High Precision Measurements Lend No Supporting Evidence of Previously Reported Large Verdet Constants for Olive Oil

Motivated by a previous report of surprisingly large Verdet constant measurements for olive oil at 633 nm and 650 nm (Shakir, et. al., 2013), and the practical utility of materials possessing such large values, we considered it worthwhile to validate those results. In this work, high precision Faraday rotation measurements were performed utilizing ac magnetic fields, phase sensitive detection, and a collection of diode lasers. Specifically, we measured the dispersion of the Verdet constant for a single brand of olive oil from 410 nm to 675 nm. In addition, we determined the Verdet constant for eight different samples of olive oil at 654 nm, very near the wavelength where the “anomalous” results, i.e. large Verdet constants, were reported. Our measurements of the Faraday rotations, and hence the determination of the respective Verdet constants, call into question those previously reported measurements. Generally, our results suggest that their experimental technique most likely led to inaccurate results for all five of the Verdet constant values they reported

Challenges for identifying the neural mechanisms that support spatial navigation: the impact of spatial scale.

Spatial navigation is a fascinating behavior that is essential for our everyday lives. It involves nearly all sensory systems, it requires numerous parallel computations, and it engages multiple memory systems. One of the key problems in this field pertains to the question of reference frames: spatial information such as direction or distance can be coded egocentrically-relative to an observer-or allocentrically-in a reference frame independent of the observer. While many studies have associated striatal and parietal circuits with egocentric coding and entorhinal/hippocampal circuits with allocentric coding, this strict dissociation is not in line with a growing body of experimental data. In this review, we discuss some of the problems that can arise when studying the neural mechanisms that are presumed to support different spatial reference frames. We argue that the scale of space in which a navigation task takes place plays a crucial role in determining the processes that are being recruited. This has important implications, particularly for the inferences that can be made from animal studies in small scale space about the neural mechanisms supporting human spatial navigation in large (environmental) spaces. Furthermore, we argue that many of the commonly used tasks to study spatial navigation and the underlying neuronal mechanisms involve different types of reference frames, which can complicate the interpretation of neurophysiological data

Type 1 Diabetes can present before the age of 6 months and is characterised by autoimmunity and rapid loss of beta-cells

This is the final version. Available on open access from Springer Verlag via the DOI in this recordAims/hypothesis Diabetes diagnosed <6 months is usually monogenic. However, 10-15% of cases do not have a pathogenic variant in one of the 26 known neonatal diabetes genes. We characterised infants diagnosed <6 months without a pathogenic variant to assess whether polygenic type 1 diabetes could arise at very early ages. Methods We studied 166 individuals diagnosed <6 months in whom pathogenic variants in all 26 known genes had been excluded and compared them to individuals with monogenic neonatal diabetes (n=164) or type 1 diabetes diagnosed at 6-24 months (n=152). We assessed the type 1 diabetes genetic risk score (T1D-GRS), islet autoantibodies, C-peptide and clinical features. Results We found an excess of patients with high T1D-GRS; 38% (63/166) had a T1D-GRS> 95th centile of healthy controls where 5% (8/166) would be expected if all were monogenic (p<0.0001). Individuals with a high T1D-GRS had a similar rate of autoantibody positivity to type 1 diabetes diagnosed between 6 and 24 months (41% vs. 58%, p=0.2), and had markedly reduced C-peptide (median <3pmol/L within 1 year of diagnosis), reflecting rapid loss of insulin secretion. These individuals also had reduced birthweights (median z-score -0.89) which were lowest in those diagnosed <3 months (-1.98). Conclusions/Interpretation We provide strong evidence that type 1 diabetes can present before age 6 months based on individuals with this extreme-early onset diabetes subtype having the classic features of childhood type 1 diabetes; high genetic risk, autoimmunity and rapid beta-cell loss. The early onset association with reduced birthweight raises the possibility that for some individuals there was reduced insulin secretion in utero. Comprehensive genetic testing for all neonatal diabetes genes remains essential for all individuals diagnosed with diabetes <6 months.Diabetes Research and Wellness Foundatio

Outer membrane protein folding from an energy landscape perspective

The cell envelope is essential for the survival of Gram-negative bacteria. This specialised membrane is densely packed with outer membrane proteins (OMPs), which perform a variety of functions. How OMPs fold into this crowded environment remains an open question. Here, we review current knowledge about OFMP folding mechanisms in vitro and discuss how the need to fold to a stable native state has shaped their folding energy landscapes. We also highlight the role of chaperones and the β-barrel assembly machinery (BAM) in assisting OMP folding in vivo and discuss proposed mechanisms by which this fascinating machinery may catalyse OMP folding

Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with longacting bronchodilators: two randomised clinical trials

Background Patients with chronic obstructive pulmonary disease (COPD) have few options for treatment. The efficacy and safety of the phosphodiesterase-4 inhibitor roflumilast have been investigated in studies of patients with moderate-to-severe COPD, but not in those concomitantly treated with longacting inhaled bronchodilators. The effect of roflumilast on lung function in patients with COPD that is moderate to severe who are already being treated with salmeterol or tiotropium was investigated. Methods In two double-blind, multicentre studies done in an outpatient setting, after a 4-week run-in, patients older than 40 years with moderate-to-severe COPD were randomly assigned to oral roflumilast 500 mu g or placebo once a day for 24 weeks, in addition to salmeterol (M2-127 study) or tiotropium (M2-128 study). The primary endpoint was change in prebronchodilator forced expiratory volume in 1s (FEV(1)). Analysis was by intention to treat. The studies are registered with ClinicalTrials.gov, number NCT00313209 for M2-127, and NCT00424268 for M2-128. Findings In the salmeterol plus roflumilast trial, 466 patients were assigned to and treated with roflumilast and 467 with placebo; in the tiotropium plus roflumilast trial, 371 patients were assigned to and treated with roflumilast and 372 with placebo. Compared with placebo, roflumilast consistently improved mean prebronchodilator FEV(1) by 49 mL (p<0.0001) in patients treated with salmeterol, and 80 mL (p<0.0001) in those treated with tiotropium. Similar improvement in postbronchodilator FEV(1) was noted in both groups. Furthermore, roflumilast had beneficial effects on other lung function measurements and on selected patient-reported outcomes in both groups. Nausea, diarrhoea, weight loss, and, to a lesser extent, headache were more frequent in patients in the roflumilast groups. These adverse events were associated with increased patient withdrawal. Interpretation Roflumilast improves lung function in patients with COPD treated with salmeterol or tiotropium, and could become an important treatment for these patients

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Equine Urine Screening for IOX Compounds Using Solid Phase Extraction and Triple Quadrupole LC-MS

