Simultaneous observation of high order multiple quantum coherences at ultralow magnetic fields

We present a method for the simultaneous observation of heteronuclear multi-quantum coherences (up to the 3rd order), which give an additional degree of freedom for ultralow magnetic field (ULF) MR experiments, where the chemical shift is negligible. The nonequilibrium spin state is generated by Signal Amplification By Reversible Exchange (SABRE) and detected at ULF with SQUID-based NMR. We compare the results obtained by the heteronuclei Correlated SpectroscopY (COSY) with a Flip Angle FOurier Series (FAFOS) method. COSY allows a quantitative analysis of homo- and heteronuclei quantum coherences

A comparison framework and review of service brokerage solutions for cloud architectures

Cloud service brokerage has been identified as a key concern for future cloud technology development and research. We compare service brokerage solutions. A range of specific concerns like architecture, programming and quality will be looked at. We apply a 2-pronged classification and comparison framework.We will identify challenges and wider research objectives based on an identification of cloud broker architecture concerns and technical requirements for service brokerage solutions. We will discuss complex cloud architecture concerns such as commoditisation and federation of integrated, vertical cloud stacks

Pattern Views: Concept and Tooling for Interconnected Pattern Languages

Patterns describe proven solutions for recurring problems. Typically, patterns in a particular domain are interrelated and organized in pattern languages. As real-world problems often require patterns of multiple domains, different pattern languages have to be considered to address these problems. However, cross-domain knowledge about how patterns of different languages relate to each other is either hidden in individual pattern descriptions or not documented at all. This makes it difficult to identify relevant patterns across pattern languages. Therefore, we introduce a concept and tooling that enables to capture patterns and their relations across pattern languages for a particular problem context

Orthogonal variability modeling to support multi-cloud application configuration

Cloud service providers benefit from a vast majority of customers due to variability and making profit from commonalities between the cloud services that they provide. Recently, application configuration dimensions has been increased dramatically due to multi-tenant, multi-device and multi-cloud paradigm. This challenges the configuration and customization of cloud-based software that are typically offered as a service due to the intrinsic variability. In this paper, we present a model-driven approach based on variability models originating from the software product line community to handle such multi-dimensional variability in the cloud. We exploit orthogonal variability models to systematically manage and create tenant-specific configuration and customizations. We also demonstrate how such variability models can be utilized to take into account the already deployed application parts to enable harmonized deployments for new tenants in a multi-cloud setting. The approach considers application functional and non-functional requirements to provide a set of valid multi-cloud configurations. We illustrate our approach through a case study

Cloud migration patterns: a multi-cloud service architecture perspective

Many organizations migrate their on-premise software systems to the cloud. However, current coarse-grained cloud migration solutions have made a transparent migration of on-premise applications to the cloud a difficult, sometimes trial-and-error based endeavor. This paper suggests a catalogue of fine-grained service-based cloud architecture migration patterns that target multi-cloud settings and are specified with architectural notations. The proposed migration patterns are based on empirical evi-dence from a number of migration projects, best practices for cloud architectures and a systematic literature review of existing research. The pattern catalogue allows an or-ganization to (1) select appropriate architecture migration patterns based on their ob-jectives, (2) compose them to define a migration plan, and (3) extend them based on the identification of new patterns in new contexts

Towards virtual machine energy-aware cost prediction in clouds

Pricing mechanisms employed by different service providers significantly influence the role of cloud computing within the IT industry. With the increasing cost of electricity, Cloud providers consider power consumption as one of the major cost factors to be maintained within their infrastructures. Consequently, modelling a new pricing mechanism that allow Cloud providers to determine the potential cost of resource usage and power consumption has attracted the attention of many researchers. Furthermore, predicting the future cost of Cloud services can help the service providers to offer the suitable services to the customers that meet their requirements. This paper introduces an Energy-Aware Cost Prediction Framework to estimate the total cost of Virtual Machines (VMs) by considering the resource usage and power consumption. The VMs’ workload is firstly predicted based on an Autoregressive Integrated Moving Average (ARIMA) model. The power consumption is then predicted using regression models. The comparison between the predicted and actual results obtained in a real Cloud testbed shows that this framework is capable of predicting the workload, power consumption and total cost for different VMs with good prediction accuracy, e.g. with 0.06 absolute percentage error for the predicted total cost of the VM

Tbet Expression in Regulatory T Cells Is Required to Initiate Th1-Mediated Colitis

In normal conditions gut homeostasis is maintained by the suppressive activity of regulatory T cells (Tregs), characterized by the expression of the transcription factor FoxP3. In human inflammatory bowel disease, which is believed to be the consequence of the loss of tolerance toward antigens normally contained in the gut lumen, Tregs have been found to be increased and functionally active, thus pointing against their possible role in the pathogenesis of this immune-mediated disease. Though, in inflammatory conditions, Tregs have been shown to upregulate the T helper (Th) type 1-related transcription factor Tbet and to express the pro-inflammatory cytokine IFN\u3b3, thus suggesting that at a certain point of the inflammatory process, Tregs might contribute to inflammation rather than suppress it. Starting from the observation that Tregs isolated from the lamina propria of active but not inactive IBD patients or uninflamed controls express Tbet and IFN\u3b3, we investigated the functional role of Th1-like Tregs in the dextran sulfate model of colitis. As observed in human IBD, Th1-like Tregs were upregulated in the inflamed lamina propria of treated mice and the expression of Tbet and IFN\u3b3 in Tregs preceded the accumulation of conventional Th1 cells. By using a Treg-specific Tbet conditional knockout, we demonstrated that Tbet expression in Tregs is required for the development of colitis. Indeed, Tbet knockout mice developed milder colitis and showed an impaired Th1 immune response. In these mice not only the Tbet deficient Tregs but also the Tbet proficient conventional T cells showed reduced IFN\u3b3 expression. However, Tbet deficiency did not affect the Tregs suppressive capacity in vitro and in vivo in the adoptive transfer model of colitis. In conclusion here we show that Tbet expression by Tregs sustains the early phase of the Th1-mediated inflammatory response in the gut

