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The region of far peripheral vision, beyond 60 degrees of visual angle, is important to the evaluation of peripheral dark shadows (negative dysphotopsia) seen by some intraocular lens (IOL) patients. Theoretical calculations show that the limited diameter of an IOL affects ray paths at large angles, leading to a dimming of the main image for small pupils, and to peripheral illumination by light bypassing the IOL for larger pupils. These effects are rarely bothersome, and cataract surgery is highly successful, but there is a need to improve the characterization of far peripheral vision, for both pseudophakic and phakic eyes. Perimetry is the main quantitative test, but the purpose is to evaluate pathologies rather than characterize vision (and object and image regions are no longer uniquely related in the pseudophakic eye). The maximum visual angle is approximately 1050, but there is limited information about variations with age, race, or refractive error (in case there is an unexpected link with the development of myopia), or about how clear cornea, iris location, and the limiting retina are related. Also, the detection of peripheral motion is widely recognized to be important, yet rarely evaluated. Overall, people rarely complain specifically about this visual region, but with "normal" vision including an IOL for >5% of people, and increasing interest in virtual reality and augmented reality, there are new reasons to characterize peripheral vision more completely. [ABSTRACT FROM AUTHOR]

Hidradenitis suppurativa (HS) is a debilitating chronic inflammatory skin condition of unclear etiology. It may segregate as an autosomal dominant trait, and heterozygous mutations in the γ-secretase genes NCSTN, PSENEN, and PSEN1 have recently been reported in a small number of multiplex kindreds and sporadic cases. These mutations highlight γ-secretase (an enzyme that has been extensively investigated in familial Alzheimer's disease) to have an integral role in cutaneous biology and, more specifically, in HS. In this article, we review the recent genetic data, how they inform disease pathogenesis, and the long-term implications in HS and related diseases. [ABSTRACT FROM AUTHOR]

Compartmentalization is essential in the organization of biological systems, playing a fundamental role in modulating biochemical activity. An appreciation of the impact that biological compartments have on chemical reactions and an understanding of the physical and chemical phenomena that affect their assembly and function have inspired the development of synthetic compartments. Organic compartments assembled from amphiphilic molecules or derived from biological materials, have formed the basis of initial work in the field. However, inorganic and hybrid organic–inorganic compartments that capitalize on the optical and catalytic properties of metal and semiconductor materials are emerging. Methods for arraying these microcompartment and nanocompartment materials in higher order systems promise to enable the scaling and integration of these technologies for industrial and commercial applications. [Copyright &y& Elsevier]

A better understanding of how confinement, crowding and reduced dimensionality modulate reactivity and reaction dynamics will aid in the rational and systematic discovery of functionality in complex biological systems. Artificial microfabricated and nanofabricated structures have helped elucidate the effects of nanoscale spatial confinement and segregation on biological behavior, particularly when integrated with microfluidics, through precise control in both space and time of diffusible signals and binding interactions. Examples of nanostructured interfaces for synthetic biology include the development of cell-like compartments for encapsulating biochemical reactions, nanostructured environments for fundamental studies of diffusion, molecular transport and biochemical reaction kinetics, and regulation of biomolecular interactions as functions of microfabricated and nanofabricated topological constraints. [ABSTRACT FROM AUTHOR]

Abstract: In order to investigate the viability of using Be as a redox agent in a molten Flibe (2LiF–BeF2) blanket, a series of kinetics experiments were performed in which HF was bubbled through Flibe with varying concentrations of dissolved Be. The feed gas consisted of 910–1800ppm HF and 0.1–0.2vol.% H2, with the balance comprised of He. A cylindrical rod of Be was contacted with the salt for periods of time ranging from 600 to 3600s, resulting in mole fractions in the salt ranging from 4.3×10−5 to 2.6×10−4. Initially, high HF conversion levels in excess of 90% were observed. As HF reacted with the Be, the conversion levels slowly dropped over a period of several hours to a few days. A simple kinetic model, which is first order in both HF and Be concentration has been coupled with a non-mixed reactor model to yield a good fit to the data. Application of this model indicates that Be should be suitable for keeping the TF concentration in the salt below 0.02ppb. [Copyright &y& Elsevier]

