Deformed Jarzynski Equality

The well-known Jarzynski equality, often written in the form $e^{-\beta\Delta F}=\langle e^{-\beta W}\rangle$, provides a non-equilibrium means to measure the free energy difference $\Delta F$ of a system at the same inverse temperature $\beta$ based on an ensemble average of non-equilibrium work $W$. The accuracy of Jarzynski's measurement scheme was known to be determined by the variance of exponential work, denoted as ${\rm var}\left(e^{-\beta W}\right)$. However, it was recently found that ${\rm var}\left(e^{-\beta W}\right)$ can systematically diverge in both classical and quantum cases. Such divergence will necessarily pose a challenge in the applications of Jarzynski equality because it may dramatically reduce the efficiency in determining $\Delta F$. In this work, we present a deformed Jarzynski equality for both classical and quantum non-equilibrium statistics, in efforts to reuse experimental data that already suffers from a diverging ${\rm var}\left(e^{-\beta W}\right)$. The main feature of our deformed Jarzynski equality is that it connects free energies at different temperatures and it may still work efficiently subject to a diverging ${\rm var}\left(e^{-\beta W}\right)$. The conditions for applying our deformed Jarzynski equality may be met in experimental and computational situations. If so, then there is no need to redesign experimental or simulation methods. Furthermore, using the deformed Jarzynski equality, we exemplify the distinct behaviors of classical and quantum work fluctuations for the case of a time-dependent driven harmonic oscillator dynamics and provide insights into the essential performance differences between classical and quantum Jarzynski equalities.Comment: 24 pages, 1 figure, accepted version to appear in Entropy (Special Issue on "Quantum Thermodynamics"

Temporal light field reconstruction for rendering distribution effects

Traditionally, effects that require evaluating multidimensional integrals for each pixel, such as motion blur, depth of field, and soft shadows, suffer from noise due to the variance of the high-dimensional integrand. In this paper, we describe a general reconstruction technique that exploits the anisotropy in the temporal light field and permits efficient reuse of samples between pixels, multiplying the effective sampling rate by a large factor. We show that our technique can be applied in situations that are challenging or impossible for previous anisotropic reconstruction methods, and that it can yield good results with very sparse inputs. We demonstrate our method for simultaneous motion blur, depth of field, and soft shadows

Cerebral oximetry during cardiac arrest : a multicenter study of neurologic outcomes and survival

OBJECTIVES Cardiac arrest is associated with morbidity and mortality because of cerebral ischemia. Therefore, we tested the hypothesis that higher regional cerebral oxygenation during resuscitation is associated with improved return of spontaneous circulation, survival, and neurologic outcomes at hospital discharge. We further examined the validity of regional cerebral oxygenation as a test to predict these outcomes. DESIGN Multicenter prospective study of in-hospital cardiac arrest. SETTING Five medical centers in the United States and the United Kingdom. PATIENTS Inclusion criteria are as follows: in-hospital cardiac arrest, age 18 years old or older, and prolonged cardiopulmonary resuscitation greater than or equal to 5 minutes. Patients were recruited consecutively during working hours between August 2011 and September 2014. Survival with a favorable neurologic outcome was defined as a cerebral performance category 1-2. INTERVENTIONS Cerebral oximetry monitoring. MEASUREMENTS AND MAIN RESULTS Among 504 in-hospital cardiac arrest events, 183 (36%) met inclusion criteria. Overall, 62 of 183 (33.9%) achieved return of spontaneous circulation, whereas 13 of 183 (7.1%) achieved cerebral performance category 1-2 at discharge. Higher mean ± SD regional cerebral oxygenation was associated with return of spontaneous circulation versus no return of spontaneous circulation (51.8% ± 11.2% vs 40.9% ± 12.3%) and cerebral performance category 1-2 versus cerebral performance category 3-5 (56.1% ± 10.0% vs 43.8% ± 12.8%) (both p < 0.001). Mean regional cerebral oxygenation during the last 5 minutes of cardiopulmonary resuscitation best predicted the return of spontaneous circulation (area under the curve, 0.76; 95% CI, 0.69-0.83); regional cerebral oxygenation greater than or equal to 25% provided 100% sensitivity (95% CI, 94-100) and 100% negative predictive value (95% CI, 79-100); regional cerebral oxygenation greater than or equal to 65% provided 99% specificity (95% CI, 95-100) and 93% positive predictive value (95% CI, 66-100) for return of spontaneous circulation. Time with regional cerebral oxygenation greater than 50% during cardiopulmonary resuscitation best predicted cerebral performance category 1-2 (area under the curve, 0.79; 95% CI, 0.70-0.88). Specifically, greater than or equal to 60% cardiopulmonary resuscitation time with regional cerebral oxygenation greater than 50% provided 77% sensitivity (95% CI,:46-95), 72% specificity (95% CI, 65-79), and 98% negative predictive value (95% CI, 93-100) for cerebral performance category 1-2. CONCLUSIONS Cerebral oximetry allows real-time, noninvasive cerebral oxygenation monitoring during cardiopulmonary resuscitation. Higher cerebral oxygenation during cardiopulmonary resuscitation is associated with return of spontaneous circulation and neurologically favorable survival to hospital discharge. Achieving higher regional cerebral oxygenation during resuscitation may optimize the chances of cardiac arrest favorable outcomes

