992 research outputs found

    Forecasting UK Industrial Production Over the Business Cycle

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    This paper examines the information available through leading indicators for modelling and forecasting the UK quarterly index of production (seasonally adjusted). The emphasis is on one-quarter ahead prediction, especially over the 1990s recession. Linear specifications considered are univariate autoregressive models together with dynamic single indicator and multiple indicator models. Both univariate and leading indicator versions of nonlinear Markov switching specifications are also examined. In the latter case, the transition probabilities are modelled as logistic functions of the leading indicators, allowing the lead times to differ for the expansion to expansion and recession to recession probabilities. Despite general evidence that the term structure of interest rates helps regime classification in the Markov switching models, these models perform relatively poorly in forecasting the 1990s production recession. It is suggested that this poor performance may be due to the nature of that recession, which differed from previous major UK postwar recessions in having no single quarter where industrial production declined substantially. However, a three indicator linear specification does well. The leading indicator variables in this latter model are a short-term interest rate, the stock market dividend yield and the optimism balance from the quarterly survey conducted by the Confederation of British Industry.

    Epigenetic Profiling Reveals a Developmental Decrease in Promoter Accessibility During Cortical Maturation in vivo

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    Axon regeneration in adult central nervous system (CNS) is limited in part by a developmental decline in the ability of injured neurons to re-express needed regeneration associated genes (RAGs). Adult CNS neurons may lack appropriate pro-regenerative transcription factors, or may display chromatin structure that restricts transcriptional access to RAGs. Here we performed epigenetic profiling around the promoter regions of key RAGs, and found progressive restriction across a time course of cortical maturation. These data identify a potential intrinsic constraint to axon growth in adult CNS neurons. Neurite outgrowth from cultured postnatal cortical neurons, however, proved insensitive to treatments that improve axon growth in other cell types, including combinatorial overexpression of AP1 factors, overexpression of histone acetyltransferases, and pharmacological inhibitors of histone deacetylases. This insensitivity could be due to intermediate chromatin closure at the time of culture, and highlights important differences in cell culture models used to test potential pro-regenerative interventions

    Modeling with Medicinal Chemistry: Practical Innovative Technology-based Activity to Enhance Student’s Learning Through Inter-Departmental Collaboration: PART I

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    Background: Concepts of formulary management and its applications in clinical practice is a challenge faced by many first professional year pharmacy students. This challenge may be attributed to a lack of foundational knowledge and practical skills at this level. Preparing students for lifelong learning mandates early exposure to practical application of concepts. This warrants the need for students to integrate knowledge, skills, abilities, and attitudes in clinical practice. As a result, a state-of-the-art one stop shopping structure of the day (SOD) activity was created for P1 pharmacy students to enable the authors to assess their skill sets. Objective: The objective of the study was to assess the impact of this technique on students’ ability to integrate science into practice. Methods: An institutionally structured curriculum permits concurrent administration of standalone but related courses through inter-departmental collaboration. Connecting the dots in drug information, medicinal chemistry, pharmacology, and pharmacokinetics was identified as a creative means to accomplish this goal. A comprehensive literature search to identify existing models was conducted in PubMed, International Pharmaceutical Abstract (IPA), Embase, Cumulative Index in Allied Health Literature (CINAHL), and alternate resources from inception to 2013 without success. A Pre-class interactive technology-based “Structure of the Day” activity was created utilizing the Moodle course platform, Accelrys®, and SoftChalk® software. Students identified functional groups on new molecular entities, determined the relationships to pharmacological properties, pharmacokinetic profiles, and their applications to drug formulary management. Application activities via in-class discussions and debate were implemented to assess knowledge, attitude and ability to integrate the basic sciences into a skill-building activity. Results:The expected outcome was captured through the sequential activities facilitated by an audience response system. The overall results of the study were promising and positive. The assessment on knowledge, ability, skills and attitude ranged from 72% to 95%. Conclusion: The investigators plan to implement this technique in the curriculum

