Using Superconducting Qubit Circuits to Engineer Exotic Lattice Systems

We propose an architecture based on superconducting qubits and resonators for the implementation of a variety of exotic lattice systems, such as spin and Hubbard models in higher or fractal dimensions and higher-genus topologies. Spin systems are realized naturally using qubits, while superconducting resonators can be used for the realization of Bose-Hubbard models. Fundamental requirements for these designs, such as controllable interactions between arbitrary qubit pairs, have recently been implemented in the laboratory, rendering our proposals feasible with current technology.Comment: 7 pages (two-column), 3 figure

Evidence for glutamate-mediated excitotoxic mechanisms during photoreceptor degeneration in the rd1 mouse retina

PURPOSE: Kinetic studies of photoreceptor cell death in the retinal degeneration (rd1) mouse model suggest that photoreceptor degeneration could result from cumulative damage. Since alterations in glutamate metabolism have been described in different models of retinitis pigmentosa, we investigated in the present work whether changes in glutamate turnover occur in the degenerating rd1 retina and whether glutamate-mediated excitotoxic mechanisms may contribute to rod photoreceptor death in this model. METHODS: Free amino acid levels were quantified in rd1 and wild-type retinas using an amino acid analyzer selecting times corresponding to early, intermediate, and terminal phases of rod photoreceptor degeneration. Reverse transcription-polymerase chain reaction (RT-PCR) was used to compare the mRNA expression levels of the glial L-glutamate/L-aspartate transporter GLAST, glutamine synthetase (GS), and vimentin, a marker for retinal glia, between rd1 and wild-type mouse retinas. 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), an antagonist of both AMPA and kainate subtypes of ionotropic glutamate receptors, was then daily administered from postnatal day 3 (PN3) to PN21 to rd1 mice while control rd1 mice received only physiological saline solution (7 per treatment). At PN22, the respective numbers of surviving rods i

The cost-effectiveness of the Argus II retinal prosthesis in Retinitis Pigmentosa patients

This is the final version of the article. Available from the publisher via the DOI in this record.BACKGROUND: Retinitis Pigmentosa (RP) is a hereditary genetic disease causing bilateral retinal degeneration. RP is a leading cause of blindness resulting in incurable visual impairment and drastic reduction in the Quality of life of the patients. Second Sight Medical Products Inc. developed Argus II, a retinal prosthesis system for treating RP. Argus II is the world's first ever-commercial implant intended to restore some vision in the blind patients. The objective of this study was to assess the cost-effectiveness of the Argus® II Retinal Prosthesis System (Argus II) in Retinitis Pigmentosa (RP) patients. METHOD: A multi -state transition Markov model was developed to determine the cost-effectiveness of Argus II versus usual care in RP from the perspective of healthcare payer. A hypothetical cohort of 1000 RP patients aged 46 years followed up over a (lifetime) 25-year time horizon. Health outcomes were expressed as quality adjusted life years (QALYs) and direct healthcare costs expressed in 2012 €. Results are reported as incremental cost per ratios (ICERs) with outcomes and costs discounted at an annual rate of 3.5%. RESULTS: The ICER for Argus II was €14,603/QALY. Taking into account the uncertainty in model inputs the ICER was €14,482/QALY in the probabilistic analysis. In the scenarios of an assumption of no reduction on cost across model visual acuity states or a model time horizon as short as 10 years the ICER increased to €31,890/QALY and €49,769/QALY respectively. CONCLUSION: This economic evaluation shows that Argus II is a cost-effective intervention compared to usual care of the RP patients. The lifetime analysis ICER for Argus II falls below the published societal willingness to pay of EuroZone countries

The Influence of Malt Extraction Adding to UF Fresh Low Fat Cheese on Its Textural Properties

Today , demands for reduced fat products such as reduced fat cheeses is growing as it has shown in other food products , however high nutritional value of milk fat as a functional food can't be ignored. This study deals with investigation of adding malt extract ( in 4 different concentration 0.075 , 0.1 , 0.15 and 0.2 % ) to ultra filtered cheese and comparing them with 2 control including a sample produced of milk containing 3.5 % fat and a 0.93 % fat and their rheological and textural properties evaluated at 3 , 20 , 40 and 60 days. Results indicate reduction of texture properties revealed. Rheological analysis exhibited the texture improvement by adding malt extraction; therefore this product can be use an additive to ultra filtered cheese to enhance its texture.[How to cite this article: Shafiei, Z., Hojjatoleslami, M., Soha, S., and Shariati, M.A. 2014. The Influence of Malt Extraction Adding to UF Fresh Low Fat Cheese on Its Textural Properties. International Journal of Science and Engineering, 6(1):57-60. Doi: 10.12777/ijse.6.1.57-6

Visual Acuity Loss and Associated Risk Factors in the Retrospective Progression of Stargardt Disease Study (ProgStar Report No. 2)

