Miracle-dz/UniFAR-FTUs huggingface dataset:
000306-4379 ( 94 ) 00020-4 Invited Project ReviewTHE COMFORT AUTOMATIC TUNING PROJECT yGerhard

| This paper reports on results and experiences from the COMFORT automatic tuning project. The objective of the project has been to investigate architectural principles of self-tuning database and transaction processing systems, and to develop self-tuning methods for speciic performance tuning problems. A particular concern of the project has been to cope with workload dynamics and workload heterogeneity in multiuser systems. As a general guideline, an adaptive feedback control approach has been adopted, where observations of the current load characteristics are used to predict performance trends and to drive the dynamic adjustment of tuning parameters. As examples of these general principles, the paper discusses adaptive approaches to two speciic tuning problems and the developed solutions. First, we present a self-tuning load control method that copes with overload caused by excessive lock connicts that may occur during load surges. This connict-driven load control method adapts the multiprogramming level of the system to the evolving load characteristics dynamically and automatically. Secondly, we discuss the self-tuning LRU-K database buuering method, which makes intelligent buuering decisions by dynamically tracking the access frequency of pages, thus coping well with evolving access patterns. We discuss the rationale of these two self-tuning methods in great detail, and we present comprehensive performance evaluation experiments for both synthetic and trace-driven workloads.
PI3K-AKT-mTOR-Signaling and beyond: the Complex Network in Gastroenteropancreatic Neuroendocrine Neoplasms

Gastroenteropancreatic neuroendocrine neoplasms are heterogeneous in their clinical behavior and require therapies specially tailored according to staging, grading, origin and expression of peptide receptors. Despite extensive scientific efforts, the therapy options are still not satisfactory. The main reasons are due to the lack of a broad mechanistic knowledge, an insufficient classification of specific diagnostic sub-groups, and predictive markers. GEP-NEN tumors evade early diagnosis because of slow asymptomatic growth behavior and are frequently not detected until metastasized. How signaling networks contribute to tumor progression and how these networks interact remains unclear in large parts. In this review we summarize the knowledge on the growth factor responsive non-angiogenetic pathways in sporadic GEP-NENs, highlight promising mechanistic research approaches, and describe important therapy targets.
Understanding the experience of patients with chronic obstructive pulmonary disease who access specialist palliative care: A qualitative study

Background: Palliative care for people with life-limiting non-malignant disease is increasingly prioritised. People with end-stage chronic obstructive pulmonary disease are among a key group of non-cancer patients likely to benefit from specialist palliative care, but it remains uncertain whether the needs of this group are met by existing services. Aim: To evaluate the experiences of patients with chronic obstructive pulmonary disease who accessed specialist palliative care. Design: Data from semi-structured interviews were analysed using a hermeneutic phenomenological approach. Setting/participants: Eight patients accessing specialist palliative care within one city in North West England. Results: Perceived benefits of specialist palliative care included reduced frequency of hospital admission, improved physical and psychological symptoms, reduced social isolation and a broadened physical environment. Participants were mainly aware of their poor prognosis, but discussion of referral to palliative care sometimes caused distress owing to the historical associations between dying and hospice care. Following engagement with services, participants’ perceptions changed: palliative care was associated with social inclusion and opportunities to engage in reciprocal and altruistic social action. Negative associations were replaced by uncertainty and anxiety about the prospect of discharge. Conclusions: Much within existing services works well for people with chronic obstructive pulmonary disease, but opportunities to enhance palliative care for this underserved group remain. Future research might focus on prospectively evaluating the impact of key components of palliative care on core patient-centred outcomes. Additionally, work must be done to raise awareness of the benefits of specialist palliative care for non-cancer patients, as negative associations can form a barrier to access.
Conserved N-Terminal Negative Charges Support Optimally Efficient N-type Inactivation of Kv1 Channels

