Chiral oxime ethers: applications in synthesis

Chapter One reviews the literature, discussing the role of nucleophilic additions to oximes and their derivatives. This introduction is primarily concerned with the formation of new carbon–carbon bonds, this is achieved by the addition of organometallic reagents to the carbon–nitrogen double bond functionality of oximes and their derivatives. [Continues.

Examining the information and communication technologies enabling servitized manufacture

Services-led competitive strategies are critically important to Western manufacturers. This paper contributes to our basic knowledge of such strategies by examining the enabling information and communication technologies that successfully servitized manufacturers appear to be adopting. Although these are preliminary findings from a longer-term research programme, through this paper we seek to offer immediate assistance to manufacturers who wish to understand how they might exploit the servitization movement

Servitization within manufacturing operations:an exploration of the impact to facilities practices

Servitization is a growing area of interest amongst practitioners, policymakers, and academics, and much is still to be learnt about its adoption in practice. This paper makes a contribution to this debate by identifying the key facilities practices that successful servitizing manufacturers appear to be deploying, and the underlying rationale behind their configuration. Although these are preliminary findings from a longer-term research programme, this short communication seeks to highlight the implications for manufacturing professionals and organizations who are considering the servitization of their operations

Transiently silencing genes associated with voluntary physical activity using intravenous injection of Vivo‐morpholinos

Physical inactivity has been associated with several diseases and conditions with multiple candidate genes proposed to regulate voluntary physical activity. However, there has not been a reliable method to silence candidate genes in vivo to determine causal mechanisms of physical activity regulation. The novel molecular biology tool, Vivo‐morpholinos, is a potential method to transiently silence specific genes. Thus, the aim of this study was to validate the use of Vivo‐morpholinos in a mouse model for voluntary physical activity with several sub‐objectives. We observed that Vivomorpholinos achieved between 60 – 97% knockdown of Drd1‐, Vmat2‐, and Glut4‐protein in skeletal muscle, the delivery moiety of Vivo‐morpholinos (scramble) did not influence physical activity and that a cocktail of multiple Vivo‐morpholinos can be given in a single treatment to achieve protein knockdown of two different targeted proteins in skeletal muscle simultaneously. Knocking down Drd1, Vmat2, or Glut4 protein in skeletal muscle did not affect physical activity. Vivo‐morpholinos injected intravenously alone did not significantly knockdown Vmat2‐protein expression in the brain (p=0.28). However, the use of a bradykinin analog to increase blood‐brain‐barrier permeability in conjunction with the Vivomorpholinos significantly (p=0.0001) decreased Vmat2‐protein in the brain with a corresponding later over‐expression of Vmat2 coincident with a significant (p=0.0016) increase in physical activity. We conclude that with appropriate research design, Vivo‐morpholinos can be a valuable tool in determining causal gene‐phenotype relationships in whole animal models

Evaluation of a Vivo-Morpholino Delivery Method to the Brain and the Affect on Physical Activity

Evaluation of a Vivo-Morpholino Delivery Method to the Brain and the Affect on Physical Activity *David P. Ferguson MS, Emily E. Schmitt MS, J. Timothy Lightfoot PhD FACSM Biology of Physical Activity Lab, Texas A&M University, College Station, TX, 77843 *To be judged in the doctoral category Physical inactivity has been shown to be correlated to various disease and conditions. Therefore, there is interest in the genetic mechanisms that control daily physical activity. Vivo-morpholinos are a new molecular biology tool that allows for the transient silencing of specific genes in an animal model, thereby allowing for a systematic method to turn off potential candidate genes involved in the regulation of physical activity. Vivo-morpholinos have not been shown to be effective at silencing genes in the brain due to the fact that the vivo-morpholino cannot cross the blood brain barrier. To counteract this, a tail vein injection (55 ul total volume; 11mg/kg vivo-morpholino; 6.5ug/kg RMP7) was given on three consecutive days containing the bradykinin analog RMP7 and a vivo-morpholino targeting Vmat2 to male C57/LJ mice (n=6). RMP7 has been shown to increase blood brain barrier permeability while Vmat2 is a dopamine transporter and is thought to be involved in the regulation of voluntary physical activity. Control animals received either RMP7 plus saline (n=6) or RMP7 plus a vivo-morpholino “scramble” control (n=6). Physical activity was measured by wheel running. Results showed there was not a significant (p=0.24) knockdown in Vmat2 in the brain with RMP7 administration as compared to control animals. Interestingly there was a significant (p=0.001) knockdown in daily physical activity in the Vmat2 treated animals compared to the control group. RMP7 may still be a viable option for vivo-morpholino delivery in the brain; however an increased dosage may be required

