Actuation of Micro-Optomechanical Systems Via Cavity-Enhanced Optical Dipole Forces

We demonstrate a new type of optomechanical system employing a movable, micron-scale waveguide evanescently-coupled to a high-Q optical microresonator. Micron-scale displacements of the waveguide are observed for milliwatt(mW)-level optical input powers. Measurement of the spatial variation of the force on the waveguide indicates that it arises from a cavity-enhanced optical dipole force due to the stored optical field of the resonator. This force is used to realize an all-optical tunable filter operating with sub-mW control power. A theoretical model of the system shows the maximum achievable force to be independent of the intrinsic Q of the optical resonator and to scale inversely with the cavity mode volume, suggesting that such forces may become even more effective as devices approach the nanoscale.Comment: 4 pages, 5 figures. High resolution version available at (http://copilot.caltech.edu/publications/CEODF_hires.pdf). For associated movie, see (http://copilot.caltech.edu/research/optical_forces/index.htm

Un nuevo instrumento para la investigación criminológica

Una investigación realizada en 36 estados miembros del Consejo de Europa ha permitido publicar una Colección Europea de Estadísticas de la Delincuencia y la Justicia Penal (1). Esta Colección permite comparar la información de carácter estadístico disponible en distintas áreas y, en particular, la manera en que esta información es recogida y las definiciones utilizadas en los distintos países. La información que aporta se compone de datos policiales sobre delitos, presuntos autores y costes, datos de las autoridades encargadas de la instrucción, datos de sentencias judiciales, datos penitenciarios que se recopilaron utilizando la Estadística Penal Anual del Consejo de Europa (Council of Europe Annual Penal Statistics, SPACE) y el cuestionario utilizado para elaborar esta colección, y datos de victimación del International Crime Victims Survey, ICVS. Algunos miembros del grupo de expertos que dirigió la investigación presentan a continuación un breve resumen de la información que contiene la Colección y los principales resultados de algunos artículos que han utilizado esa información

Application of Atomic Dielectric Resonance Spectroscopy for the screening of blood samples from patients with clinical variant and sporadic CJD

<p>Abstract</p> <p>Background</p> <p>Sub-clinical variant Creutzfeldt-Jakob disease (vCJD) infection and reports of vCJD transmission through blood transfusion emphasise the need for blood screening assays to ensure the safety of blood and transplanted tissues. Most assays aim to detect abnormal prion protein (PrP^Sc), although achieving required sensitivity is a challenge.</p> <p>Methods</p> <p>We have used innovative Atomic Dielectric Resonance Spectroscopy (ADRS), which determines dielectric properties of materials which are established by reflectivity and penetration of radio/micro waves, to analyse blood samples from patients and controls to identify characteristic ADR signatures unique to blood from vCJD and to sCJD patients. Initial sets of blood samples from vCJD, sCJD, non-CJD neurological diseases and normal healthy adults (blood donors) were screened as training samples to determine group-specific ADR characteristics, and provided a basis for classification of blinded sets of samples.</p> <p>Results</p> <p>Blood sample groups from vCJD, sCJD, non-CJD neurological diseases and normal healthy adults (blood donors) screened by ADRS were classified with 100% specificity and sensitivity, discriminating these by a co-variance expert analysis system.</p> <p>Conclusion</p> <p>ADRS appears capable of recognising and discriminating serum samples from vCJD, sCJD, non-CJD neurological diseases, and normal healthy adults, and might be developed to provide a system for primary screening or confirmatory assay complementary to other screening systems.</p

Evaluation of Ambulance Based Troponin Measurements : A Feasibility and Impact Pilot Study of the Utility of pre-Hospital POC Testing of Cardiac Biomarkers on Patients Presenting with Acute Chest Pain

