A design-build-test-learn tool for synthetic biology

Modern synthetic gene regulatory networks emerge from iterative design-build-test cycles that encompass the decisions and actions necessary to design, build, and test target genetic systems. Historically, such cycles have been performed manually, with limited formal problem-definition and progress-tracking. In recent years, researchers have devoted substantial effort to define and automate many sub-problems of these cycles and create systems for data management and documentation that result in useful tools for solving portions of certain workflows. However, biologists generally must still manually transfer information between tools, a process that frequently results in information loss. Furthermore, since each tool applies to a different workflow, tools often will not fit together in a closed-loop and, typically, additional outstanding sub-problems still require manual solutions. This thesis describes an attempt to create a tool that harnesses many smaller tools to automate a fully closed-loop decision-making process to design, build, and test synthetic biology networks and use the outcomes to inform redesigns. This tool, called Phoenix, inputs a performance-constrained signal-temporal-logic (STL) equation and an abstract genetic-element structural description to specify a design and then returns iterative sets of building and testing instructions. The user executes the instructions and returns the data to Phoenix, which then processes it and uses it to parameterize models for simulation of the behavior of compositional designs. A model-checking algorithm then evaluates these simulations, and returns to the user a new set of instructions for building and testing the next set of constructs. In cases where experimental results disagree with simulations, Phoenix uses grammars to determine where likely points of design failure might have occurred and instructs the building and testing of an intermediate composition to test where failures occurred. A design tree represents the design hierarchy displayed in the user interface where progress can be tracked and electronic datasheets generated to review results. Users can validate the computations performed by Phoenix by using them to create sets of classic and novel temporal synthetic genetic regulatory functions in E. coli.2016-12-31T00:00:00

Cloud fluid models of gas dynamics and star formation in galaxies

The large dynamic range of star formation in galaxies, and the apparently complex environmental influences involved in triggering or suppressing star formation, challenges the understanding. The key to this understanding may be the detailed study of simple physical models for the dominant nonlinear interactions in interstellar cloud systems. One such model is described, a generalized Oort model cloud fluid, and two simple applications of it are explored. The first of these is the relaxation of an isolated volume of cloud fluid following a disturbance. Though very idealized, this closed box study suggests a physical mechanism for starbursts, which is based on the approximate commensurability of massive cloud lifetimes and cloud collisional growth times. The second application is to the modeling of colliding ring galaxies. In this case, the driving processes operating on a dynamical timescale interact with the local cloud processes operating on the above timescale. The results is a variety of interesting nonequilibrium behaviors, including spatial variations of star formation that do not depend monotonically on gas density

The design and fabrication of microstrip omnidirectional array antennas for aerospace applications

A microstrip antenna design concept was developed that will provide quasi-omnidirectional radiation pattern characteristics about cylindrical and conical aerospace structures. L-band and S-band antenna arrays were designed, fabricated, and, in some cases, flight tested for rocket, satellite, and aircraft drone applications. Each type of array design is discussed along with a thermal cover design that was required for the sounding rocket applications

Multi-waveband observations of colliding galaxies

Colliding galaxies represent a major challenge to both theorists and observers because of the large variety of phenomena which are expected to come into play during the interaction. Strong gravitational fluctuations may drive non-linear waves and instabilities throughout the stars and gas leading to enhanced star formation, nuclear activity and ultimately a mixing of the morphological components of the original galaxies. One relatively uncomplicated class of colliding galaxy where stellar waves play an important role in star formation are ring galaxies. Ring galaxies are probably formed when a companion galaxy passes through the center of a disk system driving circular waves through the disk (Lynds and Toomre 1976, Toomre 1978, Struck-Marcell 1990). Off-center collisions can generate non-circular waves and can be loosely described as banana-shaped although they may exhibit more complex forms as the waves expand into the disk. The propagation of such stellar and gaseous waves through the disk leads to enhanced star formation (e.g., Appleton and Struck-Marcell 1987a; Jeske 1986) and provides a unique probe of the response of the interstellar medium (ISM) to a propagating wave (see Appleton and Struck-Marcell 1987b). Here, the authors report results for 3 systems; the irregular ring Arp 143 (=VV 117); Wakamatsu's Seyfert ring (A0959-755; see Wakamatsu and Nishida 1987) and the brighter member of the pair of ring galaxies comprising of AM 1358-221. The most complete multi-wavelength data is for Arp 143. Optical charge coupled device (CCD) observations made with the 60 inch Palomar telescope at BV and r band, near-IR images at J (1.25 microns), H (1.65 microns) and k (2.2 microns) bands from the infrared camera (IRCAM) InSb array camera on the 3.8m United Kingdon Infrared Telescope (UKIRT) telescope and very large array (VLA) observations at 20cm in both the neutral hydrogen line and radio continuum are described. The observations of Wakamatsu's ring and AM 1358 were made only in the near-IR, and a comparison is made with available optical plate material

Jet-ISM Interaction in the Radio Galaxy 3C293: Jet-driven Shocks Heat ISM to Power X-ray and Molecular H2 emission

