Reporting of adverse events in muscle strengthening interventions in youth: A systematic review

To document the extent to which AEs, resulting from intervention studies targeting muscle-strengthening training (MST) in youth, are reported by researchers

Variations in Implementation of Specifications Grading in STEM Courses

Specifications grading is an assessment strategy based on mastery learning, clear learning objectives, and frequent evaluations and feedback. Twelve instructors at a southeastern four-year public college implemented the specifications grading method across eight discrete courses in four STEM areas. In this modified assessment strategy, the students controlled their grades through multiple attempts, with limitations, on assessments of course objectives. The instructors designed and executed specifications grading in unique ways that aligned with their content areas, teaching beliefs, and individual teaching styles. Preliminary observations suggest that, regardless of subject area, specifications grading can be used as an alternative to traditional assessment methodologies in STEM courses, regardless of the content area. In general, three major variations of implementation arose from this initial trial. Major differences and commonalities among these types are discussed as they relate to the course subject area in which they are used. The results of this work add a unique set of assessment practices to the current body of knowledge in that other practitioners may gain insight on variations of the specifications grading method that may be practical and applicable in their own classrooms

SINEUP non-coding RNAs rescue defective frataxin expression and activity in a cellular model of Friedreich's Ataxia

Friedreich's ataxia (FRDA) is an untreatable disorder with neuro- and cardio-degenerative progression. This monogenic disease is caused by the hyper-expansion of naturally occurring GAA repeats in the first intron of the FXN gene, encoding for frataxin, a protein implicated in the biogenesis of iron-sulfur clusters. As the genetic defect interferes with FXN transcription, FRDA patients express a normal frataxin protein but at insufficient levels. Thus, current therapeutic strategies are mostly aimed to restore physiological FXN expression. We have previously described SINEUPs, natural and synthetic antisense long non-coding RNAs, which promote translation of partially overlapping mRNAs through the activity of an embedded SINEB2 domain. Here, by in vitro screening, we have identified a number of SINEUPs targeting human FXN mRNA and capable to up-regulate frataxin protein to physiological amounts acting at the post-transcriptional level. Furthermore, FXN-specific SINEUPs promote the recovery of disease-associated mitochondrial aconitase defects in FRDA-derived cells. In summary, we provide evidence that SINEUPs may be the first gene-specific therapeutic approach to activate FXN translation in FRDA and, more broadly, a novel scalable platform to develop new RNA-based therapies for haploinsufficient diseases

"Se ne posso spuntare una voglio stare un dì digiuna" Le doti della Confraternita della Natività della Santissima Vergine sotto la protezione di Sant'Anna di Livorno

L’indagine oggetto del seguente elaborato si è focalizzata sulle doti che furono elargite dalla Confraternita della Natività di Livorno alle fanciulle indigenti dal 1714 al 1784, e sul resoconto che i fratelli ne fecero in un paio di registri. In seguito, la ricerca si è ampliata con la ricostruzione, tramite le carte d'archivio, delle vicende che segnarono l'esistenza di tale confraternita dalla fine del XVI secolo fino al XX secolo

The Down‐Regulation of Frataxin Compromises Nrf2 Signalling and Redox Homeostasis to Promote Cardiac Remodelling

Oxidative stress is a key contributor to the neurodegeneration in Friedreich’s ataxia (FA). While studies in neuronal models of FA have reported a diminished antioxidant response, redox homeostasis has not been examined in the FA heart, which develops a fatal cardiomyopathy. Using the MCK conditional frataxin knockout (KO) mouse, which closely mimics the development of cardiomyopathy in FA, I examined the effects of the loss of Fxn on redox homeostasis in the heart and the contribution of oxidative stress towards the development of cardiomyopathy. The main findings of this study were that down-regulation of Fxn compromises redox homeostasis in the heart as evidenced by the loss of ARE binding and increased protein modifications by oxygen free radicals. The primary cause of this shift in redox balance was attenuation of the antioxidant response due to the loss of Nrf2 expression. The mechanisms driving Nrf2 loss are multifaceted, with increased Keap1 mediated degradation and enhanced nuclear export identified in the heart. This led to the down-regulation of Nrf2 target genes in frataxin-deficient heart. A second equally prominent mechanism of Nrf2 degradation occurs in the nucleus and encompasses increased export. The alteration in turnover of nuclear Nrf2 was driven by increased activation of GSK3. Pharmacological inhibition of GSK3 activity was used to distinguish the relative contribution of these two pathways to the overall phenotype of Nrf2 down-regulation. Treatment of Fxn-deficient cardiomyoblasts revealed Keap1 mediated degradation was the primary driver of Nrf2 loss and oxidative stress. Collectively, this study identified molecular mechanisms driving Nrf2 down-regulation in FA cardiomyopathy, which may be amenable to therapeutic development

Research brief: The Netherlands

This Country Report specifically examines the judgments of the District Court published on rechtspraak.nl (database of the Dutch judiciary). In total, 3,235 District Court judgments concerning the EAW have been published on rechtspraak.nl (as of 12 July 2022). A selection of case law has been made and analysed based on several themes, namely: the human rights-refusal grounds (as set out in Article 11 of the Overleveringswet (OLW; Dutch Surrender Act)), the relationship between that article and the Court of Justice’s case law (Aranyosi and Căldăraru and the application of the ‘three-step’ test to LM) in relation to the right to a fair trial), and the dialogue between the Dutch executing judicial authority and the issuing judicial authority of other Member States

Engineering recommendation report : Prosthesis electric power pack control system

Prosthesis is a two story tall, 3000 kg, four legged wearable walking machine intended to be human controlled. Its movements will be controlled by a pilot standing inside of the machine. The pilot‟s movements will be mapped to the legs of Prosthesis via an exoskeletal interface. The final machine will require approximately 60 kW of hydraulic power to reach top speed and will be 100% electric. The current prototype leg, also known as the Alpha leg, requires a 12 kW continuous power supply, which will come from a pump and electric motor combination. Our team developed the control system for the electric power pack of Prosthesis. The work involved computer programming, mostly in C, as well as the processing of sensor data. In terms of the physical components of the pack, we helped our project sponsor by providing him with a set of calculations and performance curves detailing the possible states of the electric motors that will be used on Prosthesis. To perform tests on the controller that we developed, we chose a gear pump proportional to the electric power pack available to us at the time of testing. In other words, we determined the capacity of the pump we needed to be able to move the Alpha leg with a different power pack. The control is done via an Arduino microcontroller that is programmed in C. It is in charge of keeping the pressure as close as possible to a user-specified pressure, known as the setpoint. This was done by implementing a software PID controller on the Arduino. The controller has two operating modes, one of which follows a simplified PID control scheme, using a constant pressure as the “target” or setpoint. The other controller setting, referred to as Load Sense, keeps the pressure at the pump outlet some constant amount higher than the pressure at a predetermined spot in the hydraulic line. Simply put, the pump outlet pressure adapts to the load in the hydraulic line. The setpoint based PID control was tested and found to be within acceptable operating parameters. An initial version of the Load Sense control was created, but it was neither completed nor tested by the submission of this report.Science, Faculty ofPhysics and Astronomy, Department ofUnreviewedUndergraduat