2,154 research outputs found

    The amyloid precursor protein derivative, APP96-110, is efficacious following intravenous administration after traumatic brain injury.

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    Following traumatic brain injury (TBI) neurological damage is ongoing through a complex cascade of primary and secondary injury events in the ensuing minutes, days and weeks. The delayed nature of secondary injury provides a valuable window of opportunity to limit the consequences with a timely treatment. Recently, the amyloid precursor protein (APP) and its derivative APP96-110 have shown encouraging neuroprotective activity following TBI following an intracerebroventricular administration. Nevertheless, its broader clinical utility would be enhanced by an intravenous (IV) administration. This study assessed the efficacy of IV APP96-110, where a dose-response for a single dose of 0.005mg/kg- 0.5mg/kg APP96-110 at either 30 minutes or 5 hours following moderate-severe diffuse impact-acceleration injury was performed. Male Sprague-Dawley rats were assessed daily for 3 or 7 days on the rotarod to examine motor outcome, with a separate cohort of animals utilised for immunohistochemistry analysis 3 days post-TBI to assess axonal injury and neuroinflammation. Animals treated with 0.05mg/kg or 0.5mg/kg APP96-110 after 30 minutes demonstrated significant improvements in motor outcome. This was accompanied by a reduction in axonal injury and neuroinflammation in the corpus callosum at 3 days post-TBI, whereas 0.005mg/kg had no effect. In contrast, treatment with 0.005m/kg or 0.5mg/kg APP96-110 at 5 hours post-TBI demonstrated significant improvements in motor outcome over 3 days, which was accompanied by a reduction in axonal injury in the corpus callosum. This demonstrates that APP96-110 remains efficacious for up to 5 hours post-TBI when administered IV, and supports its development as a novel therapeutic compound following TBI

    Early Gelatinase Activity Is Not a Determinant of Long-Term Recovery after Traumatic Brain Injury in the Immature Mouse.

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    The gelatinases, matrix metalloproteinases (MMP)-2 and MMP-9, are thought to be key mediators of secondary damage in adult animal models of brain injury. Moreover, an acute increase in these proteases in plasma and brain extracellular fluid of adult patients with moderate-to-severe traumatic brain injuries (TBIs) is associated with poorer clinical outcomes and mortality. Nonetheless, their involvement after TBI in the pediatric brain remains understudied. Using a murine model of TBI at postnatal day 21 (p21), approximating a toddler-aged child, we saw upregulation of active and pro-MMP-9 and MMP-2 by gelatin zymography at 48 h post-injury. We therefore investigated the role of gelatinases on long-term structural and behavioral outcomes after injury after acute inhibition with a selective gelatinase inhibitor, p-OH SB-3CT. After systemic administration, p-OH SB-3CT crossed the blood-brain barrier at therapeutically-relevant concentrations. TBI at p21 induced hyperactivity, deficits in spatial learning and memory, and reduced sociability when mice were assessed at adulthood, alongside pronounced tissue loss in key neuroanatomical regions. Acute and short-term post-injury treatment with p-OH SB-3CT did not ameliorate these long-term behavioral, cognitive, or neuropathological deficits as compared to vehicle-treated controls, suggesting that these deficits were independent of MMP-9 and MMP-2 upregulation. These findings emphasize the vulnerability of the immature brain to the consequences of traumatic injuries. However, early upregulation of gelatinases do not appear to be key determinants of long-term recovery after an early-life injury

    FH through the retrospectoscope

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    After training as a gastroenterologist in the UK, the author became interested in lipidology while he was a research fellow in the USA and switched careers after returning home. Together with Nick Myant, he introduced the use of plasma exchange to treat familial hypercholesterolemia (FH) homozygotes and undertook non-steady state studies of LDL kinetics, which showed that the fractional catabolic rate of LDL remained constant irrespective of pool size. Subsequent steady-state turnover studies showed that FH homozygotes had an almost complete lack of receptor-mediated LDL catabolism, providing in vivo confirmation of the Nobel Prize-winning discovery by Goldstein and Brown that LDL receptor dysfunction was the cause of FH. Further investigation of metabolic defects in FH revealed that a significant proportion of LDL in homozygotes and heterozygotes was produced directly via a VLDL-independent pathway. Management of heterozygous FH has been greatly facilitated by statins and proprotein convertase subtilisin/kexin type 9 inhibitors but remains dependent upon lipoprotein apheresis in homozygotes. In a recent analysis of a large cohort treated with a combination of lipid-lowering measures, survival was markedly enhanced in homozygotes in the lowest quartile of on-treatment serum cholesterol. Emerging therapies could further improve the prognosis of homozygous FH; whereas in heterozygotes, the current need is better detection

    Website accessibility : evaluating the WCAG conformance level of WordPress templates and the FH Joanneum GmbH's website

