Sample records for warburg effect revisited

  1. Catabolic efficiency of aerobic glycolysis: the Warburg effect revisited.

    PubMed

    Vazquez, Alexei; Liu, Jiangxia; Zhou, Yi; Oltvai, Zoltán N

    2010-05-06

    Cancer cells simultaneously exhibit glycolysis with lactate secretion and mitochondrial respiration even in the presence of oxygen, a phenomenon known as the Warburg effect. The maintenance of this mixed metabolic phenotype is seemingly counterintuitive given that aerobic glycolysis is far less efficient in terms of ATP yield per moles of glucose than mitochondrial respiration. Here, we resolve this apparent contradiction by expanding the notion of metabolic efficiency. We study a reduced flux balance model of ATP production that is constrained by the glucose uptake capacity and by the solvent capacity of the cell's cytoplasm, the latter quantifying the maximum amount of macromolecules that can occupy the intracellular space. At low glucose uptake rates we find that mitochondrial respiration is indeed the most efficient pathway for ATP generation. Above a threshold glucose uptake rate, however, a gradual activation of aerobic glycolysis and slight decrease of mitochondrial respiration results in the highest rate of ATP production. Our analyses indicate that the Warburg effect is a favorable catabolic state for all rapidly proliferating mammalian cells with high glucose uptake capacity. It arises because while aerobic glycolysis is less efficient than mitochondrial respiration in terms of ATP yield per glucose uptake, it is more efficient in terms of the required solvent capacity. These results may have direct relevance to chemotherapeutic strategies attempting to target cancer metabolism.

  2. Involvement of the Warburg effect in non-tumor diseases processes.

    PubMed

    Chen, Zhe; Liu, Meiqing; Li, Lanfang; Chen, Linxi

    2018-04-01

    Warburg effect, as an energy shift from mitochondrial oxidative phosphorylation to aerobic glycolysis, is extensively found in various cancers. Interestingly, increasing researchers show that Warburg effect plays a crucial role in non-tumor diseases. For instance, inhibition of Warburg effect can alleviate pulmonary vascular remodeling in the process of pulmonary hypertension (PH). Interference of Warburg effect improves mitochondrial function and cardiac function in the process of cardiac hypertrophy and heart failure. Additionally, the Warburg effect induces vascular smooth muscle cell proliferation and contributes to atherosclerosis. Warburg effect may also involve in axonal damage and neuronal death, which are related with multiple sclerosis. Furthermore, Warburg effect significantly promotes cell proliferation and cyst expansion in polycystic kidney disease (PKD). Besides, Warburg effect relieves amyloid β-mediated cell death in Alzheimer's disease. And Warburg effect also improves the mycobacterium tuberculosis infection. Finally, we also introduce some glycolytic agonists. This review focuses on the newest researches about the role of Warburg effect in non-tumor diseases, including PH, tuberculosis, idiopathic pulmonary fibrosis (IPF), failing heart, cardiac hypertrophy, atherosclerosis, Alzheimer's diseases, multiple sclerosis, and PKD. Obviously, Warburg effect may be a potential therapeutic target for those non-tumor diseases. © 2017 Wiley Periodicals, Inc.

  3. Lactate as an insidious metabolite due to the Warburg effect.

    PubMed

    Luc, Raymond; Tortorella, Stephanie M; Ververis, Katherine; Karagiannis, Tom C

    2015-04-01

    Although oncogenetics remains a critical component of cancer biology and therapeutic research, recent interest has been taken towards the non-genetic features of tumour development and progression, such as cancer metabolism. Specifically, it has been observed that tumour cells are inclined to preferentially undergo glycolysis despite presence of adequate oxygen. First reported by Otto Warburg in the 1920s, and now termed the 'Warburg effect', this aberrant metabolism has become of particular interest due to the prevalence of the fermentation phenotype in a variety of cancers studied. Consequently, this phenotype has proven to play a pivotal role in cancer proliferation. As such Warburg's observations are now being integrated within the modern paradigms of cancer and in this review we explore the role of lactate as an insidious metabolite due to the Warburg effect.

  4. The Warburg effect: molecular aspects and therapeutic possibilities.

    PubMed

    Ngo, Hanh; Tortorella, Stephanie M; Ververis, Katherine; Karagiannis, Tom C

    2015-04-01

    It has been about nine decades since the proposal of Otto Warburg on the metabolism of cancer cells. Unlike normal cells which undergo glycolysis and oxidative phosphorylation in the presence of oxygen, proliferating and cancer cells exhibit an increased uptake of glucose and increased rate of glycolysis and predominantly undergo lactic acid fermentation. Whether this phenomenon is the consequence of genetic dysregulation in cancer or is the cause of cancer still remains unknown. However, there is certainly a strong link between the genetic factors, epigenetic modulation, cancer immunosurveillance and the Warburg effect, which will be discussed in this review. Dichloroacetate and 3-bromopyruvate are among the substances that have been studied as potential cancer therapies. With our expanding knowledge of cellular metabolism, therapies targeting the Warburg effect appear very promising. This review discusses different aspects of these emerging therapies.

  5. Revisiting the Crabtree/Warburg effect in a dynamic perspective: a fitness advantage against sugar-induced cell death

    PubMed Central

    de Alteriis, Elisabetta; Cartenì, Fabrizio; Parascandola, Palma; Serpa, Jacinta; Mazzoleni, Stefano

    2018-01-01

    ABSTRACT The mechanisms behind the Warburg effect in mammalian cells, as well as for the similar Crabtree effect in the yeast Saccharomyces cerevisiae, are still a matter of debate: why do cells shift from the energy-efficient respiration to the energy-inefficient fermentation at high sugar concentration? This review reports on the strong similarities of these phenomena in both cell types, discusses the current ideas, and provides a novel interpretation of their common functional mechanism in a dynamic perspective. This is achieved by analysing another phenomenon, the sugar-induced-cell-death (SICD) occurring in yeast at high sugar concentration, to highlight the link between ATP depletion and cell death. The integration between SICD and the dynamic functioning of the glycolytic process, suggests that the Crabtree/Warburg effect may be interpreted as the avoidance of ATP depletion in those conditions where glucose uptake is higher than the downstream processing capability of the second phase of glycolysis. It follows that the down-regulation of respiration is strategic for cell survival allowing the allocation of more resources to the fermentation pathway, thus maintaining the cell energetic homeostasis. PMID:29509056

  6. Arsenic exposure induces the Warburg effect in cultured human cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhao, Fei; Severson, Paul; Pacheco, Samantha

    2013-08-15

    Understanding how arsenic exacts its diverse, global disease burden is hampered by a limited understanding of the particular biological pathways that are disrupted by arsenic and underlie pathogenesis. A reductionist view would predict that a small number of basic pathways are generally perturbed by arsenic, and manifest as diverse diseases. Following an initial observation that arsenite-exposed cells in culture acidify their media more rapidly than control cells, the report here shows that low level exposure to arsenite (75 ppb) is sufficient to induce aerobic glycolysis (the Warburg effect) as a generalized phenomenon in cultured human primary cells and cell lines.more » Expanded studies in one such cell line, the non-malignant pulmonary epithelial line, BEAS-2B, established that the arsenite-induced Warburg effect was associated with increased accumulation of intracellular and extracellular lactate, an increased rate of extracellular acidification, and inhibition by the non-metabolized glucose analog, 2-deoxy-D-glucose. Associated with the induction of aerobic glycolysis was a pathway-wide induction of glycolysis gene expression, as well as protein accumulation of an established glycolysis master-regulator, hypoxia-inducible factor 1A. Arsenite-induced alteration of energy production in human cells represents the type of fundamental perturbation that could extend to many tissue targets and diseases. - Highlights: • Chronic arsenite exposure induces aerobic glycolysis, dubbed the “Warburg effect”. • Arsenite-induced Warburg effect is a general phenomenon in cultured human cells. • HIF-1A may mediate arsenite induced Warburg effect.« less

  7. Alzheimer's disease: the amyloid hypothesis and the Inverse Warburg effect

    PubMed Central

    Demetrius, Lloyd A.; Magistretti, Pierre J.; Pellerin, Luc

    2014-01-01

    Epidemiological and biochemical studies show that the sporadic forms of Alzheimer's disease (AD) are characterized by the following hallmarks: (a) An exponential increase with age; (b) Selective neuronal vulnerability; (c) Inverse cancer comorbidity. The present article appeals to these hallmarks to evaluate and contrast two competing models of AD: the amyloid hypothesis (a neuron-centric mechanism) and the Inverse Warburg hypothesis (a neuron-astrocytic mechanism). We show that these three hallmarks of AD conflict with the amyloid hypothesis, but are consistent with the Inverse Warburg hypothesis, a bioenergetic model which postulates that AD is the result of a cascade of three events—mitochondrial dysregulation, metabolic reprogramming (the Inverse Warburg effect), and natural selection. We also provide an explanation for the failures of the clinical trials based on amyloid immunization, and we propose a new class of therapeutic strategies consistent with the neuroenergetic selection model. PMID:25642192

  8. Warburg effect increases steady-state ROS condition in cancer cells through decreasing their antioxidant capacities (anticancer effects of 3-bromopyruvate through antagonizing Warburg effect).

    PubMed

    El Sayed, Salah Mohamed; Mahmoud, Ahmed Alamir; El Sawy, Samer Ahmed; Abdelaal, Esam Abdelrahim; Fouad, Amira Murad; Yousif, Reda Salah; Hashim, Marwa Shaban; Hemdan, Shima Badawy; Kadry, Zainab Mahmoud; Abdelmoaty, Mohamed Ahmed; Gabr, Adel Gomaa; Omran, Faten M; Nabo, Manal Mohamed Helmy; Ahmed, Nagwa Sayed

    2013-11-01

    Cancer cells undergo an increased steady-state ROS condition compared to normal cells. Among the major metabolic differences between cancer cells and normal cells is the dependence of cancer cells on glycolysis as a major source of energy even in the presence of oxygen (Warburg effect). In Warburg effect, glucose is catabolized to lactate that is extruded through monocarboxylate transporters to the microenvironment of cancer cells, while in normal cells, glucose is metabolized into pyruvate that is not extruded. Pyruvate is a potent antioxidant, while lactate has no antioxidant effect. Pyruvate in normal cells may be further metabolized to acetyl CoA and then through Krebs cycle with production of antioxidant intermediates e.g. citrate, malate and oxaloacetate together with the reducing equivalents (NADH.H+). Through activity of mitochondrial transhydrogenase, NADH.H+ replenishes NADPH.H+, coenzyme of glutathione reductase which replenishes reduced form of glutathione (potent antioxidant). This enhances antioxidant capacities of normal cells, while cancer cells exhibiting Warburg effect may be deprived of all that antioxidant capabilities due to loss of extruded lactate (substrate for Krebs cycle). Although intrinsic oxidative stress in cancer cells is high, it may be prevented from reaching progressively increasing levels that are cytotoxic to cancer cells. This may be due to some antioxidant effects exerted by hexokinase II (HK II) and NADPH.H+ produced through HMP shunt. Glycolytic phenotype in cancer cells maintains a high non-toxic oxidative stress in cancer cells and may be responsible for their malignant behavior. Through HK II, glycolysis fuels the energetic arm of malignancy, the mitotic arm of malignancy (DNA synthesis through HMP shunt pathway) and the metastatic arm of malignancy (hyaluronan synthesis through uronic acid pathway) in addition to the role of phosphohexose isomerase (autocrine motility factor). All those critical three arms start with the

  9. Introduction to the molecular basis of cancer metabolism and the Warburg effect.

    PubMed

    Ngo, Darleen C; Ververis, Katherine; Tortorella, Stephanie M; Karagiannis, Tom C

    2015-04-01

    In differentiated normal cells, the conventional route of glucose metabolism involves glycolysis, followed by the citric acid cycle and electron transport chain to generate usable energy in the form of adenosine triphosphate (ATP). This occurs in the presence of oxygen. In hypoxic conditions, normal cells undergo anaerobic glycolysis to yield significantly less energy producing lactate as a product. As first highlighted in the 1920s by Otto Warburg, the metabolism exhibited by tumor cells involves an increased rate of aerobic glycolysis, known as the Warburg effect. In aerobic glycolysis, pyruvate molecules yielded from glycolysis are converted into fewer molecules of ATP even in the presence of oxygen. Evidence indicates that the reasons as to why tumor cells undergo aerobic glycolysis include: (1) the shift in priority to accumulate biomass rather than energy production, (2) the evasion of apoptosis as fewer reactive oxygen species are released by the mitochondria and (3) the production of lactate to further fuel growth of tumors. In this mini-review we discuss emerging molecular aspects of cancer metabolism and the Warburg effect. Aspects of the Warburg effect are analyzed in the context of the established hallmarks of cancer including the role of oncogenes and tumor suppressor genes.

  10. Chicken or the egg: Warburg effect and mitochondrial dysfunction

    PubMed Central

    Senyilmaz, Deniz

    2015-01-01

    Compared with normal cells, cancer cells show alterations in many cellular processes, including energy metabolism. Studies on cancer metabolism started with Otto Warburg's observation at the beginning of the last century. According to Warburg, cancer cells rely on glycolysis more than mitochondrial respiration for energy production. Considering that glycolysis yields much less energy compared with mitochondrial respiration, Warburg hypothesized that mitochondria must be dysfunctional and this is the initiating factor for cancer formation. However, this hypothesis did not convince every scientist in the field. Some believed the opposite: the reduction in mitochondrial activity is a result of increased glycolysis. This discrepancy of opinions is ongoing. In this review, we will discuss the alterations in glycolysis, pyruvate metabolism, and the Krebs cycle in cancer cells and focus on cause and consequence. PMID:26097714

  11. Cancer metabolism and the Warburg effect: the role of HIF-1 and PI3K.

    PubMed

    Courtnay, Rupert; Ngo, Darleen C; Malik, Neha; Ververis, Katherine; Tortorella, Stephanie M; Karagiannis, Tom C

    2015-04-01

    Cancer cells have been shown to have altered metabolism when compared to normal non-malignant cells. The Warburg effect describes a phenomenon in which cancer cells preferentially metabolize glucose by glycolysis, producing lactate as an end product, despite being the presence of oxygen. The phenomenon was first described by Otto Warburg in the 1920s, and has resurfaced as a controversial theory, with both supportive and opposing arguments. The biochemical aspects of the Warburg effect outline a strong explanation for the cause of cancer cell proliferation, by providing the biological requirements for a cell to grow. Studies have shown that pathways such as phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) as well as hypoxia inducible factor-1 (HIF-1) are central regulators of glycolysis, cancer metabolism and cancer cell proliferation. Studies have shown that PI3K signaling pathways have a role in many cellular processes such as metabolism, inflammation, cell survival, motility and cancer progression. Herein, the cellular aspects of the PI3K pathway are described, as well as the influence HIF has on cancer cell metabolism. HIF-1 activation has been related to angiogenesis, erythropoiesis and modulation of key enzymes involved in aerobic glycolysis, thereby modulating key processes required for the Warburg effect. In this review we discuss the molecular aspects of the Warburg effect with a particular emphasis on the role of the HIF-1 and the PI3K pathway.

  12. MicroRNA-98 Suppress Warburg Effect by Targeting HK2 in Colon Cancer Cells.

    PubMed

    Zhu, Weimin; Huang, Yijiao; Pan, Qi; Xiang, Pei; Xie, Nanlan; Yu, Hao

    2017-03-01

    Warburg effect is a hallmark of cancer cells. Accumulating evidence suggests that microRNAs (miRs) could regulate such metabolic reprograming. Aberrant expression of miR-98 has been observed in many types of cancers. However, its functions and significance in colon cancer remain largely elusive. To investigate miR-98 expression and the biological functions in colon cancer progression. miR-98 expression levels were determined by quantitative RT-PCR in 215 cases of colon cancer samples. miR-98 mimic or inhibitor was used to test the biological functions in SW480 and HCT116 cells, followed by cell proliferation assay, lactate production, glucose uptake, and cellular ATP levels assay and extracellular acidification rates measurement. Western blot and luciferase assay were used to identify the target of miR-98. miR-98 was significantly down-regulated in colon cancer tissues compared to adjacent colon tissues and acted as a suppressor for Warburg effect in cancer cells. miR-98 inhibited glycolysis by directly targeting hexokinase 2, or HK2, illustrating a novel pathway to mediate Warburg effect of cancer cells. In vitro experiments further indicated that HK2 was involved in miR-98-mediated suppression of glucose uptake, lactate production, and cell proliferation. In addition, we detected HK2 expression in colon cancer tissues and found that the expressions of miR-98 and HK2 were negatively correlated. miR-98 acts as tumor suppressor gene and inhibits Warburg effect in colon cancer cells, which provided potential targets for clinical treatments.

  13. The HK2 Dependent "Warburg Effect" and Mitochondrial Oxidative Phosphorylation in Cancer: Targets for Effective Therapy with 3-Bromopyruvate.

    PubMed

    Lis, Paweł; Dyląg, Mariusz; Niedźwiecka, Katarzyna; Ko, Young H; Pedersen, Peter L; Goffeau, Andre; Ułaszewski, Stanisław

    2016-12-15

    This review summarizes the current state of knowledge about the metabolism of cancer cells, especially with respect to the "Warburg" and "Crabtree" effects. This work also summarizes two key discoveries, one of which relates to hexokinase-2 (HK2), a major player in both the "Warburg effect" and cancer cell immortalization. The second discovery relates to the finding that cancer cells, unlike normal cells, derive as much as 60% of their ATP from glycolysis via the "Warburg effect", and the remaining 40% is derived from mitochondrial oxidative phosphorylation. Also described are selected anticancer agents which generally act as strong energy blockers inside cancer cells. Among them, much attention has focused on 3-bromopyruvate (3BP). This small alkylating compound targets both the "Warburg effect", i.e., elevated glycolysis even in the presence oxygen, as well as mitochondrial oxidative phosphorylation in cancer cells. Normal cells remain unharmed. 3BP rapidly kills cancer cells growing in tissue culture, eradicates tumors in animals, and prevents metastasis. In addition, properly formulated 3BP shows promise also as an effective anti-liver cancer agent in humans and is effective also toward cancers known as "multiple myeloma". Finally, 3BP has been shown to significantly extend the life of a human patient for which no other options were available. Thus, it can be stated that 3BP is a very promising new anti-cancer agent in the process of undergoing clinical development.

  14. Cancer Stem Cell Theory and the Warburg Effect, Two Sides of the Same Coin?

    PubMed Central

    Pacini, Nicola; Borziani, Fabio

    2014-01-01

    Over the last 100 years, many studies have been performed to determine the biochemical and histopathological phenomena that mark the origin of neoplasms. At the end of the last century, the leading paradigm, which is currently well rooted, considered the origin of neoplasms to be a set of genetic and/or epigenetic mutations, stochastic and independent in a single cell, or rather, a stochastic monoclonal pattern. However, in the last 20 years, two important areas of research have underlined numerous limitations and incongruities of this pattern, the hypothesis of the so-called cancer stem cell theory and a revaluation of several alterations in metabolic networks that are typical of the neoplastic cell, the so-called Warburg effect. Even if this specific “metabolic sign” has been known for more than 85 years, only in the last few years has it been given more attention; therefore, the so-called Warburg hypothesis has been used in multiple and independent surveys. Based on an accurate analysis of a series of considerations and of biophysical thermodynamic events in the literature, we will demonstrate a homogeneous pattern of the cancer stem cell theory, of the Warburg hypothesis and of the stochastic monoclonal pattern; this pattern could contribute considerably as the first basis of the development of a new uniform theory on the origin of neoplasms. Thus, a new possible epistemological paradigm is represented; this paradigm considers the Warburg effect as a specific “metabolic sign” reflecting the stem origin of the neoplastic cell, where, in this specific metabolic order, an essential reason for the genetic instability that is intrinsic to the neoplastic cell is defined. PMID:24857919

  15. Cancer stem cell theory and the warburg effect, two sides of the same coin?

    PubMed

    Pacini, Nicola; Borziani, Fabio

    2014-05-19

    Over the last 100 years, many studies have been performed to determine the biochemical and histopathological phenomena that mark the origin of neoplasms. At the end of the last century, the leading paradigm, which is currently well rooted, considered the origin of neoplasms to be a set of genetic and/or epigenetic mutations, stochastic and independent in a single cell, or rather, a stochastic monoclonal pattern. However, in the last 20 years, two important areas of research have underlined numerous limitations and incongruities of this pattern, the hypothesis of the so-called cancer stem cell theory and a revaluation of several alterations in metabolic networks that are typical of the neoplastic cell, the so-called Warburg effect. Even if this specific "metabolic sign" has been known for more than 85 years, only in the last few years has it been given more attention; therefore, the so-called Warburg hypothesis has been used in multiple and independent surveys. Based on an accurate analysis of a series of considerations and of biophysical thermodynamic events in the literature, we will demonstrate a homogeneous pattern of the cancer stem cell theory, of the Warburg hypothesis and of the stochastic monoclonal pattern; this pattern could contribute considerably as the first basis of the development of a new uniform theory on the origin of neoplasms. Thus, a new possible epistemological paradigm is represented; this paradigm considers the Warburg effect as a specific "metabolic sign" reflecting the stem origin of the neoplastic cell, where, in this specific metabolic order, an essential reason for the genetic instability that is intrinsic to the neoplastic cell is defined.

  16. The cancer Warburg effect may be a testable example of the minimum entropy production rate principle

    NASA Astrophysics Data System (ADS)

    Marín, Dolores; Sabater, Bartolomé

    2017-04-01

    Cancer cells consume more glucose by glycolytic fermentation to lactate than by respiration, a characteristic known as the Warburg effect. In contrast with the 36 moles of ATP produced by respiration, fermentation produces two moles of ATP per mole of glucose consumed, which poses a puzzle with regard to the function of the Warburg effect. The production of free energy (ΔG), enthalpy (ΔH), and entropy (ΔS) per mole linearly varies with the fraction (x) of glucose consumed by fermentation that is frequently estimated around 0.9. Hence, calculation shows that, in respect to pure respiration, the predominant fermentative metabolism decreases around 10% the production of entropy per mole of glucose consumed in cancer cells. We hypothesize that increased fermentation could allow cancer cells to accomplish the Prigogine theorem of the trend to minimize the rate of production of entropy. According to the theorem, open cellular systems near the steady state could evolve to minimize the rates of entropy production that may be reached by modified replicating cells producing entropy at a low rate. Remarkably, at CO2 concentrations above 930 ppm, glucose respiration produces less entropy than fermentation, which suggests experimental tests to validate the hypothesis of minimization of the rate of entropy production through the Warburg effect.

  17. The cancer Warburg effect may be a testable example of the minimum entropy production rate principle.

    PubMed

    Marín, Dolores; Sabater, Bartolomé

    2017-04-28

    Cancer cells consume more glucose by glycolytic fermentation to lactate than by respiration, a characteristic known as the Warburg effect. In contrast with the 36 moles of ATP produced by respiration, fermentation produces two moles of ATP per mole of glucose consumed, which poses a puzzle with regard to the function of the Warburg effect. The production of free energy (ΔG), enthalpy (ΔH), and entropy (ΔS) per mole linearly varies with the fraction (x) of glucose consumed by fermentation that is frequently estimated around 0.9. Hence, calculation shows that, in respect to pure respiration, the predominant fermentative metabolism decreases around 10% the production of entropy per mole of glucose consumed in cancer cells. We hypothesize that increased fermentation could allow cancer cells to accomplish the Prigogine theorem of the trend to minimize the rate of production of entropy. According to the theorem, open cellular systems near the steady state could evolve to minimize the rates of entropy production that may be reached by modified replicating cells producing entropy at a low rate. Remarkably, at CO 2 concentrations above 930 ppm, glucose respiration produces less entropy than fermentation, which suggests experimental tests to validate the hypothesis of minimization of the rate of entropy production through the Warburg effect.

  18. Metastasis suppressor KISS1 seems to reverse the Warburg effect by enhancing mitochondrial biogenesis

    USDA-ARS?s Scientific Manuscript database

    Cancer cells tend to utilize aerobic glycolysis even under normoxic conditions, commonly called the "Warburg Effect." Aerobic glycolysis often directly correlates with malignancy, but its purpose, if any, in metastasis remains unclear. When wild-type KISS1 metastasis suppressor is expressed, aerob...

  19. Vitamin C uncouples the Warburg metabolic switch in KRAS mutant colon cancer.

    PubMed

    Aguilera, Oscar; Muñoz-Sagastibelza, María; Torrejón, Blanca; Borrero-Palacios, Aurea; Del Puerto-Nevado, Laura; Martínez-Useros, Javier; Rodriguez-Remirez, María; Zazo, Sandra; García, Estela; Fraga, Mario; Rojo, Federico; García-Foncillas, Jesús

    2016-07-26

    KRAS mutation is often present in many hard-to-treat tumors such as colon and pancreatic cancer and it is tightly linked to serious alterations in the normal cell metabolism and clinical resistance to chemotherapy.In 1931, the winner of the Nobel Prize in Medicine, Otto Warburg, stated that cancer was primarily caused by altered metabolism interfering with energy processing in the normal cell. Increased cell glycolytic rates even in the presence of oxygen is fully recognized as a hallmark in cancer and known as the Warburg effect.In the late 1970's, Linus Pauling and Ewan Cameron reported that vitamin C may have positive effects in cancer treatment, although deep mechanistic knowledge about this activity is still scarce.We describe a novel antitumoral mechanism of vitamin C in KRAS mutant colorectal cancer that involves the Warburg metabolic disruption through downregulation of key metabolic checkpoints in KRAS mutant cancer cells and tumors without killing human immortalized colonocytes.Vitamin C induces RAS detachment from the cell membrane inhibiting ERK 1/2 and PKM2 phosphorylation. As a consequence of this activity, strong downregulation of the glucose transporter (GLUT-1) and pyruvate kinase M2 (PKM2)-PTB dependent protein expression are observed causing a major blockage of the Warburg effect and therefore energetic stress.We propose a combination of conventional chemotherapy with metabolic strategies, including vitamin C and/or other molecules targeting pivotal key players involved in the Warburg effect which may constitute a new horizon in anti-cancer therapies.

  20. Optical spectroscopic characteristics of lactate and mitochondrion as new biomarkers in cancer diagnosis: understanding Warburg effect

    NASA Astrophysics Data System (ADS)

    Liu, C.-H.; Ni, X. H.; Pu, Yang; Yang, Y. L.; Zhou, F.; Zuzolo, R.; Wang, W. B.; Masilamani, V.; Rizwan, A.; Alfano, R. R.

    2012-01-01

    Cancer cells display high rates of glycolysis even under normoxia and mostly under hypoxia. Warburg proposed this effect of altered metabolism in cells more than 80 years ago. It is considered as a hallmark of cancer. Optical spectroscopy can be used to explore this effect. Pathophysiological studies indicate that mitochondria of cancer cells are enlarged and increased in number. Warburg observed that cancer cells tend to convert most glucose to lactate regardless of the presence of oxygen. Previous observations show increased lactate in breast cancer lines. The focus of this study is to investigate the relative content changes of lactate and mitochondria in human cancerous and normal breast tissue samples using optical spectroscopic techniques. The optical spectra were obtained from 30 cancerous and 25 normal breast tissue samples and five model components (Tryptophan, fat, collagen, lactate and mitochondrion) using fluorescence, Stokes shift and Raman spectroscopy. The basic biochemical component analysis model (BBCA) and a set of algorithm were used to analyze the spectra. Our analyses of fluorescence spectra showed a 14 percent increase in lactate content and 2.5 times increase in mitochondria number in cancerous breast tissue as compared with normal tissue. Our findings indicate that optical spectroscopic techniques may be used to understand Warburg effect. Lactate and mitochondrion content changes in tumors examined using optical spectroscopy may be used as a prognostic molecular marker in clinic applications.

  1. CHIP/Stub1 regulates the Warburg effect by promoting degradation of PKM2 in ovarian carcinoma.

    PubMed

    Shang, Y; He, J; Wang, Y; Feng, Q; Zhang, Y; Guo, J; Li, J; Li, S; Wang, Y; Yan, G; Ren, F; Shi, Y; Xu, J; Zeps, N; Zhai, Y; He, D; Chang, Z

    2017-07-20

    Tumor cells preferentially adopt aerobic glycolysis for their energy supply, a phenomenon known as the Warburg effect. It remains a matter of debate as to how the Warburg effect is regulated during tumor progression. Here, we show that CHIP (carboxyl terminus of Hsc70-interacting protein), a U-box E3 ligase, suppresses tumor progression in ovarian carcinomas by inhibiting aerobic glycolysis. While CHIP is downregulated in ovarian carcinoma, induced expression of CHIP results in significant inhibition of the tumor growth examined by in vitro and in vivo experiments. Reciprocally, depletion of CHIP leads to promotion of tumor growth. By a SiLAD proteomics analysis, we identified pyruvate kinase isoenzyme M2 (PKM2), a critical regulator of glycolysis in tumors, as a target that CHIP mediated for degradation. Accordingly, we show that CHIP regulates PKM2 protein stability and thereafter the energy metabolic processes. Depletion or knockout of CHIP increased the glycolytic products in both tumor and mouse embryonic fibroblast cells. Simultaneously, we observed that CHIP expression inversely correlated with PKM2 levels in human ovarian carcinomas. This study reveals a mechanism that the Warburg effect is regulated by CHIP through its function as an E3 ligase, which mediates the degradation of PKM2 during tumor progression. Our findings shed new light into understanding of ovarian carcinomas and may provide a new therapeutic strategy for ovarian cancer.

  2. Thyroid Hormone Differentially Modulates Warburg Phenotype in Breast Cancer Cells

    PubMed Central

    Suhane, Sonal; Ramanujan, V Krishnan

    2011-01-01

    Sustenance of cancer cells in vivo critically depends on a variety of genetic and metabolic adaptations. Aerobic glycolysis or Warburg effect has been a defining biochemical hallmark of transformed cells for more than five decades although a clear molecular basis of this observation is emerging only in recent years. In this study, we present our findings that thyroid hormone exerts its non-genomic and genomic actions in two model human breast cancer cell lines differentially. By laying a clear foundation for experimentally monitoring the Warburg phenotype in living cancer cells, we demonstrate that thyroid hormone-induced modulation of bioenergetic profiles in these two model cell lines depends on the degree of Warburg phenotype that they display. Further we also show that thyroid hormone can sensitize mitochondria in aggressive, triple-negative breast cancer cells favorably to increase the chemotherapeutic efficacy in these cells. Even though the role of thyroid hormone in modulating mitochondrial metabolism has been known, the current study accentuates the critical role it plays in modulating Warburg phenotype in breast cancer cells. The clinical significance of this finding is the possibility to devise strategies for metabolically modulating aggressive triple-negative tumors so as to enhance their chemosensitivity in vivo. PMID:21945435

  3. Intragenic DNA methylation and BORIS-mediated cancer-specific splicing contribute to the Warburg effect

    PubMed Central

    Singh, Smriti; Narayanan, Sathiya Pandi; Biswas, Kajal; Gupta, Amit; Ahuja, Neha; Yadav, Sandhya; Panday, Rajendra Kumar; Samaiya, Atul; Sharan, Shyam K.

    2017-01-01

    Aberrant alternative splicing and epigenetic changes are both associated with various cancers, but epigenetic regulation of alternative splicing in cancer is largely unknown. Here we report that the intragenic DNA methylation-mediated binding of Brother of Regulator of Imprinted Sites (BORIS) at the alternative exon of Pyruvate Kinase (PKM) is associated with cancer-specific splicing that promotes the Warburg effect and breast cancer progression. Interestingly, the inhibition of DNA methylation, BORIS depletion, or CRISPR/Cas9-mediated deletion of the BORIS binding site leads to a splicing switch from cancer-specific PKM2 to normal PKM1 isoform. This results in the reversal of the Warburg effect and the inhibition of breast cancer cell growth, which may serve as a useful approach to inhibit the growth of breast cancer cells. Importantly, our results show that in addition to PKM splicing, BORIS also regulates the alternative splicing of several genes in a DNA methylation-dependent manner. Our findings highlight the role of intragenic DNA methylation and DNA binding protein BORIS in cancer-specific splicing and its role in tumorigenesis. PMID:29073069

  4. An integrated multidisciplinary model describing initiation of cancer and the Warburg hypothesis

    PubMed Central

    2013-01-01

    Background In this paper we propose a chemical physics mechanism for the initiation of the glycolytic switch commonly known as the Warburg hypothesis, whereby glycolytic activity terminating in lactate continues even in well-oxygenated cells. We show that this may result in cancer via mitotic failure, recasting the current conception of the Warburg effect as a metabolic dysregulation consequent to cancer, to a biophysical defect that may contribute to cancer initiation. Model Our model is based on analogs of thermodynamic concepts that tie non-equilibrium fluid dynamics ultimately to metabolic imbalance, disrupted microtubule dynamics, and finally, genomic instability, from which cancers can arise. Specifically, we discuss how an analog of non-equilibrium Rayleigh-Benard convection can result in glycolytic oscillations and cause a cell to become locked into a higher-entropy state characteristic of cancer. Conclusions A quantitative model is presented that attributes the well-known Warburg effect to a biophysical mechanism driven by a convective disturbance in the cell. Contrary to current understanding, this effect may precipitate cancer development, rather than follow from it, providing new insights into carcinogenesis, cancer treatment, and prevention. PMID:23758735

  5. PINK1 Is a Negative Regulator of Growth and the Warburg Effect in Glioblastoma.

    PubMed

    Agnihotri, Sameer; Golbourn, Brian; Huang, Xi; Remke, Marc; Younger, Susan; Cairns, Rob A; Chalil, Alan; Smith, Christian A; Krumholtz, Stacey-Lynn; Mackenzie, Danielle; Rakopoulos, Patricia; Ramaswamy, Vijay; Taccone, Michael S; Mischel, Paul S; Fuller, Gregory N; Hawkins, Cynthia; Stanford, William L; Taylor, Michael D; Zadeh, Gelareh; Rutka, James T

    2016-08-15

    Proliferating cancer cells are characterized by high rates of glycolysis, lactate production, and altered mitochondrial metabolism. This metabolic reprogramming provides important metabolites for proliferation of tumor cells, including glioblastoma. These biological processes, however, generate oxidative stress that must be balanced through detoxification of reactive oxygen species (ROS). Using an unbiased retroviral loss-of-function screen in nontransformed human astrocytes, we demonstrate that mitochondrial PTEN-induced kinase 1 (PINK1) is a regulator of the Warburg effect and negative regulator of glioblastoma growth. We report that loss of PINK1 contributes to the Warburg effect through ROS-dependent stabilization of hypoxia-inducible factor-1A and reduced pyruvate kinase muscle isozyme 2 activity, both key regulators of aerobic glycolysis. Mechanistically, PINK1 suppresses ROS and tumor growth through FOXO3a, a master regulator of oxidative stress and superoxide dismutase 2. These findings highlight the importance of PINK1 and ROS balance in normal and tumor cells. PINK1 loss was observed in a significant number of human brain tumors including glioblastoma (n > 900) and correlated with poor patient survival. PINK1 overexpression attenuates in vivo glioblastoma growth in orthotopic mouse xenograft models and a transgenic glioblastoma model in Drosophila Cancer Res; 76(16); 4708-19. ©2016 AACR. ©2016 American Association for Cancer Research.

  6. Genetics Home Reference: Walker-Warburg syndrome

    MedlinePlus

    ... also involved in development of this condition. The proteins produced from the genes listed above and others involved in Walker-Warburg syndrome modify a protein called alpha (α)-dystroglycan; this modification, called glycosylation, ...

  7. The KISS1 metastasis suppressor appears to reverse the ‘Warburg Effect’

    USDA-ARS?s Scientific Manuscript database

    In 1924, Otto Warburg described the preference of cancer cells for glycolytic metabolism, even under normoxic conditions and that these metabolic changes directly correlate with malignant potential of several cancers. Although its purpose remains unclear, the “Warburg Effect” is thought to confer pr...

  8. LncRNA IDH1-AS1 links the functions of c-Myc and HIF1α via IDH1 to regulate the Warburg effect

    PubMed Central

    Xiang, Shaoxun; Gu, Hao; Thorne, Rick F.; Zhang, Xu Dong; Wu, Mian

    2018-01-01

    The oncoprotein c-Myc plays an important role in regulating glycolysis under normoxia; yet, in cancer cells, HIF1α, which is essential for driving glycolysis under hypoxia, is often up-regulated even in the presence of oxygen. The relationship between these two major regulators of the Warburg effect remains to be fully defined. Here we demonstrate that regulation of a long noncoding RNA (lncRNA), named IDH1-AS1, enables c-Myc to collaborate with HIF1α in activating the Warburg effect under normoxia. c-Myc transcriptionally repressed IDH1-AS1, which, upon expression, promoted homodimerization of IDH1 and thus enhanced its enzymatic activity. This resulted in increased α-KG and decreased ROS production and subsequent HIF1α down-regulation, leading to attenuation of glycolysis. Hence, c-Myc repression of IDH1-AS1 promotes activation of the Warburg effect by HIF1α. As such, IDH1-AS1 overexpression inhibited cell proliferation, whereas silencing of IDH1-AS1 promoted cell proliferation and cancer xenograft growth. Restoring IDH1-AS1 expression may therefore represent a potential metabolic approach for cancer treatment. PMID:29378948

  9. Theoretical interpretation of Warburg's impedance in unsupported electrolytic cells.

    PubMed

    Barbero, G

    2017-12-13

    We discuss the origin of Warburg's impedance in unsupported electrolytic cells containing only one group of positive and one group of negative ions. Our analysis is based on the Poisson-Nernst-Planck model, where the generation-recombination phenomenon is neglected. We show that to observe Warburg-like impedance the diffusion coefficient of the positive ions has to differ from that of the negative ones, and furthermore the electrodes have to be not blocking. We assume that the non-blocking properties of the electrodes can be described by means of an Ohmic model, where the charge exchange between the cell and the external circuit is described by means of an electrode conductivity. For simplicity we consider a symmetric cell. However, our analysis can be easily generalized to more complicated situations, where the cell is not symmetric and the charge exchange is described by the Chang-Jaffe model, or by a linearized version of the Butler-Volmer equation. Our analysis allows justification of the expression for Warburg's impedance proposed previously by several groups, based on wrong assumptions.

  10. PPARs: Interference with Warburg' Effect and Clinical Anticancer Trials

    PubMed Central

    Vamecq, Joseph; Colet, Jean-Marie; Vanden Eynde, Jean Jacques; Briand, Gilbert; Porchet, Nicole; Rocchi, Stéphane

    2012-01-01

    The metabolic/cell signaling basis of Warburg's effect (“aerobic glycolysis”) and the general metabolic phenotype adopted by cancer cells are first reviewed. Several bypasses are adopted to provide a panoramic integrated view of tumoral metabolism, by attributing a central signaling role to hypoxia-induced factor (HIF-1) in the expression of aerobic glycolysis. The cancer metabolic phenotype also results from alterations of other routes involving ras, myc, p53, and Akt signaling and the propensity of cancer cells to develop signaling aberrances (notably aberrant surface receptor expression) which, when present, offer unique opportunities for therapeutic interventions. The rationale for various emerging strategies for cancer treatment is presented along with mechanisms by which PPAR ligands might interfere directly with tumoral metabolism and promote anticancer activity. Clinical trials using PPAR ligands are reviewed and followed by concluding remarks and perspectives for future studies. A therapeutic need to associate PPAR ligands with other anticancer agents is perhaps an important lesson to be learned from the results of the clinical trials conducted to date. PMID:22654896

  11. Heterogeneity and proliferation of invasive cancer subclones in game theory models of the Warburg effect.

    PubMed

    Archetti, M

    2015-04-01

    The Warburg effect, a switch from aerobic energy production to anaerobic glycolysis, promotes tumour proliferation and motility by inducing acidification of the tumour microenvironment. Therapies that reduce acidity could impair tumour growth and invasiveness. I analysed the dynamics of cell proliferation and of resistance to therapies that target acidity, in a population of cells, under the Warburg effect. The dynamics of mutant cells with increased glycolysis and motility has been assessed in a multi-player game with collective interactions in the framework of evolutionary game theory. Perturbations of the level of acidity in the microenvironment have been used to simulate the effect of therapies that target glycolysis. The non-linear effects of glycolysis induce frequency-dependent clonal selection leading to coexistence of glycolytic and non-glycolytic cells within a tumour. Mutants with increased motility can invade such a polymorphic population and spread within the tumour. While reducing acidity may produce a sudden reduction in tumour cell proliferation, frequency-dependent selection enables it to adapt to the new conditions and can enable the tumour to restore its original levels of growth and invasiveness. The acidity produced by glycolysis acts as a non-linear public good that leads to coexistence of cells with high and low glycolysis within the tumour. Such a heterogeneous population can easily adapt to changes in acidity. Therapies that target acidity can only be effective in the long term if the cost of glycolysis is high, that is, under non-limiting oxygen concentrations. Their efficacy, therefore, is reduced when combined with therapies that impair angiogenesis. © 2015 The Authors Cell Proliferation Published by John Wiley & Sons Ltd.

  12. The Warburg effect version 2.0

    PubMed Central

    Menendez, Javier A.; Joven, Jorge; Cufí, Sílvia; Corominas-Faja, Bruna; Oliveras-Ferraros, Cristina; Cuyàs, Elisabet; Martin-Castillo, Begoña; López-Bonet, Eugeni; Alarcón, Tomás; Vazquez-Martin, Alejandro

    2013-01-01

    When fighting cancer, knowledge on metabolism has always been important. Today, it matters more than ever. The restricted cataloging of cancer genomes is quite unlikely to achieve the task of curing cancer, unless it is integrated into metabolic networks that respond to and influence the constantly evolving cancer stem cell (CSC) cellular states. Once the genomic era of carcinogenesis had pushed the 1920s Otto Warburg’s metabolic cancer hypothesis into obscurity for decades, the most recent studies begin to support a new developing paradigm, in which the molecular logic behind the conversion of non-CSCs into CSCs can be better understood in terms of the “metabolic facilitators” and “metabolic impediments” that operate as proximate openings and roadblocks, respectively, for the transcriptional events and signal transduction programs that ultimately orchestrate the intrinsic and/or microenvironmental paths to CSC cellular states. Here we propose that a profound understanding of how human carcinomas install a proper “Warburg effect version 2.0” allowing them to “run” the CSCs’ “software” programs should guide a new era of metabolo-genomic-personalized cancer medicine. By viewing metabolic reprogramming of CSCs as an essential characteristic that allows dynamic, multidimensional and evolving cancer populations to compete successfully for their expansion on the organism, we now argue that CSCs bioenergetics might be another cancer hallmark. A definitive understanding of metabolic reprogramming in CSCs may complement or to some extent replace, the 30-y-old paradigm of targeting oncogenes to treat human carcinomas, because it can be possible to metabolically create non-permissive or “hostile” metabotypes to prevent the occurrence of CSC cellular states with tumor- and metastasis-initiating capacity. PMID:23549172

  13. Combined targeting of PDK1 and EGFR triggers regression of glioblastoma by reversing the Warburg effect.

    PubMed

    Velpula, Kiran Kumar; Bhasin, Arnima; Asuthkar, Swapna; Tsung, Andrew J

    2013-12-15

    Glioblastoma multiforme is the most aggressive primary brain tumor in adults. Overexpression of the EGF receptor (EGFR) is recognized as a widespread oncogenic signature in glioblastoma multiforme, but the complexity of its contributions is not fully understood, nor the most effective ways to leverage anti-EGFR therapy in this setting. Hypoxia is known to drive the aggressive character of glioblastoma multiforme by promoting aerobic glycolysis rather than pyruvate oxidation carried out in mitochondria (OXPHOS), a phenomenon termed the Warburg effect, which is a general feature of oncogenesis. In this study, we report that hypoxia drives expression of the pyruvate dehydrogenase kinase (PDK1) and EGFR along with the hypoxia-inducing factor (HIF)-1α in human glioblastoma multiforme cells. PDK1 is a HIF-1-regulated gene and our findings indicated that hypoxia-induced PDK1 expression may promote EGFR activation, initiating a feed-forward loop that can sustain malignant progression. RNAi-mediated attenuation of PDK1 and EGFR lowered PDK1-EGFR activation and decreased HIF-1α expression, shifting the Warburg phenotype to OXPHOS and inhibiting glioblastoma multiforme growth and proliferation. In clinical specimens of glioblastoma multiforme, we found that immunohistochemical expression of PDK1, EGFR, and HIF-1α were elevated in glioblastoma multiforme specimens when compared with normal brain tissues. Collectively, our studies establish PDK1 as a key driver and candidate therapeutic target in glioblastoma multiforme. ©2013 AACR.

  14. Understanding the Warburg effect: the metabolic requirements of cell proliferation.

    PubMed

    Vander Heiden, Matthew G; Cantley, Lewis C; Thompson, Craig B

    2009-05-22

    In contrast to normal differentiated cells, which rely primarily on mitochondrial oxidative phosphorylation to generate the energy needed for cellular processes, most cancer cells instead rely on aerobic glycolysis, a phenomenon termed "the Warburg effect." Aerobic glycolysis is an inefficient way to generate adenosine 5'-triphosphate (ATP), however, and the advantage it confers to cancer cells has been unclear. Here we propose that the metabolism of cancer cells, and indeed all proliferating cells, is adapted to facilitate the uptake and incorporation of nutrients into the biomass (e.g., nucleotides, amino acids, and lipids) needed to produce a new cell. Supporting this idea are recent studies showing that (i) several signaling pathways implicated in cell proliferation also regulate metabolic pathways that incorporate nutrients into biomass; and that (ii) certain cancer-associated mutations enable cancer cells to acquire and metabolize nutrients in a manner conducive to proliferation rather than efficient ATP production. A better understanding of the mechanistic links between cellular metabolism and growth control may ultimately lead to better treatments for human cancer.

  15. Expression and phosphorylation of the AS160_v2 splice variant supports GLUT4 activation and the Warburg effect in multiple myeloma

    PubMed Central

    2013-01-01

    Background Multiple myeloma (MM) is a fatal plasma cell malignancy exhibiting enhanced glucose consumption associated with an aerobic glycolytic phenotype (i.e., the Warburg effect). We have previously demonstrated that myeloma cells exhibit constitutive plasma membrane (PM) localization of GLUT4, consistent with the dependence of MM cells on this transporter for maintenance of glucose consumption rates, proliferative capacity, and viability. The purpose of this study was to investigate the molecular basis of constitutive GLUT4 plasma membrane localization in MM cells. Findings We have elucidated a novel mechanism through which myeloma cells achieve constitutive GLUT4 activation involving elevated expression of the Rab-GTPase activating protein AS160_v2 splice variant to promote the Warburg effect. AS160_v2-positive MM cell lines display constitutive Thr642 phosphorylation, known to be required for inactivation of AS160 Rab-GAP activity. Importantly, we show that enforced expression of AS160_v2 is required for GLUT4 PM translocation and activation in these select MM lines. Furthermore, we demonstrate that ectopic expression of a full-length, phospho-deficient AS160 mutant is sufficient to impair constitutive GLUT4 cell surface residence, which is characteristic of MM cells. Conclusions This is the first study to tie AS160 de-regulation to increased glucose consumption rates and the Warburg effect in cancer. Future studies investigating connections between the insulin/IGF-1/AS160_v2/GLUT4 axis and FDG-PET positivity in myeloma patients are warranted and could provide rationale for therapeutically targeting this pathway in MM patients with advanced disease. PMID:24280290

  16. Light exposure at night disrupts host/cancer circadian regulatory dynamics: impact on the Warburg effect, lipid signaling and tumor growth prevention.

    PubMed

    Blask, David E; Dauchy, Robert T; Dauchy, Erin M; Mao, Lulu; Hill, Steven M; Greene, Michael W; Belancio, Victoria P; Sauer, Leonard A; Davidson, Leslie

    2014-01-01

    The central circadian clock within the suprachiasmatic nucleus (SCN) plays an important role in temporally organizing and coordinating many of the processes governing cancer cell proliferation and tumor growth in synchrony with the daily light/dark cycle which may contribute to endogenous cancer prevention. Bioenergetic substrates and molecular intermediates required for building tumor biomass each day are derived from both aerobic glycolysis (Warburg effect) and lipid metabolism. Using tissue-isolated human breast cancer xenografts grown in nude rats, we determined that circulating systemic factors in the host and the Warburg effect, linoleic acid uptake/metabolism and growth signaling activities in the tumor are dynamically regulated, coordinated and integrated within circadian time structure over a 24-hour light/dark cycle by SCN-driven nocturnal pineal production of the anticancer hormone melatonin. Dim light at night (LAN)-induced melatonin suppression disrupts this circadian-regulated host/cancer balance among several important cancer preventative signaling mechanisms, leading to hyperglycemia and hyperinsulinemia in the host and runaway aerobic glycolysis, lipid signaling and proliferative activity in the tumor.

  17. Flux balance analysis predicts Warburg-like effects of mouse hepatocyte deficient in miR-122a

    PubMed Central

    Wu, Hsuan-Hui; Chen, Meng-Chun; Liu, Wen-Huan; Wu, Wu-Hsiung; Chang, Peter Mu-Hsin; Huang, Chi-Ying F.; Tsou, Ann-Ping; Shiao, Ming-Shi

    2017-01-01

    The liver is a vital organ involving in various major metabolic functions in human body. MicroRNA-122 (miR-122) plays an important role in the regulation of liver metabolism, but its intrinsic physiological functions require further clarification. This study integrated the genome-scale metabolic model of hepatocytes and mouse experimental data with germline deletion of Mir122a (Mir122a–/–) to infer Warburg-like effects. Elevated expression of MiR-122a target genes in Mir122a–/–mice, especially those encoding for metabolic enzymes, was applied to analyze the flux distributions of the genome-scale metabolic model in normal and deficient states. By definition of the similarity ratio, we compared the flux fold change of the genome-scale metabolic model computational results and metabolomic profiling data measured through a liquid-chromatography with mass spectrometer, respectively, for hepatocytes of 2-month-old mice in normal and deficient states. The Ddc gene demonstrated the highest similarity ratio of 95% to the biological hypothesis of the Warburg effect, and similarity of 75% to the experimental observation. We also used 2, 6, and 11 months of mir-122 knockout mice liver cell to examined the expression pattern of DDC in the knockout mice livers to show upregulated profiles of DDC from the data. Furthermore, through a bioinformatics (LINCS program) prediction, BTK inhibitors and withaferin A could downregulate DDC expression, suggesting that such drugs could potentially alter the early events of metabolomics of liver cancer cells. PMID:28686599

  18. Effect of Daytime Blue-enriched LED Light on the Nighttime Circadian Melatonin Inhibition of Hepatoma 7288CTC Warburg Effect and Progression.

    PubMed

    Dauchy, Robert T; Wren-Dail, Melissa A; Dupepe, Lynell M; Hill, Steven M; Xiang, Shulin; Anbalagan, Muralidharan; Belancio, Victoria P; Dauchy, Erin M; Blask, David E

    2018-06-06

    Liver cancer is the second leading cause of cancer death worldwide. Metabolic pathways within the liver and liver cancersare highly regulated by the central circadian clock in the suprachiasmatic nuclei (SCN). Daily light and dark cycles regulate the SCN-driven pineal production of the circadian anticancer hormone melatonin and temporally coordinate circadianrhythms of metabolism and physiology in mammals. In previous studies, we demonstrated that melatonin suppresses linoleicacid metabolism and the Warburg effect (aerobic glycolysis)in human breast cancer xenografts and that blue-enriched light(465-485 nm) from light-emitting diode lighting at daytime (bLAD) amplifies nighttime circadian melatonin levels in ratsby 7-fold over cool white fluorescent (CWF) lighting. Here we tested the hypothesis that daytime exposure of tissue-isolatedMorris hepatoma 7288CTC-bearing male rats to bLAD amplifies the nighttime melatonin signal to enhance the inhibition oftumor growth. Compared with rats housed under a 12:12-h light:dark cycle in CWF light, rats in bLAD light evinced a 7-fold higher peak plasma melatonin level at the mid-dark phase; in addition, high melatonin levels were prolonged until 4 h intothe light phase. After implantation of tissue-isolated hepatoma 7288CTC xenografts, tumor growth rates were markedly delayed,and tumor cAMP levels, LA metabolism, the Warburg effect, and growth signaling activities were decreased in rats inbLAD compared with CWF daytime lighting. These data show that the increased nighttime circadian melatonin levels dueto bLAD exposure decreases hepatoma metabolic, signaling, and proliferative activities beyond what occurs after normalmelatonin signaling under CWF light.

  19. NMR ({sup 1}H and {sup 13}C) based signatures of abnormal choline metabolism in oral squamous cell carcinoma with no prominent Warburg effect

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bag, Swarnendu, E-mail: Swarna.bag@gmail.com; Banerjee, Deb Ranjan, E-mail: debranjan2@gmail.com; Basak, Amit, E-mail: absk@chem.iitkgp.ernet.in

    At functional levels, besides genes and proteins, changes in metabolome profiles are instructive for a biological system in health and disease including malignancy. It is understood that metabolomic alterations in association with proteomic and transcriptomic aberrations are very fundamental to unravel malignant micro-ambient criticality and oral cancer is no exception. Hence deciphering intricate dimensions of oral cancer metabolism may be contributory both for integrated appreciation of its pathogenesis and to identify any critical but yet unexplored dimension of this malignancy with high mortality rate. Although several methods do exist, NMR provides higher analytical precision in identification of cancer metabolomic signature.more » Present study explored abnormal signatures in choline metabolism in oral squamous cell carcinoma (OSCC) using {sup 1}H and {sup 13}C NMR analysis of serum. It has demonstrated down-regulation of choline with concomitant up-regulation of its break-down product in the form of trimethylamine N-oxide in OSCC compared to normal counterpart. Further, no significant change in lactate profile in OSCC possibly indicated that well-known Warburg effect was not a prominent phenomenon in such malignancy. Amongst other important metabolites, malonate has shown up-regulation but D-glucose, saturated fatty acids, acetate and threonine did not show any significant change. Analyzing these metabolomic findings present study proposed trimethyl amine N-oxide and malonate as important metabolic signature for oral cancer with no prominent Warburg effect. - Highlights: • NMR ({sup 1}H and {sup 13}C) study of Oral Squamous cell Carcinoma Serum. • Abnormal Choline metabolomic signatures. • Up-regulation of Trimethylamine N-oxide. • Unchanged lactate profile indicates no prominent Warburg effect. • Proposed alternative glucose metabolism path through up-regulation of malonate.« less

  20. Ginsenoside 20(S)-Rg3 Inhibits the Warburg Effect Via Modulating DNMT3A/ MiR-532-3p/HK2 Pathway in Ovarian Cancer Cells.

    PubMed

    Zhou, Yuanyuan; Zheng, Xia; Lu, Jiaojiao; Chen, Wei; Li, Xu; Zhao, Le

    2018-01-01

    The Warburg effect is one of the main energy metabolism features supporting cancer cell growth. 20(S)-Rg3 exerts anti-tumor effect on ovarian cancer partly by inhibiting the Warburg effect. microRNAs are important regulators of the Warburg effect. However, the microRNA regulatory network mediating the anti-Warburg effect of 20(S)-Rg3 was largely unknown. microRNA deep sequencing was performed to identify the 20(S)-Rg3-influenced microRNAs in SKOV3 ovarian cancer cells. miR-532-3p was overexpressed by mimic532-3p transfection in SKOV3 and A2780 cells or inhibited by inhibitor532-3p transfection in 20(S)-Rg3-treated cells to examine the changes in HK2 and PKM2 expression, glucose consumption, lactate production and cell growth. Dual-luciferase reporter assay was conducted to verify the direct binding of miR-532-3p to HK2. The methylation status in the promoter region of pre-miR-532-3p gene was examined by methylation-specific PCR. Expression changes of key molecules controlling DNA methylation including DNMT1, DNMT3A, DNMT3B, and TET1-3 were examined in 20(S)-Rg3-treated cells. DNMT3A was overexpressed in 20(S)-Rg3-treated cells to examine its influence on miR-532-3p level, HK2 and PKM2 expression, glucose consumption and lactate production. Deep sequencing results showed that 11 microRNAs were increased and 9 microRNAs were decreased by 20(S)-Rg3 in SKOV3 cells, which were verified by qPCR. More than 2-fold increase of miR-532-3p was found in 20(S)-Rg3-treated SKOV3 cells. Forced expression of miR-532-3p reduced HK2 and PKM2 expression, glucose consumption and lactate production in SKOV3 and A2780 ovarian cancer cells. Inhibition of miR-532-3p antagonized the suppressive effect of 20(S)-Rg3 on HK2 and PKM2 expression, glucose consumption and lactate production in ovarian cancer cells. Dual-luciferase reporter assay showed that miR-532-3p directly suppressed HK2 rather than PKM2. miR-532-3p level was controlled by the methylation in the promoter region of its host

  1. Out of Warburg effect: An effective cancer treatment targeting the tumor specific metabolism and dysregulated pH.

    PubMed

    Schwartz, Laurent; Seyfried, Thomas; Alfarouk, Khalid O; Da Veiga Moreira, Jorgelindo; Fais, Stefano

    2017-04-01

    As stated by Otto Warburg nearly a century ago, cancer is a metabolic disease, a fermentation caused by malfunctioning mitochondria, resulting in increased anabolism and decreased catabolism. Treatment should, therefore, aim at restoring the energy yield. To decrease anabolism, glucose uptake should be reduced (ketogenic diet). To increase catabolism, the oxidative phosphorylation should be restored. Treatment with a combination of α-lipoic acid and hydroxycitrate has been shown to be effective in multiple animal models. This treatment, in combination with conventional chemotherapy, has yielded extremely encouraging results in glioblastoma, brain metastasis and lung cancer. Randomized trials are necessary to confirm these preliminary data. The major limitation is the fact that the combination of α-lipoic acid and hydroxycitrate can only be effective if the mitochondria are still present and/or functional. That may not be the case in the most aggressive tumors. The increased intracellular alkalosis is a strong mitogenic signal, which bypasses most inhibitory signals. Concomitant correction of this alkalosis may be a very effective treatment in case of mitochondrial failure. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. 2-Deoxyglucose induces the expression of thioredoxin interacting protein (TXNIP) by increasing O-GlcNAcylation – Implications for targeting the Warburg effect in cancer cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hong, Shin Yee; Hagen, Thilo, E-mail: bchth@nus.edu.sg

    2015-10-02

    The high proliferation rate of cancer cells and the microenvironment in the tumor tissue require the reprogramming of tumor cell metabolism. The major mechanism of metabolic reprogramming in cancer cells is the Warburg effect, defined as the preferential utilization of glucose via glycolysis even in the presence of oxygen. Targeting the Warburg effect is considered as a promising therapeutic strategy in cancer therapy. In this regard, the glycolytic inhibitor 2-deoxyglucose (2DG) has been evaluated clinically. 2DG exerts its effect by directly inhibiting glycolysis at the level of hexokinase and phosphoglucoisomerase. In addition, 2DG is also known to induce the expressionmore » of thioredoxin interacting protein (TXNIP), a tumor suppressor protein and an important negative regulator of cellular glucose uptake. Hence, characterization of the mechanism through which 2DG regulates TXNIP expression may reveal novel approaches to target the Warburg effect in cancer cells. Therefore, in this study we sought to test various hypotheses for the mechanistic basis of the 2DG dependent TXNIP regulation. We have shown that 2DG induced TXNIP expression is independent of carbohydrate response element mediated transcription. Furthermore, the induction of TXNIP is neither dependent on the ability of 2DG to deplete cellular ATP nor to cause endoplasmic reticulum stress. We found that the 2DG induced TXNIP expression is at least in part dependent on the inhibition of the O-GlcNAcase enzyme and the accumulation of O-GlcNAc modified proteins. These results have implications for the identification of therapeutic targets to increase TXNIP expression in cancer. - Highlights: • 2DG increases TXNIP expression at the mRNA and protein level. • The effect of 2DG on TXNIP is independent of ChoRE mediated transcription. • 2DG induces TXNIP independent of ER stress induction and ATP depletion. • 2DG inhibits OGA and leads to accumulation of O-GlcNAcylated proteins. • The upregulation

  3. Mitochondrial pyruvate carrier function is negatively linked to Warburg phenotype in vitro and malignant features in esophageal squamous cell carcinomas

    PubMed Central

    Li, Yaqing; Li, Xiaoran; Kan, Quancheng; Zhang, Mingzhi; Li, Xiaoli; Xu, Ruiping; Wang, Junsheng; Yu, Dandan; Goscinski, Mariusz Adam; Wen, Jian-Guo; Nesland, Jahn M.; Suo, Zhenhe

    2017-01-01

    Aerobic glycolysis is one of the emerging hallmarks of cancer cells. In this study, we investigated the relationship between blocking mitochondrial pyruvate carrier (MPC) with MPC blocker UK5099 and the metabolic alteration as well as aggressive features of esophageal squamous carcinoma. It was found that blocking pyruvate transportation into mitochondria attenuated mitochondrial oxidative phosphorylation (OXPHOS) and triggered aerobic glycolysis, a feature of Warburg effect. In addition, the HIF-1α expression and ROS production were also activated upon UK5099 application. It was further revealed that the UK5099-treated cells became significantly more resistant to chemotherapy and radiotherapy, and the UK5099-treated tumor cells also exhibited stronger invasive capacity compared to the parental cells. In contrast to esophageal squamous epithelium cells, decreased MPC protein expression was observed in a series of 157 human squamous cell carcinomas, and low/negative MPC1 expression predicted an unfavorable clinical outcome. All these results together revealed the potential connection of altered MPC expression/activity with the Warburg metabolic reprogramming and tumor aggressiveness in cell lines and clinical samples. Collectively, our findings highlighted a therapeutic strategy targeting Warburg reprogramming of human esophageal squamous cell carcinomas. PMID:27911865

  4. The Warburg effect: persistence of stem-cell metabolism in cancers as a failure of differentiation.

    PubMed

    Riester, M; Xu, Q; Moreira, A; Zheng, J; Michor, F; Downey, R J

    2018-01-01

    Two recent observations regarding the Warburg effect are that (i) the metabolism of stem cells is constitutive (aerobic) glycolysis while normal cellular differentiation involves a transition to oxidative phosphorylation and (ii) the degree of glucose uptake of a malignancy as imaged by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is associated with histologic measures of tumor differentiation. Combining these observations, we hypothesized that the high levels of glucose uptake observed in poorly differentiated cancers may reflect persistence of the glycolytic metabolism of stem cells in malignant cells that fail to fully differentiate. Tumor glucose uptake was measured by FDG-PET in 552 patients with histologically diverse cancers. We used normal mixture modeling to explore FDG-PET standardized uptake value (SUV) distributions and tested for associations between glucose uptake and histological differentiation, risk of lymph node metastasis, and survival. Using RNA-seq data, we carried out pathway and transcription factor analyses to compare tumors with high and low levels of glucose uptake. We found that well-differentiated tumors had low FDG uptake, while moderately and poorly differentiated tumors had higher uptake. The distribution of SUV for each histology was bimodal, with a low peak around SUV 2-5 and a high peak at SUV 8-14. The cancers in the two modes were clinically distinct in terms of the risk of nodal metastases and death. Carbohydrate metabolism and the pentose-related pathway were elevated in the poorly differentiated/high SUV clusters. Embryonic stem cell-related signatures were activated in poorly differentiated/high SUV clusters. Our findings support the hypothesis that the biological basis for the Warburg effect is a persistence of stem cell metabolism (i.e. aerobic glycolysis) in cancers as a failure to transition from glycolysis-utilizing undifferentiated cells to oxidative phosphorylation-utilizing differentiated cells. We

  5. EGF induces epithelial-mesenchymal transition and cancer stem-like cell properties in human oral cancer cells via promoting Warburg effect.

    PubMed

    Xu, Qilin; Zhang, Qunzhou; Ishida, Yasutaka; Hajjar, Souren; Tang, Xudong; Shi, Haoran; Dang, Chi V; Le, Anh D

    2017-02-07

    "Warburg effect", the enhanced glycolysis or aerobic glycolysis, confers cancer cells the ability to survive and proliferate even under stressed conditions. In this study, we explored the role of epidermal growth factor (EGF) in orchestrating Warburg effect, the epithelial-mesenchymal transition (EMT) process, and the acquisition of cancer stem-like cell properties in human oral squamous cell carcinoma (OSCC) cells. Our results showed that EGF induces EMT process in OSCC cells, which correlates with the acquisition of cancer stem-like properties, including the enrichment of CD44+/CD24- population of cancer cells and an increased expression of CSC-related genes, aldehyde dehydrogenase-1 (ALDH1) and Bmi-1. We also showed that EGF concomitantly enhanced L-lactate production, while blocking glycolysis by 2-deoxy-D-glucose (2-DG) robustly reversed EGF-induced EMT process and CSC-like properties in OSCC cells. Mechanistically, we demonstrated that EGF promoted EMT process and CSC generation through EGFR/PI3K/HIF-1α axis-orchestrated glycolysis. Using an orthotopic tumor model of human OSCC (UM-SCC1) injected in the tongue of BALB/c nude mice, we showed that treatment with 2-DG in vivo significantly inhibited the metastasis of tumor cells to the regional cervical lymph nodes and reduced the expression of ALDH1 and vimentin in both in situ tumors and tumor cell-invaded regional lymph nodes. Taken together, these findings have unveiled a new mechanism that EGF drives OSCC metastasis through induction of EMT process and CSC generation, which is driven by an enhanced glycolytic metabolic program in OSCC cells.

  6. MtDNA depleted PC3 cells exhibit Warburg effect and cancer stem cell features

    PubMed Central

    Li, Xiaoran; Zhong, Yali; Lu, Jie; Axcrona, Karol; Eide, Lars; Syljuåsen, Randi G.; Peng, Qian; Wang, Junbai; Zhang, Hongquan; Goscinski, Mariusz Adam; Kvalheim, Gunnar; Nesland, Jahn M.; Suo, Zhenhe

    2016-01-01

    Reducing mtDNA content was considered as a critical step in the metabolism restructuring for cell stemness restoration and further neoplastic development. However, the connections between mtDNA depletion and metabolism reprograming-based cancer cell stemness in prostate cancers are still lack of studies. Here, we demonstrated that human CRPC cell line PC3 tolerated high concentration of the mtDNA replication inhibitor ethidium bromide (EtBr) and the mtDNA depletion triggered a universal metabolic remodeling process. Failure in completing that process caused lethal consequences. The mtDNA depleted (MtDP) PC3 cells could be steadily maintained in the special medium in slow cycling status. The MtDP PC3 cells contained immature mitochondria and exhibited Warburg effect. Furthermore, the MtDP PC3 cells were resistant to therapeutic treatments and contained greater cancer stem cell-like subpopulations: CD44+, ABCG2+, side-population and ALDHbright. In conclusion, these results highlight the association of mtDNA content, mitochondrial function and cancer cell stemness features. PMID:27248169

  7. A DERL3-associated defect in the degradation of SLC2A1 mediates the Warburg effect

    PubMed Central

    Lopez-Serra, Paula; Marcilla, Miguel; Villanueva, Alberto; Ramos-Fernandez, Antonio; Palau, Anna; Leal, Lucía; Wahi, Jessica E.; Setien-Baranda, Fernando; Szczesna, Karolina; Moutinho, Catia; Martinez-Cardus, Anna; Heyn, Holger; Sandoval, Juan; Puertas, Sara; Vidal, August; Sanjuan, Xavier; Martinez-Balibrea, Eva; Viñals, Francesc; Perales, Jose C.; Bramsem, Jesper B.; Ørntoft, Torben F.; Andersen, Claus L.; Tabernero, Josep; McDermott, Ultan; Boxer, Matthew B.; Heiden, Matthew G. Vander; Albar, Juan Pablo; Esteller, Manel

    2014-01-01

    Cancer cells possess aberrant proteomes that can arise by the disruption of genes involved in physiological protein degradation. Here we demonstrate the presence of promoter CpG island hypermethylation-linked inactivation of DERL3 (Derlin-3), a key gene in the endoplasmic reticulum-associated protein degradation pathway, in human tumours. The restoration of in vitro and in vivo DERL3 activity highlights the tumour suppressor features of the gene. Using the stable isotopic labelling of amino acids in cell culture workflow for differential proteome analysis, we identify SLC2A1 (glucose transporter 1, GLUT1) as a downstream target of DERL3. Most importantly, SLC2A1 overexpression mediated by DERL3 epigenetic loss contributes to the Warburg effect in the studied cells and pinpoints a subset of human tumours with greater vulnerability to drugs targeting glycolysis. PMID:24699711

  8. A role for the mitochondrial pyruvate carrier as a repressor of the Warburg Effect and colon cancer cell growth

    PubMed Central

    Schell, John C.; Olson, Kristofor A.; Jiang, Lei; Hawkins, Amy J.; Van Vranken, Jonathan G.; Xie, Jianxin; Egnatchik, Robert A.; Earl, Espen G.; Deberardinis, Ralph J.; Rutter, Jared

    2014-01-01

    Summary Cancer cells are typically subject to profound metabolic alterations, including the Warburg effect wherein cancer cells oxidize a decreased fraction of the pyruvate generated from glycolysis. We show herein that the mitochondrial pyruvate carrier (MPC), composed of the products of the MPC1 and MPC2 genes, modulates fractional pyruvate oxidation. MPC1 is deleted or underexpressed in multiple cancers and correlates with poor prognosis. Cancer cells re-expressing MPC1 and MPC2 display increased mitochondrial pyruvate oxidation, with no changes in cell growth in adherent culture. MPC re-expression exerted profound effects in anchorage-independent growth conditions, however, including impaired colony formation in soft agar, spheroid formation, and xenograft growth. We also observed a decrease in markers of stemness and traced the growth effects of MPC expression to the stem cell compartment. We propose that reduced MPC activity is an important aspect of cancer metabolism, perhaps through altering the maintenance and fate of stem cells. PMID:25458841

  9. Revisiting the Trust Effect in Urban Elementary Schools

    ERIC Educational Resources Information Center

    Adams, Curt M.; Forsyth, Patrick B.

