growth of Vdelta1 gammadelta T cells, whereas MICA-reactive Vdelta1 gammadelta T cells might serve as a new candidate for adoptive cellular therapy of tumours.
Optimal placements of flexible objects. I. Analytical results for the unbounded case (1997)

The authors consider optimal placements of two-dimensional flexible (elastic, deformable) objects. The objects are discs of equal size placed within a rigid boundary. The paper is divided into two parts. In the first part, analytical results for three types of regular, periodic arrangements-the hexagonal, square, and triangular placements-are presented. The regular arrangements are analyzed for rectangular boundaries and radii of discs that are small compared to the area of the placement region, because, in this case, the influence of boundary conditions can be neglected. This situation is called the unbounded case. They show that, for the unbounded case among the three regular placements, the type of hexagonal arrangements provides the largest number of placed units for the same deformation depth. Furthermore, it can be proved that these regular placements are not too far from the truly optimal arrangements. For example, hexagonal placements differ at most by the factor of 1.1 from the largest possible number of generally shaped units in arbitrary arrangements. These analytical results are used as guidances for testing stochastic algorithms optimizing placements of flexible objects. In the second part, mainly two problems are considered: the underlying physical model and a simulated annealing algorithm maximizing the number of flexible discs in equilibrium placements. Along with the physical model, an approximate formula is derived, reflecting the deformation/force relationship for a large range of deformations.
Exosomes of human mesenchymal stem/stromal/medicinal signaling cells (2017)

In this review, we intend to explore the potential therapeutic effects of exosomes released from mesenchymal stem/stromal cells (MSCs). MSCs gained credibility as a therapeutic tool due to their potential to differentiate into many cell types like osteoblasts, chondrocytes, adipocytes, muscular, endothelial, cardiovascular, and neurogenic cells. They possess potent wound healing activity due to their immunosuppressive and anti-inflammatory properties. MSCs are tested in large number of clinical trials for treatment of diseases, which do not have adequate therapy at present. MSCs engineered to express suicide genes in preclinical studies have shown promising tumor targeting therapeutic tool for malignancies difficulty treatable at present. It has been increasingly observed in many different kinds of regenerative medicine and in MSCs mediated prodrug gene therapy for cancer that the intravenously administered of MSCs did not necessarily engraft at the site of injury or tumor. The therapeutic effect was exerted mainly through a paracrine action of rich secretome released from the cells. The main biocomponent of secretome are exosomes - naturally occurring membrane nanoparticles of 30-120 nm in diameter that mediate intercellular communication by delivering biomolecules like mRNA, miRNA into recipient cells. These nanosized exosomes derived from MSCs promise to be a new and valuable therapeutic strategy in regenerative medicine and cancer therapy compared with transplanted exogenous MSCs. Advantage of nanosized exosomes compared with administration of exogenous MSCs is multiple. Exosomes are easier to preserve and be transferred, have lower immunogenicity and therefore are safer for therapeutic administration.
Virus-like particles in a summer bloom of Emiliania huxleyi in the North Sea (1996)

The importance of viruses in controlling a bloom of the coccolithophorid Emiliania huxley~ in the North Sea was investigated during summer 1993. Viral infection of E. huxleyi was highest In the decaying phase of the bloom. Up to 50V0 of E h u x l e y ~ cells \yere visibly infected. For E, huxleyi, 2 types of virus-like particles are reported. Thcy differed in slze and were occassionally found within the same cell. The infection level of the large virus-like particles was never higher than 25%. Viral lysis of E. huxleyi within the nitrogen-limited decaying phase of the bloom seemed an important source of organic carbon utilized by bacteria. In addition to infection in E. huxleyi, we also found severe viral infection in Chrysochromulina sp. Our results show that in natural ecosystems viruses can be a significant source of phytoplankton mortality, influencing phytoplankton (bloom) dynamics and the microbial food web.
Cyclic-GMP-Dependent Protein Kinase Inhibits the Ras/Mitogen-Activated Protein Kinase Pathway (1998)

Agents which increase the intracellular cyclic GMP (cGMP) concentration and cGMP analogs inhibit cell growth in several different cell types, but it is not known which of the intracellular target proteins of cGMP is (are) responsible for the growth-suppressive effects of cGMP. Using baby hamster kidney (BHK) cells, which are deficient in cGMP-dependent protein kinase (G-kinase), we show that 8-(4-chlorophenylthio)guanosine-3', 5'-cyclic monophosphate and 8-bromoguanosine-3',5'-cyclic monophosphate inhibit cell growth in cells stably transfected with a G-kinase Ibeta expression vector but not in untransfected cells or in cells transfected with a catalytically inactive G-kinase. We found that the cGMP analogs inhibited epidermal growth factor (EGF)-induced activation of mitogen-activated protein (MAP) kinase and nuclear translocation of MAP kinase in G-kinase-expressing cells but not in G-kinase-deficient cells. Ras activation by EGF was not impaired in G-kinase-expressing cells treated with cGMP analogs. We show that activation of G-kinase inhibited c-Raf kinase activation and that G-kinase phosphorylated c-Raf kinase on Ser43, both in vitro and in vivo; phosphorylation of c-Raf kinase on Ser43 uncouples the Ras-Raf kinase interaction. A mutant c-Raf kinase with an Ala substitution for Ser43 was insensitive to inhibition by cGMP and G-kinase, and expression of this mutant kinase protected cells from inhibition of EGF-induced MAP kinase activity by cGMP and G-kinase, suggesting that Ser43 in c-Raf is the major target for regulation by G-kinase. Similarly, B-Raf kinase was not inhibited by G-kinase; the Ser43 phosphorylation site of c-Raf is not conserved in B-Raf. Activation of G-kinase induced MAP kinase phosphatase 1 expression, but this occurred later than the inhibition of MAP kinase activation. Thus, in BHK cells, inhibition of cell growth by cGMP analogs is strictly dependent on G-kinase and G-kinase activation inhibits the Ras/MAP kinase pathway (i) by phosphorylating c-Raf kinase on Ser43 and thereby inhibiting its activation and (ii) by inducing MAP kinase phosphatase 1 expression.
No Gain, No Pain: NaV1.7 as an Analgesic Target (2014)

