High volume fabrication of laser targets using MEMS techniques

The latest techniques for the fabrication of high power laser targets, using processes developed for the manufacture of Micro-Electro-Mechanical System (MEMS) devices are discussed. These laser targets are designed to meet the needs of the increased shot numbers that are available in the latest design of laser facilities. Traditionally laser targets have been fabricated using conventional machining or coarse etching processes and have been produced in quantities of 10s to low 100s. Such targets can be used for high complexity experiments such as Inertial Fusion Energy (IFE) studies and can have many complex components that need assembling and characterisation with high precision. Using the techniques that are common to MEMS devices and integrating these with an existing target fabrication capability we are able to manufacture and deliver targets to these systems. It also enables us to manufacture novel targets that have not been possible using other techniques. In addition, developments in the positioning systems that are required to deliver these targets to the laser focus are also required and a system to deliver the target to a focus of an F2 beam at 0.1Hz is discussed.

Measurement of electromagnetic pulses generated during interactions of high power lasers with solid targets

A target irradiated with a high power laser pulse, blows off a large amount of charge and as a consequence the target itself becomes a generator of electromagnetic pulses (EMP) owing to high return current flowing to the ground through the target holder. The first measurement of the magnetic field induced by the neutralizing current reaching a value of a few kA was performed with the use of an inductive target probe at the PALS Laser Facility (Cikhardt et al. Rev. Sci. Instrum. 85 (2014) 103507). A full description of EMP generation should contain information on the spatial distribution and temporal variation of the electromagnetic field inside and outside of the interaction chamber. For this reason, we consider the interaction chamber as a resonant cavity in which different modes of EMP oscillate for hundreds of nanoseconds, until the EMP is transmitted outside through the glass windows and EM waves are attenuated. Since the experimental determination of the electromagnetic field distribution is limited by the number of employed antennas, a mapping of the electromagnetic field has to be integrated with numerical simulations. Thus, this work reports on a detailed numerical mapping of the electromagnetic field inside the interaction chamber at the PALS Laser Facility (covering a frequency spectrum from 100 MHz to 3 GHz) using the commercial code COMSOL Multiphysics 5.2. Moreover we carried out a comparison of the EMP generated in the parallelepiped-like interaction chamber used in the Vulcan Petawatt Laser Facility at the Rutherford Appleton Laboratory, against that produced in the spherical interaction chamber of PALS.

Economic impacts of seafood production growth targets in Ireland

This paper examines the potential economic impact of the Irish government strategy for the development of the seafood sector in Ireland, Food Harvest 2020 (FH2020). The seafood industry accounts for a large proportion of income and employment in peripheral coastal areas. Many of these regions are predominantly rural and they are largely dependent on the primary fisheries sector. Moreover, the services and retail businesses in these areas are heavily dependent on direct spending from the fisheries, aquaculture and seafood processing sectors. A social accounting matrix (SAM) approach with (1) set to zero purchase coefficients for all directly impacted industries and (2) changes in output converted to final demand shocks is used to calculate the economic and employment impact on the rest of the economy from an increase in the output in the fisheries, aquaculture and seafood processing sectors in Ireland. The results suggest fisheries sectors have strong links with the rest of the economy hence an important economic impact from a policy perspective.

Transiting Exoplanet Studies and Community Targets for JWST's Early Release Science Program

