How humans solve the cocktail party problem remains unknown. However, progress has been made recently thanks to the realization that cortical activity tracks the amplitude envelope of speech. This ...has led to the development of regression methods for studying the neurophysiology of continuous speech. One such method, known as stimulus-reconstruction, has been successfully utilized with cortical surface recordings and magnetoencephalography (MEG). However, the former is invasive and gives a relatively restricted view of processing along the auditory hierarchy, whereas the latter is expensive and rare. Thus it would be extremely useful for research in many populations if stimulus-reconstruction was effective using electroencephalography (EEG), a widely available and inexpensive technology. Here we show that single-trial (≈60 s) unaveraged EEG data can be decoded to determine attentional selection in a naturalistic multispeaker environment. Furthermore, we show a significant correlation between our EEG-based measure of attention and performance on a high-level attention task. In addition, by attempting to decode attention at individual latencies, we identify neural processing at ∼200 ms as being critical for solving the cocktail party problem. These findings open up new avenues for studying the ongoing dynamics of cognition using EEG and for developing effective and natural brain-computer interfaces.
The proto-oncogene c-Myc paradoxically activates both proliferation and apoptosis. In the pathogenic state, c-Myc-induced apoptosis is bypassed via a critical, yet poorly understood escape mechanism ...that promotes cellular transformation and tumorigenesis. The accumulation of unfolded proteins in the ER initiates a cellular stress program termed the unfolded protein response (UPR) to support cell survival. Analysis of spontaneous mouse and human lymphomas demonstrated significantly higher levels of UPR activation compared with normal tissues. Using multiple genetic models, we demonstrated that c-Myc and N-Myc activated the PERK/eIF2α/ATF4 arm of the UPR, leading to increased cell survival via the induction of cytoprotective autophagy. Inhibition of PERK significantly reduced Myc-induced autophagy, colony formation, and tumor formation. Moreover, pharmacologic or genetic inhibition of autophagy resulted in increased Myc-dependent apoptosis. Mechanistically, we demonstrated an important link between Myc-dependent increases in protein synthesis and UPR activation. Specifically, by employing a mouse minute (L24+/-) mutant, which resulted in wild-type levels of protein synthesis and attenuation of Myc-induced lymphomagenesis, we showed that Myc-induced UPR activation was reversed. Our findings establish a role for UPR as an enhancer of c-Myc-induced transformation and suggest that UPR inhibition may be particularly effective against malignancies characterized by c-Myc overexpression.
Abstract
Translation initiation factor 4G (eIF4G) is an integral component of the eIF4F complex which is key to translation initiation for most eukaryotic mRNAs. Many eIF4G isoforms have been ...described in diverse eukaryotic organisms but we currently have a poor understanding of their functional roles and whether they regulate translation in an mRNA specific manner. The yeast Saccharomyces cerevisiae expresses two eIF4G isoforms, eIF4G1 and eIF4G2, that have previously been considered as functionally redundant with any phenotypic differences arising due to alteration in eIF4G expression levels. Using homogenic strains that express eIF4G1 or eIF4G2 as the sole eIF4G isoforms at comparable expression levels to total eIF4G, we show that eIF4G1 is specifically required to mediate the translational response to oxidative stress. eIF4G1 binds the mRNA cap and remains associated with actively translating ribosomes during oxidative stress conditions and we use quantitative proteomics to show that eIF4G1 promotes oxidative stress-specific proteome changes. eIF4G1, but not eIF4G2, binds the Slf1 LARP protein which appears to mediate the eIF4G1-dependent translational response to oxidative stress. We show similar isoform specific roles for eIF4G in human cells suggesting convergent evolution of multiple eIF4G isoforms offers significant advantages especially where translation must continue under stress conditions.
Graphical Abstract
Graphical Abstract
Understanding factors associated with mortality after a dementia diagnosis can provide essential information to the person with dementia, their family, and caregivers. To date very little is known ...about the factors associated with mortality after a dementia diagnosis in Northern Ireland.
To determine how demographic and other factors such as deprivation and comorbidity medications influence mortality rates after a dementia diagnosis in Northern Ireland and whether these factors are influenced through nursing home transitions.
25,418 people prescribed anti-dementia medication were identified through the enhanced prescribing database between 2010 and 2016. The impact of covariates including age, gender, marital status, deprivation measure, urban/rural classification, and comorbidity medications were examined using cox proportional hazard models with hazard ratios (HR) and 95% confidence intervals.
Between 2010 and 2016, 12,129 deaths occurred, with 114 deaths/1,000 person years. Males had significantly higher mortality rates in comparison to females (HR = 1.28; 95% CI = 1.23-1.33); this was true regardless of whether the person with dementia transitioned to a nursing home. People prescribed anti-dementia drugs living with lower levels of deprivation had significantly lower mortality rates in comparison to people living with the highest levels of deprivation (HR = 0.93; 95% CI = 0.89-0.97). Diabetic (HR = 1.18; 95% CI = 1.07-1.29) and anti-arrhythmic (HR = 2.44; 95% CI = 1.01-5.91) medication in particular significantly influenced mortality.
Male gender, higher comorbidity medications, and living in areas of higher deprivation significantly increased mortality rates for people prescribed anti-dementia drugs in our study population. When comorbidity medications were classified, only anti-arrhythmia and diabetic medications significantly increased mortality. Future research should continue to investigate factors which influence mortality after a dementia diagnosis.
