Hierarchical Reactive Control for Soccer Playing Humanoid Robots

What drives thousands of researchers worldwide to devote their creativity and energy t

Decreased plasma phospholipid concentrations and increased acid sphingomyelinase activity are accurate biomarkers for community-acquired pneumonia

Background: There continues to be a great need for better biomarkers and host-directed treatment targets for community-acquired pneumonia (CAP). Alterations in phospholipid metabolism may constitute a source of small molecule biomarkers for acute infections including CAP. Evidence from animal models of pulmonary infections and sepsis suggests that inhibiting acid sphingomyelinase (which releases ceramides from sphingomyelins) may reduce end-organ damage. Methods: We measured concentrations of 105 phospholipids, 40 acylcarnitines, and 4 ceramides, as well as acid sphingomyelinase activity, in plasma from patients with CAP (n=29, sampled on admission and 4 subsequent time points), chronic obstructive pulmonary disease exacerbation with infection (COPD, n=13) as a clinically important disease control, and 33 age- and sex-matched controls. Results: Phospholipid concentrations were greatly decreased in CAP and normalized along clinical improvement. Greatest changes were seen in phosphatidylcholines, followed by lysophosphatidylcholines, sphingomyelins and cer‑ amides (three of which were upregulated), and were least in acylcarnitines. Changes in COPD were less pronounced, but also difered qualitatively, e.g. by increases in selected sphingomyelins. We identifed highly accurate biomark‑ ers for CAP (AUC≤0.97) and COPD (AUC≤0.93) vs. Controls, and moderately accurate biomarkers for CAP vs. COPD (AUC≤0.83), all of which were phospholipids. Phosphatidylcholines, lysophosphatidylcholines, and sphingomyelins were also markedly decreased in S. aureus-infected human A549 and diferentiated THP1 cells. Correlations with C-reactive protein and procalcitonin were predominantly negative but only of mild-to-moderate extent, suggesting that these markers refect more than merely infammation. Consistent with the increased ceramide concentrations, increased acid sphingomyelinase activity accurately distinguished CAP (fold change=2.8, AUC=0.94) and COPD (1.75, 0.88) from Controls and normalized with clinical resolution Conclusions: The results underscore the high potential of plasma phospholipids as biomarkers for CAP, begin to reveal diferences in lipid dysregulation between CAP and infection-associated COPD exacerbation, and suggest that the decreases in plasma concentrations are at least partially determined by changes in host target cells. Furthermore, they provide validation in clinical blood samples of acid sphingomyelinase as a potential treatment target to improve clinical outcome of CAP

Multi-tissue integrative analysis of personal epigenomes

Evaluating the impact of genetic variants on transcriptional regulation is a central goal in biological science that has been constrained by reliance on a single reference genome. To address this, we constructed phased, diploid genomes for four cadaveric donors (using long-read sequencing) and systematically charted noncoding regulatory elements and transcriptional activity across more than 25 tissues from these donors. Integrative analysis revealed over a million variants with allele-specific activity, coordinated, locus-scale allelic imbalances, and structural variants impacting proximal chromatin structure. We relate the personal genome analysis to the ENCODE encyclopedia, annotating allele- and tissue-specific elements that are strongly enriched for variants impacting expression and disease phenotypes. These experimental and statistical approaches, and the corresponding EN-TEx resource, provide a framework for personalized functional genomics

Applications of laser-driven particle acceleration

The first book of its kind to highlight the unique capabilities of laser-driven acceleration and its diverse potential, Applications of Laser-Driven Particle Acceleration presents the basic understanding of acceleration concepts and envisioned prospects for selected applications. As the main focus, this new book explores exciting and diverse application possibilities, with emphasis on those uniquely enabled by the laser driver that can also be meaningful and realistic for potential users. A key aim of the book is to inform multiple, interdisciplinary research communities of the new possibilities available and to inspire them to engage with laser-driven acceleration, further motivating and advancing this developing field. Material is presented in a thorough yet accessible manner, making it a valuable reference text for general scientific and engineering researchers who are not necessarily subject matter experts. Applications of Laser-Driven Particle Acceleration is edited by Professors Paul R. Bolton, Katia Parodi, and Jörg Schreiber from the Department of Medical Physics at the Ludwig-Maximilians-Universität München in München, Germany

