Cooling and control of a cavity optoelectromechanical system

We implement a cavity optoelectromechanical system integrating electrical actuation capabilities of nanoelectromechanical devices with ultrasensitive mechanical transduction achieved via intracavity optomechanical coupling. Electrical gradient forces as large as 0.40 mu N are realized, with simultaneous mechanical transduction sensitivity of 1.5 x 10(-18) mHz(-1/2) representing a 3 orders of magnitude improvement over any nanoelectromechanical system to date. Optoelectromechanical feedback cooling is demonstrated, exhibiting strong squashing of the in-loop transduction signal. Out-of-loop transduction provides accurate temperature calibration even in the critical paradigm where measurement backaction induces optomechanical correlations

Efficient processing of raster and vector data

[Abstract] In this work, we propose a framework to store and manage spatial data, which includes new efficient algorithms to perform operations accepting as input a raster dataset and a vector dataset. More concretely, we present algorithms for solving a spatial join between a raster and a vector dataset imposing a restriction on the values of the cells of the raster; and an algorithm for retrieving K objects of a vector dataset that overlap cells of a raster dataset, such that the K objects are those overlapping the highest (or lowest) cell values among all objects. The raster data is stored using a compact data structure, which can directly manipulate compressed data without the need for prior decompression. This leads to better running times and lower memory consumption. In our experimental evaluation comparing our solution to other baselines, we obtain the best space/time trade-offs.Ministerio de Ciencia, Innovación y Universidades; TIN2016-78011-C4-1-RMinisterio de Ciencia, Innovación y Universidades; TIN2016-77158 C4-3-RMinisterio de Ciencia, Innovación y Universidades; RTC-2017-5908-7Xunta de Galicia; ED431C 2017/58Xunta de Galicia; ED431G/01Xunta de Galicia; IN852A 2018/14University of Bío-Bío; 192119 2/RUniversity of Bío-Bío; 195119 GI/V

Recombination in Streptococcus pneumoniae Lineages Increase with Carriage Duration and Size of the Polysaccharide Capsule.

Streptococcus pneumoniae causes a high burden of invasive pneumococcal disease (IPD) globally, especially in children from resource-poor settings. Like many bacteria, the pneumococcus can import DNA from other strains or even species by transformation and homologous recombination, which has allowed the pneumococcus to evade clinical interventions such as antibiotics and pneumococcal conjugate vaccines (PCVs). Pneumococci are enclosed in a complex polysaccharide capsule that determines the serotype; the capsule varies in size and is associated with properties including carriage prevalence and virulence. We determined and quantified the association between capsule and recombination events using genomic data from a diverse collection of serotypes sampled in Malawi. We determined both the amount of variation introduced by recombination relative to mutation (the relative rate) and how many individual recombination events occur per isolate (the frequency). Using univariate analyses, we found an association between both recombination measures and multiple factors associated with the capsule, including duration and prevalence of carriage. Because many capsular factors are correlated, we used multivariate analysis to correct for collinearity. Capsule size and carriage duration remained positively associated with recombination, although with a reduced P value, and this effect may be mediated through some unassayed additional property associated with larger capsules. This work describes an important impact of serotype on recombination that has been previously overlooked. While the details of how this effect is achieved remain to be determined, it may have important consequences for the serotype-specific response to vaccines and other interventions. IMPORTANCE: The capsule determines >90 different pneumococcal serotypes, which vary in capsule size, virulence, duration, and prevalence of carriage. Current serotype-specific vaccines elicit anticapsule antibodies. Pneumococcus can take up exogenous DNA by transformation and insert it into its chromosome by homologous recombination. This mechanism has disseminated drug resistance and generated vaccine escape variants. It is hence crucial to pneumococcal evolutionary response to interventions, but there has been no systematic study quantifying whether serotypes vary in recombination and whether this is associated with serotype-specific properties such as capsule size or carriage duration. Larger capsules could physically inhibit DNA uptake, or given the longer carriage duration for larger capsules, this may promote recombination. We find that recombination varies among capsules and is associated with capsule size, carriage duration, and carriage prevalence and negatively associated with invasiveness. The consequence of this work is that serotypes with different capsules may respond differently to selective pressures like vaccines

