1,860 research outputs found
Experimental Techniques in Nuclear and Particle Physics
I have been teaching courses on experimental techniques in nuclear and particle physics to master students in physics and in engineering for many years. This book grew out of the lecture notes I made for these students. The physics and engineering students have rather different expectations of what such a course should be like. I hope that I have nevertheless managed to write a book that can satisfy the needs of these different target audiences. The lectures themselves, of course, need to be adapted to the needs of each group of students. An engineering student will not qu- tion a statement like “the velocity of the electrons in atoms is ?1% of the velocity of light”, a physics student will. Regarding units, I have written factors h and c explicitly in all equations throughout the book. For physics students it would be preferable to use the convention that is common in physics and omit these constants in the equations, but that would probably be confusing for the engineering students. Physics students tend to be more interested in theoretical physics courses. However, physics is an experimental science and physics students should und- stand how experiments work, and be able to make experiments work. This is an open access book. ; I have been teaching courses on experimental techniques in nuclear and particle physics to master students in physics and in engineering for many years. This book grew out of the lecture notes I made for these students. The physics and engineering students have rather different expectations of what such a course should be like. I hope that I have nevertheless managed to write a book that can satisfy the needs of these different target audiences. The lectures themselves, of course, need to be adapted to the needs of each group of students. An engineering student will not qu- tion a statement like “the velocity of the electrons in atoms is ?1% of the velocity of light”, a physics student will. Regarding units, I have written factors h and c explicitly in all equations throughout the book. For physics students it would be preferable to use the convention that is common in physics and omit these constants in the equations, but that would probably be confusing for the engineering students. Physics students tend to be more interested in theoretical physics courses. However, physics is an experimental science and physics students should und- stand how experiments work, and be able to make experiments work
Treatment with mRNA coding for the necroptosis mediator MLKL induces antitumor immunity directed against neo-epitopes
Cancer immunotherapy can induce durable antitumor responses. However, many patients poorly respond to such therapies. Here we describe a generic antitumor therapy that is based on the intratumor delivery of mRNA that codes for the necroptosis executioner mixed lineage kinase domain-like (MLKL) protein. This intervention stalls primary tumor growth and protects against distal and disseminated tumor formation in syngeneic mouse melanoma and colon carcinoma models. Moreover, MLKL-mRNA treatment combined with immune checkpoint blockade further improves the antitumor activity. MLKL-mRNA treatment rapidly induces T cell responses directed against tumor neo-antigens and requires CD4(+) and CD8(+) T cells to prevent tumor growth. Type I interferon signaling and Batf3-dependent dendritic cells are essential for this mRNA treatment to elicit tumor antigen-specific T cell responses. Moreover, MLKL-mRNA treatment blunts the growth of human lymphoma in mice with a reconstituted human adaptive immune system. MLKL-based treatment can thus be exploited as an effective antitumor immunotherapy
Asymmetric data acquisition system for an endoscopic PET-US detector
According to current prognosis studies of pancreatic cancer, survival rate nowadays is still as low as 6% mainly due to late detections. Taking into account the location of the disease within the body and making use of the level of miniaturization in radiation detectors that can be achieved at the present time, EndoTOFPET-US collaboration aims at the development of a multimodal imaging technique for endoscopic pancreas exams that combines the benefits of high resolution metabolic information from time-of- flight (TOF) positron emission tomography (PET) with anatomical information from ultrasound (US). A system with such capabilities calls for an application-specific high-performance data acquisition system (DAQ) able to control and readout data from different detectors. The system is composed of two novel detectors: a PET head extension for a commercial US endoscope placed internally close to the region-of-interest (ROI) and a PET plate placed over the patient's abdomen in coincidence with the PET head. These two detectors will send asymmetric data streams that need to be handled by the DAQ system. The approach chosen to cope with these needs goes through the implementation of a DAQ capable of performing multi-level triggering and which is distributed across two different on-detector electronics and the off-detector electronics placed inside the reconstruction workstation. This manuscript provides an overview on the design of this innovative DAQ system and, based on results obtained by means of final prototypes of the two detectors and DAQ, we conclude that a distributed multi-level triggering DAQ system is suitable for endoscopic PET detectors and it shows potential for its application in different scenarios with asymmetric sources of data
Modifying Rap1-signalling by targeting Pde6δ is neuroprotective in models of Alzheimer’s disease
Background: Neuronal Ca2+ dyshomeostasis and hyperactivity play a central role in Alzheimer's disease pathology arid progression. Amyloid-beta together with non-genetic risk-factors of Alzheimer's disease contributes to increased Ca2+ influx and aberrant neuronal activity, which accelerates neurodegeneration in a feed-forward fashion. As such, identifying new targets and drugs to modulate excessive Ca2+ signalling and neuronal hyperactivity, without overly suppressing them, has promising therapeutic potential.
