Structure and Dynamics of Biological Systems: Integration of Neutron Scattering with Computer Simulation

The combination of molecular dynamics simulation and neutron scattering techniques has emerged as a highly synergistic approach to elucidate the atomistic details of the structure, dynamics and functions of biological systems. Simulation models can be tested by calculating neutron scattering structure factors and comparing the results directly with experiments. If the scattering profiles agree the simulations can be used to provide a detailed decomposition and interpretation of the experiments, and if not, the models can be rationally adjusted. Comparison with neutron experiment can be made at the level of the scattering functions or, less directly, of structural and dynamical quantities derived from them. Here, we examine the combination of simulation and experiment in the interpretation of SANS and inelastic scattering experiments on the structure and dynamics of proteins and other biopolymers

Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Congenital Diaphragmatic hernia – a review

Congenital Diaphragmatic hernia (CDH) is a condition characterized by a defect in the diaphragm leading to protrusion of abdominal contents into the thoracic cavity interfering with normal development of the lungs. The defect may range from a small aperture in the posterior muscle rim to complete absence of diaphragm. The pathophysiology of CDH is a combination of lung hypoplasia and immaturity associated with persistent pulmonary hypertension of newborn (PPHN) and cardiac dysfunction. Prenatal assessment of lung to head ratio (LHR) and position of the liver by ultrasound are used to diagnose and predict outcomes. Delivery of infants with CDH is recommended close to term gestation. Immediate management at birth includes bowel decompression, avoidance of mask ventilation and endotracheal tube placement if required. The main focus of management includes gentle ventilation, hemodynamic monitoring and treatment of pulmonary hypertension followed by surgery. Although inhaled nitric oxide is not approved by FDA for the treatment of PPHN induced by CDH, it is commonly used. Extracorporeal membrane oxygenation (ECMO) is typically considered after failure of conventional medical management for infants ≥ 34 weeks’ gestation or with weight >2 kg with CDH and no associated major lethal anomalies. Multiple factors such as prematurity, associated abnormalities, severity of PPHN, type of repair and need for ECMO can affect the survival of an infant with CDH. With advances in the management of CDH, the overall survival has improved and has been reported to be 70-90% in non-ECMO infants and up to 50% in infants who undergo ECMO

Solar versorgtes Praezisionsthermometer - Neue Funktionalitaet fuer den rauhen Industriebetrieb

For temperature measurement in the industrial field procedures are available, which do not need auxiliary energy. There are machine glass and bimetal thermometers as well as needle thermometers, which are filled with mercury or gas. The typical measuring error of these technical solutions is not under one per cent of the measuring range final value and rises with increasing mechanical aging of the elements of the thermometer. Battery-operated electronic thermometers can be used only in applications, where the limited life span and temperature range of the batteries do not represent a problem. A photovoltaic supplied electronic thermometer offers the advantages of an electronic thermometer, without needing a source of auxiliary energy. In cooperation with the ISET a photovoltaic supplied thermometer for Pt2000-sensors was developed up to production stage. A microcontroller with very small power requirement operates in the electronic circuit. The small request of supply voltage enable operation with a customized solar module. The thermometer operates already at low level of light and displays the current measured value on a large display in quasi-analog and digital form. A substantial improvement of the application parameters could be achieved in relation to conventional solutions. An point-exact recording of measurement is possible in combination with the fast responsing mode of the thermometer. The long-term stability of the measurement is achieved by the electronic signal conditioning. By the additional digital display the measured value can be read out with high accuracy. A further advantage of the device is the use of only one basic modul for a variety of different measuring ranges. The necessary adjustment takes place by an automatic calibration process during the routine check in production. Integrated diagnostic routines monitor constantly the plausibility of the sensor signal and display a break of the sensor.Zur Temperaturmessung im industriellen Umfeld stehen nach dem derzeitigen Stand der Technik Verfahren bereit, die keine Hilfsenergie benoetigen. Es handelt sich um Maschinenglas- und Bimetallthermometer sowie Zeigerthermometer, die mit Quecksilber oder Gas gefuellt sind. Diese Thermometer haben relativ grosse Messwertaufnehmer und eine relativ lange Ansprechzeit. Der typische Messfehler dieser technischen Loesungen liegt im Allgemeinen nicht unter ein Prozent vom Messbereichsendwert und steigt mit zunehmender mechanischer Alterung (ausgenommen Glasthermometer) der Bauelemente des Thermometers an. Ein photovoltaisch versorgtes elektronisches Thermometer bietet sich hier als Loesung an. Es weist die Vorteile eines elektronischen Thermometers auf, ohne eine Hilfsenergiequelle zu benoetigen. Zielstellung des gemeinsam mit dem ISET durchgefuehrten Entwicklungsprojektes war daher die Implementierung eines Messverfahrens mit einem extrem geringen Energieverbrauch. Es konnte eine wesentliche Verbesserung der Einsatzparameter gegenueber herkoemmlichen Loesungen erreicht werden. Fuer den Einsatz im industriellen Bereich wurde das Geraet entsprechend den Vibrations-klassifizierungen des Germanischen Lloyd ausgelegt. Mechanische Zeigerthermometer erfuellen diese Kriterien nur mit einer daempfenden Silikonfluessigkeitsfuellung, was deren Einsatz in vielen Anwendungsbereichen (Lackbenetzung) ausschliesst.Available from: http://www.iset.uni-kassel.de/iset/owa/veroeff / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman