Abstract Pick-off beams in Interferometric Gravitational Wave Detectors are often used to derive information on the field circulating in the interferometer. In order to retrieve the wavefront of the ...field at some chosen location, an optical system has to be deployed so to image the desired field characteristics to an optical bench and ultimately to suitable sensors. In this paper, we detail the requirements in terms of Gouy Phase and ABCD matrix for such an optical system to provide the correct information. We show also that by designing the optical system with adequate Gouy Phase evolution, the same kind of transformation holds true not only for the fundamental Gaussian mode, but also for both even and odd Higher Order Modes (HOMs) of the main interferometer beam. This is important because these HOMs are excited by the aberrations of the optical elements in the interferometer, and carry the information one is interested to. Simulations with two tools (Finesse and Zemax OpticsStudio ® ) are provided to confirm the analytical results obtained using Gaussian modes expansion of a generic field.
The second generation of ground-based interferometric gravitational wave detectors are currently being built and installed. They are designed to be better in strain sensitivity by about a factor 10 ...with respect to the first generation. Light originating from the laser and following unintended paths, called stray light, has been a major problem during the commissioning of all of the first generation detectors. Indeed, stray light carries information about the phase of the emitting object. Therefore, in the next generation all the optics will be suspended in the vacuum in order to mitigate their associated stray light displacement noise. Despite this additional precaution, the challenging target sensitivity at low frequency which is partially limited by quantum radiation pressure combined with up-conversion effects, requires more detailed investigation. In this paper, we turn our attention to stray light originating from auxiliary optical benches. We use a dedicated formalism to compute the re-coupling of back-reflected and back-scattered light. We show, in particular, how much care should be taken in designing and setting requirements for the input bench optics.
HLA-A*31:01 was reported to be associated with carbamazepine (CBZ)-induced severe cutaneous adverse reactions (SCAR), including drug reaction with eosinophilia and systemic symptoms (DRESS), ...Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). We conducted an international study using consensus diagnosis criteria to enroll a total of 93 patients with CBZ-SCAR from Europe or Asia. We found that HLA-A*31:01 showed a significant association with CBZ-DRESS in Europeans (P<0.001; odds ratio (OR) (95% confidence interval (CI))=57.6 (11.0-340)), and the strong association was also found in Chinese (P<0.001; OR (95% CI)=23.0 (4.2-125)). However, HLA-A*31:01 had no association with CBZ-SJS/TEN in neither Chinese nor Europeans. By comparison, HLA-B*15:02 showed a strong association with CBZ-SJS/TEN in Chinese (P<0.001, OR (95% CI)=58.1 (17.6-192)). A meta-analysis of this and other published studies confirmed that in all populations, HLA-A*31:01 had an extremely strong association with CBZ-DRESS (P<0.001, a pooled OR (95% CI)=13.2 (8.4-20.8)), but a much weaker association with CBZ-SJS/TEN (P=0.01, OR (95% CI)=3.94 (1.4-11.5)). Our data revealed that HLA-A*31:01 is a specific predictor for CBZ-DRESS but not for CBZ-SJS/TEN. More studies are needed to investigate the genetic determinant of CBZ-SJS/TEN in Europeans. Considering the potential clinical utility, the cost-effectiveness of the combined HLA-A*31:01 and HLA-B*15:02 genetic test to prevent CBZ-SCAR in Chinese needs further investigation.
The search for proteasome inhibitors began fifteen years ago. These inhibitors proved to be powerful tools for investigating many important cellular processes regulated by the ubiquitin-proteasome ...pathway. Targeting the proteasome pathway can also lead to new treatments for disorders like cancer, muscular dystrophies, inflammation and immune diseases. This is already true for cancer; the FDA approved bortezomib, a potent proteasome inhibitor, for treating multiple myeloma in 2003, and mantle cell lymphoma in 2006. The chemical structures identified in some of the early proteasome inhibitors have led to the development of new anti-cancer drugs (CEP-18770, Carfilzomib, NPI-0052). All these molecules are covalent bonding inhibitors that react with the catalytic Thr1-O(gamma) of the three types of active site. This review covers recent developments in medicinal chemistry of natural and synthetic proteasome inhibitors. Advances in non-covalent inhibitors that have no reactive group will be highlighted as they should minimize side-effects. New structures and new modes of action have been recently identified that open the door to new drug candidates for treating a range of diseases.
