The future of universal access? merging computing, design and engineering

Technology is advancing at a fast pace while the shape and nature of computers continues to evolve, with tablets and smartphones illustrating the move away from the traditional notion of a laptop or desktop computer. Similarly, networking and sensing technologies are also developing rapidly and innovatively. All of these technologies have the potential to enfranchise users with severe functional impairments to be better able to control and interact with other people and their surroundings. However, this is only possible if those designing the novel systems based upon these new technologies consider such users’ needs explicitly. This paper examines how these technological advances can be employed to support these users in the near future. The paper further discusses issues such as the need for security as systems evolve from control of specific environments to a potential model for interaction in any location

Role and regulation of ACC deaminase gene in Sinorhizobium meliloti: Is it a symbiotic, rhizospheric or endophytic gene?

Plant-associated bacteria exhibit a number of different strategies and specific genes allow bacteria to communicate and metabolically interact with plant tissues. Among the genes found in the genomes of plant-associated bacteria, the gene encoding the enzyme 1-aminocyclopropane-1-carboxylate (ACC) deaminase (acdS) is one of the most diffused. This gene is supposed to be involved in the cleaving of plant-produced ACC, the precursor of the plant stress-hormone ethylene toning down the plant response to infection. However, few reports are present on the actual role in rhizobia, one of the most investigated groups of plant-associated bacteria. In particular, still unclear is the origin and the role of acdS in symbiotic competitiveness and on the selective benefit it may confer to plant symbiotic rhizobia. Here we present a phylogenetic and functional analysis of acdS orthologs in the rhizobium model-species Sinorhizobium meliloti. Results showed that acdS orthologs present in S. meliloti pangenome have polyphyletic origin and likely spread through horizontal gene transfer, mediated by mobile genetic elements. When acdS ortholog from AK83 strain was cloned and assayed in S. meliloti 1021 (lacking acdS), no modulation of plant ethylene levels was detected, as well as no increase in fitness for nodule occupancy was found in the acdS-derivative strain compared to the parental one. Surprisingly, AcdS was shown to confer the ability to utilize formamide and some dipeptides as sole nitrogen source. Finally, acdS was shown to be negatively regulated by a putative leucine-responsive regulator (LrpL) located upstream to acdS sequence (acdR). acdS expression was induced by root exudates of both legumes and non-leguminous plants. We conclude that acdS in S. meliloti is not directly related to symbiotic interaction, but it could likely be involved in the rhizospheric colonization or in the endophytic behavior

Experimental Engineering of Arbitrary Qudit States with Discrete-Time Quantum Walks

The capability to generate and manipulate quantum states in high-dimensional Hilbert spaces is a crucial step for the development of quantum technologies, from quantum communication to quantum computation. One-dimensional quantum walk dynamics represents a valid tool in the task of engineering arbitrary quantum states. Here we affirm such potential in a linear-optics platform that realizes discrete-time quantum walks in the orbital angular momentum degree of freedom of photons. Different classes of relevant qudit states in a six-dimensional space are prepared and measured, confirming the feasibility of the protocol. Our results represent a further investigation of quantum walk dynamics in photonics platforms, paving the way for the use of such a quantum state-engineering toolbox for a large range of applications

Risk factors for pre-clinical atherosclerosis in adolescents with type 1 diabetes

Aims: To assess whether, besides "traditional" risk factors, overall oxidative stress, oxidized lipoproteins, and glycemic variability are associated with early macro-vascular damage in type 1 diabetes (T1D). Methods: In 267 children/adolescents with T1D (130 girls, age 9.1-23.0 years) we evaluated: derivatives of reactive oxygen metabolites [d-ROMs], serum total antioxidant capacity [TAC] and oxidized LDL-cholesterol [oxLDL]; markers of early vascular damage (Lipoprotein-associated phospholipase A2 [Lp-PLA2], z-score of carotid intima-media thickness [z-cIMT] and carotid-femoral pulse wave velocity [z-PWV]); CGM metrics of four weeks preceding the visit, central systolic/diastolic blood pressures (cSBP/cDBP), and HbA1c, z-score of BP (z-SBP/z-DBP) and circulating lipids longitudinally collected since T1D onset.. Three general linear models were built with z-cIMT, z-PWV adjusted for current cDBP, and Lp-PLA2 as independent variables. Results: The z-cIMT was associated with male gender (B = 0.491, η2 = 0.029, p = 0.005), cSBP (B = 0.023, η2 = 0.026, p = 0.008) and oxLDL (B = 0.022, η2 = 0.022, p = 0.014). The z-PWV was associated with diabetes duration (B = 0.054, η2 = 0.024, p = 0.016), daily insulin dose (B = 0.52, η2 = 0.018, p = 0.045), longitudinal z-SBP (B = 0.18, η2 = 0.018, p = 0.045) and dROMs (B = 0.003, η2 = 0.037, p = 0.004). Lp-PLA2 was associated with age (B = 0.221, η2 = 0.079, p = 3*10-6), oxLDL (B = 0.081, η2 = 0.050, p = 2*10-4), longitudinal LDL-cholesterol (B = 0.031, η2 = 0.043, p = 0.001) and male gender (B = -1.62, η2 = 0.10, p = 1.3*107). Conclusions: Oxidative stress, male gender, insulin dose, diabetes duration and longitudinal lipids and blood pressure, contributed to the variance of early vascular damage in young patients with T1D