A. Background IOX compounds belong to the family of hypoxia inducible factor stabilizers and oxygen enhancers. “The hypoxia inducible factor pathway is the major signaling pathway responsible for cellular oxygen sensing and adaptation to a hypoxia (Günter, Ruiz-Serrano, Pickel, Wenger, & Scholz, 2017).” The hypoxia inducible factor is a transcription factor, meaning it is a protein that binds to DNA and affects the expression of genes (Khan Academy, 2020). This gives the hypoxia inducible factor pathway the ability to control the expression of several downstream genes responsible for homeostasis (Ziello, Jovin, & Huang, 2007). During normoxia, the hypoxia inducible factor proteins are constantly degraded. “In the α-subunit there is an oxygen degradation (ODD) domain, which is hydroxylated by proline-hydroxylase-2 (PHD2), rendering the subunit vulnerable (Ziello et al., 2007).” The hydroxylation is carried out by enzymes known as also known as 2-oxoglutarate dependent oxygenases. These hydroxylase enzymes are dependent upon molecular oxygen and 2-oxoglutarate as substrates to function, making them cellular oxygen sensors responsible for the regulation of the pathway (Günter et al., 2017; Pagé, Chan, Giaccia, Levine, & Richard, 2008; Yang, Sun, Wang, & Jiao, 2013). The proline hydroxylation allows the hypoxia inducible factor to bind with the von Hippel-Lindau protein. The von Hippel-Lindau is a ubiquitination ligase complex that marks the hydroxylated hypoxia inducible factor for proteasomal degradation (Haase, 2013; Pagé et al., 2008; Ziello et al., 2007). In a hypoxic state, the lack of oxygen means there is a lack of substrate for the prolyl-hydroxylase enzymes to interact with, prohibiting the degradation of the hypoxia inducible factor (Pagé et al., 2008). When stabilization occurs, the hypoxia inducible factor is free to bind to its specific genes and induce their transcription. These genes are responsible for stimulating angiogenesis and erythropoiesis. (Rabinowitz, Barrett, Rosen, & Venkatesan, 2010; Strowitzki, Cummins, & Taylor, 2019). Red blood cells contain hemoglobin, otherwise known as an oxygen binding protein. Therefore, through hypoxia, the formation of red blood cells is stimulated and an increase in oxygen levels occurs. There are several therapeutic drugs in development to take advantage of the pathway. These therapeutic compounds are hypoxia inducible factor-prolyl hydroxylase domain protein inhibitors, or HIF prolyl hydroxylase inhibitors (HIF PHIs). The purpose of developing hypoxia inducible factor prolyl hydroxylase domain inhibitors is to help patients with anemia from chronic kidney disease, anemia from chemotherapy, or anemia from a chronic disease by increasing their erythropoietin levels (Haase, 2017; Kansagra et al., 2018). As a result of the oxygen enhancing capacity of these new therapeutic compounds, it follows that they have the abuse potential as many of the other erythropoietin stimulating agents that came before. The concept of blood doping began with humans in the Olympics receiving transfusions of their own blood before competing and has since continued to advance with the creation of new blood doping substances. Human sports typically set the precedent for the newest compounds and trends used for doping purposes. Eventually, these ideas and drugs find their way into non-human sports where there are even more possibilities of what substances can be used for doping purposes and what substances can be banned. B. Statement of the Issue Since IOX compounds have been developed for the purpose of increasing erythropoietin levels in anemic patients, it is obvious why they have been chosen as doping agents within the industry of horseracing. In January of 2020, the presence of IOX-2 in two standard bred horses was first documented by the New York Equine Drug Testing Program (Shoemaker, 2020). While this has been the first known case of IOX compounds detected in racehorses, other oxygen enhancing and blood doping compounds have already been banned by the International Federation of Horseracing Authorities (IFHA), as well as the World Anti-Doping Agency (WADA) for human sports. C. Significance of the Issue IOX compounds are just one type of the many substances making their way into human sports and horseracing as new doping agents. The list of prohibited and banned substances is ever-increasing, making it harder for human and equine toxicology laboratories to constantly be developing new detection methods. For example, UIC AFTL did not have a validated method for the detection of IOX compounds in equine urine prior to the completion of this project. D. Purpose of Study The purpose of this study is to establish and validate a reproducible and reliable method for extracting and detecting IOX-1, IOX-2, FG-2216, and IOX-4 from equine urine using solid phase extraction and liquid-chromatography-tandem mass spectrometry. The validation of the method followed the guidelines provided by the UIC AFTL Standard Operating Procedure ‘Validation Requirements for Methods Using Instrumental Analysis’ #AFTL GE005-04. E. Significance of the Study Limited studies and research exist on these novel compounds and the more information that is available, the easier it is for different laboratories to quickly validate and integrate these compounds into their methods. It is important for more information on these compounds to be available to assist laboratories in staying up to date and being prepared to handle the detection with newly developed compounds that have a possibility of doping use

Against Nature : A Group Show of Work by Homosexual Men

This publication was part of a group exhibition which called attention to the place of gay male sexual desire in contemporary arts - particularly video and visual art - by focusing on cultural practices engaged in the struggle against AIDS. It contains fictional texts concerned with issues of illness, loss, mourning, melancholia, nature and artificiality. Biographical notes. 4 bibl. ref

Review of issues concerning the use of reproductive inhibitors, with particular emphasis on resolving human-wildlife conflicts in North America

This manuscript provides an overview of past wildlife contraception efforts and discusses the current state of research. Two fertility control agents, an avian reproductive inhibitor containing the active ingredient nicarbazin and an immunocontraceptive vaccine, have received regulatory approval with the Environmental Protection Agency and are commercially available in the USA. OvoControl G Contraceptive Bait for Canada Geese and Ovo Control for pigeons are delivered as oral baits. An injectable immunocontraceptive vaccine (GonaCon Immunocontraceptive Vaccine) was registered with the Environmental Protection Agency for use in female white-tailed deer in September 2009. An injectable product (GonaCon Immunocontraceptive Vaccine) is registered for use in female white-tailed deer. Both products are labeled for use in urban/suburban areas where these species are overabundant. Several other compounds are currently being tested for use in wildlife in the USA, Europe, Australia and New Zealand that could have promise in the future. The development and use of reproductive inhibitors for resolving human–wildlife conflicts will depend on a number of factors, including meeting the requirements of regulatory agencies for use in the environment and on the biological and economical feasibility of their use. Use will also be dependent on health and safety issues and on public acceptance of the techniques

SJU Class of 1984 Commencement Celebration

May 27, 1984 One-Hundred and Twenty-Seventh Year Abbey & University Church Saint John\u27s University Mr. Garrison Keillor was the guest speaker and John P. Keane was the student speaker