PURPOSE: To examine the association between characteristics of Stargardt disease and visual acuity (VA), to estimate the longitudinal rate of VA loss, and to identify risk factors for VA loss. DESIGN: Retrospective, multicenter cohort study. PARTICIPANTS: A total of 176 patients (332 eyes) with molecularly and clinically confirmed Stargardt disease enrolled from the United States and Europe. METHODS: Standardized data report forms were used to collect retrospective data on participants' characteristics and best-corrected or presenting VA from medical charts. Linear models with generalized estimating equations were used to estimate the cross-sectional associations, and linear mixed effects models were used to estimate the longitudinal VA loss. MAIN OUTCOME MEASURES: Yearly change in VA. RESULTS: The median duration of observation was 3.6 years. At baseline, older age of symptom onset was associated with better VA, and a longer duration of symptoms was associated with worse VA. Longitudinal analysis estimated an average of 0.3 lines loss (P 30 years showed 0.4 lines slower change of VA per year (P = 0.01) compared with patients with onset age ≤14 years. CONCLUSIONS: Given the overall slow rate of VA loss, VA is unlikely to be a sensitive outcome measure for treatment trials of Stargardt disease. However, given the faster decline in younger patients and those with no or mild visual impairment, VA may be a potential outcome measure for trials targeting such subgroups of patients. These observations will need to be assessed in a prospective study bearing in mind the inherent limitations of retrospective datasets

Comparison of 5-year progression of retinitis pigmentosa involving the posterior pole among siblings by means of SD-OCT: a retrospective study

The blockchain technology promises to transform finance, money and evengovernments. However, analyses of blockchain applicability and robustness typicallyfocus on isolated systems whose actors contribute mainly by running the consensusalgorithm. Here, we highlight the importance of considering trustless platformswithin the broader ecosystem that includes social and communication networks. Asan example, we analyse the flash-crash observed on 21st June 2017 in the Ethereumplatform and show that a major phenomenon of social coordination led to acatastrophic cascade of events across several interconnected systems. We proposethe concept of “emergent centralisation” to describe situations where a single systembecomes critically important for the functioning of the whole ecosystem, and arguethat such situations are likely to become more and more frequent in interconnectedsocio-technical systems. We anticipate that the systemic approach we propose willhave implications for future assessments of trustless systems and call for the attentionof policy-makers on the fragility of our interconnected and rapidly changing world

Disease-causing mutations in BEST1 gene are associated with altered sorting of bestrophin-1 protein

Doumanov, Jordan A. et al.Mutations in BEST1 gene, encoding the bestrophin-1 (Best1) protein are associated with macular dystrophies. Best1 is predominantly expressed in the retinal pigment epithelium (RPE), and is inserted in its basolateral membrane. We investigated the cellular localization in polarized MDCKII cells of disease-associated Best1 mutant proteins to study specific sorting motifs of Best1. Real-time PCR and western blots for endogenous expression of BEST1 in MDCK cells were performed. Best1 mutant constructs were generated using site-directed mutagenesis and transfected in MDCK cells. For protein sorting, confocal microscopy studies, biotinylation assays and statistical methods for quantification of mislocalization were used. Analysis of endogenous expression of BEST1 in MDCK cells revealed the presence of BEST1 transcript but no protein. Confocal microscopy and quantitative analyses indicate that transfected normal human Best1 displays a basolateral localization in MDCK cells, while cell sorting of several Best1 mutants (Y85H, Q96R, L100R, Y227N, Y227E) was altered. In contrast to constitutively active Y227E, constitutively inactive Y227F Best1 mutant localized basolaterally similar to the normal Best1 protein. Our data suggest that at least three basolateral sorting motifs might be implicated in proper Best1 basolateral localization. In addition, non-phosphorylated tyrosine 227 could play a role for basolateral delivery. © 2013 by the authors; licensee MDPI, Basel, Switzerland.This work was supported by Agence Nationale de la Recherche (Chaire d’Excellence to Shomi S. Bhattacharya), Fondation Voir et Entendre (Young Investigator Grants to Christina Zeitz and Emeline F. Nandrot), Centre National de la Recherche Scientifique (CNRS) and Fondation Bettencourt Schueller (to Emeline F. Nandrot), Université Pierre et Marie Curie-Paris6 (Bonus Qualité Recherche to Christina Zeitz), Foundation Fighting Blindness (grant number CD-CL-0808-0466-CHNO to Isabelle Audo), Centre d’Investigation Clinique 503 recognized as a Foundation Fighting Blindness Center (grant number C-CMM-0907-0428-INSERM04), Fundacion Progreso y Salud (to Shomi S. Bhattacharya, Maria Luz Bellido Diaz, Abhay Krishna and Paloma Dominguez Gimenez), Instituto de Salud Carlos III (grant number CM06/00183 to Maria Luz Bellido Diaz) and Bulgarian National Science Fund (grant number DDVU 02/10). Additionally, the Institut de la Vision is funded by Institut National de la Santé et de la Recherche Médicale, Université Pierre et Marie Curie-Paris 6, Centre National de la Recherche Scientifique and Départment de Paris.Peer Reviewe

High prevalence of PRPH2 in autosomal dominant retinitis pigmentosa in france and characterization of biochemical and clinical features.