    The Impact of a New Teacher Support System on Teacher Efficacy

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    Retaining novice teachers is a major concern for school districts across the United States. At an urban high school in a Southeastern state, over 30% of novice teachers hired over a 3-year period did not return after their first year of teaching. The purpose of the study was to examine novice teachers\u27 perceptions of support received during their first year to determine how school-based support could increase novice teacher retention. The theoretical framework was Bandura\u27s theory of self-efficacy and the concept of teacher efficacy espoused by Tschannen-Moran, Woolfolk-Hoy, and Hoy. The research questions focused on the perceptions of novice teachers regarding (a) support received at their school, (b) the most beneficial support structures, and (c) needed training or assistance. Purposive sampling was used to select 8 novice teacher participants who met the inclusion criteria of being in their 1st to 5th year of teaching. The qualitative case study design involved a survey and an interview. Four themes emerged: the importance of having a mentor, guidance and support, professional development, and opportunities for collaboration. Findings from the study were used to develop a 2-year Teachers Supporting Teachers professional development project to address the needs identified by the novice teachers. Implications for social change include helping schools and districts plan and implement support programs for novice teachers to increase their retention

    The Effect of Luteolin on Human Glioblastoma

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    Glioblastoma multiforme (GBM) is widely recognized as the most common and lethal of the malignant gliomas. Few effective therapeutic treatments are available as five-year survival rates of diagnosed individuals are less than five percent. Luteolin, a common flavonoid found in a variety of fruits and vegetables, has demonstrated significant promise in combating cancers of the breast, colon, liver, lung, and bone. In this study, we investigated the effects of luteolin on glioblastoma multiforme cell lines U-251, U-87, and U-1242. Cell viability was assessed using cell count with trypan blue exclusion and MTT assays. Results revealed that luteolin reduces GBM cell viability and cell proliferation in a time and concentration-dependent manner. Western Blot analysis indicated that luteolin decreased AKT, ERK, and MAPK phosphorylation following treatment with EGF. Additionally, luteolin promoted apoptosis in GBM cells by inducing PARP and caspase-3 cleavage, and decreasing levels of the anti-apoptotic protein BCL-XL. Our results indicate that luteolin exhibits a biological effect and may be used as a therapeutic agent for glioblastoma multiforme

    Investigation of the Effects of Growth Environment on the Ferric Reducing Antioxidant Power of Selected Plant Species

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    Metabolism within the human body creates multiple oxidant by-products. These oxidants may cause cell injury, damage to DNA, and other complications leading to the development of chronic disease. Antioxidants are important dietary components which defend against oxidative damage by scavenging the oxidant by-products. Research has shown that diets rich in antioxidants offer protection against various chronic diseases. The goal of this research is to determine the effects of varying growing conditions on the production of antioxidants, and to ultimately find the best possible plant-growth environment for maximum production of antioxidants. Each plant was grown under three different environmental conditions; positive, negative, and control treatment. The positive treatment consisted of supplying water to field capacity with fertilizer, the negative treatment consisted supplying half of the water required to reach field capacity with no fertilizer, and the control treatment consisted of supplying water to field capacity with no fertilizer. Ferric reducing antioxidant levels were then determined. The ferric reducing antioxidant power evaluates antioxidant potential by reducing ferric iron (Fe3+) to its ferrous form (Fe2+). Addition of excess ferric ions result in the development of a Prussian blue color. The ferric reducing antioxidant power of the extracts was measured by reading the absorbance at 750 nm using a spectrophotometer. The ferric reducing antioxidant power assay was performed on extracts of red clover (Trifolium pratense), Amur honeysuckle (Lonicera maackii) and wild garlic (Allium vineale). The differing growing conditions resulted in variation in the production of antioxidants by the plants. The data obtained revealed that the plants grown under the negative treatment produced a significantly lower level of antioxidants when compared to the plants grown under the positive treatment. These results indicate that growing conditions can influence antioxidant production in plants

    The Tumor Suppressor HHEX Inhibits Axon Growth when Prematurely Expressed in Developing Central Nervous System Neurons