Advanced Virgo is a major upgrade of the Virgo gravitational-wave detector, aiming to increase its sensitivity by an order of magnitude. Among the main modifications of the instrument, the size of ...the laser beam inside the central area has been roughly doubled. Consequently, the input/output optics systems have been re-designed. Due to the overall Advanced Virgo optical scheme, high-magnification and compact telescopes are needed. These telescopes also have to fulfill stringent requirements in terms of aberrations, separation of secondary beams and scattered light. In this paper we describe the design of the Advanced Virgo telescopes and their estimated performances in terms of tuning capability and optical properties.
Different methods have been proposed to estimate the age of mutations, 5, 6 which are based either on allele frequencies 7 or on intra-allelic variability and the pattern of linkage disequilibrium at ...closely linked marker loci 8, 9 with extensions to the analysis of multilocus data. 9- 12 However, these latter approaches are dedicated more to the fine mapping of the mutation, and may not be appropriate for estimating the age of rare mutant alleles that are only found in very few affected individuals. ...we developed a new simple method based on likelihood that uses multilocus marker data to estimate the age of the most recent common ancestor of the mutation from a small number of patients. The problem can be understood as a survival analysis problem in which the starting point is the disease locus, the discrete time scale is the genetic distance, and the event of interest is the occurrence of a recombination. ...we define: S(x), the probability that no recombination took place during n generations between D and marker Mx: S(x)=(1-θx)n f(x), the probability that a recombination took place exactly in the xth interval between marker Mx-1 and Mx: f(x)=S(x-1)-S(x) Key points Among the causing mutations that were recently characterised in Triple-A syndrome (MIM 231550), the IVS14+1G->A mutation was found in several unrelated affected individuals of north African origin, strongly suggesting a founder effect.
Although several constitutive proteasome inhibitors have been reported these recent years, potent organic, noncovalent and readily available inhibitors are still poorly documented. Here we used a ...structure- and ligand-based in silico approach to identify commercially available 1,2,4-oxadiazole derivatives as non-covalent human 20S proteasome inhibitors. Their optimization led to the newly synthesized compound 4h that is a mixed proteasomal inhibitor of the chymotrypsin- like activity (K(i) of 26,1 nM and K'(i) of 7.5 nM) which is in addition selective versus the challenging cathepsin B and calpain proteases. Molecular modelling studies corroborated the mechanism of inhibition and suggest an unusual binding of the inhibitor within the S5 binding pocket (β6 subunit). The cellular effects of our compounds validate their utility as potential pharmacological agents for anti-cancer pre-clinical studies.
The Advanced Virgo (AdV) detector is composed of different degrees of freedom (DOFs) i.e. Michelson interferometer, two Fabry-Perot arm cavities, signal recycling cavity, and power recycling cavity. ...These DOFs need to be locked to precise accuracy with robust, fast and reliable control systems. The control signals used to lock all the DOFs are mildly decoupled in frequency and the optical response of the DOFs are nonlinear, where the linear range of operation is just some percentage of the fringe for each DOF, thus posing difficulty in resonance lock at input laser wavelength for all the cavities. In particular, the control status of the arm cavities can alter the state of the detector's operational configuration. Using Auxiliary Lasers to lock the arm cavities at different wavelength offers flexible and robust lock of the detector and more spatial margin on the control signals. Second harmonic generation offers the most direct way to have laser beam with different wavelength and phase locked to the AdV input laser beam. We generated upto 97 mW of SH beam in single configuration at 532 nm using fibered amplified laser source at 1064 nm in a 10 mm long Poled Lithium Niobate crystal.
Pet food, animal feed and other protein-based food commodities were recently found to contain melamine, an industrial chemical used in the manufacturing of plastics, flame retardants, and other ...products. The US Food and Drug Administration do not approve it for use in food or animal feed. Then there is a need for analytical methods to determine melamine that may be present in dry animal feed. Cause the validation is required for the analytical methods used in the official control of feed, we validated a Gas chromatography–mass spectroscopy method according to 2004/882/CE regulation.
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