No abstract

BACKGROUND Whole-genome sequencing may revolutionize medical diagnostics through rapid identification of alleles that cause disease. However, even in cases with simple patterns of inheritance and unambiguous diagnoses, the relationship between disease phenotypes and their corresponding genetic changes can be complicated. Comprehensive diagnostic assays must therefore identify all possible DNA changes in each haplotype and determine which are responsible for the underlying disorder. The high number of rare, heterogeneous mutations present in all humans and the paucity of known functional variants in more than 90% of annotated genes make this challenge particularly difficult. Thus, the identification of the molecular basis of a genetic disease by means of whole-genome sequencing has remained elusive. We therefore aimed to assess the usefulness of human whole-genome sequencing for genetic diagnosis in a patient with Charcot–Marie–Tooth disease. METHODS We identified a family with a recessive form of Charcot–Marie–Tooth disease for which the genetic basis had not been identified. We sequenced the whole genome of the proband, identified all potential functional variants in genes likely to be related to the disease, and genotyped these variants in the affected family members. RESULTS We identified and validated compound, heterozygous, causative alleles in SH3TC2 (the SH3 domain and tetratricopeptide repeats 2 gene), involving two mutations, in the proband and in family members affected by Charcot–Marie–Tooth disease. Separate subclinical phenotypes segregated independently with each of the two mutations; heterozygous mutations confer susceptibility to neuropathy, including the carpal tunnel syndrome. CONCLUSIONS As shown in this study of a family with Charcot–Marie–Tooth disease, whole-genome sequencing can identify clinically relevant variants and provide diagnostic information to inform the care of patients.

Immunization with this hepatitis E vaccine induced antibodies against HEV and provided protection against hepatitis E for up to 4.5 years. (Funded by the Chinese Ministry of Science and Technology and others; ClinicalTrials.gov number, NCT01014845.).

Inexpensive, robust and efficient large-scale electrical energy storage systems are vital to the utilization of electricity generated from solar and wind resources. In this regard, the low cost, robustness, and eco-friendliness of aqueous iron-based rechargeable batteries are particularly attractive and compelling. However, wasteful evolution of hydrogen during charging and the inability to discharge at high rates have limited the deployment of iron-based aqueous batteries. We report here new chemical formulations of the rechargeable iron battery electrode to achieve a ten-fold reduction in the hydrogen evolution rate, an unprecedented charging efficiency of 96%, a high specific capacity of 0.3 Ah/g, and a twenty-fold increase in discharge rate capability. We show that modifying high-purity carbonyl iron by in situ electro-deposition of bismuth leads to substantial inhibition of the kinetics of the hydrogen evolution reaction. The in situ formation of conductive iron sulfides mitigates the passivation by iron hydroxide thereby allowing high discharge rates and high specific capacity to be simultaneously achieved. These major performance improvements are crucial to advancing the prospect of a sustainable large-scale energy storage solution based on aqueous iron-based rechargeable batteries. Large-scale electrical energy storage systems are needed to accommodate the intrinsic variability of energy supply from solar and wind resources.1,2 Such energy storage systems will store the excess energy during periods of electricity production, and release the energy during periods of electricity demand. Viable energy storage systems will have to meet the following requirements: (i) low installed-cost of <$100/kWh, (ii) long operating life of over 5000 cycles, (iii) high round-trip energy efficiency of over 80%, and (iv) ease of scalability to megawatt-hour level systems.2 Rechargeable batteries are particularly suitable for such large-scale storage of electrical energy because of their high round-trip efficiency and scalability. Among the types of rechargeable batteries under consideration are vanadium-redox, sodium-sulfur, zinc-bromine, zinc-air and lithium-ion batteries. 3,4 In addressing the challenges of durability, cost, and large-scale implementation of the foregoing types of batteries, the beneficial features of iron-based alkaline batteries for large-scale energy storage have been largely overlooked. Nickel-Iron batteries have been used in various stationary and mobile applications for over 70 years in the USA and Europe until the 1980s when the iron-based batteries were largely supplanted by sealed lead-acid batteries. Iron-air batteries because of their high specific energy underwent active development for electric vehicles and military applications in the 1970s after the "oil shock" but major research in this area was abruptly discontinued after 1984. Except for some seminal research in India by Shukla et al. during the period 1986-1992, iron electrodes have not received any significant attention. [5][6][7] We e...

Iron-based alkaline rechargeable batteries have the potential of meeting the needs of large-scale electrical energy storage because of their low-cost, robustness and eco-friendliness. However, the widespread commercial deployment of iron-based batteries has been limited by the low charging efficiency and the poor discharge rate capability of the iron electrode. In this study, we have demonstrated iron electrodes containing bismuth oxide and iron sulfide with a charging efficiency of 92% and capable of being discharged at the 3C rate. Such a high value of charging efficiency combined with the ability to discharge at high rates is being reported for the first time. The bismuth oxide additive led to the in situ formation of elemental bismuth and a consequent increase in the overpotential for the hydrogen evolution reaction leading to an increase in the charging efficiency. We observed that the sulfide ions added to the electrolyte and iron sulfide added to the electrode mitigated electrode passivation and allowed for continuous discharge at high rates. At the 3C discharge rate, a utilization of 0.2 Ah/g was achieved. The performance level of the rechargeable iron electrode demonstrated here is attractive for designing economically-viable large-scale energy storage systems based on alkaline nickel-iron and iron-air batteries.

