828 research outputs found
Microbial contributions to coupled arsenic and sulfur cycling in the acid-sulfide hot spring Champagne Pool, New Zealand
Acid-sulfide hot springs are analogs of early Earth geothermal systems where microbial metal(loid) resistance likely first evolved. Arsenic is a metalloid enriched in the acid-sulfide hot spring Champagne Pool (Waiotapu, New Zealand). Arsenic speciation in Champagne Pool follows reaction paths not yet fully understood with respect to biotic contributions and coupling to biogeochemical sulfur cycling. Here we present quantitative arsenic speciation from Champagne Pool, finding arsenite dominant in the pool, rim and outflow channel (55-75% total arsenic), and dithio- and trithioarsenates ubiquitously present as 18-25% total arsenic. In the outflow channel, dimethylmonothioarsenate comprised ≤9% total arsenic, while on the outflow terrace thioarsenates were present at 55% total arsenic. We also quantified sulfide, thiosulfate, sulfate and elemental sulfur, finding sulfide and sulfate as major species in the pool and outflow terrace, respectively. Elemental sulfur concentration reached a maximum at the terrace. Phylogenetic analysis of 16S rRNA genes from metagenomic sequencing revealed the dominance of Sulfurihydrogenibium at all sites and an increased archaeal population at the rim and outflow channel. Several phylotypes were found closely related to known sulfur- and sulfide-oxidizers, as well as sulfur- and sulfate-reducers. Bioinformatic analysis revealed genes underpinning sulfur redox transformations, consistent with sulfur speciation data, and illustrating a microbial role in sulfur-dependent transformation of arsenite to thioarsenate. Metagenomic analysis also revealed genes encoding for arsenate reductase at all sites, reflecting the ubiquity of thioarsenate and a need for microbial arsenate resistance despite anoxic conditions. Absence of the arsenite oxidase gene, aio, at all sites suggests prioritization of arsenite detoxification over coupling to energy conservation. Finally, detection of methyl arsenic in the outflow channel, in conjunction with increased sequences from Aquificaceae, supports a role for methyltransferase in thermophilic arsenic resistance. Our study highlights microbial contributions to coupled arsenic and sulfur cycling at Champagne Pool, with implications for understanding the evolution of microbial arsenic resistance in sulfidic geothermal systems
An Analytical Survey of Provenance Sanitization
Security is likely becoming a critical factor in the future adoption of
provenance technology, because of the risk of inadvertent disclosure of
sensitive information. In this survey paper we review the state of the art in
secure provenance, considering mechanisms for controlling access, and the
extent to which these mechanisms preserve provenance integrity. We examine
seven systems or approaches, comparing features and identifying areas for
future work.Comment: To appear, IPAW 201
Methodology of a novel risk stratification algorithm for patients with multiple myeloma in the relapsed setting
Introduction
Risk stratification tools provide valuable information to inform treatment decisions. Existing algorithms for patients with multiple myeloma (MM) were based on patients with newly diagnosed disease, and these have not been validated in the relapsed setting or in routine clinical practice. We developed a risk stratification algorithm (RSA) for patients with MM at initiation of second-line (2L) treatment, based on data from the Czech Registry of Monoclonal Gammopathies.
Methods
Predictors of overall survival (OS) at 2L treatment were identified using Cox proportional hazards models and backward selection. Risk scores were obtained by multiplying the hazard ratios for each predictor. The K-adaptive partitioning for survival (KAPS) algorithm defined four groups of stratification based on individual risk scores.
Results
Performance of the RSA was assessed using Nagelkerke’s R2 test and Harrell’s concordance index through Kaplan–Meier analysis of OS data. Prognostic groups were successfully defined based on real-world data. Use of a multiplicative score based on Cox modeling and KAPS to define cut-off values was effective.
Conclusion
Through innovative methods of risk assessment and collaboration between physicians and statisticians, the RSA was capable of stratifying patients at 2L treatment by survival expectations. This approach can be used to develop clinical decision-making tools in other disease areas to improve patient management
The metabolic basis of adolescent idiopathic scoliosis: 2011 report of the “metabolic” workgroup of the Fondation Yves Cotrel
OBJECTIVE: The purpose of this review is to elucidate the metabolic processes involved in the pathogenesis of adolescent idiopathic scoliosis (AIS) in light of research by the present authors as well as current literature. METHODS: Pathogenetic mechanism
Assessing the role of rare genetic variants in drug-resistant, non-lesional focal epilepsy.