• Technoeconomic model integrating ICE + ORC engines for CHP applications. • Commercial ICE and ORC engines are evaluated in 30 real supermarket buildings. • Optimal ORC engine capacities in these supermarkets range from 20 to 30 kW e. • ORC engine payback times range from 4 to 9 years depending on the building. • For improved performance exhaust-gas heat recovery should be considered. We examine the opportunities and challenges of deploying integrated organic Rankine cycle (ORC) engines to recover heat from low-temperature jacket-water cooling circuits of small-scale gas-fired internal combustion engines (ICEs), for the supply of combined heat and power (CHP) to supermarkets. Based on data for commercially-available ICE and ORC engines, a techno-economic model is developed and applied to simulate system performance in real buildings. Under current market trends and for the specific (low-temperature) ICE + ORC CHP configuration investigated here, results show that the ICE determines most economic savings, while the ORC engine does not significantly impact the integrated CHP system performance. The ORC engines have long payback times (4–9 years) in this application, because: (1) they do not displace high-value electricity, as the value of exporting electricity to the grid is low, and (2) it is more profitable to use the heat from the ICEs for space heating rather than for electricity conversion. Commercial ORC engines are most viable (payback ≈ 4 years) in buildings with high electrical demands and low heat-to-power ratios. The influence of factors such as the ORC engine efficiency, capital cost and energy prices is also evaluated, highlighting performance gaps and identifying promising areas for future research. [ABSTRACT FROM AUTHOR]

The article focuses on hidradenitis suppurativa (HS), a chronic inflammatory skin disease, caused by the mutation in the gamma-secretase genes such as Nicastrin (NCSTN), Presenilins (PSENEN) and Presenilin-1 (PSEN1). It further states that HS affects one percent of Europeans and may segregate as an autosomal dominant trait and heterozygous mutations in the gamma-secretase genes. It also presents diagrams depicting the location of all mutations within the gamma-secretase complex.

A letter to the editor is presented regarding the study on the disease-associated variants identification in the RNF114 psoriasis susceptibility gene promoter region.

A letter to the editor is presented regarding Presenilin Enhancer-2 (PSENEN), and Nicastrin (NCSTN) mutations in hidradenitis suppurativa.

• Organic Rankine cycle engines are optimised for exhaust from stationary gas engines. • Two configurations are assessed using energy usage data for thirty buildings. • Use of jacket water increases power output by 20% but reduces project viability. • System with condenser heat supplied to building shows 3.5- to 7.5-year payback. For buildings with low heat-to-power demand ratios, the installation of internal combustion engines (ICEs) for the onsite provision of combined heat and power (CHP) results in large amounts of surplus heat. In the UK, such installations risk being ineligible for the CHP Quality Assurance (CHPQA) programme, thereby incurring additional levies. In this work, a technoeconomic optimisation of small-scale organic Rankine cycle (ORC) engines is performed, in which the ORC engines recover heat from the ICE exhaust gases in order to increase the overall efficiency of this combined solution and meet the CHPQA requirements. Two competing system configurations are assessed. In the first, the ORC engine also recovers heat from the CHP-ICE jacket water to generate additional power. In the second, the ORC engine operates at a higher condensing temperature, which prohibits jacket-water heat recovery but allows heat from the condenser to be delivered to the building. When optimised for minimum specific investment cost, the first configuration is initially found to deliver 20% more power (25.8 kW) at design conditions, and a minimum specific investment cost (1600 £/kW) that is 8% lower than the second configuration. However, the first configuration leads to less heat from the CHP-ICE being supplied to the building, increasing the cost of meeting the heat demand. By establishing part-load performance curves for both the CHP-ICE and ORC engines, the economic benefits from realistic operation can be evaluated. The present study goes beyond previous work by testing the configurations against a comprehensive database of real historical electricity and heating demand for thirty energy-intensive buildings at half-hour resolution. The discounted payback period for the second configuration is found to lie between 3.5 and 7.5 years for all of the buildings considered, while the first configuration is seen to recoup capital investment costs for only 23% of the buildings. The broad applicability of the second configuration offers attractive opportunities to increase manufacturing volumes and reduce unit costs. The findings are relevant to a range of buildings with heat-to-power demand ratios from 20% to 100%. [ABSTRACT FROM AUTHOR]

The article focuses on a study related to the next-generation diagnostics for genodermatoses. It mentions that the morpho-spatial nature of genodermatoses also adds the conundrum of mosaic disease; and more specific and discrete morphological phenotypes typifying many dermatoses have revealed diverse genes converging on a common phenotype in contrast to classic quantitative traits, such as metabolic disease or blood pressure.

