At the High Luminosity Large Hadron Collider the Compact Muon Solenoid detector will need to sustain five times larger instantaneous luminosity and, consequently, much higher levels of radiation, ...reaching about ten times the LHC integrated luminosity. Irradiation campaigns have been performed to assess the capability of operating under such conditions and to investigate the ageing induced by radiation. One spare CMS Drift Tube chamber installed at the CERN Gamma Irradiation Facility (GIF++) was irradiated with a high activity source along a period of about two years at different source intensities. The measurements of the effects of radiation on the performance of the Drift Tubes expected during the High Luminosity LHC run are presented. Investigations on the outgassing of cell materials and of the gas components used at GIF++ are underway. Strategies to mitigate the ageing effects are also being developed.
Very few data exist on the management of adult patients diagnosed with primary immune thrombocytopenia (ITP). The objectives of this study were to describe the diagnostic and treatment patterns for ...ITP and to compare the findings to recent ITP guidelines. We retrospectively analyzed the medical records of adult ITP patients diagnosed with primary ITP between January 2011 and June 2012 and examined whether management strategies were consistent or not with eight recent guideline-recommended practices. Overall, median age at the diagnosis of the disease (
n
= 101) was 58 years and median platelet count 12 × 10
9
/L with 75.2 % of patients having symptoms of ITP. The study perceived two major shortcomings in the diagnostic approach: (1) failure to perform peripheral blood film examination in 22.8 % of patients, a test that is mandatory by all guidelines, and (2) ordinary bone marrow assessment in more than half of the patients at diagnosis (50.5 %), a test not routinely recommended by guidelines. Low appropriateness in therapeutic management of patients included (1) unjustified use of intravenous immunoglobulin in the absence of bleeding in 54.8 % of patients and (2) splenectomy not being deferred until 6–12 months from diagnosis (median 161 days). Data also reflect a trend towards the early use of thrombopoietin receptor agonists in the treatment of patients who are refractory to any first-line therapy. We have recognized important areas of inapropriateness in the diagnostic and therapeutic management of adult ITP patients. Compliance with established guidelines should be encouraged in order to improve patient outcomes.
The LHC experiments are undergoing important upgrades for the High Luminosity LHC project. Experiments will be required to operate under three times higher instantaneous luminosity and higher levels ...of radiation when compared to LHC Run2. The integrated luminosity will increase by a factor ten. To cope with these conditions resistive Micromegas chambers were chosen by the ATLAS experiment as one of the technologies for the upgrade of the first forward muon stations. This paper describes the results of two prototype Micromegas detectors that were installed in the CERN Gamma Irradiation Facility with the aim to evaluate the detector performance under high-rate irradiation and to assess ageing effects over a 2.5 year long irradiation period and an accumulated charge in excess of 0.3 C/cm2.
A new multicomponent coupling reaction for the enantioselective synthesis of pyrrolo1,2‐aindoles under the catalysis of a chiral disulfonimide is described. The high specificity of the reaction is a ...consequence of the multidentate character of the Brønsted acid catalyst. Insights from DFT calculations helped explain the unexpected high enantioselectivity observed with the simplest 3,3′‐unsubstituted binaphthyl catalyst as a result of transition‐state stabilization by a network of cooperative noncovalent interactions. The remarkable enantioinversion resulting from the simple introduction of substituents at 3‐ and 3′‐positions, the first reported example of this phenomenon in the context of binaphthalene‐derived Brønsted acid catalysis, was instead attributed to destabilizing steric interactions.
One way or the other: Some exceptional features of chiral disulfonimide organocatalysts are demonstrated in the context of a new highly selective synthesis of pyrrolo1,2‐aindoles. A three‐point coordination model explains the high enantioselectivity observed. An unusual switch of enantioselectivity was observed upon simple structural modification of the catalyst (see scheme).
Stable and non-toxic fluorescent markers are gaining attention in molecular diagnostics as powerful tools for enabling long and reliable biological studies. Such markers should not only have a long ...half-life under several assay conditions showing no photo bleaching or blinking but also, they must allow for their conjugation or functionalization as a crucial step for numerous applications such as cellular tracking, biomarker detection and drug delivery.
We report the functionalization of stable fluorescent markers based on nanodiamonds (NDs) with a bifunctional peptide. This peptide is made of a cell penetrating peptide and a six amino acids long β-sheet breaker peptide that is able to recognize amyloid β (Aβ) aggregates, a biomarker for the Alzheimer disease. Our results indicate that functionalized NDs (fNDs) are not cytotoxic and can be internalized by the cells. The fNDs allow ultrasensitive detection (at picomolar concentrations of NDs) of in vitro amyloid fibrils and amyloid aggregates in AD mice brains.
The fluorescence of functionalized NDs is more stable than that of fluorescent markers commonly used to stain Aβ aggregates such as Thioflavin T. These results pave the way for performing ultrasensitive and reliable detection of Aβ aggregates involved in the pathogenesis of the Alzheimer disease.
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•Different silk fibroin (SF) porous microstructures have been obtained by tuning solution, regeneration and post-processing•-Physical-chemical properties of the obtained materials ...depend on processing method.•The suitability of the microstructures for water remediation has been demonstrated.