A Descriptive Morphology of the Ant Genus Procryptocerus (Hymenoptera: Formicidae)

Morphology is the most direct approach biologists have to recognize uniqueness of insect species as compared to close relatives. Ants of the genus Procryptocerus possess important morphologic characters yet have not been explored for use in a taxonomic revision. The genus is characterized by the protrusion of the clypeus forming a broad nasus and antennal scrobes over the eyes. The toruli are located right posterior to the flanks of the nasus opposite to each other. The vertex is deflexed posteriorly in most species. An in-group comparison of the external morphology is presented focusing on the workers. A general morphology for gynes and males is also presented. Previously mentioned characters as well as new ones are presented, and their character states in different species are clarified. For the metasoma a new system of ant metasomal somite nomenclature is presented that is applicable to Aculeata in general. Finally, a Glossary of morphological terms is offered for the genus (available online). Most of the terminology can be used in other members of the Formicidae and Aculeata

Concurrent exergaming and transcranial direct current stimulation to improve balance in people with Parkinson's disease: study protocol for a randomised controlled trial

BACKGROUND: People with Parkinson\u27s disease (PD) commonly experience postural instability, resulting in poor balance and an increased risk of falls. Exercise-based video gaming (exergaming) is a form of physical training that is delivered through virtual reality technology to facilitate motor learning and is efficacious in improving balance in aged populations. In addition, studies have shown that anodal transcranial direct current stimulation (a-tDCS), when applied to the primary motor cortex, can augment motor learning when combined with physical training. However, no studies have investigated the combined effects of exergaming and tDCS on balance in people with PD. METHODS/DESIGN: Twenty-four people with mild to moderate PD (Hoehn and Yahr scale score 2-4) will be randomly allocated to receive one of three interventions: (1) exergaming + a-tDCS, (2) exergaming + sham a-tDCS or (3) usual care. Participants in each exergaming group will perform two training sessions per week for 12 weeks. Each exergaming session will consist of a series of static and dynamic balance exercises using a rehabilitation-specific software programme (Jintronix) and 20 minutes of either sham or real a-tDCS (2 mA) delivered concurrently. Participants allocated to usual care will be asked to maintain their normal daily physical activities. All outcome measures will be assessed at baseline and at 6 weeks (mid-intervention), 12 weeks (post-intervention) and 24 weeks (3-month follow-up) after baseline. The primary outcome measure will be the Limits of Stability Test. Secondary outcomes will include measures of static balance, leg strength, functional capacity, cognitive task-related cortical activation, corticospinal excitability and inhibition, and cognitive inhibition. DISCUSSION: This will be the first trial to target balance in people with PD with combined exergaming and a-tDCS. We hypothesise that improvements in balance, functional and neurophysiological outcome measures, and neurocognitive outcome measures will be greater and longer-lasting following concurrent exergaming and a-tDCS than in those receiving sham tDCS or usual care

Letter processing and font information during reading: beyond distinctiveness, where vision meets design

Letter identification is a critical front end of the reading process. In general, conceptualizations of the identification process have emphasized arbitrary sets of distinctive features. However, a richer view of letter processing incorporates principles from the field of type design, including an emphasis on uniformities across letters within a font. The importance of uniformities is supported by a small body of research indicating that consistency of font increases letter identification efficiency. We review design concepts and the relevant literature, with the goal of stimulating further thinking about letter processing during reading

The ethical desirability of moral bioenhancement: A review of reasons

Background: The debate on the ethical aspects of moral bioenhancement focuses on the desirability of using biomedical as opposed to traditional means to achieve moral betterment. The aim of this paper is to systematically review the ethical reasons presented in the literature for and against moral bioenhancement. Discussion: A review was performed and resulted in the inclusion of 85 articles. We classified the arguments used in those articles in the following six clusters: (1) why we (don't) need moral bioenhancement, (2) it will (not) be possible to reach consensus on what moral bioenhancement should involve, (3) the feasibility of moral bioenhancement and the status of current scientific research, (4) means and processes of arriving at moral improvement matter ethically, (5) arguments related to the freedom, identity and autonomy of the individual, and (6) arguments related to social/group effects and dynamics. We discuss each argument separately, and assess the debate as a whole. First, there is little discussion on what distinguishes moral bioenhancement from treatment of pathological deficiencies in morality. Furthermore, remarkably little attention has been paid so far to the safety, risks and side-effects of moral enhancement, including the risk of identity changes. Finally, many authors overestimate the scientific as well as the practical feasibility of the interventions they discuss, rendering the debate too speculative. Summary: Based on our discussion of the arguments used in the debate on moral enhancement, and our assessment of this debate, we advocate a shift in focus. Instead of speculating about non-realistic hypothetical scenarios such as the genetic engineering of morality, or morally enhancing 'the whole of humanity', we call for a more focused debate on realistic options of biomedical treatment of moral pathologies and the concrete moral questions these treatments raise