Achievement of Remission Endpoints with Secukinumab Over 3 Years in Active Ankylosing Spondylitis: Pooled Analysis of Two Phase 3 Studies

INTRODUCTION: Clinical remission in patients with ankylosing spondylitis (AS) has been determined using composite indices such as the AS Disease Activity Score inactive disease (ASDAS-ID), Assessment of SpondyloArthritis international Society criteria partial remission (ASAS-PR), and low Bath AS Disease Activity Index (BASDAI) scores. The objective of this exploratory analysis was to evaluate the proportion of secukinumab-treated patients with AS achieving remission defined based on the ASDAS-ID (score < 1.3), ASAS-PR or BASDAI score ≤  2. METHODS: The analysis pooled data from the MEASURE 1 and 2 studies over 3 years. The proportion of patients who achieved ASDAS-ID, ASAS-PR, or BASDAI ≤ 2 with secukinumab was compared with placebo at week 16; results for secukinumab-treated patients were summarized through week 156. Sustainability of each criterion was assessed from week 16 to 156 using shift analysis. The association between each of these criteria and specific patient-reported outcomes (PROs), such as health-related quality of life, function, fatigue, and work impairment, was also explored. RESULTS: At week 16, a higher proportion of secukinumab-treated patients versus placebo achieved ASDAS-ID (17.6 vs. 3.5%), ASAS-PR (15.4 vs. 4.1%), or BASDAI ≤ 2 (22.3 vs. 6.4%) criteria (all P < 0.0001), which were sustained through 156 weeks. Shift analysis showed that the majority of secukinumab-treated patients achieving remission at week 16 maintained their status at week 156 (ASDAS-ID, 57.1%; ASAS-PR, 68.0% and BASDAI ≤ 2, 74.3%). Remission was also associated with improved PROs over 156 weeks. CONCLUSIONS: Secukinumab-treated patients maintained ASDAS-ID, ASAS-PR, or BASDAI ≤ 2 from week 16 up to 3 years. Patients who achieved at least one of the three responses/states, reported improvement in PROs, which suggests an association of clinical remission/ID with PROs in patients with active AS. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01358175, NCT01863732, and NCT01649375

Secukinumab efficacy on resolution of enthesitis in psoriatic arthritis: pooled analysis of two phase 3 studies

Background Enthesitis is one of the psoriatic arthritis (PsA) domains. Patients with enthesitis are associated with worse outcomes than those without enthesitis. The effect of secukinumab on the resolution of enthesitis in patients with PsA was explored using pooled data from the FUTURE 2 and 3 studies. Method Assessments of enthesitis through week 104 used the Leeds Enthesitis Index. These post hoc analyses included resolution of enthesitis count (EC = 0), median time to first resolution of enthesitis (Kaplan-Meϊer estimate), and shift analysis (as observed) of baseline EC (1, 2, or 3–6) to full resolution (FR), stable (similar or reduction of EC), or worse (EC > baseline). Efficacy outcomes (ACR, PASI, HAQ-DI, SF-36 PCS, and DAS28-CRP) were assessed in patients with or without baseline enthesitis. Results are reported for secukinumab 300 and 150 mg in the overall population and by prior TNFi treatment. Results A total of 65% (466/712) of patients had baseline enthesitis. In the overall population, FR was achieved as early as week 16 in 65% (300 mg) and 56% (150 mg) versus 44% (placebo) patients, with further improvements to 91% (300 mg) and 88% (150 mg) at week 104. The majority (89%) of patients without enthesitis at baseline maintained this status at week 104. Median days to resolution of EC were shorter with secukinumab 300 and 150 mg versus placebo (57 and 85 vs 167 days, respectively). In patients with EC of 1 or 2, shift analysis from baseline to week 24 showed that more patients achieved FR with secukinumab 300 mg and 150 mg versus placebo, whereas no difference between secukinumab and placebo was shown in the more severe patients with EC of 3–6. Increases in proportions of patients with FR were observed with secukinumab irrespective of the severity of EC from baseline to week 104. Improvements in efficacy outcomes were similar in patients with or without enthesitis treated with secukinumab 300 mg. Conclusion Secukinumab provided early and sustained resolution of enthesitis in patients with PsA over 2 years. Secukinumab 300 mg provided higher resolution than 150 mg in patients with more severe baseline EC and showed similar overall efficacy in patients with or without enthesitis. Trial registration FUTURE 2: ClinicalTrials.gov, NCT01752634 (date of study registration: December 19, 2012), and EudraCT, 2012-004439-22 (date of study registration: December 12, 2012) FUTURE 3: ClinicalTrials.gov, NCT01989468 (date of study registration: November 21, 2013), and EudraCT, 2013-004002-25 (date of study registration: December 17, 2013