myositis an evolving spectrum of disease

AbstractThe idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of disorders characterized, as common feature, by inflammation of skeletal muscle and muscle weakness. Traditionally,..

Squeezed light for advanced gravitational wave detectors and beyond

Recent experiments have demonstrated that squeezed vacuum states can be injected into gravitational wave detectors to improve their sensitivity at detection frequencies where they are quantum noise limited. Squeezed states could be employed in the next generation of more sensitive advanced detectors currently under construction, such as Advanced LIGO, to further push the limits of the observable gravitational wave Universe. To maximize the benefit from squeezing, environmentally induced disturbances such as back scattering and angular jitter need to be mitigated. We discuss the limitations of current squeezed vacuum sources in relation to the requirements imposed by future gravitational wave detectors, and show a design for squeezed light injection which overcomes these limitations

Stretch-induced Calcium Release in Smooth Muscle

Smooth muscle cells undergo substantial increases in length, passively stretching during increases in intraluminal pressure in vessels and hollow organs. Active contractile responses to counteract increased transmural pressure were first described almost a century ago (Bayliss, 1902) and several mechanisms have been advanced to explain this phenomenon. We report here that elongation of smooth muscle cells results in ryanodine receptor–mediated Ca2+ release in individual myocytes. Mechanical elongation of isolated, single urinary bladder myocytes to ∼120% of slack length (ΔL = 20) evoked Ca2+ release from intracellular stores in the form of single Ca2+ sparks and propagated Ca2+ waves. Ca2+ release was not due to calcium-induced calcium release, as release was observed in Ca2+-free extracellular solution and when free Ca2+ ions in the cytosol were strongly buffered to prevent increases in [Ca2+]i. Stretch-induced calcium release (SICR) was not affected by inhibition of InsP3R-mediated Ca2+ release, but was completely blocked by ryanodine. Release occurred in the absence of previously reported stretch-activated currents; however, SICR evoked calcium-activated chloride currents in the form of transient inward currents, suggesting a regulatory mechanism for the generation of spontaneous currents in smooth muscle. SICR was also observed in individual myocytes during stretch of intact urinary bladder smooth muscle segments. Thus, longitudinal stretch of smooth muscle cells induces Ca2+ release through gating of RYR. SICR may be an important component of the physiological response to increases in luminal pressure in smooth muscle tissues

A randomized clinical control study on the efficacy of three-dimensional upper limb robotic exoskeleton training in chronic stroke

Background : Although robotics assisted rehabilitation has proven to be effective in stroke rehabilitation, a limited functional improvements in Activities of Daily Life has been also observed after the administration of robotic training. To this aim in this study we compare the efficacy in terms of both clinical and functional outcomes of a robotic training performed with a multi-joint functional exoskeleton in goal-oriented exercises compared to a conventional physical therapy program, equally matched in terms of intensity and time. As a secondary goal of the study, it was assessed the capability of kinesiologic measurements—extracted by the exoskeleton robotic system—of predicting the rehabilitation outcomes using a set of robotic biomarkers collected at the baseline. Methods : A parallel-group randomized clinical trial was conducted within a group of 26 chronic post-stroke patients. Patients were randomly assigned to two groups receiving robotic or manual therapy. The primary outcome was the change in score on the upper extremity section of the Fugl-Meyer Assessment (FMA) scale. As secondary outcome a specifically designed bimanual functional scale, Bimanual Activity Test (BAT), was used for upper limb functional evaluation. Two robotic performance indices were extracted with the purpose of monitoring the recovery process and investigating the interrelationship between pre-treatment robotic biomarkers and post-treatment clinical improvement in the robotic group. Results : A significant clinical and functional improvements in both groups (p < 0.01) was reported. More in detail a significantly higher improvement of the robotic group was observed in the proximal portion of the FMA (p < 0.05) and in the reduction of time needed for accomplishing the tasks of the BAT (p < 0.01). The multilinear-regression analysis pointed out a significant correlation between robotic biomarkers at the baseline and change in FMA score (R2 = 0.91, p < 0.05), suggesting their potential ability of predicting clinical outcomes. Conclusion : Exoskeleton-based robotic upper limb treatment might lead to better functional outcomes, if compared to manual physical therapy. The extracted robotic performance could represent predictive indices of the recovery of the upper limb. These results are promising for their potential exploitation in implementing personalized robotic therapy. Clinical Trial Registration clinicaltrials.gov, NCT03319992 Unique Protocol ID: RH-UL-LEXOS-10. Registered 20.10.2017, https://clinicaltrials.gov/ct2/show/NCT0331999