The James Webb Space Telescope (JWST) will likely revolutionize transiting exoplanet atmospheric science, due to a combination of its capability for continuous, long duration observations and its larger collecting area, spectral coverage, and spectral resolution compared to existing space-based facilities. However, it is unclear precisely how well JWST will perform and which of its myriad instruments and observing modes will be best suited for transiting exoplanet studies. In this article, we describe a prefatory JWST Early Release Science (ERS) Cycle 1 program that focuses on testing specific observing modes to quickly give the community the data and experience it needs to plan more efficient and successful transiting exoplanet characterization programs in later cycles. We propose a multi-pronged approach wherein one aspect of the program focuses on observing transits of a single target with all of the recommended observing modes to identify and understand potential systematics, compare transmission spectra at overlapping and neighboring wavelength regions, confirm throughputs, and determine overall performances. In our search for transiting exoplanets that are well suited to achieving these goals, we identify 12 objects (dubbed “community targets”) that meet our defined criteria. Currently, the most favorable target is WASP-62b because of its large predicted signal size, relatively bright host star, and location in JWST's continuous viewing zone. Since most of the community targets do not have well-characterized atmospheres, we recommend initiating preparatory observing programs to determine the presence of obscuring clouds/hazes within their atmospheres. Measurable spectroscopic features are needed to establish the optimal resolution and wavelength regions for exoplanet characterization. Other initiatives from our proposed ERS program include testing the instrument brightness limits and performing phase-curve observations. The latter are a unique challenge compared to transit observations because of their significantly longer durations. Using only a single mode, we propose to observe a full-orbit phase curve of one of the previously characterized, short-orbital-period planets to evaluate the facility-level aspects of long, uninterrupted time-series observations.

Functional expression of a novel Kunitz type protease inhibitor from the human blood fluke Schistosoma mansoni

BACKGROUND: Schistosomes are able to survive for prolonged periods in the blood system, despite continuous contact with coagulatory factors and mediators of the host immune system. Protease inhibitors likely play a critical role in host immune modulation thereby promoting parasite survival in this extremely hostile environment. Even though Kunitz type serine protease inhibitors have been shown to play important physiological functions in a range of organisms these proteins are less well characterised in parasitic helminths.

METHODS: We have cloned one gene sequence from S. mansoni, Smp_147730 (SmKI-1) which is coded for single domain Kunitz type protease inhibitor, E. coli-expressed and purified. Immunolocalisation and western blotting was carried out using affinity purified polyclonal anti-SmKI-1 murine antibodies to determine SmKI-1 expression in the parasite. Protease inhibitor assays and coagulation assays were performed to evaluate the functional roles of SmKI-1.

RESULTS: SmKI-1 is localised in the tegument of adult worms and the sub-shell region of eggs. Furthermore, this Kunitz protein is secreted into the host in the ES products of the adult worm. Recombinant SmKI-1 inhibited mammalian trypsin, chymotrypsin, neutrophil elastase, FXa and plasma kallikrein with IC50 values of 35 nM, 61 nM, 56 nM, 142 nM and 112 nM, respectively. However, no inhibition was detected for pancreatic elastase or cathepsin G. SmKI-1 (4 μM) delayed blood clot formation, reflected in an approximately three fold increase in activated partial thromboplastin time and prothrombin time.

CONCLUSIONS: We have functionally characterised the first Kunitz type protease inhibitor (SmKI-1) from S. mansoni and show that it has anti-inflammatory and anti-coagulant properties. SmKI-1 is one of a number of putative Kunitz proteins in schistosomes that have presumably evolved as an adaptation to protect these parasites from the defence mechanisms of their mammalian hosts. As such they may represent novel vaccine candidates and/or drug targets for schistosomiasis control.

In-situ formation of solidified hydrogen thin-membrane targets using a pulse tube cryocooler

An account is given of the Central Laser Facility's work to produce a cryogenic hydrogen targetry system using a pulse tube cryocooler. Due to the increasing demand for low Z thin laser targets, CLF (in collaboration with TUD) have been developing a system which allows the production of solid hydrogen membranes by engineering a design which can achieve this remotely; enabling the gas injection, condensation and solidification of hydrogen without compromising the vacuum of the target chamber. A dynamic sealing mechanism was integrated which allows targets to be grown and then remotely exposed to open vacuum for laser interaction. Further research was conducted on the survivability of the cryogenic targets which concluded that a warm gas effect causes temperature spiking when exposing the solidified hydrogen to the outer vacuum. This effect was shown to be mitigated by improving the pumping capacity of the environment and reducing the minimum temperature obtainable on the target mount. This was achieved by developing a two-stage radiation shield encased with superinsulating blanketing; reducing the base temperature from 14 0.5 K to 7.2 0.2 K about the coldhead as well as improving temperature control stability following the installation of a high-performance temperature controller and sensor apparatus. The system was delivered experimentally and in July 2014 the first laser shots were taken upon hydrogen targets in the Vulcan TAP facility.

