The inflammation in the cytopathology of patients with mucopolysaccharidoses : immunomodulatory drugs as an approach to therapy

Mucopolysaccharidoses (MPS) are a group of lysosomal storage diseases (LSDs), characterized by the accumulation of glycosaminoglycans (GAGs). GAG storageinduced inflammatory processes are a driver of cytopathology in MPS and pharmacological immunomodulation can bring improvements in brain, cartilage and bone pathology in rodent models. This manuscript reviews current knowledge with regard to inflammation in MPS patients and provides hypotheses for the therapeutic use of immunomodulators in MPS. Thus, we aim to set the foundation for a rational repurposing of the discussed molecules to minimize the clinical unmet needs still remaining despite enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT)

A hydrogen beam to characterize the ASACUSA antihydrogen hyperfine spectrometer

The antihydrogen programme of the ASACUSA collaboration at the antiproton decelerator of CERN focuses on Rabi-type measurements of the ground-state hyperfine splitting of antihydrogen for a test of the combined Charge-Parity-Time symmetry. The spectroscopy apparatus consists of a microwave cavity to drive hyperfine transitions and a superconducting sextupole magnet for quantum state analysis via Stern-Gerlach separation. However, the small production rates of antihydrogen forestall comprehensive performance studies on the spectroscopy apparatus. For this purpose a hydrogen source and detector have been developed which in conjunction with ASACUSA's hyperfine spectroscopy equipment form a complete Rabi experiment. We report on the formation of a cooled, polarized, and time modulated beam of atomic hydrogen and its detection using a quadrupole mass spectrometer and a lock-in amplification scheme. In addition key features of ASACUSA's hyperfine spectroscopy apparatus are discussed.

BASE-STEP: A transportable antiproton reservoir for fundamental interaction studies

Currently, the only worldwide source of low-energy antiprotons is the AD/ELENA facility located at CERN. To date, all precision measurements on single antiprotons have been conducted at this facility and provide stringent tests of the fundamental interactions and their symmetries. However, the magnetic field fluctuations from the facility operation limit the precision of upcoming measurements. To overcome this limitation, we have designed the transportable antiproton trap system BASE-STEP to relocate antiprotons to laboratories with a calm magnetic environment. We anticipate that the transportable antiproton trap will facilitate enhanced tests of CPT invariance with antiprotons, and provide new experimental possibilities of using transported antiprotons and other accelerator-produced exotic ions. We present here the technical design of the transportable trap system. This includes the transportable superconducting magnet, the cryogenic inlay consisting of the trap stack and the detection systems, and the differential pumping section to suppress the residual gas flow into the cryogenic trap chamber.Comment: To be submitted to Rev. Sci. Instrument

A False Start in the Race Against Doping in Sport: Concerns With Cycling’s Biological Passport

Professional cycling has suffered from a number of doping scandals. The sport’s governing bodies have responded by implementing an aggressive new antidoping program known as the biological passport. Cycling’s biological passport marks a departure from traditional antidoping efforts, which have focused on directly detecting prohibited substances in a cyclist’s system. Instead, the biological passport tracks biological variables in a cyclist’s blood and urine over time, monitoring for fluctuations that are thought to indirectly reveal the effects of doping. Although this method of indirect detection is promising, it also raises serious legal and scientific concerns. Since its introduction, the cycling community has debated the reliability of indirect biological-passport evidence and the clarity, consistency, and transparency of its use in proving doping violations. Such uncertainty undermines the legitimacy of finding cyclists guilty of doping based on this indirect evidence alone. Antidoping authorities should address these important concerns before continuing to pursue doping sanctions against cyclists solely on the basis of their biological passports

Responsiveness to exercise training in juvenile dermatomyositis: a twin case study

<p>Abstract</p> <p>Background</p> <p>Patients with juvenile dermatomyositis (JDM) often present strong exercise intolerance and muscle weakness. However, the role of exercise training in this disease has not been investigated.</p> <p>Purpose</p> <p>this longitudinal case study reports on the effects of exercise training on a 7-year-old patient with JDM and on her unaffected monozygotic twin sister, who served as a control.</p> <p>Methods</p> <p>Both the patient who was diagnosed with JDM as well as her healthy twin underwent a 16-week exercise training program comprising aerobic and strengthening exercises. We assessed one repetition-maximum (1-RM) leg-press and bench-press strength, balance, mobility and muscle function, blood markers of inflammation and muscle enzymes, aerobic conditioning, and disease activity scores. As a result, the healthy child had an overall greater absolute strength, muscle function and aerobic conditioning compared to her JDM twin pair at baseline and after the trial. However, the twins presented comparable relative improvements in 1-RM bench press, 1-RM leg press, VO_2peak, and time-to-exhaustion. The healthy child had greater relative increments in low-back strength and handgrip, whereas the child with JDM presented a higher relative increase in ventilatory anaerobic threshold parameters and functional tests. Quality of life, inflammation, muscle damage and disease activity scores remained unchanged.</p> <p>Results and Conclusion</p> <p>this was the first report to describe the training response of a patient with non-active JDM following an exercise training regimen. The child with JDM exhibited improved strength, muscle function and aerobic conditioning without presenting an exacerbation of the disease.</p

