Nature-Inspired Interconnects for Self-Assembled Large-Scale Network-on-Chip Designs

Future nano-scale electronics built up from an Avogadro number of components needs efficient, highly scalable, and robust means of communication in order to be competitive with traditional silicon approaches. In recent years, the Networks-on-Chip (NoC) paradigm emerged as a promising solution to interconnect challenges in silicon-based electronics. Current NoC architectures are either highly regular or fully customized, both of which represent implausible assumptions for emerging bottom-up self-assembled molecular electronics that are generally assumed to have a high degree of irregularity and imperfection. Here, we pragmatically and experimentally investigate important design trade-offs and properties of an irregular, abstract, yet physically plausible 3D small-world interconnect fabric that is inspired by modern network-on-chip paradigms. We vary the framework's key parameters, such as the connectivity, the number of switch nodes, the distribution of long- versus short-range connections, and measure the network's relevant communication characteristics. We further explore the robustness against link failures and the ability and efficiency to solve a simple toy problem, the synchronization task. The results confirm that (1) computation in irregular assemblies is a promising and disruptive computing paradigm for self-assembled nano-scale electronics and (2) that 3D small-world interconnect fabrics with a power-law decaying distribution of shortcut lengths are physically plausible and have major advantages over local 2D and 3D regular topologies

p53-Mediated downregulation of H ferritin promoter transcriptional efficiency via NF-Y

The tumor suppressor protein p53 triggers many of the cellular responses to DNA damage by regulating the transcription of a series of downstream target genes. p53 acts on the promoter of the target genes by interacting with the trimeric transcription factor NF-Y. H ferritin promoter activity is tightly dependent on a multiprotein complex called Bbf; on this complex NF-Y plays a major role. The aim of this work was to study the modulation of H ferritin expression levels by p53. CAT reporter assays indicate that: (i) p53 overexpression strongly downregulates the transcriptional efficiency driven by an H ferritin promoter construct containing only the NF-Y recognition sequence and that the phenomenon is reverted by p53 siRNA; (ii) the p53 C-terminal region is sufficient to elicitate this regulation and that a correct C-terminal acetylation is also required. The H ferritin promoter displays no p53-binding sites; chromatin immunoprecipitation assays indicate that p53 is recruited on this promoter by NF-Y. The p53–NF-Y interaction does not alter the NF-Y DNA-binding ability as indicated by electrophoretic mobility shift assay (EMSA) analysis. These results demonstrate that the gene coding for the H ferritin protein belongs to the family of p53-regulated genes, therefore adding a new level of complexity to the regulation of the H ferritin transcription and delineate a role for this protein in a series of cellular events triggered by p53 activation

New experimental test of Bell inequalities by the use of a non-maximally entangled photon state

We report on the first realisation of a test of Bell inequalities using non-maximally entangled states. It is based on the superposition of type I parametric down conversion produced in two different non-linear crystals pumped by the same laser, but with different polarisations. We discuss the advantages and the possible developments of this configuration.Comment: accepted for publicatio

About entanglement properties of kaons and tests of hidden variables models

In this letter we discuss entanglement properties of neutral kaons systems and their use for testing local realism. In particular we show that, as previous proposals, also a scheme recently suggested for performing a test of hidden variable theories against standard quantum mechanics cannot be conclusive

Local Realistic Theories and Quantum Mechanics for the two-neutral-kaon system

The predictions of local realistic theories for the observables concerning the evolution of a $K^0\bar{K}^0$ quantum entangled pair (created in the decay of the $\phi$-meson) are discussed. It is shown, in agreement with Bell's theorem, that the most general local hidden-variable model fails in reproducing the whole set of quantum-mechanical joint probabilities. We achieve these conclusion by employing two different approaches. In a first one the local realistic observables are deduced from the most general premises concerning locality and realism, and Bell-like inequalities are not employed. The other approach makes use of Bell's inequalities. Within the former scheme, under particular conditions for the detection times, the discrepancy between quantum mechanics and local realism for the time-dependent asymmetry turns out to be not less than 20%. The same incompatibility can be made evident by means of a Bell-type test by employing both Wigner's and (once properly normalized probabilities are used) Clauser-Holt-Shimony-Holt's inequalities. Because of the relatively low experimental accuracy, the data obtained by the CPLEAR collaboration for the asymmetry parameter do not allow for a decisive test of local realism. Such a test, both with and without the use of Bell's inequalities, should be feasible in the future at the Frascati $\Phi$-factory.Comment: 36 pages, 4 figure

Bell State Preparation using Pulsed Non-Degenerate Two-Photon Entanglement

We report a novel Bell state preparation experiment. High-purity Bell states are prepared by using femtosecond pulse pumped \emph{nondegenerate} collinear spontaneous parametric down-conversion. The use of femtosecond pump pulse {\em does not} result in reduction of quantum interference visibility in our scheme in which post-selection of amplitudes and other traditional mechanisms, such as, using thin nonlinear crystals or narrow-band spectral filters are not used. Another distinct feature of this scheme is that the pump, the signal, and the idler wavelengths are all distinguishable, which is very useful for quantum communications.Comment: 4 pages, submitted to PR

MSH3 protein expression and nodal status in MLH1-deficient colorectal cancers.

