Improved spatial separation of neutral molecules

We have developed and experimentally demonstrated an improved electrostatic deflector for the spatial separation of molecules according to their dipole-moment-to-mass ratio. The device features a very open structure that allows for significantly stronger electric fields as well as for stronger deflection without molecules crashing into the device itself. We have demonstrated its performance using the prototypical OCS molecule and we discuss opportunities regarding improved quantum-state-selectivity for complex molecules and the deflection of unpolar molecules.Comment: 6 figure

Stark deceleration of CaF molecules in strong- and weak-field seeking states

We report the Stark deceleration of CaF molecules in the strong-field seeking ground state and in a weak-field seeking component of a rotationally-excited state. We use two types of decelerator, a conventional Stark decelerator for the weak-field seekers, and an alternating gradient decelerator for the strong-field seekers, and we compare their relative merits. We also consider the application of laser cooling to increase the phase-space density of decelerated molecules.Comment: 10 pages, 8 figure

Steering hyper-giants' traffic at scale

Large content providers, known as hyper-giants, are responsible for sending the majority of the content traffic to consumers. These hyper-giants operate highly distributed infrastructures to cope with the ever-increasing demand for online content. To achieve 40 commercial-grade performance of Web applications, enhanced end-user experience, improved reliability, and scaled network capacity, hyper-giants are increasingly interconnecting with eyeball networks at multiple locations. This poses new challenges for both (1) the eyeball networks having to perform complex inbound traffic engineering, and (2) hyper-giants having to map end-user requests to appropriate servers. We report on our multi-year experience in designing, building, rolling-out, and operating the first-ever large scale system, the Flow Director, which enables automated cooperation between one of the largest eyeball networks and a leading hyper-giant. We use empirical data collected at the eyeball network to evaluate its impact over two years of operation. We find very high compliance of the hyper-giant to the Flow Director’s recommendations, resulting in (1) close to optimal user-server mapping, and (2) 15% reduction of the hyper-giant’s traffic overhead on the ISP’s long-haul links, i.e., benefits for both parties and end-users alike.EC/H2020/679158/EU/Resolving the Tussle in the Internet: Mapping, Architecture, and Policy Making/ResolutioNe

Accuracy of prenatal diagnosis of X-linked hypohidrotic ectodermal dysplasia by tooth germ sonography

Objective: X-linked hypohidrotic ectodermal dysplasia (XLHED), a developmental disorder characterized by malformation of hair, teeth, and sweat glands, results from defective ectodysplasin A1 (EDA1) caused by EDA mutations. Inability to sweat, the major problem of XLHED which can lead to life-threatening hyperthermia, has been shown to be amenable to intrauterine therapy with recombinant EDA1. The aim of this retrospective study was to evaluate the diagnostic accuracy of tooth germ sonography to identify affected fetuses in pregnant women with EDA mutations. Methods: Tooth germ sonography was performed in 38 cases at 10 study sites between gestational weeks 18 and 28. XLHED was diagnosed if fewer than six tooth germs were detected in mandible and/or maxilla. In all subjects, diagnoses were verified postnatally by EDA sequencing and/or clinical findings (standardized clinical assessments of hair, sweating, and dentition; orthopantomograms). Estimated weights of 12 affected male fetuses and postnatal weight gain of 12 boys with XLHED were assessed using appropriate growth charts. Results: In 19 of 38 sonografic examinations of 23 male and 13 female fetuses, a prenatal diagnosis of XLHED was made. The diagnosis proved to be correct in 37 cases; one affected male fetus was missed. Specificity and positive predictive value were both 100%. Tooth counting by clinical assessment corresponded well with radiografic findings. We observed no weight deficits of subjects with XLHED in utero but occasionally during infancy. Conclusions: Tooth germ sonography is highly specific and reliable in establishing a prenatal diagnosis of XLHED

Silicon-hydroxyapatite bioactive coatings (Si-HA) from diatomaceous earth and silica. Study of adhesion and proliferation of osteoblast-like cells

The aim of this study consisted on investigating the influence of silicon substituted hydroxyapatite (Si–HA) coatings over the human osteoblast-like cell line (SaOS-2) behaviour. Diatomaceous earth and silica, together with commercial hydroxyapatite were respectively the silicon and HA sources used to produce the Si–HA coatings. HA coatings with 0 wt% of silicon were used as control of the experiment. Pulsed laser deposition (PLD) was the selected technique to deposit the coatings. The Si–HA thin films were characterized by Fourier Transformed Infrared Spectroscopy (FTIR) demonstrating the efficient transfer of Si to the HA structure. The in vitro cell culture was established to assess the cell attachment, proliferation and osteoblastic activity respectively by, Scanning Electron Microscopy (SEM), DNA and alkaline phosphatase (ALP) quantification. The SEM analysis demonstrated a similar adhesion behaviour of the cells on the tested materials and the maintenance of the typical osteoblastic morphology along the time of culture. The Si–HA coatings did not evidence any type of cytotoxic behaviour when compared with HA coatings. Moreover, both the proliferation rate and osteoblastic activity results showed a slightly better performance on the Si–HA coatings from diatoms than on the Si–HA from silica.This work was supported by the UE-Interreg IIIA (SP1.P151/03) Proteus project and Xunta de Galicia ( Projects: 2006/12 and PGIDITO5PXIC30301PN)

Prenatal Correction of X-Linked Hypohidrotic Ectodermal Dysplasia.