    2013-01-01

    More than a decade after Goddard, Tschannen-Moran, and Hoy (2001) found that collective faculty trust in clients predicts student achievement in urban elementary schools, we sought to identify a plausible link for this relationship. Our purpose in revisiting the trust effect was twofold: (1) to test the main effect of collective faculty trust on…

  10. Monitoring Mitochondrial Pyruvate Carrier Activity in Real Time Using a BRET-Based Biosensor: Investigation of the Warburg Effect.

    PubMed

    Compan, Vincent; Pierredon, Sandra; Vanderperre, Benoît; Krznar, Petra; Marchiq, Ibtissam; Zamboni, Nicola; Pouyssegur, Jacques; Martinou, Jean-Claude

    2015-08-06

    The transport of pyruvate into mitochondria requires a specific carrier, the mitochondrial pyruvate carrier (MPC). The MPC represents a central node of carbon metabolism, and its activity is likely to play a key role in bioenergetics. Until now, investigation of the MPC activity has been limited. However, the recent molecular identification of the components of the carrier has allowed us to engineer a genetically encoded biosensor and to monitor the activity of the MPC in real time in a cell population or in a single cell. We report that the MPC activity is low in cancer cells, which mainly rely on glycolysis to generate ATP, a characteristic known as the Warburg effect. We show that this low activity can be reversed by increasing the concentration of cytosolic pyruvate, thus increasing oxidative phosphorylation. This biosensor represents a unique tool to investigate carbon metabolism and bioenergetics in various cell types. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Warburg-like Glycolysis and Lactate Shuttle in Mouse Decidua during Early Pregnancy*

    PubMed Central

    Zuo, Ru-Juan; Gu, Xiao-Wei; Qi, Qian-Rong; Wang, Tong-Song; Zhao, Xu-Yu; Liu, Ji-Long; Yang, Zeng-Ming

    2015-01-01

    Decidualization is an essential process of maternal endometrial stromal cells to support pregnancy. Although it is known that enhanced glucose influx is critical for decidualization, the underlying mechanism in regulating glucose metabolism in decidua remains insufficiently understood. Here, we demonstrate that aerobic glycolysis-related genes and factors are all substantially induced during decidualization, indicating the existence of Warburg-like glycolysis in decidua. In vitro, progesterone activates hypoxia-inducible factor 1α (Hif1α) and c-Myc through Pi3k-Akt signaling pathway to maintain aerobic glycolysis in decidualizing cells. Knocking down of pyruvate kinase M2 (Pkm2) attenuates the induction of decidual marker gene. Decidual formation in vivo is also impaired by glycolysis inhibitor 3-bromopyruvate. Besides, lactate exporter monocarboxylate transporter 4 (Mct4) is induced in newly formed decidual cells, whereas lactate importer Mct1 and proliferation marker Ki-67 are complementarily located in the surrounding undifferentiated cells, which are supposed to consume lactate for proliferation. Hif1α activation is required for lactate-dependent proliferation of the undifferentiated cells. Inhibition of lactate flux leads to compromised decidualization and decelerated lactate-dependent proliferation. In summary, we reveal that Warburg-like glycolysis and local lactate shuttle are activated in decidua and play important roles for supporting early pregnancy. PMID:26178372

  12. Germline BAP1 mutations induce a Warburg effect

    PubMed Central

    Bononi, Angela; Yang, Haining; Giorgi, Carlotta; Patergnani, Simone; Pellegrini, Laura; Su, Mingming; Xie, Guoxiang; Signorato, Valentina; Pastorino, Sandra; Morris, Paul; Sakamoto, Greg; Kuchay, Shafi; Gaudino, Giovanni; Pass, Harvey I; Napolitano, Andrea; Pinton, Paolo; Jia, Wei; Carbone, Michele

    2017-01-01

    Carriers of heterozygous germline BAP1 mutations (BAP1+/−) develop cancer. We studied plasma from 16 BAP1+/− individuals from 2 families carrying different germline BAP1 mutations and 30 BAP1 wild-type (BAP1WT) controls from these same families. Plasma samples were analyzed by liquid chromatography time-of-flight mass spectrometry (LC-TOF-MS), ultra-performance liquid chromatography triple quadrupole mass spectrometry (UPLC-TQ-MS), and gas chromatography time-of-flight mass spectrometry (GC-TOF-MS). We found a clear separation in the metabolic profile between BAP1WT and BAP1+/− individuals. We confirmed the specificity of the data in vitro using 12 cell cultures of primary fibroblasts we derived from skin punch biopsies from 12/46 of these same individuals, 6 BAP1+/− carriers and 6 controls from both families. BAP1+/− fibroblasts displayed increased aerobic glycolysis and lactate secretion, and reduced mitochondrial respiration and ATP production compared with BAP1WT. siRNA-mediated downregulation of BAP1 in primary BAP1WT fibroblasts and in primary human mesothelial cells, led to the same reduced mitochondrial respiration and increased aerobic glycolysis as we detected in primary fibroblasts from carriers of BAP1+/− mutations. The plasma and cell culture results were highly reproducible and were specifically and only linked to BAP1 status and not to gender, age or family, or cell type, and required an intact BAP1 catalytic activity. Accordingly, we were able to build a metabolomic model capable of predicting BAP1 status with 100% accuracy using data from human plasma. Our data provide the first experimental evidence supporting the hypothesis that aerobic glycolysis, also known as the ‘Warburg effect’, does not necessarily occur as an adaptive process that is consequence of carcinogenesis, but rather that it may also predate malignancy by many years and facilitate carcinogenesis. PMID:28665402

  13. Revisiting the Role of Organizational Effectiveness in Educational Evaluation.

    ERIC Educational Resources Information Center

    Lotto, Linda S.

    Organizational effectiveness ought to play a role in educational evaluation, and the development of alternative perspectives for viewing organizations could be a starting point for revisiting organizational evaluation in education. Five possible perspectives and criteria for evaluating organizations have been developed. If an organization is…

  14. Revisiting "The Widget Effect": Teacher Evaluation Reforms and the Distribution of Teacher Effectiveness

    ERIC Educational Resources Information Center

    Kraft, Matthew A.; Gilmour, Allison F.

    2017-01-01

    In 2009, the New Teacher Project's "The Widget Effect" documented the failure of U.S. public school districts to recognize and act on differences in teacher effectiveness. We revisit these findings by compiling teacher performance ratings across 24 states that adopted major reforms to their teacher evaluation systems. In the vast…

  15. The Importance of Being a Complement: CED Effects Revisited

    ERIC Educational Resources Information Center

    Jurka, Johannes

    2010-01-01

    This dissertation revisits subject island effects (Ross 1967, Chomsky 1973) cross-linguistically. Controlled acceptability judgment studies in German, English, Japanese and Serbian show that extraction out of specifiers is consistently degraded compared to extraction out of complements, indicating that the Condition on Extraction domains (CED,…

  16. Hexokinase-2 bound to mitochondria: Cancer's stygian link to the “Warburg effect” and a pivotal target for effective therapy☆

    PubMed Central

    Mathupala, Saroj P.; Ko, Young H.; Pedersen, Peter L.

    2009-01-01

    The most common metabolic hallmark of malignant tumors, i.e., the “Warburg effect” is their propensity to metabolize glucose to lactic acid at a high rate even in the presence of oxygen. The pivotal player in this frequent cancer phenotype is mitochondrial-bound hexokinase [Bustamante E, Pedersen PL. High aerobic glycolysis of rat hepatoma cells in culture: role of mitochondrial hexokinase. Proc Natl Acad Sci USA 1977;74(9):3735−9; Bustamante E, Morris HP, Pedersen PL. Energy metabolism of tumor cells. Requirement for a form of hexokinase with a propensity for mitochondrial binding. J Biol Chem 1981;256(16):8699−704]. Now, in clinics worldwide this prominent phenotype forms the basis of one of the most common detection systems for cancer, i.e., positron emission tomography (PET). Significantly, HK-2 is the major bound hexokinase isoform expressed in cancers that exhibit a “Warburg effect”. This includes most cancers that metastasize and kill their human host. By stationing itself on the outer mitochondrial membrane, HK-2 also helps immortalize cancer cells, escapes product inhibition and gains preferential access to newly synthesized ATP for phosphorylating glucose. The latter event traps this essential nutrient inside the tumor cells as glucose-6-P, some of which is funneled off to serve as carbon precursors to help promote the production of new cancer cells while much is converted to lactic acid that exits the cells. The resultant acidity likely wards off an immune response while preparing surrounding tissues for invasion. With the re-emergence and acceptance of both the “Warburg effect” as a prominent phenotype of most clinical cancers, and “metabolic targeting” as a rational therapeutic strategy, a number of laboratories are focusing on metabolite entry or exit steps. One remarkable success story [Ko YH, Smith BL, Wang Y, Pomper MG, Rini DA, Torbenson MS, et al. Advanced cancers: eradication in all cases using 3-bromopyruvate therapy to

  17. Norrie-Warburg syndrome: two novel mutations in patients with classical clinical phenotype.

    PubMed

    Gal, A; Veske, A; Jojart, G; Grammatico, B; Huber, B; Gu, S; del Porto, G; Senyi, K

    1996-01-01

    Norrie-Warburg syndrome (NWS) is a rare X-linked disorder characterized by blindness, which is invariable, deafness and mental disturbances, which are present occasionally. We describe here two novel mutations, a missense mutation (C126S) and a 1-base pair insertion (insT466/T467), together with a recurrent mutation (M1V), found in patients presenting with the classical clinical phenotype of NWS. All three mutations are likely to result in prominent structural changes of the norrin protein.

  18. The Warburg effect in mycobacterial granulomas is dependent on the recruitment and activation of macrophages by interferon-γ

    PubMed Central

    Appelberg, Rui; Moreira, Diana; Barreira-Silva, Palmira; Borges, Margarida; Silva, Letícia; Dinis-Oliveira, Ricardo Jorge; Resende, Mariana; Correia-Neves, Margarida; Jordan, Michael B; Ferreira, Nuno C; Abrunhosa, Antero J; Silvestre, Ricardo

    2015-01-01

    Granulomas are the hallmark of mycobacterial disease. Here, we demonstrate that both the cell recruitment and the increased glucose consumption in granulomatous infiltrates during Mycobacterium avium infection are highly dependent on interferon-γ (IFN-γ). Mycobacterium avium-infected mice lacking IFN-γ signalling failed to developed significant inflammatory infiltrations and lacked the characteristic uptake of the glucose analogue fluorine-18-fluorodeoxyglucose (FDG). To assess the role of macrophages in glucose uptake we infected mice with a selective impairment of IFN-γ signalling in the macrophage lineage (MIIG mice). Although only a partial reduction of the granulomatous areas was observed in infected MIIG mice, the insensitivity of macrophages to IFN-γ reduced the accumulation of FDG. In vivo, ex vivo and in vitro assays showed that macrophage activated by IFN-γ displayed increased rates of glucose uptake and in vitro studies showed also that they had increased lactate production and increased expression of key glycolytic enzymes. Overall, our results show that the activation of macrophages by IFN-γ is responsible for the Warburg effect observed in organs infected with M. avium. PMID:25807843

  19. Cancer and Exercise: Warburg Hypothesis, Tumour Metabolism and High-Intensity Anaerobic Exercise.

    PubMed

    Hofmann, Peter

    2018-01-31

    There is ample evidence that regular moderate to vigorous aerobic physical activity is related to a reduced risk for various forms of cancer to suggest a causal relationship. Exercise is associated with positive changes in fitness, body composition, and physical functioning as well as in patient-reported outcomes such as fatigue, sleep quality, or health-related quality of life. Emerging evidence indicates that exercise may also be directly linked to the control of tumour biology through direct effects on tumour-intrinsic factors. Beside a multitude of effects of exercise on the human body, one underscored effect of exercise training is to target the specific metabolism of tumour cells, namely the Warburg-type highly glycolytic metabolism. Tumour metabolism as well as the tumour⁻host interaction may be selectively influenced by single bouts as well as regularly applied exercise, dependent on exercise intensity, duration, frequency and mode. High-intensity anaerobic exercise was shown to inhibit glycolysis and some studies in animals showed that effects on tumour growth might be stronger compared with moderate-intensity aerobic exercise. High-intensity exercise was shown to be safe in patients; however, it has to be applied carefully with an individualized prescription of exercise.

  20. AMP-activated Protein Kinase Stimulates Warburg-like Glycolysis and Activation of Satellite Cells during Muscle Regeneration*

    PubMed Central

    Fu, Xing; Zhu, Mei-Jun; Dodson, Mike V.; Du, Min

    2015-01-01

    Satellite cells are the major myogenic stem cells residing inside skeletal muscle and are indispensable for muscle regeneration. Satellite cells remain largely quiescent but are rapidly activated in response to muscle injury, and the derived myogenic cells then fuse to repair damaged muscle fibers or form new muscle fibers. However, mechanisms eliciting metabolic activation, an inseparable step for satellite cell activation following muscle injury, have not been defined. We found that a noncanonical Sonic Hedgehog (Shh) pathway is rapidly activated in response to muscle injury, which activates AMPK and induces a Warburg-like glycolysis in satellite cells. AMPKα1 is the dominant AMPKα isoform expressed in satellite cells, and AMPKα1 deficiency in satellite cells impairs their activation and myogenic differentiation during muscle regeneration. Drugs activating noncanonical Shh promote proliferation of satellite cells, which is abolished because of satellite cell-specific AMPKα1 knock-out. Taken together, AMPKα1 is a critical mediator linking noncanonical Shh pathway to Warburg-like glycolysis in satellite cells, which is required for satellite activation and muscle regeneration. PMID:26370082

  1. Analysis and interpretation of transcriptomic data obtained from extended Warburg effect genes in patients with clear cell renal cell carcinoma

    PubMed Central

    Sanders, Edward; Diehl, Svenja

    2015-01-01

    Background Many cancers adopt a metabolism that is characterized by the well-known Warburg effect (aerobic glycolysis). Recently, numerous attempts have been made to treat cancer by targeting one or more gene products involved in this pathway without notable success. This work outlines a transcriptomic approach to identify genes that are highly perturbed in clear cell renal cell carcinoma (CCRCC). Methods We developed a model of the extended Warburg effect and outlined the model using Cytoscape. Following this, gene expression fold changes (FCs) for tumor and adjacent normal tissue from patients with CCRCC (GSE6344) were mapped on to the network. Gene expression values with FCs of greater than two were considered as potential targets for treatment of CCRCC. Results The Cytoscape network includes glycolysis, gluconeogenesis, the pentose phosphate pathway (PPP), the TCA cycle, the serine/glycine pathway, and partial glutaminolysis and fatty acid synthesis pathways. Gene expression FCs for nine of the 10 CCRCC patients in the GSE6344 data set were consistent with a shift to aerobic glycolysis. Genes involved in glycolysis and the synthesis and transport of lactate were over-expressed, as was the gene that codes for the kinase that inhibits the conversion of pyruvate to acetyl-CoA. Interestingly, genes that code for unique proteins involved in gluconeogenesis were strongly under-expressed as was also the case for the serine/glycine pathway. These latter two results suggest that the role attributed to the M2 isoform of pyruvate kinase (PKM2), frequently the principal isoform of PK present in cancer: i.e. causing a buildup of glucose metabolites that are shunted into branch pathways for synthesis of key biomolecules, may not be operative in CCRCC. The fact that there was no increase in the expression FC of any gene in the PPP is consistent with this hypothesis. Literature protein data generally support the transcriptomic findings. Conclusions A number of key genes have

  2. The Anti-Warburg Effect Elicited by the cAMP-PGC1α Pathway Drives Differentiation of Glioblastoma Cells into Astrocytes.

    PubMed

    Xing, Fan; Luan, Yizhao; Cai, Jing; Wu, Sihan; Mai, Jialuo; Gu, Jiayu; Zhang, Haipeng; Li, Kai; Lin, Yuan; Xiao, Xiao; Liang, Jiankai; Li, Yuan; Chen, Wenli; Tan, Yaqian; Sheng, Longxiang; Lu, Bingzheng; Lu, Wanjun; Gao, Mingshi; Qiu, Pengxin; Su, Xingwen; Yin, Wei; Hu, Jun; Chen, Zhongping; Sai, Ke; Wang, Jing; Chen, Furong; Chen, Yinsheng; Zhu, Shida; Liu, Dongbing; Cheng, Shiyuan; Xie, Zhi; Zhu, Wenbo; Yan, Guangmei

    2017-01-10

    Glioblastoma multiforme (GBM) is among the most aggressive of human cancers. Although differentiation therapy has been proposed as a potential approach to treat GBM, the mechanisms of induced differentiation remain poorly defined. Here, we established an induced differentiation model of GBM using cAMP activators that specifically directed GBM differentiation into astroglia. Transcriptomic and proteomic analyses revealed that oxidative phosphorylation and mitochondrial biogenesis are involved in induced differentiation of GBM. Dibutyryl cyclic AMP (dbcAMP) reverses the Warburg effect, as evidenced by increased oxygen consumption and reduced lactate production. Mitochondrial biogenesis induced by activation of the CREB-PGC1α pathway triggers metabolic shift and differentiation. Blocking mitochondrial biogenesis using mdivi1 or by silencing PGC1α abrogates differentiation; conversely, overexpression of PGC1α elicits differentiation. In GBM xenograft models and patient-derived GBM samples, cAMP activators also induce tumor growth inhibition and differentiation. Our data show that mitochondrial biogenesis and metabolic switch to oxidative phosphorylation drive the differentiation of tumor cells. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Targeting the Warburg effect with a novel glucose transporter inhibitor to overcome gemcitabine resistance in pancreatic cancer cells

    PubMed Central

    Lai, I-Lu; Chou, Chih-Chien; Lai, Po-Ting; Fang, Chun-Sheng; Shirley, Lawrence A.; Yan, Ribai; Mo, Xiaokui; Bloomston, Mark; Kulp, Samuel K.; Bekaii-Saab, Tanios; Chen, Ching-Shih

    2014-01-01

    Gemcitabine resistance remains a significant clinical challenge. Here, we used a novel glucose transporter (Glut) inhibitor, CG-5, as a proof-of-concept compound to investigate the therapeutic utility of targeting the Warburg effect to overcome gemcitabine resistance in pancreatic cancer. The effects of gemcitabine and/or CG-5 on viability, survival, glucose uptake and DNA damage were evaluated in gemcitabine-sensitive and gemcitabine-resistant pancreatic cancer cell lines. Mechanistic studies were conducted to determine the molecular basis of gemcitabine resistance and the mechanism of CG-5-induced sensitization to gemcitabine. The effects of CG-5 on gemcitabine sensitivity were investigated in a xenograft tumor model of gemcitabine-resistant pancreatic cancer. In contrast to gemcitabine-sensitive pancreatic cancer cells, the resistant Panc-1 and Panc-1GemR cells responded to gemcitabine by increasing the expression of ribonucleotide reductase M2 catalytic subunit (RRM2) through E2F1-mediated transcriptional activation. Acting as a pan-Glut inhibitor, CG-5 abrogated this gemcitabine-induced upregulation of RRM2 through decreased E2F1 expression, thereby enhancing gemcitabine-induced DNA damage and inhibition of cell survival. This CG-5-induced inhibition of E2F1 expression was mediated by the induction of a previously unreported E2F1-targeted microRNA, miR-520f. The addition of oral CG-5 to gemcitabine therapy caused greater suppression of Panc-1GemR xenograft tumor growth in vivo than either drug alone. Glut inhibition may be an effective strategy to enhance gemcitabine activity for the treatment of pancreatic cancer. PMID:24879635

  4. The Peter Effect Revisited: Reading Habits and Attitudes of College Students

    ERIC Educational Resources Information Center

    Applegate, Anthony J.; Applegate, Mary DeKonty; Mercantini, Martha A.; McGeehan, Catherine M.; Cobb, Jeanne B.; DeBoy, Joanne R.; Modla, Virginia B.; Lewinski, Kimberly E.

    2014-01-01

    Certainly a primary goal of literacy education is the creation of avid, enthusiastic, and highly motivated readers. However, in this article revisiting the Peter Effect (Applegate & Applegate, 2004), researchers surveyed more than 1,000 college sophomores and found strikingly low levels of enthusiasm for reading. Only 46.6% of surveyed…

  5. Autophagy promotes paclitaxel resistance of cervical cancer cells: involvement of Warburg effect activated hypoxia-induced factor 1-α-mediated signaling

    PubMed Central

    Peng, X; Gong, F; Chen, Y; Jiang, Y; Liu, J; Yu, M; Zhang, S; Wang, M; Xiao, G; Liao, H

    2014-01-01

    Paclitaxel is one of the most effective chemotherapy drugs for advanced cervical cancer. However, acquired resistance of paclitaxel represents a major barrier to successful anticancer treatment. In this study, paclitaxel-resistant HeLa sublines (HeLa-R cell lines) were established by continuous exposure and increased autophagy level was observed in HeLa-R cells. 3-Methyladenine or ATG7 siRNA, autophagy inhibitors, could restore sensitivity of HeLa-R cells to paclitaxel compared with parental HeLa cells. To determine the underlying molecular mechanism, differentially expressed proteins between HeLa and HeLa-R cells were identified by two-dimensional gel electrophoresis coupled with electrospray ionization quadrupole time-of-flight MS/MS. We found glycolysis-associated proteins were upregulated in HeLa-R cell lines. Inhibition of glycolysis by 2-deoxy-D-glucose or koningic acid could decrease autophagy and enhance sensitivity of HeLa-R cells to paclitaxel. Moreover, glycolysis could activate HIF1-α. Downregulation of HIF1-α by specific siRNA could decrease autophagy and resensitize HeLa-R cells to paclitaxel. Taken together, a possible Warburg effect activated HIF1-α-mediated signaling-induced autophagic pathway is proposed, which may provide new insight into paclitaxel chemoresistance. PMID:25118927

  6. 42 CFR 488.30 - Revisit user fee for revisit surveys.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., or substantiated complaint survey and that is designed to evaluate the extent to which previously... 42 Public Health 5 2012-10-01 2012-10-01 false Revisit user fee for revisit surveys. 488.30... SERVICES (CONTINUED) STANDARDS AND CERTIFICATION SURVEY, CERTIFICATION, AND ENFORCEMENT PROCEDURES General...

  7. 42 CFR 488.30 - Revisit user fee for revisit surveys.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ..., or substantiated complaint survey and that is designed to evaluate the extent to which previously... 42 Public Health 5 2013-10-01 2013-10-01 false Revisit user fee for revisit surveys. 488.30... SERVICES (CONTINUED) STANDARDS AND CERTIFICATION SURVEY, CERTIFICATION, AND ENFORCEMENT PROCEDURES General...

  8. 42 CFR 488.30 - Revisit user fee for revisit surveys.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ..., or substantiated complaint survey and that is designed to evaluate the extent to which previously... 42 Public Health 5 2014-10-01 2014-10-01 false Revisit user fee for revisit surveys. 488.30... SERVICES (CONTINUED) STANDARDS AND CERTIFICATION SURVEY, CERTIFICATION, AND ENFORCEMENT PROCEDURES General...

  9. 42 CFR 488.30 - Revisit user fee for revisit surveys.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ..., or substantiated complaint survey and that is designed to evaluate the extent to which previously... 42 Public Health 5 2011-10-01 2011-10-01 false Revisit user fee for revisit surveys. 488.30... SERVICES (CONTINUED) STANDARDS AND CERTIFICATION SURVEY, CERTIFICATION, AND ENFORCEMENT PROCEDURES General...

  10. 42 CFR 488.30 - Revisit user fee for revisit surveys.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., or substantiated complaint survey and that is designed to evaluate the extent to which previously... 42 Public Health 5 2010-10-01 2010-10-01 false Revisit user fee for revisit surveys. 488.30... SERVICES (CONTINUED) STANDARDS AND CERTIFICATION SURVEY, CERTIFICATION, AND ENFORCEMENT PROCEDURES General...

  11. Lactate dehydrogenase downregulation mediates the inhibitory effect of diallyl trisulfide on proliferation, metastasis, and invasion in triple-negative breast cancer.

    PubMed

    Cheng, Shi-Yann; Yang, Yao-Chih; Ting, Kuan-Lun; Wen, Su-Ying; Viswanadha, Vijaya Padma; Huang, Chih-Yang; Kuo, Wei-Wen

    2017-04-01

    The Warburg effect plays a critical role in tumorigenesis, suggesting that specific agents targeting Warburg effect key proteins may be a promising strategy for cancer therapy. Previous studies have shown that diallyl trisulfide (DATS) inhibits proliferation of breast cancer cells by inducing apoptosis in vitro and in vivo. However, whether the Warburg effect is involved with the apoptosis-promoting action of DATS is unclear. Here, we show that the action of DATS is associated with downregulation of lactate dehydrogenase A (LDHA), an essential protein of the Warburg effect whose upregulation is closely related to tumorigenesis. Interestingly, inhibition of the Warburg effect by DATS in breast cancer cells did not greatly affect normal cells. Furthermore, DATS inhibited growth of breast cancer cells, particularly in MDA-MB-231, a triple-negative breast cancer (TNBC) cell, and reduced proliferation and migration; invasion was reversed by over-expression of LDHA. These data suggest that DATS inhibits breast cancer growth and aggressiveness through a novel pathway targeting the key enzyme of the Warburg effect. Our study shows that LDHA downregulation is involved in the apoptotic effect of DATS on TNBC. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1390-1398, 2017. © 2016 Wiley Periodicals, Inc.

  12. Acetyl-CoA carboxylase rewires cancer metabolism to allow cancer cells to survive inhibition of the Warburg effect by cetuximab

    PubMed Central

    Luo, Jingtao; Hong, Yun; Lu, Yang; Qiu, Songbo; Chaganty, Bharat K. R.; Zhang, Lun; Wang, Xudong; Li, Qiang; Fan, Zhen

    2016-01-01

    Cetuximab inhibits HIF-1-regulated glycolysis in cancer cells, thereby reversing the Warburg effect and leading to inhibition of cancer cell metabolism. AMP-activated protein kinase (AMPK) is activated after cetuximab treatment, and a sustained AMPK activity is a mechanism contributing to cetuximab resistance. Here, we investigated how acetyl-CoA carboxylase (ACC), a downstream target of AMPK, rewires cancer metabolism in response to cetuximab treatment. We found that introduction of experimental ACC mutants lacking the AMPK phosphorylation sites (ACC1_S79A and ACC2_S212A) into head and neck squamous cell carcinoma (HNSCC) cells protected HNSCC cells from cetuximab-induced growth inhibition. HNSCC cells with acquired cetuximab resistance contained not only high levels of T172-phosphorylated AMPK and S79-phosphorylated ACC1 but also an increased level of total ACC. These findings were corroborated in tumor specimens of HNSCC patients treated with cetuximab. Cetuximab plus TOFA (an allosteric inhibitor of ACC) achieved remarkable growth inhibition of cetuximab-resistant HNSCC xenografts. Our data suggest a novel paradigm in which cetuximab-mediated activation of AMPK and subsequent phosphorylation and inhibition of ACC is followed by a compensatory increase in total ACC, which rewires cancer metabolism from glycolysis-dependent to lipogenesis-dependent. PMID:27693630

  13. Acetyl-CoA carboxylase rewires cancer metabolism to allow cancer cells to survive inhibition of the Warburg effect by cetuximab.

    PubMed

    Luo, Jingtao; Hong, Yun; Lu, Yang; Qiu, Songbo; Chaganty, Bharat K R; Zhang, Lun; Wang, Xudong; Li, Qiang; Fan, Zhen

    2017-01-01

    Cetuximab inhibits HIF-1-regulated glycolysis in cancer cells, thereby reversing the Warburg effect and leading to inhibition of cancer cell metabolism. AMP-activated protein kinase (AMPK) is activated after cetuximab treatment, and a sustained AMPK activity is a mechanism contributing to cetuximab resistance. Here, we investigated how acetyl-CoA carboxylase (ACC), a downstream target of AMPK, rewires cancer metabolism in response to cetuximab treatment. We found that introduction of experimental ACC mutants lacking the AMPK phosphorylation sites (ACC1_S79A and ACC2_S212A) into head and neck squamous cell carcinoma (HNSCC) cells protected HNSCC cells from cetuximab-induced growth inhibition. HNSCC cells with acquired cetuximab resistance contained not only high levels of T172-phosphorylated AMPK and S79-phosphorylated ACC1 but also an increased level of total ACC. These findings were corroborated in tumor specimens of HNSCC patients treated with cetuximab. Cetuximab plus TOFA (an allosteric inhibitor of ACC) achieved remarkable growth inhibition of cetuximab-resistant HNSCC xenografts. Our data suggest a novel paradigm in which cetuximab-mediated activation of AMPK and subsequent phosphorylation and inhibition of ACC is followed by a compensatory increase in total ACC, which rewires cancer metabolism from glycolysis-dependent to lipogenesis-dependent. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Microenvironmental cooperation promotes early spread and bistability of a Warburg-like phenotype.

    PubMed

    Fernandez-de-Cossio-Diaz, Jorge; De Martino, Andrea; Mulet, Roberto

    2017-06-08

    We introduce an in silico model for the initial spread of an aberrant phenotype with Warburg-like overflow metabolism within a healthy homeostatic tissue in contact with a nutrient reservoir (the blood), aimed at characterizing the role of the microenvironment for aberrant growth. Accounting for cellular metabolic activity, competition for nutrients, spatial diffusion and their feedbacks on aberrant replication and death rates, we obtain a phase portrait where distinct asymptotic whole-tissue states are found upon varying the tissue-blood turnover rate and the level of blood-borne primary nutrient. Over a broad range of parameters, the spreading dynamics is bistable as random fluctuations can impact the final state of the tissue. Such a behaviour turns out to be linked to the re-cycling of overflow products by non-aberrant cells. Quantitative insight on the overall emerging picture is provided by a spatially homogeneous version of the model.

  15. Circular revisit orbits design for responsive mission over a single target

    NASA Astrophysics Data System (ADS)

    Li, Taibo; Xiang, Junhua; Wang, Zhaokui; Zhang, Yulin

    2016-10-01

    The responsive orbits play a key role in addressing the mission of Operationally Responsive Space (ORS) because of their capabilities. These capabilities are usually focused on supporting specific targets as opposed to providing global coverage. One subtype of responsive orbits is repeat coverage orbit which is nearly circular in most remote sensing applications. This paper deals with a special kind of repeating ground track orbit, referred to as circular revisit orbit. Different from traditional repeat coverage orbits, a satellite on circular revisit orbit can visit a target site at both the ascending and descending stages in one revisit cycle. This typology of trajectory allows a halving of the traditional revisit time and does a favor to get useful information for responsive applications. However the previous reported numerical methods in some references often cost lots of computation or fail to obtain such orbits. To overcome this difficulty, an analytical method to determine the existence conditions of the solutions to revisit orbits is presented in this paper. To this end, the mathematical model of circular revisit orbit is established under the central gravity model and the J2 perturbation. A constraint function of the circular revisit orbit is introduced, and the monotonicity of that function has been studied. The existent conditions and the number of such orbits are naturally worked out. Taking the launch cost into consideration, optimal design model of circular revisit orbit is established to achieve a best orbit which visits a target twice a day in the morning and in the afternoon respectively for several days. The result shows that it is effective to apply circular revisit orbits in responsive application such as reconnoiter of natural disaster.

  16. Revisiting the Scattering Greenhouse Effect of CO2 Ice Clouds

    NASA Astrophysics Data System (ADS)

    Kitzmann, D.

    2016-02-01

    Carbon dioxide ice clouds are thought to play an important role for cold terrestrial planets with thick CO2 dominated atmospheres. Various previous studies showed that a scattering greenhouse effect by carbon dioxide ice clouds could result in a massive warming of the planetary surface. However, all of these studies only employed simplified two-stream radiative transfer schemes to describe the anisotropic scattering. Using accurate radiative transfer models with a general discrete ordinate method, this study revisits this important effect and shows that the positive climatic impact of carbon dioxide clouds was strongly overestimated in the past. The revised scattering greenhouse effect can have important implications for the early Mars, but also for planets like the early Earth or the position of the outer boundary of the habitable zone.

  17. Setting the Revisit Interval in Primary Care

    PubMed Central

    Schwartz, Lisa M; Woloshin, Steven; Wasson, John H; Renfrew, Roger A; Welch, H Gilbert

    1999-01-01

    OBJECTIVE Although longitudinal care constitutes the bulk of primary care, physicians receive little guidance on the fundamental question of how to time follow-up visits. We sought to identify important predictors of the revisit interval and to describe the variability in how physicians set these intervals when caring for patients with common medical conditions. DESIGN Cross-sectional survey of physicians performed at the end of office visits for consecutive patients with hypertension, angina, diabetes, or musculoskeletal pain. PARTICIPANTS/SETTING One hundred sixty-four patients under the care of 11 primary care physicians in the Dartmouth Primary Care Cooperative Research Network. MEASUREMENTS The main outcome measures were the variability in mean revisit intervals across physicians and the proportion of explained variance by potential determinants of revisit intervals. We assessed the relation between the revisit interval (dependent variable) and three groups of independent variables, patient characteristics (e.g., age, physician perception of patient health), identification of individual physician, and physician characterization of the visit (e.g., routine visit, visit requiring a change in management, or visit occurring on a “hectic” day), using multiple regression that accounted for the natural grouping of patients within physician. MAIN RESULTS Revisit intervals ranged from 1 week to over 1 year. The most common intervals were 12 and 16 weeks. Physicians’ perception of fair-poor health status and visits involving a change in management were most strongly related to shorter revisit intervals. In multivariate analyses, patient characteristics explained about 18% of the variance in revisit intervals, and adding identification of the individual provider doubled the explained variance to about 40%. Physician characterization of the visit increased explained variance to 57%. The average revisit interval adjusted for patient characteristics for each of the 11

  18. Resonance Raman imaging for detecting and monitoring molecular pathological changes in human brain tumors related to Warburg effect

    NASA Astrophysics Data System (ADS)

    Zhou, Yan; Liu, Cheng-hui; Zhu, Ke; Zhang, Chunyuan; Yang, Yang; Yu, Xinguang; Hu, Hailong; Cheng, Gangge; Wu, Binlin; Shi, Lingyan; Alfano, Robert R.

    2018-02-01

    The goal of the research is to determine the prognostic molecular pathological changes in components and composition, for human brain glioma gradings in comparison with normal tissues in three-dimensional Raman imaging profiles by visible Resonance Raman (VRR) imaging. VRR images from twenty-five specimens including three healthy tissues, one normal control, and twenty-one glioma tissues of grades II, II-III and III-IV with histology examination were measured and investigated using WITec300R confocal micro Raman imaging system with laser excitation of 532nm. Two-dimensional RR spectral mappings performed in 20μm x 20μm generated 400 images which integrated the intensity of the specific biochemical bonds as the third dimension. The three-dimension (3D) map demonstrated the spatial distributions of three selected sets of RR spectra of molecular biomarkers, and revealed significant differences in the spectra between normal and glioma tissues of different grades due to the composition changes in key molimageecules. These RR molecular spectral fingerprints have displayed: a clear enhancement of RR vibrational modes at 1129-1131cm-1 and 2934cm-1 which are supposed to be arising from lipoproteins; evident decreased RR vibrational modes at 1442cm-1 and 2854cm-1 which are from saturated fatty acids bonds in all-grades of glioma brain tissues compared with normal tissues; and the enhanced RR spectral modes of 1129 cm-1 and 2938cm-1 which suggest contribution from lactate. These findings may provide a novel proof for anaerobic glycolysis metabolic process in brain glioma cancer tissues that has been explained by Warburg effects.

  19. HK2 Recruitment to Phospho-BAD Prevents Its Degradation, Promoting Warburg Glycolysis by Theileria-Transformed Leukocytes.

    PubMed

    Haidar, Malak; Lombès, Anne; Bouillaud, Frédéric; Kennedy, Eileen J; Langsley, Gordon

    2017-03-10

    Theileria annulata infects bovine leukocytes, transforming them into invasive, cancer-like cells that cause the widespread disease called tropical theileriosis. We report that in Theileria-transformed leukocytes hexokinase-2 (HK2) binds to B cell lymphoma-2-associated death promoter (BAD) only when serine (S) 155 in BAD is phosphorylated. We show that HK2 recruitment to BAD is abolished by a cell-penetrating peptide that acts as a nonphosphorylatable BAD substrate that inhibits endogenous S155 phosphorylation, leading to complex dissociation and ubiquitination and degradation of HK2 by the proteasome. As HK2 is a critical enzyme involved in Warburg glycolysis, its loss forces Theileria-transformed macrophages to switch back to HK1-dependent oxidative glycolysis that down-regulates macrophage proliferation only when they are growing on glucose. When growing on galactose, degradation of HK2 has no effect on Theileria-infected leukocyte proliferation, because metabolism of this sugar is independent of hexokinases. Thus, targeted disruption of the phosphorylation-dependent HK2/BAD complex may represent a novel approach to control Theileria-transformed leukocyte proliferation.

  20. Association of emergency department albuterol dispensing with pediatric asthma revisits and readmissions.

    PubMed

    Hall, A Brad; Novotny, April; Bhisitkul, Donna M; Melton, James; Regan, Tim; Leckie, Maureen

    2017-06-01

    Although pediatric asthma continues to be a highly studied disease, data to suggest clear strategies to decrease asthma related revisits or readmissions is lacking. The purpose of our study was to assess the effect of emergency department (ED) direct dispensing of beta-agonist metered dose inhalers on pediatric asthma ED revisit and readmission rates. We conducted a retrospective cohort study of pediatric patients discharged from the pediatric ED with a diagnosis of asthma. Our primary outcome measured the rate of asthma revisits to the ED or admissions to the hospital within 28 days. Logistic regression analysis was used to assess ED beta-agonist MDI dispensing and revisit and/or readmission as the outcome. A total of 853 patients met eligibility for inclusion in the study, with 657 enrolled in the Baseline group and 196 enrolled in the ED-MDI group. The Baseline group experienced a revisit and readmission rate of 7.0% (46/657) versus 2.6% (5/196) in the ED-MDI group, (p = 0.026). ED direct dispensing of MDIs was found to be independently associated with a decreased risk of revisit or readmission (odds ratio 0.37; 95% confidence interval 0.14-0.95). In our study, ED direct dispensing of beta-agonist MDIs resulted in a reduction in 28-day revisit and readmission to the hospital. Further studies should be performed to evaluate the economic impact of reducing these revisits and readmissions against the costs of maintaining a dispensing program. Our findings may support modification of asthma programs to include dispensing MDIs from the emergency department.

  1. Revisiting the classics: considering nonconsumptive effects in textbook examples of predator-prey interactions.

    PubMed

    Peckarsky, Barbara L; Abrams, Peter A; Bolnick, Daniel I; Dill, Lawrence M; Grabowski, Jonathan H; Luttbeg, Barney; Orrock, John L; Peacor, Scott D; Preisser, Evan L; Schmitz, Oswald J; Trussell, Geoffrey C

    2008-09-01

    Predator effects on prey dynamics are conventionally studied by measuring changes in prey abundance attributed to consumption by predators. We revisit four classic examples of predator-prey systems often cited in textbooks and incorporate subsequent studies of nonconsumptive effects of predators (NCE), defined as changes in prey traits (e.g., behavior, growth, development) measured on an ecological time scale. Our review revealed that NCE were integral to explaining lynx-hare population dynamics in boreal forests, cascading effects of top predators in Wisconsin lakes, and cascading effects of killer whales and sea otters on kelp forests in nearshore marine habitats. The relative roles of consumption and NCE of wolves on moose and consequent indirect effects on plant communities of Isle Royale depended on climate oscillations. Nonconsumptive effects have not been explicitly tested to explain the link between planktonic alewives and the size structure of the zooplankton, nor have they been invoked to attribute keystone predator status in intertidal communities or elsewhere. We argue that both consumption and intimidation contribute to the total effects of keystone predators, and that characteristics of keystone consumers may differ from those of predators having predominantly NCE. Nonconsumptive effects are often considered as an afterthought to explain observations inconsistent with consumption-based theory. Consequently, NCE with the same sign as consumptive effects may be overlooked, even though they can affect the magnitude, rate, or scale of a prey response to predation and can have important management or conservation implications. Nonconsumptive effects may underlie other classic paradigms in ecology, such as delayed density dependence and predator-mediated prey coexistence. Revisiting classic studies enriches our understanding of predator-prey dynamics and provides compelling rationale for ramping up efforts to consider how NCE affect traditional predator

  2. Founder Fukutin mutation causes Walker-Warburg syndrome in four Ashkenazi Jewish families†

    PubMed Central

    Chang, Wendy; Winder, Thomas L.; LeDuc, Charles A.; Simpson, Lynn L.; Millar, William S.; Dungan, Jeffrey; Ginsberg, Norman; Plaga, Stacey; Moore, Steven A.; Chung, Wendy K.

    2009-01-01

    Objective Walker-Warburg syndrome (WWS) is a genetically heterogeneous congenital muscular dystrophy caused by abnormal glycosylation of α-dystroglycan (α-DG) that is associated with brain malformations and eye anomalies. The Fukutin (FKTN) gene, which causes autosomal recessively inherited WWS is most often associated with Fukuyama congenital muscular dystrophy in Japan. We describe the clinical features of four nonconsanguinous Ashkenazi Jewish families with WWS and identify the underlying genetic basis for WWS. Method We screened for mutations in POMGnT1, POMT1, POMT2, and FKTN, genes causing WWS, by dideoxy sequence analysis. Results We identified an identical homozygous c.1167insA mutation in the FKTN gene on a common haplotype in all four families and identified 2/299 (0.7%) carriers for the c.1167insA mutation among normal American Ashkenazi Jewish adults. Conclusion These data suggest that the c.1167insA FKTN mutation described by us is a founder mutation that can be used to target diagnostic testing and carrier screening in the Ashkenazi Jewish population. PMID:19266496

  3. Founder Fukutin mutation causes Walker-Warburg syndrome in four Ashkenazi Jewish families.

    PubMed

    Chang, Wendy; Winder, Thomas L; LeDuc, Charles A; Simpson, Lynn L; Millar, William S; Dungan, Jeffrey; Ginsberg, Norman; Plaga, Stacey; Moore, Steven A; Chung, Wendy K

    2009-06-01

    Walker-Warburg syndrome (WWS) is a genetically heterogeneous congenital muscular dystrophy caused by abnormal glycosylation of alpha-dystroglycan (alpha-DG) that is associated with brain malformations and eye anomalies. The Fukutin (FKTN) gene, which causes autosomal recessively inherited WWS is most often associated with Fukuyama congenital muscular dystrophy in Japan. We describe the clinical features of four nonconsanguinous Ashkenazi Jewish families with WWS and identify the underlying genetic basis for WWS. We screened for mutations in POMGnT1, POMT1, POMT2, and FKTN, genes causing WWS, by dideoxy sequence analysis. We identified an identical homozygous c.1167insA mutation in the FKTN gene on a common haplotype in all four families and identified 2/299 (0.7%) carriers for the c.1167insA mutation among normal American Ashkenazi Jewish adults. These data suggest that the c.1167insA FKTN mutation described by us is a founder mutation that can be used to target diagnostic testing and carrier screening in the Ashkenazi Jewish population. Copyright (c) 2009 John Wiley & Sons, Ltd.

  4. Metabolic coupling and the Reverse Warburg Effect in cancer: Implications for novel biomarker and anticancer agent development.

    PubMed

    Wilde, Lindsay; Roche, Megan; Domingo-Vidal, Marina; Tanson, Katherina; Philp, Nancy; Curry, Joseph; Martinez-Outschoorn, Ubaldo

    2017-06-01

    Glucose is a key metabolite used by cancer cells to generate ATP, maintain redox state and create biomass. Glucose can be catabolized to lactate in the cytoplasm, which is termed glycolysis, or alternatively can be catabolized to carbon dioxide and water in the mitochondria via oxidative phosphorylation. Metabolic heterogeneity exists in a subset of human tumors, with some cells maintaining a glycolytic phenotype while others predominantly utilize oxidative phosphorylation. Cells within tumors interact metabolically with transfer of catabolites from supporting stromal cells to adjacent cancer cells. The Reverse Warburg Effect describes when glycolysis in the cancer-associated stroma metabolically supports adjacent cancer cells. This catabolite transfer, which induces stromal-cancer metabolic coupling, allows cancer cells to generate ATP, increase proliferation, and reduce cell death. Catabolites implicated in metabolic coupling include the monocarboxylates lactate, pyruvate, and ketone bodies. Monocarboxylate transporters (MCT) are critically necessary for release and uptake of these catabolites. MCT4 is involved in the release of monocarboxylates from cells, is regulated by catabolic transcription factors such as hypoxia inducible factor 1 alpha (HIF1A) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and is highly expressed in cancer-associated fibroblasts. Conversely, MCT1 is predominantly involved in the uptake of these catabolites and is highly expressed in a subgroup of cancer cells. MYC and TIGAR, which are genes involved in cellular proliferation and anabolism, are inducers of MCT1. Profiling human tumors on the basis of an altered redox balance and intra-tumoral metabolic interactions may have important biomarker and therapeutic implications. Alterations in the redox state and mitochondrial function of cells can induce metabolic coupling. Hence, there is interest in redox and metabolic modulators as anticancer agents. Also

  5. Establishment of revisit user fee program for Medicare survey and certification activities. Final rule.

    PubMed

    2007-09-19

    This final rule will establish a system of revisit user fees applicable to health care facilities that have been cited for deficiencies during initial certification, recertification, or substantiated complaint surveys and require a revisit to confirm that corrections to previously-identified deficiencies have been remedied. Consistent with the President's long-term goal to promote quality of health care and to cut the deficit in half by fiscal year (FY) 2009, the FY 2007 Department of Health and Human Services' (HHS) budget request included both new mandatory savings proposals and a requirement that user fees be applied to health care providers that have failed to comply with Federal quality of care requirements. The "Revisit User Fees" will affect only those providers or suppliers for which a revisit is required to confirm that previously-identified failures to meet federal quality of care requirements have been remedied. The fees are estimated at $37.3 million annually and will recover the costs associated with the Medicare Survey and Certification program's revisit surveys. The fees will take effect on the date of publication of the final rule and will be in effect until the date that the continued authority provided by Congress expires. At the time of publication of this regulation the applicable date is September 30, 2007. If no legislation is enacted, the fees are not retroactive to the beginning of the fiscal year. Any provider or supplier that has a revisit survey conducted on or after the date of publication will be assessed a revisit user fee and will be notified of the assessment upon data system reconciliation which can occur following the closing of the fiscal year. The fees will be available to CMS until expended. The revisit user fee is included in the President's proposed FY 2008 budget. We note through the publication of this final rule that if authority for the revisit user fee is continued, we will use the current fee schedule in this rule for

  6. The Effects of Korean Medical Service Quality and Satisfaction on Revisit Intention of the United Arab Emirates Government Sponsored Patients.

    PubMed

    Lee, Seoyoung; Kim, Eun-Kyung

    2017-06-01

    The purpose of this study was to investigate medical service quality, satisfaction and to examine factors influencing hospital revisit intention of the United Arab Emirates government sponsored patients in Korea. A total of 152 UAE government sponsored patients who visited Korean hospitals participated in the questionnaire survey from August to November 2016. Stepwise multiple regression was used to identify the factors that affected the revisit intention of the participants. The mean scores of medical service quality, satisfaction, and revisit intention were 5.72 out of 7, 88.88 out of 100, 4.59 out of 5, respectively. Medical service quality and satisfaction, Medical service quality and revisit intention, satisfaction and revisit intention were positively correlated. Medical service of physician, visiting routes and responsiveness of medical service quality explained about 23.8% of revisit intention. There are needs for physicians to communicate with patients while ensuring sufficient consultation time based on excellent medical skills and nurses to respond immediately for the patients' needs through an empathic encounter in order to improve medical service quality and patient satisfaction so that to increase the revisit intention of the United Arab Emirates government sponsored patients. Further, it is necessary for the hospitals to have support plans for providing country specialized services in consideration of the UAE culture to ensure that physicians' and nurses' competencies are not undervalued by non-medical service elements such as interpreters and meals. Copyright © 2017. Published by Elsevier B.V.

  7. Revisit rates and associated costs after an emergency department encounter: a multistate analysis.

    PubMed

    Duseja, Reena; Bardach, Naomi S; Lin, Grace A; Yazdany, Jinoos; Dean, Mitzi L; Clay, Theodore H; Boscardin, W John; Dudley, R Adams

    2015-06-02

    Return visits to the emergency department (ED) or hospital after an index ED visit strain the health system, but information about rates and determinants of revisits is limited. To describe revisit rates, variation in revisit rates by diagnosis and state, and associated costs. Observational study using the Healthcare Cost and Utilization Project databases. 6 U.S. states. Adults with ED visits between 2006 and 2010. Revisit rates and costs. Within 3 days of an index ED visit, 8.2% of patients had a revisit; 32% of those revisits occurred at a different institution. Revisit rates varied by diagnosis, with skin infections having the highest rate (23.1% [95% CI, 22.3% to 23.9%]). Revisit rates also varied by state. For skin infections, Florida had higher risk-adjusted revisit rates (24.8% [CI, 23.5% to 26.2%]) than Nebraska (10.6% [CI, 9.2% to 12.1%]). In Florida, the only state with complete cost data, total revisit costs for the 19.8% of patients with a revisit within 30 days were 118% of total index ED visit costs for all patients (including those with and without a revisit). Whether a revisit reflects inadequate access to primary care, a planned revisit, the patient's nonadherence to ED recommendations, or poor-quality care at the initial ED visit remains unknown. Revisits after an index ED encounter are more frequent than previously reported, in part because many occur outside the index institution. Among ED patients in Florida, more resources are spent on revisits than on index ED visits. Agency for Healthcare Research and Quality.

  8. Transketolase-like 1 ectopic expression is associated with DNA hypomethylation and induces the Warburg effect in melanoma cells.

    PubMed

    Jayachandran, Aparna; Lo, Pu-Han; Chueh, Anderly C; Prithviraj, Prashanth; Molania, Ramyar; Davalos-Salas, Mercedes; Anaka, Matthew; Walkiewicz, Marzena; Cebon, Jonathan; Behren, Andreas

    2016-02-22

    The metabolism of cancer cells is often reprogrammed by dysregulation of metabolic enzymes. Transketolase-like 1 (TKTL1) is a homodimeric transketolase linking the pentose-phosphate pathway with the glycolytic pathway. It is generally silenced at a transcriptional level in somatic tissues. However, in human cancers its expression is associated with the acquisition of a glycolytic phenotype (the Warburg effect) by cancer cells that contributes to the progression of malignant tumors. In melanoma, defective promoter methylation results in the expression of genes and their products that can affect the tumor cell's phenotype including the modification of immune and functional characteristics. The present study evaluates the role of TKTL1 as a mediator of disease progression in melanoma associated with a defective methylation phenotype. The expression of TKTL1 in metastatic melanoma tumors and cell lines was analysed by qRT-PCR and immunohistochemistry. The promoter methylation status of TKTL1 in melanoma cells was evaluated by quantitative methylation specific PCR. Using qRT-PCR, the effect of a DNA demethylating agent 5-aza-2'-deoxycytidine (5aza) on the expression of TKTL1 was examined. Biochemical and molecular analyses such as glucose consumption, lactate production, invasion, proliferation and cell cycle progression together with ectopic expression and siRNA mediated knockdown were used to investigate the role of TKTL1 in melanoma cells. Expression of TKTL1 was highly restricted in normal adult tissues and was overexpressed in a subset of metastatic melanoma tumors and derived cell lines. The TKTL1 promoter was activated by hypomethylation and treatment with 5aza induced TKTL1 expression in melanoma cells. Augmented expression of TKTL1 in melanoma cells was associated with a glycolytic phenotype. Loss and gain of function studies revealed that TKTL1 contributed to enhanced invasion of melanoma cells. Our data provide evidence for an important role of TKTL1 in

  9. Lakatos Revisited.

    ERIC Educational Resources Information Center

    Court, Deborah

    1999-01-01

    Revisits and reviews Imre Lakatos' ideas on "Falsification and the Methodology of Scientific Research Programmes." Suggests that Lakatos' framework offers an insightful way of looking at the relationship between theory and research that is relevant not only for evaluating research programs in theoretical physics, but in the social…

  10. Revisiting Bioaccumulation Criteria

    EPA Science Inventory

    The objective of workgroup 5 was to revisit the B(ioaccumulation) criteria that are currently being used to identify POPs under the Stockholm Convention and PBTs under CEPA, TSCA, REACh and other programs. Despite the lack of a recognized definition for a B substance, we defined ...

  11. Galactose conjugated platinum(II) complex targeting the Warburg effect for treatment of non-small cell lung cancer and colon cancer.

    PubMed

    Wu, Meng; Li, Hong; Liu, Ran; Gao, Xiangqian; Zhang, Menghua; Liu, Pengxing; Fu, Zheng; Yang, Jinna; Zhang-Negrerie, Daisy; Gao, Qingzhi

    2016-03-03

    Malignant neoplasms exhibit a higher rate of glycolysis than normal cells; this is known as the Warburg effect. To target it, a galactose-conjugated (trans-R,R-cyclohexane-1,2-diamine)-2-chloromalonato-platinum(II) complex (Gal-Pt) was designed, synthesized, and evaluated in five human cancer cell lines and against two different xenograft tumour models. Gal-Pt exhibits much higher aqueous solubility (over 25 times) and improved cytotoxicity than oxaliplatin, especially in human colon (HT29) and lung (H460) cancer cell lines. The safety profile of Gal-Pt was investigated in vivo by exploring the maximum tolerated dose (MTD) and animal mortality rate. The ratios of the animal lethal dosage values to the cytotoxicity in HT29 (LD50/IC50) showed that Gal-Pt was associated with an increased therapeutic index by over 30-fold compared to cisplatin and oxaliplatin. We evaluated in vivo antitumor activity by single agent intravenous treatment comparison studies of Gal-Pt (50 mg/kg as 65% MTD) and cisplatin (3 mg/kg, as 80% MTD) in a H460 lung cancer xenograft model, and with oxaliplatin (7 mg/kg, as 90% MTD) in a HT29 colon cancer xenograft model. The results show that Gal-Pt was more efficacious against H460 than cisplatin, and had superior potency in HT29 cells compared to oxaliplatin under nontoxic dosage conditions. The dependency between cytotoxicity of Gal-Pt and glucose transporters (GLUTs) was investigated by using quercetin as an inhibitor of GLUTs in HT29 cells. The cytotoxic potency of Gal-Pt was highly reduced by the inhibitor, suggesting that the uptake of Gal-Pt was regulated by glucose transporters. The GLUT mediated transportability and cellular uptake of Gal-Pt was also demonstrated using a fluorescent glucose bioprobe in HT29 competition assay. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  12. The Casimir effect for parallel plates revisited

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kawakami, N. A.; Nemes, M. C.; Wreszinski, Walter F.

    2007-10-15

    The Casimir effect for a massless scalar field with Dirichlet and periodic boundary conditions (bc's) on infinite parallel plates is revisited in the local quantum field theory (lqft) framework introduced by Kay [Phys. Rev. D 20, 3052 (1979)]. The model displays a number of more realistic features than the ones he treated. In addition to local observables, as the energy density, we propose to consider intensive variables, such as the energy per unit area {epsilon}, as fundamental observables. Adopting this view, lqft rejects Dirichlet (the same result may be proved for Neumann or mixed) bc, and accepts periodic bc: inmore » the former case {epsilon} diverges, in the latter it is finite, as is shown by an expression for the local energy density obtained from lqft through the use of the Poisson summation formula. Another way to see this uses methods from the Euler summation formula: in the proof of regularization independence of the energy per unit area, a regularization-dependent surface term arises upon use of Dirichlet bc, but not periodic bc. For the conformally invariant scalar quantum field, this surface term is absent due to the condition of zero trace of the energy momentum tensor, as remarked by De Witt [Phys. Rep. 19, 295 (1975)]. The latter property does not hold in the application to the dark energy problem in cosmology, in which we argue that periodic bc might play a distinguished role.« less

  13. Should the recommended number of IUD revisits be reduced?

    PubMed

    Janowitz, B; Hubacher, D; Petrick, T; Dighe, N

    1994-01-01

    This study uses data from clinical trials of intrauterine devices to examine the effect of reducing the recommended number of IUD follow-up visits. Over 11,000 follow-up forms were analyzed to estimate the number of health problems that would have escaped detection if women with no or mild symptoms had not made recommended revisits. Less than one percent of woman-visits with no or only mild symptoms had an underlying health risk that could have gone undetected if the follow-up visits that were made in the clinic trial setting had not been made. The results from this analysis suggest that a reduction in the number of recommended follow-up visits is safe, when measured according to selected conditions. Additional research is necessary to determine whether any revisits should be recommended in the absence of signs or symptoms.

  14. Revisiting Constructivist Teaching Methods in Ontario Colleges Preparing for Accreditation

    ERIC Educational Resources Information Center

    Schultz, Rachel A.

    2015-01-01

    At the time of writing, the first community colleges in Ontario were preparing for transition to an accreditation model from an audit system. This paper revisits constructivist literature, arguing that a more pragmatic definition of constructivism effectively blends positivist and interactionist philosophies to achieve both student centred…

  15. Reduced Warburg Effect in Cancer Cells Undergoing Autophagy: Steady- State 1H-MRS and Real-Time Hyperpolarized 13C-MRS Studies

    PubMed Central

    Wong Te Fong, Anne-Christine; Hill, Deborah K.; Orton, Matthew R.; Parkes, Harry G.; Koh, Dow-Mu; Robinson, Simon P.; Leach, Martin O.; Eykyn, Thomas R.; Chung, Yuen-Li

    2014-01-01

    , returning towards and exceeding control values on cellular recovery, which potentially identifies resistance. kPL (hyperpolarized 13C-MRS) and lactate (1H-MRS) provide useful biomarkers for the autophagic process, enabling non-invasive monitoring of the Warburg effect. PMID:24667972

  16. Predictors and Outcomes of Revisits in Older Adults Discharged from the Emergency Department.

    PubMed

    de Gelder, Jelle; Lucke, Jacinta A; de Groot, Bas; Fogteloo, Anne J; Anten, Sander; Heringhaus, Christian; Dekkers, Olaf M; Blauw, Gerard J; Mooijaart, Simon P

    2018-04-01

    To study predictors of emergency department (ED) revisits and the association between ED revisits and 90-day functional decline or mortality. Multicenter cohort study. One academic and two regional Dutch hospitals. Older adults discharged from the ED (N=1,093). At baseline, data on demographic characteristics, illness severity, and geriatric parameters (cognition, functional capacity) were collected. All participants were prospectively followed for an unplanned revisit within 30 days and for functional decline and mortality 90 days after the initial visit. The median age was 79 (interquartile range 74-84), and 114 participants (10.4%) had an ED revisit within 30 days of discharge. Age (hazard ratio (HR)=0.96, 95% confidence interval (CI)=0.92-0.99), male sex (HR=1.61, 95% CI=1.05-2.45), polypharmacy (HR=2.06, 95% CI=1.34-3.16), and cognitive impairment (HR=1.71, 95% CI=1.02-2.88) were independent predictors of a 30-day ED revisit. The area under the receiver operating characteristic curve to predict an ED revisit was 0.65 (95% CI=0.60-0.70). In a propensity score-matched analysis, individuals with an ED revisit were at higher risk (odds ratio=1.99 95% CI=1.06-3.71) of functional decline or mortality. Age, male sex, polypharmacy, and cognitive impairment were independent predictors of a 30-day ED revisit, but no useful clinical prediction model could be developed. However, an early ED revisit is a strong new predictor of adverse outcomes in older adults. © 2018 The Authors. The Journal of the American Geriatrics Society published by Wiley Periodicals, Inc. on behalf of The American Geriatrics Society.

  17. 14 CFR 1214.205 - Revisit and/or retrieval services.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Revisit and/or retrieval services. 1214.205... Reimbursement for Shuttle Services Provided to Civil U.S. Government Users and Foreign Users Who Have Made Substantial Investment in the STS Program § 1214.205 Revisit and/or retrieval services. These services will be...

  18. What matters to infrequent customers: a pragmatic approach to understanding perceived value and intention to revisit trendy coffee café.

    PubMed

    Ting, Hiram; Thurasamy, Ramayah

    2016-01-01

    Notwithstanding the rise of trendy coffee café, little is done to investigate revisit intention towards the café in the context of developing markets. In particular, there is a lack of study which provides theoretical and practical explanation to the perceptions and behaviours of infrequent customers. Hence, the study aims to look into the subject matter by using the theory of reasoned action and social exchange theory as the underpinning basis. The framework proposed by Pine and Gilmore (Strat Leadersh 28:18-23, 2000), which asserts the importance of product quality, service quality and experience quality in a progressive manner, is used to decompose perceived value in the model so as to determine their effects on intention to revisit the café. Given the importance to gain practical insights into revisit intention of infrequent customers, pragmatism stance is assumed. Explanatory sequential mixed-method design is thus adopted whereby qualitative approach is used to confirm and complement quantitative findings. Self-administered questionnaire-based survey is first administered before personal interview is carried out at various cafés. Partial least squares structural equation modelling and content analysis are appropriated successively. In the quantitative findings, although product quality, service quality and experience quality are found to have positive effect on perceived value and revisit intention towards trendy coffee café, experience quality is found to have the greater effect than the others among the infrequent customers. The qualitative findings not only confirm their importance, but most importantly explain the favourable impressions they have at trendy coffee café based on their last in-store experience. While product and service quality might not necessary stimulate them to revisit trendy coffee café, experience quality driven by purposes of visit would likely affect their intention to revisit. As retaining customers is of utmost importance to

  19. Cancer cells metabolically "fertilize" the tumor microenvironment with hydrogen peroxide, driving the Warburg effect: implications for PET imaging of human tumors.

    PubMed

    Martinez-Outschoorn, Ubaldo E; Lin, Zhao; Trimmer, Casey; Flomenberg, Neal; Wang, Chenguang; Pavlides, Stephanos; Pestell, Richard G; Howell, Anthony; Sotgia, Federica; Lisanti, Michael P

    2011-08-01

    Previously, we proposed that cancer cells behave as metabolic parasites, as they use targeted oxidative stress as a "weapon" to extract recycled nutrients from adjacent stromal cells. Oxidative stress in cancer-associated fibroblasts triggers autophagy and  mitophagy, resulting in compartmentalized cellular catabolism, loss of mitochondrial function, and the onset of aerobic glycolysis, in the tumor stroma. As such, cancer-associated fibroblasts produce high-energy nutrients (such as lactate and ketones) that fuel mitochondrial biogenesis, and oxidative metabolism in cancer cells. We have termed this new energy-transfer mechanism the "reverse Warburg effect." To further test the validity of this hypothesis, here we used an in vitro MCF7-fibroblast co-culture system, and quantitatively measured a variety of metabolic parameters by FACS analysis (analogous to laser-capture micro-dissection).  Mitochondrial activity, glucose uptake, and ROS production were measured with highly-sensitive fluorescent probes (MitoTracker, NBD-2-deoxy-glucose, and DCF-DA). Interestingly, using this approach, we directly show that cancer cells initially secrete hydrogen peroxide that then triggers oxidative stress in neighboring fibroblasts. Thus, oxidative stress is contagious (spreads like a virus) and is propagated laterally and vectorially from cancer cells to adjacent fibroblasts. Experimentally, we show that oxidative stress in cancer-associated fibroblasts quantitatively reduces mitochondrial activity, and increases glucose uptake, as the fibroblasts become more dependent on aerobic glycolysis.  Conversely, co-cultured cancer cells show significant increases in mitochondrial activity, and corresponding reductions in both glucose uptake and GLUT1 expression. Pre-treatment of co-cultures with extracellular catalase (an anti-oxidant enzyme that detoxifies hydrogen peroxide) blocks the onset of oxidative stress, and potently induces the death of cancer cells, likely via starvation

  20. High Resolution Rapid Revisits Insar Monitoring of Surface Deformation

    NASA Astrophysics Data System (ADS)

    Singhroy, V.; Li, J.; Charbonneau, F.

    2014-12-01

    Monitoring surface deformation on strategic energy and transportation corridors requires high resolution spatial and temporal InSAR images for mitigation and safety purposes. High resolution air photos, lidar and other satellite images are very useful in areas where the landslides can be fatal. Recently, radar interferometry (InSAR) techniques using more rapid revisit images from several radar satellites are increasingly being used in active deformation monitoring. The Canadian RADARSAT Constellation (RCM) is a three-satellite mission that will provide rapid revisits of four days interferometric (InSAR) capabilities that will be very useful for complex deformation monitoring. For instance, the monitoring of surface deformation due to permafrost activity, complex rock slide motion and steam assisted oil extraction will benefit from this new rapid revisit capability. This paper provide examples of how the high resolution (1-3 m) rapid revisit InSAR capabilities will improve our monitoring of surface deformation and provide insights in understanding triggering mechanisms. We analysed over a hundred high resolution InSAR images over a two year period on three geologically different sites with various configurations of topography, geomorphology, and geology conditions. We show from our analysis that the more frequent InSAR acquisitions are providing more information in understanding the rates of movement and failure process of permafrost triggered retrogressive thaw flows; the complex motion of an asymmetrical wedge failure of an active rock slide and the identification of over pressure zones related to oil extraction using steam injection. Keywords: High resolution, InSAR, rapid revisits, triggering mechanisms, oil extraction.

  1. The environmental carcinogen benzo[a]pyrene induces a Warburg-like metabolic reprogramming dependent on NHE1 and associated with cell survival

    PubMed Central

    Hardonnière, Kévin; Saunier, Elise; Lemarié, Anthony; Fernier, Morgane; Gallais, Isabelle; Héliès-Toussaint, Cécile; Mograbi, Baharia; Antonio, Samantha; Bénit, Paule; Rustin, Pierre; Janin, Maxime; Habarou, Florence; Ottolenghi, Chris; Lavault, Marie-Thérèse; Benelli, Chantal; Sergent, Odile; Huc, Laurence; Bortoli, Sylvie; Lagadic-Gossmann, Dominique

    2016-01-01

    Cancer cells display alterations in many cellular processes. One core hallmark of cancer is the Warburg effect which is a glycolytic reprogramming that allows cells to survive and proliferate. Although the contributions of environmental contaminants to cancer development are widely accepted, the underlying mechanisms have to be clarified. Benzo[a]pyrene (B[a]P), the prototype of polycyclic aromatic hydrocarbons, exhibits genotoxic and carcinogenic effects, and it is a human carcinogen according to the International Agency for Research on Cancer. In addition to triggering apoptotic signals, B[a]P may induce survival signals, both of which are likely to be involved in cancer promotion. We previously suggested that B[a]P-induced mitochondrial dysfunctions, especially membrane hyperpolarization, might trigger cell survival signaling in rat hepatic epithelial F258 cells. Here, we further characterized these dysfunctions by focusing on energy metabolism. We found that B[a]P promoted a metabolic reprogramming. Cell respiration decreased and lactate production increased. These changes were associated with alterations in the tricarboxylic acid cycle which likely involve a dysfunction of the mitochondrial complex II. The glycolytic shift relied on activation of the Na+/H+ exchanger 1 (NHE1) and appeared to be a key feature in B[a]P-induced cell survival related to changes in cell phenotype (epithelial-to-mesenchymal transition and cell migration). PMID:27488617

  2. Clinical ethics revisited

    PubMed Central

    Singer, Peter A; Pellegrino, Edmund D; Siegler, Mark

    2001-01-01

    A decade ago, we reviewed the field of clinical ethics; assessed its progress in research, education, and ethics committees and consultation; and made predictions about the future of the field. In this article, we revisit clinical ethics to examine our earlier observations, highlight key developments, and discuss remaining challenges for clinical ethics, including the need to develop a global perspective on clinical ethics problems. PMID:11346456

  3. Colloquial Hebrew Imperatives Revisited

    ERIC Educational Resources Information Center

    Bolozky, Shmuel

    2009-01-01

    In revisiting Bolozky's [Bolozky, Shmuel, 1979. "On the new imperative in colloquial Hebrew." "Hebrew Annual Review" 3, 17-24] and Bat-El's [Bat-El, Outi, 2002. "True truncation in colloquial Hebrew imperatives." "Language" 78(4), 651-683] analyses of colloquial Hebrew imperatives, the article argues for restricting Imperative Truncation to the…

  4. Ambiguity Advantage Revisited: Two Meanings Are Better than One when Accessing Chinese Nouns

    ERIC Educational Resources Information Center

    Lin, Chien-Jer Charles; Ahrens, Kathleen

    2010-01-01

    This paper revisits the effect of lexical ambiguity in word recognition, which has been controversial as previous research reported advantage, disadvantage, and null effects. We discuss factors that were not consistently treated in previous research (e.g., the level of lexical ambiguity investigated, parts of speech of the experimental stimuli,…

  5. Re-visiting RHIC snakes: OPERA fields, n 0 dance

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Meot, F.; Gupta, R.; Huang, H.

    In this Tech. Note RHIC snakes and stable spin directionmore » $$\\vector{n}$$ 0(s) are re-visited, based on OPERA-computed field maps of the former. The numerical simulations so undertaken provide various outcomes regarding RHIC optics and spin dynamics, in relation with orbital and focusing effects resulting from the use of this realistic 3-D representation of the snakes.« less

  6. Mentoring, Advocacy, and Leadership: Revisiting First-Year Student Advocate Award Recipients

    ERIC Educational Resources Information Center

    White, Michelle M.; Anttonen, Ralph G.

    2007-01-01

    This study revisited research on award-winning campus leaders who were effective change agents working on the behalf of first-year students (Anttonen & Chaskes, 2002). Participants were recipients of the "Outstanding First-Year Student Advocate Award" given annually by the National Resource Center for the First-Year Experience and Students in…

  7. Framing the Future: Revisiting the Place of Educational Expectations in Status Attainment

    ERIC Educational Resources Information Center

    Bozick, Robert; Alexander, Karl; Entwisle, Doris; Dauber, Susan; Kerr, Kerri

    2010-01-01

    This study revisits the Wisconsin model of status attainment from a life course developmental perspective. Fixed-effects regression analyses lend strong support to the Wisconsin framework's core proposition that academic performance and significant others' influence shape educational expectations. However, investigating the process of expectation…

  8. Revisiting the decoupling effects in the running of the Cosmological Constant

    NASA Astrophysics Data System (ADS)

    Antipin, Oleg; Melić, Blaženka

    2017-09-01

    We revisit the decoupling effects associated with heavy particles in the renormalization group running of the vacuum energy in a mass-dependent renormalization scheme. We find the running of the vacuum energy stemming from the Higgs condensate in the entire energy range and show that it behaves as expected from the simple dimensional arguments meaning that it exhibits the quadratic sensitivity to the mass of the heavy particles in the infrared regime. The consequence of such a running to the fine-tuning problem with the measured value of the Cosmological Constant is analyzed and the constraint on the mass spectrum of a given model is derived. We show that in the Standard Model (SM) this fine-tuning constraint is not satisfied while in the massless theories this constraint formally coincides with the well known Veltman condition. We also provide a remarkably simple extension of the SM where saturation of this constraint enables us to predict the radiative Higgs mass correctly. Generalization to constant curvature spaces is also given.

  9. The Linguistic Repertoire Revisited

    ERIC Educational Resources Information Center

    Busch, Brigitta

    2012-01-01

    This article argues for the relevance of poststructuralist approaches to the notion of a linguistic repertoire and introduces the notion of language portraits as a basis for empirical study of the way in which speakers conceive and represent their heteroglossic repertoires. The first part of the article revisits Gumperz's notion of a linguistic…

  10. Revisiting Professional Teacher Standards

    ERIC Educational Resources Information Center

    Watson, Amanda

    2016-01-01

    The Australian Society for Music Education's (ASME) involvement in the development of professional standards for music educators was a significant and active research time in the history of the Society. As ASME celebrates its golden jubilee, it is appropriate to revisit that history and consider the future prospects of subject-specific standards.…

  11. Revisiting the Rhetorical Curriculum

    ERIC Educational Resources Information Center

    Rutten, Kris; Soetaert, Ronald

    2012-01-01

    The aim of the special strand on "Revisiting the rhetorical curriculum" is to explore the educational potential of a new rhetorical perspective, specifically in relation to different traditions within educational and rhetorical studies. This implies that we do not only look at education "in" rhetoric, but that we position education also "as" a…

  12. Factors Associated With Length of Stay and 30-Day Revisits in Pediatric Acute Pancreatitis.

    PubMed

    Gay, Anna C; Barreto, Nicolas; Schrager, Sheree M; Russell, Christopher J

    2018-05-30

    Identify factors associated with length of stay (LOS) and 30-day hospital revisit for patients hospitalized with acute pancreatitis (AP). Multicenter, retrospective cohort study using the Pediatric Health Information System database. Multilevel linear and logistic regression was used to identify factors independently associated with the primary outcome variables of LOS and 30-day hospital revisit in children aged 1-18 years discharged with a primary discharge diagnosis of AP from participating hospitals between 2008 and 2013. For the 7693 discharges, median LOS was 4 days (interquartile range 3-7 days) and 30-day revisit rate 17.6% (n = 1356). Discharges were primarily female (55%), Caucasian (46%), and six years old or older (85%). On multilevel regression, factors independently associated with both longer LOS and higher revisit odds included malignant and gastrointestinal complex chronic conditions and total parenteral nutrition (TPN) use while hospitalized. Male gender was associated with both lower LOS (aLOS = -0.6 days, 95% CI = -0.8, -0.4) and decreased revisit odds (aOR 0.85; 95% CI = 0.74, 0.97). Hispanic ethnicity was associated with increased LOS (aLOS = +0.8 days, 95% CI = +0.5, +1.1) but no change in revisit odds. Certain demographic and clinical factors, including gender, ethnicity, and type of complex chronic condition, were independently associated with LOS and risk of 30-day hospital revisit for pediatric AP. Children with malignant and gastrointestinal complex chronic conditions who require TPN are at highest risk for both longer LOS and hospital revisit when admitted with AP. These patient populations may benefit from intensive care coordination when hospitalized for AP.

  13. Predator-prey interactions, resource depression and patch revisitation

    USGS Publications Warehouse

    Erwin, R.M.

    1989-01-01

    Generalist predators may be confronted by different types of prey in different patches: sedentary and conspicuous, cryptic (with or without refugia), conspicuous and nonsocial, or conspicuous and social. I argue that, where encounter rates with prey are of most importance, patch revisitation should be a profitable tactic where prey have short 'recovery' times (conspicuous, nonsocial prey), or where anti-predator response (e.g. shoaling) may increase conspicuousness. Predictions are made for how temporal changes in prey encounter rates should affect revisit schedules and feeding rates for the 4 different prey types.

  14. The "Mushroom Cloud" Demonstration Revisited

    ERIC Educational Resources Information Center

    Panzarasa, Guido; Sparnacci, Katia

    2013-01-01

    A revisitation of the classical "mushroom cloud" demonstration is described. Instead of aniline and benzoyl peroxide, the proposed reaction involves household chemicals such as alpha-pinene (turpentine oil) and trichloroisocyanuric acid ("Trichlor") giving an impressive demonstration of oxidation and combustion reactions that…

  15. Cancer metabolism: fatty acid oxidation in the limelight

    PubMed Central

    Carracedo, Arkaitz; Cantley, Lewis C.; Pandolfi, Pier Paolo

    2013-01-01

    Warburg suggested that the alterations in metabolism that he observed in cancer cells were due to the malfunction of mitochondria. In the past decade, we have revisited this idea and reached a better understanding of the ‘metabolic switch’ in cancer cells, including the intimate and causal relationship between cancer genes and metabolic alterations, and their potential to be targeted for cancer treatment. However, the vast majority of the research into cancer metabolism has been limited to a handful of metabolic pathways, while other pathways have remained in the dark. This Progress article brings to light the important contribution of fatty acid oxidation to cancer cell function. PMID:23446547

  16. Effective-Medium Models for Marine Gas Hydrates, Mallik Revisited

    NASA Astrophysics Data System (ADS)

    Terry, D. A.; Knapp, C. C.; Knapp, J. H.

    2011-12-01

    Hertz-Mindlin type effective-medium dry-rock elastic models have been commonly used for more than three decades in rock physics analysis, and recently have been applied to assessment of marine gas hydrate resources. Comparisons of several effective-medium models with derivative well-log data from the Mackenzie River Valley, Northwest Territories, Canada (i.e. Mallik 2L-38 and 5L-38) were made several years ago as part of a marine gas hydrate joint industry project in the Gulf of Mexico. The matrix/grain supporting model (one of the five models compared) was clearly a better representation of the Mallik data than the other four models (2 cemented sand models; a pore-filling model; and an inclusion model). Even though the matrix/grain supporting model was clearly better, reservations were noted that the compressional velocity of the model was higher than the compressional velocity measured via the sonic logs, and that the shear velocities showed an even greater discrepancy. Over more than thirty years, variations of Hertz-Mindlin type effective medium models have evolved for unconsolidated sediments and here, we briefly review their development. In the past few years, the perfectly smooth grain version of the Hertz-Mindlin type effective-medium model has been favored over the infinitely rough grain version compared in the Gulf of Mexico study. We revisit the data from the Mallik wells to review assertions that effective-medium models with perfectly smooth grains are a better predictor than models with infinitely rough grains. We briefly review three Hertz-Mindlin type effective-medium models, and standardize nomenclature and notation. To calibrate the extended effective-medium model in gas hydrates, we use a well accepted framework for unconsolidated sediments through Hashin-Shtrikman bounds. We implement the previously discussed effective-medium models for saturated sediments with gas hydrates and compute theoretical curves of seismic velocities versus gas hydrate

  17. Effects of a Structured Discharge Planning Program on Perceived Functional Status, Cardiac Self-efficacy, Patient Satisfaction, and Unexpected Hospital Revisits Among Filipino Cardiac Patients: A Randomized Controlled Study.

    PubMed

    Cajanding, Ruff Joseph

    Cardiovascular diseases remain the leading cause of morbidity and mortality among Filipinos and are responsible for a very large number of hospital readmissions. Comprehensive discharge planning programs have demonstrated positive benefits among various populations of patients with cardiovascular disease, but the clinical and psychosocial effects of such intervention among Filipino patients with acute myocardial infarction (AMI) have not been studied. In this study we aimed to determine the effectiveness of a nurse-led structured discharge planning program on perceived functional status, cardiac self-efficacy, patient satisfaction, and unexpected hospital revisits among Filipino patients with AMI. A true experimental (randomized control) 2-group design with repeated measures and data collected before and after intervention and at 1-month follow-up was used in this study. Participants were assigned to either the control (n = 68) or the intervention group (n = 75). Intervention participants underwent a 3-day structured discharge planning program implemented by a cardiovascular nurse practitioner, which is comprised of a series of individualized lecture-discussion, provision of feedback, integrative problem solving, goal setting, and action planning. Control participants received standard routine care. Measures of functional status, cardiac self-efficacy, and patient satisfaction were measured at baseline; cardiac self-efficacy and patient satisfaction scores were measured prior to discharge, and perceived functional status and number of revisits were measured 1 month after discharge. Participants in the intervention group had significant improvement in functional status, cardiac self-efficacy, and patient satisfaction scores at baseline and at follow-up compared with the control participants. Furthermore, participants in the intervention group had significantly fewer hospital revisits compared with those who received only standard care. The results demonstrate that a

  18. A Hydrostatic Paradox Revisited

    ERIC Educational Resources Information Center

    Ganci, Salvatore

    2012-01-01

    This paper revisits a well-known hydrostatic paradox, observed when turning upside down a glass partially filled with water and covered with a sheet of light material. The phenomenon is studied in its most general form by including the mass of the cover. A historical survey of this experiment shows that a common misunderstanding of the phenomenon…

  19. Acknowledgment Tokens and Speakership Incipiency Revisited.

    ERIC Educational Resources Information Center

    Zimmerman, Don H.

    1993-01-01

    Drummond and Hopper's article in this issue, "Back Channels Revisited," is argued to have decontextualized Jefferson's acknowledgement token phenomenon. The need for careful coding protocols for research on conversational practices is discussed. (eight references) (LB)

  20. Revisiting Dialogues and Monologues

    ERIC Educational Resources Information Center

    Kvernbekk, Tone

    2012-01-01

    In educational discourse dialogue tends to be viewed as being (morally) superior to monologue. When we look at them as basic forms of communication, we find that dialogue is a two-way, one-to-one form and monologue is a one-way, one-to-many form. In this paper I revisit the alleged (moral) superiority of dialogue. First, I problematize certain…

  1. Revisiting kaon physics in general Z scenario

    NASA Astrophysics Data System (ADS)

    Endo, Motoi; Kitahara, Teppei; Mishima, Satoshi; Yamamoto, Kei

    2017-08-01

    New physics contributions to the Z penguin are revisited in the light of the recently-reported discrepancy of the direct CP violation in K → ππ. Interference effects between the standard model and new physics contributions to ΔS = 2 observables are taken into account. Although the effects are overlooked in the literature, they make experimental bounds significantly severer. It is shown that the new physics contributions must be tuned to enhance B (KL →π0 ν ν bar), if the discrepancy of the direct CP violation is explained with satisfying the experimental constraints. The branching ratio can be as large as 6 ×10-10 when the contributions are tuned at the 10% level.

  2. A practical method of predicting client revisit intention in a hospital setting.

    PubMed

    Lee, Kyun Jick

    2005-01-01

    Data mining (DM) models are an alternative to traditional statistical methods for examining whether higher customer satisfaction leads to higher revisit intention. This study used a total of 906 outpatients' satisfaction data collected from a nationwide survey interviews conducted by professional interviewers on a face-to-face basis in South Korea, 1998. Analyses showed that the relationship between overall satisfaction with hospital services and outpatients' revisit intention, along with word-of-mouth recommendation as intermediate variables, developed into a nonlinear relationship. The five strongest predictors of revisit intention were overall satisfaction, intention to recommend to others, awareness of hospital promotion, satisfaction with physician's kindness, and satisfaction with treatment level.

  3. Characteristics of revisits of children at risk for serious infections in pediatric emergency care.

    PubMed

    de Vos-Kerkhof, Evelien; Geurts, Dorien H F; Steyerberg, Ewout W; Lakhanpaul, Monica; Moll, Henriette A; Oostenbrink, Rianne

    2018-04-01

    In this study, we aimed to identify characteristics of (unscheduled) revisits and its optimal time frame after Emergency Department (ED) discharge. Children with fever, dyspnea, or vomiting/diarrhea (1 month-16 years) who attended the ED of Erasmus MC-Sophia, Rotterdam (2010-2013), the Netherlands, were prospectively included. Three days after ED discharge, we applied standardized telephonic questionnaires on disease course and revisits. Multivariable logistic regression analysis was used to identify independent characteristics of revisits. Young age, parental concern, and alarming signs and symptoms (chest wall retractions, ill appearance, clinical signs of dehydration, and tachypnea) were associated with revisits (n = 527) in children at risk for serious infections discharged from the ED (n = 1765). Children revisited the ED within a median of 2 days (IQR 1.0-3.0), but this was proven to be shorter in children with vomiting/diarrhea (1.0 day (IQR 1.0-2.0)) compared to children with fever or dyspnea (2.0 (IQR 1.0-3.0)). Young age, parental concern, and alarming signs and symptoms (chest wall retractions, ill appearance, clinical signs of dehydration, and tachypnea) were associated with emergency health care revisits in children with fever, dyspnea, and vomiting/diarrhea. These characteristics could help to define targeted review of children during post-discharge period. We observed a disease specific and differential timing of control revisits after ED discharge. What is Known • Fever, dyspnea, and vomiting/diarrhea are major causes of emergency care attendance in children. • As uncertainty remains on uneventful recovery, patients at risk need to be identified on order to improve safety netting after discharge from the ED. What is New • In children with fever, dyspnea, and vomiting/diarrhea, young age, parental concern and chest wall retractions, ill appearance, clinical signs of dehydration, and tachypnea help to define targeted review of

  4. Revisiting Interpretation of Canonical Correlation Analysis: A Tutorial and Demonstration of Canonical Commonality Analysis

    ERIC Educational Resources Information Center

    Nimon, Kim; Henson, Robin K.; Gates, Michael S.

    2010-01-01

    In the face of multicollinearity, researchers face challenges interpreting canonical correlation analysis (CCA) results. Although standardized function and structure coefficients provide insight into the canonical variates produced, they fall short when researchers want to fully report canonical effects. This article revisits the interpretation of…

  5. The Evil of Banality: Arendt Revisited

    ERIC Educational Resources Information Center

    Minnich, Elizabeth

    2014-01-01

    "The banality of evil" (Arendt) remains controversial and useful. Ironically, the concept is now itself a banality. To revisit and extend it, we consider the "evil of banality", the profound dangers of cliched thoughtlessness. A distinction is proposed: "intensive" versus "extensive evils". The former takes…

  6. Glucose-dependent growth arrest of leukemia cells by MCT1 inhibition: Feeding Warburg's sweet tooth and blocking acid export as an anticancer strategy.

    PubMed

    Pivovarova, Aleksandra I; MacGregor, Gordon G

    2018-02-01

    This study aims to investigate the utilization of The Warburg Effect, cancer's "sweet tooth" and natural greed for glucose to enhance the effect of monocarboxylate transporter inhibition on cellular acidification. By simulating hyperglycemia with high glucose we may increase the effectiveness of inhibition of lactate and proton export on the dysregulation of cell pH homeostasis causing cell death or disruption of growth in cancer cells. MCT1 and MCT4 expression was determined in MCF7 and K562 cell lines using RT-PCR. Cell viability, growth, intracellular pH and cell cycle analysis was measured in the cell lines grown in 5 mM and 25 mM glucose containing media in the presence and absence of the MCT1 inhibitor AR-C155858 (1 μM) and the NHE1 inhibitor cariporide (10 μM). The MCT1 inhibitor, AR-C155858 had minimal effect on the viability, growth and intracellular pH of MCT4 expressing MCF7 cells. AR-C155858 had no effect on the viability of the MCT1 expressing K562 cells, but decreased intracellular pH and cell proliferation, by a glucose-dependent mechanism. Inhibition of NHE1 on its own had a no effect on cell growth, but together with AR-C155858 showed an additive effect on inhibition of cell growth. In cancer cells that only express MCT1, increased glucose concentrations in the presence of an MCT1 inhibitor decreased intracellular pH and reduced cell growth by G1 phase cell-cycle arrest. Thus we propose a transient hyperglycemic-clamp in combination with proton export inhibitors be evaluated as an adjunct to cancer treatment in clinical studies. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  7. Revisiting a pre-inflationary radiation era and its effect on the CMB power spectrum

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Das, Suratna; Goswami, Gaurav; Rangarajan, Raghavan

    2015-06-01

    We revisit the scenario where inflation is preceded by a radiation era by considering that the inflaton too could have been in thermal equilibrium early in the radiation era. Hence we take into account not only the effect of a pre-inflationary era on the inflaton mode functions but also that of a frozen thermal distribution of inflaton quanta. We initially discuss in detail the issues relevant to our scenario of a pre-inflationary radiation dominated era and then obtain the scalar power spectrum for this scenario. We find that the power spectrum is free from infrared divergences. We then use themore » WMAP and Planck data to determine the constraints on the inflaton comoving 'temperature' and on the duration of inflation. We find that the best fit value of the duration of inflation is less than 1 e-folding more than what is required to solve cosmological problems, while only an upper bound on the inflaton temperature can be obtained.« less

  8. Benjamin Franklin and Mesmerism, revisited.

    PubMed

    McConkey, Kevin M; Perry, Campbell

    2002-10-01

    The authors revisit and update their previous historiographical note (McConkey & Perry, 1985) on Benjamin Franklin's involvement with and investigation of animal magnetism or mesmerism. They incorporate more recent literature and offer additional comment about Franklin's role in and views about mesmerism. Franklin had a higher degree of personal involvement with and a more detailed opinion of mesmerism than has been previously appreciated.

  9. The Rotating Morse-Pekeris Oscillator Revisited

    ERIC Educational Resources Information Center

    Zuniga, Jose; Bastida, Adolfo; Requena, Alberto

    2008-01-01

    The Morse-Pekeris oscillator model for the calculation of the vibration-rotation energy levels of diatomic molecules is revisited. This model is based on the realization of a second-order exponential expansion of the centrifugal term about the minimum of the vibrational Morse oscillator and the subsequent analytical resolution of the resulting…

  10. Revisiting Hardy's paradox: counterfactual statements, real measurements, entanglement and weak values

    NASA Astrophysics Data System (ADS)

    Aharonov, Yakir; Botero, Alonso; Popescu, Sandu; Reznik, Benni; Tollaksen, Jeff

    2002-08-01

    Hardy's paradox is revisited. Usually the paradox is dismissed on grounds of counterfactuality, i.e., because the paradoxical effects appear only when one considers results of experiments which do not actually take place. We suggest a new set of measurements in connection with Hardy's scheme, and show that when they are actually performed, they yield strange and surprising outcomes. More generally, we claim that counterfactual paradoxes point to a deeper structure inherent to quantum mechanics.

  11. Revisiting the Capture of Mercury into Its 3:2 Spin-orbit Resonance

    DTIC Science & Technology

    2014-01-01

    well before differentiation. Keywords. celestial mechanics, planets and satellites: individual ( Mercury ) 1. Previous studies In the literature hitherto...2014 2. REPORT TYPE 3. DATES COVERED 00-00-2014 to 00-00-2014 4. TITLE AND SUBTITLE Revisiting the capture of Mercury into its 3:2 spin-orbit...Astronomical Union 2014 doi:10.1017/S1743921314007765 Revisiting the capture of Mercury into its 3:2 spin-orbit resonance Benôıt Noyelles1, Julien

  12. Hospital revisit rate after a diagnosis of conversion disorder.

    PubMed

    Merkler, Alexander E; Parikh, Neal S; Chaudhry, Simriti; Chait, Alanna; Allen, Nicole C; Navi, Babak B; Kamel, Hooman

    2016-04-01

    To estimate the hospital revisit rate of patients diagnosed with conversion disorder (CD). Using administrative data, we identified all patients discharged from California, Florida and New York emergency departments (EDs) and acute care hospitals between 2005 and 2011 with a primary discharge diagnosis of CD. Patients discharged with a primary diagnosis of seizure or transient global amnesia (TGA) served as control groups. Our primary outcome was the rate of repeat ED visits and hospital admissions after initial presentation. Poisson regression was used to compare rates between diagnosis groups while adjusting for demographic characteristics. We identified 7946 patients discharged with a primary diagnosis of CD. During a mean follow-up of 3.0 (±1.6) years, patients with CD had a median of three (IQR, 1-9) ED or inpatient revisits, compared with 0 (IQR, 0-2) in patients with TGA and 3 (IQR, 1-7) in those with seizures. Revisit rates were 18.25 (95% CI, 18.10 to 18.40) visits per 100 patients per month in those with CD, 3.90 (95% CI, 3.84 to 3.95) in those with TGA and 17.78 (95% CI, 17.75 to 17.81) in those with seizures. As compared to CD, the incidence rate ratio for repeat ED visits or hospitalisations was 0.89 (95% CI, 0.86 to 0.93) for seizure disorder and 0.32 (95% CI 0.31 to 0.34) for TGA. CD is associated with a substantial hospital revisit rate. Our findings suggest that CD is not an acute, time-limited response to stress, but rather that CD is a manifestation of a broader pattern of chronic neuropsychiatric disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  13. Service-Learning in Crisis Communication Education: Revisiting Coombs' Objectives for the Crisis Communication Course

    ERIC Educational Resources Information Center

    Maresh-Fuehrer, Michelle M.

    2015-01-01

    The purpose of this study was to revisit Coombs' suggestions for teaching the crisis communication course using service-learning as a framework. The author sought to assess the effectiveness of using this method in terms of the benefits to both students and the partnering organization and students' perceptions of whether they met the learning…

  14. The Future of Engineering Education--Revisited

    ERIC Educational Resources Information Center

    Wankat, Phillip C.; Bullard, Lisa G.

    2016-01-01

    This paper revisits the landmark CEE series, "The Future of Engineering Education," published in 2000 (available free in the CEE archives on the internet) to examine the predictions made in the original paper as well as the tools and approaches documented. Most of the advice offered in the original series remains current. Despite new…

  15. Polyploidy and its effect on evolutionary success: old questions revisited with new tools

    PubMed Central

    Madlung, A

    2013-01-01

    Polyploidy, the condition of possessing more than two complete genomes in a cell, has intrigued biologists for almost a century. Polyploidy is found in many plants and some animal species and today we know that polyploidy has had a role in the evolution of all angiosperms. Despite its widespread occurrence, the direct effect of polyploidy on evolutionary success of a species is still largely unknown. Over the years many attractive hypotheses have been proposed in an attempt to assign functionality to the increased content of a duplicated genome. Among these hypotheses are the proposal that genome doubling confers distinct advantages to a polyploid and that these advantages allow polyploids to thrive in environments that pose challenges to the polyploid's diploid progenitors. This article revisits these long-standing questions and explores how the integration of recent genomic developments with ecological, physiological and evolutionary perspectives has contributed to addressing unresolved problems about the role of polyploidy. Although unsatisfactory, the current conclusion has to be that despite significant progress, there still isn't enough information to unequivocally answer many unresolved questions about cause and effect of polyploidy on evolutionary success of a species. There is, however, reason to believe that the increasingly integrative approaches discussed here should allow us in the future to make more direct connections between the effects of polyploidy on the genome and the responses this condition elicits from the organism living in its natural environment. PMID:23149459

  16. Revisiting the Regenerative Possibilities of Ortiz

    ERIC Educational Resources Information Center

    Duques, Matthew

    2004-01-01

    The author of this article revisits Simon Ortiz's poem, "From Sand Creek," in which the latter can in so few words convey both the horrific tragedy of conquest and colonization, while at the same time find a space for possibility, a means for recovery that is never about forgetting but always occurs as a kind of recuperative remembering. Ortiz…

  17. Phenomenology of n - n ¯ oscillations revisited

    DOE PAGES

    Gardner, S.; Jafari, E.

    2015-05-22

    We revisit the phenomenology of n-n¯ oscillations in the presence of external magnetic fields, highlighting the role of spin. We show, contrary to long-held belief, that the n-n¯ transition rate need not be suppressed, opening new opportunities for its empirical study.

  18. Phenomenology of n - n ¯ oscillations revisited

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gardner, S.; Jafari, E.

    We revisit the phenomenology of n-n¯ oscillations in the presence of external magnetic fields, highlighting the role of spin. We show, contrary to long-held belief, that the n-n¯ transition rate need not be suppressed, opening new opportunities for its empirical study.

  19. Revisiting separation properties of convex fuzzy sets

    USDA-ARS?s Scientific Manuscript database

    Separation of convex sets by hyperplanes has been extensively studied on crisp sets. In a seminal paper separability and convexity are investigated, however there is a flaw on the definition of degree of separation. We revisited separation on convex fuzzy sets that have level-wise (crisp) disjointne...

  20. Emergency department revisits for patients with kidney stones in California.

    PubMed

    Scales, Charles D; Lin, Li; Saigal, Christopher S; Bennett, Carol J; Ponce, Ninez A; Mangione, Carol M; Litwin, Mark S

    2015-04-01

    Kidney stones affect nearly one in 11 persons in the United States, and among those experiencing symptoms, emergency care is common. In this population, little is known about the incidence of and factors associated with repeat emergency department (ED) visits. The objective was to identify associations between potentially mutable factors and the risk of an ED revisit for patients with kidney stones in a large, all-payer cohort. This was a retrospective cohort study of all patients in California initially treated and released from EDs for kidney stones between February 2008 and November 2009. A multivariable regression model was created to identify associations between patient-level characteristics, area health care resources, processes of care, and the risk of repeat ED visits. The primary outcome was a second ED visit within 30 days of the initial discharge from emergent care. Among 128,564 patients discharged from emergent care, 13,684 (11%) had at least one additional emergent visit for treatment of their kidney stone. In these patients, nearly one in three required hospitalization or an urgent temporizing procedure at the second visit. On multivariable analysis, the risk of an ED revisit was associated with insurance status (e.g., Medicaid vs. private insurance; odds ratio [OR] = 1.52, 95% confidence interval [CI] = 1.43 to 1.61; p < 0.001). Greater access to urologic care was associated with lower odds of an ED revisit (highest quartile OR = 0.88, 95% CI = 0.80 to 0.97; p < 0.01 vs. lowest quartile). In exploratory models, performance of a complete blood count was associated with a decreased odds of revisit (OR = 0.86, 95% CI = 0.75 to 0.97; p = 0.02). Repeat high-acuity care affects one in nine patients discharged from initial emergent evaluations for kidney stones. Access to urologic care and processes of care are associated with lower risk of repeat emergent encounters. Efforts are indicated to identify preventable causes of ED revisits for kidney stone

  1. Meta-analysis in clinical trials revisited.

    PubMed

    DerSimonian, Rebecca; Laird, Nan

    2015-11-01

    In this paper, we revisit a 1986 article we published in this Journal, Meta-Analysis in Clinical Trials, where we introduced a random-effects model to summarize the evidence about treatment efficacy from a number of related clinical trials. Because of its simplicity and ease of implementation, our approach has been widely used (with more than 12,000 citations to date) and the "DerSimonian and Laird method" is now often referred to as the 'standard approach' or a 'popular' method for meta-analysis in medical and clinical research. The method is especially useful for providing an overall effect estimate and for characterizing the heterogeneity of effects across a series of studies. Here, we review the background that led to the original 1986 article, briefly describe the random-effects approach for meta-analysis, explore its use in various settings and trends over time and recommend a refinement to the method using a robust variance estimator for testing overall effect. We conclude with a discussion of repurposing the method for Big Data meta-analysis and Genome Wide Association Studies for studying the importance of genetic variants in complex diseases. Published by Elsevier Inc.

  2. Meta-Analysis in Clinical Trials Revisited

    PubMed Central

    Laird, Nan

    2015-01-01

    In this paper, we revisit a 1986 article we published in this Journal, Meta-Analysis in Clinical Trials, where we introduced a random-effect model to summarize the evidence about treatment efficacy from a number of related clinical trials. Because of its simplicity and ease of implementation, our approach has been widely used (with more than 12,000 citations to date) and the “DerSimonian and Laird method” is now often referred to as the ‘standard approach’ or a ‘popular’ method for meta-analysis in medical and clinical research. The method is especially useful for providing an overall effect estimate and for characterizing the heterogeneity of effects across a series of studies. Here, we review the background that led to the original 1986 article, briefly describe the random-effects approach for meta-analysis, explore its use in various settings and trends over time and recommend a refinement to the method using a robust variance estimator for testing overall effect. We conclude with a discussion of repurposing the method for Big Data meta-analysis and Genome Wide Association Studies for studying the importance of genetic variants in complex diseases. PMID:26343745

  3. Hall-petch law revisited in terms of collective dislocation dynamics.

    PubMed

    Louchet, François; Weiss, Jérôme; Richeton, Thiebaud

    2006-08-18

    The Hall-Petch (HP) law, that accounts for the effect of grain size on the plastic yield stress of polycrystals, is revisited in terms of the collective motion of interacting dislocations. Sudden relaxation of incompatibility stresses in a grain triggers aftershocks in the neighboring ones. The HP law results from a scaling argument based on the conservation of the elastic energy during such transfers. The Hall-Petch law breakdown for nanometric sized grains is shown to stem from the loss of such a collective behavior as grains start deforming by successive motion of individual dislocations.

  4. Effect of anti-glycolytic agents on tumour cells in vitro

    NASA Astrophysics Data System (ADS)

    Korshunov, D. A.; Kondakova, I. V.

    2016-08-01

    A metabolic change is one of the tumour hallmarks, which has recently attracted a great amount of attention. One of the main metabolic characteristics of tumour cells is a high level of glycolysis even in the presence of oxygen, known as aerobic glycolysis or the Warburg effect. The energy production is much less in a glycolysis pathway than that in a tricarboxylic acid cycle. The Warburg effect constitutes a fundamental adaptation of tumour cells to a relatively hostile environment, and supports the evolution of aggressive and metastatic phenotypes. As a result, tumour glycolysis may become an attractive target for cancer therapy. Here, we research the effect of potential anticancer agents on tumour cells in vitro. In our study, we found a high sensitivity of tumour cells to anti-glycolityc drugs. In addition, tumour cells are more resistant to the agents studied in comparison with normal cells. We also observed an atypical cooperative interaction of tumour cells in the median lethal dose of drugs. They formed the specific morphological structure of the surviving cells. This behavior is not natural for the culture of tumour cells. Perhaps this is one of the mechanisms of cells' adaptation to the aggressive environment.

  5. Magnetic Braking Revisited: Activities for the Undergraduate Laboratory

    ERIC Educational Resources Information Center

    Ireson, Gren; Twidle, John

    2008-01-01

    This paper revisits the demonstration of Lenz by dropping magnets down a non-magnetic tube. Recent publications are reviewed and ideas for undergraduate laboratory investigations are suggested. Finally, an example of matching theory to observation is presented. (Contains 4 tables, 5 figures and 3 footnotes.)

  6. The Role of Glucose Metabolism and Glucose-Associated Signalling in Cancer

    PubMed Central

    Wittig, Rainer; Coy, Johannes F.

    2007-01-01

    Aggressive carcinomas ferment glucose to lactate even in the presence of oxygen. This particular metabolism, termed aerobic glycolysis, the glycolytic phenotype, or the Warburg effect, was discovered by Nobel laureate Otto Warburg in the 1920s. Since these times, controversial discussions about the relevance of the fermentation of glucose by tumours took place; however, a majority of cancer researchers considered the Warburg effect as a non-causative epiphenomenon. Recent research demonstrated, that several common oncogenic events favour the expression of the glycolytic phenotype. Moreover, a suppression of the phenotypic features by either substrate limitation, pharmacological intervention, or genetic manipulation was found to mediate potent tumour-suppressive effects. The discovery of the transketolase-like 1 (TKTL1) enzyme in aggressive cancers may deliver a missing link in the interpretation of the Warburg effect. TKTL1-activity could be the basis for a rapid fermentation of glucose in aggressive carcinoma cells via the pentose phosphate pathway, which leads to matrix acidification, invasive growth, and ultimately metastasis. TKTL1 expression in certain non-cancerous tissues correlates with aerobic formation of lactate and rapid fermentation of glucose, which may be required for the prevention of advanced glycation end products and the suppression of reactive oxygen species. There is evidence, that the activity of this enzyme and the Warburg effect can be both protective or destructive for the organism. These results place glucose metabolism to the centre of pathogenesis of several civilisation related diseases and raise concerns about the high glycaemic index of various food components commonly consumed in western diets. PMID:19812737

  7. Revisiting the Decision of Death in Hurst v. Florida.

    PubMed

    Cooke, Brian K; Ginory, Almari; Zedalis, Jennifer

    2016-12-01

    The United States Supreme Court has considered the question of whether a judge or a jury must make the findings necessary to support imposition of the death penalty in several notable cases, including Spaziano v. Florida (1984), Hildwin v. Florida (1989), and Ring v. Arizona (2002). In 2016, the U.S. Supreme Court revisited the subject in Hurst v. Florida Florida Statute § 921.141 allows the judge, after weighing aggravating and mitigating circumstances, to enter a sentence of life imprisonment or death. Before Hurst, Florida's bifurcated sentencing proceedings included an advisory sentence from jurors and a separate judicial hearing without juror involvement. In Hurst, the Court revisited the question of whether Florida's capital sentencing scheme violates the Sixth Amendment, which requires a jury, not a judge, to find each fact necessary to impose a sentence of death in light of Ring In an eight-to-one decision, the Court reversed the judgment of the Florida Supreme Court, holding that the Sixth Amendment requires a jury to find the aggravating factors necessary for imposing the death penalty. The role of Florida juries in capital sentencing proceedings was thereby elevated from advisory to determinative. We examine the Court's decision and offer commentary regarding this shift from judge to jury in the final imposition of the death penalty and the overall effect of this landmark case. © 2016 American Academy of Psychiatry and the Law.

  8. The Association Between Limited English Proficiency and Unplanned Emergency Department Revisit Within 72 Hours.

    PubMed

    Ngai, Ka Ming; Grudzen, Corita R; Lee, Roy; Tong, Vicky Y; Richardson, Lynne D; Fernandez, Alicia

    2016-08-01

    Language barriers are known to negatively affect many health outcomes among limited English proficiency patient populations, but little is known about the quality of care such patients receive in the emergency department (ED). This study seeks to determine whether limited English proficiency patients experience different quality of care than English-speaking patients in the ED, using unplanned revisit within 72 hours as a surrogate quality indicator. We conducted a retrospective cohort study in an urban adult ED in 2012, with a total of 41,772 patients and 56,821 ED visits. We compared 2,943 limited English proficiency patients with 38,829 English-speaking patients presenting to the ED after excluding patients with psychiatric complaints, altered mental status, and nonverbal states, and those with more than 4 ED visits in 12 months. Two main outcomes-the risk of inpatient admission from the ED and risk of unplanned ED revisit within 72 hours-were measured with odds ratios from generalized estimating equation multivariate models. Limited English proficiency patients were more likely than English speakers to be admitted (32.0% versus 27.2%; odds ratio [OR]=1.20; 95% confidence interval [CI] 1.11 to 1.30). This association became nonsignificant after adjustments (OR=1.04; 95% CI 0.95 to 1.15). Included in the analysis of ED revisit within 72 hours were 32,857 patients with 45,546 ED visits; 4.2% of all patients (n=1,380) had at least 1 unplanned revisit. Limited English proficiency patients were more likely than English speakers to have an unplanned revisit (5.0% versus 4.1%; OR=1.19; 95% CI 1.02 to 1.45). This association persisted (OR=1.24; 95% CI 1.02 to 1.53) after adjustment for potential confounders, including insurance status. We found no difference in hospital admission rates between limited English proficiency patients and English-speaking patients. Yet limited English proficiency patients were 24% more likely to have an unplanned ED revisit within 72 hours

  9. Satellite failures revisited

    NASA Astrophysics Data System (ADS)

    Balcerak, Ernie

    2012-12-01

    In January 1994, the two geostationary satellites known as Anik-E1 and Anik-E2, operated by Telesat Canada, failed one after the other within 9 hours, leaving many northern Canadian communities without television and data services. The outage, which shut down much of the country's broadcast television for hours and cost Telesat Canada more than $15 million, generated significant media attention. Lam et al. used publicly available records to revisit the event; they looked at failure details, media coverage, recovery effort, and cost. They also used satellite and ground data to determine the precise causes of those satellite failures. The researchers traced the entire space weather event from conditions on the Sun through the interplanetary medium to the particle environment in geostationary orbit.

  10. Children's Social Play Sequence: Parten's Classic Theory Revisited

    ERIC Educational Resources Information Center

    Xu, Yaoying

    2010-01-01

    The purpose of this article is to revisit Parten's study on social play from cultural, environmental, social and economic aspects. Young children's social play is viewed as a critical means to foster and enhance language, cognitive, social and emotional development. Social play theory has been predominately viewed from developmental perspectives.…

  11. Revisiting the Incremental Effects of Context on Word Processing: Evidence from Single-Word Event-Related Brain Potentials

    PubMed Central

    Payne, Brennan R.; Lee, Chia-Lin; Federmeier, Kara D.

    2015-01-01

    The amplitude of the N400— an event-related potential (ERP) component linked to meaning processing and initial access to semantic memory— is inversely related to the incremental build-up of semantic context over the course of a sentence. We revisited the nature and scope of this incremental context effect, adopting a word-level linear mixed-effects modeling approach, with the goal of probing the continuous and incremental effects of semantic and syntactic context on multiple aspects of lexical processing during sentence comprehension (i.e., effects of word frequency and orthographic neighborhood). First, we replicated the classic word position effect at the single-word level: open-class words showed reductions in N400 amplitude with increasing word position in semantically congruent sentences only. Importantly, we found that accruing sentence context had separable influences on the effects of frequency and neighborhood on the N400. Word frequency effects were reduced with accumulating semantic context. However, orthographic neighborhood was unaffected by accumulating context, showing robust effects on the N400 across all words, even within congruent sentences. Additionally, we found that N400 amplitudes to closed-class words were reduced with incrementally constraining syntactic context in sentences that provided only syntactic constraints. Taken together, our findings indicate that modeling word-level variability in ERPs reveals mechanisms by which different sources of information simultaneously contribute to the unfolding neural dynamics of comprehension. PMID:26311477

  12. Revisiting the incremental effects of context on word processing: Evidence from single-word event-related brain potentials.

    PubMed

    Payne, Brennan R; Lee, Chia-Lin; Federmeier, Kara D

    2015-11-01

    The amplitude of the N400-an event-related potential (ERP) component linked to meaning processing and initial access to semantic memory-is inversely related to the incremental buildup of semantic context over the course of a sentence. We revisited the nature and scope of this incremental context effect, adopting a word-level linear mixed-effects modeling approach, with the goal of probing the continuous and incremental effects of semantic and syntactic context on multiple aspects of lexical processing during sentence comprehension (i.e., effects of word frequency and orthographic neighborhood). First, we replicated the classic word-position effect at the single-word level: Open-class words showed reductions in N400 amplitude with increasing word position in semantically congruent sentences only. Importantly, we found that accruing sentence context had separable influences on the effects of frequency and neighborhood on the N400. Word frequency effects were reduced with accumulating semantic context. However, orthographic neighborhood was unaffected by accumulating context, showing robust effects on the N400 across all words, even within congruent sentences. Additionally, we found that N400 amplitudes to closed-class words were reduced with incrementally constraining syntactic context in sentences that provided only syntactic constraints. Taken together, our findings indicate that modeling word-level variability in ERPs reveals mechanisms by which different sources of information simultaneously contribute to the unfolding neural dynamics of comprehension. © 2015 Society for Psychophysiological Research.

  13. Temporal Dynamic Controllability Revisited

    NASA Technical Reports Server (NTRS)

    Morris, Paul H.; Muscettola, Nicola

    2005-01-01

    An important issue for temporal planners is the ability to handle temporal uncertainty. We revisit the question of how to determine whether a given set of temporal requirements are feasible in the light of uncertain durations of some processes. In particular, we consider how best to determine whether a network is Dynamically Controllable, i.e., whether a dynamic strategy exists for executing the network that is guaranteed to satisfy the requirements. Previous work has shown the existence of a pseudo-polynomial algorithm for testing Dynamic Controllability. Here, we greatly simplify the previous framework, and present a true polynomial algorithm with a cutoff based only on the number of nodes.

  14. Investigating predictors of visiting, using, and revisiting an online health-communication program: a longitudinal study.

    PubMed

    Van 't Riet, Jonathan; Crutzen, Rik; De Vries, Hein

    2010-09-02

    Online health communication has the potential to reach large audiences, with the additional advantages that it can be operational at all times and that the costs per visitor are low. Furthermore, research shows that Internet-delivered interventions can be effective in changing health behaviors. However, exposure to Internet-delivered health-communication programs is generally low. Research investigating predictors of exposure is needed to be able to effectively disseminate online interventions. In the present study, the authors used a longitudinal design with the aim of identifying demographic, psychological, and behavioral predictors of visiting, using, and revisiting an online program promoting physical activity in the general population. A webpage was created providing the public with information about health and healthy behavior. The website included a "physical activity check," which consisted of a physical activity computer-tailoring expert system where visitors could check whether their physical activity levels were in line with recommendations. Visitors who consented to participate in the present study (n = 489) filled in a questionnaire that assessed demographics, mode of recruitment, current physical activity levels, and health motivation. Immediately after, participants received tailored feedback concerning their current physical activity levels and completed a questionnaire assessing affective and cognitive user experience, attitude toward being sufficiently physically active, and intention to be sufficiently physically active. Three months later, participants received an email inviting them once more to check whether their physical activity level had changed. Analyses of visiting showed that more women (67.5%) than men (32.5%) visited the program. With regard to continued use, native Dutch participants (odds ratio [OR] = 2.81, 95% confidence interval [CI] = 1.16-6.81, P = .02) and participants with a strong motivation to be healthy (OR = 1.46, CI = 1

  15. Moral Judgment Development across Cultures: Revisiting Kohlberg's Universality Claims

    ERIC Educational Resources Information Center

    Gibbs, John C.; Basinger, Karen S.; Grime, Rebecca L.; Snarey, John R.

    2007-01-01

    This article revisits Kohlberg's cognitive developmental claims that stages of moral judgment, facilitative processes of social perspective-taking, and moral values are commonly identifiable across cultures. Snarey [Snarey, J. (1985). "The cross-cultural universality of social-moral development: A critical review of Kohlbergian research."…

  16. Global Instability on Laminar Separation Bubbles-Revisited

    NASA Technical Reports Server (NTRS)

    Theofilis, Vassilis; Rodriquez, Daniel; Smith, Douglas

    2010-01-01

    In the last 3 years, global linear instability of LSB has been revisited, using state-of-the-art hardware and algorithms. Eigenspectra of LSB flows have been understood and classified in branches of known and newly-discovered eigenmodes. Major achievements: World-largest numerical solutions of global eigenvalue problems are routinely performed. Key aerodynamic phenomena have been explained via critical point theory, applied to our global mode results. Theoretical foundation for control of LSB flows has been laid. Global mode of LSB at the origin of observable phenomena. U-separation on semi-infinite plate. Stall cells on (stalled) airfoil. Receptivity/Sensitivity/AFC feasible (practical?) via: Adjoint EVP solution. Direct/adjoint coupling (the Crete connection). Minor effect of compressibility on global instability in the subsonic compressible regime. Global instability analysis of LSB in realistic supersonic flows apparently quite some way down the horizon.

  17. Radiative corrections to double-Dalitz decays revisited

    NASA Astrophysics Data System (ADS)

    Kampf, Karol; Novotný, Jiři; Sanchez-Puertas, Pablo

    2018-03-01

    In this study, we revisit and complete the full next-to-leading order corrections to pseudoscalar double-Dalitz decays within the soft-photon approximation. Comparing to the previous study, we find small differences, which are nevertheless relevant for extracting information about the pseudoscalar transition form factors. Concerning the latter, these processes could offer the opportunity to test them—for the first time—in their double-virtual regime.

  18. Revisiting Feminist Identity Development Theory, Research, and Practice

    ERIC Educational Resources Information Center

    Moradi, Bonnie; Subich, Linda Mezydlo; Phillips, Julia C.

    2002-01-01

    The model of feminist identity development proposed by Downing and Roush in 1985 is revisited as a potentially useful framework in counseling psychology theory, research, and practice. An examination of the historical context from which the model arose illustrates how it advanced theory in the psychology of women. A critical review of the extant…

  19. A Feminist Revisit to the First-Year Curriculum.

    ERIC Educational Resources Information Center

    Bernstein, Anita

    1996-01-01

    A seminar at Chicago-Kent College of Law (Illinois) that reviews six first-year law school courses by focusing on feminist issues in course content and structure is described. The seminar functions as both a review and a shift in perspective. Courses revisited include civil procedure, contracts, criminal law, justice and the legal system,…

  20. Corona discharges and their effect on lightning attachment revisited: Upward leader initiation and downward leader interception

    NASA Astrophysics Data System (ADS)

    Becerra, Marley

    2014-11-01

    Previous studies have suggested the possibility of using glow corona discharges to control the frequency of lightning flashes to grounded objects. In order to revisit the theoretical basis of this proposal, the self-consistent leader inception and propagation model - SLIM - is used together with a two-dimensional glow corona drift model. The analysis is performed to quantify the effect of glow corona generated at the tip of ground-based objects on the initiation and propagation of upward positive connecting leaders under the influence of downward lightning leaders. It is found that the presence of glow corona does not influence the performance of Franklin lightning rods shorter than 15 m, while it slightly reduces the lateral distance of rods up to 60 m tall by a maximum of 10%. Furthermore, the results indicate that it is not possible to suppress the initiation of upward connecting leaders by means of glow corona. It is found instead that unconventional lightning protection systems based on the generation of glow corona attract downward lightning flashes in a similar way as a standard lightning rod with the same height.

  1. A Multi-Level Model of Moral Functioning Revisited

    ERIC Educational Resources Information Center

    Reed, Don Collins

    2009-01-01

    The model of moral functioning scaffolded in the 2008 "JME" Special Issue is here revisited in response to three papers criticising that volume. As guest editor of that Special Issue I have formulated the main body of this response, concerning the dynamic systems approach to moral development, the problem of moral relativism and the role of…

  2. Literary Origins of the Term "School Psychologist" Revisited

    ERIC Educational Resources Information Center

    Fagan, Thomas K.

    2005-01-01

    Previous research on the literary origins of the term "school psychologist" is revisited, and conclusions are revised in light of new evidence. It appears that the origin of the term in the American literature occurred as early as 1898 in an article by Hugo Munsterberg, predating the usage by Wilhelm Stern in 1911. The early references to the…

  3. Revisiting PC1/3 Mutants: Dominant-Negative Effect of Endoplasmic Reticulum-Retained Mutants.

    PubMed

    Blanco, Elias H; Ramos-Molina, Bruno; Lindberg, Iris

    2015-10-01

    Prohormone convertase 1/3 (PC1/3), encoded by the gene PCSK1, is critical for peptide hormone synthesis. An increasing number of studies have shown that inactivating mutations in PCSK1 are correlated with endocrine pathologies ranging from intestinal dysfunction to morbid obesity, whereas the common nonsynonymous polymorphisms rs6232 (N221D) and rs6234-rs6235 (Q665E-S690T) are highly associated with obesity risk. In this report, we revisited the biochemical and cellular properties of PC1/3 variants in the context of a wild-type PC1/3 background instead of the S357G hypermorph background used for all previous studies. In the wild-type background the PC1/3 N221D variant exhibited 30% lower enzymatic activity in a fluorogenic assay than wild-type PC1/3; this inhibition was greater than that detected in an equivalent experiment using the PC1/3 S357G background. A PC1/3 variant with the linked carboxyl-terminal polymorphisms Q665E-S690T did not show this difference. We also analyzed the biochemical properties of 2 PC1/3 mutants, G209R and G593R, which are retained in the endoplasmic reticulum (ER), and studied their effects on wild-type PC1/3. The expression of ER-retained mutants induced ER stress markers and also resulted in dominant-negative blockade of wild-type PC1/3 prodomain cleavage and decreased expression of wild-type PC1/3, suggesting facilitation of the entry of wild-type protein to a degradative proteasomal pathway. Dominant-negative effects of PC1/3 mutations on the expression and maturation of wild-type protein, with consequential effects on PC1/3 availability, add a new element which must be considered in population and clinical studies of this gene.

  4. Threshold corrections to the bottom quark mass revisited

    DOE PAGES

    Anandakrishnan, Archana; Bryant, B. Charles; Raby, Stuart

    2015-05-19

    Threshold corrections to the bottom quark mass are often estimated under the approximation that tan β enhanced contributions are the most dominant. In this work we revisit this common approximation made to the estimation of the supersymmetric thresh-old corrections to the bottom quark mass. We calculate the full one-loop supersymmetric corrections to the bottom quark mass and survey a large part of the phenomenological MSSM parameter space to study the validity of considering only the tan β enhanced corrections. Our analysis demonstrates that this approximation underestimates the size of the threshold corrections by ~12.5% for most of the considered parametermore » space. We discuss the consequences for fitting the bottom quark mass and for the effective couplings to Higgses. Here, we find that it is important to consider the additional contributions when fitting the bottom quark mass but the modifications to the effective Higgs couplings are typically O(few)% for the majority of the parameter space considered.« less

  5. The random field Blume-Capel model revisited

    NASA Astrophysics Data System (ADS)

    Santos, P. V.; da Costa, F. A.; de Araújo, J. M.

    2018-04-01

    We have revisited the mean-field treatment for the Blume-Capel model under the presence of a discrete random magnetic field as introduced by Kaufman and Kanner (1990). The magnetic field (H) versus temperature (T) phase diagrams for given values of the crystal field D were recovered in accordance to Kaufman and Kanner original work. However, our main goal in the present work was to investigate the distinct structures of the crystal field versus temperature phase diagrams as the random magnetic field is varied because similar models have presented reentrant phenomenon due to randomness. Following previous works we have classified the distinct phase diagrams according to five different topologies. The topological structure of the phase diagrams is maintained for both H - T and D - T cases. Although the phase diagrams exhibit a richness of multicritical phenomena we did not found any reentrant effect as have been seen in similar models.

  6. Facilitating Grade Acceleration: Revisiting the Wisdom of John Feldhusen

    ERIC Educational Resources Information Center

    Culross, Rita R.; Jolly, Jennifer L.; Winkler, Daniel

    2013-01-01

    This article revisits the 1986 Feldhusen, Proctor, and Black recommendations on grade skipping. These recommendations originally appeared as 12 guidelines. In this article, the guidelines are grouped into three general categories: how to screen accelerant candidates, how to engage with the adults in the acceleration process (e.g., teachers,…

  7. Threshold Concepts and Student Engagement: Revisiting Pedagogical Content Knowledge

    ERIC Educational Resources Information Center

    Zepke, Nick

    2013-01-01

    This article revisits the notion that to facilitate quality learning requires teachers in higher education to have pedagogical content knowledge. It constructs pedagogical content knowledge as a teaching and learning space that brings content and pedagogy together. On the content knowledge side, it suggests that threshold concepts, akin to a…

  8. Revisiting Jack Goody to Rethink Determinisms in Literacy Studies

    ERIC Educational Resources Information Center

    Collin, Ross

    2013-01-01

    This article revisits Goody's arguments about literacy's influence on social arrangements, culture, cognition, economics, and other domains of existence. Whereas some of his arguments tend toward technological determinism (i.e., literacy causes change in the world), other of his arguments construe literacy as a force that shapes and is shaped by…

  9. A Cooperative Search and Coverage Algorithm with Controllable Revisit and Connectivity Maintenance for Multiple Unmanned Aerial Vehicles.

    PubMed

    Liu, Zhong; Gao, Xiaoguang; Fu, Xiaowei

    2018-05-08

    In this paper, we mainly study a cooperative search and coverage algorithm for a given bounded rectangle region, which contains several unknown stationary targets, by a team of unmanned aerial vehicles (UAVs) with non-ideal sensors and limited communication ranges. Our goal is to minimize the search time, while gathering more information about the environment and finding more targets. For this purpose, a novel cooperative search and coverage algorithm with controllable revisit mechanism is presented. Firstly, as the representation of the environment, the cognitive maps that included the target probability map (TPM), the uncertain map (UM), and the digital pheromone map (DPM) are constituted. We also design a distributed update and fusion scheme for the cognitive map. This update and fusion scheme can guarantee that each one of the cognitive maps converges to the same one, which reflects the targets’ true existence or absence in each cell of the search region. Secondly, we develop a controllable revisit mechanism based on the DPM. This mechanism can concentrate the UAVs to revisit sub-areas that have a large target probability or high uncertainty. Thirdly, in the frame of distributed receding horizon optimizing, a path planning algorithm for the multi-UAVs cooperative search and coverage is designed. In the path planning algorithm, the movement of the UAVs is restricted by the potential fields to meet the requirements of avoiding collision and maintaining connectivity constraints. Moreover, using the minimum spanning tree (MST) topology optimization strategy, we can obtain a tradeoff between the search coverage enhancement and the connectivity maintenance. The feasibility of the proposed algorithm is demonstrated by comparison simulations by way of analyzing the effects of the controllable revisit mechanism and the connectivity maintenance scheme. The Monte Carlo method is employed to validate the influence of the number of UAVs, the sensing radius, the

  10. Cancer cells recovering from damage exhibit mitochondrial restructuring and increased aerobic glycolysis.

    PubMed

    Akakura, Shin; Ostrakhovitch, Elena; Sanokawa-Akakura, Reiko; Tabibzadeh, Siamak

    2014-06-13

    Instead of relying on mitochondrial oxidative phosphorylation, most cancer cells rely heavily on aerobic glycolysis, a phenomenon termed as "the Warburg effect". We considered that this effect is a direct consequence of damage which persists in cancer cells that recover from damage. To this end, we studied glycolysis and rate of cell proliferation in cancer cells that recovered from severe damage. We show that in vitro Damage-Recovered (DR) cells exhibit mitochondrial structural remodeling, display Warburg effect, and show increased in vitro and in vivo proliferation and tolerance to damage. To test whether cancer cells derived from tumor microenvironment can show similar properties, we isolated Damage-Recovered (T(DR)) cells from tumors. We demonstrate that T(DR) cells also show increased aerobic glycolysis and a high proliferation rate. These findings show that Warburg effect and its consequences are induced in cancer cells that survive severe damage. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Investigating Predictors of Visiting, Using, and Revisiting an Online Health-Communication Program: A Longitudinal Study

    PubMed Central

    Crutzen, Rik; De Vries, Hein

    2010-01-01

    Background Online health communication has the potential to reach large audiences, with the additional advantages that it can be operational at all times and that the costs per visitor are low. Furthermore, research shows that Internet-delivered interventions can be effective in changing health behaviors. However, exposure to Internet-delivered health-communication programs is generally low. Research investigating predictors of exposure is needed to be able to effectively disseminate online interventions. Objective In the present study, the authors used a longitudinal design with the aim of identifying demographic, psychological, and behavioral predictors of visiting, using, and revisiting an online program promoting physical activity in the general population. Methods A webpage was created providing the public with information about health and healthy behavior. The website included a “physical activity check,” which consisted of a physical activity computer-tailoring expert system where visitors could check whether their physical activity levels were in line with recommendations. Visitors who consented to participate in the present study (n = 489) filled in a questionnaire that assessed demographics, mode of recruitment, current physical activity levels, and health motivation. Immediately after, participants received tailored feedback concerning their current physical activity levels and completed a questionnaire assessing affective and cognitive user experience, attitude toward being sufficiently physically active, and intention to be sufficiently physically active. Three months later, participants received an email inviting them once more to check whether their physical activity level had changed. Results Analyses of visiting showed that more women (67.5%) than men (32.5%) visited the program. With regard to continued use, native Dutch participants (odds ratio [OR] = 2.81, 95% confidence interval [CI] = 1.16-6.81, P = .02) and participants with a strong

  12. Therapeutic targeting of cancer cell metabolism

    PubMed Central

    Hamaker, Max; Sun, Peng; Le, Anne; Gao, Ping

    2012-01-01

    In 1927, Otto Warburg and coworkers reported the increased uptake of glucose and production of lactate by tumors in vivo as compared with normal tissues. This phenomenon, now known as the Warburg effect, was recapitulated in vitro with cancer tissue slices exhibiting excessive lactate production even with adequate oxygen. Warburg's in vivo studies of tumors further suggest that the dependency of tumors in vivo on glucose could be exploited for therapy, because reduction of arterial glucose by half resulted in a four-fold reduction in tumor fermentation. Recent work in cancer metabolism indicates that the Warburg effect or aerobic glycolysis contributes to redox balance and lipid synthesis, but glycolysis is insufficient to sustain a growing and dividing cancer cell. In this regard, glutamine, which contributes its carbons to the tricarboxylic acid (TCA) cycle, has been re-discovered as an essential bioenergetic and anabolic substrate for many cancer cell types. Could alterations in cancer metabolism be exploited for therapy? Here, we address this question by reviewing current concepts of normal metabolism and altered metabolism in cancer cells with specific emphasis on molecular targets involved directly in glycolysis or glutamine metabolism. PMID:21301795

  13. Increased Serotonin Signaling Contributes to the Warburg Effect in Pancreatic Tumor Cells Under Metabolic Stress and Promotes Growth of Pancreatic Tumors in Mice.

    PubMed

    Jiang, Shu-Heng; Li, Jun; Dong, Fang-Yuan; Yang, Jian-Yu; Liu, De-Jun; Yang, Xiao-Mei; Wang, Ya-Hui; Yang, Min-Wei; Fu, Xue-Liang; Zhang, Xiao-Xin; Li, Qing; Pang, Xiu-Feng; Huo, Yan-Miao; Li, Jiao; Zhang, Jun-Feng; Lee, Ho-Young; Lee, Su-Jae; Qin, Wen-Xin; Gu, Jian-Ren; Sun, Yong-Wei; Zhang, Zhi-Gang

    2017-07-01

    of 5-HT to be increased in human PDAC tissues compared with non-tumor pancreatic tissues, and PDAC cell lines compared with non-transformed pancreatic cells. Incubation of PDAC cell lines with 5-HT increased proliferation and prevented apoptosis. Agonists of HTR2B, but not other 5-HT receptors, promoted proliferation and prevented apoptosis of PDAC cells. Knockdown of HTR2B in PDAC cells, or incubation of cells with HTR2B inhibitors, reduced their growth as xenograft tumors in mice. We observed a correlation between 5-HT and glycolytic flux in PDAC cells; levels of metabolic enzymes involved in glycolysis, the phosphate pentose pathway, and hexosamine biosynthesis pathway increased significantly in PDAC cells following 5-HT stimulation. 5-HT stimulation led to formation of the HTR2B-LYN-p85 complex, which increased PI3K-Akt-mTOR signaling and the Warburg effect by increasing protein levels of MYC and HIF1A. Administration of SB204741 to KPC mice slowed growth and metabolism of established pancreatic tumors and prolonged survival of the mice. Human PDACs have increased levels of 5-HT, and PDAC cells increase expression of its receptor, HTR2B. These increases allow for tumor glycolysis under metabolic stress and promote growth of pancreatic tumors and PDAC xenograft tumors in mice. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  14. Revisiting the Scale-Invariant, Two-Dimensional Linear Regression Method

    ERIC Educational Resources Information Center

    Patzer, A. Beate C.; Bauer, Hans; Chang, Christian; Bolte, Jan; Su¨lzle, Detlev

    2018-01-01

    The scale-invariant way to analyze two-dimensional experimental and theoretical data with statistical errors in both the independent and dependent variables is revisited by using what we call the triangular linear regression method. This is compared to the standard least-squares fit approach by applying it to typical simple sets of example data…

  15. Reconciling Hierarchical and Edge Organizations: 9-11 Revisited

    DTIC Science & Technology

    2014-06-01

    the hierarchical structure, despite claiming to be networked. Hence, our research asks whether these two archetypal forms can be reconciled with one...asks whether these two archetypal forms can be reconciled with one another. By revisiting a case study of the events of September 11th, 2001...organizational form best suited to network-centric operations. Drawing on Mintzberg’s (1979) work on organizational archetypes , five classic organizational

  16. Discussion of "Computational Electrocardiography: Revisiting Holter ECG Monitoring".

    PubMed

    Baumgartner, Christian; Caiani, Enrico G; Dickhaus, Hartmut; Kulikowski, Casimir A; Schiecke, Karin; van Bemmel, Jan H; Witte, Herbert

    2016-08-05

    This article is part of a For-Discussion-Section of Methods of Information in Medicine about the paper "Computational Electrocardiography: Revisiting Holter ECG Monitoring" written by Thomas M. Deserno and Nikolaus Marx. It is introduced by an editorial. This article contains the combined commentaries invited to independently comment on the paper of Deserno and Marx. In subsequent issues the discussion can continue through letters to the editor.

  17. Mitochondria in cancer: not just innocent bystanders.

    PubMed

    Frezza, Christian; Gottlieb, Eyal

    2009-02-01

    The first half of the 20th century produced substantial breakthroughs in bioenergetics and mitochondria research. During that time, Otto Warburg observed abnormally high glycolysis and lactate production in oxygenated cancer cells, leading him to suggest that defects in mitochondrial functions are at the heart of malignant cell transformation. Warburg's hypothesis profoundly influenced the present perception of cancer metabolism, positioning what is termed aerobic glycolysis in the mainstream of clinical oncology. While some of his ideas stood the test of time, they also frequently generated misconceptions regarding the biochemical mechanisms of cell transformation. This review examines experimental evidence which supports or refutes the Warburg effect and discusses the possible advantages conferred on cancer cells by 'metabolic transformation'.

  18. Revisiting CMB constraints on warm inflation

    NASA Astrophysics Data System (ADS)

    Arya, Richa; Dasgupta, Arnab; Goswami, Gaurav; Prasad, Jayanti; Rangarajan, Raghavan

    2018-02-01

    We revisit the constraints that Planck 2015 temperature, polarization and lensing data impose on the parameters of warm inflation. To this end, we study warm inflation driven by a single scalar field with a quartic self interaction potential in the weak dissipative regime. We analyse the effect of the parameters of warm inflation, namely, the inflaton self coupling λ and the inflaton dissipation parameter QP on the CMB angular power spectrum. We constrain λ and QP for 50 and 60 number of e-foldings with the full Planck 2015 data (TT, TE, EE + lowP and lensing) by performing a Markov-Chain Monte Carlo analysis using the publicly available code CosmoMC and obtain the joint as well as marginalized distributions of those parameters. We present our results in the form of mean and 68 % confidence limits on the parameters and also highlight the degeneracy between λ and QP in our analysis. From this analysis we show how warm inflation parameters can be well constrained using the Planck 2015 data.

  19. Electromyogenic Artifacts and Electroencephalographic Inferences Revisited

    PubMed Central

    McMenamin, Brenton W.; Shackman, Alexander J.; Greischar, Lawrence L.; Davidson, Richard J.

    2010-01-01

    Recent years have witnessed a renewed interest in using oscillatory brain electrical activity to understand the neural bases of cognition and emotion. Electrical signals originating from pericranial muscles represent a profound threat to the validity of such research. Recently, McMenamin et al (2010) examined whether independent component analysis (ICA) provides a sensitive and specific means of correcting electromyogenic (EMG) artifacts. This report sparked the accompanying commentary (Olbrich, Jödicke, Sander, Himmerich & Hegerl, in press), and here we revisit the question of how EMG can alter inferences drawn from the EEG and what can be done to minimize its pernicious effects. Accordingly, we briefly summarize salient features of the EMG problem and review recent research investigating the utility of ICA for correcting EMG and other artifacts. We then directly address the key concerns articulated by Olbrich and provide a critique of their efforts at validating ICA. We conclude by identifying key areas for future methodological work and offer some practical recommendations for intelligently addressing EMG artifact. PMID:20981275

  20. Educational Administration and the Management of Knowledge: 1980 Revisited

    ERIC Educational Resources Information Center

    Bates, Richard

    2013-01-01

    This paper revisits the thesis of a 1980 paper that suggested a new approach to educational administration based upon the New Sociology of Education. In particular it updates answers to the six key questions asked by that paper: what counts as knowledge; how is what counts as knowledge organised; how is what counts as knowledge transmitted; how is…

  1. Pair Production Constraints on Superluminal Neutrinos Revisited

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Brodsky, Stanley J.; /SLAC; Gardner, Susan

    2012-02-16

    We revisit the pair creation constraint on superluminal neutrinos considered by Cohen and Glashow in order to clarify which types of superluminal models are constrained. We show that a model in which the superluminal neutrino is effectively light-like can evade the Cohen-Glashow constraint. In summary, any model for which the CG pair production process operates is excluded because such timelike neutrinos would not be detected by OPERA or other experiments. However, a superluminal neutrino which is effectively lightlike with fixed p{sup 2} can evade the Cohen-Glashow constraint because of energy-momentum conservation. The coincidence involved in explaining the SN1987A constraint certainlymore » makes such a picture improbable - but it is still intrinsically possible. The lightlike model is appealing in that it does not violate Lorentz symmetry in particle interactions, although one would expect Hughes-Drever tests to turn up a violation eventually. Other evasions of the CG constraints are also possible; perhaps, e.g., the neutrino takes a 'short cut' through extra dimensions or suffers anomalous acceleration in matter. Irrespective of the OPERA result, Lorentz-violating interactions remain possible, and ongoing experimental investigation of such possibilities should continue.« less

  2. Fast dynamics in glass-forming polymers revisited

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Colmenero, J.; Arbe, A.; Mijangos, C.

    1997-12-31

    The so called fast-dynamics of glass-forming systems as observed by time of flight (TOF) neutron scattering techniques is revisited. TOF-results corresponding to several glass-forming polymers with different chemical microstructure and glass-transition temperature are presented together with the theoretical framework proposed by the authors to interpret these results. The main conclusion is that the TOF-data can be explained in terms of quasiharmonic vibrations and the particular short time behavior of the segmental dynamics. The segmental dynamics display in the very short time range (t {approx} 2 ps) a crossover from a simple exponential behavior towards a non-exponential regime. The first exponentialmore » decay, which is controlled by C-C rotational barriers, can be understood as a trace of the behavior of the system in absence of the effects (correlations, cooperativity, memory effects {hor_ellipsis}) which characterize the dense supercooled liquid like state against the normal liquid state. The non-exponential regime at t > 2 ps corresponds to what is usually understood as {alpha} and {beta} relaxations. Some implications of these results are also discussed.« less

  3. The Banning of Chemical Weapons: Tantalus Revisited.

    DTIC Science & Technology

    1983-04-14

    of Chemical and Biological Warfare, by Robert Harris and Jeremy Paxman. Chemical and Engineering News, Vol. 60, No. 47, 22 November 1982, p. 34. 3...1 AD-A127 792 THE BANNING OF CHEMICAL WEAPONS: TANTALUS REVISITED(U) 1/1 IARMY WAR COLL CARLISLE BARRACKS PA F N DUREL 14 APR 8 UNCLASSIFIED F/G 15/2...number) Since the mid-ninetenth century, nations have sought to limit the u.s Of chemical weapons with varying degrees of success. On-going

  4. Kinetic theory of turbulence for parallel propagation revisited: Formal results

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yoon, Peter H., E-mail: yoonp@umd.edu

    2015-08-15

    In a recent paper, Gaelzer et al. [Phys. Plasmas 22, 032310 (2015)] revisited the second-order nonlinear kinetic theory for turbulence propagating in directions parallel/anti-parallel to the ambient magnetic field. The original work was according to Yoon and Fang [Phys. Plasmas 15, 122312 (2008)], but Gaelzer et al. noted that the terms pertaining to discrete-particle effects in Yoon and Fang's theory did not enjoy proper dimensionality. The purpose of Gaelzer et al. was to restore the dimensional consistency associated with such terms. However, Gaelzer et al. was concerned only with linear wave-particle interaction terms. The present paper completes the analysis bymore » considering the dimensional correction to nonlinear wave-particle interaction terms in the wave kinetic equation.« less

  5. Response variance in functional maps: neural darwinism revisited.

    PubMed

    Takahashi, Hirokazu; Yokota, Ryo; Kanzaki, Ryohei

    2013-01-01

    The mechanisms by which functional maps and map plasticity contribute to cortical computation remain controversial. Recent studies have revisited the theory of neural Darwinism to interpret the learning-induced map plasticity and neuronal heterogeneity observed in the cortex. Here, we hypothesize that the Darwinian principle provides a substrate to explain the relationship between neuron heterogeneity and cortical functional maps. We demonstrate in the rat auditory cortex that the degree of response variance is closely correlated with the size of its representational area. Further, we show that the response variance within a given population is altered through training. These results suggest that larger representational areas may help to accommodate heterogeneous populations of neurons. Thus, functional maps and map plasticity are likely to play essential roles in Darwinian computation, serving as effective, but not absolutely necessary, structures to generate diverse response properties within a neural population.

