Code Positioning in LLVM

Given the increasing performance disparity between processor speeds and memory latency, making efficient use of cache memory is more important than ever to achieve good performance in memory-bound workloads. Many modern first-level caches store instructions separately from data, making code layout and code size an important factor in the cache behavior of a program. This work investigates two methods that attempt to improve code locality, namely procedure splitting and procedure positioning, previously investigated by Pettis and Hansen. They are implemented in the open-source compiler framework LLVM to evaluate their effect on the SPEC CPU2000 benchmark suite and a benchmark run of the PostgreSQL database system. We found that our implementation is highly situational, but can be beneficial, reducing execution time by up to 3% on suitable SPEC benchmarks and an increase of 3% in average transactions per second on PostgreSQL

Miten diabeettinen munuaistauti syntyy?

Vertaisarvioitu. English summary.Diabeettinen munuaistauti kehittyy jopa joka toiselle diabetesta sairastavalle. Siihen liittyy suurentunut riski sairastua sekä kuolla sydän- ja verisuonitauteihin. Diabeettisen munuaistaudin syntyyn vaikuttavat sekä ympäristötekijät että geneettinen alttius. Suurentunut verenglukoosipitoisuus, epäedulliset rasva-arvot ja korkea verenpaine johtavat moniin solutason muutoksiin, jotka vaikuttavat sairauden kehittymiseen ja etenemiseen. Näihin kuuluvat muun muassa insuliiniresistenssi, lievä tulehdus, hypoksia, oksidatiivinen stressi, lipotoksisuus, endoplasmakalvoston stressi ja epigeneettiset muutokset. Diabeettiselle munuaistaudille ei ole kohdennettua hoitoa eikä sen syntymistä voida estää, mutta useat jo käytössä olevat lääkkeet hidastavat sen etenemistä. Monet molekulaariset mekanismit ja signalointikaskadit liittyvät sairauden kulkuun. Niiden tarkempi ymmärtäminen luo mahdollisuuksia kehittää räätälöityjä, munuaistautiin kohdennettuja hoitoja.Peer reviewe

Short- and long-term survival after severe acute pancreatitis : A retrospective 17 years' cohort study from a single center

Purpose: To study mortality in severe acute pancreatitis (SAP) and to identify risk factors for mortality. Materials and methods: A retrospective 17-years' cohort study of 435 consecutive adult patientswith SAP treated at intensive care unit of a university hospital. Results: Overall, 357 (82.1%) patients survived at 90 days follow-up. Three-hundred six (89.5%) patients under 60 years, 38 (60.3%) patients between 60 and 69 years, and 13 (43.3%) patients over 69 years of age survived at 90 days follow-up. Independent risk factors for death within 90-days were: 60 to 69 years of age (odds ratio [OR] 5.1), >69 years of age (OR 10.4), female sex (OR 2.0), heart disease (OR 2.9), chronic liver failure (OR 12.3), open abdomen treatment (OR 4.4) and sterile necrosectomy within 4 weeks (OR 14.7). The 10-year survival estimate was Conclusions: Although younger patients have excellent short-term survival after SAP, the long-term survival estimate is disappointing mostly due to alcohol abuse. (C) 2019 Elsevier Inc. All rights reserved.Peer reviewe

Edaphic heterogeneity and the evolutionary trajectory of Amazonian plant communities

We investigated how the phylogenetic structure of Amazonian plant communities varies along an edaphic gradient within the non-inundated forests. Forty localities were sampled on three terrain types representing two kinds of soil: clayey soils of a high base cation concentration derived from the Solimões formation, and loamy soils with lower base cation concentration derived from the Içá formation and alluvial terraces. Phylogenetic community metrics were calculated for each locality for ferns and palms both with ferns as one group and for each of three fern clades with a crown group age comparable to that of palms. Palm and fern communities showed significant and contrasting phylogenetic signals along the soil gradient. Fern species richness increased but standard effect size of mean pairwise distance (SES.MPD) and variation of pairwise distances (VPD) decreased with increasing soil base cation concentration. In contrast, palm communities were more species rich on less cation-rich soils and their SES.MPD increased with soil base cation concentration. Species turnover between the communities reflected the soil gradient slightly better when based on species occurrences than when phylogenetic distances between the species were considered. Each of the three fern subclades behaved differently from each other and from the entire fern clade. The fern clade whose phylogenetic patterns were most similar to those of palms also resembled palms in being most species-rich on cation-poor soils. The phylogenetic structuring of local plant communities varies along a soil base cation concentration gradient within non-inundated Amazonian rain forests. Lineages can show either similar or different phylogenetic community structure patterns and evolutionary trajectories, and we suggest this to be linked to their environmental adaptations. Consequently, geological heterogeneity can be expected to translate into a potentially highly diverse set of evolutionarily distinct community assembly pathways in Amazonia and elsewhere.</p

Serum Creatine, Not Neurofilament Light, Is Elevated in CHCHD10-Linked Spinal Muscular Atrophy

ObjectiveTo characterize serum biomarkers in mitochondrial CHCHD10-linked spinal muscular atrophy Jokela (SMAJ) type for disease monitoring and for the understanding of pathogenic mechanisms. MethodsWe collected serum samples from a cohort of 49 patients with SMAJ, all carriers of the heterozygous c.197G>T p.G66V variant in CHCHD10. As controls, we used age- and sex-matched serum samples obtained from Helsinki Biobank. Creatine kinase and creatinine were measured by standard methods. Neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) were measured with single molecule array (Simoa), fibroblast growth factor 21 (FGF-21), and growth differentiation factor 15 (GDF-15) with an enzyme-linked immunosorbent assay. For non-targeted plasma metabolite profiling, samples were analyzed with liquid chromatography high-resolution mass spectrometry. Disease severity was evaluated retrospectively by calculating a symptom-based score. ResultsAxon degeneration marker, NfL, was unexpectedly not altered in the serum of patients with SMAJ, whereas astrocytic activation marker, GFAP, was slightly decreased. Creatine kinase was elevated in most patients, particularly men. We identified six metabolites that were significantly altered in serum of patients with SMAJ in comparison to controls: increased creatine and pyruvate, and decreased creatinine, taurine, N-acetyl-carnosine, and succinate. Creatine correlated with disease severity. Altered pyruvate and succinate indicated a metabolic response to mitochondrial dysfunction; however, lactate or mitochondrial myopathy markers FGF-21 or GDF-15 was not changed. ConclusionsBiomarkers of muscle mass and damage are altered in SMAJ serum, indicating a role for skeletal muscle in disease pathogenesis in addition to neurogenic damage. Despite the minimal mitochondrial pathology in skeletal muscle, signs of a metabolic shift can be detected.Peer reviewe

Septin 7 reduces nonmuscle myosin IIA activity in the SNAP23 complex and hinders GLUT4 storage vesicle docking and fusion

Glomerular epithelial cells, podocytes, are insulin responsive and can develop insulin resistance. Here, we demonstrate that the small GTPase septin 7 forms a complex with nonmuscle myosin heavy chain HA (NMHC-HA; encoded by MYH9), a component of the nonmuscle myosin HA (NM-IIA) hexameric complex. We observed that knockdown of NMHC-IIA decreases insulin-stimulated glucose uptake into podocytes. Both septin 7 and NM-IIA associate with SNAP23, a SNARE protein involved in GLUT4 storage vesicle (GSV) docking and fusion with the plasma membrane. We observed that insulin decreases the level of septin 7 and increases the activity of NM-IIA in the SNAP23 complex, as visualized by increased phosphorylation of myosin regulatory light chain. Also knockdown of septin 7 increases the activity of NM-IIA in the complex. The activity of NM-IIA is increased in diabetic rat glomeruli and cultured human podocytes exposed to macroalbuminuric sera from patients with type 1 diabetes. Collectively, the data suggest that the activity of NM-IIA in the SNAP23 complex plays a key role in insulin-stimulated glucose uptake into podocytes. Furthermore, we observed that septin 7 reduces the activity of NM-IIA in the SNAP23 complex and thereby hinders GSV docking and fusion with the plasma membrane.Peer reviewe

Cyclin-dependent kinase 2 protects podocytes from apoptosis

Loss of podocytes is an early feature of diabetic nephropathy (DN) and predicts its progression. We found that treatment of podocytes with sera from normoalbuminuric type 1 diabetes patients with high lipopolysaccharide (LPS) activity, known to predict progression of DN, downregulated CDK2 (cyclin-dependent kinase 2). LPS-treatment of mice also reduced CDK2 expression. LPS-induced downregulation of CDK2 was prevented in vitro and in vivo by inhibiting the Toll-like receptor (TLR) pathway using immunomodulatory agent GIT27. We also observed that CDK2 is downregulated in the glomeruli of obese Zucker rats before the onset of proteinuria. Knockdown of CDK2, or inhibiting its activity with roscovitine in podocytes increased apoptosis. CDK2 knockdown also reduced expression of PDK1, an activator of the cell survival kinase Akt, and reduced Akt phosphorylation. This suggests that CDK2 regulates the activity of the cell survival pathway via PDK1. Furthermore, PDK1 knockdown reduced the expression of CDK2 suggesting a regulatory loop between CDK2 and PDK1. Collectively, our data show that CDK2 protects podocytes from apoptosis and that reduced expression of CDK2 associates with the development of DN. Preventing downregulation of CDK2 by blocking the TLR pathway with GIT27 may provide a means to prevent podocyte apoptosis and progression of DN.Peer reviewe

A framework for mathematics curricula in engineering education: a report of the mathematics working group.

This document adapts the competence concept to the mathematical education of engineers and explains and illustrates it by giving examples. It also provides information for specifying the extent to which a competency should be acquired. It does not prescribe a particular level of progress for competence acquisition in engineering education. There are many different engineering branches and many different job profiles with various needs for mathematical competencies; consequently it is not appropriate to specify a fixed profile. The competence framework serves as an analytical framework for thinking about the current state in one’s own institution and also as a design framework for specifying the intended profile. A sketch of an example profile for a practice-oriented study course in mechanical engineering is given in the document. This document retains the list of content-related learning outcomes (slightly modified) that formed the ‘kernel’ of the previous curriculum document. These are still important because lecturers teaching application subjects want to be sure that students have at least an ‘initial familiarity’ with certain mathematical concepts and procedures which they need in their application modelling. In order to offer helpful orientation for designing teaching processes, teaching and learning environments and approaches are outlined which help students to obtain the competencies to an adequate degree. It is clear that such competencies cannot be obtained by simply listening to lectures, so adequate forms of active involvement of students need to be included. Moreover, in a competence-based approach the mathematical education must be integrated in the surrounding engineering study course to really achieve the ability to use mathematics in engineering contexts. The document presents several forms of how this integration can be realized. This integration is essential to the development of competencies and will require close co-operation between mathematics academics and their engineering counterparts. Finally, since assessment procedures determine to a great extent the behaviour of students, it is extremely important to address competency acquisition in assessment schemes. Ideas for doing this are also outlined in the document. The main purpose of this document is to provide orientation for those who set up concrete mathematics curricula for their specific engineering programme, and for lecturers who think about learning and assessment arrangements for achieving the intended level of competence acquisition. It also serves as a framework for the group’s future work and discussions