PURPOSE: To assess the prevalence of PRPH2 in autosomal dominant retinitis pigmentosa (adRP), to report 6 novel mutations, to characterize the biochemical features of a recurrent novel mutation, and to study the clinical features of adRP patients. DESIGN: Retrospective clinical and molecular genetic study. METHODS: Clinical investigations included visual field testing, fundus examination, high-resolution spectral-domain optical coherence tomography (OCT), fundus autofluorescence imaging, and electroretinogram (ERG) recording. PRPH2 was screened by Sanger sequencing in a cohort of 310 French families with adRP. Peripherin-2 protein was produced in yeast and analyzed by Western blot. RESULTS: We identified 15 mutations, including 6 novel and 9 previously reported changes in 32 families, accounting for a prevalence of 10.3% in this adRP population. We showed that a new recurrent p.Leu254Gln mutation leads to protein aggregation, suggesting abnormal folding. The clinical severity of the disease in examined patients was moderate with 78% of the eyes having 1-0.5 of visual acuity and 52% of the eyes retaining more than 50% of the visual field. Some patients characteristically showed vitelliform deposits or macular involvement. In some families, pericentral RP or macular dystrophy were found in family members while widespread RP was present in other members of the same families. CONCLUSIONS: The mutations in PRPH2 account for 10.3% of adRP in the French population, which is higher than previously reported (0%-8%) This makes PRPH2 the second most frequent adRP gene after RHO in our series. PRPH2 mutations cause highly variable phenotypes and moderate forms of adRP, including mild cases, which could be underdiagnosed

Relative frequencies of inherited retinal dystrophies and optic neuropathies in Southern France: assessment of 21-year data management

PURPOSE: Inherited retinal dystrophies (IRDs) and inherited optic neuropathies (IONs) are rare diseases defined by specific clinical and molecular features. The relative prevalence of these conditions was determined in Southern France. METHODS: Patients recruited from a specialized outpatient clinic over a 21-year period underwent extensive clinical investigations and 107 genes were screened by polymerase chain reaction/sequencing. RESULTS: There were 1957 IRD cases (1481 families) distributed in 70% of pigmentary retinopathy cases (56% non-syndromic, 14% syndromic), 20% maculopathies and 7% stationary conditions. Patients with retinitis pigmentosa were the most frequent (47%) followed by Usher syndrome (10.8%). Among non-syndromic pigmentary retinopathy patients, 84% had rod-cone dystrophy, 8% cone-rod dystrophy and 5% Leber congenital amaurosis. Macular dystrophies were encountered in 398 cases (30% had Stargardt disease and 11% had Best disease). There were 184 ION cases (127 families) distributed in 51% with dominant optic neuropathies, 33% with recessive/sporadic forms and 16% with Leber hereditary optic neuropathy. Positive molecular results were obtained in 417/609 families with IRDs (68.5%) and in 27/58 with IONs (46.5%). The sequencing of 5 genes (ABCA4, USH2A, MYO7A, RPGR and PRPH2) provided a positive molecular result in 48% of 417 families with IRDs. Except for autosomal retinitis pigmentosa, in which less than half the families had positive molecular results, about 75% of families with other forms of retinal conditions had a positive molecular diagnosis. CONCLUSIONS: Although gene discovery considerably improved molecular diagnosis in many subgroups of IRDs and IONs, retinitis pigmentosa, accounting for almost half of IRDs, remains only partly molecularly defined

NMNAT1 Mutations Cause Leber Congenital Amaurosis

Leber congenital amaurosis (LCA) is an infantile-onset form of inherited retinal degeneration characterized by severe vision loss. Two-thirds of LCA cases are caused by mutations in 17 known disease genes (RetNet Retinal Information Network). Using exome sequencing, we identified a homozygous missense mutation (c.25G>A, p.Val9Met) in NMNAT1 as likely disease-causing in two siblings of a consanguineous Pakistani kindred affected by LCA. This mutation segregated with disease in their kindred, including in three other children with LCA. NMNAT1 resides in the previously identified LCA9 locus and encodes the nuclear isoform of nicotinamide mononucleotide adenylyltransferase, a rate-limiting enzyme in nicotinamide adenine dinucleotide $(NAD^+)$ biosynthesis. Functional studies showed the p.Val9Met mutation decreased NMNAT1 enzyme activity. Sequencing NMNAT1 in 284 unrelated LCA families identified 14 rare mutations in 13 additional affected individuals. These results are the first to link an NMNAT isoform to disease and indicate that NMNAT1 mutations cause LCA