  6. Response Variance in Functional Maps: Neural Darwinism Revisited

    PubMed Central

    Takahashi, Hirokazu; Yokota, Ryo; Kanzaki, Ryohei

    2013-01-01

    The mechanisms by which functional maps and map plasticity contribute to cortical computation remain controversial. Recent studies have revisited the theory of neural Darwinism to interpret the learning-induced map plasticity and neuronal heterogeneity observed in the cortex. Here, we hypothesize that the Darwinian principle provides a substrate to explain the relationship between neuron heterogeneity and cortical functional maps. We demonstrate in the rat auditory cortex that the degree of response variance is closely correlated with the size of its representational area. Further, we show that the response variance within a given population is altered through training. These results suggest that larger representational areas may help to accommodate heterogeneous populations of neurons. Thus, functional maps and map plasticity are likely to play essential roles in Darwinian computation, serving as effective, but not absolutely necessary, structures to generate diverse response properties within a neural population. PMID:23874733

  7. Language Transmission Revisited: Family Type, Linguistic Environment and Language Attitudes

    ERIC Educational Resources Information Center

    Schupbach, Doris

    2009-01-01

    This article revisits factors in intergenerational language maintenance and shift within the family. It does so through an in-depth analysis of what 14 migrants to Australia from German-speaking Switzerland reported in written life stories and subsequent life story interviews. The participants represent four family types and a wide age range, and…

  8. Revisiting the Age-Old Question: Does Money Matter in Education?

    ERIC Educational Resources Information Center

    Baker, Bruce D.

    2012-01-01

    This policy brief revisits the long and storied literature on whether money matters in providing a quality education. Increasingly, political rhetoric adheres to the unfounded certainty that money doesn't make a difference in education, and that reduced funding is unlikely to harm educational quality. Such proclamations have even been used to…

  9. Kinetic theory of turbulence for parallel propagation revisited: Low-to-intermediate frequency regime

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yoon, Peter H., E-mail: yoonp@umd.edu; School of Space Research, Kyung Hee University, Yongin, Gyeonggi 446-701

    2015-09-15

    A previous paper [P. H. Yoon, “Kinetic theory of turbulence for parallel propagation revisited: Formal results,” Phys. Plasmas 22, 082309 (2015)] revisited the second-order nonlinear kinetic theory for turbulence propagating in directions parallel/anti-parallel to the ambient magnetic field, in which the original work according to Yoon and Fang [Phys. Plasmas 15, 122312 (2008)] was refined, following the paper by Gaelzer et al. [Phys. Plasmas 22, 032310 (2015)]. The main finding involved the dimensional correction pertaining to discrete-particle effects in Yoon and Fang's theory. However, the final result was presented in terms of formal linear and nonlinear susceptibility response functions. Inmore » the present paper, the formal equations are explicitly written down for the case of low-to-intermediate frequency regime by making use of approximate forms for the response functions. The resulting equations are sufficiently concrete so that they can readily be solved by numerical means or analyzed by theoretical means. The derived set of equations describe nonlinear interactions of quasi-parallel modes whose frequency range covers the Alfvén wave range to ion-cyclotron mode, but is sufficiently lower than the electron cyclotron mode. The application of the present formalism may range from the nonlinear evolution of whistler anisotropy instability in the high-beta regime, and the nonlinear interaction of electrons with whistler-range turbulence.« less

  10. Revisiting Individual Creativity Assessment: Triangulation in Subjective and Objective Assessment Methods

    ERIC Educational Resources Information Center

    Park, Namgyoo K.; Chun, Monica Youngshin; Lee, Jinju

    2016-01-01

    Compared to the significant development of creativity studies, individual creativity research has not reached a meaningful consensus regarding the most valid and reliable method for assessing individual creativity. This study revisited 2 of the most popular methods for assessing individual creativity: subjective and objective methods. This study…

  11. Neutrino assisted GUT baryogenesis revisited

    NASA Astrophysics Data System (ADS)

    Huang, Wei-Chih; Päs, Heinrich; Zeißner, Sinan

    2018-03-01

    Many grand unified theory (GUT) models conserve the difference between the baryon and lepton number, B -L . These models can create baryon and lepton asymmetries from heavy Higgs or gauge boson decays with B +L ≠0 but with B -L =0 . Since the sphaleron processes violate B +L , such GUT-generated asymmetries will finally be washed out completely, making GUT baryogenesis scenarios incapable of reproducing the observed baryon asymmetry of the Universe. In this work, we revisit the idea to revive GUT baryogenesis, proposed by Fukugita and Yanagida, where right-handed neutrinos erase the lepton asymmetry before the sphaleron processes can significantly wash out the original B +L asymmetry, and in this way one can prevent a total washout of the initial baryon asymmetry. By solving the Boltzmann equations numerically for baryon and lepton asymmetries in a simplified 1 +1 flavor scenario, we can confirm the results of the original work. We further generalize the analysis to a more realistic scenario of three active and two right-handed neutrinos to highlight flavor effects of the right-handed neutrinos. Large regions in the parameter space of the Yukawa coupling and the right-handed neutrino mass featuring successful baryogenesis are identified.

  12. Dynamic stall reattachment revisited

    NASA Astrophysics Data System (ADS)

    Mulleners, Karen

    2017-11-01

    Dynamic stall on pitching airfoils is an important practical problem that affects for example rotary wing aircraft and wind turbines. It also comprises a number of interesting fundamental fluid dynamical phenomena such as unsteady flow separation, vortex formation and shedding, unsteady flow reattachment, and dynamic hysteresis. Following up on past efforts focussing on the separation development, we now revisited the flow reattachment or stall recovery process. Experimental time-resolved velocity field and surface pressure data for a two-dimensional sinusoidally pitching airfoil with various reduced frequencies was analysed using different Eulerian, Lagrangian, and modal decomposition methods. This complementary analysis resulted in the identification of the chain of events that play a role in the flow reattachment process, a detailed description of that role, and characterisation of the individual events by the governing time-scales and flow features.

  13. Revisiting the block method for evaluating thermal conductivities of clay and granite

    USDA-ARS?s Scientific Manuscript database

    Determination of thermal conductivities of porous media using the contact method is revisited and revalidated with consideration of thermal contact resistance. Problems that limit the accuracy of determination of thermal conductivities of porous media are discussed. Thermal conductivities of granite...

  14. Re-Visit to the School Nurse and Adolescents' Medicine Use

    ERIC Educational Resources Information Center

    Borup, Ina K.; Andersen, Anette; Holstein, Bjorn E.

    2011-01-01

    Objective: To examine if students who re-visit the school nurse use medicines differently than other students when exposed to aches and psychological problems. Methods: The study includes all 11-, 13- and 15-year-old students from a random sample of schools in Denmark, response rate 87 per cent, n = 5,205. The data collection followed the…

  15. Changes in composition, ecology and structure of high-mountain vegetation: a re-visitation study over 42 years.

    PubMed

    Evangelista, Alberto; Frate, Ludovico; Carranza, Maria Laura; Attorre, Fabio; Pelino, Giovanni; Stanisci, Angela

    2016-01-27

    High-mountain ecosystems are increasingly threatened by climate change, causing biodiversity loss, habitat degradation and landscape modifications. However, very few detailed studies have focussed on plant biodiversity in the high mountains of the Mediterranean. In this study, we investigated the long-term changes that have occurred in the composition, structure and ecology of high-mountain vegetation in the central Apennines (Majella) over the last 42 years. We performed a re-visitation study, using historical and newly collected vegetation data to explore which ecological and structural features have been the most successful in coping with climatic changes. Vegetation changes were analysed by comparing geo-referenced phytosociological relevés collected in high-mountain habitats (dolines, gentle slopes and ridges) on the Majella massif in 1972 and in 2014. Composition analysis was performed by detrended correspondence analysis, followed by an analysis of similarities for statistical significance assessment and by similarity percentage procedure (SIMPER) for identifying which species indicate temporal changes. Changes in ecological and structural indicators were analysed by a permutational multivariate analysis of variance, followed by a post hoc comparison. Over the last 42 years, clear floristic changes and significant ecological and structural variations occurred. We observed a significant increase in the thermophilic and mesonitrophilic plant species and an increment in the frequencies of hemicryptophytes. This re-visitation study in the Apennines agrees with observations in other alpine ecosystems, providing new insights for a better understanding of the effects of global change on Mediterranean high-mountain biodiversity. The observed changes in floristic composition, the thermophilization process and the shift towards a more nutrient-demanding vegetation are likely attributable to the combined effect of higher temperatures and the increase in soil nutrients

  16. Revisiting High School Conversions: What is Sustained After the Funding Goes?

    ERIC Educational Resources Information Center

    Wallach, Catherine A.

    2009-01-01

    School reformers hope that converting comprehensive high schools into collections of small schools will produce results similar to those realized in freestanding small schools. This comparative case study revisits two "conversions" as they complete the grant funding that supported the reform, in order to explore the extent to which…

  17. Atmospheric Entry Heating of Micrometeorites Revisited: Higher Temperatures and Potential Biases

    NASA Technical Reports Server (NTRS)

    Love, S.; Alexander, C. M. OD.

    2001-01-01

    The atmospheric entry heating model of Love and Brownlee appears to have overestimated evaporation rates by as much as two orders of magnitude. Here we revisit the issue of atmospheric entry heating, using a revised prescription for evaporation rates. Additional information is contained in the original extended abstract.

  18. An analytic algorithm for global coverage of the revisiting orbit and its application to the CFOSAT satellite

    NASA Astrophysics Data System (ADS)

    Xu, Ming; Huang, Li

    2014-08-01

    This paper addresses a new analytic algorithm for global coverage of the revisiting orbit and its application to the mission revisiting the Earth within long periods of time, such as Chinese-French Oceanic Satellite (abbr., CFOSAT). In the first, it is presented that the traditional design methodology of the revisiting orbit for some imaging satellites only on the single (ascending or descending) pass, and the repeating orbit is employed to perform the global coverage within short periods of time. However, the selection of the repeating orbit is essentially to yield the suboptimum from the rare measure of rational numbers of passes per day, which will lose lots of available revisiting orbits. Thus, an innovative design scheme is proposed to check both rational and irrational passes per day to acquire the relationship between the coverage percentage and the altitude. To improve the traditional imaging only on the single pass, the proposed algorithm is mapping every pass into its ascending and descending nodes on the specified latitude circle, and then is accumulating the projected width on the circle by the field of view of the satellite. The ergodic geometry of coverage percentage produced from the algorithm is affecting the final scheme, such as the optimal one owning the largest percentage, and the balance one possessing the less gradient in its vicinity, and is guiding to heuristic design for the station-keeping control strategies. The application of CFOSAT validates the feasibility of the algorithm.

  19. Commentary: Revisiting "Guidelines for Using Technology to Prepare Social Studies Teachers"

    ERIC Educational Resources Information Center

    Hartshorne, Richard; Waring, Scott M.

    2015-01-01

    In Hicks, Lee, Berson, Bolick, and Diem (2014), the authors revisited and revised a series of principles focusing on the preparation of social studies teachers for using digital technologies in the classroom, originally presented in the inaugural issue of "Contemporary Issues in Technology and Teacher Education" (Mason et al., 2000).…

  20. Revisiting adverse effects of cross-hybridization in Affymetrix gene expression data: do they matter for correlation analysis?

    PubMed

    Klebanov, Lev; Chen, Linlin; Yakovlev, Andrei

    2007-11-07

    This work was undertaken in response to a recently published paper by Okoniewski and Miller (BMC Bioinformatics 2006, 7: Article 276). The authors of that paper came to the conclusion that the process of multiple targeting in short oligonucleotide microarrays induces spurious correlations and this effect may deteriorate the inference on correlation coefficients. The design of their study and supporting simulations cast serious doubt upon the validity of this conclusion. The work by Okoniewski and Miller drove us to revisit the issue by means of experimentation with biological data and probabilistic modeling of cross-hybridization effects. We have identified two serious flaws in the study by Okoniewski and Miller: (1) The data used in their paper are not amenable to correlation analysis; (2) The proposed simulation model is inadequate for studying the effects of cross-hybridization. Using two other data sets, we have shown that removing multiply targeted probe sets does not lead to a shift in the histogram of sample correlation coefficients towards smaller values. A more realistic approach to mathematical modeling of cross-hybridization demonstrates that this process is by far more complex than the simplistic model considered by the authors. A diversity of correlation effects (such as the induction of positive or negative correlations) caused by cross-hybridization can be expected in theory but there are natural limitations on the ability to provide quantitative insights into such effects due to the fact that they are not directly observable. The proposed stochastic model is instrumental in studying general regularities in hybridization interaction between probe sets in microarray data. As the problem stands now, there is no compelling reason to believe that multiple targeting causes a large-scale effect on the correlation structure of Affymetrix gene expression data. Our analysis suggests that the observed long-range correlations in microarray data are of a

  1. Revisiting reflexology: Concept, evidence, current practice, and practitioner training.

    PubMed

    Embong, Nurul Haswani; Soh, Yee Chang; Ming, Long Chiau; Wong, Tin Wui

    2015-10-01

    Reflexology is basically a study of how one part of the human body relates to another part of the body. Reflexology practitioners rely on the reflexes map of the feet and hands to all the internal organs and other human body parts. They believe that by applying the appropriate pressure and massage certain spots on the feet and hands, all other body parts could be energized and rejuvenated. This review aimed to revisit the concept of reflexology and examine its effectiveness, practices, and the training for reflexology practitioners. PubMed, SCOPUS, Google Scholar, and SpringerLink databases were utilized to search the following medical subject headings or keywords: foot massage, reflexology, foot reflexotherapy, reflexological treatment, and zone therapy. The articles published for the last 10 years were included. Previous systematic reviews failed to show concrete evidence for any specific effect of reflexology in any conditions. Due to its non-invasive, non-pharmacological complementary nature, reflexology is widely accepted and anecdotal evidence of positive effect reflexology in a variety of health conditions are available. Adequate training for practitioners is necessary to ensure the consistency of service provided.

  2. Revisiting reflexology: Concept, evidence, current practice, and practitioner training

    PubMed Central

    Embong, Nurul Haswani; Soh, Yee Chang; Ming, Long Chiau; Wong, Tin Wui

    2015-01-01

    Reflexology is basically a study of how one part of the human body relates to another part of the body. Reflexology practitioners rely on the reflexes map of the feet and hands to all the internal organs and other human body parts. They believe that by applying the appropriate pressure and massage certain spots on the feet and hands, all other body parts could be energized and rejuvenated. This review aimed to revisit the concept of reflexology and examine its effectiveness, practices, and the training for reflexology practitioners. PubMed, SCOPUS, Google Scholar, and SpringerLink databases were utilized to search the following medical subject headings or keywords: foot massage, reflexology, foot reflexotherapy, reflexological treatment, and zone therapy. The articles published for the last 10 years were included. Previous systematic reviews failed to show concrete evidence for any specific effect of reflexology in any conditions. Due to its non-invasive, non-pharmacological complementary nature, reflexology is widely accepted and anecdotal evidence of positive effect reflexology in a variety of health conditions are available. Adequate training for practitioners is necessary to ensure the consistency of service provided. PMID:26587391

  3. Cost-effective management of women with minor cervical lesions: Revisiting the application of HPV DNA testing.

    PubMed

    Pedersen, Kine; Burger, Emily A; Sy, Stephen; Kristiansen, Ivar S; Kim, Jane J

    2016-11-01

    Lack of consensus in management guidelines for women with minor cervical lesions, coupled with novel screening approaches, such as human papillomavirus (HPV) genotyping, necessitate revisiting prevention policies. We evaluated the cost-effectiveness and resource trade-offs of alternative triage strategies to inform cervical cancer prevention in Norway. We used a decision-analytic model to compare the lifetime health and economic consequences associated with ten novel candidate approaches to triage women with minor cervical lesions. Candidate strategies varied by: 1) the triage test(s): HPV testing in combination with cytology, HPV testing alone with or without genotyping for HPV-16 and -18, and immediate colposcopy, and 2) the length of time between index and triage testing (i.e., 6, 12 or 18months). Model outcomes included quality-adjusted life-years (QALYs), lifetime societal costs, and resource use (e.g., colposcopy referrals). The current Norwegian guidelines were less effective and more costly than candidate strategies. Given a commonly-cited willingness-to-pay threshold in Norway of $100,000 per QALY gained, the preferred strategy involved HPV genotyping with immediate colposcopy referral for HPV-16 or -18 positive and repeat HPV testing at 12months for non-HPV-16 or -18 positive ($78,010 per QALY gained). Differences in health benefits among candidate strategies were small, while resource use varied substantially. More effective strategies required a moderate increase in colposcopy referrals (e.g., a 9% increase for the preferred strategy) compared with current levels. New applications of HPV testing may improve management of women with minor cervical lesions, yet are accompanied by a trade-off of increased follow-up procedures. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Cost-effective management of women with minor cervical lesions: Revisiting the application of HPV DNA testing

    PubMed Central

    Pedersen, Kine; Burger, Emily A.; Sy, Stephen; Kristiansen, Ivar S.; Kim, Jane J.

    2016-01-01

    Background Lack of consensus in management guidelines for women with minor cervical lesions, coupled with novel screening approaches, such as human papillomavirus (HPV) genotyping, necessitate revisiting prevention policies. We evaluated the cost-effectiveness and resource trade-offs of alternative triage strategies to inform cervical cancer prevention in Norway. Methods We used a decision-analytic model to compare the lifetime health and economic consequences associated with ten novel candidate approaches to triage women with minor cervical lesions. Candidate strategies varied by: 1) the triage test(s): HPV testing in combination with cytology, HPV testing alone with or without genotyping for HPV-16 and-18, and immediate colposcopy, and 2) the length of time between index and triage testing (i.e., 6, 12 or 18 months). Model outcomes included quality-adjusted life-years (QALYs), lifetime societal costs, and resource use (e.g., colposcopy referrals). Results The current Norwegian guidelines were less effective and more costly than candidate strategies. Given a commonly-cited willingness-to-pay threshold in Norway of $100,000 per QALY gained, the preferred strategy involved HPV genotyping with immediate colposcopy referral for HPV-16 or -18 positive and repeat HPV testing at 12 months for non-HPV-16 or -18 positive ($78,010 per QALY gained). Differences in health benefits among candidate strategies were small, while resource use varied substantially. More effective strategies required a moderate increase in colposcopy referrals (e.g., a 9% increase for the preferred strategy) compared with current levels. Conclusion New applications of HPV testing may improve management for women with minor cervical lesions, yet are accompanied by a trade-off of increased follow-up procedures. PMID:27542966

  5. Taï chimpanzees anticipate revisiting high-valued fruit trees from further distances.

    PubMed

    Ban, Simone D; Boesch, Christophe; Janmaat, Karline R L

    2014-11-01

    The use of spatio-temporal memory has been argued to increase food-finding efficiency in rainforest primates. However, the exact content of this memory is poorly known to date. This study investigated what specific information from previous feeding visits chimpanzees (Pan troglodytes verus), in Taï National Park, Côte d'Ivoire, take into account when they revisit the same feeding trees. By following five adult females for many consecutive days, we tested from what distance the females directed their travels towards previously visited feeding trees and how previous feeding experiences and fruit tree properties influenced this distance. To exclude the influence of sensory cues, the females' approach distance was measured from their last significant change in travel direction until the moment they entered the tree's maximum detection field. We found that chimpanzees travelled longer distances to trees at which they had previously made food grunts and had rejected fewer fruits compared to other trees. In addition, the results suggest that the chimpanzees were able to anticipate the amount of fruit that they would find in the trees. Overall, our findings are consistent with the hypothesis that chimpanzees act upon a retrieved memory of their last feeding experiences long before they revisit feeding trees, which would indicate a daily use of long-term prospective memory. Further, the results are consistent with the possibility that positive emotional experiences help to trigger prospective memory retrieval in forest areas that are further away and have fewer cues associated with revisited feeding trees.

  6. Warburg phenotype in renal cell carcinoma: high expression of glucose-transporter 1 (GLUT-1) correlates with low CD8(+) T-cell infiltration in the tumor.

    PubMed

    Singer, Katrin; Kastenberger, Michael; Gottfried, Eva; Hammerschmied, Christine G; Büttner, Maike; Aigner, Michael; Seliger, Barbara; Walter, Bernhard; Schlösser, Hans; Hartmann, Arndt; Andreesen, Reinhard; Mackensen, Andreas; Kreutz, Marina

    2011-05-01

    Many tumor cells are characterized by a dysregulated glucose metabolism associated with increased glycolysis in the presence of oxygen ("Warburg Effect"). Here, we analyzed for the first time a possible link between glucose metabolism and immune cell infiltration in renal cell carcinoma (RCC). RCC specimens revealed a highly significant increase in the expression of lactate dehydrogenase A (LDHA) and glucose-transporter 1 (GLUT-1) compared to the corresponding normal kidney tissue on mRNA level. Accordingly, tumor cell lines of different origin such as RCC, melanoma and hepatocellular carcinoma strongly expressed LDHA and GLUT-1 compared to their nonmalignant counterparts. In line with this finding, tumor cells secreted high amounts of lactate. High expression of GLUT-1 and LDH5, a tetramer of 4 LDHA subunits, was confirmed by tissue microarray analysis of 249 RCC specimens. Overall, 55/79 (69.6%) and 46/71 (64.7%) cases of clear cell carcinoma showed a constitutive, but heterogeneous expression of GLUT-1 and LDH5, respectively. The number of CD3(+), CD8(+) and FOXP3(+) T cells was significantly elevated in RCC lesions compared to normal kidney epithelium, but effector molecules such as granzyme B and perforin were decreased in tumor infiltrating T cells. Of interest, further analysis revealed an inverse correlation between GLUT-1 expression and the number of CD8(+) T cells in RCC lesions. Together, our data suggest that an accelerated glucose metabolism in RCC tissue is associated with a low infiltration of CD8(+) effector T cells. Targeting the glucose metabolism may represent an interesting tool to improve the efficacy of specific immunotherapeutic approaches in RCC. Copyright © 2010 UICC.

  7. Orthopaedic service lines-revisited.

    PubMed

    Patterson, Cheryl

    2008-01-01

    This article revisits the application of orthopaedic service lines from early introduction and growth of this organizational approach in the 1980s, through the 1990s, and into the current decade. The author has experienced and worked in various service-line structures through these three decades, as well as the preservice-line era of 1970s orthopaedics. Past lessons learned during earlier phases and then current trends and analysis by industry experts are summarized briefly, with indication given of the future for service lines. Variation versus consistency of certain elements in service-line definitions and in operational models is discussed. Main components of service-line structures and typical processes are described briefly, along with a more detailed section on the service-line director/manager role. Current knowledge contained here will help guide the reader to more "out-of-the-box" thinking toward comprehensive orthopaedic centers of excellence.

  8. Rigor Revisited: Scaffolding College Student Learning by Incorporating Their Lived Experiences

    ERIC Educational Resources Information Center

    Castillo-Montoya, Milagros

    2018-01-01

    This chapter explores how students' lived experiences contribute to the rigor of their thinking. Insights from research indicate faculty can enhance rigor by accounting for the many ways it may surface in the classroom. However, to see this type of rigor, we must revisit the way we conceptualize it for higher education.

  9. Revisit, Subsequent Hospitalization, Recurrent Fall, and Death Within 6 Months After a Fall Among Elderly Emergency Department Patients.

    PubMed

    Sri-On, Jiraporn; Tirrell, Gregory P; Bean, Jonathan F; Lipsitz, Lewis A; Liu, Shan W

    2017-10-01

    We seek to describe the risk during 6 months and specific risk factors for recurrent falls, emergency department (ED) revisits, subsequent hospitalizations, and death within 6 months after a fall-related ED presentation. This was a secondary analysis of a retrospective cohort of elderly fall patients who presented to the ED from one urban teaching hospital. We included patients aged 65 years and older who had an ED fall visit in 2012. We examined the frequency and risk factors of adverse events (composite of recurrent falls, ED revisits, subsequent hospitalization, and death, selected a priori) at 6 months. Our study included 350 older adults. Adverse events steadily increased, from 7.7% at 7 days, 21.4% at 30 days, and 50.3% at 6 months. Within 6 months, 22.6% of patients had at least one recurrent fall, 42.6% revisited the ED, 31.1% had subsequent hospitalizations, and 2.6% died. In multivariable logistic regression analysis, psychological or sedative drug use predicted recurrent falls, ED revisits, subsequent hospitalizations, and adverse events. More than half of fall patients had an adverse event within 6 months of presenting to the ED after a fall. The risk during 6 months of these adverse events increased with psychological or sedative drug use. Larger future studies should confirm this association and investigate methods to minimize recurrent falls through management of such medications. Copyright © 2017 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

  10. DNA as Genetic Material: Revisiting Classic Experiments through a Simple, Practical Class

    ERIC Educational Resources Information Center

    Malago, Wilson, Jr.; Soares-Costa, Andrea; Henrique-Silva, Flavio

    2009-01-01

    In 1928, Frederick Griffith demonstrated a transmission process of genetic information by transforming "Pneumococcus". In 1944, Avery et al. demonstrated that Griffith's transforming principle was DNA. We revisited these classic experiments in a practical class for undergraduate students. Both experiments were reproduced in simple, adapted forms.…

  11. Commentary on "Distributed Revisiting: An Analytic for Retention of Coherent Science Learning"

    ERIC Educational Resources Information Center

    Hewitt, Jim

    2015-01-01

    The article, "Distributed Revisiting: An Analytic for Retention of Coherent Science Learning" is an interesting study that operates at the intersection of learning theory and learning analytics. The authors observe that the relationship between learning theory and research in the learning analytics field is constrained by several…

  12. Where Are They Now? LJ Revisits a Decade's Worth of Graduates

    ERIC Educational Resources Information Center

    Kuzyk, Raya

    2006-01-01

    In this article, the author revisits 11 graduates who were profiled as part of LJ's annual Placements & Salaries issue. Armed with a library science degree from various institutions, they had just secured jobs in librarianship and were off to a good start forging their careers. Since then, they have worked at elementary school, college, and…

  13. Nuclear factor E2-related factor-2 has a differential impact on MCT1 and MCT4 lactate carrier expression in colonic epithelial cells: a condition favoring metabolic symbiosis between colorectal cancer and stromal cells.

    PubMed

    Diehl, K; Dinges, L-A; Helm, O; Ammar, N; Plundrich, D; Arlt, A; Röcken, C; Sebens, S; Schäfer, H

    2018-01-04

    Malignant tumors, such as colorectal cancer (CRC), are heterogeneous diseases characterized by distinct metabolic phenotypes. These include Warburg- and reverse Warburg phenotypes depending on differential distribution of the lactate carrier proteins monocarboxylate transporter-4 and -1 (MCT4 and MCT1). Here, we elucidated the role of the antioxidant transcription factor nuclear factor E2-related factor-2 (Nrf2) as the key regulator of cellular adaptation to inflammatory/environmental stress in shaping the metabolism toward a reverse Warburg phenotype in malignant and premalignant colonic epithelial cells. Immunohistochemistry of human CRC tissues revealed reciprocal expression of MCT1 and MCT4 in carcinoma and stroma cells, respectively, accompanied by strong epithelial Nrf2 activation. In colorectal tissue from inflammatory bowel disease patients, MCT1 and Nrf2 were coexpressed as well, relating to CD68+inflammatory infiltrates. Indirect coculture of human NCM460 colonocytes with M1- but not M2 macrophages induces MCT1 as well as G6PD, LDHB and TALDO expression, whereas MCT4 expression was decreased. Nrf2 knockdown or reactive oxygen species (ROS) scavenging blocked these coculture effects in NCM460 cells. Likewise, Nrf2 knockdown inhibited similar effects of tBHQ-mediated Nrf2 activation on NCM460 and HCT15 CRC cells. M1 coculture or Nrf2 activation/overexpression greatly altered the lactate uptake but not glucose uptake and mitochondrial activities in these cells, reflecting the reverse Warburg phenotype. Depending on MCT1-mediated lactate uptake, Nrf2 conferred protection from TRAIL-induced apoptosis in NCM460 and HCT15 cells. Moreover, metabolism-dependent clonal growth of HCT15 cells was induced by Nrf2-dependent activation of MCT1-driven lactate exchange. These findings indicate that Nrf2 has an impact on the metabolism already in premalignant colonic epithelial cells exposed to inflammatory M1 macrophages, an effect accompanied by growth and survival

  14. Transformation of Learning in Education and Training: Key Qualifications Revisited. CEDEFOP Reference Series.

    ERIC Educational Resources Information Center

    Kamarainen, Pekka, Ed.; Attwell, Graham, Ed.; Brown, Alan, Ed.

    This book contains 15 papers examining European approaches to the theme of key qualifications. The following papers are included: "Key Qualifications Revisited: An Introduction" (Pekka Kamarainen); "Exploring Key Qualifications: Context, Theory, and Practice in Europe" (Pekka Kamarainen); "Rethinking Key Qualifications:…

  15. Rotation and anisotropy of galaxies revisited

    NASA Astrophysics Data System (ADS)

    Binney, James

    2005-11-01

    The use of the tensor virial theorem (TVT) as a diagnostic of anisotropic velocity distributions in galaxies is revisited. The TVT provides a rigorous global link between velocity anisotropy, rotation and shape, but the quantities appearing in it are not easily estimated observationally. Traditionally, use has been made of a centrally averaged velocity dispersion and the peak rotation velocity. Although this procedure cannot be rigorously justified, tests on model galaxies show that it works surprisingly well. With the advent of integral-field spectroscopy it is now possible to establish a rigorous connection between the TVT and observations. The TVT is reformulated in terms of sky-averages, and the new formulation is tested on model galaxies.

  16. Revisiting Learning in Higher Education--Framing Notions Redefined through an Ecological Perspective

    ERIC Educational Resources Information Center

    Damsa, Crina; Jornet, Alfredo

    2016-01-01

    This article employs an ecological perspective as a means of revisiting the notion of learning, with a particular focus on learning in higher education. Learning is reconceptualised as a process entailing mutually constitutive, epistemic, social and affective relations in which knowledge, identity and agency become collective achievements of whole…

  17. The Concept of Experience by John Dewey Revisited: Conceiving, Feeling and "Enliving"

    ERIC Educational Resources Information Center

    Hohr, Hansjorg

    2013-01-01

    "The concept of experience by John Dewey revisited: conceiving, feeling and 'enliving'." Dewey takes a few steps towards a differentiation of the concept of experience, such as the distinction between primary and secondary experience, or between ordinary (partial, raw, primitive) experience and complete, aesthetic experience. However, he does not…

  18. Teacher Communication Concerns Revisited: Calling into Question the Gnawing Pull towards Equilibrium

    ERIC Educational Resources Information Center

    Dannels, Deanna P.

    2015-01-01

    This study revisits the long-standing teacher communication concerns framework originating over three decades ago. Analysis of 10 years of contemporary GTA teacher communication concerns reveals a typology of 10 concerns, which taken together construct teaching as a process of negotiating relationships, managing identities, and focusing attention.…

  19. Globalisation, the Singapore Developmental State and Education Policy: A Thesis Revisited

    ERIC Educational Resources Information Center

    Gopinathan, S.

    2007-01-01

    In this article I revisit and extend arguments made in 1996 and 1997 about the relationship between globalisation, the state and education policy. I was particularly concerned then to see how a small but strong state, Singapore, was responding in the education arena to globalisation. I also wished to draw attention to the literature on the high…

  20. Log-periodic crashes revisited

    NASA Astrophysics Data System (ADS)

    Matsushita, Raul; da Silva, Sergio; Figueiredo, Annibal; Gleria, Iram

    2006-05-01

    We revisit the finding that crashes can be deterministic and governed by log-periodic formulas [D. Sornette, A. Johansen, Significance of log-periodic precursors to financial crashes, Quant. Finance 1 (2001) 452-471; D. Sornette, W.X. Zhou, The US 2000-2002 market descent: how much longer and deeper?, Quant. Finance 2 (2002) 468-481]. One- and two-harmonic equations are usually employed to fit daily data during bubble episodes. But a three-harmonics has been shown to fit anti-bubbles [A. Johansen, D. Sornette, Financial “anti-bubbles”: log-periodicity in gold and Nikkei collapses, Int. J. Mod. Phys. C 10 (1999) 563-575]. Here we show that the three-harmonic formula can work for bubble episodes as well as anti-bubbles. This is illustrated with daily data from the Brazilian real-US dollar exchange rate. And we also show that the three-harmonics can fit an intraday data set from that foreign exchange rate.

  1. My First CMC Article Revisited: A Window on Spanish L2 Interlanguage

    ERIC Educational Resources Information Center

    Blake, Robert

    2016-01-01

    The computer-assisted language learning (CALL) field seems to change overnight with new technological affordances. Blake revisits his 2000 "LLT" article on computer-mediation communication (CMC) in order to reflect on how the field has examined this topic over the past decade or so. While the Interaction Hypothesis continues to guide…

  2. Parentocracy Revisited: Still a Relevant Concept for Understanding Middle Class Educational Advantage?

    ERIC Educational Resources Information Center

    Barrett DeWiele, Corinne E.; Edgerton, Jason D.

    2016-01-01

    In this paper, we revisit Brown's ("Br J Soc Educ" 14: 65-85, 1990) concept of "parentocracy" which has been informatively applied in educational research in a number of studies in various countries internationally--but almost none in North America. We provide an expanded conceptualization of parentocracy and suggest that it…

  3. Sunday School Revisited: An Alternative to Christian Education of the Church Today?

    ERIC Educational Resources Information Center

    Song, Nam Soon

    2013-01-01

    This article attempts to demonstrate similarities between the socioeconomic, cultural, and religious contexts of 18th-century England and 21st-century Canada. Revisiting the Sunday School movement in 18th-century England provides insights for the development of renewed Sunday School models in the current Canadian context of transnational…

  4. 3-Bromopyruvate (3BP) a fast acting, promising, powerful, specific, and effective "small molecule" anti-cancer agent taken from labside to bedside: introduction to a special issue.

    PubMed

    Pedersen, Peter L

    2012-02-01

    Although the "Warburg effect", i.e., elevated glucose metabolism to lactic acid (glycolysis) even in the presence of oxygen, has been recognized as the most common biochemical phenotype of cancer for over 80 years, its biochemical and genetic basis remained unknown for over 50 years. Work focused on elucidating the underlying mechanism(s) of the "Warburg effect" commenced in the author's laboratory in 1969. By 1985 among the novel findings made two related most directly to the basis of the "Warburg effect", the first that the mitochondrial content of tumors exhibiting this phenotype is markedly decreased relative to the tissue of origin, and the second that such mitochondria have markedly elevated amounts of the enzyme hexokinase-2 (HK2) bound to their outer membrane. HK2 is the first of a number of enzymes in cancer cells involved in metabolizing the sugar glucose to lactic acid. At its mitochondrial location HK2 binds at/near the protein VDAC (voltage dependent anion channel), escapes inhibition by its product glucose-6-phosphate, and gains access to mitochondrial produced ATP. As shown by others, it also helps immortalize cancer cells, i.e., prevents cell death. Based on these studies, the author's laboratory commenced experiments to elucidate the gene basis for the overexpression of HK2 in cancer. These studies led to both the discovery of a unique HK2 promoter region markedly activated by both hypoxic conditions and moderately activated by several metabolites (e.g., glucose), Also discovered was the promoter's regulation by epigenetic events (i.e., methylation, demethylation). Finally, the author's laboratory turned to the most important objective. Could they selectively and completely destroy cancerous tumors in animals? This led to the discovery in an experiment conceived, designed, and conducted by Young Ko that the small molecule 3-bromopyruvate (3BP), the subject of this mini-review series, is an incredibly powerful and swift acting anticancer agent

  5. The Safety of Adjuvanted Vaccines Revisited: Vaccine-Induced Narcolepsy.

    PubMed

    Ahmed, S Sohail; Montomoli, Emanuele; Pasini, Franco Laghi; Steinman, Lawrence

    2016-01-01

    Despite the very high benefit-to-risk ratio of vaccines, the fear of negative side effects has discouraged many people from getting vaccinated, resulting in the reemergence of previously controlled diseases such as measles, pertussis and diphtheria. This fear has been amplified more recently by multiple epidemiologic studies that confirmed the link of an AS03-adjuvanted pandemic influenza vaccine (Pandemrix, GlaxoSmithKline Biologicals, Germany) used in Europe during the 2009 H1N1 influenza pandemic [A(H1N1) pdm09] with the development of narcolepsy, a chronic sleep disorder, in children and adolescents. However, public misperceptions of what adjuvants are and why they are used in vaccines has created in some individuals a closed "black box" attitude towards all vaccines. The focus of this review article is to revisit this "black box" using the example of narcolepsy associated with the European AS03-adjuvanted pandemic influenza vaccine.

  6. The Best and the Rest: Revisiting the Norm of Normality of Individual Performance

    ERIC Educational Resources Information Center

    O'Boyle, Ernest, Jr.; Aguinis, Herman

    2012-01-01

    We revisit a long-held assumption in human resource management, organizational behavior, and industrial and organizational psychology that individual performance follows a Gaussian (normal) distribution. We conducted 5 studies involving 198 samples including 633,263 researchers, entertainers, politicians, and amateur and professional athletes.…

  7. Cystic kidneys in fetal Walker-Warburg syndrome with POMT2 mutation: Intrafamilial phenotypic variability in four siblings and review of literature.

    PubMed

    Nabhan, Marwa M; ElKhateeb, Nour; Braun, Daniela A; Eun, Sungho; Saleem, Sahar N; YungGee, Heon; Hildebrandt, Friedhelm; Soliman, Neveen A

    2017-10-01

    Walker-Warburg syndrome (WWS) is a severe form of congenital muscular dystrophy secondary to α-dystroglycanopathy with muscle, brain, and eye abnormalities often leading to death in the first weeks of life. It is transmitted in an autosomal recessive pattern, and has been linked to at least 15 different genes; including protein O-mannosyltransferase 1 (POMT1), protein O-mannosyltransferase 2 (POMT2), protein O-mannose beta-1,2-N acetylglucosaminyltransferase (POMGNT1), fukutin (FKTN), isoprenoid synthase domain-containing protein (ISPD), and other genes. We report on a consanguineous family with four consecutive siblings affected by this condition with lethal outcome in three (still birth), and termination of the fourth pregnancy based on antenatal MRI identification of brain and kidney anomalies that heralded proper and deep clinical phenotyping. The diagnosis of WWS was suggested based on the unique collective phenotype comprising brain anomalies in the form of lissencephaly, subcortical/subependymal heterotopia, and cerebellar hypoplasia shared by all four siblings; microphthalmia in one sibling; and large cystic kidneys in the fetus and another sibling. Other unshared neurological abnormalities included hydrocephalus and Dandy-Walker malformation. Whole exome sequencing of the fetus revealed a highly conserved missense mutation in POMT2 that is known to cause WWS with brain and eye anomalies.In conclusion, the heterogeneous clinical presentation in the four affected conceptions with POMT2 mutation expands the current clinical spectrum of POMT2-associated WWS to include large cystic kidneys; and confirms intra-familial variability in terms of brain, kidney, and eye anomalies. © 2017 Wiley Periodicals, Inc.

  8. The Levy sections theorem revisited

    NASA Astrophysics Data System (ADS)

    Figueiredo, Annibal; Gleria, Iram; Matsushita, Raul; Da Silva, Sergio

    2007-06-01

    This paper revisits the Levy sections theorem. We extend the scope of the theorem to time series and apply it to historical daily returns of selected dollar exchange rates. The elevated kurtosis usually observed in such series is then explained by their volatility patterns. And the duration of exchange rate pegs explains the extra elevated kurtosis in the exchange rates of emerging markets. In the end, our extension of the theorem provides an approach that is simpler than the more common explicit modelling of fat tails and dependence. Our main purpose is to build up a technique based on the sections that allows one to artificially remove the fat tails and dependence present in a data set. By analysing data through the lenses of the Levy sections theorem one can find common patterns in otherwise very different data sets.

  9. "Rapid Revisit" Measurements of Sea Surface Winds Using CYGNSS

    NASA Astrophysics Data System (ADS)

    Park, J.; Johnson, J. T.

    2017-12-01

    The Cyclone Global Navigation Satellite System (CYGNSS) is a space-borne GNSS-R (GNSS-Reflectometry) mission that launched December 15, 2016 for ocean surface wind speed measurements. CYGNSS includes 8 small satellites in the same LEO orbit, so that the mission provides wind speed products having unprecedented coverage both in time and space to study multi-temporal behaviors of oceanic winds. The nature of CYGNSS coverage results in some locations on Earth experiencing multiple wind speed measurements within a short period of time (a "clump" of observations in time resulting in a "rapid revisit" series of measurements). Such observations could seemingly provide indications of regions experiencing rapid changes in wind speeds, and therefore be of scientific utility. Temporally "clumped" properties of CYGNSS measurements are investigated using early CYGNSS L1/L2 measurements, and the results show that clump durations and spacing vary with latitude. For example, the duration of a clump can extend as long as a few hours at higher latitudes, with gaps between clumps ranging from 6 to as high as 12 hours depending on latitude. Examples are provided to indicate the potential of changes within a clump to produce a "rapid revisit" product for detecting convective activity. Also, we investigate detector design for identifying convective activities. Results from analyses using recent CYGNSS L2 winds will be provided in the presentation.

  10. The coordinate coherent states approach revisited

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Miao, Yan-Gang, E-mail: miaoyg@nankai.edu.cn; Zhang, Shao-Jun, E-mail: sjzhang@mail.nankai.edu.cn

    2013-02-15

    We revisit the coordinate coherent states approach through two different quantization procedures in the quantum field theory on the noncommutative Minkowski plane. The first procedure, which is based on the normal commutation relation between an annihilation and creation operators, deduces that a point mass can be described by a Gaussian function instead of the usual Dirac delta function. However, we argue this specific quantization by adopting the canonical one (based on the canonical commutation relation between a field and its conjugate momentum) and show that a point mass should still be described by the Dirac delta function, which implies thatmore » the concept of point particles is still valid when we deal with the noncommutativity by following the coordinate coherent states approach. In order to investigate the dependence on quantization procedures, we apply the two quantization procedures to the Unruh effect and Hawking radiation and find that they give rise to significantly different results. Under the first quantization procedure, the Unruh temperature and Unruh spectrum are not deformed by noncommutativity, but the Hawking temperature is deformed by noncommutativity while the radiation specturm is untack. However, under the second quantization procedure, the Unruh temperature and Hawking temperature are untack but the both spectra are modified by an effective greybody (deformed) factor. - Highlights: Black-Right-Pointing-Pointer Suggest a canonical quantization in the coordinate coherent states approach. Black-Right-Pointing-Pointer Prove the validity of the concept of point particles. Black-Right-Pointing-Pointer Apply the canonical quantization to the Unruh effect and Hawking radiation. Black-Right-Pointing-Pointer Find no deformations in the Unruh temperature and Hawking temperature. Black-Right-Pointing-Pointer Provide the modified spectra of the Unruh effect and Hawking radiation.« less

  11. Orthorhombic Zr2Co11 phase revisited

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Li, X. -Z.; Zhang, W. Y.; Sellmyer, D. J.

    2014-10-01

    The structure of the orthorhombic Zr2Co11 phase was revisited in the present work. Selected-area electron diffraction (SAED) and high-resolution electron microscopy (HREM) techniques were used to investigate the structure. They show the orthorhombic Zr2Co11 phase has a 1-D incommensurate modulated structure. The structure can be approximately described as a B-centered orthorhombic lattice. The lattice parameters of the orthorhombic Zr2Co11 phase have been determined by a tilt series of SAED patterns. A hexagonal network with a modulation wave has been observed in the HREM image and the hexagonal motif is considered as the basic structural unit.

  12. Exciton coupling between enones: Quassinoids revisited.

    PubMed

    Pescitelli, Gennaro; Di Bari, Lorenzo

    2017-09-01

    The electronic circular dichroism (ECD) spectra of two previously reported quassinoids containing a pair of enone chromophores are revisited to gain insight into the consistency and applicability of the exciton chirality method. Our study is based on time-dependent Density Functional Theory calculations, transition and orbital analysis, and numerical exciton coupling calculations. In quassin (1) the enone/enone exciton coupling is quasi-degenerate, yielding strong rotational strengths that account for the observed ECD spectrum in the enone π-π* region. In perforalactone C (2) the nondegenerate coupling produces weak rotational strengths, and the ECD spectrum is dominated by other mechanisms of optical activity. We remark the necessity of a careful application of the nondegenerate exciton coupling method in similar cases. © 2017 Wiley Periodicals, Inc.

  13. New Orleans Revisited and Revised: Recommendations for the Field of Speech Communication.

    ERIC Educational Resources Information Center

    Roever, James E.; And Others

    This collection of four papers is the result of an action caucus held in association with the Speech Communication Association's 1972 convention, focusing on developments in the speech communication field since the 1968 USOE/SAA New Orleans conference (ED 028 164). In the first paper, "New Orleans Revisited but Briefly," James E. Roever summarizes…

  14. Life-history traits and effective population size in species with overlapping generations revisited: the importance of adult mortality.

    PubMed

    Waples, R S

    2016-10-01

    The relationship between life-history traits and the key eco-evolutionary parameters effective population size (Ne) and Ne/N is revisited for iteroparous species with overlapping generations, with a focus on the annual rate of adult mortality (d). Analytical methods based on populations with arbitrarily long adult lifespans are used to evaluate the influence of d on Ne, Ne/N and the factors that determine these parameters: adult abundance (N), generation length (T), age at maturity (α), the ratio of variance to mean reproductive success in one season by individuals of the same age (φ) and lifetime variance in reproductive success of individuals in a cohort (Vk•). Although the resulting estimators of N, T and Vk• are upwardly biased for species with short adult lifespans, the estimate of Ne/N is largely unbiased because biases in T are compensated for by biases in Vk• and N. For the first time, the contrasting effects of T and Vk• on Ne and Ne/N are jointly considered with respect to d and φ. A simple function of d and α based on the assumption of constant vital rates is shown to be a robust predictor (R(2)=0.78) of Ne/N in an empirical data set of life tables for 63 animal and plant species with diverse life histories. Results presented here should provide important context for interpreting the surge of genetically based estimates of Ne that has been fueled by the genomics revolution.

  15. Revisiting the safety of aspartame.

    PubMed

    Choudhary, Arbind Kumar; Pretorius, Etheresia

    2017-09-01

    Aspartame is a synthetic dipeptide artificial sweetener, frequently used in foods, medications, and beverages, notably carbonated and powdered soft drinks. Since 1981, when aspartame was first approved by the US Food and Drug Administration, researchers have debated both its recommended safe dosage (40 mg/kg/d) and its general safety to organ systems. This review examines papers published between 2000 and 2016 on both the safe dosage and higher-than-recommended dosages and presents a concise synthesis of current trends. Data on the safe aspartame dosage are controversial, and the literature suggests there are potential side effects associated with aspartame consumption. Since aspartame consumption is on the rise, the safety of this sweetener should be revisited. Most of the literature available on the safety of aspartame is included in this review. Safety studies are based primarily on animal models, as data from human studies are limited. The existing animal studies and the limited human studies suggest that aspartame and its metabolites, whether consumed in quantities significantly higher than the recommended safe dosage or within recommended safe levels, may disrupt the oxidant/antioxidant balance, induce oxidative stress, and damage cell membrane integrity, potentially affecting a variety of cells and tissues and causing a deregulation of cellular function, ultimately leading to systemic inflammation. © The Author(s) 2017. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. Cancer -- Pathological Breakdown of Coherent Energy States

    NASA Astrophysics Data System (ADS)

    Pokorný, Jiří Pokorný, Jan; Kobilková, Jitka; Jandová, Anna; Vrba, Jan; Vrba, Jan

    The fundamental property of biological systems is a coherent state far from thermodynamic equilibrium excited and sustained by energy supply. Mitochondria in eukaryotic cells produce energy and form conditions for excitation of oscillations in microtubules. Microtubule polar oscillations generate a coherent state far from thermodynamic equilibrium which makes possible cooperation of cells in the tissue. Mitochondrial dysfunction (the Warburg effect) in cancer development breaks down energy of the coherent state far from thermodynamic equilibrium and excludes the afflicted cell from the ordered multicellular tissue system. Cancer lowering of energy and coherence of the state far from thermodynamic equilibrium is the biggest difference from the healthy cells. Cancer treatment should target mitochondrial dysfunction to restore the coherent state far from thermodynamic equilibrium, apoptotic pathway, and subordination of the cell in the tissue. A vast variety of genetic changes and other disturbances in different cancers can result in several triggers of mitochondrial dysfunction. In cancers with the Warburg effect, mitochondrial dysfunction can be treated by inhibition of four isoforms of pyruvate dehydrogenase kinases. Treatment of the reverse Warburg effect cancers would be more complicated. Disturbances of cellular electromagnetic activity by conducting and asbestos fibers present a special problem of treatment.

  17. Instant Video Revisiting for Reflection: Extending the Learning of Children and Teachers.

    ERIC Educational Resources Information Center

    Hong, Seong B.; Broderick, Jane T.

    This article discusses how instant video revisiting (IVR) promotes reflective thinking for both teachers and children. IVR was used as a daily classroom experience with both the children and the teachers throughout one semester in two preschool classrooms with children 2.5 to 5 years old. The teachers used a digital video camera to generate data…

  18. Primaquine revisited six decades after its discovery.

    PubMed

    Vale, Nuno; Moreira, Rui; Gomes, Paula

    2009-03-01

    Primaquine was firstly synthesized in 1946 in the USA, and is the most representative member of the anti-malarial 8-aminoquinolines. Six decades have passed and primaquine is still the only transmission-blocking anti-malarial clinically available, displaying a marked activity against gametocytes of all species of human malaria, including multi-resistant Plasmodium falciparum strains. Primaquine is also effective against all exoerythrocytic forms of the parasite and is used in conjunction with other anti-malarials for the treatment of vivax and ovale malaria. However, primaquine is often associated with serious adverse effects, in consequence of its toxic metabolites. 5-Hydroxyprimaquine or 6-methoxy-8-aminoquinoline has been considered to be directly responsible for complications such as hemolytic anemia. Primaquine toxicity is aggravated in people deficient of 6-glucose phosphate dehydrogenase or glutathione synthetase. Adverse effects are further amplified by the fact that primaquine must be repeatedly administered at high doses, due to its limited oral bioavailability. Over the last two decades, Medicinal Chemists have battled against primaquine's disadvantages, while keeping or even improving its unequalled performance as an anti-malarial. The present text revisits primaquine and its properties on the occasion of its 60th anniversary and aims to give a general overview of what has been the path towards the development of effective and safe primaquine-based anti-malarials. Presently, aablaquine and tafenoquine the two most promising primaquine analogues are already in the final stages of clinical trials against Plasmodium vivax and P. falciparum. Both compounds are a new hope against malaria and other primaquine-sensitive illnesses, such as Pneumocystis Pneumonia or the Chagas disease.

  19. Metabolic reprogramming in glioblastoma: the influence of cancer metabolism on epigenetics and unanswered questions

    PubMed Central

    Agnihotri, Sameer; Zadeh, Gelareh

    2016-01-01

    A defining hallmark of glioblastoma is altered tumor metabolism. The metabolic shift towards aerobic glycolysis with reprogramming of mitochondrial oxidative phosphorylation, regardless of oxygen availability, is a phenomenon known as the Warburg effect. In addition to the Warburg effect, glioblastoma tumor cells also utilize the tricarboxylic acid cycle/oxidative phosphorylation in a different capacity than normal tissue. Altered metabolic enzymes and their metabolites are oncogenic and not simply a product of tumor proliferation. Here we highlight the advantages of why tumor cells, including glioblastoma cells, require metabolic reprogramming and how tumor metabolism can converge on tumor epigenetics and unanswered questions in the field. PMID:26180081

  20. Revisiting and Computing Reaction Coordinates with Directional Milestoning

    PubMed Central

    Kirmizialtin, Serdal; Elber, Ron

    2011-01-01

    The method of Directional Milestoning is revisited. We start from an exact and more general expression and state the conditions and validity of the memory-loss approximation. An algorithm to compute a reaction coordinate from Directional Milestoning data is presented. The reaction coordinate is calculated as a set of discrete jumps between Milestones that maximizes the flux between two stable states. As an application we consider a conformational transition in solvated Adenosine. We compare a long molecular dynamic trajectory with Directional Milestoning and discuss the differences between the maximum flux path and minimum energy coordinates. PMID:21500798

  1. Revisiting the Metaphor of the Island: Challenging "World Culture" from an Island Misunderstood

    ERIC Educational Resources Information Center

    Rappleye, Jeremy

    2015-01-01

    This article revisits the newly "discovered" island that world culture theorists have repeatedly utilised to explain their theoretical stance, conceptual preferences and methodological approach. Yet, it seeks to (re)connect world culture with the real world by replacing their imagined atoll with a real one--the island-nation of Japan. In…

  2. Effects of tooth scaling reminders for dental outpatients.

    PubMed

    Cheng, Chi-Chia J; Li, Chung-Yi; Hu, Yih-Jin; Shen, Hsi-Che; Huang, Shay-Min

    2013-06-01

    We investigated the effect of sending reminders for patients to attend appointments for tooth scaling. A total of 389 outpatients were assigned to three intervention groups (reminders sent by postcard, mobile-phone text message or telephone call) and one control group. Reminders accompanied by short health education messages were sent to patients in each of the intervention groups. The outpatient revisiting behaviour of the patients was monitored. Patients who were reminded to come in for tooth scaling were 2.6 (95% CI 1.3-5.4) to 2.9 (CI 1.1-7.8) times more likely to revisit compared to those who were not reminded. For every one point increase in the patient satisfaction score, patients were 3.8 (CI 1.2-11.6) times more likely to revisit. Patients with a high level of patient satisfaction and who had also received a reminder had the highest return rates (26%). Most patients (89-96%) had good feelings regarding the reminders; 65% of the patients agreed that reminders had enhanced their intention to revisit; 91% of patients hoped to continue to receive reminders concerning broader dental health information. A reminder combined with health education is an effective way of improving preventative dental visiting behaviour.

  3. Enceladus' tidal dissipation revisited

    NASA Astrophysics Data System (ADS)

    Tobie, Gabriel; Behounkova, Marie; Choblet, Gael; Cadek, Ondrej; Soucek, Ondrej

    2016-10-01

    A series of chemical and physical evidence indicates that the intense activity at Enceladus' South Pole is related to a subsurface salty water reservoir underneath the tectonically active ice shell. The detection of a significant libration implies that this water reservoir is global and that the average ice shell thickness is about 20-25km (Thomas et al. 2016). The interpretation of gravity and topography data further predicts large variations in ice shell thickness, resulting in a shell potentially thinner than 5 km in the South Polar Terrain (SPT) (Cadek et al. 2016). Such an ice shell structure requires a very strong heat source in the interior, with a focusing mechanism at the SPT. Thermal diffusion through the ice shell implies that at least 25-30 GW is lost into space by passive diffusion, implying a very efficient dissipation mechanism in Enceladus' interior to maintain such an ocean/ice configuration thermally stable.In order to determine in which conditions such a large dissipation power may be generated, we model the tidal response of Enceladus including variable ice shell thickness. For the rock core, we consider a wide range of rheological parameters representative of water-saturated porous rock materials. We demonstrate that the thinning toward the South Pole leads to a strong increase in heat production in the ice shell, with a optimal thickness obtained between 1.5 and 3 km, depending on the assumed ice viscosity. Our results imply that the heat production in the ice shell within the SPT may be sufficient to counterbalance the heat loss by diffusion and to power eruption activity. However, outside the SPT, a strong dissipation in the porous core is required to counterbalance the diffusive heat loss. We show that about 20 GW can be generated in the core, for an effective viscosity of 1012 Pa.s, which is comparable to the effective viscosity estimated in water-saturated glacial tills on Earth. We will discuss the implications of this revisited tidal

  4. Deja vu: The Unified Command Plan of the Future Revisited

    DTIC Science & Technology

    2011-05-19

    Command Plan of the Future Revisited. 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR( S ) Col( S ) Edward F...Martignetti 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME( S ) AND ADDRESS(ES) Advanced Operational Art... S ) AND ADDRESS(ES) U.S. Army Command and General Staff College 100 Stimson Avenue Fort Leavenworth, KS 66027-2301 10. SPONSOR/MONITOR’S ACRONYM

  5. Distributed Memory Breadth-First Search Revisited: Enabling Bottom-Up Search

    DTIC Science & Technology

    2013-01-03

    Jun. 1972. [2] W. McLendon III, B. Hendrickson, S . J. Plimpton , and L. Rauchwerger, “Finding strongly connected components in distributed graphs,” J...Breadth-First Search Revisited: Enabling Bottom-Up Search 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR( S ) 5d. PROJECT...NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME( S ) AND ADDRESS(ES) University of California at Berkeley,Electrical

  6. Effect of heating strategies on whey protein denaturation--Revisited by liquid chromatography quadrupole time-of-flight mass spectrometry.

    PubMed

    Akkerman, M; Rauh, V M; Christensen, M; Johansen, L B; Hammershøj, M; Larsen, L B

    2016-01-01

    Previous standards in the area of effect of heat treatment processes on milk protein denaturation were based primarily on laboratory-scale analysis and determination of denaturation degrees by, for example, electrophoresis. In this study, whey protein denaturation was revisited by pilot-scale heating strategies and liquid chromatography quadrupole time-of-flight mass spectrometer (LC/MC Q-TOF) analysis. Skim milk was heat treated by the use of 3 heating strategies, namely plate heat exchanger (PHE), tubular heat exchanger (THE), and direct steam injection (DSI), under various heating temperatures (T) and holding times. The effect of heating strategy on the degree of denaturation of β-lactoglobulin and α-lactalbumin was determined using LC/MC Q-TOF of pH 4.5-soluble whey proteins. Furthermore, effect of heating strategy on the rennet-induced coagulation properties was studied by oscillatory rheometry. In addition, rennet-induced coagulation of heat-treated micellar casein concentrate subjected to PHE was studied. For skim milk, the whey protein denaturation increased significantly as T and holding time increased, regardless of heating method. High denaturation degrees were obtained for T >100°C using PHE and THE, whereas DSI resulted in significantly lower denaturation degrees, compared with PHE and THE. Rennet coagulation properties were impaired by increased T and holding time regardless of heating method, although DSI resulted in less impairment compared with PHE and THE. No significant difference was found between THE and PHE for effect on rennet coagulation time, whereas the curd firming rate was significantly larger for THE compared with PHE. Micellar casein concentrate possessed improved rennet coagulation properties compared with skim milk receiving equal heat treatment. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  7. The lisse effect revisited

    USGS Publications Warehouse

    Weeks, E.P.

    2002-01-01

    The Lisse effect is a rarely noted phenomenon occurring when infiltration caused by intense rain seals the surface soil layer to airflow, trapping air in the unsaturated zone. Compression of air by the advancing front results in a pressure increase that produces a water-level rise in an observation well screened below the water table that is several times as large as the distance penetrated by the wetting front. The effect is triggered by intense rains and results in a very rapid water-level rise, followed by a recession lasting a few days. The Lisse effect was first noted and explained by Thal Larsen in 1932 from water-level observations obtained in a shallow well in the village of Lisse, Holland. The original explanation does not account for the increased air pressure pushing up on the bottom of the wetting front. Analysis of the effect of this upward pressure indicates that a negative pressure head at the base of the wetting front, ??f, analogous to that postulated by Green and Ampt (1911) to explain initially rapid infiltration rates into unsaturated soils, is involved in producing the Lisse effect. Analysis of recorded observations of the Lisse effect by Larsen and others indicates that the water-level rise, which typically ranges from 0.10 to 0.55 m, should be only slightly larger than |??f| and that the depth of penetration of the wetting front is no more than several millimeters.

  8. Thymic emigration revisited

    PubMed Central

    McCaughtry, Tom M.; Wilken, Matthew S.; Hogquist, Kristin A.

    2007-01-01

    Conventional αβ T cell precursors undergo positive selection in the thymic cortex. When this is successful, they migrate to the medulla and are exposed to tissue-specific antigens (TSA) for purposes of central tolerance, and they undergo maturation to become functionally responsive T cells. It is commonly understood that thymocytes spend up to 2 wk in the medulla undergoing these final maturation steps before emigrating to peripheral lymphoid tissues. In addition, emigration is thought to occur via a stochastic mechanism whereby some progenitors leave early and others leave late—a so-called “lucky dip” process. However, recent research has revealed that medullary thymocytes are a heterogeneous mix of naive αβ T cell precursors, memory T cells, natural killer T cells, and regulatory T cells. Given this, we revisited the question of how long it takes naive αβ T cell precursors to emigrate. We combined the following three approaches to study this question: BrdU labeling, intrathymic injection of a cellular tag, and RAG2p-GFP reporter mice. We established that, on average, naive αβ T cell precursors emigrate only 4–5 d after becoming single-positive (SP) thymocytes. Furthermore, emigration occurs via a strict “conveyor belt” mechanism, where the oldest thymocytes leave first. PMID:17908937

  9. Understanding and revisiting the most complex perovskite system via atomistic simulations

    NASA Astrophysics Data System (ADS)

    Yang, Yali; Xu, Bin; Xu, Changsong; Ren, Wei; Bellaiche, Laurent

    2018-05-01

    A first-principles-based effective Hamiltonian is developed and used, along with direct ab initio techniques, to investigate finite-temperature properties of the system commonly coined the most complex perovskite, that is NaNbO3. Such simulations successfully reproduce the existence of seven different phases in its phase diagram. The decomposition of the total energy of this effective Hamiltonian into different terms, altogether with the values of the parameters associated with these terms, also allow us to shed some light into puzzling features of such a compound. Examples include revealing the microscopic reasons of why R 3 c is its ground state and why it solely adopts in-phase tiltings at high temperatures versus complex nanotwins for intermediate temperatures. The results of the computations also call for a revisiting of the so-called P ,R , and S states, in the sense that an unexpected and previously overlooked inhomogeneous electrical polarization is numerically found in the P state while complex tiltings associated with the simultaneous condensation of several k points are predicted for the controversial R and S phases.

  10. Making Productive Use of Four Models of School English: A Case Study Revisited

    ERIC Educational Resources Information Center

    Macken-Horarik, Mary

    2014-01-01

    At a time when political leaders and media pundits seek to narrow the English curriculum and reduce its knowledge structure to the "basics," it is helpful to revisit the potential of different approaches to learning in English that have evolved over time. In this paper I reflect on the semantic features of personal growth, cultural…

  11. Finite density two color chiral perturbation theory revisited

    NASA Astrophysics Data System (ADS)

    Adhikari, Prabal; Beleznay, Soma B.; Mannarelli, Massimo

    2018-06-01

    We revisit two-color, two-flavor chiral perturbation theory at finite isospin and baryon density. We investigate the phase diagram obtained varying the isospin and the baryon chemical potentials, focusing on the phase transition occurring when the two chemical potentials are equal and exceed the pion mass (which is degenerate with the diquark mass). In this case, there is a change in the order parameter of the theory that does not lend itself to the standard picture of first order transitions. We explore this phase transition both within a Ginzburg-Landau framework valid in a limited parameter space and then by inspecting the full chiral Lagrangian in all the accessible parameter space. Across the phase transition between the two broken phases the order parameter becomes an SU(2) doublet, with the ground state fixing the expectation value of the sum of the magnitude squared of the pion and the diquark fields. Furthermore, we find that the Lagrangian at equal chemical potentials is invariant under global SU(2) transformations and construct the effective Lagrangian of the three Goldstone degrees of freedom by integrating out the radial fluctuations.

  12. Revisiting "Grutter" and "Gratz" in the Wake of "Fisher": Looking Back to Move Forward

    ERIC Educational Resources Information Center

    Ledesma, Maria C.

    2013-01-01

    This article revisits the University of Michigan's 2003 affirmative action cases, "Grutter v. Bollinger" and "Gratz v. Bollinger." Through the aid of critical textual analysis and critical race theory, the author looks back at the predominant narratives that framed the challenge to, and defense of, race-conscious affirmative…

  13. Rural-Nonrural Disparities in Postsecondary Educational Attainment Revisited

    PubMed Central

    Byun, Soo-yong; Meece, Judith L.; Irvin, Matthew J.

    2013-01-01

    Using data from the National Educational Longitudinal Study, this study revisited rural-nonrural disparities in educational attainment by considering a comprehensive set of factors that constrain and support youth's college enrollment and degree completion. Results showed that rural students were more advantaged in community social resources compared to nonrural students, and these resources were associated with a significant increase in the likelihood of bachelor's degree attainment. Yet results confirmed that rural students lagged behind nonrural students in attaining a bachelor's degree largely due to their lower socioeconomic background. The findings present a more comprehensive picture of the complexity of geographic residence in shaping college enrollment and degree attainment. PMID:24285873

  14. NP-hardness of the cluster minimization problem revisited

    NASA Astrophysics Data System (ADS)

    Adib, Artur B.

    2005-10-01

    The computational complexity of the 'cluster minimization problem' is revisited (Wille and Vennik 1985 J. Phys. A: Math. Gen. 18 L419). It is argued that the original NP-hardness proof does not apply to pairwise potentials of physical interest, such as those that depend on the geometric distance between the particles. A geometric analogue of the original problem is formulated, and a new proof for such potentials is provided by polynomial time transformation from the independent set problem for unit disk graphs. Limitations of this formulation are pointed out, and new subproblems that bear more direct consequences to the numerical study of clusters are suggested.

  15. MacIntyre's Revolutionary Aristotelian Philosophy and His Idea of an Educated Public Revisited

    ERIC Educational Resources Information Center

    Macallister, James

    2016-01-01

    In this article I revisit MacIntyre's lecture on the idea of an educated public. I argue that the full significance of MacIntyre's views on the underlying purposes of universities only become clear when his lecture on the educated public is situated in the context of his wider 'revolutionary Aristotelian' philosophical project. I claim that for…

  16. Dr. Polio: Revisiting FDR's Medical Legacy.

    PubMed

    Dorfman, Robert G; Orkaby, Asher; Desai, Sukumar P

    2018-01-01

    The National Foundation for Infantile Paralysis (NFIP), the March of Dimes, and the Georgia Warm Springs Resort were reflections of Franklin D. Roosevelt's (FDR) complicated and personal relationship with polio. Between 1934 and 1957, significant advances were made in the care of polio survivors, and new and innovative medical fields gained both public attention and funding. The plight of disabled Americans and questions of accessibility also received widespread national attention. The NFIP helped establish a new prototype for grassroots philanthropy and personified FDR's vision for national health insurance. Drawing upon a variety of archival and primary sources, this article aims to revisit Roosevelt's contribution to the medical field. Rather than condone or defend FDR's public persona as a survivor of polio, this article argues that Roosevelt and his affiliated organizations played an important medical role during this period.

  17. Revisiting Evidence for Modularity and Functional Equivalence across Verbal and Spatial Domains in Memory

    ERIC Educational Resources Information Center

    Guerard, Katherine; Tremblay, Sebastien

    2008-01-01

    The authors revisited evidence in favor of modularity and of functional equivalence between the processing of verbal and spatial information in short-term memory. This was done by investigating the patterns of intrusions, omissions, transpositions, and fill-ins in verbal and spatial serial recall and order reconstruction tasks under control,…

  18. Reading Researchers in Search of Common Ground: The Expert Study Revisited. 2nd Edition

    ERIC Educational Resources Information Center

    Flippo, Rona F., Ed.

    2011-01-01

    In "Reading Researchers in Search of Common Ground, Second Edition", Rona F. Flippo revisits her study, in which she set out to find common ground among experts in the much-fragmented field of reading research. The original edition, featuring contributions from participants in the study, commentary from additional distinguished literacy scholars…

  19. The Relationship between Undergraduate Attendance and Performance Revisited: Alignment of Student and Instructor Goals

    ERIC Educational Resources Information Center

    Westerman, James W.; Perez-Batres, Luis A.; Coffey, Betty S.; Pouder, Richard W.

    2011-01-01

    We revisit the relationship between attendance and performance in the undergraduate university setting and apply agency theory in the instructor-student context. Building on agency theory propositions in the educational setting advanced by Smith, Zsidisin, and Adams (2005), we propose that the student and instructor must align goals to promote the…

  20. Structuralism's Relevance in a Post-Structural Era: Re-Visiting Research on Multicultural Curricular Studies

    ERIC Educational Resources Information Center

    Shim, Jenna Min

    2011-01-01

    At the current historical juncture in which differences and inequalities are surfacing greater than ever in the world, societies, and schools, the main goal of this essay is to revisit the aspects of structuralism that can potentially contribute productively to understanding the invisible structures and forces that everyone carries (mostly…

  1. Cancer cells recovering from damage exhibit mitochondrial restructuring and increased aerobic glycolysis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Akakura, Shin; Ostrakhovitch, Elena; Sanokawa-Akakura, Reiko

    2014-06-13

    Highlights: • Some cancer cells recover from severe damage that causes cell death in majority of cells. • Damage-Recovered (DR) cancer cells show reduced mitochondria, mDNA and mitochondrial enzymes. • DR cells show increased aerobic glycolysis, ATP, cell proliferation, and resistance to damage. • DR cells recovered from in vivo damage also show increased glycolysis and proliferation rate. - Abstract: Instead of relying on mitochondrial oxidative phosphorylation, most cancer cells rely heavily on aerobic glycolysis, a phenomenon termed as “the Warburg effect”. We considered that this effect is a direct consequence of damage which persists in cancer cells that recovermore » from damage. To this end, we studied glycolysis and rate of cell proliferation in cancer cells that recovered from severe damage. We show that in vitro Damage-Recovered (DR) cells exhibit mitochondrial structural remodeling, display Warburg effect, and show increased in vitro and in vivo proliferation and tolerance to damage. To test whether cancer cells derived from tumor microenvironment can show similar properties, we isolated Damage-Recovered (T{sup DR}) cells from tumors. We demonstrate that T{sup DR} cells also show increased aerobic glycolysis and a high proliferation rate. These findings show that Warburg effect and its consequences are induced in cancer cells that survive severe damage.« less

  2. Mitochondrial Dysfunction and Disturbed Coherence: Gate to Cancer

    PubMed Central

    Pokorný, Jiří; Pokorný, Jan; Foletti, Alberto; Kobilková, Jitka; Vrba, Jan; Vrba, Jan

    2015-01-01

    Continuous energy supply, a necessary condition for life, excites a state far from thermodynamic equilibrium, in particular coherent electric polar vibrations depending on water ordering in the cell. Disturbances in oxidative metabolism and coherence are a central issue in cancer development. Oxidative metabolism may be impaired by decreased pyruvate transfer to the mitochondrial matrix, either by parasitic consumption and/or mitochondrial dysfunction. This can in turn lead to disturbance in water molecules’ ordering, diminished power, and coherence of the electromagnetic field. In tumors with the Warburg (reverse Warburg) effect, mitochondrial dysfunction affects cancer cells (fibroblasts associated with cancer cells), and the electromagnetic field generated by microtubules in cancer cells has low power (high power due to transport of energy-rich metabolites from fibroblasts), disturbed coherence, and a shifted frequency spectrum according to changed power. Therapeutic strategies restoring mitochondrial function may trigger apoptosis in treated cells; yet, before this step is performed, induction (inhibition) of pyruvate dehydrogenase kinases (phosphatases) may restore the cancer state. In tumor tissues with the reverse Warburg effect, Caveolin-1 levels should be restored and the transport of energy-rich metabolites interrupted to cancer cells. In both cancer phenotypes, achieving permanently reversed mitochondrial dysfunction with metabolic-modulating drugs may be an effective, specific anti-cancer strategy. PMID:26437417

  3. Re-visiting the Endocannabinoid System and Its Therapeutic Potential in Obesity and Associated Diseases.

    PubMed

    Richey, Joyce M; Woolcott, Orison

    2017-09-14

    The purpose of the review was to revisit the possibility of the endocannabinoid system being a therapeutic target for the treatment of obesity by focusing on the peripheral roles in regulating appetite and energy metabolism. Previous studies with the global cannabinoid receptor blocker rimonabant, which has both central and peripheral properties, showed that this drug has beneficial effects on cardiometabolic function but severe adverse psychiatric side effects. Consequently, focus has shifted to peripherally restricted cannabinoid 1 (CB1) receptor blockers as possible therapeutic agents that mitigate or eliminate the untoward effects in the central nervous system. Targeting the endocannabinoid system using novel peripheral CB1 receptor blockers with negligible penetrance across the blood-brain barrier may prove to be effective therapy for obesity and its co-morbidities. Perhaps the future of blockers targeting CB1 receptors will be tissue-specific neutral antagonists (e.g., skeletal muscle specific to treat peripheral insulin resistance, adipocyte-specific to treat fat excess, liver-specific to treat fatty liver and hepatic insulin resistance).

