Three-dimensional structure of human serum albumin

The binding locations to human serum albumin (HSA) of several drug molecules were determined at low resolution using crystallographic methods. The principal binding sites are located within subdomains IIA and IIIA. Preliminary studies suggest that an approach to increasing the in vivo efficacy of drugs which are rendered less effective or ineffective by virtue of their interaction with HSA, would be the use of competitive displacement in drug therapies and/or the development of a general inhibitor to the site within subdomain IIIA. These findings also suggest that the facilitated transfer of various ligands across organ/circulatory interfaces such as liver, kidney, and brain may be associated with binding to the IIIA subdomain

Coherent addition of two dimensional array of fiber lasers

Configurations for efficient free space coherent addition of four separate fiber lasers arranged in two dimensional array are presented. They include compact and robust interferometric combiners that can be inserted either inside or outside the cavity of the combined lasers system. The results reveal that over 85% combining efficiency can be obtained.Comment: To be published in Optics Communicatio

Assessing the Value of Complex Refractive Index and Particle Density for Calibration of Low-Cost Particle Matter Sensor for Size-Resolved Particle Count and PM2.5 Measurements

Commercially available low-cost particulate matter (PM) sensors provide output as total or size-specific particle counts and mass concentrations. These quantities are not measured directly but are estimated by the original equipment manufacturers' (OEM) proprietary algorithms and have inherent limitations since particle scattering depends on their composition, size, shape, and complex index of refraction (CRI). Hence, there is a need to characterize and calibrate their performance under a controlled environment. We present calibration algorithms for Plantower PMS A003 sensor as a function of particle size and concentration. A standardized experimental protocol was used to control the PM level, environmental conditions and to evaluate sensor-to-sensor reproducibility. The calibration was based on tests when PMS A003 were exposed to different polydisperse standardized testing aerosols. The results suggested particle size distribution from PMS A003 was shifted compared to reference instrument measures. For calibration of number concentration, linear model without adjusting aerosol properties corrects the raw PMS A003 measurement for specific size bins with normalized mean absolute error within 4.0% of the reference instrument. Although the Bayesian Information Criterion suggests that models adjusting for particle optical properties and relative humidity are technically superior, they should be used with caution as the particle properties used in fitting were within a narrow range for challenge aerosols. The calibration models adjusted for particle CRI and density account for non-linearity in the OEM's mass concentrations estimates and demonstrated lower error. These results have significant implications for using PMS A003 in high concentration environments, including indoor air quality and occupational/industrial exposure assessments, wildfire smoke, or near-source monitoring scenarios

Learning neutrino effects in Cosmology with Convolutional Neural Networks

Measuring the sum of the three active neutrino masses, $M_\nu$, is one of the most important challenges in modern cosmology. Massive neutrinos imprint characteristic signatures on several cosmological observables in particular on the large-scale structure of the Universe. In order to maximize the information that can be retrieved from galaxy surveys, accurate theoretical predictions in the non-linear regime are needed. Currently, one way to achieve those predictions is by running cosmological numerical simulations. Unfortunately, producing those simulations requires high computational resources -- seven hundred CPU hours for each neutrino mass case. In this work, we propose a new method, based on a deep learning network (U-Net), to quickly generate simulations with massive neutrinos from standard $\Lambda$CDM simulations without neutrinos. We computed multiple relevant statistical measures of deep-learning generated simulations, and conclude that our method accurately reproduces the 3-dimensional spatial distribution of matter down to non-linear scales: $k < 0.7$ h/Mpc. Finally, our method allows us to generate massive neutrino simulations 10,000 times faster than the traditional methods.Comment: 8 pages, 7 figure

Impaired mitochondrial biogenesis is a common feature to myocardial hypertrophy and end-stage ischemic heart failure

Mitochondrial (mt) DNA depletion and oxidative mtDNA damage have been implicated in the process of pathological cardiac remodeling. Whether these features are present in the early phase of maladaptive cardiac remodeling, that is, during compensated cardiac hypertrophy, is still unknown. We compared the morphologic and molecular features of mt biogenesis and markers of oxidative stress in human heart from adult subjects with compensated hypertrophic cardiomyopathy and heart failure. We have shown that mtDNA depletion is a constant feature of both conditions. A quantitative loss of mtDNA content was associated with significant down-regulation of selected modulators of mt biogenesis and decreased expression of proteins involved in mtDNA maintenance. Interestingly, mtDNA depletion characterized also the end-stage phase of cardiomyopathies due to a primary mtDNA defect. Oxidative stress damage was detected only in failing myocardium

Novel compound mutations in the mitochondrial translation elongation factor (TSFM) gene cause severe cardiomyopathy with myocardial fibro-adipose replacement

Primary mitochondrial dysfunction is an under-appreciated cause of cardiomyopathy, especially when cardiac symptoms are the unique or prevalent manifestation of disease. Here, we report an unusual presentation of mitochondrial cardiomyopathy, with dilated phenotype and pathologic evidence of biventricular fibro-adipose replacement, in a 33-year old woman who underwent cardiac transplant. Whole exome sequencing revealed two novel compound heterozygous variants in the TSFM gene, coding for the mitochondrial translation elongation factor EF-Ts. This protein participates in the elongation step of mitochondrial translation by binding and stabilizing the translation elongation factor Tu (EF-Tu). Bioinformatics analysis predicted a destabilization of the EF-Ts variants complex with EF-Tu, in agreement with the dramatic steady-state level reduction of both proteins in the clinically affected myocardium, which demonstrated a combined respiratory chain enzyme deficiency. In patient fibroblasts, the decrease of EF-Ts was paralleled by up-regulation of EF-Tu and induction of genes involved in mitochondrial biogenesis, along with increased expression of respiratory chain subunits and normal oxygen consumption rate. Our report extends the current picture of morphologic phenotypes associated with mitochondrial cardiomyopathies and confirms the heart as a main target of TSFM dysfunction. The compensatory response detected in patient fibroblasts might explain the tissue-specific expression of TSFM-associated disease