On integrating a proprietary and a commercial architecture for optimal BIST performances in SoCs

This paper presents the integration of a proprietary hierarchical and distributed test access mechanism called HD2BIST and a BIST insertion commercial tool. The paper briefly describes the architecture and the features of both the environments and it presents some experimental results obtained on an industrial So

Modeling biological complexity using Biology System Description Language (BiSDL)

The Nets-within-Nets formalism (NWN) allows to model complex biological systems expressing hierarchy, encapsulation, selective communication, spatiality, quantitative mechanisms, and stochasticity. To make NWN usable by life science researchers as well as systems biologists, we introduce a new human-readable description language able to express these same NWN model properties, at different levels of abstraction. BiSDL (Biology Systems Description Language) is derived from the VHDL specification, a standard description language for hardware systems. In this paper we chose a simple signaling pathway example to show how BiSDL enables modeling complex biological systems by separating the behavioral model from the architectural details

A Computational Study to Identify TP53 and SREBF2 as Regulation Mediators of miR-214 in Melanoma Progression

In the complex world of post-transcriptional regulation, miR-214 is known to control in vitro tumor cell move- ment and survival to anoikis, as well as in vivo malignant cell extravasation from blood vessels and lung metastasis formation. miR-214 has also been found to be highly expressed in human melanomas, and to directly and indirectly regulate several genes involved in tumor progression and in the establishment of dis- tant metastases (Penna et al., 2011). In this work, we exploit a computational pipeline integrating data from multiple online data repositories to identify the presence of transcriptional or post-transcriptional regulatory modules involving miR-214 and a set of 73 previously identified miR-214 regulated genes. We identified 27 putative regulatory modules involving miR-214, NFKB1, SREBPF2, miR-33a and 9 out of the 73 miR-214 modulated genes (ALCAM, POSTN, TFAP2A, ADAM9, NCAM1, SEMA3A, PVRL2, JAG1, EGFR1). As a pre- liminary experimental validation we focused on 9 out of the 27 identified regulatory modules that involve two main players, miR-33a and SREBF2. The results confirm the importance of the predictions obtained with the presented computational approach

HD2BIST: a hierarchical framework for BIST scheduling, data patterns delivering and diagnosis in SoCs

Proposes HD2BIST, a complete hierarchical framework for BIST scheduling, data patterns delivering, and diagnosis of a complex system including embedded cores with different test requirements as full scan cores, partial scan cores, or BIST-ready cores. The main goal of HD2BIST is to maximize and simplify the reuse of the built-in test architectures, giving the chip designer the highest flexibility in planning the overall SoC test strategy. HD2BIST defines a test access method able to provide a direct “virtual” access to each core of the system, and can be conceptually considered as a powerful complement to the P1500 standard, whose main target is to make the test interface of each core independent from the vendo

Endocrine activities of cortistatin-14 and its interaction with GHRH and ghrelin in humans.

Cortistatin (CST)-14, a neuropeptide with high homology with somatostatin (SS)-14, binds all sst subtypes but, unlike SS, also ghrelin's receptor. In six normal adults, we studied the effects of CST-14 or SS-14 administration (2.0 micro g/kg/h iv) on: 1) GH and insulin secretion; 2) the GH response to GHRH (1.0 microg/kg i.v.); and 3) the GH, prolactin (PRL), ACTH, cortisol, insulin, and glucose responses to ghrelin (1.0 microg/kg i.v.). CST-14 inhibited GH and insulin secretion (P < 0.01) to the same extent of SS-14. The GH response to GHRH was similarly inhibited (P < 0.01) by either CST-14 or SS-14. Ghrelin released more GH than GHRH (P < 0.01); these responses were similarly inhibited (P < 0.05) by either CST-14 or SS-14, that made ghrelin-induced GH rise similar to that after GHRH alone. Neither CST-14 nor SS-14 modified PRL, ACTH, or cortisol responses to ghrelin. The inhibitory effect of CST-14 and SS-14 on insulin was unaffected by ghrelin that, in turn, reduced insulin secretion per se (P < 0.01). Ghrelin increased glucose levels (P < 0.05); CST-14 and SS-14 did not modify this effect. Thus, CST-14 inhibits both basal and stimulated GH secretion in humans to the same extent of SS-14. The GH-releasing activity of ghrelin seems partially resistant to CST-14 as well as SS-14. CST-14 and SS-14 do not affect PRL and ACTH secretion but, like ghrelin, inhibit insulin secretion; the ghrelin-induced inhibition is not additive with that of CST-14 or SS-14, suggesting a common mechanism of action on beta cell secretion

Cortistatin-17 and -14 exert the same endocrine activities as somatostatin in humans