  4. Reflecting Back and Looking Forward: Revisiting "Teaching about Writing, Righting Misconceptions" Five Years on

    ERIC Educational Resources Information Center

    Wardle, Elizabeth; Downs, Doug

    2013-01-01

    In this Retrospective, we revisit our 2007 "College Composition and Communication" article in order to clarify our primary argument, address some questions and critiques that have arisen, and consider anew the value of composition courses that study writing. We review our core argument that engaging students with the research and ideas of writing…

  5. Searle's"Dualism Revisited"

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    P., Henry

    2008-11-20

    A recent article in which John Searle claims to refute dualism is examined from a scientific perspective. John Searle begins his recent article 'Dualism Revisited' by stating his belief that the philosophical problem of consciousness has a scientific solution. He then claims to refute dualism. It is therefore appropriate to examine his arguments against dualism from a scientific perspective. Scientific physical theories contain two kinds of descriptions: (1) Descriptions of our empirical findings, expressed in an every-day language that allows us communicate to each other our sensory experiences pertaining to what we have done and what we have learned; andmore » (2) Descriptions of a theoretical model, expressed in a mathematical language that allows us to communicate to each other certain ideas that exist in our mathematical imaginations, and that are believed to represent, within our streams of consciousness, certain aspects of reality that we deem to exist independently of their being perceived by any human observer. These two parts of our scientific description correspond to the two aspects of our general contemporary dualistic understanding of the total reality in which we are imbedded, namely the empirical-mental aspect and the theoretical-physical aspect. The duality question is whether this general dualistic understanding of ourselves should be regarded as false in some important philosophical or scientific sense.« less

  6. THE CONCEPT OF REFERENCE CONDITION, REVISITED ...

    EPA Pesticide Factsheets

    Ecological assessments of aquatic ecosystems depend on the ability to compare current conditions against some expectation of how they could be in the absence of significant human disturbance. The concept of a ‘‘reference condition’’ is often used to describe the standard or benchmark against which current condition is compared. If assessments are to be conducted consistently, then a common understanding of the definitions and complications of reference condition is necessary. A 2006 paper (Stoddard et al., 2006, Ecological Applications 16:1267-1276) made an early attempt at codifying the reference condition concept; in this presentation we will revisit the points raised in that paper (and others) and examine how our thinking has changed in a little over 10 years.Among the issues to be discussed: (1) the “moving target” created when reference site data are used to set thresholds in large scale assessments; (2) natural vs. human disturbance and their effects on reference site distributions; (3) circularity and the use of biological data to assist in reference site identification; (4) using site-scale (in-stream or in-lake) measurements vs. landscape-level human activity to identify reference conditions. Ecological assessments of aquatic ecosystems depend on the ability to compare current conditions against some expectation of how they could be in the absence of significant human disturbance. The concept of a ‘‘reference condition’’ is often use

  7. Revisiting Feminism and Australian Education: Who Speaks? What Questions? What Contexts? What Impact?

    ERIC Educational Resources Information Center

    Yates, Lyn

    2008-01-01

    This article revisits the development of feminist research and policy in education in Australia in the mid-1970s to mid-1980s from the perspective of the present decade. The purpose is to give one insider's account of the specificities of that initial period, and to use that analysis to draw attention to changes evident in the context and agendas…

  8. Revisiting the 'Low BirthWeight paradox' using a model-based definition.

    PubMed

    Juárez, Sol; Ploubidis, George B; Clarke, Lynda

    2014-01-01

    Immigrant mothers in Spain have a lower risk of delivering Low BirthWeight (LBW) babies in comparison to Spaniards (LBW paradox). This study aimed at revisiting this finding by applying a model-based threshold as an alternative to the conventional definition of LBW. Vital information data from Madrid was used (2005-2006). LBW was defined in two ways (less than 2500g and Wilcox's proposal). Logistic and linear regression models were run. According to common definition of LBW (less than 2500g) there is evidence to support the LBW paradox in Spain. Nevertheless, when an alternative model-based definition of LBW is used, the paradox is only clearly present in mothers from the rest of Southern America, suggesting a possible methodological bias effect. In the future, any examination of the existence of the LBW paradox should incorporate model-based definitions of LBW in order to avoid methodological bias. Copyright © 2013 SESPAS. Published by Elsevier Espana. All rights reserved.

  9. The Demand for Special Education Teachers in Rural Schools Revisited: An Update on Progress

    ERIC Educational Resources Information Center

    Sindelar, Paul T.; Pua, Daisy J.; Fisher, Tiffany; Peyton, David J.; Brownell, Mary T.; Mason-Williams, Loretta

    2018-01-01

    In this commentary, we revisit "NCLB and the Demand for Highly Qualified Teachers: Challenges and Solutions for Rural Schools," an article we published in this journal in 2005. We consider the predictions we made then about the impact of the Highly Qualified Teacher mandate on special education teacher (SET) shortages in rural states and…

  10. Re-visiting the electrophysiology of language.

    PubMed

    Obleser, Jonas

    2015-09-01

    This editorial accompanies a special issue of Brain and Language re-visiting old themes and new leads in the electrophysiology of language. The event-related potential (ERP) as a series of characteristic deflections ("components") over time and their distribution on the scalp has been exploited by speech and language researchers over decades to find support for diverse psycholinguistic models. Fortunately, methodological and statistical advances have allowed human neuroscience to move beyond some of the limitations imposed when looking at the ERP only. Most importantly, we currently witness a refined and refreshed look at "event-related" (in the literal sense) brain activity that relates itself more closely to the actual neurobiology of speech and language processes. It is this imminent change in handling and interpreting electrophysiological data of speech and language experiments that this special issue intends to capture. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Considerations of the Social, Individual, and Embodied: A Response to Comments on "Schema Theory Revisited"

    ERIC Educational Resources Information Center

    McVee, Mary B.; Gavelek, James R.; Dunsmore, Kailonnie L.

    2007-01-01

    This article presents the authors' response and clarifications to the comments of Margaret E. Gredler and of Karen A. Krasny, Mark Sadoski, and Allan Paivio on their article "Schema Theory Revisited." The authors first respond to Gredler's criticism contending that they "transmogrified" Harre's (1984) "ignominiously named...Vygotsky space" in…

  12. Silent cries, dancing tears: the metapsychology of art revisited/revised.

    PubMed

    Aragno, Anna

    2011-04-01

    Against the backdrop of a broad survey of the literature on applied psychoanalysis, a number of concepts underpinning the metapsychology of art are revisited and revised: sublimation; interrelationships between primary and secondary processes; symbolization; "fantasy"; and "cathexis." Concepts embedded in dichotomous or drive/energic contexts are examined and reformulated in terms of a continuum of semiotic processes. Freudian dream structure is viewed as a biological/natural template for nonrepressive artistic forms of sublimation. The synthesis presented proposes a model of continuous rather than discontinuous processes, in a nonenergic, biosemiotic metatheoretical framework.

  13. Inverse Faraday Effect Revisited

    NASA Astrophysics Data System (ADS)

    Mendonça, J. T.; Ali, S.; Davies, J. R.

    2010-11-01

    The inverse Faraday effect is usually associated with circularly polarized laser beams. However, it was recently shown that it can also occur for linearly polarized radiation [1]. The quasi-static axial magnetic field by a laser beam propagating in plasma can be calculated by considering both the spin and the orbital angular momenta of the laser pulse. A net spin is present when the radiation is circularly polarized and a net orbital angular momentum is present if there is any deviation from perfect rotational symmetry. This orbital angular momentum has recently been discussed in the plasma context [2], and can give an additional contribution to the axial magnetic field, thus enhancing or reducing the inverse Faraday effect. As a result, this effect that is usually attributed to circular polarization can also be excited by linearly polarized radiation, if the incident laser propagates in a Laguerre-Gauss mode carrying a finite amount of orbital angular momentum.[4pt] [1] S. ALi, J.R. Davies and J.T. Mendonca, Phys. Rev. Lett., 105, 035001 (2010).[0pt] [2] J. T. Mendonca, B. Thidé, and H. Then, Phys. Rev. Lett. 102, 185005 (2009).

  14. Pharmacy School Survey Standards Revisited

    PubMed Central

    Barnett, Mitchell J.; Lenth, Russell V.; Knapp, Katherine K.

    2013-01-01

    In a series of 3 papers on survey practices published from 2008 to 2009, the editors of the American Journal of Pharmaceutical Education presented guidelines for reporting survey research, and these criteria are reflected in the Author Instructions provided on the Journal’s Web site. This paper discusses the relevance of these criteria for publication of survey research regarding pharmacy colleges and schools. In addition, observations are offered about surveying of small "universes" like that comprised of US colleges and schools of pharmacy. The reason for revisiting this issue is the authors’ concern that, despite the best of intentions, overly constraining publication standards might discourage research on US colleges and schools of pharmacy at a time when the interest in the growth of colleges and schools, curricular content, clinical education, competence at graduation, and other areas is historically high. In the best traditions of academia, the authors share these observations with the community of pharmacy educators in the hope that the publication standards for survey research about US pharmacy schools will encourage investigators to collect and disseminate valuable information. PMID:23459404

  15. Pharmacy school survey standards revisited.

    PubMed

    Mészáros, Károly; Barnett, Mitchell J; Lenth, Russell V; Knapp, Katherine K

    2013-02-12

    In a series of 3 papers on survey practices published from 2008 to 2009, the editors of the American Journal of Pharmaceutical Education presented guidelines for reporting survey research, and these criteria are reflected in the Author Instructions provided on the Journal's Web site. This paper discusses the relevance of these criteria for publication of survey research regarding pharmacy colleges and schools. In addition, observations are offered about surveying of small "universes" like that comprised of US colleges and schools of pharmacy. The reason for revisiting this issue is the authors' concern that, despite the best of intentions, overly constraining publication standards might discourage research on US colleges and schools of pharmacy at a time when the interest in the growth of colleges and schools, curricular content, clinical education, competence at graduation, and other areas is historically high. In the best traditions of academia, the authors share these observations with the community of pharmacy educators in the hope that the publication standards for survey research about US pharmacy schools will encourage investigators to collect and disseminate valuable information.

  16. Civil-Military Relations in Latin America: The Hedgehog and the Fox Revisited

    DTIC Science & Technology

    2005-01-01

    and the Fox Revisited Thomas C. Bruneau Naval Postgraduate School, Estados Unidos Resumen El siguiente artículo propone un nuevo enfoque hacia el...puede lograr solamente por medio de la creación de instituciones que incorporan y personifican conocimientos y mecanismos de control tanto del poder...ejecutivo como legislativo del estado democrático. Abstract This article argues for a new focus in the study of civil-military relations. It seeks to

  17. Entropy of measurement and erasure: Szilard's membrane model revisited

    NASA Astrophysics Data System (ADS)

    Leff, Harvey S.; Rex, Andrew F.

    1994-11-01

    It is widely believed that measurement is accompanied by irreversible entropy increase. This conventional wisdom is based in part on Szilard's 1929 study of entropy decrease in a thermodynamic system by intelligent intervention (i.e., a Maxwell's demon) and Brillouin's association of entropy with information. Bennett subsequently argued that information acquisition is not necessarily irreversible, but information erasure must be dissipative (Landauer's principle). Inspired by the ensuing debate, we revisit the membrane model introduced by Szilard and find that it can illustrate and clarify (1) reversible measurement, (2) information storage, (3) decoupling of the memory from the system being measured, and (4) entropy increase associated with memory erasure and resetting.

  18. Revisiting Individualism and Collectivism: A Multinational Examination of Pre-Service Teachers' Perceptions on Student Academic Performances

    ERIC Educational Resources Information Center

    Jiang, Heng

    2016-01-01

    This study explores how pre-service teachers in Singapore, Hong Kong, Taiwan, and the United States perceive educational diversity in relation to students' academic achievement by means of qualitative content analysis. It takes cultural psychological perspectives to revisit the attribute reasoning embedded in individualist and collectivist…

  19. The Species Problem in Myxomycetes Revisited.

    PubMed

    Walker, Laura M; Stephenson, Steven L

    2016-08-01

    Species identification in the myxomycetes (plasmodial slime molds or myxogastrids) poses particular challenges to researchers as a result of their morphological plasticity and frequent alteration between sexual and asexual life strategies. Traditionally, myxomycete morphology has been used as the primary method of species delimitation. However, with the increasing availability of genetic information, traditional myxomycete taxonomy is being increasingly challenged, and new hypotheses continue to emerge. Due to conflicts that sometimes occur between traditional and more modern species concepts that are based largely on molecular data, there is a pressing need to revisit the discussion surrounding the species concept used for myxomycetes. Biological diversity is being increasingly studied with molecular methods and data accumulates at ever-faster rates, making resolution of this matter urgent. In this review, currently used and potentially useful species concepts (biological, morphological, phylogenetic and ecological) are reviewed, and an integrated approach to resolve the myxomycete species problem is discussed. Copyright © 2016 Elsevier GmbH. All rights reserved.

  20. Visser's massive graviton bimetric theory revisited

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Roany, Alain de; Chauvineau, Bertrand; Freitas Pacheco, Jose A. de

    2011-10-15

    A massive gravity theory was proposed by Visser in the late 1990s. This theory, based on a background metric b{sub {alpha}{beta}} and on an usual dynamical metric g{sub {alpha}{beta}} has the advantage of being free of ghosts as well as discontinuities present in other massive theories proposed in the past. In the present investigation, the equations of Visser's theory are revisited with particular care on the related conservation laws. It will be shown that a multiplicative factor is missing in the graviton tensor originally derived by Visser, which has no incidence on the weak field approach but becomes important inmore » the strong field regime when, for instance, cosmological applications are considered. In this case, contrary to some previous claims found in the literature, we conclude that a nonstatic background metric is required in order to obtain a solution able to mimic the {Lambda}CDM cosmology.« less

  1. Metabolic mysteries of the inflammatory response: T cell polarization and plasticity.

    PubMed

    Fracchia, Kelley M; Walsh, Craig M

    2015-01-01

    While simultaneously maintaining homeostasis and reducing further harm to the host, the immune system is equipped to eliminate both tumors and pathogenic microorganisms. Bifurcated into cell-mediated and humoral immunity, the adaptive immune system requires a series of complex and coordinated signals to drive the proliferation and differentiation of appropriate subsets. These include signals that modulate cellular metabolism. When first published in the 1920s, "the Warburg effect" was used to describe a phenomenon in which most cancer cells relied on aerobic glycolysis to meet their biosynthetic demands. Despite the early observations of Warburg and his colleagues, targeting cancer cell metabolism for therapeutic purposes still remains theoretical. Notably, many T cells exhibit the same Warburg metabolism as cancer cells and the therapeutic benefit of targeting their metabolic pathways has since been reexamined. Emerging evidence suggests that specific metabolic alterations associated with T cells may be ancillary to their subset differentiation and influential in their inflammatory response. Thus, T cell lymphocyte activation leads to skewing in metabolic plasticity, and issue that will be the subject of this review.

  2. Revisiting Valley Development on Martian Volcanoes Using MGS and Odyssey Data

    NASA Technical Reports Server (NTRS)

    Gulick, Virginia C.

    2005-01-01

    The valley networks found on the slopes of Martian volcanoes represent an interesting subset of the Martian valley networks. Not only do the volcanoes constrain the possible geologic settings, they also provide a window into Martian valley development through time, as the volcanoes formed throughout the geologic history of Mars. Here I take another look at this intriguing subset of networks by revisiting conclusions reached in my earlier studies using the Viking imagery and the valleys on Hawaii as an analog. I then examine more recent datasets.

  3. Responsible health insurance revisited: pouring liberal wine into a conservative bottle.

    PubMed

    Seidman, Laurence

    2005-01-01

    In 1991, an article appeared proposing a plan for "Responsible National Health Insurance" (RHI) that contained three crucial elements supported by economists affiliated with two conservative policy institutions (the American Enterprise Institute and the Heritage Foundation). The central purpose of this article is to revisit RHI in light of developments over the past decade, and to make the case that liberals, rather than reject RHI, now should support it, provided conservatives agree to sufficient funding. In this article, I recommend "pouring liberal wine into this conservative bottle."

  4. Quantization of the nonlinear sigma model revisited

    NASA Astrophysics Data System (ADS)

    Nguyen, Timothy

    2016-08-01

    We revisit the subject of perturbatively quantizing the nonlinear sigma model in two dimensions from a rigorous, mathematical point of view. Our main contribution is to make precise the cohomological problem of eliminating potential anomalies that may arise when trying to preserve symmetries under quantization. The symmetries we consider are twofold: (i) diffeomorphism covariance for a general target manifold; (ii) a transitive group of isometries when the target manifold is a homogeneous space. We show that there are no anomalies in case (i) and that (ii) is also anomaly-free under additional assumptions on the target homogeneous space, in agreement with the work of Friedan. We carry out some explicit computations for the O(N)-model. Finally, we show how a suitable notion of the renormalization group establishes the Ricci flow as the one loop renormalization group flow of the nonlinear sigma model.

  5. The Postgraduate Premium: Revisiting Trends in Social Mobility and Educational Inequalities in Britain and America

    ERIC Educational Resources Information Center

    Lindley, Joanne; Machin, Stephen

    2013-01-01

    This report revisits the debate about why social mobility levels are relatively low in Great Britain and the United States of America compared to other countries. It focuses on three main areas within this debate: (1) the changing role of educational inequalities; (2) the expectation of ever higher levels of education as revealed in increasing…

  6. Using destination image to predict visitors' intention to revisit three Hudson River Valley, New York, communities

    Treesearch

    Rudy M. Schuster; Laura Sullivan; Duarte Morais; Diane Kuehn

    2009-01-01

    This analysis explores the differences in Affective and Cognitive Destination Image among three Hudson River Valley (New York) tourism communities. Multiple regressions were used with six dimensions of visitors' images to predict future intention to revisit. Two of the three regression models were significant. The only significantly contributing independent...

  7. Revisiting therapeutic strategies in radiation casualties.

    PubMed

    Hérodin, Francis; Grenier, Nancy; Drouet, Michel

    2007-04-01

    Nuclear/radiological threats have evolved and scenarios for terrorist attacks involving radioactive material have been identified as complex situations. Mass casualty scenarios may happen, and individuals may be exposed to intentionally hidden sources of high activity, resulting in delayed diagnosis and treatment of acute radiation syndrome (ARS). Moreover, ARS must be considered as an emergency in order to better anticipate delayed radiation toxicity. In this context, therapeutic strategies in radiation casualties have to be revisited and new pharmacological approaches developed. B6D2F1 mice were total-body irradiated (TBI) with a 9 Gy gamma dose and then received intraperitoneal doses of either early (stem cell factor + FLT-3 ligand + thrombopoietin + interleukin-3 [SFT3] +/- keratinocyte growth factor (KGF); stem cell factor + erythropoietin + Peg-filgrastim [SEG]) or delayed treatments (SFT3 +/- KGF, erythropoietin, or hyaluronic acid). Survival was monitored and bone marrow hematopoiesis evaluated at 300 days following early treatments. SFT3 anti-apoptotic cytokine combination administered early (2 hours and 24 hours) after lethal TBI induced 60% survival versus 5% in controls. Early SEG treatment may be an alternative to SFT3 in terms of survival (55%), but SEG benefit might be obtained at the expense of long-term hematopoiesis. SFT3 + KGF induced 75% survival. No effectiveness was observed, over antimicrobial supportive care, when administration of SFT3 or its tested combinations was delayed at 48 hours. As a potentially multi-organ failure, ARS requires global therapy, beyond the hematopoietic syndrome, which may include pleiotropic cytokines such as KGF.

  8. Revisiting Deng et al.'s Multiparty Quantum Secret Sharing Protocol

    NASA Astrophysics Data System (ADS)

    Hwang, Tzonelih; Hwang, Cheng-Chieh; Yang, Chun-Wei; Li, Chuan-Ming

    2011-09-01

    The multiparty quantum secret sharing protocol [Deng et al. in Chin. Phys. Lett. 23: 1084-1087, 2006] is revisited in this study. It is found that the performance of Deng et al.'s protocol can be much improved by using the techniques of block-transmission and decoy single photons. As a result, the qubit efficiency is improved 2.4 times and only one classical communication, a public discussion, and two quantum communications between each agent and the secret holder are needed rather than n classical communications, n public discussions, and 3n/2 quantum communications required in the original scheme.

  9. Metabolic cancer biology: structural-based analysis of cancer as a metabolic disease, new sights and opportunities for disease treatment.

    PubMed

    Masoudi-Nejad, Ali; Asgari, Yazdan

    2015-02-01

    The cancer cell metabolism or the Warburg effect discovery goes back to 1924 when, for the first time Otto Warburg observed, in contrast to the normal cells, cancer cells have different metabolism. With the initiation of high throughput technologies and computational systems biology, cancer cell metabolism renaissances and many attempts were performed to revise the Warburg effect. The development of experimental and analytical tools which generate high-throughput biological data including lots of information could lead to application of computational models in biological discovery and clinical medicine especially for cancer. Due to the recent availability of tissue-specific reconstructed models, new opportunities in studying metabolic alteration in various kinds of cancers open up. Structural approaches at genome-scale levels seem to be suitable for developing diagnostic and prognostic molecular signatures, as well as in identifying new drug targets. In this review, we have considered these recent advances in structural-based analysis of cancer as a metabolic disease view. Two different structural approaches have been described here: topological and constraint-based methods. The ultimate goal of this type of systems analysis is not only the discovery of novel drug targets but also the development of new systems-based therapy strategies. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Mitochondria and cancer: a growing role in apoptosis, cancer cell metabolism and dedifferentiation.

    PubMed

    Scatena, Roberto

    2012-01-01

    At the beginning of the twentieth century, Otto Warburg demonstrated that cancer cells have a peculiar metabolism. These cells preferentially utilise glycolysis for energetic and anabolic purposes, producing large quantities of lactic acid. He defined this unusual metabolism "aerobic glycolysis". At the same time, Warburg hypothesised that a disruption of mitochondrial activities played a precise pathogenic role in cancer. Because of this so-called "Warburg effect", mitochondrial physiology and cellular respiration in particular have been overlooked in pathophysiological studies of cancer. Over time, however, many studies have shown that mitochondria play a fundamental role in cell death by apoptosis or necrosis. Moreover, metabolic enzymes of the Krebs cycle have also recently been recognised as oncosuppressors. Recently, a series of studies were undertaken to re-evaluate the role of oxidative mitochondrial metabolism in cancer cell growth and progression. Some of these data indicate that modulation of mitochondrial respiration may induce an arrest of cancer cell proliferation and differentiation (pseudodifferentiation) and/or or death, suggesting that iatrogenic manipulation of some mitochondrial activities may induce anticancer effects. Moreover, studying the role of mitochondria in cancer cell dedifferentiation/differentiation processes may allow further insight into the pathophysiology and therapy of so-called cancer stem cells.

  11. Geography, Not Health System Affiliations, Determines Patients' Revisits to the Emergency Department.

    PubMed

    Rising, Kristin L; Karp, David N; Powell, Rhea E; Victor, Timothy W; Carr, Brendan G

    2018-04-01

    To determine how frequently patients revisit the emergency department after an initial encounter, and to describe revisit capture rates for the same hospital, health system, and geographic region. Florida state data from January 1, 2010, to June 30, 2011, from the Healthcare Cost and Utilization Project. This is a retrospective cohort study of emergency department return visits among Florida adults over an 18-month period. We evaluated pairs of index and 30-day return emergency department visits and compared capture rates for hospital, health system, and geographic units. Data were obtained from the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project and the American Hospital Association Annual Survey Database. Among 9,416,212 emergency department visits, 22.6 percent (2,124,441) were associated with a 30-day return. Seventy percent (1,477,772) of 30-day returns occurred to the same hospital. The 30-day return capture rates were highest within the same geographic area: county-level capture at 92 percent (IQR=86-96 percent) versus health system capture at 75 percent (IQR = 68-81 percent). Acute care utilization patterns are often independent of health system boundaries. Current population-based health care models that attribute patients to a single provider or health system may be strengthened by considering geographic patterns of acute care utilization. © Health Research and Educational Trust.

  12. Asian Lifelong Learning in the Context of a Global Knowledge Economy: A Task Re-Visited

    ERIC Educational Resources Information Center

    Han, Soonghee

    2007-01-01

    This article revisits and reinterprets my previous paper. It is a snapshot of the lifelong learning system building in selected Asian countries, reflected in the mirror of the Asian Financial Crisis in the 1997s and the aftermath of that event. I reconsidered the arguments (1) the economic recession had delivered a global dimension of lifelong…

  13. Three-Alarm System: Revisited to treat Thumb-sucking Habit

    PubMed Central

    Shetty, Manoj; Shetty, N Shridhar; Deoghare, Anushka

    2015-01-01

    ABSTRACT Thumb and digit-sucking habits or non-nutritive sucking are considered to be the most prevalent among oral habits. Most children stop thumb sucking on their own. If the habit continues beyond 3 to 4 years of age, it not only affects the dental occlusion, but the shape of the thumb/digit may be altered as well. This article presents the management of thumb sucking by modified RURS, elbow guard incorporated with revised ‘three-alarm’ system. How to cite this article: Shetty RM, Shetty M, Shetty NS, Deoghare A. Three-Alarm System: Revisited to treat Thumb-sucking Habit. Int J Clin Pediatr Dent 2015;8(1):82-86. PMID:26124588

  14. Revisiting NMR composite pulses for broadband 2H excitation

    PubMed Central

    Shen, Ming; Roopchand, Rabia; Mananga, Eugene S.; Amoureux, Jean-Paul; Chen, Qun; Boutis, Gregory S.; Hu, Bingwen

    2014-01-01

    Quadrupolar echo NMR spectroscopy of static solids often requires RF excitation that covers spectral widths exceeding 100 kHz, which is difficult to obtain due to instrumental limitations. In this work we revisit four well-known composite pulses (COM-I, II, III and IV) for broadband excitation in deuterium quadrupolar echo spectroscopy. These composite pulses are combined with several phase cycling schemes that were previously shown to decrease finite pulse width distortions in deuterium solid-echo experiments performed with two single pulses. The simulations and experiments show that COM-II and IV composite pulses combined with an 8-step phase cycling aid in achieving broadband excitation with limited pulse width distortions. PMID:25583576

  15. Revisiting the quantum Szilard engine with fully quantum considerations

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Li, Hai; School of Information and Electronics Engineering, Shandong Institute of Business and Technology, Yantai 264000; Zou, Jian, E-mail: zoujian@bit.edu.cn

    2012-12-15

    By considering level shifting during the insertion process we revisit the quantum Szilard engine (QSZE) with fully quantum consideration. We derive the general expressions of the heat absorbed from thermal bath and the total work done to the environment by the system in a cycle with two different cyclic strategies. We find that only the quantum information contributes to the absorbed heat, and the classical information acts like a feedback controller and has no direct effect on the absorbed heat. This is the first demonstration of the different effects of quantum information and classical information for extracting heat from themore » bath in the QSZE. Moreover, when the well width L{yields}{infinity} or the temperature of the bath T{yields}{infinity} the QSZE reduces to the classical Szilard engine (CSZE), and the total work satisfies the relation W{sub tot}=k{sub B}Tln2 as obtained by Sang Wook Kim et al. [S.W. Kim, T. Sagawa, S. De Liberato, M. Ueda, Phys. Rev. Lett. 106 (2011) 070401] for one particle case. - Highlights: Black-Right-Pointing-Pointer For the first time analyze the QSZE by considering energy level shifts. Black-Right-Pointing-Pointer Find different roles played by classical and quantum information in the QSZE. Black-Right-Pointing-Pointer The amount of work extracted depends on the cyclic strategies of the QSZE. Black-Right-Pointing-Pointer Verify that the QSZE will reduce to the CSZE in the classical limits.« less

  16. Critical Language Awareness in the United States: Revisiting Issues and Revising Pedagogies in a Resegregated Society

    ERIC Educational Resources Information Center

    Alim, H. Samy

    2005-01-01

    As scholars examine the successes and failures of more than 50 years of court-ordered desegregation since "Brown v. Board of Education of Topeka, Kansas," and 25 years of language education of Black youth since "Martin Luther King Elementary School Children v. Ann Arbor School District Board," this article revisits the key…

  17. Revisiting Supernova 1987A constraints on dark photons

    DOE PAGES

    Chang, Jae Hyeok; Essig, Rouven; McDermott, Samuel D.

    2017-01-25

    We revisit constraints on dark photons with masses below ~ 100 MeV from the observations of Supernova 1987A. If dark photons are produced in sufficient quantity, they reduce the amount of energy emitted in the form of neutrinos, in conflict with observations. For the first time, we include the effects of finite temperature and density on the kinetic-mixing parameter,ϵ, in this environment. This causes the constraints on ϵ to weaken with the dark-photon mass below ~ 15 MeV. For large-enough values of ϵ, it is well known that dark photons can be reabsorbed within the supernova. Since the rates ofmore » reabsorption processes decrease as the dark-photon energy increases, we point out that dark photons with energies above the Wien peak can escape without scattering, contributing more to energy loss than is possible assuming a blackbody spectrum. Furthermore, we estimate the systematic uncertainties on the cooling bounds by deriving constraints assuming one analytic and four different simulated temperature and density profiles of the proto-neutron star. Finally, we estimate also the systematic uncertainty on the bound by varying the distance across which dark photons must propagate from their point of production to be able to affect the star. Finally, this work clarifies the bounds from SN1987A on the dark-photon parameter space.« less

  18. THE EFFECTS OF PANTOTHENIC ACID ON RESPIRATORY ACTIVITY.

    PubMed

    Pratt, E F; Williams, R J

    1939-05-20

    Experiments using the Warburg-Barcroft apparatus led to the following results and conclusions: (1) Two yeasts in three different media were strikingly stimulated in their respiration by minute amounts of pantothenic acid. (2) Nine other compounds (vitamins and other biologically important substances) were tested and found in all cases to have on the deficient G.M. yeast, lesser and in some cases no appreciable stimulative effect. Thiamin was the most effective of these compounds. Its action was shown to be different and in some ways antagonistic to that of pantothenic acid. (3) Liver extract (Lilly's Number 343) contains substances capable of speeding up respiration (and growth) to a much higher level than seems possible with known compounds. (4) Pantothenic acid was found to have a definite stimulative effect on fermentation by dialyzed maceration juice from yeast. (5) It likewise stimulated respiration of apple and potato tissue and indications of a similar effect on certain animal tissues were obtained.

  19. Revisiting the Quantitative-Qualitative Debate: Implications for Mixed-Methods Research

    PubMed Central

    SALE, JOANNA E. M.; LOHFELD, LYNNE H.; BRAZIL, KEVIN

    2015-01-01

    Health care research includes many studies that combine quantitative and qualitative methods. In this paper, we revisit the quantitative-qualitative debate and review the arguments for and against using mixed-methods. In addition, we discuss the implications stemming from our view, that the paradigms upon which the methods are based have a different view of reality and therefore a different view of the phenomenon under study. Because the two paradigms do not study the same phenomena, quantitative and qualitative methods cannot be combined for cross-validation or triangulation purposes. However, they can be combined for complementary purposes. Future standards for mixed-methods research should clearly reflect this recommendation. PMID:26523073

  20. New constraints on kinetic isotope effects during CO2(aq) hydration and hydroxylation: Revisiting theoretical and experimental data

    NASA Astrophysics Data System (ADS)

    Sade, Ziv; Halevy, Itay

    2017-10-01

    CO2 (de)hydration (i.e., CO2 hydration/HCO3- dehydration) and (de)hydroxylation (i.e., CO2 hydroxylation/HCO3- dehydroxylation) are key reactions in the dissolved inorganic carbon (DIC) system. Kinetic isotope effects (KIEs) during these reactions are likely to be expressed in the DIC and recorded in carbonate minerals formed during CO2 degassing or dissolution of gaseous CO2. Thus, a better understanding of KIEs during CO2 (de)hydration and (de)hydroxylation would improve interpretations of disequilibrium compositions in carbonate minerals. To date, the literature lacks direct experimental constraints on most of the oxygen KIEs associated with these reactions. In addition, theoretical estimates describe oxygen KIEs during separate individual reactions. The KIEs of the related reverse reactions were neither derived directly nor calculated from a link to the equilibrium fractionation. Consequently, KIE estimates of experimental and theoretical studies have been difficult to compare. Here we revisit experimental and theoretical data to provide new constraints on oxygen KIEs during CO2 (de)hydration and (de)hydroxylation. For this purpose, we provide a clearer definition of the KIEs and relate them both to isotopic rate constants and equilibrium fractionations. Such relations are well founded in studies of single isotope source/sink reactions, but they have not been established for reactions that involve dual isotopic sources/sinks, such as CO2 (de)hydration and (de)hydroxylation. We apply the new quantitative constraints on the KIEs to investigate fractionations during simultaneous CaCO3 precipitation and HCO3- dehydration far from equilibrium.

  1. Dual beta-lactam therapy for serious Gram-negative infections: is it time to revisit?

    PubMed

    Rahme, Christine; Butterfield, Jill M; Nicasio, Anthony M; Lodise, Thomas P

    2014-12-01

    We are rapidly approaching a crisis in antibiotic resistance, particularly among Gram-negative pathogens. This, coupled with the slow development of novel antimicrobial agents, underscores the exigency of redeploying existing antimicrobial agents in innovative ways. One therapeutic approach that was heavily studied in the 1980s but abandoned over time is dual beta-lactam therapy. This article reviews the evidence for combination beta-lactam therapy. Overall, in vitro, animal and clinical data are positive and suggest that beta-lactam combinations produce a synergistic effect against Gram-negative pathogens that rivals that of beta-lactam-aminoglycoside or beta-lactam-fluoroquinolone combination therapy. Although the precise mechanism of improved activity is not completely understood, it is likely attributable to an enhanced affinity to the diverse penicillin-binding proteins found among Gram negatives. The collective data indicate that dual beta-lactam therapy should be revisited for serious Gram-negative infections, especially in light of the near availability of potent beta-lactamase inhibitors, which neutralize the effect of problematic beta-lactamases. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Cost-effectiveness acceptability curves revisited.

    PubMed

    Al, Maiwenn J

    2013-02-01

    Since the introduction of the cost-effectiveness acceptability curve (CEAC) in 1994, its use as a method to describe uncertainty around incremental cost-effectiveness ratios (ICERs) has steadily increased. In this paper, first the construction and interpretation of the CEAC is explained, both in the context of modelling studies and in the context of cost-effectiveness (CE) studies alongside clinical trials. Additionally, this paper reviews the advantages and limitations of the CEAC. Many of the perceived limitations can be attributed to the practice of interpreting the CEAC as a decision rule while it was not developed as such. It is argued that the CEAC is still a useful tool in describing and quantifying uncertainty around the ICER, especially in combination with other tools such as plots on the CE plane and value-of-information analysis.

  3. Long-acting family planning method switching among revisit clients of public health facilities in Dire Dawa, Ethiopia.

    PubMed

    Atnafe, Meselu; Assefa, Nega; Alemayehu, Tadesse

    2016-01-01

    "Contraceptive switching" from one method to another is a common phenomenon. Switching from a more effective long-acting method to a less effective method exposes women for unplanned pregnancy. The aim of this study was to assess the level and factors associated with long-acting family planning method switching to other methods. A facility-based cross-sectional study was conducted from January to March 2013 on 634 women attending public health facilities in Dire Dawa City Administration, Ethiopia. Participants of the study were revisit clients of family planning service and were interviewed as they appear in the clinics. Data were analyzed using crude and adjusted logistic regression, and results were reported using OR and corresponding 95 % CI. Long-acting family planning method switching among revisit clients was 40.4 %; switching from implant was 29.8 % and from IUCD, it was 10.6 %. The main reasons for methods switching were side effects of the methods such as bleeding, weight loss, and feeling of arm numbness. The tendency of switching was less among married women (AOR = 2.41, 95 % CI: 1.01, 5.74), women who had 2-4 and 5 and more children (AOR 3.00, 95 % CI: 1.59, 5.67) and (AOR 2.07, 95 % CI: 1.17, 3.66), respectively. It was also less among women who want to stop birth (AOR 5.11, 95 % CI: 1.15, 24.8), among those who mentioned health care providers as source of information for family planning (AOR 1.88, 95 % CI: 1.18, 3.01), and among women whose husbands were aware of their use of the methods (AOR 3.05, 95 % CI: 1.88, 4.94). Method switching from long-acting contraceptives to less effective methods is high. Method switching was significant among unmarried women, who had one child, plan to postpone fertility, and whose husbands were not aware of their wive's use of the method. In the provision of family planning service, the health care providers should give adequate information about each method and risks of method switching. Appropriate family

  4. Revisiting Insider-Outsider Research in Comparative and International Education. Bristol Papers in Education: Comparative and International Studies

    ERIC Educational Resources Information Center

    Crossley, Michael, Ed.; Arthur, Lore, Ed.; McNess, Elizabeth, Ed.

    2016-01-01

    This volume recognises how many researchers across the social sciences, and in comparative and international education in particular, see themselves as insiders or outsiders or, more pertinently, shifting combinations of both, in the research process. The book revisits and problematises these concepts in an era where the global mobility of…

  5. Revisiting Risk in the 21st Century. Forum Focus. Volume 3, Issue 1, January-February 2005

    ERIC Educational Resources Information Center

    Forum for Youth Investment, 2005

    2005-01-01

    Over the past year, dozens of articles have been published about excessive youth borrowing and spending (leading to high amounts of debt), new reactions to negative body image (such as plastic surgery), as well as more familiar risks like premarital sex and smoking. In Forum Focus: Revisiting Risk in the 21st Century, we explore these challenges…

  6. A RAB3GAP1 SINE Insertion in Alaskan Huskies with Polyneuropathy, Ocular Abnormalities, and Neuronal Vacuolation (POANV) Resembling Human Warburg Micro Syndrome 1 (WARBM1)

    PubMed Central

    Wiedmer, Michaela; Oevermann, Anna; Borer-Germann, Stephanie E.; Gorgas, Daniela; Shelton, G. Diane; Drögemüller, Michaela; Jagannathan, Vidhya; Henke, Diana; Leeb, Tosso

    2015-01-01

    We observed a hereditary phenotype in Alaskan Huskies that was characterized by polyneuropathy with ocular abnormalities and neuronal vacuolation (POANV). The affected dogs developed a progressive severe ataxia, which led to euthanasia between 8 and 16 months of age. The pedigrees were consistent with a monogenic autosomal recessive inheritance. We localized the causative genetic defect to a 4 Mb interval on chromosome 19 by a combined linkage and homozygosity mapping approach. Whole genome sequencing of one affected dog, an obligate carrier, and an unrelated control revealed a 218-bp SINE insertion into exon 7 of the RAB3GAP1 gene. The SINE insertion was perfectly associated with the disease phenotype in a cohort of 43 Alaskan Huskies, and it was absent from 541 control dogs of diverse other breeds. The SINE insertion induced aberrant splicing and led to a transcript with a greatly altered exon 7. RAB3GAP1 loss-of-function variants in humans cause Warburg Micro Syndrome 1 (WARBM1), which is characterized by additional developmental defects compared to canine POANV, whereas Rab3gap1-deficient mice have a much milder phenotype than either humans or dogs. Thus, the RAB3GAP1 mutant Alaskan Huskies provide an interesting intermediate phenotype that may help to better understand the function of RAB3GAP1 in development. Furthermore, the identification of the presumed causative genetic variant will enable genetic testing to avoid the nonintentional breeding of affected dogs. PMID:26596647

  7. Dynamic Topography Revisited

    NASA Astrophysics Data System (ADS)

    Moresi, Louis

    2015-04-01

    Dynamic Topography Revisited Dynamic topography is usually considered to be one of the trinity of contributing causes to the Earth's non-hydrostatic topography along with the long-term elastic strength of the lithosphere and isostatic responses to density anomalies within the lithosphere. Dynamic topography, thought of this way, is what is left over when other sources of support have been eliminated. An alternate and explicit definition of dynamic topography is that deflection of the surface which is attributable to creeping viscous flow. The problem with the first definition of dynamic topography is 1) that the lithosphere is almost certainly a visco-elastic / brittle layer with no absolute boundary between flowing and static regions, and 2) the lithosphere is, a thermal / compositional boundary layer in which some buoyancy is attributable to immutable, intrinsic density variations and some is due to thermal anomalies which are coupled to the flow. In each case, it is difficult to draw a sharp line between each contribution to the overall topography. The second definition of dynamic topography does seem cleaner / more precise but it suffers from the problem that it is not measurable in practice. On the other hand, this approach has resulted in a rich literature concerning the analysis of large scale geoid and topography and the relation to buoyancy and mechanical properties of the Earth [e.g. refs 1,2,3] In convection models with viscous, elastic, brittle rheology and compositional buoyancy, however, it is possible to examine how the surface topography (and geoid) are supported and how different ways of interpreting the "observable" fields introduce different biases. This is what we will do. References (a.k.a. homework) [1] Hager, B. H., R. W. Clayton, M. A. Richards, R. P. Comer, and A. M. Dziewonski (1985), Lower mantle heterogeneity, dynamic topography and the geoid, Nature, 313(6003), 541-545, doi:10.1038/313541a0. [2] Parsons, B., and S. Daly (1983), The

  8. Revisiting Hansen Solubility Parameters by Including Thermodynamics.

    PubMed

    Louwerse, Manuel J; Maldonado, Ana; Rousseau, Simon; Moreau-Masselon, Chloe; Roux, Bernard; Rothenberg, Gadi

    2017-11-03

    The Hansen solubility parameter approach is revisited by implementing the thermodynamics of dissolution and mixing. Hansen's pragmatic approach has earned its spurs in predicting solvents for polymer solutions, but for molecular solutes improvements are needed. By going into the details of entropy and enthalpy, several corrections are suggested that make the methodology thermodynamically sound without losing its ease of use. The most important corrections include accounting for the solvent molecules' size, the destruction of the solid's crystal structure, and the specificity of hydrogen-bonding interactions, as well as opportunities to predict the solubility at extrapolated temperatures. Testing the original and the improved methods on a large industrial dataset including solvent blends, fit qualities improved from 0.89 to 0.97 and the percentage of correct predictions rose from 54 % to 78 %. Full Matlab scripts are included in the Supporting Information, allowing readers to implement these improvements on their own datasets. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Revisiting The First Galaxies: The effects of Population III stars on their host galaxies

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Muratov, Alexander L.; Gnedin, Oleg Y.; Gnedin, Nickolay Y.

    2013-07-12

    We revisit the formation and evolution of the first galaxies using new hydrodynamic cosmological simulations with the adaptive refinement tree code. Our simulations feature a recently developed model for H 2 formation and dissociation, and a star formation recipe that is based on molecular rather than atomic gas. Here, we develop and implement a recipe for the formation of metal-free Population III (Pop III) stars in galaxy-scale simulations that resolve primordial clouds with sufficiently high density. We base our recipe on the results of prior zoom-in simulations that resolved the protostellar collapse in pre-galactic objects. We find the epoch duringmore » which Pop III stars dominated the energy and metal budget of the first galaxies to be short-lived. Galaxies that host Pop III stars do not retain dynamical signatures of their thermal and radiative feedback for more than 10 8 years after the lives of the stars end in pair-instability supernovae, even when we consider the maximum reasonable efficiency of the feedback. Though metals ejected by the supernovae can travel well beyond the virial radius of the host galaxy, they typically begin to fall back quickly, and do not enrich a large fraction of the intergalactic medium. Galaxies with a total mass in excess of 3 × 10 6 M ⊙ re-accrete most of their baryons and transition to metal-enriched Pop II star formation.« less

  10. REVISITING THE FIRST GALAXIES: THE EFFECTS OF POPULATION III STARS ON THEIR HOST GALAXIES

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Muratov, Alexander L.; Gnedin, Oleg Y.; Zemp, Marcel

    2013-08-01

    We revisit the formation and evolution of the first galaxies using new hydrodynamic cosmological simulations with the adaptive refinement tree code. Our simulations feature a recently developed model for H{sub 2} formation and dissociation, and a star formation recipe that is based on molecular rather than atomic gas. Here, we develop and implement a recipe for the formation of metal-free Population III (Pop III) stars in galaxy-scale simulations that resolve primordial clouds with sufficiently high density. We base our recipe on the results of prior zoom-in simulations that resolved the protostellar collapse in pre-galactic objects. We find the epoch duringmore » which Pop III stars dominated the energy and metal budget of the first galaxies to be short-lived. Galaxies that host Pop III stars do not retain dynamical signatures of their thermal and radiative feedback for more than 10{sup 8} years after the lives of the stars end in pair-instability supernovae, even when we consider the maximum reasonable efficiency of the feedback. Though metals ejected by the supernovae can travel well beyond the virial radius of the host galaxy, they typically begin to fall back quickly, and do not enrich a large fraction of the intergalactic medium. Galaxies with a total mass in excess of 3 Multiplication-Sign 10{sup 6} M{sub Sun} re-accrete most of their baryons and transition to metal-enriched Pop II star formation.« less

  11. PGK1 Drives Hepatocellular Carcinoma Metastasis by Enhancing Metabolic Process.

    PubMed

    Xie, Huijun; Tong, Guihui; Zhang, Yupei; Liang, Shu; Tang, Kairui; Yang, Qinhe

    2017-07-27

    During the proliferation and metastasis, the tumor cells prefer glycolysis (Warburg effect), but its exact mechanism remains largely unknown. In this study, we demonstrated that phosphoglycerate kinase 1 (PGK1) is an important enzyme in the pathway of metabolic glycolysis. We observed a significant overexpression of PGK1 in hepatocellular carcinoma tissues, and a correlation between PGK1 expression and poor survival of hepatocellular carcinoma patients. Also, the depletion of PGK1 dramatically reduced cancer cell proliferation and metastasis, indicating an oncogenic role of PGK1 in liver cancer progression. Further experiments showed that PGK1 played an important role in MYC -induced metabolic reprogramming, which led to an enhanced Warburg effect. Our results revealed a new effect of PGK1, which can provide a new treatment strategy for hepatocellular carcinoma, as PGK1 is used to indicate the prognosis of hepatocellular carcinoma (HCC).

  12. Revisiting the Schönbein ozone measurement methodology

    NASA Astrophysics Data System (ADS)

    Ramírez-González, Ignacio A.; Añel, Juan A.; Saiz-López, Alfonso; García-Feal, Orlando; Cid, Antonio; Mejuto, Juan Carlos; Gimeno, Luis

    2017-04-01

    Trough the XIX century the Schönbein method gained a lot of popularity by its easy way to measure tropospheric ozone. Traditionally it has been considered that Schönbein measurements are not accurate enough to be useful. Detractors of this method argue that it is sensitive to meteorological conditions, being the most important the influence of relative humidity. As a consequence the data obtained by this method have usually been discarded. Here we revisit this method taking into account that values measured during the 19th century were taken using different measurement papers. We explore several concentrations of starch and potassium iodide, the basis for this measurement method. Our results are compared with the previous ones existing in the literature. The validity of the Schönbein methodology is discussed having into account humidity and other meteorological variables.

  13. The super-GUT CMSSM revisited

    DOE PAGES

    Ellis, John; Evans, Jason L.; Mustafayev, Azar; ...

    2016-10-28

    Here, we revisit minimal supersymmetric SU(5) grand unification (GUT) models in which the soft supersymmetry-breaking parameters of the minimal supersymmetric Standard Model (MSSM) are universal at some input scale, M in, above the supersymmetric gauge-coupling unification scale, M GUT. As in the constrained MSSM (CMSSM), we assume that the scalar masses and gaugino masses have common values, m 0 and m 1/2, respectively, at M in, as do the trilinear soft supersymmetry-breaking parameters A 0. Going beyond previous studies of such a super-GUT CMSSM scenario, we explore the constraints imposed by the lower limit on the proton lifetime and themore » LHC measurement of the Higgs mass, m h. We find regions of m 0, m 1/2 A 0 and the parameters of the SU(5) superpotential that are compatible with these and other phenomenological constraints such as the density of cold dark matter, which we assume to be provided by the lightest neutralino. Typically, these allowed regions appear for m 0 and m 1/2 in the multi-TeV region, for suitable values of the unknown SU(5) GUT-scale phases and superpotential couplings, and with the ratio of supersymmetric Higgs vacuum expectation values tan β≲6.« less

  14. Gerogogy in patient education--revisited.

    PubMed

    Pearson, Mary

    2011-01-01

    Gerogogy in Patient Education was first printed in Home Healthcare Nurse, Volume 14, Number 8, (1996), Lippincott. Writers Mary Pearson, M.Ed, RN- BC and Joan Wessman, MA. have revisited and updated the material to meet the needs of a new generation of health care professionals. Baby Boomers are retiring; they will reach their peak in 2030, with an estimated 72 million drawing social security. With these numbers comes an increase in services to the elderly, mostly in the form of medical expenditure. The problem will not only impact the financial system of Medicare but will have a great toll on families. How will the retirees remain independent in their homes? How will they learn new medical information? Will new health care professions be able to teach them while taking into consideration the physical and psychological alterations that occur with aging and illness? Gerogogy takes into account the person's disease process, age-related changes, educational level and motivation. Then incorporates these factors into practice, utilizing the same foundations found within the nursing process: assessment, planning, implementation, and evaluation. As stated, the methods for teaching the elderly are unique and require modifications. Gerogogy meets these needs so individuals can remain at home while also reducing unnecessary medical costs.

  15. No-scale ripple inflation revisited

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Li, Tianjun; Li, Zhijin; Nanopoulos, Dimitri V., E-mail: tli@itp.ac.cn, E-mail: lizhijin@physics.tamu.edu, E-mail: dimitri@physics.tamu.edu

    We revisit the no-scale ripple inflation model, where no-scale supergravity is modified by an additional term for the inflaton field in the Kähler potential. This term not only breaks one SU(N,1) symmetry explicitly, but also plays an important role for inflation. We generalize the superpotential in the no-scale ripple inflation model slightly. There exists a discrete Z{sub 2} symmetry/parity in the scalar potential in general, which can be preserved or violated by the non-canonical nomalized inflaton kinetic term. Thus, there are three inflation paths: one parity invariant path, and the left and right paths for parity violating scenario. We showmore » that the inflations along the parity invariant path and right path are consistent with the Planck results. However, the gavitino mass for the parity invariant path is so large that the inflation results will be invalid if we consider the inflaton supersymmetry breaking soft mass term. Thus, only the inflation along the right path gives the correct and consistent results. Notably, the tensor-to-scalar ratio in such case can be large, with a value around 0.05, which may be probed by the future Planck experiment.« less

  16. SIRT3 opposes reprogramming of cancer cell metabolism through HIF1α destabilization

    PubMed Central

    Finley, Lydia W.S.; Carracedo, Arkaitz; Lee, Jaewon; Souza, Amanda; Egia, Ainara; Zhang, Jiangwen; Teruya-Feldstein, Julie; Moreira, Paula I.; Cardoso, Sandra M.; Clish, Clary B.; Pandolfi, Pier Paolo; Haigis, Marcia C.

    2011-01-01

    Summary Tumor cells exhibit aberrant metabolism characterized by high glycolysis even in the presence of oxygen. This metabolic reprogramming, known as the Warburg effect, provides tumor cells with the substrates required for biomass generation. Here, we show that the mitochondrial NAD-dependent deacetylase SIRT3 is a crucial regulator of the Warburg effect. Mechanistically, SIRT3 mediates metabolic reprogramming by destabilizing hypoxia-inducible factor-1α (HIF1α), a transcription factor that controls glycolytic gene expression. SIRT3 loss increases reactive oxygen species production, leading to HIF1α stabilization. SIRT3 expression is reduced in human breast cancers, and its loss correlates with the upregulation of HIF1α target genes. Finally, we find that SIRT3 overexpression represses glycolysis and proliferation in breast cancer cells, providing a metabolic mechanism for tumor suppression. PMID:21397863

  17. Revisiting doxycycline in pregnancy and early childhood--time to rebuild its reputation?

    PubMed

    Cross, Ruby; Ling, Clare; Day, Nicholas P J; McGready, Rose; Paris, Daniel H

    2016-01-01

    Doxycycline is highly effective, inexpensive with a broad therapeutic spectrum and exceptional bioavailability. However these benefits have been overshadowed by its classification alongside the tetracyclines - class D drugs, contraindicated in pregnancy and in children under 8 years of age. Doxycycline-treatable diseases are emerging as leading causes of undifferentiated febrile illness in Southeast Asia. For example scrub typhus and murine typhus have an unusually severe impact on pregnancy outcomes, and current mortality rates for scrub typhus reach 12-13% in India and Thailand. The emerging evidence for these important doxycycline-treatable diseases prompted us to revisit doxycycline usage in pregnancy and childhood. A systematic review of the available literature on doxycycline use in pregnant women and children revealed a safety profile of doxycycline that differed significantly from that of tetracycline; no correlation between the use of doxycycline and teratogenic effects during pregnancy or dental staining in children was found. The change of the US FDA pregnancy classification scheme to an evidence-based approach will enable adequate evaluation of doxycycline in common tropical illnesses and in vulnerable populations in clinical treatment trials, dosage-optimization pharmacokinetic studies and for the empirical treatment of undifferentiated febrile illnesses, especially in pregnant women and children.

  18. Energy in synthetic fertilizers and pesticides: Revisited. Final project report

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bhat, M.G.; English, B.C.; Turhollow, A.F.

    1994-01-01

    Agricultural chemicals that are derived from fossil-fuels are the major energy intensive inputs in agriculture. Growing scarcity of the world`s fossil resources stimulated research and development of energy-efficient technology for manufacturing these chemicals in the last decade. The purpose of this study is to revisit the energy requirements of major plant nutrients and pesticides. The data from manufacturers energy survey conducted by The Fertilizer Institute are used to estimate energy requirements of fertilizers. Energy estimates for pesticides are developed from consulting previously published literature. The impact of technical innovation in the fertilizer industry to US corn, cotton, soybean and wheatmore » producers is estimated in terms of energy-saving.« less

  19. Nutrient deprivation-related OXPHOS/glycolysis interconversion via HIF-1α/C-MYC pathway in U251 cells.

    PubMed

    Liu, Zhongjian; Sun, Yang; Tan, Shirui; Liu, Liang; Hu, Suqiong; Huo, Hongyu; Li, Meizhang; Cui, Qinghua; Yu, Min

    2016-05-01

    Although the Warburg effect is a dominant metabolic phenotype observed in cancers, the metabolic changes and adaptation occurring in tumors have been demonstrated to extend beyond the Warburg effect and thus considered a secondary effect to the transformation process of carcinogenesis, including nutritional deficiencies. However, the role of nutritional deficiencies in this metabolic reprogramming (e. g., oxidative phosphorylation (OXPHOS)/glycolysis interconversion) is not completely known yet. Here, we showed that under regular culture condition, the proliferation of U251 cells, but not other tumor cell lines, preferentially performed the Warburg effect and was remarkably inhibited by oxamic acid which can inhibit the activity of lactate dehydrogenase (LDH); whereas under serum starvation, glycolysis was depressed, tricarboxylic acid cycle (TCA) was enhanced, and the activity of OXPHOS was reinforced to maintain cellular ATP content in a high level, but interestingly, we observed a decreased expression of reactive oxygen species (ROS). Moreover, the upregulated activity of mitochondrial complex I was confirmed by Western blots and showed that the mitochondrial-related protein, NDUFA9, NDUFB8, ND1, and VDAC1 were remarkably increased after serum starved. Mechanistically, nutritional deficiencies could reduce hypoxia-inducible factor α (HIF-1α) protein expression to increase C-MYC protein level, which in turn increased nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM) transcription to enhance the activity of OXPHOS, suggesting that metabolic reprogramming by the changes of microenvironment during the carcinogenesis can provide some novel therapeutic clues to traditional cancer treatments.

  20. Revisiting adoption of high transmission PSM: pros, cons and path forward

    NASA Astrophysics Data System (ADS)

    Ma, Z. Mark; McDonald, Steve; Progler, Chris

    2009-12-01

    High transmission attenuated phase shift masks (Hi-T PSM) have been successfully applied in volume manufacturing for certain memory devices. Moreover, numerous studies have shown the potential benefits of Hi-T PSM for specific lithography applications. In this paper, the potential for extending Hi-T PSM to logic devices, is revisited with an emphasis on understanding layout, transmission, and manufacturing of Hi-T PSM versus traditional 6% embedded attenuated phase shift mask (EAPSM). Simulations on various layouts show Hi-T PSM has advantage over EAPSM in low duty cycle line patterns and high duty cycle space patterns. The overall process window can be enhanced when Hi- T PSM is combined with optimized optical proximity correction (OPC), sub-resolution assist features (SRAF), and source illumination. Therefore, Hi-T PSM may be a viable and lower cost alternative to other complex resolution enhancement technology (RET) approaches. Aerial image measurement system (AIMS) results on test masks, based on an inverse lithography technology (ILT) generated layout, confirm the simulation results. New advancement in high transmission blanks also make low topography Hi-T PSM a reality, which can minimize scattering effects in high NA lithography.

  1. Franklin Delano Roosevelt: The Diagnosis of Poliomyelitis Revisited.

    PubMed

    Ditunno, John F; Becker, Bruce E; Herbison, Gerald J

    2016-09-01

    Revisiting the ailments of famous historical persons in light of contemporary medical understanding has become a common academic hobby. Public discussion of Franklin Delano Roosevelt's (FDR) diagnosis of poliomyelitis after his sudden onset of paralysis in 1921 has received just such a revisitation. Recently, this 2003 historical analysis has been referenced widely on the Internet and in biographies, raising speculation that his actual diagnosis should have been Guillain-Barré Syndrome, a noncontagious disease of the peripheral nervous system rather than poliomyelitis. The authors of that 2003 analysis used a statistical analysis of his case by selectively choosing some of his reported symptoms. FDR's diagnosis of poliomyelitis, however, was fully supported by the findings of leading expert physicians of that time, who were very knowledgeable in the then-common disease and who periodically examined him during the period of 1921-1924. The most significant diagnostic features of polio are the absence of objective sensory findings in the presence of flaccid motor paralysis. These features are consistent with diagnostic criteria extant during the periods of major poliomyelitis epidemics as well as those of the Center for Disease Control 90 years later. Additional findings of fever, prodromal hyperesthesia, more severe residual proximal muscle weakness, and extensive lower extremity impairment requiring mobility with long leg braces or a wheelchair give further evidence for the diagnosis in FDR's case. Nonbulbar Guillain-Barré Syndrome, which shares the features of a flaccid paralysis and thus mimicking the initial presentation of poliomyelitis, has more than an 80% complete recovery with no reported cases of eventual wheelchair use. The most severe cases of Guillain-Barré Syndrome often have persistent objective sensory loss, associated with greater weakness in the feet and hands, which show no resemblance to FDR's impairment and disability. In light of the expert

  2. Revisiting inconsistency in large pharmacogenomic studies

    PubMed Central

    Safikhani, Zhaleh; Smirnov, Petr; Freeman, Mark; El-Hachem, Nehme; She, Adrian; Rene, Quevedo; Goldenberg, Anna; Birkbak, Nicolai J.; Hatzis, Christos; Shi, Leming; Beck, Andrew H.; Aerts, Hugo J.W.L.; Quackenbush, John; Haibe-Kains, Benjamin

    2017-01-01

    In 2013, we published a comparative analysis of mutation and gene expression profiles and drug sensitivity measurements for 15 drugs characterized in the 471 cancer cell lines screened in the Genomics of Drug Sensitivity in Cancer (GDSC) and Cancer Cell Line Encyclopedia (CCLE). While we found good concordance in gene expression profiles, there was substantial inconsistency in the drug responses reported by the GDSC and CCLE projects. We received extensive feedback on the comparisons that we performed. This feedback, along with the release of new data, prompted us to revisit our initial analysis. We present a new analysis using these expanded data, where we address the most significant suggestions for improvements on our published analysis — that targeted therapies and broad cytotoxic drugs should have been treated differently in assessing consistency, that consistency of both molecular profiles and drug sensitivity measurements should be compared across cell lines, and that the software analysis tools provided should have been easier to run, particularly as the GDSC and CCLE released additional data. Our re-analysis supports our previous finding that gene expression data are significantly more consistent than drug sensitivity measurements. Using new statistics to assess data consistency allowed identification of two broad effect drugs and three targeted drugs with moderate to good consistency in drug sensitivity data between GDSC and CCLE. For three other targeted drugs, there were not enough sensitive cell lines to assess the consistency of the pharmacological profiles. We found evidence of inconsistencies in pharmacological phenotypes for the remaining eight drugs. Overall, our findings suggest that the drug sensitivity data in GDSC and CCLE continue to present challenges for robust biomarker discovery. This re-analysis provides additional support for the argument that experimental standardization and validation of pharmacogenomic response will be necessary to

  3. Changes in Sea Levels around the British Isles Revisited (Invited)

    NASA Astrophysics Data System (ADS)

    Teferle, F. N.; Hansen, D. N.; Bingley, R. M.; Williams, S. D.; Woodworth, P. L.; Gehrels, W. R.; Bradley, S. L.; Stocchi, P.

    2009-12-01

    Recently a number of new and/or updated sources for estimates of vertical land movements for the British Isles have become available allowing the relative and average changes in sea levels for this region to be revisited. The geodetic data set stems from a combination of re-processed continuous Global Positioning System (GPS) measurements from stations in the British Isles and from a global reference frame network, and absolute gravity (AG) measurements from two stations in the British Isles. The geologic data set of late Holocene sea level indicators has recently been updated, now applying corrections for the 20th century sea level rise, syphoning effect and late Holocene global ice melt, and expanded to Northern Ireland and Ireland. Several new model predictions of the glacial isostatic adjustment (GIA) process active in this region form the modelling data set of vertical land movements for the British Isles. Correcting the updated revised local reference (RLR) trends from the Permanent Service for Mean Sea Level (PSMSL) with these vertical land movement data sets, regional and averaged changes in sea levels around the British Isles have been investigated. Special focus is thereby also given to the coastal areas that have recently been identified within the UK Climate Projections 2009.

  4. Computational Electrocardiography: Revisiting Holter ECG Monitoring.

    PubMed

    Deserno, Thomas M; Marx, Nikolaus

    2016-08-05

    Since 1942, when Goldberger introduced the 12-lead electrocardiography (ECG), this diagnostic method has not been changed. After 70 years of technologic developments, we revisit Holter ECG from recording to understanding. A fundamental change is fore-seen towards "computational ECG" (CECG), where continuous monitoring is producing big data volumes that are impossible to be inspected conventionally but require efficient computational methods. We draw parallels between CECG and computational biology, in particular with respect to computed tomography, computed radiology, and computed photography. From that, we identify technology and methodology needed for CECG. Real-time transfer of raw data into meaningful parameters that are tracked over time will allow prediction of serious events, such as sudden cardiac death. Evolved from Holter's technology, portable smartphones with Bluetooth-connected textile-embedded sensors will capture noisy raw data (recording), process meaningful parameters over time (analysis), and transfer them to cloud services for sharing (handling), predicting serious events, and alarming (understanding). To make this happen, the following fields need more research: i) signal processing, ii) cycle decomposition; iii) cycle normalization, iv) cycle modeling, v) clinical parameter computation, vi) physiological modeling, and vii) event prediction. We shall start immediately developing methodology for CECG analysis and understanding.

  5. Gaussian entanglement revisited

    NASA Astrophysics Data System (ADS)

    Lami, Ludovico; Serafini, Alessio; Adesso, Gerardo

    2018-02-01

    We present a novel approach to the separability problem for Gaussian quantum states of bosonic continuous variable systems. We derive a simplified necessary and sufficient separability criterion for arbitrary Gaussian states of m versus n modes, which relies on convex optimisation over marginal covariance matrices on one subsystem only. We further revisit the currently known results stating the equivalence between separability and positive partial transposition (PPT) for specific classes of Gaussian states. Using techniques based on matrix analysis, such as Schur complements and matrix means, we then provide a unified treatment and compact proofs of all these results. In particular, we recover the PPT-separability equivalence for: (i) Gaussian states of 1 versus n modes; and (ii) isotropic Gaussian states. In passing, we also retrieve (iii) the recently established equivalence between separability of a Gaussian state and and its complete Gaussian extendability. Our techniques are then applied to progress beyond the state of the art. We prove that: (iv) Gaussian states that are invariant under partial transposition are necessarily separable; (v) the PPT criterion is necessary and sufficient for separability for Gaussian states of m versus n modes that are symmetric under the exchange of any two modes belonging to one of the parties; and (vi) Gaussian states which remain PPT under passive optical operations can not be entangled by them either. This is not a foregone conclusion per se (since Gaussian bound entangled states do exist) and settles a question that had been left unanswered in the existing literature on the subject. This paper, enjoyable by both the quantum optics and the matrix analysis communities, overall delivers technical and conceptual advances which are likely to be useful for further applications in continuous variable quantum information theory, beyond the separability problem.

  6. 'Counterfeit deviance' revisited.

    PubMed

    Griffiths, Dorothy; Hingsburger, Dave; Hoath, Jordan; Ioannou, Stephanie

    2013-09-01

    The field has seen a renewed interest in exploring the theory of 'counterfeit deviance' for persons with intellectual disability who sexually offend. The term was first presented in 1991 by Hingsburger, Griffiths and Quinsey as a means to differentiate in clinical assessment a subgroup of persons with intellectual disability whose behaviours appeared like paraphilia but served a function that was not related to paraphilia sexual urges or fantasies. Case observations were put forward to provide differential diagnosis of paraphilia in persons with intellectual disabilities compared to those with counterfeit deviance. The brief paper was published in a journal that is no longer available and as such much of what is currently written on the topic is based on secondary sources. The current paper presents a theoretical piece to revisit the original counterfeit deviance theory to clarify the myths and misconceptions that have arisen and evaluate the theory based on additional research and clinical findings. The authors also propose areas where there may be a basis for expansion of the theory. The theory of counterfeit deviance still has relevance as a consideration for clinicians when assessing the nature of a sexual offence committed by a person with an intellectual disability. Clinical differentiation of paraphilia from counterfeit deviance provides a foundation for intervention that is designed to specifically treat the underlying factors that contributed to the offence for a given individual. Counterfeit deviance is a concept that continues to provide areas for consideration for clinicians regarding the assessment and treatment of an individual with an intellectual disability who has sexually offended. It is not and never was an explanation for all sexually offending behavior among persons with intellectual disabilities. © 2013 John Wiley & Sons Ltd.

  7. Metformin: Multi-faceted protection against cancer

    PubMed Central

    Cufí, Sílvia; Oliveras-Ferraros, Cristina; Bosch-Barrera, Joaquim; Joven, Jorge; Martin-Castillo, Begoña; Menendez, Javier A.

    2011-01-01

    The biguanide metformin, a widely used drug for the treatment of type 2 diabetes, may exert cancer chemopreventive effects by suppressing the transformative and hyperproliferative processes that initiate carcinogenesis. Metformin's molecular targets in cancer cells (e.g., mTOR, HER2) are similar to those currently being used for directed cancer therapy. However, metformin is nontoxic and might be extremely useful for enhancing treatment efficacy of mechanism-based and biologically targeted drugs. Here, we first revisit the epidemiological, preclinical, and clinical evidence from the last 5 years showing that metformin is a promising candidate for oncology therapeutics. Second, the anticancer effects of metformin by both direct (insulin-independent) and indirect (insulin-dependent) mechanisms are discussed in terms of metformin-targeted processes and the ontogenesis of cancer stem cells (CSC), including Epithelial-to-Mesenchymal Transition (EMT) and microRNAs-regulated dedifferentiation of CSCs. Finally, we present preliminary evidence that metformin may regulate cellular senescence, an innate safeguard against cellular immortalization. There are two main lines of evidence that suggest that metformin's primary target is the immortalizing step during tumorigenesis. First, metformin activates intracellular DNA damage response checkpoints. Second, metformin attenuates the anti-senescence effects of the ATP-generating glycolytic metabotype-the Warburg effect-, which is required for self-renewal and proliferation of CSCs. If metformin therapy presents an intrinsic barrier against tumorigenesis by lowering the threshold for stress-induced senescence, metformin therapeutic strategies may be pivotal for therapeutic intervention for cancer. Current and future clinical trials will elucidate whether metformin has the potential to be used in preventive and treatment settings as an adjuvant to current cancer therapeutics. PMID:22203527

  8. Revisiting flow maps: a classification and a 3D alternative to visual clutter

    NASA Astrophysics Data System (ADS)

    Gu, Yuhang; Kraak, Menno-Jan; Engelhardt, Yuri

    2018-05-01

    Flow maps have long been servicing people in exploring movement by representing origin-destination data (OD data). Due to recent developments in data collecting techniques the amount of movement data is increasing dramatically. With such huge amounts of data, visual clutter in flow maps is becoming a challenge. This paper revisits flow maps, provides an overview of the characteristics of OD data and proposes a classification system for flow maps. For dealing with problems of visual clutter, 3D flow maps are proposed as potential alternative to 2D flow maps.