N-type inactivation is produced by the binding of a potassium channel's N-terminus within the open pore, blocking conductance. Previous studies have found that introduction of negative charges into N-terminal inactivation domains disrupts inactivation; however, the Aplysia AKv1 N-type inactivation domain contains two negatively charged residues, E2 and E9. Rather than being unusual, sequence analysis shows that this N-terminal motif is highly conserved among Kv1 sequences across many phyla. Conservation analysis shows some tolerance at position 9 for other charged residues, like D9 and K9, whereas position 2 is highly conserved as E2. To examine the functional importance of these residues, site directed mutagenesis was performed and effects on inactivation were recorded by two electrode voltage clamp in Xenopus oocytes. We find that inclusion of charged residues at positions 2 and 9 prevents interactions with non-polar sites along the inactivation pathway increasing the efficiency of pore block. In addition, E2 appears to have additional specific electrostatic interactions that stabilize the inactivated state likely explaining its high level of conservation. One possible explanation for E2's unique importance, consistent with our data, is that E2 interacts electrostatically with a positive charge on the N-terminal amino group to stabilize the inactivation domain at the block site deep within the pore. Simple electrostatic modeling suggests that due to the non-polar environment in the pore in the blocked state, even a 1 Å larger separation between these charges, produced by the E2D substitution, would be sufficient to explain the 65× reduced affinity of the E2D N-terminus for the pore. Finally, our studies support a multi-step, multi-site N-type inactivation model where the N-terminus interacts deep within the pore in an extended like structure placing the most N-terminal residues 35% of the way across the electric field in the pore blocked state.
Planning end effector trajectories for a serially linked, floating-base robot with changing support polygon

We present a framework for the planning of end effector trajectories for serially linked robots with a non-fixed, also known as floating, support base. The FBSR (Floating Base, Serial Reach) planning algorithm extends the capabilities of serially linked, floating-base robots by planning to maintain stability while transferring modules from a weight-bearing role to the active, manipulator-like portion of the robot as needed to extend the robot's reach. During planning, we employ several methods such as random restarts and dynamic weighting of the optimization cost function sub-goals to reliably provide stable solution trajectories. We experimentally validate this algorithm on a 16 degree of freedom snake robot, and demonstrate the successful execution of generated plans.
Optimal topology of multi-agent systems with two leaders: a zero-sum game perspective

It is typical to assume that there is no conflict of interest among leaders. Under such assumption, it is known that, for a multi-agent system with two leaders, if the followers' interaction subgraph is undirected and connected, then followers will converge to a convex combination of two leaders' states with linear consensus protocol. In this paper, we introduce the conflict between leaders: by choosing k followers to connect with, every leader attempts all followers converge to himself closer than that of the other. By using graph theory and matrix theory, we formulate this conflict as a standard two-player zero-sum game and give some properties about it. It is noteworthy that the interaction graph here is generated from the conflict between leaders. Interestingly, we find that to find the optimal topology of the system is equivalent to solve a Nash equilibrium. Especially for the case of choosing one connected follower, the necessary and sufficient condition for an interaction graph to be the optimal one is given. Moreover, if followers' interaction graph is a circulant graph or a graph with a center node, then the system's optimal topology is obtained. Simulation examples are provided to validate the effectiveness of the theoretical results.
Self‐reported Competency Ratings of Graduates of a Problem‐based Medical Curriculum

Purpose To study the self-reports of professional competencies by graduates of a problem-based medical curriculum. Method All graduates from a medical school and a faculty of health sciences with a problem-based curriculum were sent a questionnaire asking them to compare their own performances in 19 domains with those of colleagues trained at schools with conventional curricula. Results Overall, alumni of the medical school rated themselves as better than colleagues who were trained at schools with conventional curricula for cooperation skills, problem-solving skills, skills relevant to running meetings, and the ability to work independently. There was no difference for possession of general academic knowledge and writing reports or articles. The self-reported ratings of better competencies were maintained after correcting the data for self-overestimation. Conclusion The problem-based medical curriculum appears to contribute to the development of professional competencies. Further study is needed, however, to control for the effect of selection bias and respondents' emotional commitment to their alma mater.
Impaired aortic elastic properties in normotensive patients with psoriasis