Fluorescence properties of whole water samples and molecular characteristics of ultrafiltrated dissolved organic matter (UDOM Ͼ 1,000 D) such as lignin phenol and neutral sugar compositions and 13 C nuclear magnetic resonance (NMR) spectra were determined along a freshwater to marine gradient in Everglades National Park. Furthermore, UDOM samples were categorized by hierarchical cluster analysis based on their pyrolysis gas chromatography/mass spectrometry products. Fluorescence properties suggest that autochthonous DOM leached/exuded from biomass is quantitatively important in this system. 13C NMR spectra showed that UDOM from the oligotrophic Taylor Slough (TS) and Florida Bay (FB) ecosystems has low aromatic C (13% Ϯ 3% for TS; 2% Ϯ 2% for FB) and very high O-alkyl C (54% Ϯ 4% for TS; 75% Ϯ 4% for FB) concentrations. High O-alkyl C concentrations in FB suggest seagrass/phytoplankton communities as dominant sources of UDOM. The amount of neutral sugars was not appreciably different between the TS and FB sites (115 Ϯ 12 mg C g C Ϫ1 UDOM) but their concentrations suggest a low level of diagenesis and high production rates of this material in this oligotrophic environment. Total yield of lignin phenols (vanillyl ϩ syringyl phenols) in TS was low (0.20-0.39 mg 100 mg C Ϫ1 UDOM) compared with other riverine environments and even lower in FB (0.04-0.07 mg 100 mg C Ϫ1 UDOM) and could be a result of photodegradation and/or dilution by other autochthonous DOM. The high O-alkyl and low aromatic nature of this UDOM suggests significant biogenic inputs (as compared with soils) and limited bioavailability in this ecosystem.

Rechargeable iron-based alkaline batteries such as iron -air and nickel -iron batteries are attractive for large-scale electrical energy storage because iron is inexpensive, globally-abundant and environmentally-friendly. Further, the iron electrode is known for its robustness to repeated charge/discharge cycling. During manufacturing these batteries are charged and discharged 20 to 50 times during which the discharge capacity of the iron electrode increases gradually and attains a stable value. This process of achieving stable capacity is called formation. In this study we have focused our efforts on understanding the effect of electrode design on formation. We have investigated the role of wetting agent, pore-former additive, and sulfide additive on the formation of carbonyl iron electrodes. The wetting agent increased the rate of formation while the pore-former additive increased the final capacity. Sodium sulfide added to the electrolyte worked as a de-passivation agent and increased the final discharge capacity. We have proposed a phenomenological model for the formation process that predicts the rate of formation and final discharge capacity given the design parameters for the electrode. The understanding gained here will be useful in reducing the time lost in formation and in maximizing the utilization of the iron electrode.Iron-based rechargeable battery systems using alkaline electrolyte such as nickel -iron and iron -air batteries are promising candidates for large-scale electrical energy storage needed for integrating renewable energy generation into the electricity grid. 1-4 Iron, the primary raw material for these systems, is globally abundant and relatively inexpensive. In addition, the iron electrode is robust and provides the battery system with long cycle life. 5-7 However, the iron electrodes suffer from poor charging efficiency and poor discharge rate capability. These limitations of electrical performance have prevented the large-scale commercialization of iron-based batteries. 1,5,6,8 There is renewed focus on addressing these limitations because of the dire need for a long-lasting and inexpensive battery system for grid-scale energy storage. [1][2][3][4]9 At the University of Southern California, we have demonstrated significant improvements to the charging efficiency and discharge rate capability of rechargeable iron electrodes. 3,4,10 These high-performance electrodes consist of carbonyl iron as the active battery material and also additives to suppress the parasitic process of hydrogen evolution. As a result, a high charging efficiency of 96% and a high utilization of 0.3 Ah/g have been realized.In the present study, we focus on understanding the process of formation of carbonyl iron-based rechargeable electrodes in aqueous alkaline batteries. A newly-prepared iron electrode in a nickel-iron or iron-air battery undergoes formation during which the electrode is charged and discharged repeatedly for 20 to 50 cycles after which a stable discharge capacity is reached. 5,11-15 The formation of...

Immunity acquired from infection or vaccination protects humans from symptomatic hepatitis E. However, whether the risk of hepatitis E virus (HEV) infection is reduced by the immunity remains unknown. To understand this issue, a cohort with 12 409 participants randomized to receive the hepatitis E vaccine Hecolin(®) or placebo were serologically followed up for 2 years after vaccination. About half (47%) of participants were initially seropositive. A total of 139 infection episodes, evidenced by four-fold or greater rise of anti-HEV level or positive seroconversion, occurred in participants who received three doses of treatment. Risk of infection was highest among the baseline seronegative placebo group participants (2.04%). Pre-existing immunity and vaccine-induced immunity lower the risk significantly, to 0.52% and 0.30%, respectively. In conclusion, both vaccine-induced and naturally acquired immunity can effectively protect against HEV infection.