  9. Aztec arithmetic revisited: land-area algorithms and Acolhua congruence arithmetic.

    PubMed

    Williams, Barbara J; Jorge y Jorge, María del Carmen

    2008-04-04

    Acolhua-Aztec land records depicting areas and side dimensions of agricultural fields provide insight into Aztec arithmetic. Hypothesizing that recorded areas resulted from indigenous calculation, in a study of sample quadrilateral fields we found that 60% of the area values could be reproduced exactly by computation. In remaining cases, discrepancies between computed and recorded areas were consistently small, suggesting use of an unknown indigenous arithmetic. In revisiting the research, we discovered evidence for the use of congruence principles, based on proportions between the standard linear Acolhua measure and their units of shorter length. This procedure substitutes for computation with fractions and is labeled "Acolhua congruence arithmetic." The findings also clarify variance between Acolhua and Tenochca linear units, long an issue in understanding Aztec metrology.

  10. How long will honey bees (Apis mellifera L.) be stimulated by scent to revisit past-profitable forage sites?

    PubMed

    Beekman, Madeleine

    2005-12-01

    Honey bees utilise floral food sources that vary temporally in their relative and absolute quality. Via a sophisticated colony organisation, a honey bee colony allocates its foragers such that the colony focuses on the most profitable forage sites while keeping track of changes within its foraging environment. One important mechanism of the allocation of foragers is the ability of experienced foragers to revisit past-profitable forage sites after a period of temporary dearth caused by, for example, inclement weather. The scent of past-profitable forage within the colony brought back by other foragers is sufficient to reactivate these experienced foragers. Here I determine for how long bees react to the scent of a past-profitable forage site. I show that the ability of foragers to revisit the location of a past-profitable food source diminishes rapidly over a period of 10 days, until no forager reacts to the cue (scent). I discuss the implications of these findings with respect to the colony's ability to react rapidly to changing foraging conditions.

  11. Carbon emission from global hydroelectric reservoirs revisited.

    PubMed

    Li, Siyue; Zhang, Quanfa

    2014-12-01

    Substantial greenhouse gas (GHG) emissions from hydropower reservoirs have been of great concerns recently, yet the significant carbon emitters of drawdown area and reservoir downstream (including spillways and turbines as well as river reaches below dams) have not been included in global carbon budget. Here, we revisit GHG emission from hydropower reservoirs by considering reservoir surface area, drawdown zone and reservoir downstream. Our estimates demonstrate around 301.3 Tg carbon dioxide (CO2)/year and 18.7 Tg methane (CH4)/year from global hydroelectric reservoirs, which are much higher than recent observations. The sum of drawdown and downstream emission, which is generally overlooked, represents 42 % CO2 and 67 % CH4 of the total emissions from hydropower reservoirs. Accordingly, the global average emissions from hydropower are estimated to be 92 g CO2/kWh and 5.7 g CH4/kWh. Nonetheless, global hydroelectricity could currently reduce approximate 2,351 Tg CO2eq/year with respect to fuel fossil plant alternative. The new findings show a substantial revision of carbon emission from the global hydropower reservoirs.

  12. Gurtin-Murdoch surface elasticity theory revisit: An orbital-free density functional theory perspective

    NASA Astrophysics Data System (ADS)

    Zhu, Yichao; Wei, Yihai; Guo, Xu

    2017-12-01

    In the present paper, the well-established Gurtin-Murdoch theory of surface elasticity (Gurtin and Murdoch, 1975, 1978) is revisited from an orbital-free density functional theory (OFDFT) perspective by taking the boundary layer into consideration. Our analysis indicates that firstly, the quantities introduced in the Gurtin-Murdoch theory of surface elasticity can all find their explicit expressions in the derived OFDFT-based theoretical model. Secondly, the derived expression for surface energy density captures a competition between the surface normal derivatives of the electron density and the electrostatic potential, which well rationalises the onset of signed elastic constants that are observed both experimentally and computationally. Thirdly, the established model naturally yields an inversely linear relationship between the materials surface stiffness and its size, which conforms to relevant findings in literature. Since the proposed OFDFT-based model is established under arbitrarily imposed boundary condition of electron density, electrostatic potential and external load, it also has the potential of being used to investigate the electro-mechanical behaviour of nanoscale materials manifesting surface effect.

  13. Diffusion orientation transform revisited.

    PubMed

    Canales-Rodríguez, Erick Jorge; Lin, Ching-Po; Iturria-Medina, Yasser; Yeh, Chun-Hung; Cho, Kuan-Hung; Melie-García, Lester

    2010-01-15

    Diffusion orientation transform (DOT) is a powerful imaging technique that allows the reconstruction of the microgeometry of fibrous tissues based on diffusion MRI data. The three main error sources involving this methodology are the finite sampling of the q-space, the practical truncation of the series of spherical harmonics and the use of a mono-exponential model for the attenuation of the measured signal. In this work, a detailed mathematical description that provides an extension to the DOT methodology is presented. In particular, the limitations implied by the use of measurements with a finite support in q-space are investigated and clarified as well as the impact of the harmonic series truncation. Near- and far-field analytical patterns for the diffusion propagator are examined. The near-field pattern makes available the direct computation of the probability of return to the origin. The far-field pattern allows probing the limitations of the mono-exponential model, which suggests the existence of a limit of validity for DOT. In the regimen from moderate to large displacement lengths the isosurfaces of the diffusion propagator reveal aberrations in form of artifactual peaks. Finally, the major contribution of this work is the derivation of analytical equations that facilitate the accurate reconstruction of some orientational distribution functions (ODFs) and skewness ODFs that are relatively immune to these artifacts. The new formalism was tested using synthetic and real data from a phantom of intersecting capillaries. The results support the hypothesis that the revisited DOT methodology could enhance the estimation of the microgeometry of fiber tissues.

  14. Revisiting doxycycline in pregnancy and early childhood – time to rebuild its reputation?

    PubMed Central

    Cross, Ruby; Ling, Clare; Day, Nicholas P. J.; McGready, Rose; Paris, Daniel H.

    2016-01-01

    ABSTRACT Introduction: Doxycycline is highly effective, inexpensive with a broad therapeutic spectrum and exceptional bioavailability. However these benefits have been overshadowed by its classification alongside the tetracyclines – class D drugs, contraindicated in pregnancy and in children under 8 years of age. Doxycycline-treatable diseases are emerging as leading causes of undifferentiated febrile illness in Southeast Asia. For example scrub typhus and murine typhus have an unusually severe impact on pregnancy outcomes, and current mortality rates for scrub typhus reach 12-13% in India and Thailand. The emerging evidence for these important doxycycline-treatable diseases prompted us to revisit doxycycline usage in pregnancy and childhood. Areas Covered: A systematic review of the available literature on doxycycline use in pregnant women and children revealed a safety profile of doxycycline that differed significantly from that of tetracycline; no correlation between the use of doxycycline and teratogenic effects during pregnancy or dental staining in children was found. Expert Opinion: The change of the US FDA pregnancy classification scheme to an evidence-based approach will enable adequate evaluation of doxycycline in common tropical illnesses and in vulnerable populations in clinical treatment trials, dosage-optimization pharmacokinetic studies and for the empirical treatment of undifferentiated febrile illnesses, especially in pregnant women and children. PMID:26680308

  15. Foregrounding Effects during Reading, Revisited

    ERIC Educational Resources Information Center

    Cook, Anne E.; Gueraud, Sabine; Was, Christopher A.; O'Brien, Edward J.

    2007-01-01

    Previous researchers have argued that objects associated with a protagonist may be foregrounded, or held active, in memory. This study expanded on previous work by using an inconsistency paradigm to investigate the effects of protagonist association on object accessibility. Readers experienced more processing difficulty when a target sentence…

  16. B3GALNT2-Related Dystroglycanopathy: Expansion of the Phenotype with Novel Mutation Associated with Muscle-Eye-Brain Disease, Walker-Warburg Syndrome, Epileptic Encephalopathy-West Syndrome, and Sensorineural Hearing Loss.

    PubMed

    Al Dhaibani, Muna A; El-Hattab, Ayman W; Ismayl, Omar; Suleiman, Jehan

    2018-05-23

    Mutations in B3GALNT2 , encoding a glycosyltransferase enzyme involved in α-dystroglycan glycosylation, have been recently associated with dystroglycanopathy, a well-recognized subtype of congenital muscular dystrophy (CMD). Only a few cases have been reported with B3GALNT2 -related dystroglycanopathy with variable severity ranging from mild CMD to severe muscle-eye-brain disease. Here, we describe a child with a novel homozygous nonsense mutation in B3GALNT2 . The affected child has severe neurological disease since birth, including muscle disease manifested as hypotonia, muscle weakness, and wasting with elevated creatine kinase, eye disease including microphthalmia and blindness, brain disease with extensive brain malformations including massive hydrocephalus, diffuse cobblestone-lissencephaly, deformed craniocervical junction, and pontocerebellar hypoplasia. The clinical and radiologic findings are compatible with a diagnosis of severe muscle-eye-brain disease and more specifically Walker-Warburg syndrome. A more distinct aspect of the clinical phenotype in this child is the presence of refractory epilepsy in the form of epileptic spasms, epileptic encephalopathy, and West syndrome, as well as sensorineural hearing loss. These findings could expand the phenotype of B3GALNT2 -related dystroglycanopathy. In this report, we also provide a detailed review of previously reported cases with B3GALNT2 -related dystroglycanopathy and compare them to our reported child. In addition, we study the genotype-phenotype correlation in these cases. Georg Thieme Verlag KG Stuttgart · New York.

  17. Effects of Weather on Tourism and its Moderation

    NASA Astrophysics Data System (ADS)

    Park, J. H.; Kim, S.; Lee, D. K.

    2016-12-01

    Tourism is weather sensitive industry (Gómez Martín, 2005). As climate change has been intensifying, the concerns about negative effects of weather on tourism also have been increasing. This study attempted to find ways that mitigate the negative effects from weather on tourism, by analyzing a path of the effects of weather on intention to revisit and its moderation. The data of the study were collected by a self-recording online questionnaire survey of South Korean domestic tourists during August 2015, and 2,412 samples were gathered. A path model of effects of weather on intention to revisit that including moderating effects from physical attraction satisfaction and service satisfaction was ran. Season was controlled in the path model. The model fit was adequate (CMIN/DF=2.372(p=.000), CFI=.974, RMSEA=.024, SRMR=0.040), and the Model Comparison, which assumes that the base model to be correct with season constrained model, showed that there was a seasonal differences in the model ( DF=24, CMIN=32.430, P=.117). By the analysis, it was figured out that weather and weather expectation affected weather satisfaction, and the weather satisfaction affected intention to revisit (spring/fall: .167**, summer: .104**, and winter: .114**). Meanwhile physical attraction satisfaction (.200**), and service satisfaction (.210**) of tourism positively moderated weather satisfaction in summer, and weather satisfaction positively moderated physical attraction (.238**) satisfaction and service satisfaction (.339**). In other words, in summer, dissatisfaction from hot weather was moderated by satisfaction from physical attractions and services, and in spring/fall, comfort weather conditions promoted tourists to accept tourism experience and be satisfied from attractions and services positively. Based on the result, it was expected that if industries focus on offering the good attractions and services based on weather conditions, there would be positive effects to alleviate tourists

  18. A revisit to the temperature dependence of electrical resistivity of α - Titanium at low temperatures

    NASA Astrophysics Data System (ADS)

    Sharath Chandra, L. S.; Mondal, R.; Thamizhavel, A.; Dhar, S. K.; Roy, S. B.

    2017-09-01

    The temperature dependence of resistivity ρ(T) of a polycrystalline sample and a single crystal sample (current along the [0001] direction) of α - Titanium (Ti) at low temperatures is revisited to understand the electrical charge transport phenomena in this hexagonal closed pack metal. We show that the ρ(T) in single crystal Ti can be explained by considering the scattering of electrons due to electron-phonon, electron-electron, inter-band s-d and electron-impurity interactions, whereas the ρ(T) of polycrystalline Ti could not be explained by these interactions alone. We observed that the effects of the anisotropy of the hexagonal structure on the electronic band structure and the phonon dispersion need to be taken into account to explain ρ(T) of polycrystalline Ti. Two Debye temperatures corresponding to two different directions for the electron-phonon interactions and inter-band s-d scattering are needed to account the observed ρ(T) in polycrystalline Ti.

  19. The U.S.-Canada Border Effect : Smaller Than Previously Thought and Becoming Smaller

    DOT National Transportation Integrated Search

    2012-05-30

    We revisit the effect of the U.S.-Canada national border on trade, considering to what extent the border reduces trade when : observable economic factors are controlled. A reexamination of the data yields estimates of the border effect that are 50% :...

  20. Today's Teens, Their Problems, and Their Literature: Revisiting G. Robert Carlsen's "Books and the Teenage Reader" Thirty Years Later.

    ERIC Educational Resources Information Center

    Carroll, Pamela Sissi

    1997-01-01

    Revisits G. Robert Carlsen's call for the use of young adult literature in the classroom by looking specifically at the emotional and reading needs of older adolescents, those in the upper grades. Discusses problems associated with adolescence in the late twentieth century and lists recommended young adult books that touch on those issues. (TB)

  1. Cancer metabolism in space and time: Beyond the Warburg effect.

    PubMed

    Danhier, Pierre; Bański, Piotr; Payen, Valéry L; Grasso, Debora; Ippolito, Luigi; Sonveaux, Pierre; Porporato, Paolo E

    2017-08-01

    Altered metabolism in cancer cells is pivotal for tumor growth, most notably by providing energy, reducing equivalents and building blocks while several metabolites exert a signaling function promoting tumor growth and progression. A cancer tissue cannot be simply reduced to a bulk of proliferating cells. Tumors are indeed complex and dynamic structures where single cells can heterogeneously perform various biological activities with different metabolic requirements. Because tumors are composed of different types of cells with metabolic activities affected by different spatial and temporal contexts, it is important to address metabolism taking into account cellular and biological heterogeneity. In this review, we describe this heterogeneity also in metabolic fluxes, thus showing the relative contribution of different metabolic activities to tumor progression according to the cellular context. This article is part of a Special Issue entitled Mitochondria in Cancer, edited by Giuseppe Gasparre, Rodrigue Rossignol and Pierre Sonveaux. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Revisiting the argument from fetal potential

    PubMed Central

    Manninen, Bertha Alvarez

    2007-01-01

    One of the most famous, and most derided, arguments against the morality of abortion is the argument from potential, which maintains that the fetus' potential to become a person and enjoy the valuable life common to persons, entails that its destruction is prima facie morally impermissible. In this paper, I will revisit and offer a defense of the argument from potential. First, I will criticize the classical arguments proffered against the importance of fetal potential, specifically the arguments put forth by philosophers Peter Singer and David Boonin, by carefully unpacking the claims made in these arguments and illustrating why they are flawed. Secondly, I will maintain that fetal potential is morally relevant when it comes to the morality of abortion, but that it must be accorded a proper place in the argument. This proper place, however, cannot be found until we first answer a very important and complex question: we must first address the issue of personal identity, and when the fetus becomes the type of being who is relevantly identical to a future person. I will illustrate why the question of fetal potential can only be meaningfully addressed after we have first answered the question of personal identity and how it relates to the human fetus. PMID:17509146

  3. The Kickstart of the Age of the Earth Race: Revisiting the Experiment of the Comte de Buffon at School

    ERIC Educational Resources Information Center

    Pincelli, M. M.; Prat, M. R.; Lescano, G. M.; Formichella, M. del C.; Brustle, M.; Otranto, S.

    2018-01-01

    In this work, the first experiment ever done to determine the age of the Earth is revisited. The benefits of its application at primary and secondary school levels are presented and discussed. In particular, emphasis is placed on the advantage of facing students with the challenges that scientists have had to overcome during the past three…

  4. Warburg and Crabtree Effects in Premalignant Barrett's Esophagus Cell Lines with Active Mitochondria

    PubMed Central

    Suchorolski, Martin T.; Paulson, Thomas G.; Sanchez, Carissa A.; Hockenbery, David; Reid, Brian J.

    2013-01-01

    Background Increased glycolysis is a hallmark of cancer metabolism, yet relatively little is known about this phenotype at premalignant stages of progression. Periodic ischemia occurs in the premalignant condition Barrett's esophagus (BE) due to tissue damage from chronic acid-bile reflux and may select for early adaptations to hypoxia, including upregulation of glycolysis. Methodology/Principal Findings We compared rates of glycolysis and oxidative phosphorylation in four cell lines derived from patients with BE (CP-A, CP-B, CP-C and CP-D) in response to metabolic inhibitors and changes in glucose concentration. We report that cell lines derived from patients with more advanced genetically unstable BE have up to two-fold higher glycolysis compared to a cell line derived from a patient with early genetically stable BE; however, all cell lines preserve active mitochondria. In response to the glycolytic inhibitor 2-deoxyglucose, the most glycolytic cell lines (CP-C and CP-D) had the greatest suppression of extra-cellular acidification, but were able to compensate with upregulation of oxidative phosphorylation. In addition, these cell lines showed the lowest compensatory increases in glycolysis in response to mitochondrial uncoupling by 2,4-dinitrophenol. Finally, these cell lines also upregulated their oxidative phosphorylation in response to glucose via the Crabtree effect, and demonstrate a greater range of modulation of oxygen consumption. Conclusions/Significance Our findings suggest that cells from premalignant Barrett's esophagus tissue may adapt to an ever-changing selective microenvironment through changes in energy metabolic pathways typically associated with cancer cells. PMID:23460817

  5. Mitochondria: 3-bromopyruvate vs. mitochondria? A small molecule that attacks tumors by targeting their bioenergetic diversity.

    PubMed

    Galina, Antonio

    2014-09-01

    Enhanced glycolysis, the classic bioenergetic phenotype of cancer cells was described by Otto Warburg approximately 90 years ago. However, the Warburg hypothesis does not necessarily imply mitochondrial dysfunction. The alkyl-halogen, 3-bromopyruvate (3BP), would not be expected to have selective targets for cancer therapy due to its high potential reactivity toward many SH side groups. Contrary to predictions, 3BP interferes with glycolysis and oxidative phosphorylation in cancer cells without side effects in normal tissues. The mitochondrial hexokinase II has been claimed as the main target. This "Organelle in focus" article presents a historical view of the use of 3BP in biochemistry and its effects on ATP-producing pathways of cancer cells. I will discuss how the alkylated enzymes contribute to the cooperative collapse of mitochondria and apoptosis. Perspectives for targeting 3BP to bioenergetics enzymes for cancer treatment will be considered. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Lactic acidosis switches cancer cells from aerobic glycolysis back to dominant oxidative phosphorylation

    PubMed Central

    Wu, Hao; Ying, Minfeng; Hu, Xun

    2016-01-01

    While transformation of normal cells to cancer cells is accompanied with a switch from oxidative phosphorylation (OXPHOS) to aerobic glycolysis, it is interesting to ask if cancer cells can revert from Warburg effect to OXPHOS. Our previous works suggested that cancer cells reverted to OXPHOS, when they were exposed to lactic acidosis, a common factor in tumor environment. However, the conclusion cannot be drawn unless ATP output from glycolysis and OXPHOS is quantitatively determined. Here we quantitatively measured ATP generation from glycolysis and OXPHOS in 9 randomly selected cancer cell lines. Without lactic acidosis, glycolysis and OXPHOS generated 23.7% − 52.2 % and 47.8% − 76.3% of total ATP, respectively; with lactic acidosis (20 mM lactate with pH 6.7), glycolysis and OXPHOS provided 5.7% − 13.4% and 86.6% − 94.3% of total ATP. We concluded that cancer cells under lactic acidosis reverted from Warburg effect to OXPHOS phenotype. PMID:27259254

  7. Lactic acidosis switches cancer cells from aerobic glycolysis back to dominant oxidative phosphorylation.

    PubMed

    Wu, Hao; Ying, Minfeng; Hu, Xun

    2016-06-28

    While transformation of normal cells to cancer cells is accompanied with a switch from oxidative phosphorylation (OXPHOS) to aerobic glycolysis, it is interesting to ask if cancer cells can revert from Warburg effect to OXPHOS. Our previous works suggested that cancer cells reverted to OXPHOS, when they were exposed to lactic acidosis, a common factor in tumor environment. However, the conclusion cannot be drawn unless ATP output from glycolysis and OXPHOS is quantitatively determined. Here we quantitatively measured ATP generation from glycolysis and OXPHOS in 9 randomly selected cancer cell lines. Without lactic acidosis, glycolysis and OXPHOS generated 23.7% - 52.2 % and 47.8% - 76.3% of total ATP, respectively; with lactic acidosis (20 mM lactate with pH 6.7), glycolysis and OXPHOS provided 5.7% - 13.4% and 86.6% - 94.3% of total ATP. We concluded that cancer cells under lactic acidosis reverted from Warburg effect to OXPHOS phenotype.

  8. CREB1 regulates glucose transport of glioma cell line U87 by targeting GLUT1.

    PubMed

    Chen, Jiaying; Zhang, Can; Mi, Yang; Chen, Fuxue; Du, Dongshu

    2017-12-01

    Glioma is stemmed from the glial cells in the brain, which is accounted for about 45% of all intracranial tumors. The characteristic of glioma is invasive growth, as well as there is no obvious boundary between normal brain tissue and glioma tissue, so it is difficult to resect completely with worst prognosis. The metabolism of glioma is following the Warburg effect. Previous researches have shown that GLUT1, as a glucose transporter carrier, affected the Warburg effect, but the molecular mechanism is not very clear. CREB1 (cAMP responsive element-binding protein1) is involved in various biological processes, and relevant studies confirmed that CREB1 protein regulated the expression of GLUT1, thus mediating glucose transport in cells. Our experiments mainly reveal that the CREB1 could affect glucose transport in glioma cells by regulating the expression of GLUT1, which controlled the metabolism of glioma and affected the progression of glioma.

  9. Revisiting the relaxation dynamics of isolated pyrrole

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Montero, Raúl; Ovejas, Virginia; Fernández-Fernández, Marta

    Herein, the interpretation of the femtosecond-scale temporal evolution of the pyrrole ion signal, after excitation in the 267–217 nm interval, recently published by our group [R. Montero, A. Peralta Conde, V. Ovejas, M. Fernández-Fernández, F. Castaño, J. R. Vázquez de Aldana, and A. Longarte, J. Chem. Phys.137, 064317 (2012)] is re-visited. The observation of a shift in the pyrrole{sup +} transient respect to zero delay reference, initially attributed to ultrafast dynamics on the πσ{sup *} type state (3s a{sub 1} ← π 1a{sub 2}), is demonstrated to be caused by the existence of pump + probe populated states, along themore » ionization process. The influence of these resonances in pump-prone ionization experiments, when multi-photon probes are used, and the significance of a proper zero-time reference, is discussed. The possibility of preparing the πσ{sup *} state by direct excitation is investigated by collecting 1 + 1 photoelectron spectra, at excitation wavelengths ranging from 255 to 219 nm. No conclusive evidences of ionization through this state are found.« less

  10. Revisiting Stephan's Quintet with deep optical images

    NASA Astrophysics Data System (ADS)

    Duc, Pierre-Alain; Cuillandre, Jean-Charles; Renaud, Florent

    2018-03-01

    Stephan's Quintet, a compact group of galaxies, is often used as a laboratory to study a number of phenomena, including physical processes in the interstellar medium, star formation, galaxy evolution, and the formation of fossil groups. As such, it has been subject to intensive multiwavelength observation campaigns. Yet, models lack constrains to pin down the role of each galaxy in the assembly of the group. We revisit here this system with multiband deep optical images obtained with MegaCam on the Canada-France-Hawaii Telescope (CFHT), focusing on the detection of low surface brightness (LSB) structures. They reveal a number of extended LSB features, some new, and some already visible in published images but not discussed before. An extended diffuse, reddish, lopsided, halo is detected towards the early-type galaxy NGC 7317, the role of which had so far been ignored in models. The presence of this halo made of old stars may indicate that the group formed earlier than previously thought. Finally, a number of additional diffuse filaments are visible, some close to the foreground galaxy NGC 7331 located in the same field. Their structure and association with mid-infrared emission suggest contamination by emission from Galactic cirrus.

  11. Solar system anomalies: Revisiting Hubble's law

    NASA Astrophysics Data System (ADS)

    Plamondon, R.

    2017-12-01

    This paper investigates the impact of a new metric recently published [R. Plamondon and C. Ouellet-Plamondon, in On Recent Developments in Theoretical and Experimental General Relativity, Astrophysics, and Relativistic Field Theories, edited by K. Rosquist, R. T. Jantzen, and R. Ruffini (World Scientific, Singapore, 2015), p. 1301] for studying the space-time geometry of a static symmetric massive object. This metric depends on a complementary error function (erfc) potential that characterizes the emergent gravitation field predicted by the model. This results in two types of deviations as compared to computations made on the basis of a Newtonian potential: a constant and a radial outcome. One key feature of the metric is that it postulates the existence of an intrinsic physical constant σ , the massive object-specific proper length that scales measurements in its surroundings. Although σ must be evaluated experimentally, we use a heuristic to estimate its value and point out some latent relationships between the Hubble constant, the secular increase in the astronomical unit, and the Pioneers delay. Indeed, highlighting the systematic errors that emerge when the effect of σ is neglected, one can link the Hubble constant H 0 to σ Sun and the secular increase V AU to σ Earth . The accuracy of the resulting numerical predictions, H 0 = 74 . 42 ( 0 . 02 ) ( km / s ) / Mpc and V AU ≅ 7.8 cm yr-1 , calls for more investigations of this new metric by specific experts. Moreover, we investigate the expected impacts of the new metric on the flyby anomalies, and we revisit the Pioneers delay. It is shown that both phenomena could be partly taken into account within the context of this unifying paradigm, with quite accurate numerical predictions. A correction for the osculating asymptotic velocity at the perigee of the order of 10 mm/s and an inward radial acceleration of 8 . 34 × 10 - 10 m / s 2 affecting the Pioneer ! space crafts could be explained by this new model.

  12. "Ultra High Dilution 1994" revisited 2015--the state of follow-up research.

    PubMed

    Endler, P Christian; Schulte, Jurgen; Stock-Schroeer, Beate; Stephen, Saundra

    2015-10-01

    The "Ultra High Dilution 1994" project was an endeavour to take stock of the findings and theories on homeopathic extreme dilutions that were under research at the time in areas of biology, biophysics, physics and medicine. The project finally materialized into an anthology assembling contributions of leading scientists in the field. Over the following two decades, it became widely quoted within the homeopathic community and also known in other research communities. The aim of the present project was to re-visit and review the 1994 studies from the perspective of 2015. The original authors from 1994 or close laboratory colleagues were asked to contribute papers covering their research efforts and learnings in the period from 1994 up to 2015. These contributions were edited and cross-referenced, and a selection of further contributions was added. About a dozen contributions reported on follow-up experiments and studies, including further developments in theory. Only few of the models that had seemed promising in 1994 had not been followed up later. Most models presented in the original publication had meanwhile been submitted to intra-laboratory, multicentre or independent scrutiny. The results of the follow-up research seemed to have rewarded the efforts. Furthermore, contributions were provided on new models that had been inspired by the original ones or that may be candidates for further in-depth ultra high dilution (UHD) research. The project "Ultra High Dilution 1994 revisited 2015" is the latest output of what might be considered the "buena vista social club" of homeopathy research. However, it presents new developments and results of the older, established experimental models as well as a general survey of the state of UHD research. Copyright © 2015 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

  13. Perceived parenting style and adolescent adjustment: revisiting directions of effects and the role of parental knowledge.

    PubMed

    Kerr, Margaret; Stattin, Håkan; Ozdemir, Metin

    2012-11-01

    In the present research on parenting and adolescent behavior, there is much focus on reciprocal, bidirectional, and transactional processes, but parenting-style research still adheres to a unidirectional perspective in which parents affect youth behavior but are unaffected by it. In addition, many of the most cited parenting-style studies have used measures of parental behavioral control that are questionable because they include measures of parental knowledge. The goals of this study were to determine whether including knowledge items might have affected results of past studies and to test the unidirectional assumption. Data were from 978 adolescents participating in a longitudinal study. Parenting-style and adolescent adjustment measures at 2 time points were used, with a 2-year interval between time points. A variety of internal and external adjustment measures were used. Results showed that including knowledge items in measures of parental behavioral control elevated links between behavioral control and adjustment. Thus, the results and conclusions of many of the most highly cited studies are likely to have been stronger than if the measures had focused strictly on parental behavior. In addition, adolescent adjustment predicted changes in authoritative and neglectful parenting styles more robustly than these styles predicted changes in adolescent adjustment. Adolescent adjustment also predicted changes in authoritativeness more robustly than authoritativeness predicted changes in adjustment. Thus, parenting style cannot be seen as independent of the adolescent. In summary, both the theoretical premises of parenting-style research and the prior findings should be revisited.

  14. Tensions of Reimagining Our Roles as Teacher Educators in a Third Space: Revisiting a Co/Autoethnography through a Faculty Lens

    ERIC Educational Resources Information Center

    Taylor, Monica; Klein, Emily J.; Abrams, Linda

    2014-01-01

    This co/autoethnography uses our lens as university faculty to examine how engaging in a year-long self-study with mentors nurtured a complicated third space where we could together begin to reimagine our roles as teacher educators. Two secondary faculty members and a doctoral assistant used co/autoethnography to revisit a collaborative self-study…

  15. Repurposing the anti-malarial drug dihydroartemisinin suppresses metastasis of non-small-cell lung cancer via inhibiting NF-κB/GLUT1 axis

    PubMed Central

    Jiang, Jie; Geng, Guojun; Yu, Xiuyi; Liu, Hongming; Gao, Jing; An, Hanxiang; Cai, Chengfu; Li, Ning; Shen, Dongyan; Wu, Xiaoqiang; Zheng, Lisheng; Mi, Yanjun; Yang, Shuyu

    2016-01-01

    Non-small-cell lung cancer (NSCLC) is an aggressive malignancy and long-term survival remains unsatisfactory for patients with metastatic and recurrent disease. Repurposing the anti-malarial drug dihydroartemisinin (DHA) has been proved to possess potent antitumor effect on various cancers. However, the effects of DHA in preventing the invasion of NSCLC cells have not been studied. In the present study, we determined the inhibitory effects of DHA on invasion and migration and the possible mechanisms involved using A549 and H1975 cells. DHA inhibited in vitro migration and invasion of NSCLC cells even in low concentration with little cytotoxicity. Additionally, low concentration DHA also inhibited Warburg effect in NSCLC cells. Mechanically, DHA negatively regulates NF-κB signaling to inhibit the GLUT1 translocation. Blocking the NF-κB signaling largely abolishes the inhibitory effects of DHA on the translocation of GLUT1 to the plasma membrane and the Warburg effect. Furthermore, GLUT1 knockdown significantly decreased the inhibition of invasion, and migration by DHA. Our results suggested that DHA can inhibit metastasis of NSCLC by targeting glucose metabolism via inhibiting NF-κB signaling pathway and DHA may deserve further investigation in NSCLC treatment. PMID:27895313

  16. Targeting Energy Metabolic Pathways as Therapeutic Intervention for Breast Cancer

    DTIC Science & Technology

    2013-10-01

    known as the Warburg effect. Glycolytic cancer cells are believed to be resistant to anticancer treatment and to induction of apoptosis mediated...autophagy and apoptosis by EEF2K controls cellular fate and modulates the efficacy of curcumin and velcade against tumor cells. Autophagy. 2013, 9: 208-219

  17. Leber's Hereditary Optic Neuropathy: The Mitochondrial Connection Revisited.

    PubMed

    Abu-Amero, Khaled K

    2011-01-01

    Our current understanding of Leber's hereditary optic neuropathy (LHON)-mitochondrial connection falls short of comprehensive. Twenty years of intensive investigation have yielded a wealth of information about mitochondria, the mitochondrial genome, the metabolism of the optic nerve and other structures, and the phenotypic variability of classic LHON. However, we still cannot completely explain how primary LHON mutations injure the optic nerve or why the optic nerve is particularly at risk. We cannot explain the incomplete penetrance or the male predominance of LHON, the typical onset in young adult life without warning, or the synchronicity of visual loss. Moreover, primary LHON mutations clearly are not present in every family with the LHON phenotype (including multigenerational maternal inheritance), and they are present in only a minority of individuals who have the LHON optic neuropathy phenotype without a family history. All lines of evidence point to abnormalities of the mitochondria as the direct or indirect cause of LHON. Therefore, the mitochondria-LHON connection needs to be revisited and examined closely. This review will attempt to do that and provide an update on various aspects of LHON.

  18. Revisiting Einstein's Happiest Thought: On Ernst Mach and the Early History of Relativity

    NASA Astrophysics Data System (ADS)

    Staley, Richard

    2016-03-01

    This paper argues we should distinguish three phases in the formation of relativity. The first involved relational approaches to perception, and physiological and geometrical space and time in the 1860s and 70s. The second concerned electrodynamics and mechanics (special relativity). The third concerned mechanics, gravitation, and physical and geometrical space and time. Mach's early work on the Doppler effect, together with studies of visual and motor perception linked physiology, physics and psychology, and offered new approaches to physiological space and time. These informed the critical conceptual attacks on Newtonian absolutes that Mach famously outlined in The Science of Mechanics. Subsequently Mach identified a growing group of ``relativists,'' and his critiques helped form a foundation for later work in electrodynamics (in which he did not participate). Revisiting Mach's early work will suggest he was still more important to the development of new approaches to inertia and gravitation than has been commonly appreciated. In addition to what Einstein later called ``Mach's principle,'' I will argue that a thought experiment on falling bodies in Mach's Science of Mechanics also provided a point of inspiration for the happy thought that led Einstein to the equivalence principle.

  19. V838 Monocerotis revisited: Space phenomenon imitates art

    NASA Astrophysics Data System (ADS)

    2004-03-01

    V838 Monocerotis revisited: Space phenomenon imitates art hi-res Size hi-res: 558 Kb Credits: NASA, the Hubble Heritage Team (AURA/STScI) and ESA V838 Monocerotis revisited: Space phenomenon imitates art "Starry Night", Vincent van Gogh's famous painting, is renowned for its bold whorls of light sweeping across a raging night sky. Although this image of the heavens came only from the artist's restless imagination, a new picture from the NASA/ESA Hubble Space Telescope bears remarkable similarities to the van Gogh work, complete with never-before-seen spirals of dust swirling across trillions of kilometres of interstellar space. This image, obtained with the Advanced Camera for Surveys on February 8, 2004, is Hubble's latest view of an expanding halo of light around a distant star, named V838 Monocerotis (V838 Mon). The illumination of interstellar dust comes from the red supergiant star at the middle of the image, which gave off a flashbulb-like pulse of light two years ago. V838 Mon is located about 20,000 light-years away from Earth in the direction of the constellation Monoceros, placing the star at the outer edge of our Milky Way galaxy V838 Monocerotis revisited: Space phenomenon imitates art hi-res Size hi-res: 1989 kb Credits: NASA, the Hubble Heritage Team (AURA/STScI) and ESA V838 Monocerotis revisited: Space phenomenon imitates art "Starry Night", Vincent van Gogh's famous painting, is renowned for its bold whorls of light sweeping across a raging night sky. Although this image of the heavens came only from the artist's restless imagination, a new picture from the NASA/ESA Hubble Space Telescope bears remarkable similarities to the van Gogh work, complete with never-before-seen spirals of dust swirling across trillions of kilometres of interstellar space. This image, obtained with the Advanced Camera for Surveys on February 8, 2004, is Hubble's latest view of an expanding halo of light around a distant star, named V838 Monocerotis (V838 Mon). The

  20. Revisiting the diffusion mechanism of helium in UO2: A DFT+U study

    NASA Astrophysics Data System (ADS)

    Liu, X.-Y.; Andersson, D. A.

    2018-01-01

    The understanding of migration properties of helium atoms after their generation through α-decay of actinides in spent nuclear fuels is important for the safety of nuclear fuel storage and disposal. The diffusion of helium in UO2 is revisited by using the DFT+U simulation methodology employing the "U-ramping" method to address the issue of metastable energy states. A novel diffusion mechanism by helium interstitials, the "asymmetric hop" mechanism, is reported and compared to other diffusion mechanisms including an oxygen vacancy mediated mechanism and available experimental diffusion data. The new mechanism is shown to be the dominant one over a wide temperature range.

  1. Regime change: re-visiting the 1961 Single Convention on Narcotic Drugs.

    PubMed

    Bewley-Taylor, David; Jelsma, Martin

    2012-01-01

    March 2011 marked the 50th anniversary of the Single Convention on Narcotic Drugs. This legal instrument, the bedrock of the current United Nations based global drug control regime, is often viewed as merely a consolidating treaty bringing together the multilateral drug control agreements that preceded it; an erroneous position that does little to provide historical context for contemporary discussions surrounding revision of the international treaty system. This article applies both historical and international relations perspectives to revisit the development of the Convention. Framing discussion within the context of regime theory, a critique of the foundational pre-1961 treaties is followed by detailed content analysis of the official records of the United Nations conference for the adoption of a Single Convention on Narcotic Drugs and, mindful of later treaties, an examination of the treaty's status as a 'single' convention. The Single Convention on Narcotic Drugs represents a significant break with the regulative focus of the preceding multilateral treaties; a shift towards a more prohibitive outlook that within international relations terms can be regarded as a change of regime rather than the straightforward codification of earlier instruments. In this respect, the article highlights the abolition of drug use that for centuries had been embedded in the social, cultural and religious traditions of many non-Western states. Further, although often-overlooked, the Convention has failed in its aim of being the 'single' instrument within international drug control. The supplementing treaties developed in later years and under different socio-economic and political circumstances have resulted in significant inconsistencies within the control regime. Having established that a shift in normative focus has taken place in the past, the article concludes that it is timely for the international community to revisit the Single Convention on Narcotic Drugs with a view to

  2. N = 2 S-duality revisited

    NASA Astrophysics Data System (ADS)

    Buican, Matthew; Laczko, Zoltan; Nishinaka, Takahiro

    2017-09-01

    Using the chiral algebra bootstrap, we revisit the simplest Argyres-Douglas (AD) generalization of Argyres-Seiberg S-duality. We argue that the exotic AD superconformal field theory (SCFT), T_{3,3/2} , emerging in this duality splits into a free piece and an interacting piece, T_X , even though this factorization seems invisible in the Seiberg-Witten (SW) curve derived from the corresponding M5-brane construction. Without a Lagrangian, an associated topological field theory, a BPS spectrum, or even an SW curve, we nonetheless obtain exact information about T_X by bootstrapping its chiral algebra, {}_X(T_X) , and finding the corresponding vacuum character in terms of Affine Kac-Moody characters. By a standard 4D/2D correspondence, this result gives us the Schur index for T_X and, by studying this quantity in the limit of small S 1, we make contact with a proposed S 1 reduction. Along the way, we discuss various properties of T_X : as an N = 1 theory, it has flavor symmetry SU(3) × SU(2) × U(1), the central charge of {}_X(T_X) matches the central charge of the bc ghosts in bosonic string theory, and its global SU(2) symmetry has a Witten anomaly. This anomaly does not prevent us from building conformal manifolds out of arbitrary numbers of T_X theories (giving us a surprisingly close AD relative of Gaiotto's T N theories), but it does lead to some open questions in the context of the chiral algebra/4D N =2SCFT correspondence.

  3. Spontaneous revisitation during visual exploration as a link among strategic behavior, learning, and the hippocampus.

    PubMed

    Voss, Joel L; Warren, David E; Gonsalves, Brian D; Federmeier, Kara D; Tranel, Dan; Cohen, Neal J

    2011-08-02

    Effective exploratory behaviors involve continuous updating of sensory sampling to optimize the efficacy of information gathering. Despite some work on this issue in animals, little information exists regarding the cognitive or neural mechanisms for this sort of behavioral optimization in humans. Here we examined a visual exploration phenomenon that occurred when human subjects studying an array of objects spontaneously looked "backward" in their scanning paths to view recently seen objects again. This "spontaneous revisitation" of recently viewed objects was associated with enhanced hippocampal activity and superior subsequent memory performance in healthy participants, but occurred only rarely in amnesic patients with severe damage to the hippocampus. These findings demonstrate the necessity of the hippocampus not just in the aspects of long-term memory with which it has been associated previously, but also in the short-term adaptive control of behavior. Functional neuroimaging showed hippocampal engagement occurring in conjunction with frontocerebellar circuits, thereby revealing some of the larger brain circuitry essential for the strategic deployment of information-seeking behaviors that optimize learning.

  4. Nuclear magnetic resonance signal dynamics of liquids in the presence of distant dipolar fields, revisited

    PubMed Central

    Barros, Wilson; Gochberg, Daniel F.; Gore, John C.

    2009-01-01

    The description of the nuclear magnetic resonance magnetization dynamics in the presence of long-range dipolar interactions, which is based upon approximate solutions of Bloch–Torrey equations including the effect of a distant dipolar field, has been revisited. New experiments show that approximate analytic solutions have a broader regime of validity as well as dependencies on pulse-sequence parameters that seem to have been overlooked. In order to explain these experimental results, we developed a new method consisting of calculating the magnetization via an iterative formalism where both diffusion and distant dipolar field contributions are treated as integral operators incorporated into the Bloch–Torrey equations. The solution can be organized as a perturbative series, whereby access to higher order terms allows one to set better boundaries on validity regimes for analytic first-order approximations. Finally, the method legitimizes the use of simple analytic first-order approximations under less demanding experimental conditions, it predicts new pulse-sequence parameter dependencies for the range of validity, and clarifies weak points in previous calculations. PMID:19425789

  5. Revisiting Ionosphere-Thermosphere Responses to Solar Wind Driving in Superstorms of November 2003 and 2004

    NASA Astrophysics Data System (ADS)

    Verkhoglyadova, O. P.; Komjathy, A.; Mannucci, A. J.; Mlynczak, M. G.; Hunt, L. A.; Paxton, L. J.

    2017-10-01

    We revisit three complex superstorms of 19-20 November 2003, 7-8 November 2004, and 9-11 November 2004 to analyze ionosphere-thermosphere (IT) effects driven by different solar wind structures associated with complex interplanetary coronal mass ejections (ICMEs) and their upstream sheaths. The efficiency of the solar wind-magnetosphere connection throughout the storms is estimated by coupling functions. The daytime IT responses to the complex driving are characterized by combining and collocating (where possible) measurements of several physical parameters (total electron content or TEC, thermospheric infrared nitric oxide emission, and composition ratio) from multiple satellite platforms and ground-based measurements. A variety of metrics are utilized to examine global IT phenomena at 1 h timescales. The role of direct driving of IT dynamics by solar wind structures and the role of IT preconditioning in these storms, which feature complex unusual TEC responses, are examined and contrasted. Furthermore, IT responses to ICME magnetic clouds and upstream sheaths are separately characterized. We identify IT feedback effects that can be important for long-lasting strong storms. The role of the interplanetary magnetic field By component on ionospheric convection may not be well captured by existing coupling functions. Mechanisms of thermospheric overdamping and consequential ionospheric feedback need to be further studied.

  6. Revisiting the role of erythropoietin for treatment of ocular disorders

    PubMed Central

    Shirley Ding, S L; Leow, S N; Munisvaradass, R; Koh, E H; Bastion, M L C; Then, K Y; Kumar, S; Mok, P L

    2016-01-01

    Erythropoietin (EPO) is a glycoprotein hormone conventionally thought to be responsible only in producing red blood cells in our body. However, with the discovery of the presence of EPO and EPO receptors in the retinal layers, the EPO seems to have physiological roles in the eye. In this review, we revisit the role of EPO in the eye. We look into the biological role of EPO in the development of the eye and the physiologic roles that it has. Apart from that, we seek to understand the mechanisms and pathways of EPO that contributes to the therapeutic and pathological conditions of the various ocular disorders such as diabetic retinopathy, retinopathy of prematurity, glaucoma, age-related macular degeneration, optic neuritis, and retinal detachment. With these understandings, we discuss the clinical applications of EPO for treatment of ocular disorders, modes of administration, EPO formulations, current clinical trials, and its future directions. PMID:27285322

  7. [Structural Equation Modeling for Public Hospital Quality of Care, Image, Role Performance, Satisfaction, Intent to (Re)visit, and Intent to Recommend Hospital as Perceived by Community Residents].

    PubMed

    Hwang, Eun Jeong; Sim, In Ok

    2016-02-01

    The study purposes were to construct and test structural equation modeling on the causal relationship of community residents' perceived quality of care, image, and role performance with satisfaction, intention to (re)visit and intention to recommend hospital. A cross-sectional survey was conducted with 3,900 community residents from 39 district public hospitals. The questionnaire was designed to collected information on personal characteristics and community awareness of public hospitals. Community awareness consisted of 6 factors and 18 items. The data were collected utilizing call-interview by a survey company. Research data were collected via questionnaires and analyzed using SPSS version 20.0 and AMOS version 20.0. Model fit indices for the hypothetical model were suitable for the recommended level: χ²=796.40 (df=79, p<.001), GFI=.93, AGFI=.90, RMSR=.08, NFI=.94. Quality of care, image, and role performance explained 68.1% of variance in community awareness. Total effect of quality of care process factors on satisfaction (path coefficients=3.67), intention to (re)visit (path coefficients=2.67) and intention to recommend hospital (coefficients=2.45) were higher than other factors. Findings show that public hospitals have to make an effort to improve community image through the provision of quality care, and excellent role performance. Support for these activities is available from both Central and Local Governments.

  8. Spectral structure of laser light scattering revisited: bandwidths of nonresonant scattering lidars.

    PubMed

    She, C Y

    2001-09-20

    It is well known that scattering lidars, i.e., Mie, aerosol-wind, Rayleigh, high-spectral-resolution, molecular-wind, rotational Raman, and vibrational Raman lidars, are workhorses for probing atmospheric properties, including the backscatter ratio, aerosol extinction coefficient, temperature, pressure, density, and winds. The spectral structure of molecular scattering (strength and bandwidth) and its constituent spectra associated with Rayleigh and vibrational Raman scattering are reviewed. Revisiting the correct name by distinguishing Cabannes scattering from Rayleigh scattering, and sharpening the definition of each scattering component in the Rayleigh scattering spectrum, the review allows a systematic, logical, and useful comparison in strength and bandwidth between each scattering component and in receiver bandwidths (for both nighttime and daytime operation) between the various scattering lidars for atmospheric sensing.

  9. Effects of TFM and Bayer 73 on in vivo oxygen consumption of the aquatic midge Chironomus tentans

    USGS Publications Warehouse

    Kawatski, J.A.; Dawson, V.K.; Reuvers, J.L.

    1974-01-01

    Exposure of fourth instar larvae of Chironomus tentans to 2.0-8.0 mg/liter of TFM (3-trifluormethyl-4-nitrophenol) for 6 hr at 22 A? 0.5 C in soft water resulted in a significantly increased rate of larval oxygen consumption compared to that of control larvae, as measured with the Warburg respirometer. Maximum stimulation of oxygen consumption occurred with 8.0 mg/liter of TFM, and 1.0 mg/liter of TFM had no measurable effect on basal respiration. When hardness of exposure water was progressively increased, the effect of TFM on oxygen consumption was diminished. Bayer 73 (5,2'-dichloro-4'-nitrosalicylanilide) stimulated oxygen consumption at 0.75 and 1.0 mg/liter, had no significant effect at concentrations less that 0.75 mg/liter, and inhibited oxygen consumption at concentrations of 1.20 mg/liter or greater. Mixtures of TFM and Bayer 73, in the ratio of 98:2, had no greater effect on oxygen consumption than TFM alone.

  10. Testosterone metabolism revisited: discovery of new metabolites.

    PubMed

    Pozo, Oscar J; Marcos, Josep; Ventura, Rosa; Fabregat, Andreu; Segura, Jordi

    2010-10-01

    The metabolism of testosterone is revisited. Four previously unreported metabolites were detected in urine after hydrolysis with KOH using a liquid chromatography-tandem mass spectrometry method and precursor ion scan mode. The metabolites were characterized by a product ion scan obtained with accurate mass measurements. Androsta-4,6-dien-3,17-dione, androsta-1,4-dien-3,17-dione, 17-hydroxy-androsta-4,6-dien-3-one and 15-androsten-3,17-dione were proposed as feasible structures for these metabolites on the basis of the mass spectrometry data. The proposed structures were confirmed by analysis of synthetic reference compounds. Only 15-androsten-3,17-dione could not be confirmed, owing to the lack of a commercially available standard. That all four compounds are testosterone metabolites was confirmed by the qualitative analysis of several urine samples collected before and after administration of testosterone undecanoate. The metabolite androsta-1,4-dien-3,17-dione has a structure analogous to that of the exogenous anabolic steroid boldenone. Specific transitions for boldenone and its metabolite 17β-hydroxy-5β-androst-1-en-3-one were also monitored. Both compounds were also detected after KOH treatment, suggesting that this metabolic pathway is involved in the endogenous detection of boldenone previously reported by several authors.

  11. Equal-area criterion in power systems revisited

    NASA Astrophysics Data System (ADS)

    Sun, Yong; Ma, Jinpeng; Kurths, Jürgen; Zhan, Meng

    2018-02-01

    The classic equal-area criterion (EAC) is of key importance in power system analysis, and provides a powerful, pictorial and quantitative means of analysing transient stability (i.e. the system's ability to maintain stable operation when subjected to a large disturbance). Based on the traditional EAC, it is common sense in engineering that there is a critical cleaning time (CCT); namely, a power system is stable (unstable) if a fault is cleared before (after) this CCT. We regard this form of CCT as bipartite. In this paper, we revisit the EAC theory and, surprisingly, find different kinds of transient stability behaviour. Based on these analyses, we discover that the bipartite CCT is only one type among four major types, and, actually, the forms of CCT can be diversified. In particular, under some circumstances, a system may have no CCT or show a periodic CCT. Our theoretical analysis is verified by numerical simulations in a single-machine-infinite-bus system and also in multi-machine systems. Thus, our study provides a panoramic framework for diverse transient stability behaviour in power systems and also may have a significant impact on applications of multi-stability in various other systems, such as neuroscience, climatology or photonics.

  12. Climatology and trend of wind power resources in China and its surrounding regions: a revisit using Climate Forecast System Reanalysis data

    Treesearch

    Lejiang Yu; Shiyuan Zhong; Xindi Bian; Warren E. Heilman

    2015-01-01

    The mean climatology, seasonal and interannual variability and trend of wind speeds at the hub height (80 m) of modern wind turbines over China and its surrounding regions are revisited using 33-year (1979–2011) wind data from the Climate Forecast System Reanalysis (CFSR) that has many improvements including higher spatial resolution over previous global reanalysis...

  13. Revisiting final state interaction in charmless Bq→P P decays

    NASA Astrophysics Data System (ADS)

    Chua, Chun-Khiang

    2018-05-01

    Various new measurements in charmless Bu ,d ,s→P P modes, where P is a low lying pseudoscalar meson, are reported by Belle and LHCb. These include the rates of B0→π0π0, η π0, Bs→η'η', B0→K+K- and Bs0→π+π- decays. Some of these modes are highly suppressed and are among the rarest B decays. Direct C P asymmetries on various modes are constantly updated. It is well known that direct C P asymmetries and rates of suppressed modes are sensitive to final state interaction (FSI). As new measurements are reported and more data will be collected, it is interesting and timely to revisit the rescattering effects in Bu ,d ,s→P P states. We perform a χ2 analysis with all available data on C P -averaged rates and C P asymmetries in B¯u ,d ,s→P P decays. Our numerical results are compared to data and those from factorization approach. The quality of the fit is improved significantly from the factorization results in the presence of rescattering. The relations on topological amplitudes and rescattering are explored and they help to provide a better understanding of the effects of FSI. As suggested by U(3) symmetry on topological amplitudes and FSI, a vanishing exchange rescattering scenario is considered. The exchange, annihilation, u -penguin, u -penguin annihilation, and some electroweak penguin amplitudes are enhanced significantly via annihilation and total annihilation rescatterings. In particular, the u -penguin annihilation amplitude is sizably enhanced by the tree amplitude via total annihilation rescattering. These enhancements affect rates and C P asymmetries. Predictions can be checked in the near future.

  14. Introducing the Mean Absolute Deviation "Effect" Size

    ERIC Educational Resources Information Center

    Gorard, Stephen

    2015-01-01

    This paper revisits the use of effect sizes in the analysis of experimental and similar results, and reminds readers of the relative advantages of the mean absolute deviation as a measure of variation, as opposed to the more complex standard deviation. The mean absolute deviation is easier to use and understand, and more tolerant of extreme…

  15. Revisiting the diffusion mechanism of helium in UO 2 : A DFT+ U study

    DOE PAGES

    Liu, X. -Y.; Andersson, D. A.

    2017-11-03

    The understanding of migration properties of helium atoms after their generation through α-decay of actinides in spent nuclear fuels is important for the safety of nuclear fuel storage and disposal. The diffusion of helium in UO 2 is revisited by using the DFT+U simulation methodology employing the “U-ramping” method to address the issue of metastable energy states. A novel diffusion mechanism by helium interstitials, the “asymmetric hop” mechanism, is reported and compared to other diffusion mechanisms including an oxygen vacancy mediated mechanism and available experimental diffusion data. We show that the new mechanism is the dominant one over a widemore » temperature range.« less

  16. Revisiting the diffusion mechanism of helium in UO 2 : A DFT+ U study

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Liu, X. -Y.; Andersson, D. A.

    The understanding of migration properties of helium atoms after their generation through α-decay of actinides in spent nuclear fuels is important for the safety of nuclear fuel storage and disposal. The diffusion of helium in UO 2 is revisited by using the DFT+U simulation methodology employing the “U-ramping” method to address the issue of metastable energy states. A novel diffusion mechanism by helium interstitials, the “asymmetric hop” mechanism, is reported and compared to other diffusion mechanisms including an oxygen vacancy mediated mechanism and available experimental diffusion data. We show that the new mechanism is the dominant one over a widemore » temperature range.« less

  17. Toward a North-South dialogue: revisiting nursing theory (from the South).

    PubMed

    Santos Salas, Anna

    2005-01-01

    In nursing, the current world situation calls us to revisit our knowledge schemes and revise the extent to which they assist us in improving the health of the world peoples. In this discussion, I offer a Latin American nursing perspective to knowledge development in our discipline. I suggest that a persistent concern to develop elaborate conceptualizations has distracted our attention from the realities practicing nurses face throughout the world. In their abstractness, (North) American nursing theories have conveyed a view that presumingly universal imposes itself as hegemonic in the international nursing community. Yet the exportation of these theories to other countries introduces a view that is foreign to practicing nurses. The world situation as well as the disparate and concurrent human paths that we witness and experience calls for approaches that are more in tune with the local realities of nursing practices.

  18. What drives health care expenditure?--Baumol's model of 'unbalanced growth' revisited.

    PubMed

    Hartwig, Jochen

    2008-05-01

    The share of health care expenditure in GDP rises rapidly in virtually all OECD countries, causing increasing concern among politicians and the general public. Yet, economists have to date failed to reach an agreement on what the main determinants of this development are. This paper revisits Baumol's [Baumol, W.J., 1967. Macroeconomics of unbalanced growth: the anatomy of urban crisis. American Economic Review 57 (3), 415-426] model of 'unbalanced growth', showing that the latter offers a ready explanation for the observed inexorable rise in health care expenditure. The main implication of Baumol's model in this context is that health care expenditure is driven by wage increases in excess of productivity growth. This hypothesis is tested empirically using data from a panel of 19 OECD countries. Our tests yield robust evidence in favor of Baumol's theory.

  19. Revisiting an open access monograph experiment: measuring citations and tweets 5 years later.

    PubMed

    Snijder, Ronald

    An experiment run in 2009 could not assess whether making monographs available in open access enhanced scholarly impact. This paper revisits the experiment, drawing on additional citation data and tweets. It attempts to answer the following research question: does open access have a positive influence on the number of citations and tweets a monograph receives, taking into account the influence of scholarly field and language? The correlation between monograph citations and tweets is also investigated. The number of citations and tweets measured in 2014 reveal a slight open access advantage, but the influence of language or subject should also be taken into account. However, Twitter usage and citation behaviour hardly overlap.

  20. Marginalization: A Revisitation With Integration of Scholarship on Globalization, Intersectionality, Privilege, Microaggressions, and Implicit Biases.

    PubMed

    Hall, Joanne M; Carlson, Kelly

    2016-01-01

    In 1994, the concept of marginalization was explored in an article in Advances in Nursing Science. This is a revisitation of the concept incorporating new scholarship. This update is founded on feminism, postcolonialism, critical race theory, and discourse deconstruction, all viewpoints that have been explicated in nursing. The purpose of this analysis is to look at new scholarship and concepts useful to applying marginalization in nursing knowledge development from the standpoint of Bourdieu's macro, meso, and micro levels. New scholarship includes globalization, intersectionality, privilege, microaggressions, and implicit bias. Implications for decreasing health disparities through this new scholarship are discussed.

  1. Revisiting the 1761 Transatlantic Tsunami

    NASA Astrophysics Data System (ADS)

    Baptista, Maria Ana; Wronna, Martin; Miranda, Jorge Miguel

    2016-04-01

    The tsunami catalogs of the Atlantic include two transatlantic tsunamis in the 18th century the well known 1st November 1755 and the 31st March 1761. The 31st March 1761 earthquake struck Portugal, Spain, and Morocco. The earthquake occurred around noontime in Lisbon alarming the inhabitants and throwing down ruins of the past 1st November 1755 earthquake. According to several sources, the earthquake was followed by a tsunami observed as far as Cornwall (United Kingdom), Cork (Ireland) and Barbados (Caribbean). The analysis of macroseismic information and its compatibility with tsunami travel time information led to a source area close to the Ampere Seamount with an estimated epicenter circa 34.5°N 13°W. The estimated magnitude of the earthquake was 8.5. In this study, we revisit the tsunami observations, and we include a report from Cadiz not used before. We use the results of the compilation of the multi-beam bathymetric data, that covers the area between 34°N - 38°N and 12.5°W - 5.5°W and use the recent tectonic map published for the Southwest Iberian Margin to select among possible source scenarios. Finally, we use a non-linear shallow water model that includes the discretization and explicit leap-frog finite difference scheme to solve the shallow water equations in the spherical or Cartesian coordinate to compute tsunami waveforms and tsunami inundation and check the results against the historical descriptions to infer the source of the event. This study received funding from project ASTARTE- Assessment Strategy and Risk Reduction for Tsunamis in Europe a collaborative project Grant 603839, FP7-ENV2013 6.4-3

  2. Proper temperature of the Schwarzschild AdS black hole revisited

    NASA Astrophysics Data System (ADS)

    Eune, Myungseok; Kim, Wontae

    2017-10-01

    The Unruh temperature calculated by using the global embedding of the Schwarzschild AdS spacetime into the Minkowski spacetime was identified with the local proper temperature; however, it became imaginary in a certain region outside the event horizon. So, the temperature was assumed to be zero of non-thermal radiation for that region. In this work, we revisit this issue in an exactly soluble two-dimensional Schwarzschild AdS black hole and present an alternative resolution to this problem in terms of the Tolman's procedure. However, the process appears to be non-trivial in the sense that the original procedure assuming the traceless energy-momentum tensor should be extended in such a way that it should cover the non-vanishing case of the energy-momentum tensor in the presence of the trace anomaly. Consequently, we show that the proper temperature turns out to be real everywhere outside the event horizon without any imaginary value, in particular, it vanishes at both the horizon and the asymptotic infinity.

  3. Evans Blue Dye: A Revisit of Its Applications in Biomedicine.

    PubMed

    Yao, Linpeng; Xue, Xing; Yu, Peipei; Ni, Yicheng; Chen, Feng

    2018-01-01

    Evans blue (EB) dye has owned a long history as a biological dye and diagnostic agent since its first staining application by Herbert McLean Evans in 1914. Due to its high water solubility and slow excretion, as well as its tight binding to serum albumin, EB has been widely used in biomedicine, including its use in estimating blood volume and vascular permeability, detecting lymph nodes, and localizing the tumor lesions. Recently, a series of EB derivatives have been labeled with PET isotopes and can be used as theranostics with a broad potential due to their improved half-life in the blood and reduced release. Some of EB derivatives have even been used in translational applications in clinics. In addition, a novel necrosis-avid feature of EB has recently been reported in some preclinical animal studies. Given all these interesting and important advances in EB study, a comprehensive revisiting of EB has been made in its biomedical applications in the review.

  4. Revisiting Ebola, a quiet river in the heart of Africa.

    PubMed

    Gonzalez, J P; Wauquier, N; Vincent, T

    2018-02-01

    In 1995, 20 years after the first known Ebola outbreak, one of us (JPG) wrote an editorial about Ebola Virus Disease that captured the knowledge and attitudes toward viral diseases of that time and discussed the future of viruses in our world. Now, 21 years later, in the wake of the West African Ebola pandemic of 2013-2016, and after 22 other Ebola outbreaks, we revisit the article to determine if knowledge, attitudes, and practices have changed. We conclude that the necessary infrastructures (surveillance, financial, treatment/preventative health) have improved with each outbreak, and knowledge of the virus (vaccines, therapies, diagnostics) has increased. However, the global reach of the virus has also increased due to expanded means of global transportation. Furthermore, the knowledge of the virus that has increased with each outbreak has not translated into the necessary marginal increase in preparedness; we do not seem to be learning from our mistakes.

  5. The flux qubit revisited to enhance coherence and reproducibility

    PubMed Central

    Yan, Fei; Gustavsson, Simon; Kamal, Archana; Birenbaum, Jeffrey; Sears, Adam P; Hover, David; Gudmundsen, Ted J.; Rosenberg, Danna; Samach, Gabriel; Weber, S; Yoder, Jonilyn L.; Orlando, Terry P.; Clarke, John; Kerman, Andrew J.; Oliver, William D.

    2016-01-01

    The scalable application of quantum information science will stand on reproducible and controllable high-coherence quantum bits (qubits). Here, we revisit the design and fabrication of the superconducting flux qubit, achieving a planar device with broad-frequency tunability, strong anharmonicity, high reproducibility and relaxation times in excess of 40 μs at its flux-insensitive point. Qubit relaxation times T1 across 22 qubits are consistently matched with a single model involving resonator loss, ohmic charge noise and 1/f-flux noise, a noise source previously considered primarily in the context of dephasing. We furthermore demonstrate that qubit dephasing at the flux-insensitive point is dominated by residual thermal-photons in the readout resonator. The resulting photon shot noise is mitigated using a dynamical decoupling protocol, resulting in T2≈85 μs, approximately the 2T1 limit. In addition to realizing an improved flux qubit, our results uniquely identify photon shot noise as limiting T2 in contemporary qubits based on transverse qubit–resonator interaction. PMID:27808092

  6. Guarana: revisiting a highly caffeinated plant from the Amazon.

    PubMed

    Schimpl, Flávia Camila; da Silva, José Ferreira; Gonçalves, José Francisco de Carvalho; Mazzafera, Paulo

    2013-10-28

    Guarana (Paullinia cupana Kunth var. sorbilis (Mart.) Ducke) has been traditionally consumed by indigenous communities of the Amazon region. It is valued mainly for its stimulant property because of its high content of caffeine, which can be up to 6% in the seeds. The purpose of this review is to revisit this typically Brazilian plant, addressing economic considerations, the chemical makeup of the seeds and pharmacological properties so far investigated. Guarana is primarily produced in the Brazilian states of Amazonas and Bahia, and approximately 70% of the production is used by the industry of soft and energy drinks. The other 30% becomes guarana powder for direct consumption in capsules or dilution in water, or it serves as a raw material for the pharmaceutical and cosmetics industries. In addition to its stimulant property, guarana has other therapeutic properties, which have aroused the interest of the scientific community. This review shows that other guarana properties may be explored and how scarce are the studies regarding agronomic, plant pathology, physiology and breeding. So far, caffeine has been the main reason to study guarana and still will lead the researches because the demand for this alkaloid by food and pharmaceutical industry, and a strongly growing market related with beauty products. However, guarana has other components and there is great interest in studies designed to elucidate the effects of guarana's bioactive components and their potential pharmacological applications. Significant part of the guarana production in Brazil still comes from Indians tribes in the Amazon State, and any improvement in this plant, in any aspect, may propitiate a positive economic impact in their lives. © 2013 Elsevier Ireland Ltd. All rights reserved.

  7. Energy metabolism in neuroblastoma and Wilms tumor

    PubMed Central

    Aminzadeh, Sepideh; Vidali, Silvia; Sperl, Wolfgang; Feichtinger, René G.

    2015-01-01

    To support high proliferation, the majority of cancer cells undergo fundamental metabolic changes such as increasing their glucose uptake and shifting to glycolysis for ATP production at the expense of far more efficient mitochondrial energy production by oxidative phosphorylation (OXPHOS), which at first glance is a paradox. This phenomenon is known as the Warburg effect. However, enhanced glycolysis is necessary to provide building blocks for anabolic growth. Apart from the generation of ATP, intermediates of glycolysis serve as precursors for a variety of biosynthetic pathways essential for cell proliferation. In the last 10-15 years the field of tumor metabolism has experienced an enormous boom in interest. It is now well established that tumor suppressor genes and oncogenes often play a central role in the regulation of cellular metabolism. Therefore, they significantly contribute to the manifestation of the Warburg effect. While much attention has focused on adult solid tumors, so far there has been comparatively little effort directed at elucidation of the mechanism responsible for the Warburg effect in childhood cancers. In this review we focus on metabolic pathways in neuroblastoma (NB) and Wilms tumor (WT), the two most frequent solid tumors in children. Both tumor types show alterations of the OXPHOS system and glycolytic features. Chromosomal alterations and activation of oncogenes like MYC or inactivation of tumor suppressor genes like TP53 can in part explain the changes of energy metabolism in these cancers. The strict dependence of cancer cells on glucose metabolism is a fairly common feature among otherwise biologically diverse types of cancer. Therefore, inhibition of glycolysis or starvation of cancer cells through glucose deprivation via a high-fat low-carbohydrate diet may be a promising avenue for future adjuvant therapeutic strategies. PMID:26835356

  8. Re-visiting protein-centric two-tier classification of existing DNA-protein complexes.

    PubMed

    Malhotra, Sony; Sowdhamini, Ramanathan

    2012-07-16

    Precise DNA-protein interactions play most important and vital role in maintaining the normal physiological functioning of the cell, as it controls many high fidelity cellular processes. Detailed study of the nature of these interactions has paved the way for understanding the mechanisms behind the biological processes in which they are involved. Earlier in 2000, a systematic classification of DNA-protein complexes based on the structural analysis of the proteins was proposed at two tiers, namely groups and families. With the advancement in the number and resolution of structures of DNA-protein complexes deposited in the Protein Data Bank, it is important to revisit the existing classification. On the basis of the sequence analysis of DNA binding proteins, we have built upon the protein centric, two-tier classification of DNA-protein complexes by adding new members to existing families and making new families and groups. While classifying the new complexes, we also realised the emergence of new groups and families. The new group observed was where β-propeller was seen to interact with DNA. There were 34 SCOP folds which were observed to be present in the complexes of both old and new classifications, whereas 28 folds are present exclusively in the new complexes. Some new families noticed were NarL transcription factor, Z-α DNA binding proteins, Forkhead transcription factor, AP2 protein, Methyl CpG binding protein etc. Our results suggest that with the increasing number of availability of DNA-protein complexes in Protein Data Bank, the number of families in the classification increased by approximately three fold. The folds present exclusively in newly classified complexes is suggestive of inclusion of proteins with new function in new classification, the most populated of which are the folds responsible for DNA damage repair. The proposed re-visited classification can be used to perform genome-wide surveys in the genomes of interest for the presence of DNA

  9. Application of mitochondrial pyruvate carrier blocker UK5099 creates metabolic reprogram and greater stem-like properties in LnCap prostate cancer cells in vitro.

    PubMed

    Zhong, Yali; Li, Xiaoran; Yu, Dandan; Li, Xiaoli; Li, Yaqing; Long, Yuan; Yuan, Yuan; Ji, Zhenyu; Zhang, Mingzhi; Wen, Jian-Guo; Nesland, Jahn M; Suo, Zhenhe

    2015-11-10

    Aerobic glycolysis is one of the important hallmarks of cancer cells and eukaryotic cells. In this study, we have investigated the relationship between blocking mitochondrial pyruvate carrier (MPC) with UK5099 and the metabolic alteration as well as stemness phenotype of prostatic cancer cells. It was found that blocking pyruvate transportation into mitochondrial attenuated mitochondrial oxidative phosphorylation (OXPHOS) and increased glycolysis. The UK5099 treated cells showed significantly higher proportion of side population (SP) fraction and expressed higher levels of stemness markers Oct3/4 and Nanog. Chemosensitivity examinations revealed that the UK5099 treated cells became more resistant to chemotherapy compared to the non-treated cells. These results demonstrate probably an intimate connection between metabolic reprogram and stem-like phenotype of LnCap cells in vitro. We propose that MPC blocker (UK5099) application may be an ideal model for Warburg effect studies, since it attenuates mitochondrial OXPHOS and increases aerobic glycolysis, a phenomenon typically reflected in the Warburg effect. We conclude that impaired mitochondrial OXPHOS and upregulated glycolysis are related with stem-like phenotype shift in prostatic cancer cells.