The present work reports on the control of silk fibroin (SF) porous structures performance through various processing methods. The study includes the analysis of two dissolving techniques (CaCl2/H2O/EtOH ternary and LiBr/H2O binary solutions), three regeneration methods (gelation, lyophilization and gas foaming) and one post-processing (EtOH). In all the cases, followed steps lead to SF structures with porosity values above 94% and large surface areas. Also, results about samples microstructure, secondary organization, crystallinity and water behavior, reveal a direct correlation between processing and SF properties.
Thanks to the achieved progress, the SF varying porous structures were evaluated for metalloids (As5+ and As3+) and heavy metals (Cr6+ and Cr3+) adsorption, observing a direct relationship between samples processing and ionic species adsorption ability.
Thus, it is shown that the control of the properties of SF based porous structures through processing, represents a suitable and ecofriendly approach for the development of bio-based materials for environmental applications.
The Compact Muon Solenoid (CMS) experiment prepares its Phase-2 upgrade for the high-luminosity era of the LHC operation (HL-LHC). Due to the increase of occupancy, trigger latency and rates, the ...full electronics of the CMS Drift Tube (DT) chambers will need to be replaced. In the new design, the time bin for the digitization of the chamber signals will be of around 1 ns, and the totality of the signals will be forwarded asynchronously to the service cavern at full resolution. The new backend system will be in charge of building the trigger primitives of each chamber. These trigger primitives contain the information at chamber level about the muon candidates position, direction, and collision time, and are used as input in the L1 CMS trigger. The added functionalities will improve the robustness of the system against ageing. An algorithm based on analytical solutions for reconstructing the DT trigger primitives, called Analytical Method, has been implemented both as a software C++ emulator and in firmware. Its performance has been estimated using the software emulator with simulated and real data samples, and through hardware implementation tests. Measured efficiencies are 96 to 98% for all qualities and time and spatial resolutions are close to the ultimate performance of the DT chambers. A prototype chain of the HL-LHC electronics using the Analytical Method for trigger primitive generation has been installed during Long Shutdown 2 of the LHC and operated in CMS cosmic data taking campaigns in 2020 and 2021. Results from this validation step, the so-called Slice Test, are presented.
A new and straightforward metal-organo orthogonal-relay catalytic asymmetric reaction for the enantioselective synthesis of hexahydrofuro3,2-cquinolines is reported. The process involves a ...three-component coupling reaction between an alkynol, an aldehyde and an arylamine catalyzed by a gold complex and a chiral BINOL-derived phosphoric acid. Quantum chemical calculations of the reaction mechanism suggest that the involved acid-catalyzed Povarov reaction is better described as a sequential Mannich/intramolecular Friedel-Crafts process between the 5-phenyl-2,3-dihydrofuran and protonated N-phenylaldimine reactants generated in situ. Moreover, computations of the reaction mechanisms for the formation of the four stereoisomers of the hexahydrofuro3,2-cquinoline adduct using (R)-TRIP-suggested a rationale for the face selectivity of the asymmetric Povarov cycloaddition. With a single coordination mode by ion pairing of the chiral phosphoric acid and the imine, the preferred approach of 5-phenyl-2,3-dihydrofuran to the iminium ion results from a combination of more favourable pi -stacking and reduced steric interactions in the Re-exo transition state relative to the alternative diastereoisomeric orientations.
An unprecedented stereoselective 3+2 carbocyclization reaction of indole‐2‐carboxaldehydes, anilines, and electron‐rich alkenes to obtain cyclopentabindoles is disclosed. This pathway is different ...from the well‐established Povarov reaction: the formal 4+2 cycloaddition involving the same components, which affords tetrahydroquinolines. Moreover, by simply changing the Brønsted acid catalyst, this multicomponent coupling process could be divergently directed towards the conventional Povarov pathway to produce tetrahydroquinolines or to the new pathway (anti‐Povarov) to generate cyclopentabindoles. Supported by computational studies, a stepwise Mannich/Friedel–Crafts cascade is proposed for the new anti‐Povarov reaction, whereas a concerted 4+2 cycloaddition mechanism is proposed for the Povarov reaction.
The proper selection of an acid catalyst, HBF4 or (PhO)2PO2H, allows the divergent synthesis of cyclopentabindoles or tetrahydroquinolines. These compounds are formed through a new 3+2 carbocyclization (anti‐Povarov reaction) or a conventional 4+2 cycloaddition (Povarov reaction) of the in situ‐formed imines derived from 2‐carboxaldehydes and the electron‐rich alkenes.
We present a resistive Micromegas detector built with two different pillar shapes. The pillars are elongated and extend in the direction orthogonal to the readout strips. One region features pillars ...of 2 mm x 0.2 mm with 4.8 mm pitch while in the other region the pillars extend over the full width of the detector. The larger surface of the pillars allows for a better adhesion to the readout structure and a more uniform amplification gap. Results on the detector performance for the two regions are presented. No striking performance differences between the two regions were found.
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![Stereoselective [3+2] Carbo...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/0947-6539/small "Stereoselective [3+2] Carbocyclization of Indole-Derived Imines and Electron-Rich Alkenes: A Divergent Synthesis of Cyclopenta[b]indole or Tetrahydroquinoline Derivatives")