Ultrasonography for the diagnosis of Lyme disease in cases of acute facial paralysis

Ultrasonography of the parotid gland was introduced in 1989 as part of the diagnostic protocol of every patient treated in our clinics with acute facial paralysis. Ten of 50 patients so tested were found to have unilateral nonpalpable enlarged lymph nodes in the caudal portion of the parotid gland around the stylomastoid foramen. All 10 patients were eventually diagnosed as having Lyme disease. It is suggested that in patients with acute facial paralysis, ultrasonography is an inexpensive tool to improve diagnosis of Lyme disease and may have a more useful purpose in monitoring therapy

Mutation in the transcriptional regulator PhoP contributes to avirulence of Mycobacterium tuberculosis H37Ra strain.

Attenuated strains of mycobacteria can be exploited to determine genes essential for their pathogenesis and persistence. To this goal, we sequenced the genome of H37Ra, an attenuated variant of Mycobacterium tuberculosis H37Rv strain. Comparison with H37Rv revealed three unique coding region polymorphisms. One polymorphism was located in the DNA-binding domain of the transcriptional regulator PhoP, causing the protein's diminished DNA-binding capacity. Temporal gene expression profiles showed that several genes with reduced expression in H37Ra were also repressed in an H37Rv phoP knockout strain. At later time points, genes of the dormancy regulon, typically expressed in a state of nonreplicating persistence, were upregulated in H37Ra. Complementation of H37Ra with H37Rv phoP partially restored its persistence in a murine macrophage infection model. Our approach demonstrates the feasibility of identifying minute but distinct differences between isogenic strains and illustrates the consequences of single point mutations on the survival stratagem of M. tuberculosis

Decreased plasma phospholipid concentrations and increased acid sphingomyelinase activity are accurate biomarkers for community-acquired pneumonia

Background: There continues to be a great need for better biomarkers and host-directed treatment targets for community-acquired pneumonia (CAP). Alterations in phospholipid metabolism may constitute a source of small molecule biomarkers for acute infections including CAP. Evidence from animal models of pulmonary infections and sepsis suggests that inhibiting acid sphingomyelinase (which releases ceramides from sphingomyelins) may reduce end-organ damage. Methods: We measured concentrations of 105 phospholipids, 40 acylcarnitines, and 4 ceramides, as well as acid sphingomyelinase activity, in plasma from patients with CAP (n=29, sampled on admission and 4 subsequent time points), chronic obstructive pulmonary disease exacerbation with infection (COPD, n=13) as a clinically important disease control, and 33 age- and sex-matched controls. Results: Phospholipid concentrations were greatly decreased in CAP and normalized along clinical improvement. Greatest changes were seen in phosphatidylcholines, followed by lysophosphatidylcholines, sphingomyelins and cer‑ amides (three of which were upregulated), and were least in acylcarnitines. Changes in COPD were less pronounced, but also difered qualitatively, e.g. by increases in selected sphingomyelins. We identifed highly accurate biomark‑ ers for CAP (AUC≤0.97) and COPD (AUC≤0.93) vs. Controls, and moderately accurate biomarkers for CAP vs. COPD (AUC≤0.83), all of which were phospholipids. Phosphatidylcholines, lysophosphatidylcholines, and sphingomyelins were also markedly decreased in S. aureus-infected human A549 and diferentiated THP1 cells. Correlations with C-reactive protein and procalcitonin were predominantly negative but only of mild-to-moderate extent, suggesting that these markers refect more than merely infammation. Consistent with the increased ceramide concentrations, increased acid sphingomyelinase activity accurately distinguished CAP (fold change=2.8, AUC=0.94) and COPD (1.75, 0.88) from Controls and normalized with clinical resolution Conclusions: The results underscore the high potential of plasma phospholipids as biomarkers for CAP, begin to reveal diferences in lipid dysregulation between CAP and infection-associated COPD exacerbation, and suggest that the decreases in plasma concentrations are at least partially determined by changes in host target cells. Furthermore, they provide validation in clinical blood samples of acid sphingomyelinase as a potential treatment target to improve clinical outcome of CAP