Polycystic Ovary Syndrome: Pathophysiology and therapeutic opportunities

Polycystic ovary syndrome (PCOS) is characterised by androgen excess and ovulatory dysfunction, and is one of the commonest endocrine disorders in women of reproductive age. PCOS arises as a result of polygenic susceptibility in combination with environmental influences that may include epigenetic alterations and in utero programming. In addition to the well-recognised clinical manifestations of hyperandrogenism and ovulatory dysfunction, women with PCOS are at increased risk of adverse mental health outcomes, pregnancy complications and cardiometabolic disease. Existing unlicensed treatments have limited efficacy, not least because drug development has been hampered by an incomplete understanding of the underlying pathophysiological processes. Advances in genetics, metabolomics and adipocyte biology have improved our understanding of key changes in neuroendocrine, enteroendocrine and steroidogenic pathways, including increased gonadotrophin-releasing hormone (GnRH) pulsatility, androgen excess, insulin resistance and alterations in the gut microbiome. 11-oxygenated androgens, with high androgenic potency, are abundant in many patients with PCOS and may mediate metabolic risk. These advances have prompted the development of new treatments, including those which target the neurokinin-kisspeptin axis upstream of GnRH, with the potential to mitigate adverse clinical sequelae and improve patient outcomes

The spatial and temporal dynamics of commuting : examining the impacts of urban growth patterns, 1980-2000

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Urban Studies and Planning, 2005.Includes bibliographical references (p. 158-165).The dissertation is broadly concerned with the issues of urban transportation and urban spatial structure change. The focus of the research is to interpret the increase in commuting time and distance in the last two decades. The major hypothesis is that a significant proportion of commuting length increase can be explained by land development patterns, particularly the spatial relationship between workplace and residence. The biggest challenge to address the above problem is to design a method that characterizes job-housing proximity and correlates commuting with job-housing proximity consistently across space, over time and among different regions. A thorough evaluation of existing measures, including ratios of jobs to employed residents, gravity type accessibility and minimum required commuting, shows that all have serious problems. The dissertation presents a new approach - the commuting spectrum - for measuring and interpreting the commuting impacts of metropolitan changes in terms of job-housing distribution. This method is then used to explain commuting in two sizable but contrasting regions, Boston and Atlanta. Journey-to-work data from Census Transportation Planning Packages (CTPP) over three decades (1980, 1990 and 1990) are utilized.(cont.) Results indicate that the configuration of commuting spectrums mirror the changes in urban spatial structure in terms of job-housing proximity. In addition, the spatial variation, temporal change and regional differences in commuting can be significantly explained with job-housing proximity. Empirical results suggest that spatial decentralization pathways in Atlanta and Boston change the regional patterns of job-housing proximity, attracting people to commute longer distances. The relatively constrained spatial decentralization in Boston results in shorter commuting time and distance than in Atlanta. The empirical results point to a constrained and balanced vision of urban growth for achieving a commuting economy. Both urban growth management and transportation policies are needed to help achieve this vision.by Jiawen Yang.Ph.D

