\epsilon-regularity for systems involving non-local, antisymmetric operators

We prove an epsilon-regularity theorem for critical and super-critical systems with a non-local antisymmetric operator on the right-hand side. These systems contain as special cases, Euler-Lagrange equations of conformally invariant variational functionals as Rivi\`ere treated them, and also Euler-Lagrange equations of fractional harmonic maps introduced by Da Lio-Rivi\`ere. In particular, the arguments presented here give new and uniform proofs of the regularity results by Rivi\`ere, Rivi\`ere-Struwe, Da-Lio-Rivi\`ere, and also the integrability results by Sharp-Topping and Sharp, not discriminating between the classical local, and the non-local situations

Motivation and Satisfaction of Software Engineers

Context: The proper management of people can help software organisations to achieve higher levels of success. However, the limited attention paid to the appropriate use of theories to underpin the research in this area leaves it unclear how to deal with human aspects of software engineers, such as motivation and satisfaction. Objectives: This article aims to expose what drives the motivation and satisfaction of software engineers at work. Methods: A multiple case study was conducted at four software organisations in Brazil. For 11 months, data was collected using semi-structured interviews, diary studies, and document analyses. Results: The Theory of Motivation and Satisfaction of Software Engineers (TMS-SE), presented in this article, combines elements from well established theories with new findings, and translates them into the software engineering context. Conclusion: The TMS-SE advances the understanding of people management in the software engineering field and presents a strong conceptual framework for future investigations in this area

Elevating microRNA-122 in blood improves outcomes after temporary middle cerebral artery occlusion in rats.

Because our recent studies have demonstrated that miR-122 decreased in whole blood of patients and in whole blood of rats following ischemic stroke, we tested whether elevating blood miR-122 would improve stroke outcomes in rats. Young adult rats were subjected to a temporary middle cerebral artery occlusion (MCAO) or sham operation. A polyethylene glycol-liposome-based transfection system was used to administer a miR-122 mimic after MCAO. Neurological deficits, brain infarction, brain vessel integrity, adhesion molecule expression and expression of miR-122 target and indirect-target genes were examined in blood at 24 h after MCAO with or without miR-122 treatment. miR-122 decreased in blood after MCAO, whereas miR-122 mimic elevated miR-122 in blood 24 h after MCAO. Intravenous but not intracerebroventricular injection of miR-122 mimic decreased neurological deficits and brain infarction, attenuated ICAM-1 expression, and maintained vessel integrity after MCAO. The miR-122 mimic also down-regulated direct target genes (e.g. Vcam1, Nos2, Pla2g2a) and indirect target genes (e.g. Alox5, Itga2b, Timp3, Il1b, Il2, Mmp8) in blood after MCAO which are predicted to affect cell adhesion, diapedesis, leukocyte extravasation, eicosanoid and atherosclerosis signaling. The data show that elevating miR-122 improves stroke outcomes and we postulate this occurs via downregulating miR-122 target genes in blood leukocytes

Degeneracy and stability in neural circuits of dopamine and serotonin neuromodulators: A theoretical consideration

Degenerate neural circuits perform the same function despite being structurally different. However, it is unclear whether neural circuits with interacting neuromodulator sources can themselves degenerate while maintaining the same neuromodulatory function. Here, we address this by computationally modeling the neural circuits of neuromodulators serotonin and dopamine, local glutamatergic and GABAergic interneurons, and their possible interactions, under reward/punishment-based conditioning tasks. The neural modeling is constrained by relevant experimental studies of the VTA or DRN system using, e.g., electrophysiology, optogenetics, and voltammetry. We first show that a single parsimonious, sparsely connected neural circuit model can recapitulate several separate experimental findings that indicated diverse, heterogeneous, distributed, and mixed DRNVTA neuronal signaling in reward and punishment tasks. The inability of this model to recapitulate all observed neuronal signaling suggests potentially multiple circuits acting in parallel. Then using computational simulations and dynamical systems analysis, we demonstrate that several different stable circuit architectures can produce the same observed network activity profile, hence demonstrating degeneracy. Due to the extensive D2-mediated connections in the investigated circuits, we simulate the D2 receptor agonist by increasing the connection strengths emanating from the VTA DA neurons. We found that the simulated D2 agonist can distinguish among sub-groups of the degenerate neural circuits based on substantial deviations in specific neural populations’ activities in reward and punishment conditions. This forms a testable model prediction using pharmacological means. Overall, this theoretical work suggests the plausibility of degeneracy within neuromodulator circuitry and has important implications for the stable and robust maintenance of neuromodulatory functions

Comparison of medical and surgical treatment for acute cervical compressive hydrated nucleus pulposus extrusion in dogs