Abstract Objective. Psoriasis is a chronic inflammatory disease affecting approximately 1.5–3% of the general population. Several studies have demonstrated an association between psoriasis and atherosclerosis. The aim of this study is the investigate relation between aortic wall stiffness and duration and severity of the disease in patients with psoriasis. Method. The study population included 58 patients with psoriasis (27 men, mean age = 36.3 ± 10.6 years, and mean disease duration = 9.8 ± 6.7 years) and 36 healthy control subjects (17 men, and mean age = 40.0 ± 11.1 years). Aortic stiffness index, aortic strain and distensibility, were calculated from the aortic systolic and diastolic diameters measured by echocardiography and blood pressure obtained by sphygmomanometer. Cardiac functions were determined by using echocardiography, consisting of standard two-dimensional and conventional Doppler. Results. The conventional echocardiographic parameters were similar between patients and controls. There were significant differences between the control and the patient groups in aortic stiffness index (2.7 ± 1.0 vs 2.0 ± 0.8, p = 0.001), aortic strain (10.3±3.3% vs 14.2±4.5%, p <0.001) and distensibility (4.2 ± 1.7 × 10−6 cm2/dyn vs 5.8 ± 2.0 × 10−6 cm2/dyn, p=0.001). There were significant negative correlations between the disease duration and distensibility (r = −0.54, p < 0.001), aortic strain (r=−0.41, p=0.001), aortic diameter change (r = −0.35, p = 0.007) and positive correlations between the disease duration and aortic stiffness index (r = 0.58, p < 0.001). Also heart rate and high-sensitive C reactive protein were significantly higher in psoriasis patients than in healthy controls (80.0 ± 11.8 beats/min vs 72.4 ± 8.8 beats/min, p = 0.001 and 9.7 ± 21.4 mg/l vs 3.7 ± 2.1 mg/l, p = 0.04, respectively). Conclusion. Aortic stiffness measurements were found abnormal in patients with psoriasis. We have also demonstrated that there were significant correlations between aortic stiffness parameters and disease duration. This study suggests that aortic stiffness measurement could be used for assessment of cardiovascular risk in psoriasis patients, and that only continuous long-term disease control may be helpful in reducing the cardiovascular risk associated with psoriasis.
Single Versus Repeat Courses of Antenatal Steroids to Improve Neonatal Outcomes: Risks and Benefits

Recent additions to the literature provide evidence supporting the use of repeat courses of antenatal steroids. Both human and animal studies offer evidence that repeat courses of corticosteroids improve neonatal pulmonary outcomes, especially for the infants delivered at earlier gestational ages. Although there is also evidence to suggest altered neuronal maturation and intrauterine growth restriction in animals treated with repeat steroids, randomized controlled studies in humans have shown that birth weight reduction was only seen in those infants treated with 4 or more courses of corticosteroids. In addition, the reduction in neonatal birth weight and head circumference seen after multiple courses of antenatal corticosteroids normalizes by the time of hospital discharge. Studies are ongoing to investigate the 24-month postdelivery physical and neurodevelopmental outcomes in infants exposed to repeat courses of antenatal corticosteroids. Although there is evidence demonstrating the safety of a single repeat, or “rescue”, dose of antenatal corticosteroids, this must be tempered against the adverse effects seen after multiple courses of weekly repeat steroids. Randomized controlled trials are needed to determine the optimal number of courses of antenatal steroids to reduce the frequency of neonatal respiratory distress syndrome (RDS) without adversely affecting other neonatal outcomes. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader should be able to recall that although there are studies that support repeated courses of antenatal steroids, 24-month postdelivery and neurodevelopmental studies in infants exposed to repeated antenatal steroids are ongoing and also state that a “rescue”, single repeat dose, seven days after the first dose, appears prudent in only those mothers who are imminent of delivery prior to 32 weeks’ gestation.
Phase measuring deflectometry: a new approach to measure specular free-form surfaces