Genetic deficiency of ectodysplasin A (EDA) causes X-linked hypohidrotic ectodermal dysplasia (XLHED), in which the development of sweat glands is irreversibly impaired, an condition that can lead to life-threatening hyperthermia. We observed normal development of mouse fetuses with Eda mutations after they had been exposed in utero to a recombinant protein that includes the receptor-binding domain of EDA. We administered this protein intraamniotically to two affected human twins at gestational weeks 26 and 31 and to a single affected human fetus at gestational week 26; the infants, born in week 33 (twins) and week 39 (singleton), were able to sweat normally, and XLHED-related illness had not developed by 14 to 22 months of age. (Funded by Edimer Pharmaceuticals and others.)

Investigation of the Role of Mitochondrial DNA in Multiple Sclerosis Susceptibility

Several lines of evidence suggest that mitochondrial genetic factors may influence susceptibility to multiple sclerosis. To explore this hypothesis further, we re-sequenced the mitochondrial genome (mtDNA) from 159 patients with multiple sclerosis and completed a haplogroup analysis including a further 835 patients and 1,506 controls. A trend towards over-representation of super-haplogroup U was the only evidence for association with mtDNA that we identified in these samples. In a parallel analysis of nuclear encoded mitochondrial genes, we also found a trend towards association with the complex I gene, NDUFS2. These results add to the evidence suggesting that variation in mtDNA and nuclear encoded mitochondrial genes may contribute to disease susceptibility in multiple sclerosis

Molecular pathway-based classification of ectodermal dysplasias: first five-yearly update

To keep pace with the rapid advancements in molecular genetics and rare diseases research, we have updated the list of ectodermal dysplasias based on the latest classification approach that was adopted in 2017 by an international panel of experts. For this purpose, we searched the databases PubMed and OMIM for the term “ectodermal dysplasia”, referring mainly to changes in the last 5 years. We also tried to obtain information about those diseases on which the last scientific report appeared more than 15 years ago by contacting the authors of the most recent publication. A group of experts, composed of researchers who attended the 8th International Conference on Ectodermal Dysplasias and additional members of the previous classification panel, reviewed the proposed amendments and agreed on a final table listing all 49 currently known ectodermal dysplasias for which the molecular genetic basis has been clarified, including 15 new entities. A newly reported ectodermal dysplasia, linked to the gene LRP6, is described here in more detail. These ectodermal dysplasias, in the strict sense, should be distinguished from syndromes with features of ectodermal dysplasia that are related to genes extraneous to the currently known pathways involved in ectodermal development. The latter group consists of 34 syndromes which had been placed on the previous list of ectodermal dysplasias, but most if not all of them could actually be classified elsewhere. This update should streamline the classification of ectodermal dysplasias, provide guidance to the correct diagnosis of rare disease entities, and facilitate the identification of individuals who could benefit from novel treatment options

Extramuscular myofascial force transmission alters substantially the acute effects of surgical aponeurotomy: assessment by finite element modeling

Effects of extramuscular myofascial force transmission on the acute effects of aponeurotomy were studied using finite element modeling and implications of such effects on surgery were discussed. Aponeurotomized EDL muscle of the rat was modeled in two conditions: (1) fully isolated (2) with intact extramuscular connections. The specific goal was to assess the alterations in muscle length-force characteristics in relation to sarcomere length distributions and to investigate how the mechanical mechanism of the intervention is affected if the muscle is not isolated. Major effects of extramuscular myofascial force transmission were shown on muscle length-force characteristics. In contrast to the identical proximal and distal forces of the aponeurotomized isolated muscle, substantial proximo-distal force differences were shown for aponeurotomized muscle with extramuscular connections (for all muscle lengths F dist > F prox after distal muscle lengthening). Proximal optimal length did not change whereas distal optimal length was lower (by 0.5 mm). The optimal forces of the aponeurotomized muscle with extramuscular connections exerted at both proximal and distal tendons were lower than that of isolated muscle (by 15 and 7%, respectively). The length of the gap separating the two cut ends of the intervened aponeurosis decreases substantially due to extramuscular myofascial force transmission. The amplitude of the difference in gap length was muscle length dependent (maximally 11.6% of the gap length of the extramuscularly connected muscle). Extramuscular myofascial force transmission has substantial effects on distributions of lengths of sarcomeres within the muscle fiber populations distal and proximal to the location of intervention: (a) Within the distal population, the substantial sarcomere shortening at the proximal ends of muscle fibers due to the intervention remained unaffected however, extramuscular myofascial force transmission caused a more pronounced serial distribution towards the distal ends of muscle fibers. (b) In contrast, extramuscular myofascial force transmission limits the serial distribution of sarcomere lengths shown for the aponeurotomized isolated muscle in the proximal population. Fiber stress distributions showed that extramuscular myofascial force transmission causes most sarcomeres within the aponeurotomized muscle to attain lengths favorable for higher force exertion. It is concluded that acute effects of aponeurotomy on muscular mechanics are affected greatly by extramuscular myofascial force transmission. Such effects have important implications for the outcome of surgery performed to improve impeded function since muscle in vivo is not isolated both anatomically and mechanically