Autonomic Performance-Aware Resource Management in Dynamic IT Service Infrastructures

Model-based techniques are a powerful approach to engineering autonomic and self-adaptive systems. This thesis presents a model-based approach for proactive and autonomic performance-aware resource management in dynamic IT infrastructures. Core of the approach is an architecture-level modeling language to describe performance and resource management related aspects in such environments. With this approach, it is possible to autonomically find suitable system configurations at the model level

Automated extraction of architecture-level performance models of distributed component-based systems

Abstract—Modern enterprise applications have to satisfy in-creasingly stringent Quality-of-Service requirements. To ensure that a system meets its performance requirements, the ability to predict its performance under different configurations and workloads is essential. Architecture-level performance models describe performance-relevant aspects of software architectures and execution environments allowing to evaluate different usage profiles as well as system deployment and configuration options. However, building performance models manually requires a lot of time and effort. In this paper, we present a novel automated method for the extraction of architecture-level performance models of distributed component-based systems, based on mon-itoring data collected at run-time. The method is validated in a case study with the industry-standard SPECjEnterprise2010 Enterprise Java benchmark, a representative software system executed in a realistic environment. The obtained performance predictions match the measurements on the real system within an error margin of mostly 10-20 percent. I

Identification of a novel SERPINA-1 mutation causing alpha-1 antitrypsin deficiency in a patient with severe bronchiectasis and pulmonary embolism

Deficiency in the serine protease inhibitor, alpha-1 antitrypsin (AAT), is known to cause emphysema and liver disease. Other manifestations, including airway disease or skin disorders, have also been described. A 44-year-old woman presented to our emergency department with dyspnea and respiratory insufficiency. She had never smoked, and had been diagnosed with COPD 9 years earlier. Three months previously, she had suffered a pulmonary embolism. Chest computed tomography scan revealed severe cystic bronchiectasis with destruction of the lung parenchyma. The sweat test was normal and there was no evidence of the cystic fibrosis transmembrane conductance regulator (CFTR) mutation. Capillary zone electrophoresis showed a decrease of alpha-1 globin band and AAT levels were below the quantification limit (<25 mg/dL). No S or Z mutation was identified, but sequencing analysis found a homozygous cytosine and adenine (CA) insertion in exon 2 of the SERPINA-1 gene, probably leading to a dysfunctional protein (PI Null/Null). This mutation has not been previously identified. The atypical presentation of the patient, with severe cystic bronchiectasis, highlights AAT deficiency as a differential diagnosis in bronchiectasis. Further, awareness should be raised regarding a possible increased risk of thromboembolism associated with AAT deficiency

Physical Exercise Training versus Relaxation in Allogeneic stem cell transplantation (PETRA Study) – Rationale and design of a randomized trial to evaluate a yearlong exercise intervention on overall survival and side-effects after allogeneic stem cell transplantation

Background: Allogeneic stem cell transplantation (allo-HCT) is associated with high treatment-related mortality and innumerable physical and psychosocial complications and side-effects, such as high fatigue levels, loss of physical performance, infections, graft-versus-host disease (GvHD) and distress. This leads to a reduced quality of life, not only during and after transplantation, but also in the long term. Exercise interventions have been shown to be beneficial in allo-HCT patients. However, to date, no study has focused on long-term effects and survival. Previous exercise studies used ‘usual care’ control groups, leaving it unclear to what extent the observed effects are based on the physical effects of exercise itself, or rather on psychosocial factors such as personal attention. Furthermore, effects of exercise on and severity of GvHD have not been examined so far. We therefore aim to investigate the effects and biological mechanisms of exercise on side-effects, complications and survival in allo-HCT patients during and after transplantation. Methods/design: The PETRA study is a randomized, controlled intervention trial investigating the effects of a yearlong partly supervised mixed exercise intervention (endurance and resistance exercises, 3–5 times per week) in 256 patients during and after allogeneic stem cell transplantation. Patients in the control group perform progressive muscle relaxation training (Jacobsen method) with the same frequency. Main inclusion criterion is planned allo-HCT. Main exclusion criteria are increased fracture risk, no walking capability or severe cardiorespiratory problems. Primary endpoint is overall survival after two years; secondary endpoints are non-relapse mortality, median survival, patient reported outcomes including cancer related fatigue and quality of life, physical performance, body composition, haematological/immunological reconstitution, inflammatory parameters, severity of complications and side-effects (e.g. GvHD and infections), and cognitive capacity. Discussion: The PETRA study will contribute to a better understanding of the physiological and psychological effects of exercise training and their biological mechanisms in cancer patients after allo-HCT. The ultimate goal is the implementation of optimized intervention programs to reduce side-effects and improve quality of life and potentially prognosis after allogeneic stem cell transplantation. Trial registration: ClinicalTrials.gov Identifier: NCT0137439

Post-release Movement Behaviour and Survival of Kulan Reintroduced to the Steppes and Deserts of Central Kazakhstan