High-performance versatile setup for simultaneous Brillouin-Raman micro-spectroscopy

This is the author accepted manuscript. The final version is available from American Physical Society via the DOI in this record.Brillouin and Raman scattering spectroscopy are established techniques for the nondestructive contactless and label-free readout of mechanical, chemical and structural properties of condensed matter. Brillouin-Raman investigations currently require separate measurements and a site-matched approach to obtain complementary information from a sample. Here we demonstrate a new concept of fully scanning multimodal micro-spectroscopy for simultaneous detection of Brillouin and Raman light scattering in an exceptionally wide spectral range, from fractions of GHz to hundreds of THz. It yields an unprecedented 150 dB contrast, which is especially important for the analysis of opaque or turbid media such as biomedical samples, and spatial resolution on a sub-cellular scale. We report the first applications of this new multimodal method to a range of systems, from a single cell to the fast reaction kinetics of a curing process, and the mechano-chemical mapping of highly scattering biological samples.S. Corezzi acknowledges financial support from MIUR-PRIN (Project No. 2012J8X57P). S. Caponi acknowledges support from PAT (Provincia Autonoma di Trento) (GP/PAT/2012) “Grandi Progetti 2012” Project “MaDEleNA.” P. S., A. M., M. P. acknowledge financial support from Centro Nazionale Trapianti (Project: “Studio di cellule per uso clinico umano, con particolare riferimento a modelli cellulari (liposomi) e linee cellulari in interazione con crioconservanti e con materiali biocompatibili”). L. C. and S. Caponi acknowledge financial support from Consiglio Nazionale delle Ricerche-Istituto Officina dei Materiali. F. P. acnowledges support from the UK Engineering and Physical Sciences Research Council (Grant No. EP/M028739/1 (F. P.)). The authors acknowledge Jacopo Scarponi for valuable help in setting up the hardware and software system for simultaneous Raman and BLS measurements

Early intrathecal infusion of everolimus restores cognitive function and mood in a murine model of Alzheimer's disease

The discovery that mammalian target of rapamycin (mTOR) inhibition increases lifespan in mice and restores/delays many aging phenotypes has led to the identification of a novel potential therapeutic target for the treatment of Alzheimer's disease (AD). Among mTOR inhibitors, everolimus, which has been developed to improve the pharmacokinetic characteristics of rapamycin, has been extensively profiled in preclinical and clinical studies as anticancer and immunosuppressive agent, but no information is available about its potential effects on neurodegenerative disorders. Using a reliable mouse model of AD (3 × Tg-AD mice), we explored whether short-term treatment with everolimus injected directly into the brain by osmotic pumps was able to modify AD-like pathology with low impact on peripheral organs. We first established in non-transgenic mice the stability of everolimus at 37 °C in comparison with rapamycin and, then, evaluated its pharmacokinetics and pharmacodynamics profiles through either a single peripheral (i.p.) or central (i.c.v.) route of administration. Finally, 6-month-old (symptomatic phase) 3 × Tg-AD mice were treated with continuous infusion of either vehicle or everolimus (0.167 μg/μl/day, i.c.v.) using the osmotic pumps. Four weeks after the beginning of infusion, we tested our hypothesis following an integrated approach, including behavioral (tests for cognitive and depressive-like alterations), biochemical and immunohistochemical analyses. Everolimus (i) showed higher stability than rapamycin at 37 °C, (ii) poorly crossed the blood-brain barrier after i.p. injection, (iii) was slowly metabolized in the brain due to a longer t 1/2 in the brain compared to blood, and (iv) was more effective in the CNS when administered centrally compared to a peripheral route. Moreover, the everolimus-induced mTOR inhibition reduced human APP/Aβ and human tau levels and improved cognitive function and depressive-like phenotype in the 3 × Tg-AD mice. The intrathecal infusion of everolimus may be effective to treat early stages of AD-pathology through a short and cyclic administration regimen, with short-term outcomes and a low impact on peripheral organs

SNPs array karyotyping reveals a novel recurrent 20p13 amplification in primary myelofibrosis.

The molecular pathogenesis of primary mielofibrosis (PMF) is still largely unknown. Recently, single-nucleotide polymorphism arrays (SNP-A) allowed for genome-wide profiling of copy-number alterations and acquired uniparental disomy (aUPD) at high-resolution. In this study we analyzed 20 PMF patients using the Genome-Wide Human SNP Array 6.0 in order to identify novel recurrent genomic abnormalities. We observed a complex karyotype in all cases, detecting all the previously reported lesions (del(5q), del(20q), del(13q), +8, aUPD at 9p24 and abnormalities on chromosome 1). In addition, we identified several novel cryptic lesions. In particular, we found a recurrent alteration involving cytoband 20p13 in 55% of patients. We defined a minimal affected region (MAR), an amplification of 9,911 base-pair (bp) overlapping the SIRPB1 gene locus. Noteworthy, by extending the analysis to the adjacent areas, the cytoband was overall affected in 95% of cases. Remarkably, these results were confirmed by real-time PCR and validated in silico in a large independent series of myeloproliferative diseases. Finally, by immunohistochemistry we found that SIRPB1 was over-expressed in the bone marrow of PMF patients carrying 20p13 amplification. In conclusion, we identified a novel highly recurrent genomic lesion in PMF patients, which definitely warrant further functional and clinical characterization