A Gravitational Wave Detector with Cosmological Reach

Twenty years ago, construction began on the Laser Interferometer Gravitational-wave Observatory (LIGO). Advanced LIGO, with a factor of ten better design sensitivity than Initial LIGO, will begin taking data this year, and should soon make detections a monthly occurrence. While Advanced LIGO promises to make first detections of gravitational waves from the nearby universe, an additional factor of ten increase in sensitivity would put exciting science targets within reach by providing observations of binary black hole inspirals throughout most of the history of star formation, and high signal to noise observations of nearby events. Design studies for future detectors to date rely on significant technological advances that are futuristic and risky. In this paper we propose a different direction. We resurrect the idea of a using longer arm lengths coupled with largely proven technologies. Since the major noise sources that limit gravitational wave detectors do not scale trivially with the length of the detector, we study their impact and find that 40~km arm lengths are nearly optimal, and can incorporate currently available technologies to detect gravitational wave sources at cosmological distances $(z \gtrsim 7)$

Frequency-Dependent Squeezing for Advanced LIGO

The first detection of gravitational waves by the Laser Interferometer Gravitational-wave Observatory (LIGO) in 2015 launched the era of gravitational wave astronomy. The quest for gravitational wave signals from objects that are fainter or farther away impels technological advances to realize ever more sensitive detectors. Since 2019, one advanced technique, the injection of squeezed states of light is being used to improve the shot noise limit to the sensitivity of the Advanced LIGO detectors, at frequencies above $\sim 50$ Hz. Below this frequency, quantum back action, in the form of radiation pressure induced motion of the mirrors, degrades the sensitivity. To simultaneously reduce shot noise at high frequencies and quantum radiation pressure noise at low frequencies requires a quantum noise filter cavity with low optical losses to rotate the squeezed quadrature as a function of frequency. We report on the observation of frequency-dependent squeezed quadrature rotation with rotation frequency of 30Hz, using a 16m long filter cavity. A novel control scheme is developed for this frequency-dependent squeezed vacuum source, and the results presented here demonstrate that a low-loss filter cavity can achieve the squeezed quadrature rotation necessary for the next planned upgrade to Advanced LIGO, known as "A+."Comment: 6 pages, 2 figures, to be published in Phys. Rev. Let

Effect of platelet lysate on human cells involved in different phases of wound healing

Background Platelets are rich in mediators able to positively affect cell activity in wound healing. Aim of this study was to characterize the effect of different concentrations of human pooled allogeneic platelet lysate on human cells involved in the different phases of wound healing (inflammatory phase, angiogenesis, extracellular matrix secretion and epithelialization). Methodology/Principal Findings Platelet lysate effect was studied on endothelial cells, monocytes, fibroblasts and keratinocytes, in terms of viability and proliferation, migration, angiogenesis, tissue repair pathway activation (ERK1/2) and inflammatory response evaluation (NFκB). Results were compared both with basal medium and with a positive control containing serum and growth factors. Platelet lysate induced viability and proliferation at the highest concentrations tested (10% and 20% v/v). Whereas both platelet lysate concentrations increased cell migration, only 20% platelet lysate was able to significantly promote angiogenic activity (p<0.05 vs. control), comparably to the positive control. Both platelet lysate concentrations activated important inflammatory pathways such as ERK1/2 and NFκB with the same early kinetics, whereas the effect was different for later time-points. Conclusion/Significance These data suggest the possibility of using allogeneic platelet lysate as both an alternative to growth factors commonly used for cell culture and as a tool for clinical regenerative application for wound healing

Approaching the motional ground state of a 10-kg object

The motion of a mechanical object— even a human-sized object— should be governed by the rules of quantum mechanics. Coaxing them into a quantum state is, however, difficult: the thermal environment effectively masks any quantum signature of the object’s motion. Indeed, it also masks effects of proposed modifications of quantum mechanics at large mass scales. We prepare the center-of-mass motion of a 10 kg mechanical oscillator in a state with an average phonon occupation of 10.8. The reduction in oscillator temperature, from room temperature to 77 nK, represents a 100-fold improvement in the reduction of temperature of a solid-state mechanical oscillator— commensurate with a 11 orders-of-magnitude suppression of quantum back-action by feedback — and a 10 orders-of-magnitude increase in the mass of an object prepared close to its motional ground state