Methods: Here we show, using biochemical, electrophysiological, imaging, and behavioural tools, that pharmacological modulation of Rap1 signalling by inhibiting its interaction with Pde6 delta normalises disease associated Ca2+ aberrations and neuronal activity, conferring neuroprotection in models of Alzheimer's disease.
Results: The newly identified inhibitors of the Rap1-Pde6 delta interaction counteract AD phenotypes, by reconfiguring Rapt signalling underlying synaptic efficacy, Ca2+ influx, and neuronal repolarisation, without adverse effects in-cellulo or invivo. Thus, modulation of Rap1 by Pde6 delta accommodates key mechanisms underlying neuronal activity, and therefore represents a promising new drug target for early or late intervention in neurodegenerative disorders.
Conclusion: Targeting the Pde6 delta-Rap1 interaction has promising therapeutic potential for disorders characterised by neuronal hyperactivity, such as Alzheimer's disease
Evading innate immunity in nonviral mRNA delivery : don't shoot the messenger
In de field of non-viral gene therapy, in vitro transcribed (IVT) mRNA has emerged as a promising tool for the delivery of genetic information. Over the past few years it has become widely known the introduction of IVT mRNA into mammalian cells elicits an innate immune response which has favored mRNA use towards immunotherapeutic vaccination strategies. However, for non-immunotherapy related applications this intrinsic immune-stimulatory activity directly interferes with the aimed therapeutic outcome, as it can seriously compromise the expression of the desired protein. This review presents an overview of the immune-related obstacles that limit mRNA advance for non-immunotherapy related applications
Extensive studies on CeF crystals, a good candidate for electromagnetic calorimetry at future accelerators
Reception Test of Petals for the End Cap TEC+ of the CMS Silicon Strip Tracker
The silicon strip tracker of the CMS experiment has been completed and was inserted into the CMS detector in late 2007. The largest sub system of the tracker are its end caps, comprising two large end caps (TEC) each containing 3200 silicon strip modules. To ease construction, the end caps feature a modular design: groups of about 20 silicon modules are placed on sub-assemblies called petals and these self-contained elements are then mounted onto the TEC support structures. Each end cap consists of 144 such petals, which were built and fully qualified by several institutes across Europe. Fro
Integration of the End Cap TEC+ of the CMS Silicon Strip Tracker
The silicon strip tracker of the CMS experiment has been completed and inserted into the CMS detector in late 2007. The largest sub-system of the tracker is its end cap system, comprising two large end caps (TEC) each containing 3200 silicon strip modules. To ease construction, the end caps feature a modular design: groups of about 20 silicon modules are placed on sub-assemblies called petals and these self-contained elements are then mounted into the TEC support structures. Each end cap consists of 144 petals, and the insertion of these petals into the end cap structure is referred to as TEC integration. The two end caps were integrated independently in Aachen (TEC+) and at CERN (TEC--). This note deals with the integration of TEC+, describing procedures for end cap integration and for quality control during testing of integrated sections of the end cap and presenting results from the testing
The potential of antigen and TriMix sonoporation using mRNA-loaded microbubbles for ultrasound-triggered cancer immunotherapy
Measurement of differential cross sections for top quark pair production using the lepton plus jets final state in proton-proton collisions at 13 TeV
National Science Foundation (U.S.
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