  10. Application of mitochondrial pyruvate carrier blocker UK5099 creates metabolic reprogram and greater stem-like properties in LnCap prostate cancer cells in vitro

    PubMed Central

    Zhong, Yali; Li, Xiaoran; Yu, Dandan; Li, Xiaoli; Li, Yaqing; Long, Yuan; Yuan, Yuan; Ji, Zhenyu; Zhang, Mingzhi; Wen, Jian-Guo; Nesland, Jahn M.; Suo, Zhenhe

    2015-01-01

    Aerobic glycolysis is one of the important hallmarks of cancer cells and eukaryotic cells. In this study, we have investigated the relationship between blocking mitochondrial pyruvate carrier (MPC) with UK5099 and the metabolic alteration as well as stemness phenotype of prostatic cancer cells. It was found that blocking pyruvate transportation into mitochondrial attenuated mitochondrial oxidative phosphorylation (OXPHOS) and increased glycolysis. The UK5099 treated cells showed significantly higher proportion of side population (SP) fraction and expressed higher levels of stemness markers Oct3/4 and Nanog. Chemosensitivity examinations revealed that the UK5099 treated cells became more resistant to chemotherapy compared to the non-treated cells. These results demonstrate probably an intimate connection between metabolic reprogram and stem-like phenotype of LnCap cells in vitro. We propose that MPC blocker (UK5099) application may be an ideal model for Warburg effect studies, since it attenuates mitochondrial OXPHOS and increases aerobic glycolysis, a phenomenon typically reflected in the Warburg effect. We conclude that impaired mitochondrial OXPHOS and upregulated glycolysis are related with stem-like phenotype shift in prostatic cancer cells. PMID:26413751

  11. Polycarbonate crowns for primary teeth revisited: restorative options, technique and case reports.

    PubMed

    Venkataraghavan, Karthik; Chan, John; Karthik, Sandhya

    2014-01-01

    Esthetics by definition is the science of beauty - that particular detail of an animate or inanimate object that makes it appealing to the eye. In the modern, civilized, and cosmetically conscious world, well-contoured and well-aligned white teeth set the standard for beauty. Such teeth are not only considered attractive but are also indicative of nutritional health, self esteem, hygienic pride, and economic status. Numerous treatment approaches have been proposed to address the esthetics and retention of restorations in primary teeth. Even though researchers have claimed that certain restorations are better than the others, particularly owing to the issues mentioned above, the search for the ideal esthetic restoration for the primary teeth continues. This paper revisits and attempts to reintroduce the full coverage restoration, namely, polycarbonate crown, for use in primary anterior teeth.

  12. The Changing Patterns of Individual and School Effects on Educational Transitions. Evidence from Catalan Data (Spain)

    ERIC Educational Resources Information Center

    Benito, Ricard; Alegre, Miquel Angel

    2012-01-01

    Background: This article engages with the tradition of educational transitions research, particularly with its attempt to evaluate the effect of exogenous variables on educational attainment. The study revisits a number of hypotheses that have attempted to explain the changing patterns of such effects throughout students' educational career,…

  13. The kickstart of the age of the Earth race: revisiting the experiment of the Comte de Buffon at school

    NASA Astrophysics Data System (ADS)

    Pincelli, M. M.; Prat, M. R.; Lescano, G. M.; Formichella, M. del C.; Brustle, M.; Otranto, S.

    2018-01-01

    In this work, the first experiment ever done to determine the age of the Earth is revisited. The benefits of its application at primary and secondary school levels are presented and discussed. In particular, emphasis is placed on the advantage of facing students with the challenges that scientists have had to overcome during the past three centuries to reach our present knowledge in contrast to the mere transmission of the latest facts.

  14. Influence of velocity effects on the shape of N2 (and air) broadened H2O lines revisited with classical molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Ngo, N. H.; Tran, H.; Gamache, R. R.; Bermejo, D.; Domenech, J.-L.

    2012-08-01

    The modeling of the shape of H2O lines perturbed by N2 (and air) using the Keilson-Storer (KS) kernel for collision-induced velocity changes is revisited with classical molecular dynamics simulations (CMDS). The latter have been performed for a large number of molecules starting from intermolecular-potential surfaces. Contrary to the assumption made in a previous study [H. Tran, D. Bermejo, J.-L. Domenech, P. Joubert, R. R. Gamache, and J.-M. Hartmann, J. Quant. Spectrosc. Radiat. Transf. 108, 126 (2007)], 10.1016/j.jqsrt.2007.03.009, the results of these CMDS show that the velocity-orientation and -modulus changes statistically occur at the same time scale. This validates the use of a single memory parameter in the Keilson-Storer kernel to describe both the velocity-orientation and -modulus changes. The CMDS results also show that velocity- and rotational state-changing collisions are statistically partially correlated. A partially correlated speed-dependent Keilson-Storer model has thus been used to describe the line-shape. For this, the velocity changes KS kernel parameters have been directly determined from CMDS, while the speed-dependent broadening and shifting coefficients have been calculated with a semi-classical approach. Comparisons between calculated spectra and measurements of several lines of H2O broadened by N2 (and air) in the ν3 and 2ν1 + ν2 + ν3 bands for a wide range of pressure show very satisfactory agreement. The evolution of non-Voigt effects from Doppler to collisional regimes is also presented and discussed.

  15. Radiolytic Cryovolcanism Revisited

    NASA Astrophysics Data System (ADS)

    Cooper, J. F.; Cooper, P. D.; Sittler, E. C.; Wesenberg, R. P.

    2013-12-01

    Active geysers of water vapor and ice grains from the south pole of Enceladus are not yet definitively explained in terms of energy sources and processes. Other instances of hot (Io) and cold (Mars, Triton) volcanism beyond Earth are known if not fully understood. We revisit, in comparison to other models, the 'Old Faithful' theory of radiolytic gas-driven cryovolcanism first proposed by Cooper et al. [Plan. Sp. Sci. 2009]. In the energetic electron irradiation environment of Enceladus within Saturn's magnetosphere, a 10-percent duty cycle could be maintained for current geyser activity driven by gases from oxidation of ammonia to N2 and methane to CO2 in the thermal margins of a south polar sea. Much shorter duty cycles down to 0.01 percent would be required to account for thermal power output up to 16 GW, Steady accumulation of oxidant energy over four billion years could have powered all Enceladus emissions over the past four hundred thousand to four hundred million years. There could be separate energy sources driving mass flow and thermal emission over vastly different time scales. Since episodic tidal dissipation on 10 Myr time scales at 0.1 - 1 Gyr intervals [O'Neill and Nimmo, Nature 2010], and thus duty cycles 1 - 10 percent, could heat the polar sea to the current level, the radiolytic energy source could easily power and modulate the geyser mass flow on million-year time scales. Maximum thermal emission temperature 223 K [Abramov and Spencer, Icarus 2009] hints at thermal buffering in the basal and vent wall layers by a 1:1 H2O:H2O2 radiolytic eutectic, assuming deep ice crust saturation with H2O2 from long cumulative surface irradiation and downward ice convection. Due to density stratification the peroxide eutectic and salt water layers could separate, so that the denser peroxide layer (1.2 g/cc) descends to the polar sea while the lighter salt water (1.05 g/cc) rises along separate channels. Methane reservoirs could be found dissolved into the polar

  16. The Rotational Spectrum of Ketene Isotopomers with 18O and 13C Revisited

    NASA Astrophysics Data System (ADS)

    Guarnieri, A.; Huckaufa, A.

    2003-06-01

    The pure rotational spectra of [18O]ketene, H2C=C18O, [1-13C]ketene, H2C=13CO, and [2-13C]ketene, H213C=CO, have been revisited in the frequency region 200 - 350 GHz in the ground vibrational state. From more than 100 R-branch transitions for each isotopomer a set of rotational and centrifugal distortion constants could be derived using the Watson S-reduction formalism. The values obtained for the rotational constants B and C agree very well with results of former investigations. The agreement is worse with respect to the A constants, but our newly determined A values agree well with the corresponding values of the main species and the 17O isotopomer.

  17. Economy and job contract as contexts of sickness absence practices: revisiting locality and habitus.

    PubMed

    Virtanen, P; Vahtera, J; Nakari, R; Pentti, J; Kivimäki, M

    2004-04-01

    This study revisits two Finnish local governments-Raisio and Nokia-that in an earlier study showed different sickness absence rates in the early 1990s. The locality difference was interpreted sociologically, within a framework inspired by Bourdieu's theory of social field, habitus and practice. The same framework is applied in the present study, starting out from the hypothesis that a constant historical and cultural locality context tends to reproduce prevailing sickness absence practices. The hypothesis was tested by extending the context beyond the locality to the macroeconomic fluctuations that occurred during the 1990s and to the type of employment contract. In both localities a 30% rise was observed in levels of sickness absence from 1991-1993 to 1997-2000. At the beginning of the 1990s the absence rate among permanent employees was 1.86 times higher in Nokia than in Raisio; at the end of the decade the corresponding rate ratio was 1.88. The absence rates were significantly lower among fixed-term employees than permanent employees, but the locality difference was seen in their case, too. Both results support the hypothesis. In spite of major changes taking place in the national economy, the differences between the two towns' sickness absence rates persisted, which in this particular case probably reflects the persisting working-class character of Nokia and middle-class character of Raisio. The theory also applies to the difference between permanent and fixed-term employees: the peripheral power position of the latter on work related social fields leads to the observed practices, i.e. to the relatively low absence rate. The results of our revisit give reason to recapitulate and elaborate upon our theoretical interpretation with a view to deepening our understanding of the social origins of sickness absence practices in the post-industrial workplace, which is characterised by increasing atypical employment and growing job insecurity.

  18. Oleanolic acid suppresses aerobic glycolysis in cancer cells by switching pyruvate kinase type M isoforms.

    PubMed

    Liu, Jia; Wu, Ning; Ma, Leina; Liu, Ming; Liu, Ge; Zhang, Yuyan; Lin, Xiukun

    2014-01-01

    Warburg effect, one of the hallmarks for cancer cells, is characterized by metabolic switch from mitochondrial oxidative phosphorylation to aerobic glycolysis. In recent years, increased expression level of pyruvate kinase M2 (PKM2) has been found to be the culprit of enhanced aerobic glycolysis in cancer cells. However, there is no agent inhibiting aerobic glycolysis by targeting PKM2. In this study, we found that Oleanolic acid (OA) induced a switch from PKM2 to PKM1, and consistently, abrogated Warburg effect in cancer cells. Suppression of aerobic glycolysis by OA is mediated by PKM2/PKM1 switch. Furthermore, mTOR signaling was found to be inactivated in OA-treated cancer cells, and mTOR inhibition is required for the effect of OA on PKM2/PKM1 switch. Decreased expression of c-Myc-dependent hnRNPA1 and hnRNPA1 was responsible for OA-induced switch between PKM isoforms. Collectively, we identified that OA is an antitumor compound that suppresses aerobic glycolysis in cancer cells and there is potential that PKM2 may be developed as an important target in aerobic glycolysis pathway for developing novel anticancer agents.

  19. Metabolism Goes Viral

    PubMed Central

    Miyake-Stoner, Shigeki J.; O’Shea, Clodagh C.

    2014-01-01

    Viral and cellular oncogenes converge in targeting critical protein interaction networks to reprogram the cellular DNA and protein replication machinery for pathological replication. In this issue, Thai et al. (2014) show that adenovirus E4ORF1 activates MYC glycolytic targets to induce a Warburg-like effect that converts glucose into nucleotides for viral replication. PMID:24703688

  20. Revisiting first type self-similar solutions of explosions containing ultrarelativistic shocks

    NASA Astrophysics Data System (ADS)

    Tian, Jun

    2018-05-01

    We revisit the first type self-similar solutions for ultrarelativistic shock waves produced by explosions propagating into cold external medium whose density profile decreases with radius as ρ ∝ r-k. The first-type solutions proposed by Blandford and McKee (hereafter BM solution) conforms to the global conservation of energy and applies when k < 4. They have been found to be invalid when k > 17/4 because of the divergence of total energy contained in the shocked fluids. So far no attention has been paid to the particle number. We use the BM solution to calculate the total particle number traversed by the shock and find that it diverges when k > 3. This is inconsistent with the finite particles in the surrounding medium. We propose a possible solution when k > 3 based on the conservation of particle number and discuss its implication for the second-type solutions.

  1. Escitalopram dose-response revisited: an alternative psychometric approach to evaluate clinical effects of escitalopram compared to citalopram and placebo in patients with major depression.

    PubMed

    Bech, Per; Tanghøj, Per; Cialdella, Philippe; Andersen, Henning Friis; Pedersen, Anders Gersel

    2004-09-01

    In continuation of a previous psychometric analysis of dose-response data for citalopram in depression, the corresponding study data for escitalopram is of interest, since escitalopram is the active enantiomer of citalopram and because citalopram was used as the active control. Revisiting those corresponding data, the psychometric properties of the Montgomery-Asberg Depression Scale (MADRS) and the Hamilton Depression Scale (HAMD) were investigated by focusing on the unidimensional HAMD6 and MADRS6. Effect sizes were calculated and compared for two dosages of escitalopram (10 mg and 20 mg daily) and between each of these two dosages and 40 mg citalopram daily. The results showed that the three depression scales MADRS6, MADRS10 and HAMD6 were psychometrically acceptable (coefficient of homogeneity of 0.40 or higher). In the severely depressed patients (MADRS10> or =30) a rather clear dose-response relationship for escitalopram was seen on all three scales after 6 and 8 wk of therapy. Thus, the effect size for 10 mg escitalopram ranged from 0.28 to 0.38 while the effect sizes for 20 mg escitalopram ranged from 0.57 to 0.77. This difference was statistically significant (p<0.01). The effect size for 40 mg citalopram ranged from 0.36 to 0.47, which is within the range found for 40 mg citalopram in our previous dose-response analysis of citalopram after 6 wk of therapy. The numerically largest difference between 20 mg escitalopram and 40 mg citalopram was seen after 8 wk of therapy for MADRS10 (effect size 0.71 vs. 0.37). An item analysis identified 'suicidal thoughts' to be the most discriminating item in this respect. These results for the severely depressed patients were confirmed by the patients self-reported quality of life evaluation. When all included patients were analysed, however, no clear dose-response relationship was seen. In conclusion, a dose-response relationship for escitalopram was seen in the severely depressed patients on all outcome scales after 6

  2. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Xu, Ting; Zhao, Jing; Hu, Ping

    Pentachlorophenol (PCP) is a prevalent pollutant in the environment and has been demonstrated to be a serious toxicant to humans and animals. However, little is known regarding the molecular mechanism underlying its toxic effects on vertebrate early development. To explore the impacts and underlying mechanisms of PCP on early development, zebrafish (Danio rerio) embryos were exposed to PCP at concentrations of 0, 20 and 50 μg/L, and microscopic observation and cDNA microarray analysis were subsequently conducted at gastrulation stage. The morphological observations revealed that PCP caused a developmental delay of zebrafish embryos in a concentration-dependent manner. Transcriptomic data showed thatmore » 50 μg/L PCP treatment resulted in significant changes in gene expression level, and the genes involved in energy metabolism and cell behavior were identified based on gene functional enrichment analysis. The energy production of embryos was influenced by PCP via the activation of glycolysis along with the inhibition of oxidative phosphorylation (OXPHOS). The results suggested that PCP acts as an inhibitor of OXPHOS at 8 hpf (hours postfertilization). Consistent with the activated glycolysis, the cell cycle activity of PCP-treated embryos was higher than the controls. These characteristics are similar to the Warburg effect, which occurs in human tumors. The microinjection of exogenous ATP confirmed that an additional energy supply could rescue PCP-treated embryos from the developmental delay due to the energy deficit. Taken together, our results demonstrated that PCP causes a Warburg-like effect on zebrafish embryos during gastrulation, and the affected embryos had the phenotype of developmental delay. - Highlights: • We treat zebrafish embryos with PCP at gastrula stage. • PCP acts as an oxidative phosphorylation inhibitor, not an uncoupler, in gastrulation. • Exogenous ATP injection will rescue the development of effected embryos. • The transcriptome

  3. Vacuum Ultraviolet Photodissociation and Fourier Transform-Ion Cyclotron Resonance (FT-ICR) Mass Spectrometry: Revisited.

    PubMed

    Shaw, Jared B; Robinson, Errol W; Paša-Tolić, Ljiljana

    2016-03-15

    We revisited the implementation of 193 nm ultraviolet photodissociation (UVPD) within the ion cyclotron resonance (ICR) cell of a Fourier transform-ion cyclotron resonance (FT-ICR) mass spectrometer. UVPD performance characteristics were examined in the context of recent developments in the understanding of UVPD and in-cell tandem mass spectrometry. Efficient UVPD and photo-ECD of a model peptide and proteins within the ICR cell of a FT-ICR mass spectrometer are accomplished through appropriate modulation of laser pulse timing, relative to ion magnetron motion and the potential applied to an ion optical element upon which photons impinge. It is shown that UVPD yields efficient and extensive fragmentation, resulting in excellent sequence coverage for model peptide and protein cations.

  4. Vacuum Ultraviolet Photodissociation and Fourier Transform–Ion Cyclotron Resonance (FT-ICR) Mass Spectrometry: Revisited

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Shaw, Jared B.; Robinson, Errol W.; Pasa-Tolic, Ljiljana

    2016-02-16

    We revisited the implementation of UVPD within the ICR cell of a FT-ICR mass spectrometer. UVPD performance characteristics were examined in the context of recent developments in the understanding of UVPD and in-cell tandem mass spectrometry. Efficient UVPD and photo-ECD of a model peptide and small protein within the ICR cell of a FT-ICR mass spectrometer are accomplished through appropriate modulation of laser pulse timing relative to ion magnetron motion and the potential applied to an ion optical element that photons impinge on. It is shown that UVPD yields efficient and extensive fragmentation resulting in excellent sequence coverage for modelmore » peptide and protein cations.« less

  5. Revisiting sea level changes in the North Sea during the Anthropocene

    NASA Astrophysics Data System (ADS)

    Jensen, Jürgen; Dangendorf, Sönke; Wahl, Thomas; Niehüser, Sebastian

    2016-04-01

    The North Sea is one of the best instrumented ocean basins in the world. Here we revisit sea level changes in the North Sea region from tide gauges, satellite altimetry, hydrographic profiles and ocean reanalysis data from the beginning of the 19th century to present. This includes an overview of the sea level chapter of the North Sea Climate Change Assessment (NOSCCA) complemented by results from more recent investigations. The estimates of long-term changes from tide gauge records are significantly affected by vertical land motion (VLM), which is related to both the large-scale viscoelastic response of the solid earth to ice melting since the last deglaciation and local effects. Removing VLM (estimated from various data sources such as GPS, tide gauge minus altimetry and GIA) significantly reduces the spatial variability of long-term trends in the basin. VLM corrected tide gauge records suggest a transition from relatively moderate changes in the 19th century towards modern trends of roughly 1.5 mm/yr during the 20th century. Superimposed on the long-term changes there is a considerable inter-annual to multi-decadal variability. On inter-annual timescales this variability mainly reflects the barotropic response of the ocean to atmospheric forcing with the inverted barometer effect dominating along the UK and Norwegian coastlines and wind forcing controlling the southeastern part of the basin. The decadal variability is mostly remotely forced and dynamically linked to the North Atlantic via boundary waves in response to long-shore winds along the continental slope. These findings give valuable information about the required horizontal resolution of ocean models and the necessary boundary conditions and are therefore important for the dynamical downscaling of sea level projections for the North Sea coastlines.

  6. The Effect of Utilization Review on Emergency Department Operations.

    PubMed

    Desai, Shoma; Gruber, Phillip F; Eiting, Erick; Seabury, Seth A; Mack, Wendy J; Voyageur, Christian; Vasquez, Veronica; Kim, Hyung T; Terp, Sophie

    2017-11-01

    Increasingly, hospitals are using utilization review software to reduce hospital admissions in an effort to contain costs. Such practices have the potential to increase the number of unsafe discharges, particularly in public safety-net hospitals. Utilization review software tools are not well studied with regard to their effect on emergency department (ED) operations. We study the effect of prospectively used admission decision support on ED operations. In 2012, Los Angeles County + University of Southern California Medical Center implemented prospective use of computerized admission criteria. After implementation, only ED patients meeting primary review (diagnosis-based criteria) or secondary review (medical necessity as determined by an on-site emergency physician) were assigned inpatient beds. Data were extracted from electronic medical records from September 2011 through December 2013. Outcomes included operational metrics, 30-day ED revisits, and 30-day admission rates. Excluding a 6-month implementation period, monthly summary metrics were compared pre- and postimplementation with nonparametric and negative binomial regression methods. All adult ED visits, excluding incarcerated and purely behavioral health visits, were analyzed. The primary outcomes were disposition rates. Secondary outcomes were 30-day ED revisits, 30-day admission rate among return visitors to the ED, and estimated cost. Analysis of 245,662 ED encounters was performed. The inpatient admission rate decreased from 14.2% to 12.8%. Increases in discharge rate (82.4% to 83.4%) and ED observation unit utilization (2.5% to 3.4%) were found. Thirty-day revisits increased (20.4% to 24.4%), although the 30-day admission rate decreased (3.2% to 2.8%). Estimated cost savings totaled $193.17 per ED visit. The prospective application of utilization review software in the ED led to a decrease in the admission rate. This was tempered by a concomitant increase in ED observation unit utilization and 30-day

  7. Tumor microenvironment and metabolic synergy in breast cancers: critical importance of mitochondrial fuels and function.

    PubMed

    Martinez-Outschoorn, Ubaldo; Sotgia, Federica; Lisanti, Michael P

    2014-04-01

    Metabolic synergy or metabolic coupling between glycolytic stromal cells (Warburg effect) and oxidative cancer cells occurs in human breast cancers and promotes tumor growth. The Warburg effect or aerobic glycolysis is the catabolism of glucose to lactate to obtain adenosine triphosphate (ATP). This review summarizes the main findings on this stromal metabolic phenotype, and the associated signaling pathways, as well as the critical role of oxidative stress and autophagy, all of which promote carcinoma cell mitochondrial metabolism and tumor growth. Loss of Caveolin 1 (Cav-1) and the upregulation of monocarboxylate transporter 4 (MCT4) in stromal cells are novel markers of the Warburg effect and metabolic synergy between stromal and carcinoma cells. MCT4 and Cav-1 are also breast cancer prognostic biomarkers. Reactive oxygen species (ROS) are key mediators of the stromal Warburg effect. High ROS also favors cancer cell mitochondrial metabolism and tumorigenesis, and anti-oxidants can reverse this altered stromal and carcinoma metabolism. A pseudo-hypoxic state with glycolysis and low mitochondrial metabolism in the absence of hypoxia is a common feature in breast cancer. High ROS induces loss of Cav-1 in stromal cells and is sufficient to generate a pseudo-hypoxic state. Loss of Cav-1 in the stroma drives glycolysis and lactate extrusion via HIF-1α stabilization and the upregulation of MCT4. Stromal cells with loss of Cav-1 and/or high expression of MCT4 also show a catabolic phenotype, with enhanced macroautophagy. This catabolic state in stromal cells is driven by hypoxia-inducible factor (HIF)-1α, nuclear factor κB (NFκB), and JNK activation and high ROS generation. A feed-forward loop in stromal cells regulates pseudo-hypoxia and metabolic synergy, with Cav-1, MCT4, HIF-1α, NFκB, and ROS as its key elements. Metabolic synergy also may occur between cancer cells and cells in distant organs from the tumor. Cancer cachexia, which is due to severe organismal

  8. Effective Mass Theory of 2D Excitons Revisited

    NASA Astrophysics Data System (ADS)

    Gonzalez, Joseph; Oleynik, Ivan

    Two-dimensional (2D) semiconducting materials possess an exceptionally unique set of electronic and excitonic properties due to the combined effects of quantum and dielectric confinement. Reliable determination of exciton binding energies from both first-principles many-body perturbation theory (GW/BSE) and experiment is very challenging due to the enormous computational expense as well as the tremendous technical difficulties in experiment.. Very recently, effective mass theories of 2D excitons have been developed as an attractive alternative for inexpensive and accurate evaluation of the exciton binding energies. In this presentation, we evaluate two effective mass theory approaches by Velizhanin et al and Olsen et al in predicting exciton binding energies across a wide range of 2D materials. We specifically analyze the trends related to the varying screening lengths and exciton effective masses. We also extended the effective mass theory of 2D excitons to include effects of electron and hole mass anisotropies (mx ≠ my) , the latter showing a substantial influence on exciton binding energies. The recent predictions of exciton binding energies being independent of the exciton effective mass and a linear correlation with the band gap of a specific material are also critically reexamined.

  9. Spherical indentation of a freestanding circular membrane revisited: Analytical solutions and experiments

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jin, Congrui; Davoodabadi, Ali; Li, Jianlin

    Because of the development of novel micro-fabrication techniques to produce ultra-thin materials and increasing interest in thin biological membranes, in recent years, the mechanical characterization of thin films has received a significant amount of attention. To provide a more accurate solution for the relationship among contact radius, load and deflection, the fundamental and widely applicable problem of spherical indentation of a freestanding circular membrane have been revisited. The work presented here significantly extends the previous contributions by providing an exact analytical solution to the governing equations of Föppl–Hecky membrane indented by a frictionless spherical indenter. In this study, experiments ofmore » spherical indentation has been performed, and the exact analytical solution presented in this article is compared against experimental data from existing literature as well as our own experimental results.« less

  10. Spherical indentation of a freestanding circular membrane revisited: Analytical solutions and experiments

    DOE PAGES

    Jin, Congrui; Davoodabadi, Ali; Li, Jianlin; ...

    2017-01-11

    Because of the development of novel micro-fabrication techniques to produce ultra-thin materials and increasing interest in thin biological membranes, in recent years, the mechanical characterization of thin films has received a significant amount of attention. To provide a more accurate solution for the relationship among contact radius, load and deflection, the fundamental and widely applicable problem of spherical indentation of a freestanding circular membrane have been revisited. The work presented here significantly extends the previous contributions by providing an exact analytical solution to the governing equations of Föppl–Hecky membrane indented by a frictionless spherical indenter. In this study, experiments ofmore » spherical indentation has been performed, and the exact analytical solution presented in this article is compared against experimental data from existing literature as well as our own experimental results.« less

  11. Revisiting the age of enlightenment from a collective decision making systems perspective

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rodriguez, Marko A; Watkins, Jennifer H

    2009-01-01

    The ideals of the eighteenth century's Age of Enlightenment are the foundation of modern democracies. The era was characterized by thinkers who promoted progressive social reforms that opposed the long-established aristocracies and monarchies of the time. Prominent examples of such reforms include the establishment of inalienable human rights, self-governing republics, and market capitalism. Twenty-first century democratic nations can benefit from revisiting the systems developed during the Enlightenment and reframing them within the techno-social context of the Information Age. This article explores the application of social algorithms that make use of Thomas Paine's (English: 1737--1809) representatives, Adam Smith's (Scottish: 1723--1790) self-interestedmore » actors, and Marquis de Condorcet's (French: 1743--1794) optimal decision making groups. It is posited that technology-enabled social algorithms can better realize the ideals articulated during the Enlightenment.« less

  12. Advanced Single-Aisle Transport Propulsion Design Options Revisited

    NASA Technical Reports Server (NTRS)

    Guynn, Mark D.; Berton, Jeffrey J.; Tong, Michael T.; Haller, William J.

    2013-01-01

    Future propulsion options for advanced single-aisle transports have been investigated in a number of previous studies by the authors. These studies have examined the system level characteristics of aircraft incorporating ultra-high bypass ratio (UHB) turbofans (direct drive and geared) and open rotor engines. During the course of these prior studies, a number of potential refinements and enhancements to the analysis methodology and assumptions were identified. This paper revisits a previously conducted UHB turbofan fan pressure ratio trade study using updated analysis methodology and assumptions. The changes incorporated have decreased the optimum fan pressure ratio for minimum fuel consumption and reduced the engine design trade-offs between minimizing noise and minimizing fuel consumption. Nacelle drag and engine weight are found to be key drivers in determining the optimum fan pressure ratio from a fuel efficiency perspective. The revised noise analysis results in the study aircraft being 2 to 4 EPNdB (cumulative) quieter due to a variety of reasons explained in the paper. With equal core technology assumed, the geared engine architecture is found to be as good as or better than the direct drive architecture for most parameters investigated. However, the engine ultimately selected for a future advanced single-aisle aircraft will depend on factors beyond those considered here.

  13. The Mantel-Haenszel procedure revisited: models and generalizations.

    PubMed

    Fidler, Vaclav; Nagelkerke, Nico

    2013-01-01

    Several statistical methods have been developed for adjusting the Odds Ratio of the relation between two dichotomous variables X and Y for some confounders Z. With the exception of the Mantel-Haenszel method, commonly used methods, notably binary logistic regression, are not symmetrical in X and Y. The classical Mantel-Haenszel method however only works for confounders with a limited number of discrete strata, which limits its utility, and appears to have no basis in statistical models. Here we revisit the Mantel-Haenszel method and propose an extension to continuous and vector valued Z. The idea is to replace the observed cell entries in strata of the Mantel-Haenszel procedure by subject specific classification probabilities for the four possible values of (X,Y) predicted by a suitable statistical model. For situations where X and Y can be treated symmetrically we propose and explore the multinomial logistic model. Under the homogeneity hypothesis, which states that the odds ratio does not depend on Z, the logarithm of the odds ratio estimator can be expressed as a simple linear combination of three parameters of this model. Methods for testing the homogeneity hypothesis are proposed. The relationship between this method and binary logistic regression is explored. A numerical example using survey data is presented.

  14. The Mantel-Haenszel Procedure Revisited: Models and Generalizations

    PubMed Central

    Fidler, Vaclav; Nagelkerke, Nico

    2013-01-01

    Several statistical methods have been developed for adjusting the Odds Ratio of the relation between two dichotomous variables X and Y for some confounders Z. With the exception of the Mantel-Haenszel method, commonly used methods, notably binary logistic regression, are not symmetrical in X and Y. The classical Mantel-Haenszel method however only works for confounders with a limited number of discrete strata, which limits its utility, and appears to have no basis in statistical models. Here we revisit the Mantel-Haenszel method and propose an extension to continuous and vector valued Z. The idea is to replace the observed cell entries in strata of the Mantel-Haenszel procedure by subject specific classification probabilities for the four possible values of (X,Y) predicted by a suitable statistical model. For situations where X and Y can be treated symmetrically we propose and explore the multinomial logistic model. Under the homogeneity hypothesis, which states that the odds ratio does not depend on Z, the logarithm of the odds ratio estimator can be expressed as a simple linear combination of three parameters of this model. Methods for testing the homogeneity hypothesis are proposed. The relationship between this method and binary logistic regression is explored. A numerical example using survey data is presented. PMID:23516463

  15. Phase diagram of the relaxor ferroelectric (1- x )Pb(Mg 1/3Nb 2/3)O 3+ x PbTiO 3 revisited: a neutron powder diffraction study of the relaxor skin effect

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Phelan, D.; Rodriguez, E. E.; Gao, J.

    2014-11-17

    We revisit the phase diagram of the relaxor ferroelectric PMN- xPT using neutron powder diffraction to test suggestions that residual oxygen vacancies and/or strain affect the ground state crystal structure. Powdered samples of PMN- xPT were prepared with nominal compositions of x = 0:10, 0.20, 0.30, and 0.40 and divided into two identical sets, one of which was annealed in air to relieve grinding-induced strain and to promote an ideal oxygen stoichiometry. For a given composition and temperature the same structural phase is observed for each specimen. However, the distortions in all of the annealed samples are smaller than thosemore » in the as-grown samples. Further, the diffraction patterns for x = 0:10, 0.20, and 0.30 are best refined using the monoclinic Cm space group. By comparing our neutron diffraction results to those obtained on single crystals having similar compositions, we conclude that the relaxor skin effect in PMN- xPT vanishes on the Ti-rich side of the morphotropic phase boundary.« less

  16. Reforestation in southern China: revisiting soil N mineralization and nitrification after 8 years restoration

    PubMed Central

    Mo, Qifeng; Li, Zhi’an; Zhu, Weixing; Zou, Bi; Li, Yingwen; Yu, Shiqin; Ding, Yongzhen; Chen, Yao; Li, Xiaobo; Wang, Faming

    2016-01-01

    Nitrogen availability and tree species selection play important roles in reforestation. However, long-term field studies on the effects and mechanisms of tree species composition on N transformation are very limited. Eight years after tree seedlings were planted in a field experiment, we revisited the site and tested how tree species composition affects the dynamics of N mineralization and nitrification. Both tree species composition and season significantly influenced the soil dissolved organic carbon (DOC) and nitrogen (DON). N-fixing Acacia crassicarpa monoculture had the highest DON, and 10-mixed species plantation had the highest DOC. The lowest DOC and DON concentrations were both observed in Eucalyptus urophylla monoculture. The tree species composition also significantly affected net N mineralization rates. The highest rate of net N mineralization was found in A. crassicarpa monoculture, which was over twice than that in Castanopsis hystrix monoculture. The annual net N mineralization rates of 10-mixed and 30-mixed plantations were similar as that of N-fixing monoculture. Since mixed plantations have good performance in increasing soil DOC, DON, N mineralization and plant biodiversity, we recommend that mixed species plantations should be used as a sustainable approach for the restoration of degraded land in southern China. PMID:26794649

  17. Gray and Green Revisited: A Multidisciplinary Perspective of Gardens, Gardening, and the Aging Process

    PubMed Central

    Wright, Scott D.; Wadsworth, Amy Maida

    2014-01-01

    Over fourteen years ago, the concept of “gray and green” was first introduced by Wright and Lund (2000) to represent a new awareness and a call for increased scholarship at the intersection of environmental issues and the aging process. This review paper revisits that concept with a fresh perspective on the specific role of gardens and gardening in the aging experience. As example, gardening is one of the most popular home-based leisure activities in the US and represents an important activity in the lives of older adults in a variety of residential settings. Yet, there has been a lack of any comprehensive and multidisciplinary (science and humanities) examination of the nexus between gardening and the aging experience, and in particular with research connections to stewardship and caring. In this paper, we review contemporary articles demonstrating the multidisciplinarity of gardening and the aging process. First, we will focus on the beneficial psychological effects resulting from the cultivation of caring, including personal contentment and artistic expression. Second, we will focus on stewardship and how gardening increases health, community awareness, and a connection to future generations. On the surface, this may demonstrate a separation between the humanities and science, but we will clarify a symbiotic relationship between the two disciplines in our conclusion. PMID:24734179

  18. Reforestation in southern China: revisiting soil N mineralization and nitrification after 8 years restoration

    NASA Astrophysics Data System (ADS)

    Mo, Qifeng; Li, Zhi'An; Zhu, Weixing; Zou, Bi; Li, Yingwen; Yu, Shiqin; Ding, Yongzhen; Chen, Yao; Li, Xiaobo; Wang, Faming

    2016-01-01

    Nitrogen availability and tree species selection play important roles in reforestation. However, long-term field studies on the effects and mechanisms of tree species composition on N transformation are very limited. Eight years after tree seedlings were planted in a field experiment, we revisited the site and tested how tree species composition affects the dynamics of N mineralization and nitrification. Both tree species composition and season significantly influenced the soil dissolved organic carbon (DOC) and nitrogen (DON). N-fixing Acacia crassicarpa monoculture had the highest DON, and 10-mixed species plantation had the highest DOC. The lowest DOC and DON concentrations were both observed in Eucalyptus urophylla monoculture. The tree species composition also significantly affected net N mineralization rates. The highest rate of net N mineralization was found in A. crassicarpa monoculture, which was over twice than that in Castanopsis hystrix monoculture. The annual net N mineralization rates of 10-mixed and 30-mixed plantations were similar as that of N-fixing monoculture. Since mixed plantations have good performance in increasing soil DOC, DON, N mineralization and plant biodiversity, we recommend that mixed species plantations should be used as a sustainable approach for the restoration of degraded land in southern China.

  19. Reforestation in southern China: revisiting soil N mineralization and nitrification after 8 years restoration.

    PubMed

    Mo, Qifeng; Li, Zhi'an; Zhu, Weixing; Zou, Bi; Li, Yingwen; Yu, Shiqin; Ding, Yongzhen; Chen, Yao; Li, Xiaobo; Wang, Faming

    2016-01-22

    Nitrogen availability and tree species selection play important roles in reforestation. However, long-term field studies on the effects and mechanisms of tree species composition on N transformation are very limited. Eight years after tree seedlings were planted in a field experiment, we revisited the site and tested how tree species composition affects the dynamics of N mineralization and nitrification. Both tree species composition and season significantly influenced the soil dissolved organic carbon (DOC) and nitrogen (DON). N-fixing Acacia crassicarpa monoculture had the highest DON, and 10-mixed species plantation had the highest DOC. The lowest DOC and DON concentrations were both observed in Eucalyptus urophylla monoculture. The tree species composition also significantly affected net N mineralization rates. The highest rate of net N mineralization was found in A. crassicarpa monoculture, which was over twice than that in Castanopsis hystrix monoculture. The annual net N mineralization rates of 10-mixed and 30-mixed plantations were similar as that of N-fixing monoculture. Since mixed plantations have good performance in increasing soil DOC, DON, N mineralization and plant biodiversity, we recommend that mixed species plantations should be used as a sustainable approach for the restoration of degraded land in southern China.

  20. Antimetabolic Effects of Polyphenols in Breast Cancer Cells: Focus on Glucose Uptake and Metabolism.

    PubMed

    Keating, Elisa; Martel, Fátima

    2018-01-01

    In the last years, metabolic reprogramming became a new key hallmark of tumor cells. One of its components is a deviant energetic metabolism, known as Warburg effect-an aerobic lactatogenesis- characterized by elevated rates of glucose uptake and consumption with high-lactate production even in the presence of oxygen. Because many cancer cells display a greater sensitivity to glucose deprivation-induced cytotoxicity than normal cells, inhibitors of glucose cellular uptake (facilitative glucose transporter 1 inhibitors) and oxidative metabolism (glycolysis inhibitors) are potential therapeutic targets in cancer treatment. Polyphenols, abundantly contained in fruits and vegetables, are dietary components with an established protective role against cancer. Several molecular mechanisms are involved in the anticancer effect of polyphenols, including effects on apoptosis, cell cycle regulation, plasma membrane receptors, signaling pathways, and epigenetic mechanisms. Additionally, inhibition of glucose cellular uptake and metabolism in cancer cell lines has been described for several polyphenols, and this effect was shown to be associated with their anticarcinogenic effect. This work will review data showing an antimetabolic effect of polyphenols and its involvement in the chemopreventive/chemotherapeutic potential of these dietary compounds, in relation to breast cancer.

  1. Revisiting spin-lattice relaxation time measurements for dilute spins in high-resolution solid-state NMR spectroscopy

    NASA Astrophysics Data System (ADS)

    Fu, Riqiang; Li, Jun; Cui, Jingyu; Peng, Xinhua

    2016-07-01

    Numerous nuclear magnetic resonance (NMR) measurements of spin-lattice relaxation times (T1S) for dilute spins such as 13C have led to investigations of the motional dynamics of individual functional groups in solid materials. In this work, we revisit the Solomon equations and analyze how the heteronuclear cross relaxation between the dilute S (e.g. 13C) and abundant I (e.g. 1H) spins affects the measured T1S values in solid-state NMR in the absence of 1H saturation during the recovery time. It is found theoretically that at the beginning of the S spin magnetization recovery, the existence of non-equilibrium I magnetization introduces the heteronuclear cross relaxation effect onto the recovery of the S spin magnetization and confirmed experimentally that such a heteronuclear cross relaxation effect results in the recovery overshoot phenomena for the dilute spins when T1S is on the same order of T1H, leading to inaccurate measurements of the T1S values. Even when T1S is ten times larger than T1H, the heteronuclear cross relaxation effect on the measured T1S values is still noticeable. Furthermore, this cross relaxation effect on recovery trajectory of the S spins can be manipulated and even suppressed by preparing the initial I and S magnetization, so as to obtain the accurate T1S values. A sample of natural abundance L-isoleucine powder has been used to demonstrate the T1S measurements and their corresponding measured T1C values under various experimental conditions.

  2. Student's perceptions of effective clinical teaching revisited.

    PubMed

    Kelly, Claudette

    2007-11-01

    Despite a wealth of research on clinical teaching, the criteria for determining what constitutes effective clinical teaching remain poorly defined [Cholowski, K., 2002. Nursing students' and clinical educators' perceptions of characteristics of effective clinical educators in an Australian university school of nursing. Journal of Advanced Nursing 39 (5), 412-420]. This paper reports on two studies exploring second and third year nursing student's perceptions of effective clinical teaching over 14 years (1989-2003). The aim of the inquiry was to compare student's perceptions in diploma and baccalaureate programs within existing clinical contexts. This research used a generative approach to elicit learner's views of what teacher characteristics and contextual influences impact them in clinical settings. A convenience sample of 30 students at the end of second and third years volunteered to be interviewed in-depth for each study. The first study was conducted in a diploma program, whereas in the second study all but a few students were elected to complete a four year baccalaureate nursing degree. Findings from both studies are remarkably consistent. Students in both studies rated teacher knowledge as most important followed by feedback and communication skills. Teacher knowledge appeared critical in four areas: as it pertains to the clinical setting, the curriculum, the learner and teaching/learning theory. How well students perceived that they were accepted by staff, student-teacher ratios and peer support also appeared to impact student's views of effective clinical teaching. This research has implications for employment and evaluation practices for teachers in applied fields such as nursing. The study raises questions about the recent trend toward temporary employment of clinical teachers and in the separation of academic and clinical roles of nurse educators.

  3. Updating energy security and environmental policy: Energy security theories revisited.

    PubMed

    Proskuryakova, L

    2018-06-18

    The energy security theories are based on the premises of sufficient and reliable supply of fossil fuels at affordable prices in centralized supply systems. Policy-makers and company chief executives develop energy security strategies based on the energy security theories and definitions that dominate in the research and policy discourse. It is therefore of utmost importance that scientists revisit these theories in line with the latest changes in the energy industry: the rapid advancement of renewables and smart grid, decentralization of energy systems, new environmental and climate challenges. The study examines the classic energy security concepts (neorealism, neoliberalism, constructivism and international political economy) and assesses if energy technology changes are taken into consideration. This is done through integrative literature review, comparative analysis, identification of 'international relations' and 'energy' research discourse with the use of big data, and case studies of Germany, China, and Russia. The paper offers suggestions for revision of energy security concepts through integration of future technology considerations. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Photobiology of Symbiodinium revisited: bio-physical and bio-optical signatures

    NASA Astrophysics Data System (ADS)

    Hennige, S. J.; Suggett, D. J.; Warner, M. E.; McDougall, K. E.; Smith, D. J.

    2009-03-01

    Light is often the most abundant resource within the nutrient-poor waters surrounding coral reefs. Consequently, zooxanthellae ( Symbiodinium spp.) must continually photoacclimate to optimise productivity and ensure coral success. In situ coral photobiology is becoming dominated by routine assessments using state-of-the-art non-invasive bio-optical or chlorophyll a fluorescence (bio-physical) techniques. Multiple genetic types of Symbiodinium are now known to exist; however, little focus has been given as to how these types differ in terms of characteristics that are observable using these techniques. Therefore, this investigation aimed to revisit and expand upon a pivotal study by Iglesias-Prieto and Trench (1994) by comparing the photoacclimation characteristics of different Symbiodinium types based on their bio-physical (chlorophyll a fluorescence, reaction centre counts) and bio-optical (optical absorption, pigment concentrations) ‘signatures’. Signatures described here are unique to Symbiodinium type and describe phenotypic responses to set conditions, and hence are not suitable to describe taxonomic structure of in hospite Symbiodinium communities. In this study, eight Symbiodinium types from clades and sub-clades (A-B, F) were grown under two PFDs (Photon Flux Density) and examined. The photoacclimation response by Symbiodinium was highly variable between algal types for all bio-physical and for many bio-optical measurements; however, a general preference to modifying reaction centre content over effective antennae-absorption was observed. Certain bio-optically derived patterns, such as light absorption, were independent of algal type and, when considered per photosystem, were matched by reaction centre stoichiometry. Only by better understanding genotypic and phenotypic variability between Symbiodinium types can future studies account for the relative taxonomic and physiological contribution by Symbiodinium to coral acclimation.

  5. Hydrodynamic limit of Wigner-Poisson kinetic theory: Revisited

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Akbari-Moghanjoughi, M.; International Centre for Advanced Studies in Physical Sciences and Institute for Theoretical Physics, Ruhr University Bochum, D-44780 Bochum

    2015-02-15

    In this paper, we revisit the hydrodynamic limit of the Langmuir wave dispersion relation based on the Wigner-Poisson model in connection with that obtained directly from the original Lindhard dielectric function based on the random-phase-approximation. It is observed that the (fourth-order) expansion of the exact Lindhard dielectric constant correctly reduces to the hydrodynamic dispersion relation with an additional term of fourth-order, beside that caused by the quantum diffraction effect. It is also revealed that the generalized Lindhard dielectric theory accounts for the recently discovered Shukla-Eliasson attractive potential (SEAP). However, the expansion of the exact Lindhard static dielectric function leads tomore » a k{sup 4} term of different magnitude than that obtained from the linearized quantum hydrodynamics model. It is shown that a correction factor of 1/9 should be included in the term arising from the quantum Bohm potential of the momentum balance equation in fluid model in order for a correct plasma dielectric response treatment. Finally, it is observed that the long-range oscillatory screening potential (Friedel oscillations) of type cos(2k{sub F}r)/r{sup 3}, which is a consequence of the divergence of the dielectric function at point k = 2k{sub F} in a quantum plasma, arises due to the finiteness of the Fermi-wavenumber and is smeared out in the limit of very high electron number-densities, typical of white dwarfs and neutron stars. In the very low electron number-density regime, typical of semiconductors and metals, where the Friedel oscillation wavelength becomes much larger compared to the interparticle distances, the SEAP appears with a much deeper potential valley. It is remarked that the fourth-order approximate Lindhard dielectric constant approaches that of the linearized quantum hydrodynamic in the limit if very high electron number-density. By evaluation of the imaginary part of the Lindhard dielectric function, it is shown

  6. Is it time to revisit the role of psychedelic drugs in enhancing human creativity?

    PubMed

    Sessa, B

    2008-11-01

    Human creativity is difficult to define and measure, but it is undoubtedly an important cognitive process. This makes it an interesting challenge for modern neuroscientific exploration - especially given the current interest in developing cognitive enhancers for commercial and clinical uses. There are similarities between the typical traits of creative people and the subjective psychological characteristics of the psychedelic (hallucinogenic) drug experience. This phenomenon was studied in a number of small trials and case studies in the 1960s. Results were inconclusive, and the quality of these studies - by modern research standards - was merely anecdotal. Nevertheless, with today's current renaissance in psychedelic drug research and the growing interest in cognitive enhancing drugs, now may be the time to re-visit these studies with contemporary research methods.

  7. Re-visiting protein-centric two-tier classification of existing DNA-protein complexes

    PubMed Central

    2012-01-01

    Background Precise DNA-protein interactions play most important and vital role in maintaining the normal physiological functioning of the cell, as it controls many high fidelity cellular processes. Detailed study of the nature of these interactions has paved the way for understanding the mechanisms behind the biological processes in which they are involved. Earlier in 2000, a systematic classification of DNA-protein complexes based on the structural analysis of the proteins was proposed at two tiers, namely groups and families. With the advancement in the number and resolution of structures of DNA-protein complexes deposited in the Protein Data Bank, it is important to revisit the existing classification. Results On the basis of the sequence analysis of DNA binding proteins, we have built upon the protein centric, two-tier classification of DNA-protein complexes by adding new members to existing families and making new families and groups. While classifying the new complexes, we also realised the emergence of new groups and families. The new group observed was where β-propeller was seen to interact with DNA. There were 34 SCOP folds which were observed to be present in the complexes of both old and new classifications, whereas 28 folds are present exclusively in the new complexes. Some new families noticed were NarL transcription factor, Z-α DNA binding proteins, Forkhead transcription factor, AP2 protein, Methyl CpG binding protein etc. Conclusions Our results suggest that with the increasing number of availability of DNA-protein complexes in Protein Data Bank, the number of families in the classification increased by approximately three fold. The folds present exclusively in newly classified complexes is suggestive of inclusion of proteins with new function in new classification, the most populated of which are the folds responsible for DNA damage repair. The proposed re-visited classification can be used to perform genome-wide surveys in the genomes of

  8. Effective inhibition of nasopharyngeal carcinoma in vitro and in vivo by targeting glycolysis with oxamate.

    PubMed

    Li, Xiaobing; Lu, Wenhua; Hu, Yumin; Wen, Shijun; Qian, Chaonan; Wu, Wenjing; Huang, Peng

    2013-11-01

    Elevated aerobic glycolysis in cancer cells (Warburg effect) has been observed in many tumor types including nasopharyngeal carcinoma (NPC), which can often be detected clinically using FDG-PET. However, the role of glycolysis in supporting the growth of NPC cells and its therapeutic implications still remain to be investigated. In the present study, we showed that the LDH inhibitor oxamate significantly suppressed NPC cell proliferation in vitro and tumor growth in vivo, yet exhibited minimum toxicity to normal nasopharyngeal epithelial cells in vitro and was well tolerated in mice. Moreover, oxamate exhibited cytotoxic effect in NPC cells under hypoxia. Mechanistic study showed that oxamate significantly inhibited LDH activity, leading to a substantial decrease in glucose uptake and lactate production. Combination of oxamate with a mitochondrial respiratory complex I inhibitor resulted in a significant depletion of cellular ATP and a synergistic killing of cancer cells. Our results suggest that inhibition of glycolysis by oxamate is an effective therapeutic strategy for treatment of NPC and that combination of this compound with mitochondrial-targeted agents may improve the therapeutic activity.

  9. DOE Office of Scientific and Technical Information (OSTI.GOV)

    den Hollander, J.A.; Ugurbil, K.; Brown, T.R.

    Glucose metabolism was followed in suspensions of Saccharomyces cerevisiae by using 13C NMR and 14C radioactive labeling techniques and by Warburg manometer experiments. These experiments were performed for cells grown with various carbon sources in the growth medium, so as to evaluate the effect of catabolite repression. The rate of glucose utilization was most conveniently determined by the 13C NMR experiments, which measured the concentration of (1-13C)glucose, whereas the distribution of end products was determined from the 13C and the 14C experiments. By combining these measurements the flows into the various pathways that contribute to glucose catabolism were estimated, andmore » the effect of oxygen upon glucose catabolism was evaluated. From these measurements, the Pasteur quotient (PQ) for glucose catabolism was calculated to be 2.95 for acetate-grown cells and 1.89 for cells grown on glucose into saturation. The Warburg experiments provided an independent estimate of glucose catabolism. The PQ estimated from Warburg experiments was 2.9 for acetate-grown cells in excellent agreement with the labeled carbon experiments and 4.6 for cells grown into saturation, which did not agree. Possible explanations of these differences are discussed. From these data an estimate is obtained of the net flow through the Embden-Meyerhof-Parnas pathway. The backward flow through fructose-1,6-bisphosphatase (Fru-1,6-P2-ase) was calculated from the scrambling of the 13C label of (1-13C)glucose into the C1 and C6 positions of trehalose. Combining these data allowed us to calculate the net flux through phosphofructokinase (PFK). For acetate-grown cells we found that the relative flow through PFK is a factor of 1.7 faster anaerobically than aerobically.« less

  10. Revisiting Adiabatic Switching for Initial Conditions in Quasi-Classical Trajectory Calculations: Application to CH4.

    PubMed

    Qu, Chen; Bowman, Joel M

    2016-07-14

    Semiclassical quantization of vibrational energies, using adiabatic switching (AS), is applied to CH4 using a recent ab initio potential energy surface, for which exact quantum calculations of vibrational energies are available. Details of the present calculations, which employ a harmonic normal-mode zeroth-order Hamiltonian, emphasize the importance of transforming to the Eckart frame during the propagation of the adiabatically switched Hamiltonian. The AS energies for the zero-point, and fundamental excitations of two modes are in good agreement with the quantum ones. The use of AS in the context of quasi-classical trajectory calculations is revisited, following previous work reported in 1995, which did not recommend the procedure. We come to a different conclusion here.

  11. Extended Versus Narrow-spectrum Antibiotics in the Management of Uncomplicated Appendicitis in Children: A Propensity-matched Comparative Effectiveness Study.

    PubMed

    Cameron, Danielle B; Melvin, Patrice; Graham, Dionne A; Glass, Charity C; Serres, Stephanie K; Kronman, Matthew P; Saito, Jacqueline M; Rangel, Shawn J

    2018-07-01

    The aim of this study was to compare the effectiveness of extended versus narrow spectrum antibiotics in preventing surgical site infections (SSIs) and hospital revisits in children with uncomplicated appendicitis. There is a paucity of high-quality evidence in the pediatric literature comparing the effectiveness of extended versus narrow-spectrum antibiotics in the prevention of SSIs associated with uncomplicated appendicitis. Clinical data from the ACS NSQIP-Pediatric Appendectomy Pilot Project were merged with antibiotic utilization data from the Pediatric Health Information System database for patients undergoing appendectomy for uncomplicated appendicitis at 17 hospitals from January 1, 2013 to June 30, 2015. Patients who received piperacillin/tazobactam (extended spectrum) were compared with those who received either cefoxitin or ceftriaxone with metronidazole (narrow spectrum) after propensity matching on demographic and severity characteristics. Study outcomes were 30-day SSI and hospital revisit rates. Of the 1389 patients included, 39.1% received piperacillin/tazobactam (range by hospital: 0% to 100%), and the remainder received narrow-spectrum agents. No differences in demographics or severity characteristics were found between groups following matching. In the matched analysis, the rates of SSI were similar between groups [extended spectrum: 2.4% vs narrow spectrum 1.8% (odds ratio, OR: 1.05, 95% confidence interval, 95% CI 0.34-3.26)], as was the rate of revisits [extended spectrum: 7.9% vs narrow spectrum 5.1% (OR: 1.46, 95% CI 0.75-2.87)]. Use of extended-spectrum antibiotics was not associated with lower rates of SSI or hospital revisits when compared with narrow-spectrum antibiotics in children with uncomplicated appendicitis. Our results challenge the routine use of extended-spectrum antibiotics observed at many hospitals, particularly given the increasing incidence of antibiotic-resistant organisms.

  12. Revisiting the Corrosion of the Aluminum Current Collector in Lithium-Ion Batteries.

    PubMed

    Ma, Tianyuan; Xu, Gui-Liang; Li, Yan; Wang, Li; He, Xiangming; Zheng, Jianming; Liu, Jun; Engelhard, Mark H; Zapol, Peter; Curtiss, Larry A; Jorne, Jacob; Amine, Khalil; Chen, Zonghai

    2017-03-02

    The corrosion of aluminum current collectors and the oxidation of solvents at a relatively high potential have been widely investigated with an aim to stabilize the electrochemical performance of lithium-ion batteries using such components. The corrosion behavior of aluminum current collectors was revisited using a home-build high-precision electrochemical measurement system, and the impact of electrolyte components and the surface protection layer on aluminum foil was systematically studied. The electrochemical results showed that the corrosion of aluminum foil was triggered by the electrochemical oxidation of solvent molecules, like ethylene carbonate, at a relative high potential. The organic radical cations generated from the electrochemical oxidation are energetically unstable and readily undergo a deprotonation reaction that generates protons and promotes the dissolution of Al 3+ from the aluminum foil. This new reaction mechanism can also shed light on the dissolution of transitional metal at high potentials.

  13. Revisiting the Corrosion of the Aluminum Current Collector in Lithium-Ion Batteries

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ma, Tianyuan; Xu, Gui-Liang; Li, Yan

    The corrosion of aluminum current collectors and the oxidation of solvents at a relatively high potential have been widely investigated with an aim to stabilize the electrochemical performance of lithium-ion batteries using such components. The corrosion behavior of aluminum current collectors was revisited using a home-build high-precision electrochemical measurement system, and the impact of electrolyte components and the surface protection layer on aluminum foil was systematically studied. The electrochemical results showed that the corrosion of aluminum foil was triggered by the electrochemical oxidation of solvent molecules, like ethylene carbonate, at a relative high potential. The organic radical cations generated frommore » the electrochemical oxidation are energetically unstable, and readily undergo a deprotonation reaction that generates protons and promote the dissolution of Al3+ from the aluminum foil. This new reaction mechanism can also shed light on the dissolution of transitional metal at high potentials.« less

  14. Estrogen-Related Receptor Alpha Modulates Lactate Dehydrogenase Activity in Thyroid Tumors

    PubMed Central

    Mirebeau-Prunier, Delphine; Le Pennec, Soazig; Jacques, Caroline; Fontaine, Jean-Fred; Gueguen, Naig; Boutet-Bouzamondo, Nathalie; Donnart, Audrey; Malthièry, Yves; Savagner, Frédérique

    2013-01-01

    Metabolic modifications of tumor cells are hallmarks of cancer. They exhibit an altered metabolism that allows them to sustain higher proliferation rates in hostile environment outside the cell. In thyroid tumors, the expression of the estrogen-related receptor α (ERRα), a major factor of metabolic adaptation, is closely related to the oxidative metabolism and the proliferative status of the cells. To elucidate the role played by ERRα in the glycolytic adaptation of tumor cells, we focused on the regulation of lactate dehydrogenases A and B (LDHA, LDHB) and the LDHA/LDHB ratio. Our study included tissue samples from 10 classical and 10 oncocytic variants of follicular thyroid tumors and 10 normal thyroid tissues, as well as samples from three human thyroid tumor cell lines: FTC-133, XTC.UC1 and RO82W-1. We identified multiple cis-acting promoter elements for ERRα, in both the LDHA and LDHB genes. The interaction between ERRα and LDH promoters was confirmed by chromatin immunoprecipitation assays and in vitro analysis for LDHB. Using knock-in and knock-out cellular models, we found an inverse correlation between ERRα expression and LDH activity. This suggests that thyroid tumor cells may reprogram their metabolic pathways through the up-regulation of ERRα by a process distinct from that proposed by the recently revisited Warburg hypothesis. PMID:23516535

  15. Inhibition of the pentose phosphate pathway by dichloroacetate unravels a missing link between aerobic glycolysis and cancer cell proliferation.

    PubMed

    De Preter, Géraldine; Neveu, Marie-Aline; Danhier, Pierre; Brisson, Lucie; Payen, Valéry L; Porporato, Paolo E; Jordan, Bénédicte F; Sonveaux, Pierre; Gallez, Bernard

    2016-01-19

    Glucose fermentation through glycolysis even in the presence of oxygen (Warburg effect) is a common feature of cancer cells increasingly considered as an enticing target in clinical development. This study aimed to analyze the link between metabolism, energy stores and proliferation rates in cancer cells. We found that cell proliferation, evaluated by DNA synthesis quantification, is correlated to glycolytic efficiency in six cancer cell lines as well as in isogenic cancer cell lines. To further investigate the link between glycolysis and proliferation, a pharmacological inhibitor of the pentose phosphate pathway (PPP) was used. We demonstrated that reduction of PPP activity decreases cancer cells proliferation, with a profound effect in Warburg-phenotype cancer cells. The crucial role of the PPP in sustaining cancer cells proliferation was confirmed using siRNAs against glucose-6-phosphate dehydrogenase, the first and rate-limiting enzyme of the PPP. In addition, we found that dichloroacetate (DCA), a new clinically tested compound, induced a switch of glycolytic cancer cells to a more oxidative phenotype and decreased proliferation. By demonstrating that DCA decreased the activity of the PPP, we provide a new mechanism by which DCA controls cancer cells proliferation.

  16. Revisiting the Master-Signifier, or, Mandela and Repression.

    PubMed

    Hook, Derek; Vanheule, Stijn

    2015-01-01

    The concept of the master-signifier has been subject to a variety of applications in Lacanian forms of political discourse theory and ideology critique. While there is much to be commended in literature of this sort, it often neglects salient issues pertaining to the role of master signifiers in the clinical domain of (individual) psychical economy. The popularity of the concept of the master (or "empty") signifier in political discourse analysis has thus proved a double-edged sword. On the one hand it demonstrates how crucial psychical processes are performed via the operations of the signifier, extending thus the Lacanian thesis that identification is the outcome of linguistic and symbolic as opposed to merely psychological processes. On the other, the use of the master signifier concept within the political realm to track discursive formations tends to distance the term from the dynamics of the unconscious and operation of repression. Accordingly, this paper revisits the master signifier concept, and does so within the socio-political domain, yet while paying particular attention to the functioning of unconscious processes of fantasy and repression. More specifically, it investigates how Nelson Mandela operates as a master signifier in contemporary South Africa, as a vital means of knitting together diverse elements of post-apartheid society, enabling the fantasy of the post-apartheid nation, and holding at bay a whole series of repressed and negated undercurrents.

  17. Single-shot work extraction in quantum thermodynamics revisited

    NASA Astrophysics Data System (ADS)

    Wang, Shang-Yung

    2018-01-01

    We revisit the problem of work extraction from a system in contact with a heat bath to a work storage system, and the reverse problem of state formation from a thermal system state in single-shot quantum thermodynamics. A physically intuitive and mathematically simple approach using only elementary majorization theory and matrix analysis is developed, and a graphical interpretation of the maximum extractable work, minimum work cost of formation, and corresponding single-shot free energies is presented. This approach provides a bridge between two previous methods based respectively on the concept of thermomajorization and a comparison of subspace dimensions. In addition, a conceptual inconsistency with regard to general work extraction involving transitions between multiple energy levels of the work storage system is clarified and resolved. It is shown that an additional contribution to the maximum extractable work in those general cases should be interpreted not as work extracted from the system, but as heat transferred from the heat bath. Indeed, the additional contribution is an artifact of a work storage system (essentially a suspended ‘weight’ that can be raised or lowered) that does not truly distinguish work from heat. The result calls into question the common concept that a work storage system in quantum thermodynamics is simply the quantum version of a suspended weight in classical thermodynamics.

  18. [Revisiting the chemical diversity in prostatic calculi: a SEM and FT-IR investigation].

    PubMed

    Dessombz, A; Méria, P; Bazin, D; Foy, E; Rouzière, S; Weil, R; Daudon, M

    2011-12-01

    Revisiting the chemical diversity of the crystalline phases of prostatic calculi by means of SEM and FT-IR analysis. A set of 32 prostatic calculi has been studied by FT-IR and SEM. FT-IR analysis has determined the chemical composition of each prostatic calculus and the SEM observation has described the morphology of the calculi surfaces and layers. Infrared analysis revealed that 90.7% of the stones were mainly composed of calcium phosphates. However, several mineral phases previously not reported in prostatic calculi were observed, as brushite or octocalcium phosphate pentahydrate. Prostatic calculi exhibited a diversity of crystalline composition and morphology. As previously reported for urinary calculi, relationships between composition and morphology of prostatic stones and étiopathogenic conditions could be of interest in clinical practice. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  19. Age Changes in the Missing-Letter Effect Revisited

    ERIC Educational Resources Information Center

    Saint-Aubin, J.; Klein, R.M.; Landry, T.

    2005-01-01

    When participants search for a target letter while reading, they make more omissions if the target letter is embedded in frequent function words than in less frequent content words. Reflecting developmental changes in component language and literacy skills, the size of this effect increases with age. With adults, the missing-letter effect is due…

  20. The 1959 MW 7.3 Hebgen Lake earthquake revisited: morphology and mechanics from lidar

    NASA Astrophysics Data System (ADS)

    Johnson, K. L.; Nissen, E.; Lajoie, L. J.

    2016-12-01

    This study demonstrates how we can glean new information by revisiting an early instrumental earthquake with high-resolution topography and modern thinking about the mechanics of surface rupturing. The 1959 MW 7.3 Hebgen Lake earthquake is among the largest and most deadly historic earthquakes within the conterminous United States outside of California, and one of the largest normal faulting earthquakes on record globally. The earthquake ruptured the subparallel Hebgen and Red Canyon faults within the slowly extending ( 3 mm/yr) Centennial Mountain Belt, and is one of the first to be field mapped in detail, modeled from global seismograms, and surveyed geodetically. Here, we augment these early studies with an investigation of the surface rupture in its current state. We use a 50 cm-resolution airborne lidar digital terrain model collected by the National Center for Airborne Laser Mapping (NCALM) in 2014 to document the fault scarp morphology, constrain its evolution, and speculate on the mechanical rupture properties. Using a dense set of scarp profiles, we add >400 displacement measurements to the 143 published data points from early field work, allowing more rigorous quantification of along-strike slip variability and strain gradients. Evidence of off-fault deformation is sparse along most of the scarp, though damage zone width increases where the earthquake ruptured closely spaced sedimentary contacts rather than unconsolidated Quaternary deposits. In a few places, we can identify composite scarps from which we estimate the number of earthquakes that have offset Holocene surfaces. We assess the scarp's degraded state, including some sites that were surveyed in 1980 and 2009 and others that have not been revisited since the initial investigation. Where the rupture crosses unconsolidated surfaces, we compute local sediment diffusion coefficients and analyze their variability along strike. Lastly, we model subsurface fault geometry by fitting dipping planes to its

  1. Targeting Key Transporters in Tumor Glycolysis as a Novel Anticancer Strategy.

    PubMed

    Shi, Yunli; Liu, Shengnan; Ahmad, Shabir; Gao, Qingzhi

    2018-05-22

    Increased glycolysis has been one of the metabolic characteristics known as the Warburg effect. The functional and therapeutic importance of the Warburg effect in targeted therapy is scientifically recognized and the glucose metabolic pathway has become a desirable target of anticancer strategies. Glucose transporters (GLUTs) play an important role in cancer glycolysis to sustain cancer cell proliferation, metastasis and survival. Utilizing the knowledge of differential expression and biological functions of GLUTs offers us the possibility of designing and delivering chemotherapeutics toward targeted tumor tissues for improved cancer selectivity. Inhibition of glucose uptake or glycolysis may effectively kill hypoxic cancer cells. Facilitative drug uptake via active transportation provides the potential opportunity to circumvent the drug resistance in chemotherapy. GLUTs as the hallmarks and biotargets of cancer metabolism enable the design and development of novel targeted theranostic agents. In this updated review, we examine the current scenario of the GLUTs as strategic targets in cancer and the unique concepts for discovery and development of GLUTs-targeted anticancer agents. We highlight the recent progresses on structural biology and underlying mechanism studies of GLUTs, with a brief introduction to the computational approaches in GLUT-mediated drug transport and tumor targeting. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Genetic alterations in fatty acid transport and metabolism genes are associated with metastatic progression and poor prognosis of human cancers.

    PubMed

    Nath, Aritro; Chan, Christina

    2016-01-04

    Reprogramming of cellular metabolism is a hallmark feature of cancer cells. While a distinct set of processes drive metastasis when compared to tumorigenesis, it is yet unclear if genetic alterations in metabolic pathways are associated with metastatic progression of human cancers. Here, we analyzed the mutation, copy number variation and gene expression patterns of a literature-derived model of metabolic genes associated with glycolysis (Warburg effect), fatty acid metabolism (lipogenesis, oxidation, lipolysis, esterification) and fatty acid uptake in >9000 primary or metastatic tumor samples from the multi-cancer TCGA datasets. Our association analysis revealed a uniform pattern of Warburg effect mutations influencing prognosis across all tumor types, while copy number alterations in the electron transport chain gene SCO2, fatty acid uptake (CAV1, CD36) and lipogenesis (PPARA, PPARD, MLXIPL) genes were enriched in metastatic tumors. Using gene expression profiles, we established a gene-signature (CAV1, CD36, MLXIPL, CPT1C, CYP2E1) that strongly associated with epithelial-mesenchymal program across multiple cancers. Moreover, stratification of samples based on the copy number or expression profiles of the genes identified in our analysis revealed a significant effect on patient survival rates, thus confirming prominent roles of fatty acid uptake and metabolism in metastatic progression and poor prognosis of human cancers.

  3. Language planning for the 21st century: revisiting bilingual language policy for deaf children.

    PubMed

    Knoors, Harry; Marschark, Marc

    2012-01-01

    For over 25 years in some countries and more recently in others, bilingual education involving sign language and the written/spoken vernacular has been considered an essential educational intervention for deaf children. With the recent growth in universal newborn hearing screening and technological advances such as digital hearing aids and cochlear implants, however, more deaf children than ever before have the potential for acquiring spoken language. As a result, the question arises as to the role of sign language and bilingual education for deaf children, particularly those who are very young. On the basis of recent research and fully recognizing the historical sensitivity of this issue, we suggest that language planning and language policy should be revisited in an effort to ensure that they are appropriate for the increasingly diverse population of deaf children.

  4. CFHTLenS revisited: assessing concordance with Planck including astrophysical systematics

    NASA Astrophysics Data System (ADS)

    Joudaki, Shahab; Blake, Chris; Heymans, Catherine; Choi, Ami; Harnois-Deraps, Joachim; Hildebrandt, Hendrik; Joachimi, Benjamin; Johnson, Andrew; Mead, Alexander; Parkinson, David; Viola, Massimo; van Waerbeke, Ludovic

    2017-02-01

    We investigate the impact of astrophysical systematics on cosmic shear cosmological parameter constraints from the Canada-France-Hawaii Telescope Lensing Survey (CFHTLenS) and the concordance with cosmic microwave background measurements by Planck. We present updated CFHTLenS cosmic shear tomography measurements extended to degree scales using a covariance calibrated by a new suite of N-body simulations. We analyse these measurements with a new model fitting pipeline, accounting for key systematic uncertainties arising from intrinsic galaxy alignments, baryonic effects in the non-linear matter power spectrum, and photometric redshift uncertainties. We examine the impact of the systematic degrees of freedom on the cosmological parameter constraints, both independently and jointly. When the systematic uncertainties are considered independently, the intrinsic alignment amplitude is the only degree of freedom that is substantially preferred by the data. When the systematic uncertainties are considered jointly, there is no consistently strong preference in favour of the more complex models. We quantify the level of concordance between the CFHTLenS and Planck data sets by employing two distinct data concordance tests, grounded in Bayesian evidence and information theory. We find that the two data concordance tests largely agree with one another and that the level of concordance between the CFHTLenS and Planck data sets is sensitive to the exact details of the systematic uncertainties included in our analysis, ranging from decisive discordance to substantial concordance as the treatment of the systematic uncertainties becomes more conservative. The least conservative scenario is the one most favoured by the cosmic shear data, but it is also the one that shows the greatest degree of discordance with Planck. The data and analysis code are publicly available at https://github.com/sjoudaki/cfhtlens_revisited.