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    Neurons in the embryonic and peripheral nervoussystem respond to injury by activating transcriptional programs supportive of axon growth, ultimately resulting in functional recovery. In contrast, neurons in the adult central nervous system (CNS) possess a limited capacity to regenerate axons after injury, fundamentally constraining repair. Activating pro-regenerative gene expression in CNS neurons is a promising therapeutic approach, but progress is hampered by incomplete knowledge of the relevant transcription factors. An emerging hypothesis is that factors implicated in cellular growth and motility outside the nervous system may also control axon growth in neurons. We therefore tested sixty-nine transcription factors, previously identified as possessing tumor suppressive or oncogenic properties in non-neuronal cells, in assays of neurite outgrowth. This screen identified YAP1 and E2F1 as enhancers of neurite outgrowth, and PITX1, RBM14, ZBTB16, and HHEX as inhibitors. Follow-up experiments are focused on the tumor suppressor HHEX, one of the strongest growth inhibitors. HHEX is widely expressed in adult CNS neurons, including corticospinal tract neurons after spinal injury, but is present only in trace amounts in immature cortical neurons and adult peripheral neurons. HHEX overexpression in early postnatal cortical neurons reduced both initial axonogenesis and the rate of axon elongation, and domain deletion analysis strongly implicated transcriptional repression as the underlying mechanism. These findings suggest a role for HHEX in restricting axon growth in the developing CNS, and substantiate the hypothesis that previously identified oncogenes and tumor suppressors can play conserved roles in axon extension

    Antinociceptive Effects of Herkinorin, a MOP Receptor Agonist Derived from Salvinorin A in the Formalin Test in Rats: New Concepts in Mu Opioid Receptor Pharmacology

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    Herkinorin is the first μ opioid (MOP) selective agonist derived from salvinorin A, a hallucinogenic natural product. Previous work has shown that, unlike other opioids, herkinorin does not promote the recruitment of β-arrestin-2 to the MOP receptor and does not lead to receptor internalization. This paper presents the first in vivo evaluation of herkinorin’s antinociceptive effects in rats, using the formalin test as a model of tonic inflammatory pain. Herkinorin was found to produce a dose-dependent decrease in the number of flinches evoked by formalin. These antinociceptive effects were substantially blocked by pretreatment with the nonselective antagonist naloxone, indicating that the antinociception is mediated by opioid receptors. Contralateral administration of herkinorin did not attenuate the number of flinches evoked by formalin, indicating that its effects are peripherally restricted to the site of injection. Following chronic administration (5-day), herkinorin maintained antinociceptive efficacy in both phases of the formalin test. Furthermore, unlike morphine, herkinorin was still able to inhibit flinching in both phases of the formalin test in animals made tolerant to chronic systemic morphine treatment. Collectively, these results suggest that herkinorin may produce peripheral antinociception with decreased tolerance liability and thereby represents a promising template for the development of agents for the treatment of a variety of pain states

    The Effects of Apigenin on Cell Proliferation and Apoptosis in Glioblastoma Multiforme

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    Glioblastoma multiforme (GBM) is a WHO grade IV brain tumor. These tumors are highly proliferative, infiltrative, necrotic, angiogenic, and resistant to apoptosis. One major characteristic of GBM is the overexpression of epidermal growth factor receptor (EGFR), which leads to cell growth and proliferation when activated. GBM is very difficult to treat due to its location, heterogeneity, and invasiveness; an effective treatment is therefore needed. The use of flavonoids, which are natural compounds found in many fruits and vegetables, has been studied in the treatment of many different tumor types. Apigenin is a specific flavonoid that has previously been shown to have antitumor activity in a number of cancer cells. Our study set out to investigate the molecular effects of apigenin treatment on glioblastoma cell proliferation and viability using the trypan blue exclusion assay, MTT assay, and an LDH assay. In addition, Western blot analyses were utilized out to determine the signaling pathways through which apigenin treatment exerts its effects on cell proliferation and apoptosis. Finally, hoechst-propidium iodide staining and flow cytometry were used to examine the extent of apoptosis and the cell cycle context of these effects. Our results show that apigenin reduces cell viability and proliferation in a dose and time dependent manner while increasing cytotoxicity in GBM cells. Additionally, apigenin inhibits the EGFR mediated phosphorylation in the presence of EGF treatment of AKT, mTOR, and s6k resulting in decreased cell survival, growth and proliferation. It also inhibits the MAPK pathways in one cell line thereby reducing cell growth and proliferation. It also inhibits the anti-apoptotic effects of BCL-XL and increases PARP cleavage, which leads to increased apoptosis. Finally, apigenin induced cycle arrest at the G2M checkpoint, meaning that apoptosis primarily occurred at the DNA repair checkpoint in the cell cycle. In conclusion, apigenin has demonstrated some in vitro biological effects on glioblastoma cell lines that show promises in limiting the growth, proliferation and survival of these cell lines. Future research should look to identify means through which apigenin can be administered in clinically significant concentrations to the brain
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