Abstract In a molten salt nuclear reactor system, the redox potential must be controlled for mitigating corrosion of structural materials. The paper presented a critical review on the available knowledge of redox potential control in molten fluoride salt systems. The major phenomena that affect the redox potential and material corrosion are fission, TF production by transmutation, and salt contamination with metal fluorides or other oxidizing impurities. Redox potential control methodologies include gas sparging, contacting the salt with a reducing metal, and adding soluble salt redox buffers to the salt. Redox potential measurement technologies include electrochemical sensors and optical spectroscopy. The paper also analyzed the current technology issues and recommended near future studies. [ABSTRACT FROM AUTHOR]

Abstract: A parametric study has been conducted to identify the effects of several parameters on the separation of CsCl from molten LiCl–KCl salt via a melt crystallization process. A reverse vertical Bridgman technique was used to grow the salt ingots. The investigated parameters were: (1) the advancement rate, (2) the crucible lid configuration, (3) the amount of salt mixture, (4) the initial composition of CsCl, and (5) the temperature difference between the high and low furnace zones. From each grown salt ingot, samples were taken axially and analyzed using inductively coupled plasma mass spectrometry. Results show that CsCl concentrations at the top of the ingots were low and increased to a maximum at the bottom of the salt. Salt (LiCl–KCl) recycle percentages for the experiments ranged from 50% to 75% and the CsCl composition in the waste salt was low. To increase the recycle percentage and the concentration of CsCl in the waste form, multiple crystallization stages were explored showing that they were practical under the optimal experimental conditions at 5.0mm/h rate with a lid configuration and temperature difference of 200°C for a total of five crystallization stages. Up to 88% of the LiCl–KCl salt can be recycled under these proposed conditions. [Copyright &y& Elsevier]

Abstract: Objective: Acrocallosal syndrome (ACLS) is a rare genetically heterogeneous disorder characterised by a variety of developmental anomalies including agenesis or hypoplasia of the corpus callosum. ACLS and the related disorder, hydrolethalus syndrome, have recently been reported to be caused by mutations in the KIF7 gene. In the present study we report a 15 year follow up of a consanguineous family with ACLS and the results of exome sequencing. Results: A novel in-frame deletion KIF7 mutation (p.218-221del) was detected. This is the first deletion mutation in KIF7 described in ACLS and is predicted to disrupt the KIF7 protein within the kinesin motor domain. Also present, in addition to the homozygous KIF7 mutation, were loss of function variants in known ciliopathy genes; AHI1 (p.R830W), BBS2 (p.N70S) and BBS4 (p.M472V). Conclusion: KIF7 has previously been demonstrated to regulate function of primary cilia and ACLS is now categorised as a ciliopathy – a group of disorders in which oligogenic disease is frequent. The finding of known loss of function variants in ciliopathy associated genes, AHI1, BBS2 and BBS4 in addition to KIF7 mutations provides evidence for oligogenic inheritance in ACLS and suggests that this might contribute to the phenotypic variability of KIF7-related disorders. [Copyright &y& Elsevier]

Abstract: The second Japan/US Program on Irradiation Tests for Fusion Research (JUPITER-II) began on April 1, 2001. Part of the collaborative research centers on studies of the molten salt 2LiF2–BeF2 (also known as Flibe) for fusion applications. Flibe has been proposed as a self-cooled breeder in both magnetic and inertial fusion power plant designs over the last 25 years. The key feasibility issues associated with the use of Flibe are the corrosion of structural material by the molten salt, tritium behavior and control in the molten salt blanket system, and safe handling practices and releases from Flibe during an accidental spill. These issues are all being addressed under the JUPITER-II program at the Idaho National Laboratory in the Safety and Tritium Applied Research (STAR) facility. In this paper, we review the program to date in the area of tritium/deuterium behavior, Flibe mobilization under accident conditions and testing of Be as a redox agent to control corrosion. Future activities planned through the end of the collaboration are also presented. [Copyright &y& Elsevier]

A novel nuclear waste form was synthesized for the disposal of electrorefiner salt from pyrometallurgical reprocessing of used nuclear fuel. Its synthesis constitutes two steps: waste salt dehalogenation via ion exchange with H–Y zeolite, followed by thermal treatment for phase transition and consolidation. Salt cation-loaded zeolite exhibiting greater than 90% dehalogenation was sintered for 12 h at 925 °C and achieved 3 vol% open porosity (determined via Archimedes method). Microstructural imaging and structural characterization revealed a multiphase assemblage of alkali aluminosilicate and mixed oxide phases. Chemical durability experiments were performed using modified ASTM C1308 tests in demineralized water and different silica solutions. Si-containing species appear to exhibit congruent dissolution, while the release behaviors of alkali elements appear to include diffusion-limited contributions. The 4-day cumulative releases for the dehalogenated salt waste form (DSWF) are less than 33% of those measured for the baseline glass-bonded sodalite advanced ceramic waste form (GBS ACWF). Furthermore, the dehalogenation and consolidation processing steps provide a 35% decrease in required storage volume for a given waste salt mass relative to the GBS ACWF. Image 1 [ABSTRACT FROM AUTHOR]