Chronic pain is one of the most complex and difficult to manage clinical problems, with the therapeutic utility of current-generation analgesics restricted by problems such as dose-limiting side effects, tolerance, and the potential for addiction. The voltage-gated sodium channel NaV1.7 plays a key role in setting the threshold for action potential generation in primary sensory neurons, and humans that lack this channel are completely insensitive to pain. In this Viewpoint, we examine the potential of NaV1.7 as an analgesic target a well as the challenges involved in developing therapeutically useful subtype-selective inhibitors of this ion channel.
NKT Cells and Type-1 Diabetes and the "Hygiene Hypothesis" to Explain the Rising Incidence Rates (2002)

Immune-mediated (type-1) diabetes (IMD) is a multigenetic disease that is strongly influenced by the environment. Whereas the incidence rates are steadily rising worldwide, less than half of affected identical twins ever become concordant for IMD or even beta-cell autoimmunity. Worldwide, it is the tropical regions of the world that are replete in infectious and parasitic diseases that are the least affected. Repeated efforts to identify the putative inductive agents for beta-cell autoimmunity have proved unrewarding. Rather, we suggest that some environments are less protective than others and argue that it is the fall in incidences of infectious diseases and intestinal parasites that are likely responsible for the rise in autoimmune diseases like IMD in the West. Nonobese diabetic (NOD) mice reared in gnotobiotic environments have only worsened diabetes, while recent studies suggest that multiple defects in immune tolerance to self must be present before IMD can develop in the human or mouse. We speculate herein that the deficiency in natural killer T (NKT) cells in IMD in both species may be both genetic and environmentally influenced, predisposing to pancreatic beta-cell autoimmunity through a dysfunction of immunoregulatory T cells, with defective peripheral control of islet cell protein autoreactive cytotoxic CD8+ T cells. The encouraging results in NOD mice using alpha-galactosylceramide to stimulate NKT cells now warrant trials with this and other glycolipid NKT cell-stimulating agents in humans. Since it has become apparent that autoimmune diseases such as IMD are the result of an underlying immunodeficiency state, we strongly argue that its effective prevention will likely come through the use of immunostimulation and not through side effect-prone immunosuppression.
Assessment of a Combined, Adenovirus-Mediated Oncolytic and Immunostimulatory Tumor Therapy (2005)

In this study, we identified murine breast cancer cell lines that support DNA replication of E1-deleted adenovirus vectors and which can be killed by an oncolytic adenovirus expressing adenovirus E1A and tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) in a replication-dependent manner (Ad.IR-E1A/TRAIL). We showed that systemic or intratumoral (i.t.) injection of adenovirus vectors into mice increases plasma levels of proinflammatory cytokines and chemokines, including TNF-alpha, INF-gamma, and MCP-1, which are potent inducers of dendritic cell maturation. Furthermore, we showed that in vivo expression of Flt3L from an adenovirus vector increases the number of CD11b+ and CD11c+ cells (populations that include dendritic cells) in the blood circulation. Based on these findings, we tested whether Ad.IR-E1A/TRAIL induced killing of tumor cells in combination with dendritic cell mobilization by Ad.Flt3L or, for comparison, Ad.GM-CSF would have an additive antitumor effect. As a model, we used immunocompetent C3H mice with syngeneic s.c. tumors derived from C3L5 cells. We found that vaccination of mice with C3L5 cells that underwent viral oncolysis in combination with Flt3L or granulocyte-macrophage colony-stimulating factor (GM-CSF) expression induces a systemic antitumor immune response. I.t. injection of the oncolytic and Flt3L expressing vectors into established tumors delayed tumor growth but did not cause efficient tumor elimination. This study shows the effectiveness of a combined oncolytic/immunostimulatory tumor therapy approach.
Multiplexed In Situ Immunofluorescence Using Dynamic DNA Complexes (2012)

DNA-based erasers: The designed strand-displacement reactions between dynamic DNA probes (carrying fluorescent dyes (★) and quencher domains (•)) and DNA–antibody conjugates generate detachable immunofluoresence-reporting complexes that can be assembled (first image) and disassembled (second image) reversibly within fixed cells. With this system, different protein targets can be imaged sequentially within the same cells (third image). Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.