Although successful outcomes have been reported after medical and surgical treatment for dogs with cervical hydrated nucleus pulposus extrusion (HNPE), it is unknown which treatment option is preferred. Thirty-four dogs treated medically (n=18) or surgically (n=16) for cervical HNPE were retrospectively identified. Signalment, clinical presentation and imaging findings were compared between medically and surgically treated dogs. Medical management consisted of restricted exercise in combination with physiotherapy. Surgical treatment consisted of a ventral slot procedure. Short-term follow-up information was retrieved from re-examination visits. Long-term outcome was obtained via telephone interviews. More dogs in the surgical group demonstrated cervical hyperaesthesia on initial clinical presentation (P=0.045), otherwise there was no significant difference in signalment, clinical presentation or imaging findings between both groups. Two dogs in the medically managed group underwent surgical decompression due to an unsatisfactory response to medical management. All cases for which long-term information was available (n=30) were neurologically normal at the time of data collection. There were no significant differences for any of the short-term or long-term outcome variables between both treatment groups. This study demonstrated successful outcomes after medical or surgical treatment and suggests that both treatment modalities can be considered for dogs with cervical HNPE

Characterizing near-surface firn using the scattered signal component of the glacier surface return from airborne radio-echo sounding

We derive the scattered component (hereafter referred to as the incoherent component) of glacier surface echoes from airborne radio-echo sounding measurements over Devon Ice Cap, Arctic Canada, and compare the scattering distribution to firn stratigraphy observations from ground-based radar data. Low scattering correlates to laterally homogeneous firn above 1800m elevation containing thin, flat, and continuous ice layers and below 1200m elevation where firn predominantly consists of ice. Increased scattering between elevations of 1200-1800m corresponds to firn with inhomogeneous, undulating ice layers. No correlation was found to surface roughness and its theoretical incoherent backscattering values. This indicates that the scattering component is mainly influenced by the near-surface firn stratigraphy, whereas surface roughness effects are minor. Our results suggest that analyzing the scattered signal component of glacier surface echoes is a promising approach to characterize the spatial heterogeneity of firn that is affected by melting and refreezing processes.This work was supported by grants from UK NERC (NE/K004999), NASA (13-ICEE13-00018), NSERC (Discovery Grant/Northern Research Supplement), Alberta Innovates Technology Futures, the CRYSYS Program (Environment Canada), and a University of Alberta Northern Research Award

Opportunities for multiscale computational modelling of serotonergic drug effects in Alzheimer’s disease

Alzheimer's disease (AD) is an age-specific neurodegenerative disease that compromises cognitive functioning and impacts the quality of life of an individual. Pathologically, AD is characterised by abnormal accumulation of beta-amyloid (A$\beta$) and hyperphosphorylated tau protein. Despite research advances over the last few decades, there is currently still no cure for AD. Although, medications are available to control some behavioural symptoms and slow the disease's progression, most prescribed medications are based on cholinesterase inhibitors. Over the last decade, there has been increased attention towards novel drugs, targeting alternative neurotransmitter pathways, particularly those targeting serotonergic (5-HT) system. In this review, we focused on 5-HT receptor (5-HTR) mediated signalling and drugs that target these receptors. These pathways regulate key proteins and kinases such as GSK-3 that are associated with abnormal levels of A$\beta$ and tau in AD. We then review computational studies related to 5-HT signalling pathways with the potential for providing deeper understanding of AD pathologies. In particular, we suggest that multiscale and multilevel modelling approaches could potentially provide new insights into AD mechanisms, and towards discovering novel 5-HTR based therapeutic targets.Comment: Accepted manuscript in Neuropharmacolog

Alterations of the mitochondrial proteome caused by the absence of mitochondrial DNA: A proteomic view

The proper functioning of mitochondria requires that both the mitochondrial and the nuclear genome are functional. To investigate the importance of the mitochondrial genome, which encodes only 13 subunits of the respiratory complexes, the mitochondrial rRNAs and a few tRNAs, we performed a comparative study on the 143B cell line and on its Rho-0 counterpart, i.e., devoid of mitochondrial DNA. Quantitative differences were found, of course in the respiratory complexes subunits, but also in the mitochondrial translation apparatus, mainly mitochondrial ribosomal proteins, and in the ion and protein import system, i.e., including membrane proteins. Various mitochondrial metabolic processes were also altered, especially electron transfer proteins and some dehydrogenases, but quite often on a few proteins for each pathway. This study also showed variations in some hypothetical or poorly characterized proteins, suggesting a mitochondrial localization for these proteins. Examples include a stomatin-like protein and a protein sharing homologies with bacterial proteins implicated in tyrosine catabolism. Proteins involved in apoptosis control are also found modulated in Rho-0 mitochondria.Comment: website publisher: http://www3.interscience.wiley.com