Digestive enzymes during development of Ceratitis capitata (Diptera:Tephritidae) and effects of SBTI on its digestive serine proteinase targets

SILVA, Fatima C. B. L. et al. Digestive enzymes during development of Ceratitis capitata (Diptera:Tephritidae) and effects of SBTI on its digestive serine proteinase targets. Insect Biochemistry and Molecular Biology, v. 36, p. 561-569, 2006.ISSN: 0965-1748.DOI: 10.1016/j.ibmb.2006.04.004.

Identification of protein targets of nevirapine reactive metabolites using click chemistry and mass spectrometry-based differential proteomics

Abstract : Adverse drug reactions (ADRs) are undesirable effects caused after administration of a single dose or prolonged administration of drug or result from the combination of two or more drugs. Idiosyncratic drug reaction (IDR) is an adverse reaction that does not occur in most patients treated with a drug and does not involve the therapeutic effect of the drug. IDRs are unpredictable and often life-threatening. Idiosyncratic reaction is dependent on drug chemical characteristics or individual immunological response. IDRs are a major problem for drug development because they are usually not detected during clinical trials. In this study we focused on IDRs of Nevirapine (NVP), which is a non-nucleoside reverse transcriptase inhibitor used for the treatment of Human Immunodeficiency Virus (HIV) infections. The use of NVP is limited by a relatively high incidence of skin rash. NVP also causes a rash in female Brown Norway (BN) rats, which we use as animal model for this study. Our hypothesis is that idiosyncratic skin reactions associated with NVP treatment are due to post-translational modifications of proteins (e.g., glutathionylation) detectable by MS. The main objective of this study was to identify the proteins that are targeted by a reactive metabolite of Nevirapine in the skin. The specific objectives derived from the general objective were as follow: 1) To implement the click chemistry approach to detect proteins modified by a reactive NVP-Alkyne (NVP-ALK) metabolite. The purpose of using NVP-ALK was to couple it with Biotin using cycloaddition Click Chemistry reaction. 2) To detect protein modification using Western blotting and Mass Spectrometry techniques, which is important to understand the mechanism of NVP induced toxicity. 3) To identify the proteins using MASCOT search engine for protein identification, by comparing obtained spectrum from Mass Spectrometry with theoretical spectrum to find a matching peptide sequence. 4) To test if the drug or drug metabolites can cause harmful effects, as the induction of oxidative stress in cells (via protein glutathionylation). Oxidative stress causes cell damage that mediates signals, which likely induces the immune response. The results showed that Nevirapine is metabolized to a reactive metabolite, which causes protein modification. The extracted protein from the treated BN rats matched 10% of keratin, which implies that keratin was the protein targeted by the NVP-ALK.

A fast parallel hyperspectral coded aperture algorithm for compressive sensing using OpenCL

In this paper, we develop a fast implementation of an hyperspectral coded aperture (HYCA) algorithm on different platforms using OpenCL, an open standard for parallel programing on heterogeneous systems, which includes a wide variety of devices, from dense multicore systems from major manufactures such as Intel or ARM to new accelerators such as graphics processing units (GPUs), field programmable gate arrays (FPGAs), the Intel Xeon Phi and other custom devices. Our proposed implementation of HYCA significantly reduces its computational cost. Our experiments have been conducted using simulated data and reveal considerable acceleration factors. This kind of implementations with the same descriptive language on different architectures are very important in order to really calibrate the possibility of using heterogeneous platforms for efficient hyperspectral imaging processing in real remote sensing missions.

Potential Therapeutic Targets in Triple Negative Breast Cancer

Triple negative breast cancers (TNBC) are often described as biologically aggressive tumors, with poorer survival compared to other breast cancer subtypes. The fact that TNBC lacks an obvious target like estrogen receptor and HER2 represents a major challenge in the management of these patients. Genomic analyses have revealed that TNBC comprises a diverse group of cancers, which have distinct molecular profiles and different prognosis. These studies also highlighted molecular aberrations that could serve as potential treatment targets. On the other hand, a high percentage of TNBCs express some important surface receptors that have been already exploited in the development of promising targeted therapies, which are currently tested in clinical trials. In this review, we will provide an overview on the molecular diversity of TNBC with special emphasis on the evolving role of some potential biomarkers that may be utilized in the near future.