  5. Character Building or Subversive Consequences of Employment during High School: Causal Effects Based on Propensity Score Models for Categorical Treatments

    ERIC Educational Resources Information Center

    Nagengast, Benjamin; Marsh, Herbert W.; Chiorri, Carlo; Hau, Kit-Tai

    2014-01-01

    The present study revisited the unresolved issue of the long-term effects of part-time working intensity during high school on students' achievement, participation in postsecondary education, time allocation, and work-related values and expectations. Using data from the Educational Longitudinal Study of 2002 (N = 14,654), the effects of part-time…

  6. Metabolism goes viral.

    PubMed

    Miyake-Stoner, Shigeki J; O'Shea, Clodagh C

    2014-04-01

    Viral and cellular oncogenes converge in targeting critical protein interaction networks to reprogram the cellular DNA and protein replication machinery for pathological replication. In this issue, Thai et al. (2014) show that adenovirus E4ORF1 activates MYC glycolytic targets to induce a Warburg-like effect that converts glucose into nucleotides for viral replication. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Revisiting the Corrosion of the Aluminum Current Collector in Lithium-Ion Batteries

    DOE PAGES

    Ma, Tianyuan; Xu, Gui -Liang; Li, Yan; ...

    2017-02-16

    The corrosion of aluminum current collectors and the oxidation of solvents at a relatively high potential have been widely investigated with an aim to stabilize the electrochemical performance of lithium-ion batteries using such components. The corrosion behavior of aluminum current collectors was revisited using a home-build high-precision electrochemical measurement system, and the impact of electrolyte components and the surface protection layer on aluminum foil was systematically studied. The electrochemical results showed that the corrosion of aluminum foil was triggered by the electrochemical oxidation of solvent molecules, like ethylene carbonate, at a relative high potential. The organic radical cations generated frommore » the electrochemical oxidation are energetically unstable, and readily undergo a deprotonation reaction that generates protons and promote the dissolution of Al 3+ from the aluminum foil. Finally, this new reaction mechanism can also shed light on the dissolution of transitional metal at high potentials.« less

  8. Revisiting the Corrosion of the Aluminum Current Collector in Lithium-Ion Batteries

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ma, Tianyuan; Xu, Gui -Liang; Li, Yan

    The corrosion of aluminum current collectors and the oxidation of solvents at a relatively high potential have been widely investigated with an aim to stabilize the electrochemical performance of lithium-ion batteries using such components. The corrosion behavior of aluminum current collectors was revisited using a home-build high-precision electrochemical measurement system, and the impact of electrolyte components and the surface protection layer on aluminum foil was systematically studied. The electrochemical results showed that the corrosion of aluminum foil was triggered by the electrochemical oxidation of solvent molecules, like ethylene carbonate, at a relative high potential. The organic radical cations generated frommore » the electrochemical oxidation are energetically unstable, and readily undergo a deprotonation reaction that generates protons and promote the dissolution of Al 3+ from the aluminum foil. Finally, this new reaction mechanism can also shed light on the dissolution of transitional metal at high potentials.« less

  9. Introduction: revisiting the "negrito" hypothesis: a transdisciplinary approach to human prehistory in southeast Asia.

    PubMed

    Endicott, Phillip

    2013-01-01

    The "negrito" hypothesis predicts that a shared phenotype among various contemporary groups of hunter-gatherers in Southeast Asia--dark skin, short stature, tight curly hair--is due to common descent from a region-wide, pre-Neolithic substrate of humanity. The alternative is that their distinctive phenotype results from convergent evolution. The core issues of the negrito hypothesis are today more relevant than ever to studies of human evolution, including the out-of-Africa migration, admixture with Denisovans, and the effects of environment and ecology on life-history traits. Understanding the current distribution of the negrito phenotype dictates a wide-ranging remit for study, including the articulation of the relationship between foragers and farmers in the present, the development of settled agriculture in the mid-Holocene, and terminal Pleistocene population expansions. The consensus reached by the contributors to this special double issue of Human Biology is that there is not yet conclusive evidence either for or against the negrito hypothesis. Nevertheless, the process of revisiting the problem will benefit the knowledge of the human prehistory of Southeast Asia. Whether the term negrito accurately reflects the all-encompassing nature of the resulting inquiry is in itself questionable, but the publication of this double issue is testament to the enduring ability of this hypothesis to unite disparate academic disciplines in a common purpose. Copyright © 2013 Wayne State University Press, Detroit, Michigan 48201-1309.

  10. Sub-Chandrasekhar-mass White Dwarf Detonations Revisited

    NASA Astrophysics Data System (ADS)

    Shen, Ken J.; Kasen, Daniel; Miles, Broxton J.; Townsley, Dean M.

    2018-02-01

    The detonation of a sub-Chandrasekhar-mass white dwarf (WD) has emerged as one of the most promising Type Ia supernova (SN Ia) progenitor scenarios. Recent studies have suggested that the rapid transfer of a very small amount of helium from one WD to another is sufficient to ignite a helium shell detonation that subsequently triggers a carbon core detonation, yielding a “dynamically driven double-degenerate double-detonation” SN Ia. Because the helium shell that surrounds the core explosion is so minimal, this scenario approaches the limiting case of a bare C/O WD detonation. Motivated by discrepancies in previous literature and by a recent need for detailed nucleosynthetic data, we revisit simulations of naked C/O WD detonations in this paper. We disagree to some extent with the nucleosynthetic results of previous work on sub-Chandrasekhar-mass bare C/O WD detonations; for example, we find that a median-brightness SN Ia is produced by the detonation of a 1.0 {M}ȯ WD instead of a more massive and rarer 1.1 {M}ȯ WD. The neutron-rich nucleosynthesis in our simulations agrees broadly with some observational constraints, although tensions remain with others. There are also discrepancies related to the velocities of the outer ejecta and light curve shapes, but overall our synthetic light curves and spectra are roughly consistent with observations. We are hopeful that future multidimensional simulations will resolve these issues and further bolster the dynamically driven double-degenerate double-detonation scenario’s potential to explain most SNe Ia.

  11. SU-E-J-102: Separation of Metabolic Supply and Demand: From Power Grid Economics to Cancer Metabolism

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Epstein, T; Xu, L; Gillies, R

    2014-06-01

    Purpose: To study a new model of glucose metabolism which is primarily governed by the timescale of the energetic demand and not by the oxygen level, and its implication on cancer metabolism (Warburg effect) Methods: 1) Metabolic profiling of membrane transporters activity in several cell lines, which represent the spectrum from normal breast epithelium to aggressive, metastatic cancer, using Seahorse XF reader.2) Spatial localization of oxidative and non-oxidative metabolic components using immunocytochemical imaging of the glycolytic ATP-producing enzyme, pyruvate kinase and mitochondria. 3) Finite element simulations of coupled partial differential equations using COMSOL and MATLAB. Results: Inhibition or activation ofmore » pumps on the cell membrane led to reduction or increase in aerobic glycolysis, respectively, while oxidative phosphorylation remained unchanged. These results were consistent with computational simulations of changes in short-timescale demand for energy by cell membrane processes. A specific model prediction was that the spatial distribution of ATP-producing enzymes in the glycolytic pathway must be primarily localized adjacent to the cell membrane, while mitochondria should be predominantly peri-nuclear. These predictions were confirmed experimentally. Conclusion: The results in this work support a new model for glucose metabolism in which glycolysis and oxidative phosphorylation supply different types of energy demand. Similar to power grid economics, optimal metabolic control requires the two pathways, even in normoxic conditions, to match two different types of energy demands. Cells use aerobic metabolism to meet baseline, steady energy demand and glycolytic metabolism to meet short-timescale energy demands, mainly from membrane transport activities, even in the presence of oxygen. This model provides a mechanism for the origin of the Warburg effect in cancer cells. Here, the Warburg effect emerges during carcinogenesis is a

  12. Implementation of an emergency department atrial fibrillation and flutter pathway improves rates of appropriate anticoagulation, reduces length of stay and thirty-day revisit rates for congestive heart failure.

    PubMed

    Barbic, David; DeWitt, Chris; Harris, Devin; Stenstrom, Robert; Grafstein, Eric; Wu, Crane; Vadeanu, Cristian; Heilbron, Brett; Haaf, Jenelle; Tung, Stanley; Kalla, Dan; Marsden, Julian; Christenson, Jim; Scheuermeyer, Frank

    2018-05-01

    An evidence-based emergency department (ED) atrial fibrillation and flutter (AFF) pathway was developed to improve care. The primary objective was to measure rates of new anticoagulation (AC) on ED discharge for AFF patients who were not AC correctly upon presentation. This is a pre-post evaluation from April to December 2013 measuring the impact of our pathway on rates of new AC and other performance measures in patients with uncomplicated AFF solely managed by emergency physicians. A standardized chart review identified demographics, comorbidities, and ED treatments. The primary outcome was the rate of new AC. Secondary outcomes were ED length of stay (LOS), referrals to AFF clinic, ED revisit rates, and 30-day rates of return visits for congestive heart failure (CHF), stroke, major bleeding, and death. ED AFF patients totalling 301 (129 pre-pathway [PRE]; 172 post-pathway [POST]) were included; baseline demographics were similar between groups. The rates of AC at ED presentation were 18.6% (PRE) and 19.7% (POST). The rates of new AC on ED discharge were 48.6 % PRE (95% confidence interval [CI] 42.1%-55.1%) and 70.2% POST (62.1%-78.3%) (20.6% [p<0.01; 15.1-26.3]). Median ED LOS decreased from 262 to 218 minutes (44 minutes [p<0.03; 36.2-51.8]). Thirty-day rates of ED revisits for CHF decreased from 13.2% to 2.3% (10.9%; p<0.01; 8.1%-13.7%), and rates of other measures were similar. The evidence-based pathway led to an improvement in the rate of patients with new AC upon discharge, a reduction in ED LOS, and decreased revisit rates for CHF.

  13. Double neutron stars: merger rates revisited

    NASA Astrophysics Data System (ADS)

    Chruslinska, Martyna; Belczynski, Krzysztof; Klencki, Jakub; Benacquista, Matthew

    2018-03-01

    We revisit double neutron star (DNS) formation in the classical binary evolution scenario in light of the recent Laser Interferometer Gravitational-wave Observatory (LIGO)/Virgo DNS detection (GW170817). The observationally estimated Galactic DNS merger rate of R_MW = 21^{+28}_{-14} Myr-1, based on three Galactic DNS systems, fully supports our standard input physics model with RMW = 24 Myr-1. This estimate for the Galaxy translates in a non-trivial way (due to cosmological evolution of progenitor stars in chemically evolving Universe) into a local (z ≈ 0) DNS merger rate density of Rlocal = 48 Gpc-3 yr-1, which is not consistent with the current LIGO/Virgo DNS merger rate estimate (1540^{+3200}_{-1220} Gpc-3 yr-1). Within our study of the parameter space, we find solutions that allow for DNS merger rates as high as R_local ≈ 600^{+600}_{-300} Gpc-3 yr-1 which are thus consistent with the LIGO/Virgo estimate. However, our corresponding BH-BH merger rates for the models with high DNS merger rates exceed the current LIGO/Virgo estimate of local BH-BH merger rate (12-213 Gpc-3 yr-1). Apart from being particularly sensitive to the common envelope treatment, DNS merger rates are rather robust against variations of several of the key factors probed in our study (e.g. mass transfer, angular momentum loss, and natal kicks). This might suggest that either common envelope development/survival works differently for DNS (˜10-20 M⊙ stars) than for BH-BH (˜40-100 M⊙ stars) progenitors, or high black hole (BH) natal kicks are needed to meet observational constraints for both types of binaries. Our conclusion is based on a limited number of (21) evolutionary models and is valid within this particular DNS and BH-BH isolated binary formation scenario.

  14. Revisiting NLTE Rovibrational Excitation of CO in UV Irradiated Environments

    NASA Astrophysics Data System (ADS)

    Zhang, Ziwei; Yang, Benhui H.; Stancil, Phillip C.; Walker, Kyle M.; Forrey, Robert C.; Naduvalath, Balakrishnan

    2018-06-01

    Being the second most abundant molecule in the ISM, CO has been well observed and studied as a tracer for many astrophysical processes. Highly rovibrationally excited CO emission is used to reveal features in intense UV-irradiated regions such as the inner rim of protoplanetary disks, carbon star envelopes, and star forming regions. Collisional rate coefficients are crucial for non-local thermodynamic equilibrium (NLTE) molecular analysis in such regions, while data for high rovibrational levels for CO were previously unavailable. Here we revisit CO excitation properties with comprehensive collisional data including high rovibrational states (up to v=5 and J=40) colliding with H2, H and He, in various NLTE astrophysical environments with the spectral modeling packages RADEX and Cloudy. We studied line ratio diagnostics between low- and high-vibrational transitions with RADEX. Using Cloudy, we investigated molecular properties in complex environments, such as photodissociation regions and the outflow of the carbon star IRC+10216, illustrating the potential for utilizing high rovibrational NLTE analysis in future astrophysical modeling.This work was supported by NASA Grants NNX15AI61G and NNX16AF09G.

  15. Biogas from Macroalgae: is it time to revisit the idea?

    PubMed Central

    2012-01-01

    The economic and environmental viability of dedicated terrestrial energy crops is in doubt. The production of large scale biomass (macroalgae) for biofuels in the marine environment was first tested in the late 1960’s. The culture attempts failed due to the engineering challenges of farming offshore. However the energy conversion via anaerobic digestion was successful as the biochemical composition of macroalgae makes it an ideal feedstock. The technology for the mass production of macroalgae has developed principally in China and Asia over the last 50 years to such a degree that it is now the single largest product of aquaculture. There has also been significant technology transfer and macroalgal cultivation is now well tried and tested in Europe and America. The inherent advantage of production of biofuel feedstock in the marine environment is that it does not compete with food production for land or fresh water. Here we revisit the idea of the large scale cultivation of macroalgae at sea for subsequent anaerobic digestion to produce biogas as a source of renewable energy, using a European case study as an example. PMID:23186536

  16. Revisiting streamside trees that do not use stream water: can the two water worlds hypothesis and snowpack isotopic effects explain a missing water source?: Riparian tree water sources

    DOE PAGES

    Bowling, David R.; Schulze, Emily S.; Hall, Steven J.

    2016-10-14

    We revisit a classic ecohydrological study that showed streamside riparian trees in a semiarid mountain catchment did not use perennial stream water. The original study suggested that mature individuals of Acer negundo, Acer grandidentatum, and other species were dependent on water from “deeper strata,” possibly groundwater. We used a dual stable isotope approach (δ 18O and δ 2H) to further examine the water sources of these trees. We tested the hypothesis that groundwater was the main tree water source, but found that neither groundwater nor stream water matched the isotope composition of xylem water during two growing seasons. Soil watermore » (0–1 m depth) was closest to and periodically overlapped with xylem water isotope composition, but overall, xylem water was isotopically enriched compared to all measured water sources. The “two water worlds” hypothesis postulates that soil water comprises isotopically distinct mobile and less mobile pools that do not mix, potentially explaining this disparity. We further hypothesized that isotopic effects during snowpack metamorphosis impart a distinct isotope signature to the less mobile soil water that supplies summer transpiration. Depth trends in water isotopes following snowmelt were consistent with the two water worlds hypothesis, but snow metamorphic isotope effects could not explain the highly enriched xylem water. Thus, the dual isotope approach did not unambiguously determine the water source(s) of these riparian trees. Further exploration of physical, geochemical, and biological mechanisms of water isotope fractionation and partitioning is necessary to resolve these data, highlighting critical challenges in the isotopic determination of plant water sources.« less

  17. Revisiting streamside trees that do not use stream water: can the two water worlds hypothesis and snowpack isotopic effects explain a missing water source?: Riparian tree water sources

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bowling, David R.; Schulze, Emily S.; Hall, Steven J.

    We revisit a classic ecohydrological study that showed streamside riparian trees in a semiarid mountain catchment did not use perennial stream water. The original study suggested that mature individuals of Acer negundo, Acer grandidentatum, and other species were dependent on water from “deeper strata,” possibly groundwater. We used a dual stable isotope approach (δ 18O and δ 2H) to further examine the water sources of these trees. We tested the hypothesis that groundwater was the main tree water source, but found that neither groundwater nor stream water matched the isotope composition of xylem water during two growing seasons. Soil watermore » (0–1 m depth) was closest to and periodically overlapped with xylem water isotope composition, but overall, xylem water was isotopically enriched compared to all measured water sources. The “two water worlds” hypothesis postulates that soil water comprises isotopically distinct mobile and less mobile pools that do not mix, potentially explaining this disparity. We further hypothesized that isotopic effects during snowpack metamorphosis impart a distinct isotope signature to the less mobile soil water that supplies summer transpiration. Depth trends in water isotopes following snowmelt were consistent with the two water worlds hypothesis, but snow metamorphic isotope effects could not explain the highly enriched xylem water. Thus, the dual isotope approach did not unambiguously determine the water source(s) of these riparian trees. Further exploration of physical, geochemical, and biological mechanisms of water isotope fractionation and partitioning is necessary to resolve these data, highlighting critical challenges in the isotopic determination of plant water sources.« less

  18. Side-effects of topical steroids: A long overdue revisit.

    PubMed

    Coondoo, Arijit; Phiske, Meghana; Verma, Shyam; Lahiri, Koushik

    2014-10-01

    The introduction of topical steroids (TS) of varying potency have rendered the therapy of inflammatory cutaneous disorders more effective and less time-consuming. However the usefulness of these has become a double edged sword with constantly rising instances of abuse and misuse leading to serious local, systemic and psychological side effects. These side effects occur more with TS of higher potency and on particular areas of the body like face and genitalia. The article reviews the side effects of TS with special mention about peadiatric age group, also includes the measures for preventing the side effects.

  19. Revisiting the returns-volume relationship: Time variation, alternative measures and the financial crisis

    NASA Astrophysics Data System (ADS)

    Cook, Steve; Watson, Duncan

    2017-03-01

    Following its introduction in the seminal study of Osborne (1959), a voluminous literature has emerged examining the returns-volume relationship for financial assets. The present paper revisits this relationship in an examination of the FTSE100 which extends the existing literature in two ways. First, alternative daily measures of the FTSE100 index are used to create differing returns and absolute returns series to employ in an examination of returns-volume causality. Second, rolling regression analysis is utilised to explore potential time variation in the returns-volume relationship. The findings obtained depict a hitherto unconsidered complexity in this relationship with the type of returns series considered and financial crisis found to be significant underlying factors. The implications of the newly derived results for both the understanding of the nature of the returns-volume relationship and the development of theories in connection to it are discussed.

  20. Effect Modification and Interaction Terms: It Takes Two to Tango.

    PubMed

    Jupiter, Daniel C

    2016-01-01

    In this Investigators' Corner I look more deeply into the previously discussed phenomenon of effect modification. I revisit an explanation and examples of the phenomenon and then examine how to account for it statistically. Specifically, I show, in detail, how to write a regression equation that includes interaction terms that account for the effect modification. Finally, I look at interpretation of regression coefficients both with and without the presence of effect modification, and the associated interaction terms. Copyright © 2016 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  1. Revisiting the use of hyperdiffusivities in numerical dynamo models

    NASA Astrophysics Data System (ADS)

    Fournier, A.; Aubert, J.

    2012-04-01

    The groundbreaking numerical dynamo models of Glatzmaier & Roberts (1995) and Kuang & Bloxham (1997) received some criticism due to their use of hyperdiffusivities, whereby small scale processes artificially experience much stronger dissipation than large scale processes. This stronger dissipation they chose was anisotropic, in that it was only effective in the horizontal direction, and parameterized in spectral space using the following generic formula for any diffusive parameter ν ν(l) = ν0 ifl ≤ l0, ν(l) = ν0[1 + a(l- l0)n] ifl > l0, in which l is the spherical harmonic degree, ν0 is a reference value, l0 is the degree above which hyperdiffusivities start operating, and a and n are real numbers. Following the same choice as the studies mentioned above (which had most notably l0 = 0), Grote & Busse (2000) showed in a fully nonlinear context that the usage of hyperdiffusivities could lead to substantially different dynamics and magnetic field generation mechanisms. Without questioning the physical relevance of this parameterization of subgrid scale processes, we wish here to revisit the use of hyperdiffusivities (as defined mathematically above), on the account of the observation that today's models are run with a truncation at much larger spherical harmonic degree than early models. Consequently, they do not require hyperdiffusivities to kick in at the largest scales (l0 can be set to several tens). An exploration of those regions of parameter space less accessible to numerical models could therefore benefit from their use, provided they do not alter noticeably the largest scales of the dynamo (which are the ones expressing themselves in the record of the geomagnetic secular variation). We compare the statistics of a direct numerical simulation with the statistics of several hyperdiffusive simulations. In the prospect of exploring the parameter space and constructing statistics for their subsequent use for geomagnetic data assimilation practice, we

  2. Corrosion Properties of Dissimilar Friction Stir Welded 6061 Aluminum and HT590 Steel

    NASA Astrophysics Data System (ADS)

    Seo, Bosung; Song, Kuk Hyun; Park, Kwangsuk

    2018-05-01

    Corrosion properties of dissimilar friction stir welded 6061 aluminum and HT590 steel were investigated to understand effects of galvanic corrosion. As cathode when coupled, HT590 was cathodically protected. However, the passivation of AA6061 made the aluminum alloy cathode temporarily, which leaded to corrosion of HT590. From the EIS analysis showing Warburg diffusion plot in Nyquist plots, it can be inferred that the stable passivation layer was formed on AA6061. However, the weld as well as HT590 did not show Warburg diffusion plot in Nyquist plots, suggesting that there was no barrier for corrosion or even if it exists, the barrier had no function for preventing and/or retarding charge transport through the passivation layer. The open circuit potential measurements showed that the potential of the weld was similar to that of HT590, which lied in the pitting region for AA6061, making the aluminum alloy part of the weld keep corrosion state. That resulted in the cracked oxide film on AA6061 of the weld, which could not play a role of corrosion barrier.

  3. Betaine is a positive regulator of mitochondrial respiration

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lee, Icksoo, E-mail: icksoolee@dankook.ac.kr

    2015-01-09

    Highlights: • Betaine enhances cytochrome c oxidase activity and mitochondrial respiration. • Betaine increases mitochondrial membrane potential and cellular energy levels. • Betaine’s anti-tumorigenic effect might be due to a reversal of the Warburg effect. - Abstract: Betaine protects cells from environmental stress and serves as a methyl donor in several biochemical pathways. It reduces cardiovascular disease risk and protects liver cells from alcoholic liver damage and nonalcoholic steatohepatitis. Its pretreatment can rescue cells exposed to toxins such as rotenone, chloroform, and LiCl. Furthermore, it has been suggested that betaine can suppress cancer cell growth in vivo and in vitro.more » Mitochondrial electron transport chain (ETC) complexes generate the mitochondrial membrane potential, which is essential to produce cellular energy, ATP. Reduced mitochondrial respiration and energy status have been found in many human pathological conditions including aging, cancer, and neurodegenerative disease. In this study we investigated whether betaine directly targets mitochondria. We show that betaine treatment leads to an upregulation of mitochondrial respiration and cytochrome c oxidase activity in H2.35 cells, the proposed rate limiting enzyme of ETC in vivo. Following treatment, the mitochondrial membrane potential was increased and cellular energy levels were elevated. We propose that the anti-proliferative effects of betaine on cancer cells might be due to enhanced mitochondrial function contributing to a reversal of the Warburg effect.« less

  4. Revisiting the Effect of Anthropomorphizing a Social Cause Campaign.

    PubMed

    Williams, Lisa A; Masser, Barbara; Sun, Jessie

    2015-01-01

    Recent research suggests that anthropomorphism can be harnessed as a tool to boost intentions to comply with social cause campaigns. Drawing on the human tendency to extend moral concern to entities portrayed as humanlike, it has been argued that adding personified features to a social campaign elevates anticipated guilt at failing to comply, and this subsequently boosts intentions to comply with that campaign. The present research aimed to extend extant research by disentangling the effects of emotional and non-emotional anthropomorphism, and differentiating amongst other emotional mechanisms of the anthropomorphism-compliance effect (namely, anticipated pride and anticipated regret). Experiment 1 (N = 294) compared the effectiveness of positive, negative, and emotionally-neutral anthropomorphized campaign posters for boosting campaign compliance intentions against non-anthropomorphized posters. We also measured potential mechanisms including anticipated guilt, regret, and pride. Results failed to support the anthropomorphism-compliance effect, and no changes in anticipated emotion according to anthropomorphism emerged. Experiments 2 (N = 150) and 3 (N = 196) represented further tests of the anthropomorphism-compliance effect. Despite high statistical power and efforts to closely replicate the conditions under which the anthropomorphism-compliance effect had been previously observed, no differences in compliance intention or anticipated emotion according to anthropomorphism emerged. A meta-analysis of the effects of anthropomorphism on compliance and anticipated emotion across the three experiments revealed effect size estimates that did not differ significantly from zero. The results of these three experiments suggest that the anthropomorphism-compliance effect is fragile and perhaps subject to contextual and idiographic influences. Thus, this research provides important insight and impetus for future research on the applied and theoretical utility of

  5. Revisiting the Effect of Anthropomorphizing a Social Cause Campaign

    PubMed Central

    Williams, Lisa A.; Masser, Barbara; Sun, Jessie

    2015-01-01

    Recent research suggests that anthropomorphism can be harnessed as a tool to boost intentions to comply with social cause campaigns. Drawing on the human tendency to extend moral concern to entities portrayed as humanlike, it has been argued that adding personified features to a social campaign elevates anticipated guilt at failing to comply, and this subsequently boosts intentions to comply with that campaign. The present research aimed to extend extant research by disentangling the effects of emotional and non-emotional anthropomorphism, and differentiating amongst other emotional mechanisms of the anthropomorphism-compliance effect (namely, anticipated pride and anticipated regret). Experiment 1 (N = 294) compared the effectiveness of positive, negative, and emotionally-neutral anthropomorphized campaign posters for boosting campaign compliance intentions against non-anthropomorphized posters. We also measured potential mechanisms including anticipated guilt, regret, and pride. Results failed to support the anthropomorphism-compliance effect, and no changes in anticipated emotion according to anthropomorphism emerged. Experiments 2 (N = 150) and 3 (N = 196) represented further tests of the anthropomorphism-compliance effect. Despite high statistical power and efforts to closely replicate the conditions under which the anthropomorphism-compliance effect had been previously observed, no differences in compliance intention or anticipated emotion according to anthropomorphism emerged. A meta-analysis of the effects of anthropomorphism on compliance and anticipated emotion across the three experiments revealed effect size estimates that did not differ significantly from zero. The results of these three experiments suggest that the anthropomorphism-compliance effect is fragile and perhaps subject to contextual and idiographic influences. Thus, this research provides important insight and impetus for future research on the applied and theoretical utility of

  6. Revisiting the Master-Signifier, or, Mandela and Repression

    PubMed Central

    Hook, Derek; Vanheule, Stijn

    2016-01-01

    The concept of the master-signifier has been subject to a variety of applications in Lacanian forms of political discourse theory and ideology critique. While there is much to be commended in literature of this sort, it often neglects salient issues pertaining to the role of master signifiers in the clinical domain of (individual) psychical economy. The popularity of the concept of the master (or “empty”) signifier in political discourse analysis has thus proved a double-edged sword. On the one hand it demonstrates how crucial psychical processes are performed via the operations of the signifier, extending thus the Lacanian thesis that identification is the outcome of linguistic and symbolic as opposed to merely psychological processes. On the other, the use of the master signifier concept within the political realm to track discursive formations tends to distance the term from the dynamics of the unconscious and operation of repression. Accordingly, this paper revisits the master signifier concept, and does so within the socio-political domain, yet while paying particular attention to the functioning of unconscious processes of fantasy and repression. More specifically, it investigates how Nelson Mandela operates as a master signifier in contemporary South Africa, as a vital means of knitting together diverse elements of post-apartheid society, enabling the fantasy of the post-apartheid nation, and holding at bay a whole series of repressed and negated undercurrents. PMID:26834664

  7. SU-E-I-43: Photoelectric Cross Section Revisited

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Haga, A; Nakagawa, K; Kotoku, J

    2015-06-15

    Purpose: The importance of the precision in photoelectric cross-section value increases for recent developed technology such as dual energy computed tomography, in which some reconstruction algorithms require the energy dependence of the photo-absorption in each material composition of human being. In this study, we revisited the photoelectric cross-section calculation by self-consistent relativistic Hartree-Fock (HF) atomic model and compared with that widely distributed as “XCOM database” in National Institute of Standards and Technology, which was evaluated with localdensity approximation for electron-exchange (Fock)z potential. Methods: The photoelectric cross section can be calculated with the electron wave functions in initial atomic state (boundmore » electron) and final continuum state (photoelectron). These electron states were constructed based on the selfconsistent HF calculation, where the repulsive Coulomb potential from the electron charge distribution (Hartree term) and the electron exchange potential with full electromagnetic interaction (Fock term) were included for the electron-electron interaction. The photoelectric cross sections were evaluated for He (Z=2), Be (Z=4), C (Z=6), O (Z=8), and Ne (Z=10) in energy range of 10keV to 1MeV. The Result was compared with XCOM database. Results: The difference of the photoelectric cross section between the present calculation and XCOM database was 8% at a maximum (in 10keV for Be). The agreement tends to be better as the atomic number increases. The contribution from each atomic shell has a considerable discrepancy with XCOM database except for K-shell. However, because the photoelectric cross section arising from K-shell is dominant, the net photoelectric cross section was almost insensitive to the different handling in Fock potential. Conclusion: The photoelectric cross-section program has been developed based on the fully self-consistent relativistic HF atomic model. Due to small effect on the

  8. Evaluating the effect of clinical decision units on patient flow in seven Canadian emergency departments.

    PubMed

    Schull, Michael J; Vermeulen, Marian J; Stukel, Therese A; Guttmann, Astrid; Leaver, Chad A; Rowe, Brian H; Sales, Anne

    2012-07-01

    To evaluate the effect of emergency department (ED) clinical decision units (CDUs) on overall ED patient flow in a pilot project funded in 2008 by the Ontario Ministry of Health and Long-Term Care (MOHLTC). A retrospective analysis of unscheduled ED visits at seven CDU pilot and nine control sites was conducted using administrative data. The authors examined trends in CDU utilization and compared outcomes between pilot-CDU and control sites 1 year prior to implementation, with the first 18 months of CDU operation. Sites that were unsuccessful in their applications for CDU program funding served as controls. Outcomes included ED length of stay (LOS), admission rates, and ED revisit rates. At CDU sites, roughly 4% of ED patients were admitted to CDUs. The presence of a pilot-CDU was independently associated with a small reduction in ED LOS for all low-acuity patients (-0.14 hour, 95% confidence interval [CI]=-0.22 to -0.07) and nonadmitted patients (-0.11 hour, 95% CI=-0.16 to -0.07). A small independent effect on absolute hospital admission rate for all high-acuity patients (-0.8%, 95% CI=-1.5% to -0.03%) and moderate-acuity patients (-0.6%, 95% CI=-1.1% to -0.2%) was also observed. Pilot-CDUs were not associated with changes in ED revisit rates. With only 4% of ED patients admitted to CDUs, the potential for efficiency gains in these EDs was limited. Nonetheless, these findings suggest small improvements in the operation of the ED through CDU implementation. Although marginal, the observed effects of CDU operation were in the desired direction of reduced ED LOS, reduced admission rate, and no increase in ED revisit rate. © 2012 by the Society for Academic Emergency Medicine.

  9. Structure and Dynamics of the Instantaneous Water/Vapor Interface Revisited by Path-Integral and Ab Initio Molecular Dynamics Simulations.

    PubMed

    Kessler, Jan; Elgabarty, Hossam; Spura, Thomas; Karhan, Kristof; Partovi-Azar, Pouya; Hassanali, Ali A; Kühne, Thomas D

    2015-08-06

    The structure and dynamics of the water/vapor interface is revisited by means of path-integral and second-generation Car-Parrinello ab initio molecular dynamics simulations in conjunction with an instantaneous surface definition [Willard, A. P.; Chandler, D. J. Phys. Chem. B 2010, 114, 1954]. In agreement with previous studies, we find that one of the OH bonds of the water molecules in the topmost layer is pointing out of the water into the vapor phase, while the orientation of the underlying layer is reversed. Therebetween, an additional water layer is detected, where the molecules are aligned parallel to the instantaneous water surface.

  10. Clifford Algebra Implying Three Fermion Generations Revisited

    NASA Astrophysics Data System (ADS)

    Krolikowski, Wojciech

    2002-09-01

    The author's idea of algebraic compositeness of fundamental particles, allowing to understand the existence in Nature of three fermion generations, is revisited. It is based on two postulates. Primo, for all fundamental particles of matter the Dirac square-root procedure √ {p2} → {Γ }(N)p works, leading to a sequence N = 1,2,3, ... of Dirac-type equations, where four Dirac-type matrices {Γ }(N)μ are embedded into a Clifford algebra via a Jacobi definition introducing four ``centre-of-mass'' and (N-1)× four ``relative'' Dirac-type matrices. These define one ``centre-of-mass'' and (N-1) ``relative'' Dirac bispinor indices. Secundo, the ``centre-of-mass'' Dirac bispinor index is coupled to the Standard Model gauge fields, while (N-1) ``relative'' Dirac bispinor indices are all free indistinguishable physical objects obeying Fermi statistics along with the Pauli principle which requires the full antisymmetry with respect to ``relative'' Dirac indices. This allows only for three Dirac-type equations with N = 1,3,5 in the case of N odd, and two with N = 2,4 in the case of N even. The first of these results implies unavoidably the existence of three and only three generations of fundamental fermions, namely leptons and quarks, as labelled by the Standard Model signature. At the end, a comment is added on the possible shape of Dirac 3x3 mass matrices for four sorts of spin-1/2 fundamental fermions appearing in three generations. For charged leptons a prediction is mτ = 1776.80 MeV, when the input of experimental me and mμ is used.

  11. Quality of medical service, patient satisfaction and loyalty with a focus on interpersonal-based medical service encounters and treatment effectiveness: a cross-sectional multicenter study of complementary and alternative medicine (CAM) hospitals.

    PubMed

    Kim, Chang Eun; Shin, Joon-Shik; Lee, Jinho; Lee, Yoon Jae; Kim, Me-Riong; Choi, Areum; Park, Ki Byung; Lee, Ho-Joo; Ha, In-Hyuk

    2017-03-28

    Treatment effectiveness holds considerable importance in the association between service quality and satisfaction in medical service studies. While complementary and alternative medicine (CAM) use grows more prominent, comprehensive evaluations of the quality of medical service at CAM-oriented hospitals are scarce. This study assesses the quality of medical services provided at a CAM-oriented hospital of Korean medicine using the service encounter system approach and analyzes the influence of treatment effectiveness on patient loyalty. A survey study using one-on-one interviews was conducted using a cross-sectional design in outpatients visiting one of fifteen Korean medicine facilities located throughout Korea. A total of 880 surveys were completed from June to July, 2014, and 728 surveys were included in the final analysis after excluding incomplete or incorrect questionnaires. The reliability and validity of the surveys was confirmed using Cronbach's alpha coefficient and confirmatory factor analysis, and a structural equation modeling analysis was performed to verify causality and association between factors (quality of medical service, treatment effectiveness, patient satisfaction, and intent to revisit). The measured factors of physician performance and quality of service procedures had a positive effect on treatment effectiveness. The impression of the facilities and environment directly impacted satisfaction rates for interpersonal-based medical service encounters, while treatment effectiveness positively affected satisfaction regarding quality of medical service. However, treatment effectiveness had a more significant effect on satisfaction compared to facilities and environment, and it indirectly affected satisfaction and directly influenced intent to revisit. Treatment effectiveness and satisfaction both positively influenced intent to revisit. The importance of treatment effectiveness should be recognized when examining quality of medical services, and

  12. Unruh effect for mixing neutrinos

    NASA Astrophysics Data System (ADS)

    Cozzella, Gabriel; Fulling, Stephen A.; Landulfo, André G. S.; Matsas, George E. A.; Vanzella, Daniel A. T.

    2018-05-01

    Recently, the inverse β -decay rate calculated with respect to uniformly accelerated observers (experiencing the Unruh thermal bath) was revisited. Concerns have been raised regarding the compatibility of inertial and accelerated observers' results when neutrino mixing is taken into account. Here, we show that these concerns are unfounded by discussing the properties of the Unruh thermal bath with mixing neutrinos and explicitly calculating the decay rates according to both sets of observers, confirming thus that they are in agreement. The Unruh effect is perfectly valid for mixing neutrinos.

  13. Psychological Well-Being Revisited: Advances in Science and Practice

    PubMed Central

    Ryff, Carol D.

    2014-01-01

    This article reviews the research and interventions that have grown up around a model of psychological well-being (Ryff, 1989) generated more than two decades ago to address neglected aspects of positive functioning, such as purposeful engagement in life, realization of personal talents and capacities, and enlightened self-knowledge. The conceptual origins of this formulation are revisited and scientific products emerging from six thematic areas are examined: (1) how well-being changes across adult development and later life, (2) what are the personality correlates of well-being, (3) how well-being is linked with experiences in family life, (4) how well-being relates to work and other community activities, (5) what are the connections between well-being and health, including biological risk factors, (6) and via clinical and intervention studies, how psychological well-being can be promoted for ever greater segments of society. Together, these topics illustrate flourishing interest across diverse scientific disciplines in understanding adults as striving, meaning-making, proactive organisms who are actively negotiating the challenges of life. A take-home message is that increasing evidence supports the health protective features of psychological well-being in reducing risk for disease and promoting length of life. A recurrent and increasingly important theme is resilience – the capacity to maintain or regain well-being in the face of adversity. Implications for future research and practice are considered. PMID:24281296

  14. Revisiting directed flow in relativistic heavy-ion collisions from a multiphase transport model

    NASA Astrophysics Data System (ADS)

    Guo, Chong-Qiang; Zhang, Chun-Jian; Xu, Jun

    2017-12-01

    We have revisited several interesting questions on how the rapidity-odd directed flow is developed in relativistic 197Au+197Au collisions at √{s_{NN}} = 200 and 39 GeV based on a multiphase transport model. As the partonic phase evolves with time, the slope of the parton directed flow at midrapidity region changes from negative to positive as a result of the later dynamics at 200 GeV, while it remains negative at 39 GeV due to the shorter life time of the partonic phase. The directed flow splitting for various quark species due to their different initial eccentricities is observed at 39 GeV, while the splitting is very small at 200GeV. From a dynamical coalescence algorithm with Wigner functions, we found that the directed flow of hadrons is a result of competition between the coalescence in momentum and coordinate space as well as further modifications by the hadronic rescatterings.

  15. Ethylene Control of Fruit Ripening: Revisiting the Complex Network of Transcriptional Regulation1

    PubMed Central

    Chervin, Christian; Bouzayen, Mondher

    2015-01-01

    The plant hormone ethylene plays a key role in climacteric fruit ripening. Studies on components of ethylene signaling have revealed a linear transduction pathway leading to the activation of ethylene response factors. However, the means by which ethylene selects the ripening-related genes and interacts with other signaling pathways to regulate the ripening process are still to be elucidated. Using tomato (Solanum lycopersicum) as a reference species, the present review aims to revisit the mechanisms by which ethylene regulates fruit ripening by taking advantage of new tools available to perform in silico studies at the genome-wide scale, leading to a global view on the expression pattern of ethylene biosynthesis and response genes throughout ripening. Overall, it provides new insights on the transcriptional network by which this hormone coordinates the ripening process and emphasizes the interplay between ethylene and ripening-associated developmental factors and the link between epigenetic regulation and ethylene during fruit ripening. PMID:26511917

  16. High-dilution effects revisited. 1. Physicochemical aspects.

    PubMed

    Bellavite, Paolo; Marzotto, Marta; Olioso, Debora; Moratti, Elisabetta; Conforti, Anita

    2014-01-01

    Several lines of evidence suggest that homeopathic high dilutions (HDs) can effectively have a pharmacological action, and so cannot be considered merely placebos. However, until now there has been no unified explanation for these observations within the dominant paradigm of the dose-response effect. Here the possible scenarios for the physicochemical nature of HDs are reviewed. A number of theoretical and experimental approaches, including quantum physics, conductometric and spectroscopic measurements, thermoluminescence, and model simulations investigated the peculiar features of diluted/succussed solutions. The heterogeneous composition of water could be affected by interactive phenomena such as coherence, epitaxy and formation of colloidal nanobubbles containing gaseous inclusions of oxygen, nitrogen, carbon dioxide, silica and, possibly, the original material of the remedy. It is likely that the molecules of active substance act as nucleation centres, amplifying the formation of supramolecular structures and imparting order to the solvent. Three major models for how this happens are currently being investigated: the water clusters or clathrates, the coherent domains postulated by quantum electrodynamics, and the formation of nanoparticles from the original solute plus solvent components. Other theoretical approaches based on quantum entanglement and on fractal-type self-organization of water clusters are more speculative and hypothetical. The problem of the physicochemical nature of HDs is still far from to be clarified but current evidence strongly supports the notion that the structuring of water and its solutes at the nanoscale can play a key role. Copyright © 2013 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

  17. On the stimulated Raman sidescattering in inhomogeneous plasmas: revisit of linear theory and three-dimensional particle-in-cell simulations

    NASA Astrophysics Data System (ADS)

    Xiao, C. Z.; Zhuo, H. B.; Yin, Y.; Liu, Z. J.; Zheng, C. Y.; Zhao, Y.; He, X. T.

    2018-02-01

    Stimulated Raman sidescattering (SRSS) in inhomogeneous plasma is comprehensively revisited on both theoretical and numerical aspects due to the increasing concern of its detriments to inertial confinement fusion. Firstly, two linear mechanisms of finite beam width and collisional effects that could suppress SRSS are investigated theoretically. Thresholds for the eigenmode and wave packet in a finite-width beam are derived as a supplement to the theory proposed by Mostrom and Kaufman (1979 Phys. Rev. Lett. 42 644). Collisional absorption of SRSS is efficient at high-density plasma and high-Z material, otherwise, it allows emission of sidescattering. Secondly, we have performed the first three-dimensional particle-in-cell simulations in the context of SRSS to investigate its linear and nonlinear effects. Simulation results are qualitatively agreed with the linear theory. SRSS with the maximum growth gain is excited at various densities, grows to an amplitude that is comparable with the pump laser, and evolutes to lower densities with a large angle of emergence. Competitions between SRSS and other parametric instabilities such as stimulated Raman backscattering, two-plasmon decay, and stimulated Brillouin scattering are discussed. These interaction processes are determined by gains, occurrence sites, scattering geometries of each instability, and will affect subsequent evolutions. Nonlinear effects of self-focusing and azimuthal magnetic field generation are observed to be accompanied with SRSS. In addition, it is found that SRSS is insensitive to ion motion, collision (low-Z material), and electron temperature.

  18. Malaria resurgence in the East African highlands: Temperature trends revisited

    PubMed Central

    Pascual, M.; Ahumada, J. A.; Chaves, L. F.; Rodó, X.; Bouma, M.

    2006-01-01

    The incidence of malaria in the East African highlands has increased since the end of the 1970s. The role of climate change in the exacerbation of the disease has been controversial, and the specific influence of rising temperature (warming) has been highly debated following a previous study reporting no evidence to support a trend in temperature. We revisit this result using the same temperature data, now updated to the present from 1950 to 2002 for four high-altitude sites in East Africa where malaria has become a serious public health problem. With both nonparametric and parametric statistical analyses, we find evidence for a significant warming trend at all sites. To assess the biological significance of this trend, we drive a dynamical model for the population dynamics of the mosquito vector with the temperature time series and the corresponding detrended versions. This approach suggests that the observed temperature changes would be significantly amplified by the mosquito population dynamics with a difference in the biological response at least 1 order of magnitude larger than that in the environmental variable. Our results emphasize the importance of considering not just the statistical significance of climate trends but also their biological implications with dynamical models. PMID:16571662

  19. Revisiting head circumference of Brazilian newborns in public and private maternity hospitals.

    PubMed

    Amorim, Maria do Socorro Teixeira; Melo, Aurea Nogueira de

    2017-06-01

    To revisit the head circumference (HC) of newborns in public and private maternity hospitals; to correlate our findings with the gestational age, gender, and type of delivery; and build and validate graphs and curves. This was a prospective study performed on healthy newborns. Differences in HC were analyzed as a function of gestational age, gender, the healthcare system and the type of delivery. Smoothed percentile curves were created using the least mean squares method. Of the included newborns, 697 were born in private maternity hospitals and 2,150 were born in public maternity hospitals. In all, 839 were born by vaginal delivery, and 1,311 were born by cesarean delivery. At 37 to 42 weeks of gestation, male newborns had a larger HC than females. Infants born in private maternity and those born by cesarean delivery had a larger HC. An important result of the present study is that our analyses allowed us to generate curves and statistically-validated graphs that can be used in clinical neonatal practice.

  20. Re-visiting the tympanic membrane vicinity as core body temperature measurement site

    PubMed Central

    Gan, Chee Wee; Liang, Wenyu

    2017-01-01

    Core body temperature (CBT) is an important and commonly used indicator of human health and endurance performance. A rise in baseline CBT can be attributed to an onset of flu, infection or even thermoregulatory failure when it becomes excessive. Sites which have been used for measurement of CBT include the pulmonary artery, the esophagus, the rectum and the tympanic membrane. Among them, the tympanic membrane is an attractive measurement site for CBT due to its unobtrusive nature and ease of measurement facilitated, especially when continuous CBT measurements are needed for monitoring such as during military, occupational and sporting settings. However, to-date, there are still polarizing views on the suitability of tympanic membrane as a CBT site. This paper will revisit a number of key unresolved issues in the literature and also presents, for the first time, a benchmark of the middle ear temperature against temperature measurements from other sites. Results from experiments carried out on human and primate subjects will be presented to draw a fresh set of insights against the backdrop of hypotheses and controversies. PMID:28414722

  1. Re-visiting the tympanic membrane vicinity as core body temperature measurement site.

    PubMed

    Yeoh, Wui Keat; Lee, Jason Kai Wei; Lim, Hsueh Yee; Gan, Chee Wee; Liang, Wenyu; Tan, Kok Kiong

    2017-01-01

    Core body temperature (CBT) is an important and commonly used indicator of human health and endurance performance. A rise in baseline CBT can be attributed to an onset of flu, infection or even thermoregulatory failure when it becomes excessive. Sites which have been used for measurement of CBT include the pulmonary artery, the esophagus, the rectum and the tympanic membrane. Among them, the tympanic membrane is an attractive measurement site for CBT due to its unobtrusive nature and ease of measurement facilitated, especially when continuous CBT measurements are needed for monitoring such as during military, occupational and sporting settings. However, to-date, there are still polarizing views on the suitability of tympanic membrane as a CBT site. This paper will revisit a number of key unresolved issues in the literature and also presents, for the first time, a benchmark of the middle ear temperature against temperature measurements from other sites. Results from experiments carried out on human and primate subjects will be presented to draw a fresh set of insights against the backdrop of hypotheses and controversies.

  2. Infant attachment, adult attachment, and maternal sensitivity: revisiting the intergenerational transmission gap.

    PubMed

    Behrens, Kazuko Y; Haltigan, John D; Bahm, Naomi I Gribneau

    2016-08-01

    This study investigated the intergenerational transmission of attachment, utilizing the Adult Attachment Interview (AAI), the Strange Situation Procedure (SSP), and the Maternal Behavioral Q-Set (MBQS). We revisited fundamental questions in attachment theory and research by examining: (1) the level of intergenerational agreement between maternal attachment representations and infant attachment security, and (2) whether maternal sensitivity serves as an intergenerational mediator between adult and infant attachment security. Significant categorical matches between the AAI and the SSP as well as mean differences for MBQS scores between adult attachment secure-insecure groups were found. Consistent with earlier intergenerational research, maternal sensitivity only partially mediated the AAI-SSP link, indicating the transmission gap remains. Consistent with recent mediation studies, using more contemporary analytical techniques, it was confirmed that maternal sensitivity did mediate the direct pathway between AAI security and SSP security. Thus, the transmission gap appears somewhat different depending on the statistical method used to measure mediation. Post hoc analyses considered mothers' childhood experiences of separation/divorce and this helped make sense of intergenerational mismatches.

  3. Revisiting photon-statistics effects on multiphoton ionization

    NASA Astrophysics Data System (ADS)

    Mouloudakis, G.; Lambropoulos, P.

    2018-05-01

    We present a detailed analysis of the effects of photon statistics on multiphoton ionization. Through a detailed study of the role of intermediate states, we evaluate the conditions under which the premise of nonresonant processes is valid. The limitations of its validity are manifested in the dependence of the process on the stochastic properties of the radiation and found to be quite sensitive to the intensity. The results are quantified through detailed calculations for coherent, chaotic, and squeezed vacuum radiation. Their significance in the context of recent developments in radiation sources such as the short-wavelength free-electron laser and squeezed vacuum radiation is also discussed.

  4. Mitochondrial Dysfunction in Cancer

    PubMed Central

    Boland, Michelle L.; Chourasia, Aparajita H.; Macleod, Kay F.

    2013-01-01

    A mechanistic understanding of how mitochondrial dysfunction contributes to cell growth and tumorigenesis is emerging beyond Warburg as an area of research that is under-explored in terms of its significance for clinical management of cancer. Work discussed in this review focuses less on the Warburg effect and more on mitochondria and how dysfunctional mitochondria modulate cell cycle, gene expression, metabolism, cell viability, and other established aspects of cell growth and stress responses. There is increasing evidence that key oncogenes and tumor suppressors modulate mitochondrial dynamics through important signaling pathways and that mitochondrial mass and function vary between tumors and individuals but the significance of these events for cancer are not fully appreciated. We explore the interplay between key molecules involved in mitochondrial fission and fusion and in apoptosis, as well as in mitophagy, biogenesis, and spatial dynamics of mitochondria and consider how these distinct mechanisms are coordinated in response to physiological stresses such as hypoxia and nutrient deprivation. Importantly, we examine how deregulation of these processes in cancer has knock on effects for cell proliferation and growth. We define major forms of mitochondrial dysfunction and address the extent to which the functional consequences of such dysfunction can be determined and exploited for cancer diagnosis and treatment. PMID:24350057

  5. Arctic Ice Dynamics Joint Experiment (AIDJEX) assumptions revisited and found inadequate

    NASA Astrophysics Data System (ADS)

    Coon, Max; Kwok, Ron; Levy, Gad; Pruis, Matthew; Schreyer, Howard; Sulsky, Deborah

    2007-11-01

    This paper revisits the Arctic Ice Dynamics Joint Experiment (AIDJEX) assumptions about pack ice behavior with an eye to modeling sea ice dynamics. The AIDJEX assumptions were that (1) enough leads were present in a 100 km by 100 km region to make the ice isotropic on that scale; (2) the ice had no tensile strength; and (3) the ice behavior could be approximated by an isotropic yield surface. These assumptions were made during the development of the AIDJEX model in the 1970s, and are now found inadequate. The assumptions were made in part because of insufficient large-scale (10 km) deformation and stress data, and in part because of computer capability limitations. Upon reviewing deformation and stress data, it is clear that a model including deformation on discontinuities and an anisotropic failure surface with tension would better describe the behavior of pack ice. A model based on these assumptions is needed to represent the deformation and stress in pack ice on scales from 10 to 100 km, and would need to explicitly resolve discontinuities. Such a model would require a different class of metrics to validate discontinuities against observations.

  6. Intracellular drug delivery by poly(lactic-co-glycolic acid) nanoparticles, revisited

    PubMed Central

    Xu, Peisheng; Gullotti, Emily; Tong, Ling; Highley, Christopher B.; Errabelli, Divya R.; Hasan, Tayyaba; Cheng, Ji-Xin; Kohane, Daniel S.; Yeo, Yoon

    2008-01-01

    We reexamined the cellular drug delivery mechanism by poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) to determine their utility and limitations as an intracellular drug delivery system. First, we prepared PLGA NPs which physically encapsulated Nile red (a hydrophobic fluorescent dye), in accordance with the usual procedure for labeling PLGA NPs, incubated them with mesothelial cells, and observed an increase in the intracellular fluorescence. We then prepared NPs from PLGA chemically conjugated to a fluorescent dye and observed their uptake by the mesothelial cells using confocal microscopy. We also used Coherent Anti-Stokes Raman Scattering (CARS) microscopy to image cellular uptake of unlabeled PLGA NPs. Results of this study coherently suggest that PLGA NPs (i) are not readily taken up by cells, but (ii) deliver the payload to cells by extracellular drug release and/or direct drug transfer to contacting cells, which are contrasted with the prevalent view. From this alternative standpoint, we analyzed cytotoxicities of doxorubicin and paclitaxel delivered by PLGA NPs and compared with those of free drugs. Finally, we revisit previous findings in the literature and discuss potential strategies to achieve efficient drug delivery to the target tissues using PLGA NPs. PMID:19035785

  7. Genetic alterations in fatty acid transport and metabolism genes are associated with metastatic progression and poor prognosis of human cancers

    PubMed Central

    Nath, Aritro; Chan, Christina

    2016-01-01

    Reprogramming of cellular metabolism is a hallmark feature of cancer cells. While a distinct set of processes drive metastasis when compared to tumorigenesis, it is yet unclear if genetic alterations in metabolic pathways are associated with metastatic progression of human cancers. Here, we analyzed the mutation, copy number variation and gene expression patterns of a literature-derived model of metabolic genes associated with glycolysis (Warburg effect), fatty acid metabolism (lipogenesis, oxidation, lipolysis, esterification) and fatty acid uptake in >9000 primary or metastatic tumor samples from the multi-cancer TCGA datasets. Our association analysis revealed a uniform pattern of Warburg effect mutations influencing prognosis across all tumor types, while copy number alterations in the electron transport chain gene SCO2, fatty acid uptake (CAV1, CD36) and lipogenesis (PPARA, PPARD, MLXIPL) genes were enriched in metastatic tumors. Using gene expression profiles, we established a gene-signature (CAV1, CD36, MLXIPL, CPT1C, CYP2E1) that strongly associated with epithelial-mesenchymal program across multiple cancers. Moreover, stratification of samples based on the copy number or expression profiles of the genes identified in our analysis revealed a significant effect on patient survival rates, thus confirming prominent roles of fatty acid uptake and metabolism in metastatic progression and poor prognosis of human cancers. PMID:26725848

  8. Terminology Revisited: Effective Communications for the Agricultural Community

    USDA-ARS?s Scientific Manuscript database

    Pasture-based finishing systems for meat goats, sheep and cattle are growing rapidly in the eastern USA, particularly on small farms. Increasing demand for pasture-raised meat and dairy products requires renewed efforts to communicate the best practical information as effectively as possible. Many...

  9. Murabutide revisited: a review of its pleiotropic biological effects.

    PubMed

    Jakopin, Žiga

    2013-01-01

    Despite the great efforts put into their development, the list of clinically approved immunological adjuvants is still very short. Evolution of the knowledge of the immune system has enabled for rational design of novel adjuvants and has led to the conclusion that more than one type of adjuvant will be required. Derivatives of muramyl dipeptide (MDP), the minimal immunomodulatory structure of bacterial cell wall peptidoglycan, have gained considerable attention in the past decades, because of their potent adjuvant effects. Murabutide is a safe derivative of MDP, which interacts with cells of the immune system, both innate and adaptive, and exerts its effect through activation of Nod2. The transcriptional response of murabutide-stimulated macrophages revealed enhanced expression of genes coding for various proteins such as immune mediators and their receptors, transcription factors and kinases, ion channels/transporters and proteins involved in cell metabolic activity, thus reflecting a broad spectrum of biological effects. In addition to its well recognized adjuvant effect, murabutide has also been shown to enhance the host's resistance against microbial infections, nonspecific resistance against tumors and the induction of cytokines and chemokines implicated in enhancing the immune response and hematopoesis. This article provides an insight into the mechanism of action of murabutide and its interactions with the cells of the immune system in vitro and in vivo. On account of its numerous biological effects, murabutide has been the subject of several clinical studies. Many of these have confirmed its potential to synergize with cytokines of therapeutic interest in potentiating the tumoricidal activity of macrophages or targeting chronic viral diseases, as well as reducing the cytokine dosage needed to achieve a therapeutic effect. This review covers the findings of all relevant studies and focuses on the role of murabutide and its potential in the treatment of

  10. Revisit the Effect of Teaching and Learning with Technology

    ERIC Educational Resources Information Center

    Lee, Yuan-Hsuan; Waxman, Hersh; Wu, Jiun-Yu; Michko, Georgette; Lin, Grace

    2013-01-01

    We re-examined the effect of teaching and learning with technology on student cognitive and affective outcomes using the meta-analytic technique. Screening studies obtained from an electric search of databases such as PsyInfo and ERIC resulted in 58 studies (1997-2011). Overall, effect sizes were small to moderate across the cognitive and…

  11. The Use of Theory in School Effectiveness Research Revisited

    ERIC Educational Resources Information Center

    Scheerens, Jaap

    2013-01-01

    From an international review of 109 school effectiveness research studies, only 6 could be seen as theory driven. As the border between substantive conceptual models of educational effectiveness and theory-based models is not always very sharp, this number might be increased to 11 by including those studies that are based on models that make…

  12. Active Nuclear Import of Membrane Proteins Revisited

    PubMed Central

    Laba, Justyna K.; Steen, Anton; Popken, Petra; Chernova, Alina; Poolman, Bert; Veenhoff, Liesbeth M.

    2015-01-01

    It is poorly understood how membrane proteins destined for the inner nuclear membrane pass the crowded environment of the Nuclear Pore Complex (NPC). For the Saccharomyces cerevisiae proteins Src1/Heh1 and Heh2, a transport mechanism was proposed where the transmembrane domains diffuse through the membrane while the extralumenal domains encoding a nuclear localization signal (NLS) and intrinsically disordered linker (L) are accompanied by transport factors and travel through the NPC. Here, we validate the proposed mechanism and explore and discuss alternative interpretations of the data. First, to disprove an interpretation where the membrane proteins become membrane embedded only after nuclear import, we present biochemical and localization data to support that the previously used, as well as newly designed reporter proteins are membrane-embedded irrespective of the presence of the sorting signals, the specific transmembrane domain (multipass or tail anchored), independent of GET, and also under conditions that the proteins are trapped in the NPC. Second, using the recently established size limit for passive diffusion of membrane proteins in yeast, and using an improved assay, we confirm active import of polytopic membrane protein with extralumenal soluble domains larger than those that can pass by diffusion on similar timescales. This reinforces that NLS-L dependent active transport is distinct from passive diffusion. Thirdly, we revisit the proposed route through the center of the NPC and conclude that the previously used trapping assay is, unfortunately, poorly suited to address the route through the NPC, and the route thus remains unresolved. Apart from the uncertainty about the route through the NPC, the data confirm active, transport factor dependent, nuclear transport of membrane-embedded mono- and polytopic membrane proteins in baker’s yeast. PMID:26473931

  13. [Negative Symptoms Revisited--Toward the Recovery of Persons with Schizophrenia].

    PubMed

    Ikebuchi, Emi

    2015-01-01

    The negative symptoms of schizophrenia are usually treatment-refractory, and considered to be a major cause of a poor outcome. Recently, it has become an important issue to elucidate the etiology of and develop treatment for negative symptoms in order to improve the outcome of schizophrenia patients. Firstly, the history of negative symptoms was reviewed. Several lines of factor-analysis studies have suggested that negative symptoms are independent from other symptoms of schizophrenia, and consist of two factors, the poverty of expression and avolition, while the results depend upon the assessment scale employed in each analysis. Anhedonia, a part of avolition, may be considered as the impairment of pleasure-seeking behavior, the impairment of remembering non-current feelings, and a person's belief that he/she cannot experience pleasure, rather than the loss of pleasure itself. As neurological bases for avolition, decreases in reward expectancy, value representation, and the behavior to seek uncertain reward were observed, which resulted in poor social functioning due to the difficulties of initiating adaptive behaviors for the future. These impairments are the bases of decreased intrinsic motivation. The negative symptoms were considered to result in poor social functioning mediated by neuro-and social cognitive dysfunction and dysfunctional cognition, such as low self-efficacy and self-stigma. Pharmacotherapy for negative symptoms remains to be established due to a lack of evidence. Several psycho-social interventions in self-efficacy, self-stigma, intrinsic motivation, and environmental contexts are now being developed, while their effects are rather limited. The principles of psychiatric rehabilitation, i.e., respecting one's own value system and preference, self-determination, and motivation, are worth revisiting from the viewpoint of neuro-cognitive science. Furthermore, a hope-oriented approach, the presence of peers, and reconstructing social values as

  14. Correlating Subjective and Objective Sleepiness: Revisiting the Association Using Survival Analysis

    PubMed Central

    Aurora, R. Nisha; Caffo, Brian; Crainiceanu, Ciprian; Punjabi, Naresh M.

    2011-01-01

    clinical practice. Given the ease of administering the ESS, it represents a relatively simple and cost-effective method for identifying individuals at risk for daytime sleepiness. Citation: Aurora RN; Caffo B; Crainiceanu C; Punjabi NM. Correlating subjective and objective sleepiness: revisiting the association using survival analysis. SLEEP 2011;34(12):1707-1714. PMID:22131609

  15. The E3Σ1+ (63S1) ← A3Π0+(53P1) transition in CdAr revisited: The spectrum and new analysis of the E3Σ1+ Rydberg state interatomic potential

    NASA Astrophysics Data System (ADS)

    Urbańczyk, T.; Krośnicki, M.; Kędziorski, A.; Koperski, J.

    2018-05-01

    Revisited study of the E3Σ1+ (63S1) ← A3Π0+(53P1) transition in CdAr using both theoretical and experimental approach is presented. Systematic detection of the E3Σ1+in,υ' ← A3Π0+,υ″ = 6 transition frequencies with higher accuracy and spectrally narrower laser extended and improved analysis and simulation of the LIF excitation spectrum. More consistent characterization of the E3Σ1+in-Rydberg state inner well using inversed perturbation approach methodology was achieved. Free ← bound transitions in the E3Σ1+in ← A3Π0+,υ″ = 6 excitation were taken into account in the analysis and simulation of the recorded spectrum. The updated spectroscopic characterization of the A3Π0+ state was also revisited.

  16. Temperature Effect on Micelle Formation: Molecular Thermodynamic Model Revisited.

    PubMed

    Khoshnood, Atefeh; Lukanov, Boris; Firoozabadi, Abbas

    2016-03-08

    Temperature affects the aggregation of macromolecules such as surfactants, polymers, and proteins in aqueous solutions. The effect on the critical micelle concentration (CMC) is often nonmonotonic. In this work, the effect of temperature on the micellization of ionic and nonionic surfactants in aqueous solutions is studied using a molecular thermodynamic model. Previous studies based on this technique have predicted monotonic behavior for ionic surfactants. Our investigation shows that the choice of tail transfer energy to describe the hydrophobic effect between the surfactant tails and the polar solvent molecules plays a key role in the predicted CMC. We modify the tail transfer energy by taking into account the effect of the surfactant head on the neighboring methylene group. The modification improves the description of the CMC and the predicted micellar size for aqueous solutions of sodium n-alkyl sulfate, dodecyl trimethylammonium bromide (DTAB), and n-alkyl polyoxyethylene. The new tail transfer energy describes the nonmonotonic behavior of CMC versus temperature. In the DTAB-water system, we redefine the head size by including the methylene group, next to the nitrogen, in the head. The change in the head size along with our modified tail transfer energy improves the CMC and aggregation size prediction significantly. Tail transfer is a dominant energy contribution in micellar and microemulsion systems. It also promotes the adsorption of surfactants at fluid-fluid interfaces and affects the formation of adsorbed layer at fluid-solid interfaces. Our proposed modifications have direct applications in the thermodynamic modeling of the effect of temperature on molecular aggregation, both in the bulk and at the interfaces.

  17. Putting the Learning in Case Learning? The Effects of Case-Based Approaches on Student Knowledge, Attitudes, and Engagement

    ERIC Educational Resources Information Center

    Krain, Matthew

    2016-01-01

    This study revisits case learning's effects on student engagement and assesses student learning as a result of the use of case studies and problem-based learning. The author replicates a previous study that used indirect assessment techniques to get at case learning's impact, and then extends the analysis using a pre- and post-test experimental…

  18. Cation dyshomeostasis and cardiomyocyte necrosis: the Fleckenstein hypothesis revisited.

    PubMed

    Borkowski, Brian J; Cheema, Yaser; Shahbaz, Atta U; Bhattacharya, Syamal K; Weber, Karl T

    2011-08-01

    An ongoing loss of cardiomyocytes to apoptotic and necrotic cell death pathways contributes to the progressive nature of heart failure. The pathophysiological origins of necrotic cell loss relate to the neurohormonal activation that accompanies acute and chronic stressor states and which includes effector hormones of the adrenergic nervous system. Fifty years ago, Albrecht Fleckenstein and coworkers hypothesized the hyperadrenergic state, which accompanies such stressors, causes cardiomyocyte necrosis based on catecholamine-initiated excessive intracellular Ca(2+) accumulation (EICA), and mitochondrial Ca(2+) overloading in particular, in which the ensuing dysfunction and structural degeneration of these organelles leads to necrosis. In recent years, two downstream factors have been identified which, together with EICA, constitute a signal-transducer-effector pathway: (i) mitochondria-based induction of oxidative stress, in which the rate of reactive oxygen metabolite generation exceeds their rate of detoxification by endogenous antioxidant defences; and (ii) the opening of the mitochondrial inner membrane permeability transition pore (mPTP) followed by organellar swelling and degeneration. The pathogenesis of stress-related cardiomyopathy syndromes is likely related to this pathway. Other factors which can account for cytotoxicity in stressor states include: hypokalaemia; ionized hypocalcaemia and hypomagnesaemia with resultant elevations in parathyroid hormone serving as a potent mediator of EICA; and hypozincaemia with hyposelenaemia, which compromise antioxidant defences. Herein, we revisit the Fleckenstein hypothesis of EICA in leading to cardiomyocyte necrosis and the central role played by mitochondria.

  19. Large-scale Filamentary Structures around the Virgo Cluster Revisited

    NASA Astrophysics Data System (ADS)

    Kim, Suk; Rey, Soo-Chang; Bureau, Martin; Yoon, Hyein; Chung, Aeree; Jerjen, Helmut; Lisker, Thorsten; Jeong, Hyunjin; Sung, Eon-Chang; Lee, Youngdae; Lee, Woong; Chung, Jiwon

    2016-12-01

    We revisit the filamentary structures of galaxies around the Virgo cluster, exploiting a larger data set, based on the HyperLeda database, than previous studies. In particular, this includes a large number of low-luminosity galaxies, resulting in better sampled individual structures. We confirm seven known structures in the distance range 4 h -1 Mpc < SGY < 16 h -1 Mpc, now identified as filaments, where SGY is the axis of the supergalactic coordinate system roughly along the line of sight. The Hubble diagram of the filament galaxies suggests they are infalling toward the main body of the Virgo cluster. We propose that the collinear distribution of giant elliptical galaxies along the fundamental axis of the Virgo cluster is smoothly connected to two of these filaments (Leo II A and B). Behind the Virgo cluster (16 h -1 Mpc < SGY < 27 h -1 Mpc), we also identify a new filament elongated toward the NGC 5353/4 group (“NGC 5353/4 filament”) and confirm a sheet that includes galaxies from the W and M clouds of the Virgo cluster (“W-M sheet”). In the Hubble diagram, the NGC 5353/4 filament galaxies show infall toward the NGC 5353/4 group, whereas the W-M sheet galaxies do not show hints of gravitational influence from the Virgo cluster. The filamentary structures identified can now be used to better understand the generic role of filaments in the build-up of galaxy clusters at z ≈ 0.

  20. Laryngeal vibratory mechanisms: the notion of vocal register revisited.

    PubMed

    Roubeau, Bernard; Henrich, Nathalie; Castellengo, Michèle

    2009-07-01

    This study, focused on the laryngeal source level, introduces the concept of laryngeal vibratory mechanism. Human phonation is characterized by the use of four laryngeal mechanisms, labeled M0-M3, as evidenced by the electroglottographic (EGG) study of the transition phenomena between mechanisms with a population of men and women, trained and untrained singers. Macroscopic and local descriptions of the EGG signal are analyzed during the production of glissandos and held notes with different mechanisms. The transition from one mechanism to another of higher rank is characterized by a jump in frequency, a reduction of EGG amplitude, and a change in the shape of the derivative of the EGG (which may correspond to a reduction of the vibratory mass). These characteristics are used to identify a transition between two mechanisms, in complement with acoustic spectrographic analyses. The pitches of transitions between the two main mechanisms M1 and M2 and the range of the frequency-overlap region are described in detail. The notion of vocal register is revisited in the light of these concepts of laryngeal mechanism. The literature on vocal registers is reviewed, and it is shown that the confusion often cited with respect to this notion may be related to the heterogeneity of the approaches and methods used to describe the phenomena and to the multiplicity of descriptors. Therefore, the terminology of the registers is organized depending on their relation to the four laryngeal vibratory mechanisms.