As large-scale studies of gene expression with multiple sources of biological and technical variation become widely adopted, characterizing these drivers of variation becomes essential to ...understanding disease biology and regulatory genetics.
We describe a statistical and visualization framework, variancePartition, to prioritize drivers of variation based on a genome-wide summary, and identify genes that deviate from the genome-wide trend. Using a linear mixed model, variancePartition quantifies variation in each expression trait attributable to differences in disease status, sex, cell or tissue type, ancestry, genetic background, experimental stimulus, or technical variables. Analysis of four large-scale transcriptome profiling datasets illustrates that variancePartition recovers striking patterns of biological and technical variation that are reproducible across multiple datasets.
Our open source software, variancePartition, enables rapid interpretation of complex gene expression studies as well as other high-throughput genomics assays. variancePartition is available from Bioconductor: http://bioconductor.org/packages/variancePartition .
Monolayer FeSe on SrTiO3 Huang, Dennis; Hoffman, Jennifer E
Annual review of condensed matter physics,
03/2017, Letnik:
8
Journal Article
Recenzirano
Epitaxial engineering of solid state heterointerfaces is a leading avenue to realizing enhanced or novel electronic states of matter. As a recent example, bulk FeSe is an unconventional ...superconductor with a modest transition temperature (
T
c
) of 9 K. However, when a single atomic layer of FeSe is grown on SrTiO
3
, its
T
c
can skyrocket by an order of magnitude to 65 K or 109 K. Since this discovery in 2012, efforts to reproduce, understand, and extend these findings continue to draw both excitement and scrutiny. In this review, we first present a critical survey of experimental measurements performed using a wide range of techniques. We then turn to the open question of microscopic mechanisms of superconductivity. We examine contrasting indications for both phononic (conventional) and magnetic/orbital (unconventional) means of electron pairing, as well as speculations about whether they could work cooperatively to boost
T
c
in a monolayer of FeSe.
In this work, we present WALK‐MAN, a humanoid platform that has been developed to operate in realistic unstructured environment, and demonstrate new skills including powerful manipulation, robust ...balanced locomotion, high‐strength capabilities, and physical sturdiness. To enable these capabilities, WALK‐MAN design and actuation are based on the most recent advancements of series elastic actuator drives with unique performance features that differentiate the robot from previous state‐of‐the‐art compliant actuated robots. Physical interaction performance is benefited by both active and passive adaptation, thanks to WALK‐MAN actuation that combines customized high‐performance modules with tuned torque/velocity curves and transmission elasticity for high‐speed adaptation response and motion reactions to disturbances. WALK‐MAN design also includes innovative design optimization features that consider the selection of kinematic structure and the placement of the actuators with the body structure to maximize the robot performance. Physical robustness is ensured with the integration of elastic transmission, proprioceptive sensing, and control. The WALK‐MAN hardware was designed and built in 11 months, and the prototype of the robot was ready four months before DARPA Robotics Challenge (DRC) Finals. The motion generation of WALK‐MAN is based on the unified motion‐generation framework of whole‐body locomotion and manipulation (termed loco‐manipulation). WALK‐MAN is able to execute simple loco‐manipulation behaviors synthesized by combining different primitives defining the behavior of the center of gravity, the motion of the hands, legs, and head, the body attitude and posture, and the constrained body parts such as joint limits and contacts. The motion‐generation framework including the specific motion modules and software architecture is discussed in detail. A rich perception system allows the robot to perceive and generate 3D representations of the environment as well as detect contacts and sense physical interaction force and moments. The operator station that pilots use to control the robot provides a rich pilot interface with different control modes and a number of teleoperated or semiautonomous command features. The capability of the robot and the performance of the individual motion control and perception modules were validated during the DRC in which the robot was able to demonstrate exceptional physical resilience and execute some of the tasks during the competition.
Biotechnology can provide a valuable tool to meet UN Sustainable Development Goals and U.S. initiatives to find climate solutions and improve agricultural sustainability. The literature contains ...hundreds of examples of crops that may serve this purpose, yet most remain un-launched due to high regulatory barriers. Recently the USDA revised its biotechnology regulations to make them more risk-proportionate, science-based, and streamlined. Here, we review some of the promising leads that may enable agriculture to contribute to UN sustainability goals. We further describe and discuss how the revised biotechnology regulation would hypothetically apply to these cases.
We present a number of results about (finite) multiple harmonic sums modulo a prime, which provide interesting parallels to known results about multiple zeta values (i.e. infinite multiple harmonic ...series). In particular, we prove a ‘duality' result for mod p harmonic sums similar to (but distinct from) that for multiple zeta values. We also exploit the Hopf algebra structure of the quasi-symmetric functions to perform calculations with multiple harmonic sums mod p, and obtain, for each weight n through nine, a set of generators for the space of weight-n multiple harmonic sums mod p. When combined with recent work, the results of this paper offer significant evidence that the number of quantities needed to generate the weight-n multiple harmonic sums mod p is the nth Padovan number (OEIS sequence A000931).