Characterization of 30 76^{76}Ge enriched Broad Energy Ge detectors for GERDA Phase II

The GERmanium Detector Array (GERDA) is a low background experiment located at the Laboratori Nazionali del Gran Sasso in Italy, which searches for neutrinoless double beta decay of $^{76}$Ge into $^{76}$Se+2e$^-$. GERDA has been conceived in two phases. Phase II, which started in December 2015, features several novelties including 30 new Ge detectors. These were manufactured according to the Broad Energy Germanium (BEGe) detector design that has a better background discrimination capability and energy resolution compared to formerly widely-used types. Prior to their installation, the new BEGe detectors were mounted in vacuum cryostats and characterized in detail in the HADES underground laboratory in Belgium. This paper describes the properties and the overall performance of these detectors during operation in vacuum. The characterization campaign provided not only direct input for GERDA Phase II data collection and analyses, but also allowed to study detector phenomena, detector correlations as well as to test the strength of pulse shape simulation codes.Comment: 29 pages, 18 figure

Background free search for neutrinoless double beta decay with GERDA Phase II

The Standard Model of particle physics cannot explain the dominance of matter over anti-matter in our Universe. In many model extensions this is a very natural consequence of neutrinos being their own anti-particles (Majorana particles) which implies that a lepton number violating radioactive decay named neutrinoless double beta ($0\nu\beta\beta$) decay should exist. The detection of this extremely rare hypothetical process requires utmost suppression of any kind of backgrounds. The GERDA collaboration searches for $0\nu\beta\beta$ decay of $^{76}$Ge (^{76}\rm{Ge} \rightarrow\,^{76}\rm{Se} + 2e^-) by operating bare detectors made from germanium with enriched $^{76}$Ge fraction in liquid argon. Here, we report on first data of GERDA Phase II. A background level of $\approx10^{-3}$ cts/(keV$\cdot$kg$\cdot$yr) has been achieved which is the world-best if weighted by the narrow energy-signal region of germanium detectors. Combining Phase I and II data we find no signal and deduce a new lower limit for the half-life of $5.3\cdot10^{25}$ yr at 90 % C.L. Our sensitivity of $4.0\cdot10^{25}$ yr is competitive with the one of experiments with significantly larger isotope mass. GERDA is the first $0\nu\beta\beta$ experiment that will be background-free up to its design exposure. This progress relies on a novel active veto system, the superior germanium detector energy resolution and the improved background recognition of our new detectors. The unique discovery potential of an essentially background-free search for $0\nu\beta\beta$ decay motivates a larger germanium experiment with higher sensitivity.Comment: 14 pages, 9 figures, 1 table; ; data, figures and images available at http://www.mpi-hd.mpg/gerda/publi

Limits on uranium and thorium bulk content in GERDA Phase I detectors

Internal contaminations of $^{238}$U, $^{235}$U and $^{232}$Th in the bulk of high purity germanium detectors are potential backgrounds for experiments searching for neutrinoless double beta decay of $^{76}$Ge. The data from GERDA Phase~I have been analyzed for alpha events from the decay chain of these contaminations by looking for full decay chains and for time correlations between successive decays in the same detector. No candidate events for a full chain have been found. Upper limits on the activities in the range of a few nBq/kg for $^{226}$Ra, $^{227}$Ac and $^{228}$Th, the long-lived daughter nuclides of $^{238}$U, $^{235}$U and $^{232}$Th, respectively, have been derived. With these upper limits a background index in the energy region of interest from $^{226}$Ra and $^{228}$Th contamination is estimated which satisfies the prerequisites of a future ton scale germanium double beta decay experiment.Comment: 2 figures, 7 page

Ultra thin polymer foil cryogenic window for antiproton deceleration and storage

We present the design and characterisation of a cryogenic window based on an ultra-thin aluminised PET foil at T < 10K, which can withstand a pressure difference larger than 1bar at a leak rate < $1\times 10^{-9}$ mbar$\cdot$ l/s. Its thickness of approximately 1.7 $\mu$m makes it transparent to various types of particles over a broad energy range. To optimise the transfer of 100keV antiprotons through the window, we tested the degrading properties of different aluminium coated PET foils of thicknesses between 900nm and 2160nm, concluding that 1760nm foil decelerates antiprotons to an average energy of 5 keV. We have also explicitly studied the permeation as a function of coating thickness and temperature, and have performed extensive thermal and mechanical endurance and stress tests. Our final design integrated into the experiment has an effective open surface consisting of 7 holes with 1 mm diameter and will transmit up to 2.5% of the injected 100keV antiproton beam delivered by the AD/ELENA-facility of CERN