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    Durch Content Management Systeme wie WordPress ist es auch Menschen ohne Ausbildung in Design oder Webentwicklung möglich, Webseiten schnell und günstig zu erstellen. Dies wird den BenutzerInnen dieser Systeme durch sogenannte Templates oder Vorlagen ermöglicht. Damit geht jedoch auch ein großes Problem bezüglich der Barrierefreiheit einher, da diese Templates nicht den gegebenen Standards unterliegen müssen. Zu Beginn dieser Arbeit wurden notwendige Begriffe wie Barrierefreiheit definiert. Ebenfalls wurden Behinderungen, welche die Benutzung von Webseiten negativ beeinflussen können, aufgezeigt und in vier Kategorien unterteilt. Daraufhin wurden drei Standards vorgestellt, mit deren Hilfe barrierefreie Webseiten, oder Templates, erstellt werden können. Diese Standards wurden von der Autorin aus dem Englischen ins Deutsche übersetzt und zusammengefasst. Anschließend wurden die vier meist genutzten, kostenlose WordPress Templates aus der Kategorie ‘Food & Drink’, sowie das einzige Template dieser Kategorie, welches als ‘Accessibility Ready’ gekennzeichnet wurde, auf ihre Barrierefreiheit untersucht. Diese Evaluierungen wurden manuell anhand der Demo-Versionen der Templates durchgeführt. Zusätzlich wird die Webseite der FH JOANNEUM GmbH, welche ebenfalls mit WordPress erstellt wurde, manuell untersucht. Ziel der Evaluierung war es herauszufinden welche Konformitätsstufe, nach den Web Content Accessibility Guidelines, diese Templates und die Webseite erreichen können. Die Evaluierung ergab, dass weder die untersuchten Templates, noch die Webseite der FH JOANNEUM GmbH auch nur die niedrigste Konformitätsstufe erreichen konnten. Die gesamten Ergebnisse der Evaluierung der FH JOANNEUM GmbH und des Templates, welches als ‘Accessibility Ready’ gekennzeichnet ist, wurden in einer Tabelle festgehalten. In diesen Tabellen wurden sowohl gute Umsetzungen, als auch Fehler besonders hervorgehoben. Für einfach zu behebende Fehler wurden ebenfalls Lösungsvorschläge angegeben. Zuletzt wurden die Ergebnisse auch in textueller Form und in einer vereinfachten Tabelle in dieser Arbeit festgehalten.Content management systems like WordPress enables people without training in design or web development to create websites quickly and cheaply. This is made possible for the users of these systems due to the use of so-called templates. However, this is also accompanied by a major concern regarding accessibility, as these templates do not have to be subject to any given standards. At the beginning of this thesis, necessary terms such as accessibility were defined. Likewise disabilities, which can affect the use of web pages negatively, were pointed out and divided into four categories. Then, three standards were presented that can be used to create accessible websites, or templates. These standards were translated from English into German by the author of this thesis and summarized. Subsequently, the four most used free WordPress templates from the category 'Food & Drink', as well as the only template of this category, which was tagged as 'Accessibility Ready', were evaluated for their accessibility. These evaluations were performed manually using the demo versions of the templates. Additionally, the website of FH Joanneum Ltd., which was also created with WordPress, was manually examined. The goal of the evaluation was to find out what level of compliance, according to the Web Content Accessibility Guidelines, these templates and the website can achieve. The evaluation showed that neither the examined templates nor the website of the FH Joanneum Ltd. could reach even the lowest level of conformance. The entire results of the evaluation of the website of FH Joanneum Ltd. and the template, which is tagged as 'Accessibility Ready', were noted in a table. In these tables, both good implementations and errors were highlighted. Suggested solutions were also given for errors that are easy to fix. Finally, the results were also recorded in textual form and in a simplified table in this thesis.eingereicht von: Darlene AntonioAbweichender Titel laut Übersetzung der Verfasserin/des VerfassersBachelorarbeit FH JOANNEUM 202