1. Concern about climate change and energy security is stimulating land-use change, which in turn precipitates social, economic and environmental responses. It is predicted that within 20 years in ...the UK, bioenergy crops could occupy significant areas of rural land. Among these, dedicated biomass crops, such as Miscanthus (Miscanthus spp.) grass and short rotation willow (Salix spp.) coppice, differ significantly from arable crops in their growth characteristics and management. It is important that the potential impacts of these differences are assessed before large-scale, long-term planting occurs. 2. We used a Sustainability Appraisal Framework (SAF) approach to landscape planning in the UK to identify stakeholder aspirations (objectives) and associated criteria (indicators) for the planting of dedicated biomass crops. 3. The use of environmental and physical constraints mapping allowed the SAF to focus only on environmentally-acceptable locations, thereby avoiding unsustainable trade-offs. The mapping identified 3·1 million ha of land in England as suitable for planting, suggesting the UK government target of 1·1 million ha by 2020 is feasible. 4. Evaluation of the SAF identified that while biodiversity was of concern to stakeholders, some current indicators of biodiversity are not appropriate. Butterfly abundance proved the most appropriate indicator, and it was found that total abundance was greater in field margins of both willow and Miscanthus biomass crops than in arable field margins. 5. Synthesis and applications. The potential conflicts of assuring food security, water availability, energy security and biodiversity conservation are recognized as a key challenge by governments worldwide. Methods with which decision-makers can compare the performance of different land-use scenarios against sustainability objectives will be crucial for achieving optimized and sustainable use of land-based resources to meet all four challenges. Using biomass crops planting as an example, this work illustrates the potential of a Sustainability Appraisal Framework, subject to identification and agreement of appropriate indicators, in securing a holistic understanding of the wide-ranging implications of large-scale, long-term changes to rural land-use in the wider context of sustainable land-use planning per se.
Objective:
Research has suggested that congruence between patient characteristics and contextual characteristics is a more robust predictor of outcomes than either patient or context characteristics ...alone. The goal of the present study was to examine the degree of congruence between patient preferences for the clinical encounter and reports of analogous dimensions of provider behavior and the effects of this congruence on patient outcomes.
Design:
Two hundred eighteen patients with diabetes (predominately Type II) completed measures of preference for and ratings of perceived provider behavior in three domains (1) information sharing, (2) behavioral involvement, and (3) socioemotional support.
Main Outcome Measures:
Patient satisfaction, self-reported adherence, and a clinical marker of diabetic control (hemoglobin A1c) were the outcomes of interest.
Results:
Congruence in information sharing and congruence in behavioral involvement were predictive of glycemic control and self-reported adherence, respectively. Congruence in behavioral involvement and congruence in socioemotional support were predictive of greater patient satisfaction.
Conclusion:
These findings provide further support for the importance of congruence between patient characteristics and contextual characteristics in predicting patient outcomes.
A nuclear forensics investigation involving a uranium ore concentrate relies on accurate and precise analysis of impurities. Analytical data defensibility requires the use of reference materials as ...part of quality control. This study presents a compilation of trace element concentration results of the CUP-2 Uranium Ore Concentrate Standard measured by 11 different laboratories. The laboratories employed various dissolution methods, analytical preparation methods, and instrumental platforms. The data presented here contain concentrations of 66 impurities with up to 138 individual data points for each impurity. Consensus values have been assigned to each impurity following a statistical analysis of the data set.
THE CHUVA PROJECT Machado, Luiz A. T.; Dias, Maria A. F. Silva; Morales, Carlos ...
Bulletin of the American Meteorological Society,
09/2014, Letnik:
95, Številka:
9
Journal Article
Recenzirano
Odprti dostop
CHUVA, meaning “rain” in Portuguese, is the acronym for the Cloud Processes of the Main Precipitation Systems in Brazil: A Contribution to Cloud-Resolving Modeling and to the Global Precipitation ...Measurement (GPM). The CHUVA project has conducted five field campaigns; the sixth and last campaign will be held in Manaus in 2014. The primary scientific objective of CHUVA is to contribute to the understanding of cloud processes, which represent one of the least understood components of the weather and climate system. The five CHUVA campaigns were designed to investigate specific tropical weather regimes. The first two experiments, in Alcantara and Fortaleza in northeastern Brazil, focused on warm clouds. The third campaign, which was conducted in Belém, was dedicated to tropical squall lines that often form along the sea-breeze front. The fourth campaign was in the Vale do Paraiba of southeastern Brazil, which is a region with intense lightning activity. In addition to contributing to the understanding of cloud process evolution from storms to thunderstorms, this fourth campaign also provided a high-fidelity total lightning proxy dataset for the NOAA Geostationary Operational Environmental Satellite (GOES)-R program. The fifth campaign was carried out in Santa Maria, in southern Brazil, a region of intense hailstorms associated with frequent mesoscale convective complexes. This campaign employed a multimodel high-resolution ensemble experiment. The data collected from contrasting precipitation regimes in tropical continental regions allow the various cloud processes in diverse environments to be compared. Some examples of these previous experiments are presented to illustrate the variability of convection across the tropics.
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