Digestive enzymes during development of Ceratitis capitata (Diptera:Tephritidae) and effects of SBTI on its digestive serine proteinase targets

SILVA, Fatima C. B. L. et al. Digestive enzymes during development of Ceratitis capitata (Diptera:Tephritidae) and effects of SBTI on its digestive serine proteinase targets. Insect Biochemistry and Molecular Biology, v. 36, p. 561-569, 2006.ISSN: 0965-1748.DOI: 10.1016/j.ibmb.2006.04.004.

Optimisation of digitally coded test vectors for mixed-signal components

International audience

A tentative argument for regional quality targets in assimilating schwa

Amerikanenglannin redusoitunut švaa-vokaali tuotetaan puheessa laadultaan huomattavan monimuotoisena. Kirjallisuudessa ei kuitenkaan vallitse selkeää käsitystä siitä, mitkä tekijät ehdollistavat tätä švaan laatuvaihtelua, ja etenkin sen mahdollinen sosiaalinen ulottuvuus on jäänyt aiemmissa tutkimuksissa varsin vähälle huomiolle. Tässä tutkielmassa pyritäänkin selvittämään, millainen vaikutus puhujan alueellisella murteella on hänen tuottamansa švaan akustiikkaan. Tutkimukseen valittiin 21 informanttia muutamista Yhdysvaltain eteläisistä ja läntisistä osavaltioista. Informanttien haastattelunauhoitteista poimittiin analyysiin yhteensä 433 švaan F1- ja F2-formanttiarvot siten kuin ne esiintyivät sanassa the. Analyysissä havaittiin, että eteläisten puhujien švaat keskittyivät vokaalien [u,U] tuntumaan, kun taas läntisten informanttien švaat asettuivat vokaalien [i,u] väliin. Tulokset antoivat aihetta kysyä, onko eteläinen švaa sulautunut takavokaaleihin [u,U]. Kysymystä varten suoritettiin jatkotutkimus, johon valittiin yksi ensimmäisen tutkimuksen eteläisistä puhujista. Puhujalta mitattiin 66 švaan ja 45 [U]:n formantit. Näitä tarkastellessa löydettiin tilastollista viitettä siitä, että puhujan švaa oli saattanut sulautua vokaaliin [U]. Tulostensa pohjalta tutkielma ehdottaa, että the-sanassa esiintyvässä amerikanenglannin švaassa saattaa toteutua puhujan alueellista murretta mukaileva tavoitevaihe siitä huolimatta, että tämä vokaali on samanaikaisesti huomattavasti kontekstiinsa assimiloitunut. Tavoitevaihe näyttäisi lähtökohtaisesti sijoittuvan F2:ssa vokaalialueen keskelle, ollen kuitenkin eteläisten puhujien kohdalla altis siirtymään taaemmas kohti vokaalilaatuja [u,U].

The conformational landscape of RNA translational regulators and their potential as drug discovery targets

RNA is an underutilized target for drug discovery. Once thought to be a passive carrier of genetic information, RNA is now known to play a critical role in essentially all aspects of biology including signaling, gene regulation, catalysis, and retroviral infection. It is now well-established that RNA does not exist as a single static structure, but instead populates an ensemble of energetic minima along a free-energy landscape. Knowledge of this structural landscape has become an important goal for understanding its diverse biological functions. In this case, NMR spectroscopy has emerged as an important player in the characterization of RNA structural ensembles, with solution-state techniques accounting for almost half of deposited RNA structures in the PDB, yet the rate of RNA structure publication has been stagnant over the past decade. Several bottlenecks limit the pace of RNA structure determination by NMR: the high cost of isotopic labeling, tedious and ambiguous resonance assignment methods, and a limited database of RNA optimized pulse programs. We have addressed some of these challenges to NMR characterization of RNA structure with applications to various RNA-drug targets. These approaches will increasingly become integral to designing new therapeutics targeting RNA.