Cortistatin (CST) is a neuropeptide, which binds with high affinity all somatostatin (SS) receptor subtypes and shows high structural homology with SS itself. A receptor specific for CST only, i.e., not recognized by SS, has been recently described in agreement with data reporting that not all CST actions are shared by SS. Interestingly, CST but not SS also binds ghrelin receptor (GHS-R1a) in vitro, suggesting a potential interplay between CST and ghrelin system. The aim of this study was to investigate in humans the endocrine and metabolic activities of human CST-17 in comparison with rat CST-14 that has previously been shown to exert the same endocrine actions of SS in healthy volunteers. To this aim, in six healthy male volunteers (age [median, 3rd-97th centiles]: 28.5; 23.6-34.3 years; Body Mass Index: 23.5; 21.0-25.1 kg/m2), we studied the effects of human CST-17 (2.0 μg/kg/h iv over 120 min), rat CST-14 (2.0 μg/kg/h iv over 120 min) and SS-14 (2.0 μg/kg/h iv over 120 min) on: (a) spontaneous GH, ACTH, PRL, cortisol, insulin and glucose levels; (b) the GH responses to GHRH (1.0 μg/kg iv at 0 min); (c) the GH, PRL, ACTH, cortisol, insulin and glucose responses to ghrelin (1.0 μg/kg iv at 0 min). CST-17 inhibited (p<0.01) basal GH secretion to the same extent of CST-14 and SS-14. Spontaneous PRL, ACTH and cortisol secretion were not significantly modified by CST-17, CST-14 or SS-14. CST-17 as well as CST-14 and SS-14 also inhibited (p<0.05) spontaneous insulin secretion to a similar extent. None of these peptides modified glucose levels. The GH response to GHRH was inhibited to the same extent by CST-17 (p<0.01), CST-14 (p<0.01) and SS-14 (p<0.05). The ghrelin-induced GH response was higher than that elicited by GHRH (p<0.01) and inhibited by CST-17 (p<0.05) as well as by CST-14 (p<0.05) and SS-14 (p<0.01). The PRL, ACTH and cortisol responses to ghrelin were unaffected by CST-17, CST-14 or SS-14. On the other hand, the inhibitory effect of ghrelin on insulin levels was abolished by CST-17, CST-14 or SS-14 (p<0.05) that, in turn, did not modify the ghrelin-induced increase in glucose levels. In conclusion, this study demonstrates that human CST-17 and rat CST-14 exert the same endocrine activities of SS in humans. The endocrine actions of human and rat CST therefore are likely to reflect activation of classical SS receptors

Metabolic effects of overnight continuous infusion of unacylated ghrelin in humans

Objective: To clarify the metabolic effects of an overnight i.v. infusion of unacylated ghrelin (UAG) in humans. UAG exerts relevant metabolic actions, likely mediated by a still unknown ghrelin receptor subtype, including effects on β-cell viability and function, insulin secretion and sensitivity, and glucose and lipid metabolism. Design: We studied the effects of a 16-h infusion (from 2100 to 1300 h) of UAG (1.0 μg/kg per h) or saline in eight normal subjects (age (mean±S.E.M.), 29.6±2.4 years; body mass index (BMI), 22.4±1.7 kg/m2), who were served, at 2100 and 0800 h respectively, with isocaloric balanced dinner and breakfast. Glucose, insulin, and free fatty acid (FFA) levels were measured every 20 min. Results: In comparison with saline, UAG induced significant (P<0.05) changes in glucose, insulin, and FFA profiles. UAG infusion decreased glucose area under the curve (AUC) values by 10% (UAG0-960 min: 79.0±1.7×10 3 mg/dl per min vs saline0-960 min: 87.5±3. 8×103 mg/dl per min) and the AUC at night by 14% (UAG 180-660 min: 28.4±0.5×103 mg/dl per min vs saline180-660 min: 33.2±1.1×103 mg/dl per min). The overall insulin AUC was not significantly modified by UAG infusion; however, insulin AUC observed after meals was significantly increased under the exposure to UAG with respect to saline at either dinner or breakfast. The FFA AUC values were decreased by 52% under the exposure to UAG in comparison with saline (UAG0-960 min: 0.3±0.02×103 mEq/l per min vs saline0-960 min: 0.6±0.05×103 mEq/l per min). Conclusions: Exposure to the i.v. administration of UAG improves glucose metabolism and inhibits lipolysis in healthy volunteers. Thus, in contrast to the diabetogenic action of AG, UAG displays hypoglycemic properties

Tanner-Whitehouse skeletal ages in male youth soccer players : TW2 or TW3?

BACKGROUND: The Tanner-Whitehouse radius-ulna-short bone protocol (TW2 RUS) for the assessment of skeletal age (SA) is widely used to estimate the biological (skeletal) maturity status of children and adolescents. The scale for converting TW RUS ratings to an SA has been revised (TW3 RUS) and has implications for studies of youth athletes in age-group sports. OBJECTIVES: The aim of this study was to compare TW2 and TW3 RUS SAs in an international sample of male youth soccer players and to compare distributions of players by maturity status defined by each SA protocol. METHODS: SA assessments with the TW RUS method were collated for 1831 male soccer players aged 11-17 years from eight countries. RUS scores were converted to TW2 and TW3 SAs using the appropriate tables. SAs were related to chronological age (CA) in individual athletes and compared by CA groups. The difference of SA minus CA with TW2 SA and with TW3 SA was used to classify players as late, average, or early maturing with each method. Concordance of maturity classifications was evaluated with Cohen's Kappa coefficients. RESULTS: For the same RUS score, TW3 SAs were systematically and substantially reduced compared with TW2 SAs; mean differences by CA group ranged from - 0.97 to - 1.16 years. Kappa coefficients indicated at best fair concordance of TW2 and TW3 maturity classifications. Across the age range, 42% of players classified as average with TW2 SA were classified as late with TW3 SA, and 64% of players classified as early with TW2 SA were classified as average with TW3 SA. CONCLUSION: TW3 SAs were systematically lower than corresponding TW2 SAs in male youth soccer players. The differences between scales have major implications for the classification of players by maturity status, which is central to some talent development programs