We present a new method to measure specular free-form surfaces within seconds. We call the measuring principle `Phase Measuring Deflectometry' (PMD). With a stereo based enhancement of PMD we are able to measure both the height and the slope of the surface. The basic principle is to project sinusoidal fringe patterns onto a screen located remotely from the surface under test and to observe the fringe patterns reflected via the surface. Any slope variations of the surface lead to distortions of the patterns. Using well-known phase-shift algorithms, we can precisely measure these distortions and thus calculate the surface normal in each pixel. We will deduce the method's diffraction-theoretical limits and explain how to reach them. A major challenge is the necessary calibration. We solved this task by combining various photogrammetric methods. We reach a repeatability of the local slope down to a few arc seconds and an absolute accuracy of a few arc minutes. One important field of application is the measurement of the local curvature of progressive eyeglass lenses. We will present experimental results and compare these results with the theoretical limits.
Association of pre-onset cannabis, alcohol, and tobacco use with age at onset of prodrome and age at onset of psychosis in first-episode patients.

OBJECTIVE Several reports suggest that cannabis use is associated with an earlier age at onset of psychosis, although not all studies have operationalized cannabis use as occurring prior to onset of symptoms. This study addressed whether pre-onset cannabis use, alcohol use, and tobacco use are associated with an earlier age at onset of prodromal and psychotic symptoms. Effects of the progression of frequency of use were examined through time-dependent covariates in survival analyses. METHOD First-episode patients (N=109) hospitalized in three public-sector inpatient psychiatric units underwent in-depth cross-sectional retrospective assessments. Prior substance use and ages at onset of prodromal and psychotic symptoms were determined by standardized methods, and analyses were conducted using Cox regression modeling. RESULTS Whereas classifying participants according to maximum frequency of use prior to onset (none, ever, weekly, or daily) revealed no significant effects of cannabis or tobacco use on risk of onset, analysis of change in frequency of use prior to onset indicated that progression to daily cannabis and tobacco use was associated with an increased risk of onset of psychotic symptoms. Similar or even stronger effects were observed when onset of illness or prodromal symptoms was the outcome. A gender-by-daily-cannabis-use interaction was observed; progression to daily use resulted in a much larger increased relative risk of onset of psychosis in females than in males. CONCLUSIONS Pre-onset cannabis use may hasten the onset of psychotic as well as prodromal symptoms. Age at onset is a key prognostic factor in schizophrenia, and discovering modifiable predictors of age at onset is crucial.
Association of Common Variants in eNOS Gene with Primary Open Angle Glaucoma: A Meta-Analysis

Purpose. To clarify the association of endothelial nitric oxide synthase (eNOS) polymorphisms and primary open angle glaucoma (POAG). Methods. After a systematic literature search in the MEDLINE, EMBASE, and ISI Web of Science databases, all relevant studies evaluating the association between the polymorphisms (rs2070744 and rs1799983) of eNOS gene and POAG were screened and included. The pooled odds ratios (ORs) and the 95% confidence interval (CI) of each single-nucleotide polymorphism (SNP) in five genetic models were estimated using fixed-effect model if I 2 < 50% in the test for heterogeneity; otherwise the random-effects model was used. Results. Thirty-one records were obtained, with five being suitable for meta-analysis. The overall results showed that both TT genotype in rs2070744 and GG genotype in rs1799983 are associated with decreased risk of POAG susceptibility. Stratified analysis based on ethnicity showed that the association of rs2070744 with POAG remained only in Caucasians. Results of subgroup analysis by sex indicated association between both polymorphisms and POAG in female group, but not in male group. Conclusions. TT genotype and/or T-allele in rs2070744, as well as GG genotype and/or G-allele in rs1799983, was associated with decreased risk for POAG overall and in female group.
Semantic Frame Identification with Distributed Word Representations

