An architecture for certification-aware service discovery

Service-orientation is an emerging paradigm for building complex systems based on loosely coupled components, deployed and consumed over the network. Despite the original intent of the paradigm, its current instantiations are limited to a single trust domain (e.g., a single organization). Also, some of the key promises of service-orientation - such as the dynamic orchestration of externally provided software services, using runtime service discovery and deployment - are still unachieved. One of the main reasons for this is the trust gap that normally arises when software services, offered by previously unknown providers, are to be selected at run-time, without any human intervention. To close this gap, the concept of machine-readable security certificates (called asserts) has been recently introduced, which paves the way to automated processing about security properties of services. Similarly to current security certification schemes, the assessment of the security properties of a service is delegated to an independent third party (certification authority), who issues a corresponding assert, bound to the service. In this paper, we propose an architecture, which exploits the assert concept to realise a certification-aware service discovery framework. The architecture supports the discovery of single services based on certified security properties (in additional to the usual functional properties), as well as the dynamic synthesis of service compositions, that satisfy the given security properties. The architecture is extensible, thus allowing for a range of domain specific matchmaking components, to cover dimensions related to, e.g., performance, cost and other non-functional characteristics

Counteracting effects operating on Src homology 2 domain-containing protein-tyrosine phosphatase 2 (SHP2) function drive selection of the recurrent Y62D and Y63C substitutions in Noonan syndrome

Activating mutations in PTPN11 cause Noonan syndrome, the most common nonchromosomal disorder affecting development and growth. PTPN11 encodes SHP2, an Src homology 2 (SH2) domain-containing protein-tyrosine phosphatase that positively modulates RAS function. Here, we characterized functionally all possible amino acid substitutions arising from single-base changes affecting codons 62 and 63 to explore the molecular mechanisms lying behind the largely invariant occurrence of the Y62D and Y63C substitutions recurring in Noonan syndrome. We provide structural and biochemical data indicating that the autoinhibitory interaction between the N-SH2 and protein-tyrosine phosphatase (PTP) domains is perturbed in both mutants as a result of an extensive structural rearrangement of the N-SH2 domain. Most mutations affecting Tyr(63) exerted an unpredicted disrupting effect on the structure of the N-SH2 phosphopeptide-binding cleft mediating the interaction of SHP2 with signaling partners. Among all the amino acid changes affecting that codon, the disease-causing mutation was the only substitution that perturbed the stability of the inactive conformation of SHP2 without severely impairing proper phosphopeptide binding of N-SH2. On the other hand, the disruptive effect of the Y62D change on the autoinhibited conformation of the protein was balanced, in part, by less efficient binding properties of the mutant. Overall, our data demonstrate that the selection-by-function mechanism acting as driving force for PTPN11 mutations affecting codons 62 and 63 implies balancing of counteracting effects operating on the allosteric control of the function of SHP2

Peak expiratory flow rate shows a gender-specific association with vitamin D deficiency

Context: To our knowledge, no previous studies examined the longitudinal relationship between vitamin D status and pulmonary function in a population-based sample of older persons. Objective: Our objective was to examine the cross-sectional as well as the longitudinal relationship between vitamin D status and peak expiratory flow rate (PEFR) in a representative sample of the Dutch older population. Design, Setting, and Participants: Participants included men and women in the Longitudinal Aging Study Amsterdam, an ongoing cohort study in older people. Main Outcome Measure: PEFR was measured using the mini-Wright peak flow meter. Results: Men with serum 25-hydroxyvitamin D (25-OHD) levels below 10 ng/ml (25 nmol/liter) had a significantly lower PEFR in the cross-sectional analyses, and men with serum 25-OHD levels below 20 ng/ml (50 nmol/liter) had a significantly lower PEFR in the longitudinal analyses as compared with men with serum 25-OHD levels above 30 ng/ml (75 nmol/liter) (cross-sectional: β = -47.0, P = 0.01 for serum 25-OHD<10 ng/ml; longitudinal: β = -45.0, P<0.01 for serum 25-OHD<10 ng/ml; and β = -20.2, P = 0.03 for serum 25-OHD = 10-20 ng/ml in the fully adjusted models). Physical performance (β = -32.5, P = 0.08 for serum 25-OHD<10 ng/ml) and grip strength (β = -40.0, P = 0.03 for serum 25-OHD <10 ng/ml) partly mediated the cross-sectional associations but not the longitudinal associations. In women, statistically significant associations between 25-OHD and PEFR were observed in the cross-sectional analyses after adjustment for age and season of blood collection but not in the fully adjusted models or in the longitudinal analyses. Conclusions: A strong relationship between serum 25-OHD and PEFR was observed in older men, both in the cross-sectional as well as longitudinal analyses, but not in older women. The association in men could partly be explained by physical performance and muscle strength. Copyright © 2012 by The Endocrine Society

Automated Mapping of Vulnerability Advisories onto their Fix Commits in Open Source Repositories

The lack of comprehensive sources of accurate vulnerability data represents a critical obstacle to studying and understanding software vulnerabilities (and their corrections). In this paper, we present an approach that combines heuristics stemming from practical experience and machine-learning (ML) - specifically, natural language processing (NLP) - to address this problem. Our method consists of three phases. First, an advisory record containing key information about a vulnerability is extracted from an advisory (expressed in natural language). Second, using heuristics, a subset of candidate fix commits is obtained from the source code repository of the affected project by filtering out commits that are known to be irrelevant for the task at hand. Finally, for each such candidate commit, our method builds a numerical feature vector reflecting the characteristics of the commit that are relevant to predicting its match with the advisory at hand. The feature vectors are then exploited for building a final ranked list of candidate fixing commits. The score attributed by the ML model to each feature is kept visible to the users, allowing them to interpret of the predictions. We evaluated our approach using a prototype implementation named Prospector on a manually curated data set that comprises 2,391 known fix commits corresponding to 1,248 public vulnerability advisories. When considering the top-10 commits in the ranked results, our implementation could successfully identify at least one fix commit for up to 84.03% of the vulnerabilities (with a fix commit on the first position for 65.06% of the vulnerabilities). In conclusion, our method reduces considerably the effort needed to search OSS repositories for the commits that fix known vulnerabilities

Src family kinases as therapeutic targets in advanced solid tumors. What we have learned so far

Src is the prototypal member of Src Family tyrosine Kinases (SFKs), a large non-receptor kinase class that controls multiple signaling pathways in animal cells. SFKs activation is necessary for the mitogenic signal from many growth factors, but also for the acquisition of migratory and invasive phenotype. Indeed, oncogenic activation of SFKs has been demonstrated to play an important role in solid cancers; promoting tumor growth and formation of distant metastases. Several drugs targeting SFKs have been developed and tested in preclinical models and many of them have successfully reached clinical use in hematologic cancers. Although in solid tumors SFKs inhibitors have consistently confirmed their ability in blocking cancer cell progression in several experimental models; their utilization in clinical trials has unveiled unexpected complications against an effective utilization in patients. In this review, we summarize basic molecular mechanisms involving SFKs in cancer spreading and metastasization; and discuss preclinical and clinical data highlighting the main challenges for their future application as therapeutic targets in solid cancer progression