This final report is a Summary of a Phase 1 Program to determine the feasibility and logistics of performing Cardiac Biomarker measurements in the ambulance setting with paramedics. Specifically the report presents the findings and a list of recommendations relative to the measurement of cardiac TnI (cTnI) from patients presenting with chest pain prior to and during transit to a primary care hospital (Borders General Hospital-BGH) via the Scottish Ambulance Service. (SAS). The immunoassay system used to quantitatively determine cTnI was the Samsung LABGEOIB10 (BCA-IB10). While patients presenting with chest pain suggestive of myocardial infarction (MI) can be diagnosed by paramedics almost immediately via 12 lead ECG telemetry, that subset of patients with no significant and persistent ST segment elevation (NSTEMI) or normal ECG are not eligible for administration of thrombolytic agents and are routinely dispatched according to the current chest pain pathway to the Borders General Hospital in Melrose. STEMI patients are immediately rerouted to a secondary or tertiary hospital with interventional cardiology capability to perform angiography, PCI or more complicated procedures to identify and resolve cardiac ischemia (Royal Infirmary of Edinburgh). Patients with NSTEMI or acute coronary syndrome (ACS) require, as part of their differential diagnosis, at least 1 elevated concentration of cTnI which may include serial measurements if the initial concentration is near or just below the designated cut –off, usually defined as the 99th percentile concentration of an apparently healthy reference population. Every cTnI assay establishes it’s own cut point and they may vary significantly. Elevated cTnI levels correlate with the risk of mortality, MI or increased probability of ischemic events, requiring urgent revascularization. The recently published Third Universal Definition of Myocardial Infarction approved by an International Task Force endorsed by the European Society of Cardiology (ESC), American College of Cardiology Federation (ACCF), World Heart Federation (WHF) and the American Heart Association (AHA) requires at least one elevation of cTnI above the 99 percentile of a reference population (Table 1) with 2-3 samples taken over a period up to 12 h. Several previous studies using quantitative point of care devices (POC) in the Emergency Department have demonstrated total turn around times (TAT) of 30 minutes or less compared to cTnI report times from the central lab of > 1 h.2 One such study found a TAT reduction of 50-60% in both urban and community based hospitals for reporting ED cardiac marker test results compared to cTnI results reported submitted to the laboratory. A more recent report from a randomized study comprising 6 ED departments in the UK ,with approximately 1130 patients in each arm (ED cardiac marker testing compared to standard laboratory based reporting), was undertaken to assess the possibility of earlier dismissal from the hospital compared to the current National Institute for Health and Clinical Excellence guidelines of 10-12 h3 The RATPAC (Randomized Assessment of Treatment using a Panel Assay of Cardiac Markers) protocol was based on POC testing at presentation and a second test 90 minutes later. Main outcome measures for RATPAC were: * Successful discharge by 4 hr after attendance -32% vs 13% (rapid rule out); * Reduced median length of initial hospital stay; * Greater use of coronary care uni

exoplanet : gradient-based probabilistic inference for exoplanet data & other astronomical time series

Funding: This research was partially conducted during the Exostar19 program at the Kavli Institute for Theoretical Physics at UC Santa Barbara, which was supported in part by the National Science Foundation under Grant No. NSF PHY-1748958."exoplanet" is a toolkit for probabilistic modeling of astronomical time series data, with a focus on observations of exoplanets, using PyMC3 (Salvatier et al., 2016). PyMC3 is a flexible and high-performance model-building language and inference engine that scales well to problems with a large number of parameters. "exoplanet" extends PyMC3's modeling language to support many of the custom functions and probability distributions required when fitting exoplanet datasets or other astronomical time series. While it has been used for other applications, such as the study of stellar variability, the primary purpose of "exoplanet" is the characterization of exoplanets or multiple star systems using time-series photometry, astrometry, and/or radial velocity. In particular, the typical use case would be to use one or more of these datasets to place constraints on the physical and orbital parameters of the system, such as planet mass or orbital period, while simultaneously taking into account the effects of stellar variability.Publisher PDFPeer reviewe

Developmental delay in a Streptomyces venezuelae glgE null mutant is associated with the accumulation of alpha-maltose 1-phosphate

The GlgE pathway is thought to be responsible for the conversion of trehalose into a glycogen-like alpha-glucan polymer in bacteria. Trehalose is first converted to maltose, which is phosphorylated by maltose kinase Pep2 to give alpha-maltose 1-phosphate. This is the donor substrate of the maltosyl transferase GlgE that is known to extend alpha-1,4-linked maltooligosaccharides, which are thought to be branched with alpha-1,6 linkages. The genome of Streptomyces venezuelae contains all the genes coding for the GlgE pathway enzymes but none of those of related pathways, including glgC and glgA of the glycogen pathway. This provides an opportunity to study the GlgE pathway in isolation. The genes of the GlgE pathway were upregulated at the onset of sporulation, consistent with the known timing of a-glucan deposition. A constructed Delta glgE null mutant strain was viable but showed a delayed developmental phenotype when grown on maltose, giving less cell mass and delayed sporulation. Pre-spore cells and spores of the mutant were frequently double the length of those of the wild-type, implying impaired cross-wall formation, and spores showed reduced tolerance to stress. The mutant accumulated alpha-maltose 1-phosphate and maltose but no alpha-glucan. Therefore, the GlgE pathway is necessary and sufficient for polymer biosynthesis. Growth of the Delta glgE mutant on galactose and that of a Delta pep2 mutant on maltose were analysed. In both cases, neither accumulation of alpha-maltose 1-phosphate/alpha-glucan nor a developmental delay was observed. Thus, high levels of alpha-maltose 1-phosphate are responsible for the developmental phenotype of the Delta glgE mutant, rather than the lack of a-glucan