Background: Sudden infant death syndrome (SIDS) is a leading cause of postneonatal mortality. Genetic heart diseases (GHDs) underlie some cases of SIDS.Objectives: This study aimed to determine the spectrum and prevalence of GHD-associated mutations as a potential monogenic basis for SIDS.Methods: A cohort of 419 unrelated SIDS cases (257 male; average age 2.7 ± 1.9 months) underwent whole exome sequencing and a targeted analysis of 90 GHD-susceptibility genes. The yield of "potentially informative," ultra-rare variants (minor allele frequency <0.00005) in GHD-associated genes was assessed.Results: Overall, 53 of 419 (12.6%) SIDS cases had ≥1 "potentially informative," GHD-associated variant. The yield was 14.9% (21 of 141) for mixed-European ancestry cases and 11.5% (32 of 278) for European ancestry SIDS cases. Infants older than 4 months were more likely to host a "potentially informative" GHD-associated variant. There was significant overrepresentation of ultra-rare nonsynonymous variants in European SIDS cases (18 of 278 [6.5%]) versus European control subjects (30 of 973 [3.1%]; p = 0.013) when combining all 4 major cardiac channelopathy genes (KCNQ1, KCNH2, SCN5A, and RYR2). According to the American College of Medical Genetics guidelines, only 18 of 419 (4.3%) SIDS cases hosted a "pathogenic" or "likely pathogenic" variant.Conclusions: Less than 15% of more than 400 SIDS cases had a "potentially informative" variant in a GHD-susceptibility gene, predominantly in the 4- to 12-month age group. Only 4.3% of cases possessed immediately clinically actionable variants. Consistent with previous studies, ultra-rare, nonsynonymous variants within the major cardiac channelopathy-associated genes were overrepresented in SIDS cases in infants of European ethnicity. These findings have major implications for the investigation of SIDS cases and families. [ABSTRACT FROM AUTHOR]

Alzheimer disease (AD) is a degenerative tauopathy characterized by aggregation of Tau protein through the repeat domain to form intraneuronal paired helical filaments (PHFs). We report two cell models in which we control the inherent toxicity of the core Tau fragment. These models demonstrate the properties of prion-like recruitment of full-length Tau into an aggregation pathway in which template-directed, endogenous truncation propagates aggregation through the core Tau binding domain. We use these in combination with dissolution of native PHFs to quantify the activity of Tau aggregation inhibitors (TAIs). We report the synthesis of novel stable crystalline leucomethylthioninium salts (LMTX®), which overcome the pharmacokinetic limitations of methylthioninium chloride. LMTX®, as either a dihydromesylate or a dihydrobromide salt, retains TAI activity in vitro and disrupts PHFs isolated from AD brain tissues at 0.16 µM. The KI value for intracellular TAI activity, which we have been able to determine for the first time, is 0.12 µM. These values are close to the steady state trough brain concentration of methylthioninium ion (0.18 µM) that is required to arrest progression ofADon clinical and imaging end points and the minimum brain concentration (0.13 µM) required to reverse behavioral deficits and pathology in Tau transgenic mice. [ABSTRACT FROM AUTHOR]

The article focuses on a study that discusses hereditary epidermolysis bullosa (EB), inherited connective tissue disease, causing blisters in the skin. Topics discussed include EB caused by mutation, EB classified into four different types including EB simplex, dystrophic EB, junctional EB and Kindler syndrome and distinct phenotypes causes loss of dermatoglyphs, skin blistering and progressive skin atrophy. It also discusses about missense mutation p.R1303Q in type XVII Collagen.

A letter to the editor is presented which discusses rare variations in IL36RN in adverse drug reactions demonstration as acute generalized exanthematous pustulosis (AGEP).

The article presents a study which aims to characterize the psoriasis-associated pustular phenotypes spectrum that are caused by IL36RN alleles. The study analyzed an extended collection of generalized pustular psoriasis (GPP) cases and the possibility that IL36RN may contribute to palmarplantar pustulosis (PPP) and acrodermatitis continua of hallopeau (ACH) was investigated. Results in the study showed the association of IL36RN with a phenotypic spectrum that encompasses ACH, PPP, and GPP.

The article offers information on a research related to generalized pustular psoriasis. Topics of discussion included were presence of IL36RN variants in GPP, avoiding amoxicillin administration to known patients with clinically manifest deficiency of the IL-36 receptor antagonist (DITRA) and patch testing for β-lactam antibiotics. It also discusses the importance of pretreatment genetic testing for human leukocyte antigen risks and HIV before administration of abacavir.