We present a novel technique for semantic frame identiﬁcation using distributed representations of predicates and their syntactic context; this technique leverages automatic syntactic parses and a generic set of word embeddings. Given labeled data annotated with frame-semantic parses, we learn a model that projects the set of word representations for the syntactic context around a predicate to a low dimensional representation. The latter is used for semantic frame identiﬁcation; with a standard argument identiﬁcation method inspired by prior work, we achieve state-of-the-art results on FrameNet-style frame-semantic analysis. Additionally, we report strong results on PropBank-style semantic role labeling in comparison to prior work.
Architectural Decision Making for Service-Based Platform Integration: A Qualitative Multi-Method Study

Nowadays the software architecture of a system is often seen as a set of design decisions providing the rationale for the system design. When designing a software architecture multiple levels of design decisions need to be considered. For example, the service-based integration of heterogeneous platforms and the development of applications on top of those integration services requires high-level as well as technology-, domain-, and application-dependent architectural decisions. In this context, we performed a series of qualitative studies following a multi-method approach. First, we conducted a systematic literature review from which we derived a pattern language for platform integration featuring 40 patterns, as well as a pattern-based architectural decision model. Then, we performed interviews with 9 platform experts from 3 companies for revising the architectural knowledge captured by the pattern language and the decision model. Finally, we participated in a case study and observed the decision-making process to validate the results further. Our observations resulted in 1) a qualitatively validated, pattern-based architectural decision model and 2) a generalized model of the different levels and stages of architectural decision making for service-based platform integration.
Mechanical Properties of Advanced Pore Morphology Foam Elements

Advanced pore morphology (APM) foam, consisting of sphere-like metallic foam elements, exhibits some particular mechanical properties with unique application possibilities. The article presents the results of experimental and computational testing of APM foam elements to determine their mechanical behavior under quasi-static and dynamic compressive loading conditions. Additionally, an infrared thermal imaging camera has been used during experimental testing. Evaluated mechanical properties give better insight into the behavior of single APM foam elements under different types of loading and provide a good base for further studies of the topology and morphology influence on the global behavior of composite structures, based on APM foam elements.
Dissecting a Role for Melanopsin in Behavioural Light Aversion Reveals a Response Independent of Conventional Photoreception

Melanopsin photoreception plays a vital role in irradiance detection for non-image forming responses to light. However, little is known about the involvement of melanopsin in emotional processing of luminance. When confronted with a gradient in light, organisms exhibit spatial movements relative to this stimulus. In rodents, behavioural light aversion (BLA) is a well-documented but poorly understood phenomenon during which animals attribute salience to light and remove themselves from it. Here, using genetically modified mice and an open field behavioural paradigm, we investigate the role of melanopsin in BLA. While wildtype (WT), melanopsin knockout (Opn4−/−) and rd/rd cl (melanopsin only (MO)) mice all exhibit BLA, our novel methodology reveals that isolated melanopsin photoreception produces a slow, potentiating response to light. In order to control for the involvement of pupillary constriction in BLA we eliminated this variable with topical atropine application. This manipulation enhanced BLA in WT and MO mice, but most remarkably, revealed light aversion in triple knockout (TKO) mice, lacking three elements deemed essential for conventional photoreception (Opn4−/− Gnat1−/− Cnga3−/−). Using a number of complementary strategies, we determined this response to be generated at the level of the retina. Our findings have significant implications for the understanding of how melanopsin signalling may modulate aversive responses to light in mice and humans. In addition, we also reveal a clear potential for light perception in TKO mice.
The influence of litter size and favourable conditions on mortality and weaning weights in rats

Litters of 12 pups produced the optimum results for survival (P<0·005) and for weaning weights (P<0·05) when compared with litters of 8 and 10 pups. This number is similar to the normal litter size and normal number of teats in rats. In our study, the normal litter size was X = 12·5. Our results were obtained under favourable conditions without disturbing the animals and facilitating access to food and water for the mothers and pups.