Summary
Introduction
We characterized four unrelated patients with von Willebrand disease type 2A/IIE, sharing the same von Willebrand factor (VWF) in‐frame deletion (p.P1127_G1180delinsR;=) ...resulting from exon 26 skipping (Δ26).
Objectives
To identify the VWF mutations and how they caused the mRNA splicing alteration, to evaluate the deletion by in vitro expression studies, and to assess whether or not the heterogeneity of the patients’ phenotype might be related to a different degree of expression of the deleted subunit in patient plasma VWF.
Methods
Sequence analysis was performed with patient genomic DNA and platelet mRNA. Semiquantitative RT‐PCR was also carried out to compare the expression of the wild‐type (WT) and Δ26 alleles in the four patients. In silico analysis was performed with prediction splicing programs. Expression studies were performed to evaluate mutant recombinant VWF (rVWF) (Δ26 and Δ26/WT) as compared with WT rVWF.
Results
Three patients shared the synonymous single‐nucleotide substitution (SSS) c.3390C>T;=, whereas the novel mutation c.3380‐2A>G;= was present in the fourth patient. Semiquantitative RT‐PCR of platelet mRNA revealed a different ratio of the WT and Δ26 alleles in the patients, consistent with the different VWF:FVIIIB values present in patient plasma. Expression studies confirmed reduced VWF–FVIII binding of rVWF‐Δ26/WT.
Conclusions
SSS can induce alternative splicing, and those like c.3390C>T, which impact on the poorly conserved splicing regulatory elements, are difficult to predict, so that their role can be evaluated only by mRNA analysis. Moreover, these mutations seem to have different effects on the efficiency of alternative splicing, producing heterogeneous VWF variants among the four patients.
The Cherenkov Telescope Array (CTA), as the next generation ground-based very high-energy gamma-ray observatory, is defining new areas beyond those related to physics. It is also creating new demands ...on the control and data acquisition system. CTA will consist of two installations, one in each hemisphere, containing tens of telescopes of different sizes. The ACTL (array control and data acquisition) system will consist of the hardware and software that is necessary to control and monitor the CTA array, as well as to time-stamp, read-out, filter and store the scientific data at aggregated rates of a few GB s. The ACTL system must implement a flexible software architecture to permit the simultaneous automatic operation of multiple sub-arrays of telescopes with a minimum personnel effort on site. In addition ACTL must be able to modify the observation schedule on timescales of a few tens of seconds, to account for changing environmental conditions or to prioritize incoming scientific alerts from time-critical transient phenomena such as gamma-ray bursts. This contribution summarizes the status of the development of the software architecture and the main design choices and plans.
The Cherenkov Telescope Array (CTA) is the next-generation atmospheric Cherenkov gamma-ray observatory. The Observation Execution System (OES) team within the CTA project is designing and prototyping ...the software to execute the observations and to handle the acquisition of scientific data at GB/s rates. In this contribution we show the OES system as it is being designed using the Unified Modeling Language (UML) and Systems Modeling (SysML) formalisms. In addition, we present the status of the associated prototyping activities.
Urban health authorities in the United States have been charged with developing plans for providing the infrastructure necessary to dispense prophylactic medications to their populations in the case ...of epidemic disease outbreak or bioterrorist attack. However, no specific method for such plans has been prescribed. This article formulates and demonstrates the use of an integer programming technique for helping to solve a part of the dispensing problem faced by cities, namely that of providing the federally required infrastructure at minimum cost, using their limited time and resources. Specifically, the technique minimizes the number of point-of-dispensing (POD) centers while covering every resident in all the census tracts within the city's jurisdiction. It also determines the optimal staffing requirement in terms of the number of nurses at each POD. This article includes a demonstration of the model using real data from Cleveland, OH, a mid-sized US city. Examples are provided of data and computational results for a variety of input parameter values such as population throughput rate, POD capacities, and distance limitations. The technique can be readily adapted to a wide range of urban areas.
We have numerically studied the effect of temperature on the flux-flow behavior in a stack of intrinsic Josephson junctions by using the inductive coupling Josephson junctions model taking into ...account thermal fluctuations. In the absence of noise, the current-voltage characteristic shows a series of clear Fiske and flux-flow steps depending on an external magnetic field. With increasing temperature the Fiske steps corresponding to the out-of-phase mode remain on the current-voltage characteristic but other steps disappear. This suggests that the out-of-phase cavity mode becomes more stable than other modes due to the fluctuations. Furthermore, it is found that the in-phase flux flow mode is also strongly affected by the thermal noise in contrast to the out-of-phase one and fluctuations disturb the formation of the rectangular lattice of vortices even in the flux-flow mode driven by a strong Lorentz force Our results can qualitatively explain recent experimental observations in intrinsic Josephson junctions in the flux-flow state.
We have numerically and experimentally investigated multijunction superconducting quantum interference device (SQUID) based on intrinsic Josephson junctions (IJJs) of in order to improve the flux to ...voltage transfer coefficient. Numerical simulations suggest that the modulation depth of critical current decreases with an increase in the number of junctions in the stack and the SQUID consisting of few junctions will yield the best performance. The SQUIDs with in-plane loop geometry incorporating two stacks of IJJs were successfully fabricated from (BSCCO). The advantages of this layout are that the multijunction SQUID can be achieved without an increase in device size and the stack of IJJs is less affected by an applying magnetic field. At 4.2 K, the SQUIDs showed hysteretic current-voltage characteristics with typical multiple resistive branches. As the temperature was increased, the hysteresis disappeared and the SQUID showed clear periodic voltage-flux characteristics due to the quantum interference between the weakest junctions in the stacks.
The Cherenkov Telescope Array (CTA) is one of the major ground-based astronomy projects being pursued and will be the largest facility for ground-based y-ray observations ever built. CTA will consist ...of two arrays: one in the Northern hemisphere composed of about 20 telescopes, and the other one in the Southern hemisphere composed of about 100 telescopes, both arrays containing telescopes of different type and size. A prototype for the Mid-Size Telescope (MST) with a diameter of 12 m has been installed in Berlin and is currently being commissioned. This prototype is composed of a mechanical structure, a drive system and mirror facets mounted with powered actuators to enable active control. Five Charge-Coupled Device (CCD) cameras, and a wide set of sensors allow the evaluation of the performance of the instrument. The design of the control software is following concepts and tools under evaluation within the CTA consortium in order to provide a realistic test-bed for the middleware: 1) The readout and control system for the MST prototype is implemented with the Atacama Large Millimeter/submillimeter Array (ALMA) Common Software (ACS) distributed control middleware; 2) the OPen Connectivity-Unified Architecture (OPC UA) is used for hardware access; 3) the document oriented MongoDB database is used for an efficient storage of CCD images, logging and alarm information: and 4) MySQL and MongoDB databases are used for archiving the slow control monitoring data and for storing the operation configuration parameters. In this contribution, the details of the implementation of the control system for the MST prototype telescope are described.
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