We present a 70ks Chandra observation of the radio galaxy 3C293. This galaxy belongs to the class of molecular hydrogen emission galaxies (MOHEGs) that have very luminous emission from warm molecular hydrogen. In radio galaxies, the molecular gas appears to be heated by jet-driven shocks, but exactly how this mechanism works is still poorly understood. With Chandra, we observe X-ray emission from the jets within the host galaxy and along the 100 kpc radio jets. We model the X-ray spectra of the nucleus, the inner jets, and the X-ray features along the extended radio jets. Both the nucleus and the inner jets show evidence of 10^7 K shock-heated gas. The kinetic power of the jets is more than sufficient to heat the X-ray emitting gas within the host galaxy. The thermal X-ray and warm H2 luminosities of 3C293 are similar, indicating similar masses of X-ray hot gas and warm molecular gas. This is consistent with a picture where both derive from a multiphase, shocked interstellar medium (ISM). We find that radio-loud MOHEGs that are not brightest cluster galaxies (BCGs), like 3C293, typically have LH2/LX~1 and MH2/MX~1, whereas MOHEGs that are BCGs have LH2/LX~0.01 and MH2/MX~0.01. The more massive, virialized, hot atmosphere in BCGs overwhelms any direct X-ray emission from current jet-ISM interaction. On the other hand, LH2/LX~1 in the Spiderweb BCG at z=2, which resides in an unvirialized protocluster and hosts a powerful radio source. Over time, jet-ISM interaction may contribute to the establishment of a hot atmosphere in BCGs and other massive elliptical galaxies.Comment: Accepted by ApJ 21 pages in ApJ format, 9 figures, 8 table

Protocol for a longitudinal qualitative interview study: maintaining psychological well-being in advanced cancer - what can we learn from patients' and carers' own coping strategies?

IntroductionPeople with advanced cancer and their carers experience stress and uncertainty which affects the quality of life and physical and mental health. This study aims to understand how patients and carers recover or maintain psychological well-being by exploring the strategies employed to self-manage stress and uncertainty.Methods and analysisA longitudinal qualitative interview approach with 30 patients with advanced cancer and 30 associated family or informal carers allows the exploration of contexts, mechanisms and outcomes at an individual level. Two interviews, 4–12?weeks apart, will not only enable the exploration of individuals’ evolving coping strategies in response to changing contexts but also how patients’ and carers’ strategies inter-relate. Patient and Carer focus groups will then consider how the findings may be used in developing an intervention. Recruiting through two major tertiary cancer centres in the North West and using deliberately broad and inclusive criteria will enable the sample to capture demographic and experiential breadth.Ethics and disseminationThe research team will draw on their considerable experience to ensure that the study is sensitive to a patient and carer group, which may be considered vulnerable but still values being able to contribute its views. Public and patient involvement (PPI) is integral to the design and is evidenced by: a research advisory group incorporating patient and carers, prestudy consultations with the PPI group at one of the study sites and a user as the named applicant. The study team will use multiple methods to disseminate the findings to clinical, policy and academic audiences. A key element will be engaging health professionals in patient and carer ideas for promoting self-management of psychological well-being. The study has ethical approval from the North West Research Ethics Committee and the appropriate NHS governance clearance.RegistrationNational Institute for Health Research (NIHR) Clinical Studies Portfolio, UK Clinical Research Network (UKCRN) Study number 11725

Ventricular Tachycardia in the Absence of Structural Heart Disease

In up to 10% of patients who present with ventricular tachycardia (VT), obvious structural heart disease is not identified. In such patients, causes of ventricular arrhythmia include right ventricular outflow tract (RVOT) VT, extrasystoles, idiopathic left ventricular tachycardia (ILVT), idiopathic propranolol-sensitive VT (IPVT), catecholaminergic polymorphic VT (CPVT), Brugada syndrome, and long QT syndrome (LQTS). RVOT VT, ILVT, and IPVT are referred to as idiopathic VT and generally do not have a familial basis. RVOT VT and ILVT are monomorphic, whereas IPVT may be monomorphic or polymorphic. The idiopathic VTs are classified by the ventricle of origin, the response to pharmacologic agents, catecholamine dependence, and the specific morphologic features of the arrhythmia. CPVT, Brugada syndrome, and LQTS are inherited ion channelopathies. CPVT may present as bidirectional VT, polymorphic VT, or catecholaminergic ventricular fibrillation. Syncope and sudden death in Brugada syndrome are usually due to polymorphic VT. The characteristic arrhythmia of LQTS is torsades de pointes. Overall, patients with idiopathic VT have a better prognosis than do patients with ventricular arrhythmias and structural heart disease. Initial treatment approach is pharmacologic and radiofrequency ablation is curative in most patients. However, radiofrequency ablation is not useful in the management of inherited ion channelopathies. Prognosis for patients with VT secondary to ion channelopathies is variable. High-risk patients (recurrent syncope and sudden cardiac death survivors) with inherited ion channelopathies benefit from implantable cardioverter-defibrillator placement. This paper reviews the mechanism, clinical presentation, and management of VT in the absence of structural heart disease