The contribution of microlensing surveys to the distance scale

In the early nineties several teams started large scale systematic surveys of the Magellanic Clouds and the Galactic Bulge to search for microlensing effects. As a by product, these groups have created enormous time-series databases of photometric measurements of stars with a temporal sampling duration and accuracy which are unprecedented. They provide the opportunity to test the accuracy of primary distance indicators, such as Cepheids, RRLyrae stars, the detached eclipsing binaries, or the luminosity of the red clump. We will review the contribution of the microlensing surveys to the understanding of the physics of the primary distance indicators, recent differential studies and direct distance determinations to the Magellanic Clouds and the Galactic Bulge.Comment: Invited review article to appear in: `Post-Hipparcos Cosmic Candles', A. Heck & F. Caputo (Eds), Kluwer Academic Publ., Dordrecht, in press. 21 pages; uses Kluwer's crckapb.sty LaTeX style file, enclose

Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study

BACKGROUND: Isocitrate dehydrogenase 1 (IDH1) mutations occur in approximately 13% of patients with intrahepatic cholangiocarcinoma, a relatively uncommon cancer with a poor clinical outcome. The aim of this international phase 3 study was to assess the efficacy and safety of ivosidenib (AG-120)-a small-molecule targeted inhibitor of mutated IDH1-in patients with previously treated IDH1-mutant cholangiocarcinoma. METHODS: This multicentre, randomised, double-blind, placebo-controlled, phase 3 study included patients from 49 hospitals in six countries aged at least 18 years with histologically confirmed, advanced, IDH1-mutant cholangiocarcinoma who had progressed on previous therapy, and had up to two previous treatment regimens for advanced disease, an Eastern Cooperative Oncology Group performance status score of 0 or 1, and a measurable lesion as defined by Response Evaluation Criteria in Solid Tumors version 1.1. Patients were randomly assigned (2:1) with a block size of 6 and stratified by number of previous systemic treatment regimens for advanced disease to oral ivosidenib 500 mg or matched placebo once daily in continuous 28-day cycles, by means of an interactive web-based response system. Placebo to ivosidenib crossover was permitted on radiological progression per investigator assessment. The primary endpoint was progression-free survival by independent central review. The intention-to-treat population was used for the primary efficacy analyses. Safety was assessed in all patients who had received at least one dose of ivosidenib or placebo. Enrolment is complete; this study is registered with ClinicalTrials.gov, NCT02989857. FINDINGS: Between Feb 20, 2017, and Jan 31, 2019, 230 patients were assessed for eligibility, and as of the Jan 31, 2019 data cutoff date, 185 patients were randomly assigned to ivosidenib (n=124) or placebo (n=61). Median follow-up for progression-free survival was 6·9 months (IQR 2·8-10·9). Progression-free survival was significantly improved with ivosidenib compared with placebo (median 2·7 months [95% CI 1·6-4·2] vs 1·4 months [1·4-1·6]; hazard ratio 0·37; 95% CI 0·25-0·54; one-sided p<0·0001). The most common grade 3 or worse adverse event in both treatment groups was ascites (four [7%] of 59 patients receiving placebo and nine [7%] of 121 patients receiving ivosidenib). Serious adverse events were reported in 36 (30%) of 121 patients receiving ivosidenib and 13 (22%) of 59 patients receiving placebo. There were no treatment-related deaths. INTERPRETATION: Progression-free survival was significantly improved with ivosidenib compared with placebo, and ivosidenib was well tolerated. This study shows the clinical benefit of targeting IDH1 mutations in advanced, IDH1-mutant cholangiocarcinoma. FUNDING: Agios Pharmaceuticals