The Correlation of Physical Activity and Body Composition in Inbred Mice

The Correlation of Physical Activity and Body Composition in Inbred Mice. Analisa .M Jimenez*; David .P Ferguson MS RCEP; J. Timothy Lightfoot, PhD FACSM RCEPCES I would like to participate in the undergraduate category. Biology of Physical Activity Lab, Texas A&M University, College Station TX, 77843-4243 Obesity is a growing epidemic related to physical inactivity, cardiovascular disease, and Type II diabetes. In smaller mouse cohorts, there has been no association reported between physical activity and body composition indices. The purpose of this experiment was to determine if there was a correlation between the physical activity level and body composition in a large cohort of inbred mouse strains. Using a GE Lunar Piximus (Madison, WI), body composition of 420 mice across 17 strains was analyzed for association with percent body fat, lean mass, and fat mass. Activity data using a running wheel had previously been measured in each of these mice. Pearson correlations were determined using the indices of body composition and physical activity level with alpha \u3c0.05 set a priori. There was a significant (p=0.013) correlation (r2 = 0.87) between mouse strain and fat mass (p \u3c 0.05). Additionally, there trends for lean mass (p=0.053) and total body weight (p=0.056) to be correlated to mouse strain. There was not a significance association between the body composition characteristics (fat mass (p=0.013), lean mass (p=0.053), and percent body fat (p=0.068)) and physical activity in the mice. From these results, we have supported previous literature showing a genetic predisposition for fat mass within each mouse strain. Further, the lack of significant relationship between body composition and daily activity is not surprising given previous published data in smaller mouse cohorts. Our data support previous suggestions that body composition and the inherent drive to be active are independent of each other

Infrared scintillation yield in gaseous and liquid argon

The study of primary and secondary scintillations in noble gases and liquids is of paramount importance to rare-event experiments using noble gas media. In the present work, the scintillation yield in gaseous and liquid Ar has for the first time been measured in the near infrared (NIR) and visible region, both for primary and secondary (proportional) scintillations, using Geiger-mode avalanche photodiodes (G-APDs) and pulsed X-ray irradiation. The primary scintillation yield of the fast component was measured to be 17000 photon/MeV in gaseous Ar in the NIR, in the range of 690-1000 nm, and 510 photon/MeV in liquid Ar, in the range of 400-1000 nm. Proportional NIR scintillations (electroluminescence) in gaseous Ar have been also observed; their amplification parameter at 163 K was measured to be 13 photons per drifting electron per kV. Possible applications of NIR scintillations in high energy physics experiments are discussed.Comment: 6 pages, 5 figures. Submitted to Europhysics Letter. Revised Figs. 3 and

Biochemical assessment of patients following ketogenic diets for epilepsy : current practice in the UK and Ireland