View the MathML source: Colorectal tumors manifesting high-frequency microsatellite instability (MSI-H) develop genetically as a consequence of mutations in genes harboring repetitive DNA sequences. The activin type 2 receptor (ACVR2), possessing 2 polyadenine coding sequences, was identified as a mutational target, but it is not clear if expression is abrogated. Here, we analyzed MSI-H colorectal cancers for ACVR2 mutation and expression to assess if biallelic inactivation occurs. View the MathML source: All 54 MSI-H colon cancers and 20 random microsatellite stable (MSS) tumors from a population-based cohort of 503 patients were analyzed for mutations in 2 A8 tracts (exon 3 and 10) of ACVR2 and the A10 tract of transforming growth factor \u3b2 receptor 2 (TGFBR2). Additionally, we sequenced exon 10 of ACVR2 in select cancers. ACVR2 expression was determined by immunohistochemistry using an antibody targeting an epitope beyond the predicted truncated protein. View the MathML source: Forty-five of 54 MSI-H cancers (83%) showed mutation (A8 to A7) in the polyadenine tract of exon 10 compared with no MSS tumors. Of tumors with mutant ACVR2, 62% lacked protein expression but all MSS and MSI-H tumors with wild-type ACVR2 expressed protein. We found no evidence of loss of heterozygosity at the ACVR2 locus in MSS tumors. Comparatively, 69% of MSI-H cancers had frameshift mutation in TGFBR2. View the MathML source:ACVR2 mutations are highly frequent in MSI-H colon cancers and in most cases cause loss of ACVR2 expression, indicating biallelic inactivation of the gene. Loss of activin signaling through mutation of ACVR2, similar to observations with TGFBR2, may be important in the genesis of MSI-H colorectal cancer

Effectiveness of dolutegravir-based regimens as either first-line or switch antiretroviral therapy: data from the Icona cohort

Introduction: Concerns about dolutegravir (DTG) tolerability in the real-life setting have recently arisen. We aimed to estimate the risk of treatment discontinuation and virological failure of DTG-based regimens from a large cohort of HIV-infected individuals. Methods: We performed a multicentre, observational study including all antiretroviral therapy (ART)-naïve and virologically suppressed treatment-experienced (TE) patients from the Icona (Italian Cohort Naïve Antiretrovirals) cohort who started, for the first time, a DTG-based regimen from January 2015 to December 2017. We estimated the cumulative risk of DTG discontinuation regardless of the reason and for toxicity, and of virological failure using Kaplan–Meier curves. We used Cox regression model to investigate predictors of DTG discontinuation. Results: About 1679 individuals (932 ART-naïve, 747 TE) were included. The one- and two-year probabilities (95% CI) of DTG discontinuation were 6.7% (4.9 to 8.4) and 11.5% (8.7 to 14.3) for ART-naïve and 6.6% (4.6 to 8.6) and 7.6% (5.4 to 9.8) for TE subjects. In both ART-naïve and TE patients, discontinuations of DTG were mainly driven by toxicity with an estimated risk (95% CI) of 4.0% (2.6 to 5.4) and 2.5% (1.3 to 3.6) by one year and 5.6% (3.8 to 7.5) and 4.0% (2.4 to 5.6) by two years respectively. Neuropsychiatric events were the main reason for stopping DTG in both ART-naïve (2.1%) and TE (1.7%) patients. In ART-naïve, a concomitant AIDS diagnosis predicted the risk of discontinuing DTG for any reason (adjusted relative hazard (aRH) = 3.38, p = 0.001), whereas starting DTG in combination with abacavir (ABC) was associated with a higher risk of discontinuing because of toxicity (aRH = 3.30, p = 0.009). TE patients starting a DTG-based dual therapy compared to a triple therapy had a lower risk of discontinuation for any reason (adjusted hazard ratio (aHR) = 2.50, p = 0.037 for ABC-based triple-therapies, aHR = 3.56, p = 0.012 for tenofovir-based) and for toxicity (aHR = 5.26, p = 0.030 for ABC-based, aHR = 6.60, p = 0.024 for tenofovir-based). The one- and two-year probabilities (95% CI) of virological failure were 1.2% (0.3 to 2.0) and 4.6% (2.7 to 6.5) in the ART naïve group and 2.2% (1.0 to 3.3) and 2.9% (1.5 to 4.3) in the TE group. Conclusions: In this large cohort, DTG showed excellent efficacy and optimal tolerability both as first-line and switching ART. The low risk of treatment-limiting toxicities in ART-naïve as well as in treated individuals reassures on the use of DTG in everyday clinical practice