    Searching for Novel Candidate Biomarkers of RLS in Blood by Proteomic Analysis

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    Stefania Mondello,1 Firas H Kobeissy,2 Yehia Mechref,2 Jingfu Zhao,3 Samer El Hayek,4 Kazem Zibara,5 Monica Moresco,6,7 Giuseppe Plazzi,6 Filomena II Cosentino,8 Raffaele Ferri8 1Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy; 2Faculty of Medicine, American University of Beirut Medical Center, Beirut, Lebanon; 3Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX, 79409, USA; 4Department of Psychiatry, American University of Beirut, Beirut, Lebanon; 5Department of Biology, Faculty of Sciences-I, PRASE, DSST, Lebanese University, Beirut, Lebanon; 6Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy; 7IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; 8Sleep Research Centre, Oasi Research Institute - IRCCS, Troina, ItalyCorrespondence: Raffaele FerriSleep Research Centre, Oasi Research Institute - IRCCS, Troina, 94018, ItalyTel +39 0935 936111Fax +39 0935 936231Email [email protected]: We performed comparative proteomic analyses of blood of patients with RLS and healthy individuals aiming to identify potential biomarker and therapeutic target candidate for RLS.Patients and Methods: Blood serum samples from 12 patients with a clinical diagnosis of RLS (8 females and 4 males, with a mean age of 68.52 years) and 10 healthy controls (5 females and 5 males, with a mean age of 67.61 years) underwent proteomic profiling by liquid chromatography coupled with tandem mass spectrometry. Pathway analysis incorporating protein–protein interaction networks was carried out to identify pathological processes linked to the differentially expressed proteins.Results: We quantified 272 proteins in patients with RLS and healthy controls, of which 243 were shared. Five proteins – apolipoprotein C-II, leucine-rich alpha-2-glycoprotein 1, FLJ92374, extracellular matrix protein 1, and FLJ93143 – were substantially increased in RLS patients, whereas nine proteins – vitamin D-binding protein, FLJ78071, alpha-1-antitrypsin, CD5 antigen-like, haptoglobin, fibrinogen alpha chain, complement factor H-related protein 1, platelet factor 4, and plasma protease C1 inhibitor – were decreased. Bioinformatics analyses revealed that these proteins were linked to 1) inflammatory and immune response, and complement activation, 2) brain-related development, cell aging, and memory disorders, 3) pregnancy and associated complications, 4) myocardial infarction, and 5) reactive oxygen species generation and subsequent diabetes mellitus.Conclusion: Our findings shed light on the multifactorial nature of RLS and identified a set of circulating proteins that may have clinical importance as biomarkers and therapeutic targets.Keywords: idiopathic restless legs syndrome, biomarkers, LC-MS/MS, proteome, interactom

    Het ontwerp van een synchronisatiemethode voor een muitiplex-systeem volgens het FH-MFSK principe ten behoeve van dataoverdracht van een basisstation naar een aantal mobiele stations

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    Frequency Hopping-Multiple Frequency Shift Keying (FH-MFSK) is een principe waarmee gegevens kunnen worden overgedragen in een mobiel communicatiesysteem voor meerdere gebruikers. Met behulp van Code Division Multiple Access (CDMA)-techniek is het mogelijk het effect van interferentie tussen de gebruikers onderling te beperken, In de mobiele communicatie heeft men te maken met diverse omgevingsinvloeden, zoals meerwegfading en interferentie. Het FH-MFSK principe biedt mogelijkheden de kwaliteit en net frequentierendement van de overdracht op een acceptabel niveau te brengen. Onderzocht is noe in een FH-MFSK systeem synchronisatie tot stand gebracht kan worden.Electrical Engineering, Mathematics and Computer ScienceTelecommunicatie- en Verkeersbegeleidingssysteme

    Website accessibility : evaluating the WCAG conformance level of WordPress templates and the FH Joanneum GmbH's website