Asiatic wild ass, or kulan (Equus hemionus kulan) were once a key species of the Eurasian steppes and deserts. In Kazakhstan they went extinct by the 1930s. Early reintroductions have reestablished the species in two protected areas, but the species has reclaimed <1% of their former range and remained absent from central Kazakhstan. To initiate restoration in this vast region, we captured and transported a first group of nine wild kulan to a large pre-release enclosure in the Torgai region in 2017, and two more in 2019. We used direct observations and post-release movement data of four kulan equipped with GPS-Iridium collars to document their adaptation process in a vast novel habitat without conspecifics. For comparison with movements in the source populations, we additionally equipped two kulan in Altyn Emel National Park and six in Barsa Kelmes State Nature Reserve. The nine transported kulan formed a cohesive group with very high movement correlation in the enclosure. After release, the group initially stayed tightly together but started to break up by mid-May and all kulan travelled independently by mid-August. With 48,680–136,953 km2, the 95% Autocorrelated Kernel Density Estimation ranges of the reintroduced kulan were huge and about 10–100 times larger than those in the source populations. The reintroduced mares never reconnected, there was no evidence of successful reproduction, and two of the four collared mares were killed by poachers and one died of natural causes. At least one stallion survived in the wild, but the fate of the other uncollared animals remains unclear. We speculate that the fission-fusion dynamics and low movement correlation of kulan societies and the need for migratory movements harbours the risk that animals released into a novel environment loose contact with each other. This risk is likely enhanced in steppe habitats where movement constraining factors are absent. Further kulan reintroductions to the steppes and deserts of central Kazakhstan should aim to release larger groups and build up the free-ranging population quickly to reach a critical mass, increasing the chance of kulan encountering conspecifics to successfully breed and increase their chances of survival.publishedVersio

Leukocyte coping capacity as a complementary stress metric in migrating birds

Corticosterone (Cort) is involved in multiple physiological processes during bird migration, complicating its interpretation in a stress context. We investigated whether the leukocyte coping capacity (LCC) provides useful complementary information on the stress response in migratory Garden Warblers (Sylvia borin) and how it relates to Cort and energetic condition. Contrary to Cort levels, LCC significantly decreased, implying high-stress levels and a diminished capacity to recover after a stressful event. The absence of significant effects of body conditions on the stress parameters shows no simple relationship between these traits and highlights the need for additional stress metrics to measure stress in life-history contexts

Structural basis for selective targeting of Rac subfamily GTPases by a bacterial effector protein

Ras-homology (Rho) family GTPases are conserved molecular switches controlling fundamental cellular activities in eukaryotic cells. As such, they are targeted by numerous bacterial toxins and effector proteins, which have been intensively investigated regarding their biochemical activities and discrete target spectra; however, molecular mechanisms of target selectivity have remained elusive. Here, we report a bacterial effector protein that targets all four Rac subfamily members of Rho family GTPases, but none of the closely related Cdc42 or RhoA subfamilies. This exquisite target selectivity of the FIC domain AMP-transferase Bep1 from Bartonella rochalimae is based on electrostatic interactions with a subfamily-specific pair of residues in the nucleotide-binding motif and the Rho insert helix. Residue substitutions at the identified positions in Cdc42 facilitate modification by Bep1, while corresponding Cdc42-like substitutions in Rac1 greatly diminish modification. Our study establishes a structural paradigm for target selectivity towards Rac subfamily GTPases and provides a highly selective tool for their functional analysis

Functional ADA Polymorphism Increases Sleep Depth and Reduces Vigilant Attention in Humans

Homeostatically regulated slow-wave oscillations in non-rapid eye movement (REM) sleep may reflect synaptic changes across the sleep-wake continuum and the restorative function of sleep. The nonsynonymous c.22G>A polymorphism (rs73598374) of adenosine deaminase (ADA) reduces the conversion of adenosine to inosine and predicts baseline differences in sleep slow-wave oscillations. We hypothesized that this polymorphism affects cognitive functions, and investigated whether it modulates electroencephalogram (EEG), behavioral, subjective, and biochemical responses to sleep deprivation. Attention, learning, memory, and executive functioning were quantified in healthy adults. Right-handed carriers of the variant allele (G/A genotype, n = 29) performed worse on the d2 attention task than G/G homozygotes (n = 191). To test whether this difference reflects elevated homeostatic sleep pressure, sleep and sleep EEG before and after sleep deprivation were studied in 2 prospectively matched groups of G/A and G/G genotype subjects. Deep sleep and EEG 0.75- to 1.5-Hz oscillations in non-REM sleep were significantly higher in G/A than in G/G genotype. Moreover, attention and vigor were reduced, whereas waking EEG alpha activity (8.5-12 Hz), sleepiness, fatigue, and α-amylase in saliva were enhanced. These convergent data demonstrate that genetic reduction of ADA activity elevates sleep pressure and plays a key role in sleep and waking quality in human

In vivo evidence of remote neural degeneration in the lumbar enlargement after cervical injury

OBJECTIVE To characterize remote secondary neurodegeneration of spinal tracts and neurons below a cervical spinal cord injury (SCI) and its relation to the severity of injury, the integrity of efferent and afferent pathways, and clinical impairment. METHODS A comprehensive high-resolution MRI protocol was acquired in 17 traumatic cervical SCI patients and 14 controls at 3T. At the cervical lesion, a sagittal T2-weighted scan provided information on the width of preserved midsagittal tissue bridges. In the lumbar enlargement, high-resolution T2*-weighted and diffusion-weighted scans were used to calculate tissue-specific cross-sectional areas and diffusion indices, respectively. Regression analyses determined associations between MRI readouts and the electrophysiologic and clinical measures. RESULTS At the cervical injury level, preserved midsagittal tissue bridges were present in the majority of patients. In the lumbar enlargement, neurodegeneration-in terms of macrostructural and microstructural MRI changes-was evident in the white matter and ventral and dorsal horns. Patients with thinner midsagittal tissue bridges had smaller ventral horn area, higher radial diffusivity in the gray matter, smaller motor evoked potential amplitude from the lower extremities, and lower motor score. In addition, smaller width of midsagittal tissue bridges was also associated with smaller tibialis sensory evoked potential amplitude and lower light-touch score. CONCLUSIONS This study shows extensive tissue-specific cord pathology in infralesional spinal networks following cervical SCI, its magnitude relating to lesion severity, electrophysiologic integrity, and clinical impairment of the lower extremity. The clinical eloquence of remote neurodegenerative changes speaks to the application of neuroimaging biomarkers in diagnostic workup and planning of clinical trials