MagicalRsq: Machine-learning-based genotype imputation quality calibration

Whole-genome sequencing (WGS) is the gold standard for fully characterizing genetic variation but is still prohibitively expensive for large samples. To reduce costs, many studies sequence only a subset of individuals or genomic regions, and genotype imputation is used to infer genotypes for the remaining individuals or regions without sequencing data. However, not all variants can be well imputed, and the current state-of-the-art imputation quality metric, denoted as standard Rsq, is poorly calibrated for lower-frequency variants. Here, we propose MagicalRsq, a machine-learning-based method that integrates variant-level imputation and population genetics statistics, to provide a better calibrated imputation quality metric. Leveraging WGS data from the Cystic Fibrosis Genome Project (CFGP), and whole-exome sequence data from UK BioBank (UKB), we performed comprehensive experiments to evaluate the performance of MagicalRsq compared to standard Rsq for partially sequenced studies. We found that MagicalRsq aligns better with true R2 than standard Rsq in almost every situation evaluated, for both European and African ancestry samples. For example, when applying models trained from 1,992 CFGP sequenced samples to an independent 3,103 samples with no sequencing but TOPMed imputation from array genotypes, MagicalRsq, compared to standard Rsq, achieved net gains of 1.4 million rare, 117k low-frequency, and 18k common variants, where net gains were gained numbers of correctly distinguished variants by MagicalRsq over standard Rsq. MagicalRsq can serve as an improved post-imputation quality metric and will benefit downstream analysis by better distinguishing well-imputed variants from those poorly imputed. MagicalRsq is freely available on GitHub

Mosaic Chromosomal alterations in Blood across ancestries Using Whole-Genome Sequencing

Megabase-scale mosaic chromosomal alterations (mCAs) in blood are prognostic markers for a host of human diseases. Here, to gain a better understanding of mCA rates in genetically diverse populations, we analyzed whole-genome sequencing data from 67,390 individuals from the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine program. We observed higher sensitivity with whole-genome sequencing data, compared with array-based data, in uncovering mCAs at low mutant cell fractions and found that individuals of European ancestry have the highest rates of autosomal mCAs and the lowest rates of chromosome X mCAs, compared with individuals of African or Hispanic ancestry. Although further studies in diverse populations will be needed to replicate our findings, we report three loci associated with loss of chromosome X, associations between autosomal mCAs and rare variants in DCPS, ADM17, PPP1R16B and TET2 and ancestry-specific variants in ATM and MPL with mCAs in cis

Growth of centimeter scale carbon wires using in-liquid AC arc discharge:

A novel observation of the formation of carbon wire in a carbon-based liquid solvent, using in liquid high voltage AC arc discharge is described. The authors describe the observed phenomenon, technical equipment needed to achieve the effect and preliminary qualitative results of obtained material. The wire consisted of well packed layers of carbon elements. The arc-discharge method is a simple, low cost method for the production of three dimensional carbon structures. A further research is needed to get a thorough understanding of the phenomenon

Genomic and phenotypic correlates of mosaic loss of chromosome Y in blood

Mosaic loss of Y (mLOY) is the most common somatic chromosomal alteration detected in human blood. The presence of mLOY is associated with altered blood cell counts and increased risk of Alzheimer disease, solid tumors, and other age-related diseases. We sought to gain a better understanding of genetic drivers and associated phenotypes of mLOY through analyses of whole-genome sequencing (WGS) of a large set of genetically diverse males from the Trans-Omics for Precision Medicine (TOPMed) program. We show that haplotype-based calling methods can be used with WGS data to successfully identify mLOY events. This approach enabled us to identify differences in mLOY frequencies across populations defined by genetic similarity, revealing a higher frequency of mLOY in the European (EUR) ancestry group compared to other ancestries. We identify multiple loci associated with mLOY susceptibility and show that subsets of human hematopoietic stem cells are enriched for the activity of mLOY susceptibility variants. Finally, we found that certain alleles on chromosome Y are more likely to be lost than others in detectable mLOY clones