    No full text
    Durch Content Management Systeme wie WordPress ist es auch Menschen ohne Ausbildung in Design oder Webentwicklung möglich, Webseiten schnell und günstig zu erstellen. Dies wird den BenutzerInnen dieser Systeme durch sogenannte Templates oder Vorlagen ermöglicht. Damit geht jedoch auch ein großes Problem bezüglich der Barrierefreiheit einher, da diese Templates nicht den gegebenen Standards unterliegen müssen. Zu Beginn dieser Arbeit wurden notwendige Begriffe wie Barrierefreiheit definiert. Ebenfalls wurden Behinderungen, welche die Benutzung von Webseiten negativ beeinflussen können, aufgezeigt und in vier Kategorien unterteilt. Daraufhin wurden drei Standards vorgestellt, mit deren Hilfe barrierefreie Webseiten, oder Templates, erstellt werden können. Diese Standards wurden von der Autorin aus dem Englischen ins Deutsche übersetzt und zusammengefasst. Anschließend wurden die vier meist genutzten, kostenlose WordPress Templates aus der Kategorie ‘Food & Drink’, sowie das einzige Template dieser Kategorie, welches als ‘Accessibility Ready’ gekennzeichnet wurde, auf ihre Barrierefreiheit untersucht. Diese Evaluierungen wurden manuell anhand der Demo-Versionen der Templates durchgeführt. Zusätzlich wird die Webseite der FH JOANNEUM GmbH, welche ebenfalls mit WordPress erstellt wurde, manuell untersucht. Ziel der Evaluierung war es herauszufinden welche Konformitätsstufe, nach den Web Content Accessibility Guidelines, diese Templates und die Webseite erreichen können. Die Evaluierung ergab, dass weder die untersuchten Templates, noch die Webseite der FH JOANNEUM GmbH auch nur die niedrigste Konformitätsstufe erreichen konnten. Die gesamten Ergebnisse der Evaluierung der FH JOANNEUM GmbH und des Templates, welches als ‘Accessibility Ready’ gekennzeichnet ist, wurden in einer Tabelle festgehalten. In diesen Tabellen wurden sowohl gute Umsetzungen, als auch Fehler besonders hervorgehoben. Für einfach zu behebende Fehler wurden ebenfalls Lösungsvorschläge angegeben. Zuletzt wurden die Ergebnisse auch in textueller Form und in einer vereinfachten Tabelle in dieser Arbeit festgehalten.Content management systems like WordPress enables people without training in design or web development to create websites quickly and cheaply. This is made possible for the users of these systems due to the use of so-called templates. However, this is also accompanied by a major concern regarding accessibility, as these templates do not have to be subject to any given standards. At the beginning of this thesis, necessary terms such as accessibility were defined. Likewise disabilities, which can affect the use of web pages negatively, were pointed out and divided into four categories. Then, three standards were presented that can be used to create accessible websites, or templates. These standards were translated from English into German by the author of this thesis and summarized. Subsequently, the four most used free WordPress templates from the category 'Food & Drink', as well as the only template of this category, which was tagged as 'Accessibility Ready', were evaluated for their accessibility. These evaluations were performed manually using the demo versions of the templates. Additionally, the website of FH Joanneum Ltd., which was also created with WordPress, was manually examined. The goal of the evaluation was to find out what level of compliance, according to the Web Content Accessibility Guidelines, these templates and the website can achieve. The evaluation showed that neither the examined templates nor the website of the FH Joanneum Ltd. could reach even the lowest level of conformance. The entire results of the evaluation of the website of FH Joanneum Ltd. and the template, which is tagged as 'Accessibility Ready', were noted in a table. In these tables, both good implementations and errors were highlighted. Suggested solutions were also given for errors that are easy to fix. Finally, the results were also recorded in textual form and in a simplified table in this thesis.eingereicht von: Darlene AntonioAbweichender Titel laut Übersetzung der Verfasserin/des VerfassersBachelorarbeit FH JOANNEUM 202

    Two Novel Colorimetric Probes (5-HMBA-FH and 3-HMBA-FH) Based on Fluorescein for Copper(II) ion Detection

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    Two novel isomeric colorimetric probes are established for simultaneous determination of copper ions using 2-Hydroxy-5-methoxybenzaldehyde fluorescein hydrazone (5-HMBA-FH) and 2-Hydroxy-3-methoxybenzaldehyde fluorescein hydrazone (3-HMBA-FH). They are synthesized by reacting fluorescein hydrazide with 2-Hydroxy-5-methoxybenzaldehyde and 2-Hydroxy-3-methoxybenzaldehyde, respectively, and then characterized by 1H-NMR, 13C-NMR and Infrared spectrum. In addition of copper ions to the solutions of two novel colorimetric probes can generate the obviously peaks at 498 nm in UV-vis absorption spectra along with a rapid color change from colorless to dark yellow. The detection limits of the method for Cu2+ ion were 3.442 Ă 10-6 mol/L and 3.682 Ă 10-6 mol/L separately, for 5-HMBA-FH and 3-HMBA-FH. The additions of other metal ions hardly affect the copper ions determination. The proposed method was successfully applied to the analysis of Cu2+ ions in various samples. This method possessing high sensitivity, simplicity and minimized interfere will provide a great advantage in detecting copper ions in the environmental, food, medical applications.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

    A critical assessment of the Flory-Huggins (FH) theory to predict aqueous two-phase behaviour

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    This article provides an analysis on published models used to calculate phase separation in aqueous two-phase systems (ATPS) based on Flory-Huggins (FH) theory, in terms of problem formulation and mathematical solving algorithm. An integrated algorithm is presented, showing different mathematical approaches of using the FH theory. The algorithm involves the estimation of interchange energy, and the calculation of phase compositions. Based on experimental data, the thermodynamic model can provide a useful framework to perform a sensitivity analysis on parameters, in order to understand the influence of salt type, polymer molecular mass, and ionic strength on phase separation. However, this model, restricted to entropic and enthalpic terms, cannot quantitatively describe the data. This occurs mainly because of the strong influence of random experimental errors on the estimation of interchange energy and FH not being an exact description of phase separation in salt based ATPS. After providing a literature overview and mathematical analysis, we bring to the field the application of the FH theory for selecting ATPS and its limitations.BT/Bioprocess EngineeringBT/Design and Engineering Educatio

    ASIL upgrade of a safety element out of context

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    Author: Marco TerlerScientific Paper Wien, FH Campus Wien 202
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