A systematic molecular level and spectroscopic investigation is presented to show the cooperative role of Brønsted acid and Lewis acid sites in zeolites for the conversion of methanol. ...Extra-framework alkaline-earth metal containing species and aluminum species decrease the number of Brønsted acid sites, as protonated metal clusters are formed. A combined experimental and theoretical effort shows that postsynthetically modified ZSM-5 zeolites, by incorporation of extra-framework alkaline-earth metals or by demetalation with dealuminating agents, contain both mononuclear MOH+ and double protonated binuclear metal clusters M(μ-OH)2M2+ (M = Mg, Ca, Sr, Ba, and HOAl). The metal in the extra-framework clusters has a Lewis acid character, which is confirmed experimentally and theoretically by IR spectra of adsorbed pyridine. The strength of the Lewis acid sites (Mg > Ca > Sr > Ba) was characterized by a blue shift of characteristic IR peaks, thus offering a tool to sample Lewis acidity experimentally. The incorporation of extra-framework Lewis acid sites has a substantial influence on the reactivity of propene and benzene methylations. Alkaline-earth Lewis acid sites yield increased benzene methylation barriers and destabilization of typical aromatic intermediates, whereas propene methylation routes are less affected. The effect on the catalytic function is especially induced by the double protonated binuclear species. Overall, the extra-framework metal clusters have a dual effect on the catalytic function. By reducing the number of Brønsted acid sites and suppressing typical catalytic reactions in which aromatics are involved, an optimal propene selectivity and increased lifetime for methanol conversion over zeolites is obtained. The combined experimental and theoretical approach gives a unique insight into the nature of the supramolecular zeolite catalyst for methanol conversion which can be meticulously tuned by subtle interplay of Brønsted and Lewis acid sites.
Population structure and kinship are widespread confounding factors in genome-wide association studies (GWAS). It has been standard practice to include principal components of the genotypes in a ...regression model in order to account for population structure. More recently, the linear mixed model (LMM) has emerged as a powerful method for simultaneously accounting for population structure and kinship. The statistical theory underlying the differences in empirical performance between modeling principal components as fixed versus random effects has not been thoroughly examined. We undertake an analysis to formalize the relationship between these widely used methods and elucidate the statistical properties of each. Moreover, we introduce a new statistic, effective degrees of freedom, that serves as a metric of model complexity and a novel low rank linear mixed model (LRLMM) to learn the dimensionality of the correction for population structure and kinship, and we assess its performance through simulations. A comparison of the results of LRLMM and a standard LMM analysis applied to GWAS data from the Multi-Ethnic Study of Atherosclerosis (MESA) illustrates how our theoretical results translate into empirical properties of the mixed model. Finally, the analysis demonstrates the ability of the LRLMM to substantially boost the strength of an association for HDL cholesterol in Europeans.
To examine the impact of marital status on stage at diagnosis, use of definitive therapy, and cancer-specific mortality among each of the 10 leading causes of cancer-related death in the United ...States.
We used the Surveillance, Epidemiology and End Results program to identify 1,260,898 patients diagnosed in 2004 through 2008 with lung, colorectal, breast, pancreatic, prostate, liver/intrahepatic bile duct, non-Hodgkin lymphoma, head/neck, ovarian, or esophageal cancer. We used multivariable logistic and Cox regression to analyze the 734,889 patients who had clinical and follow-up information available.
Married patients were less likely to present with metastatic disease (adjusted odds ratio OR, 0.83; 95% CI, 0.82 to 0.84; P < .001), more likely to receive definitive therapy (adjusted OR, 1.53; 95% CI, 1.51 to 1.56; P < .001), and less likely to die as a result of their cancer after adjusting for demographics, stage, and treatment (adjusted hazard ratio, 0.80; 95% CI, 0.79 to 0.81; P < .001) than unmarried patients. These associations remained significant when each individual cancer was analyzed (P < .05 for all end points for each malignancy). The benefit associated with marriage was greater in males than females for all outcome measures analyzed (P < .001 in all cases). For prostate, breast, colorectal, esophageal, and head/neck cancers, the survival benefit associated with marriage was larger than the published survival benefit of chemotherapy.
Even after adjusting for known confounders, unmarried patients are at significantly higher risk of presentation with metastatic cancer, undertreatment, and death resulting from their cancer. This study highlights the potentially significant impact that social support can have on cancer detection, treatment, and survival.
Transcriptome-wide association studies integrate gene expression data with common risk variation to identify gene-trait associations. By incorporating epigenome data to estimate the functional ...importance of genetic variation on gene expression, we generate a small but significant improvement in the accuracy of transcriptome prediction and increase the power to detect significant expression-trait associations. Joint analysis of 14 large-scale transcriptome datasets and 58 traits identify 13,724 significant expression-trait associations that converge on biological processes and relevant phenotypes in human and mouse phenotype databases. We perform drug repurposing analysis and identify compounds that mimic, or reverse, trait-specific changes. We identify genes that exhibit agonistic pleiotropy for genetically correlated traits that converge on shared biological pathways and elucidate distinct processes in disease etiopathogenesis. Overall, this comprehensive analysis provides insight into the specificity and convergence of gene expression on susceptibility to complex traits.
The methanol-to-hydrocarbons reaction refers collectively to a series of important industrial catalytic processes to produce either olefins or gasoline. Mechanistically, methanol conversion proceeds ...through a 'pool' of hydrocarbon species. For the methanol-to-olefins process, these species can be delineated broadly into 'desired' lighter olefins and 'undesired' heavier fractions that cause deactivation in a matter of hours. The crux in further catalyst optimization is the ability to follow the formation of carbonaceous species during operation. Here, we report the combined results of an operando Kerr-gated Raman spectroscopic study with state-of-the-art operando molecular simulations, which allowed us to follow the formation of hydrocarbon species at various stages of methanol conversion. Polyenes are identified as crucial intermediates towards formation of polycyclic aromatic hydrocarbons, with their fate determined largely by the zeolite topology. Notably, we provide the missing link between active and deactivating species, which allows us to propose potential design rules for future-generation catalysts.
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