OBJECTIVE: Resistance to antiseizure medications (ASMs) is one of the major concerns in the treatment of epilepsy. Despite the increasing number of ASMs available, the proportion of individuals with drug-resistant epilepsy remains unchanged. In this study, we aimed to investigate the role of rare genetic variants in ASM resistance. METHODS: We performed exome sequencing of 1,128 individuals with non-familial non-acquired focal epilepsy (NAFE) (762 non-responders, 366 responders) and were provided with 1,734 healthy controls. We undertook replication in a cohort of 350 individuals with NAFE (165 non-responders, 185 responders). We performed gene-based and gene-set-based kernel association tests to investigate potential enrichment of rare variants in relation to drug response status and to risk for NAFE. RESULTS: We found no gene or gene set that reached genome-wide significance. Yet, we identified several prospective candidate genes - among them DEPDC5, which showed a potential association with resistance to ASMs. We found some evidence for an enrichment of truncating variants in dominant familial NAFE genes in our cohort of non-familial NAFE and in association with drug-resistant NAFE. INTERPRETATION: Our study identifies potential candidate genes for ASM resistance. Our results corroborate the role of rare variants for non-familial NAFE and imply their involvement in drug-resistant epilepsy. Future large-scale genetic research studies are needed to substantiate these findings
Recommended from our members
SEIS: Insight's Seismic Experiment for Internal Structure of Mars.
By the end of 2018, 42 years after the landing of the two Viking seismometers on Mars, InSight will deploy onto Mars' surface the SEIS (Seismic Experiment for Internal Structure) instrument; a six-axes seismometer equipped with both a long-period three-axes Very Broad Band (VBB) instrument and a three-axes short-period (SP) instrument. These six sensors will cover a broad range of the seismic bandwidth, from 0.01 Hz to 50 Hz, with possible extension to longer periods. Data will be transmitted in the form of three continuous VBB components at 2 sample per second (sps), an estimation of the short period energy content from the SP at 1 sps and a continuous compound VBB/SP vertical axis at 10 sps. The continuous streams will be augmented by requested event data with sample rates from 20 to 100 sps. SEIS will improve upon the existing resolution of Viking's Mars seismic monitoring by a factor of ∼ 2500 at 1 Hz and ∼ 200 000 at 0.1 Hz. An additional major improvement is that, contrary to Viking, the seismometers will be deployed via a robotic arm directly onto Mars' surface and will be protected against temperature and wind by highly efficient thermal and wind shielding. Based on existing knowledge of Mars, it is reasonable to infer a moment magnitude detection threshold of M w ∼ 3 at 40 ∘ epicentral distance and a potential to detect several tens of quakes and about five impacts per year. In this paper, we first describe the science goals of the experiment and the rationale used to define its requirements. We then provide a detailed description of the hardware, from the sensors to the deployment system and associated performance, including transfer functions of the seismic sensors and temperature sensors. We conclude by describing the experiment ground segment, including data processing services, outreach and education networks and provide a description of the format to be used for future data distribution.Electronic supplementary materialThe online version of this article (10.1007/s11214-018-0574-6) contains supplementary material, which is available to authorized users
Emergent Phenomena Induced by Spin-Orbit Coupling at Surfaces and Interfaces
Spin-orbit coupling (SOC) describes the relativistic interaction between the
spin and momentum degrees of freedom of electrons, and is central to the rich
phenomena observed in condensed matter systems. In recent years, new phases of
matter have emerged from the interplay between SOC and low dimensionality, such
as chiral spin textures and spin-polarized surface and interface states. These
low-dimensional SOC-based realizations are typically robust and can be
exploited at room temperature. Here we discuss SOC as a means of producing such
fundamentally new physical phenomena in thin films and heterostructures. We put
into context the technological promise of these material classes for developing
spin-based device applications at room temperature
The Mitochondrial Ca(2+) Uniporter: Structure, Function, and Pharmacology.
Mitochondrial Ca(2+) uptake is crucial for an array of cellular functions while an imbalance can elicit cell death. In this chapter, we briefly reviewed the various modes of mitochondrial Ca(2+) uptake and our current understanding of mitochondrial Ca(2+) homeostasis in regards to cell physiology and pathophysiology. Further, this chapter focuses on the molecular identities, intracellular regulators as well as the pharmacology of mitochondrial Ca(2+) uniporter complex
- …