Rapid-Onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD): Exome sequencing of trios, monozygotic twins and tumours

BACKGROUND: Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) is thought to be a genetic disease caused by de novo mutations, though causative mutations have yet to be identified. We searched for de novo coding mutations among a carefully-diagnosed and clinically homogeneous cohort of 35 ROHHAD patients. METHODS: We sequenced the exomes of seven ROHHAD trios, plus tumours from four of these patients and the unaffected monozygotic (MZ) twin of one (discovery cohort), to identify constitutional and somatic de novo sequence variants. We further analyzed this exome data to search for candidate genes under autosomal dominant and recessive models, and to identify structural variations. Candidate genes were tested by exome or Sanger sequencing in a replication cohort of 28 ROHHAD singletons. RESULTS: The analysis of the trio-based exomes found 13 de novo variants. However, no two patients had de novo variants in the same gene, and additional patient exomes and mutation analysis in the replication cohort did not provide strong genetic evidence to implicate any of these sequence variants in ROHHAD. Somatic comparisons revealed no coding differences between any blood and tumour samples, or between the two discordant MZ twins. Neither autosomal dominant nor recessive analysis yielded candidate genes for ROHHAD, and we did not identify any potentially causative structural variations. CONCLUSIONS: Clinical exome sequencing is highly unlikely to be a useful diagnostic test in patients with true ROHHAD. As ROHHAD has a high risk for fatality if not properly managed, it remains imperative to expand the search for non-exomic genetic risk factors, as well as to investigate other possible mechanisms of disease. In so doing, we will be able to confirm objectively the ROHHAD diagnosis and to contribute to our understanding of obesity, respiratory control, hypothalamic function, and autonomic regulation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13023-015-0314-x) contains supplementary material, which is available to authorized users

Combined In Silico, In Vivo, and In Vitro Studies Shed Insights into the Acute Inflammatory Response in Middle-Aged Mice

We combined in silico, in vivo, and in vitro studies to gain insights into age-dependent changes in acute inflammation in response to bacterial endotoxin (LPS). Time-course cytokine, chemokine, and NO2-/NO3- data from "middle-aged" (6-8 months old) C57BL/6 mice were used to re-parameterize a mechanistic mathematical model of acute inflammation originally calibrated for "young" (2-3 months old) mice. These studies suggested that macrophages from middle-aged mice are more susceptible to cell death, as well as producing higher levels of pro-inflammatory cytokines, vs. macrophages from young mice. In support of the in silico-derived hypotheses, resident peritoneal cells from endotoxemic middle-aged mice exhibited reduced viability and produced elevated levels of TNF-α, IL-6, IL-10, and KC/CXCL1 as compared to cells from young mice. Our studies demonstrate the utility of a combined in silico, in vivo, and in vitro approach to the study of acute inflammation in shock states, and suggest hypotheses with regard to the changes in the cytokine milieu that accompany aging. © 2013 Namas et al

An Adequately Robust Early TNF-α Response Is a Hallmark of Survival Following Trauma/Hemorrhage

Background: Trauma/hemorrhagic shock (T/HS) results in cytokine-mediated acute inflammation that is generally considered detrimental. Methodology/Principal Findings: Paradoxically, plasma levels of the early inflammatory cytokine TNF-α (but not IL-6, IL-10, or NO2-/NO3-) were significantly elevated within 6 h post-admission in 19 human trauma survivors vs. 4 non-survivors. Moreover, plasma TNF-α was inversely correlated with Marshall Score, an index of organ dysfunction, both in the 23 patients taken together and in the survivor cohort. Accordingly, we hypothesized that if an early, robust pro-inflammatory response were to be a marker of an appropriate response to injury, then individuals exhibiting such a response would be predisposed to survive. We tested this hypothesis in swine subjected to various experimental paradigms of T/HS. Twenty-three anesthetized pigs were subjected to T/HS (12 HS-only and 11 HS + Thoracotomy; mean arterial pressure of 30 mmHg for 45-90 min) along with surgery-only controls. Plasma obtained at pre-surgery, baseline post-surgery, beginning of HS, and every 15 min thereafter until 75 min (in the HS only group) or 90 min (in the HS + Thoracotomy group) was assayed for TNF-α, IL-6, IL-10, and NO2-/NO3-. Mean post-surgery±HS TNF-α levels were significantly higher in the survivors vs. non-survivors, while non-survivors exhibited no measurable change in TNF-α levels over the same interval. Conclusions/Significance: Contrary to the current dogma, survival in the setting of severe, acute T/HS appears to be associated with an immediate increase in serum TNF-α. It is currently unclear if this response was the cause of this protection, a marker of survival, or both. This abstract won a Young Investigator Travel Award at the SHOCK 2008 meeting in Cologne, Germany. © 2009 Namas et al