Biochemical assessment is recommended for patients prior to initiating and following a ketogenic diet (KD). There is no published literature regarding current practice in the UK and Ireland. We aimed to explore practice in comparison with international guidelines, determine approximate costs of biochemical testing in KD patients across the UK and Ireland, and promote greater consistency in KD services nationally. A survey was designed to determine the biochemical tests requested for patients at baseline, 3, 6, 12, 18, and 24 months + on KD. The survey was circulated to 39 centers across the UK and Ireland. Sixteen centers completed the survey. Full blood count, electrolytes, calcium, liver function tests (LFTs), lipid profile, and vitamin D were requested at all centers at baseline, in keeping with international guidelines. Bicarbonate, total protein, and urinalysis were less consistently requested. Magnesium and zinc were requested by all centers, despite not being specifically recommended for pre-diet evaluation in guidelines. Urea and electrolyte profiles and some LFTs were consistently requested at follow-up, in accordance with guidelines. Other LFTs and renal tests, full blood count, lipid profile, acylcarnitine profile, selenium, vitamin D, and urinalysis were less consistently requested at follow-up. The mean costs of the lowest and highest number of tests requested at baseline in our participating centers were £167.54 and £501.93; the mean costs of the lowest and highest number of tests requested at 3-month follow-up were £19.17 and £450.06. Biochemical monitoring of KD patients varies widely across the UK and Ireland and does not fully correspond to international best practice guidelines. With an ongoing drive for cost-effectiveness within health care, further work is needed to streamline practice while ensuring patient safety. [Abstract copyright: © 2019 The Authors. Epilepsia Open published by Wiley Periodicals Inc. on behalf of International League Against Epilepsy.

Major histocompatibility complex I‐induced endoplasmic reticulum stress mediates the secretion of pro‐inflammatory muscle‐derived cytokines

© 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. This is an open access article distributed under the Creative Commons Attribution License, to view a copy of the license, see: This is an open access article under the terms of the Creative Commons Attribution License,https://creativecommons.org/licenses/by/4.0/Major histocompatibility complex (MHC) I is an important component of intracellular antigen presentation. However, improper expression of MHC I upon the cell surface has been associated with several autoimmune diseases. Myositis is a rare acquired autoimmune disease which targets skeletal muscle, and MHC I overexpression on the surface of muscle fibres and immune cell infiltration are clinical hallmarks. MHC I overexpression may have an important pathogenic role, mediated by the activation of the endoplasmic reticulum (ER) stress response. Given the evidence that muscle is a diverse source of cytokines, we aimed to investigate whether MHC I overexpression can modify the profile of muscle‐derived cytokines and what role the ER stress pathway may play. Using C2C12 myoblasts we overexpressed MHC I with a H‐2kb vector in the presence or absence of salubrinal an ER stress pathway modifying compound. MHC I overexpression induced ER stress pathway activation and elevated cytokine gene expression. MHC I overexpression caused significant release of cytokines and chemokines, which was attenuated in the presence of salubrinal. Conditioned media from MHC I overexpressing cells induced in vitro T‐cell chemotaxis, atrophy of healthy myotubes and modified mitochondrial function, features which were attenuated in the presence of salubrinal. Collectively, these data suggest that MHC I overexpression can induce pro‐inflammatory cytokine/chemokine release from C2C12 myoblasts, a process which appears to be mediated in‐part by the ER stress pathway.Peer reviewe

Orientation dependence of ferroelectric properties of pulsed-laser-ablated Bi4-xNdxTi3O12 films

Epitaxial (001)-, (118)-, and (104)-oriented Nd-doped Bi4Ti3O12 films have been grown by pulsed-laser deposition from a Bi4-xNdxTi3O12 (x=0.85) target on SrRuO3 coated single-crystal (100)-, (110)-, and (111)-oriented SrTiO3 substrates, respectively. X-ray diffraction illustrated a unique epitaxial relationship between film and substrate for all orientations. We observed a strong dependence of ferroelectric properties on the film orientation, with no ferroelectric activity in an (001)-oriented film; a remanent polarization 2P(r) of 12 muC/cm(2) and coercive field E-c of 120 kV/cm in a (118)-oriented film; and 2P(r)=40 muC/cm(2), E-c=50 kV/cm in a (104)-oriented film. The lack of ferroelectric activity along the c-axis is consistent with the orthorhombic nature of the crystal structure of the bulk material, as determined by powder neutron diffraction. (C) 2003 American Institute of Physics