Extracellular ATP released by osteoblasts is a key local inhibitor of bone mineralisation

Previous studies have shown that exogenous ATP (>1µM) prevents bone formation in vitro by blocking mineralisation of the collagenous matrix. This effect is thought to be mediated via both P2 receptor-dependent pathways and a receptor-independent mechanism (hydrolysis of ATP to produce the mineralisation inhibitor pyrophosphate, PPi). Osteoblasts are also known to release ATP constitutively. To determine whether this endogenous ATP might exert significant biological effects, bone-forming primary rat osteoblasts were cultured with 0.5-2.5U/ml apyrase (which sequentially hydrolyses ATP to ADP to AMP + 2Pi). Addition of 0.5U/ml apyrase to osteoblast culture medium degraded extracellular ATP to <1% of control levels within 2 minutes; continuous exposure to apyrase maintained this inhibition for up to 14 days. Apyrase treatment for the first 72 hours of culture caused small decreases (≤25%) in osteoblast number, suggesting a role for endogenous ATP in stimulating cell proliferation. Continuous apyrase treatment for 14 days (≥0.5U/ml) increased mineralisation of bone nodules by up to 3-fold. Increases in bone mineralisation were also seen when osteoblasts were cultured with the ATP release inhibitors, NEM and brefeldin A, as well as with P2X1 and P2X7 receptor antagonists. Apyrase decreased alkaline phosphatase (TNAP) activity by up to 60%, whilst increasing the activity of the PPi-generating ecto-nucleotide pyrophosphatase/phosphodiesterases (NPPs) up to 2.7-fold. Both collagen production and adipocyte formation were unaffected. These data suggest that nucleotides released by osteoblasts in bone could act locally, via multiple mechanisms, to limit mineralisation

Neural Networks Reduction via Lumping

The increasing size of recently proposed Neural Networks makes it hard to implement them on embedded devices, where memory, battery and computational power are a non-trivial bottleneck. For this reason during the last years network compression literature has been thriving and a large number of solutions has been published to reduce both the number of operations and the parameters involved with the models. Unfortunately, most of these reducing techniques are actually heuristic methods and usually require at least one re-training step to recover the accuracy. The need of procedures for model reduction is well-known also in the fields of Verification and Performances Evaluation, where large efforts have been devoted to the definition of quotients that preserve the observable underlying behaviour. In this paper we try to bridge the gap between the most popular and very effective network reduction strategies and formal notions, such as lumpability, introduced for verification and evaluation of Markov Chains. Elaborating on lumpability we propose a pruning approach that reduces the number of neurons in a network without using any data or fine-tuning, while completely preserving the exact behaviour. Relaxing the constraints on the exact definition of the quotienting method we can give a formal explanation of some of the most common reduction techniques

Speeding up Answer Set Programming by Quantum Computing

Quantum Computing has become a more and more prominent research field in the last few decades. This growth in interest is mainly related to the so-called quantum speed up that some quantum procedure exhibits. The two main examples are Shor and Grover algorithms. The latter will be a key ingredient of this paper. In particular, we propose an attempt to speed up Answer Set Programming (ASP) exploiting Quantum Computing. We rely on two proposals in the literature that use quantum computation for: finding stable models of ASP programs; counting solutions of propositional formulae. For combining such proposals we embed in the quantum framework a third proposal from the literature, namely a purely classical approach for navigating the solution space of ASP models. We end up with a quantum method for counting stable models of ASP programs. After providing the details of our method, we briefly describe a Proof of Concept implementation of these techniques

Bidirectional Communication System on Power Line Integrated on Electronic Board for Driving of LED and HID Lamps

We present the bidirectional power line communication system developed in parallel to an electronic board for driving and control of HID (high-intensity discharge) and LED (light-emitting diode) lamps. The communication system, developed to be applied in the sector of public illumination, is been designed to combine high efficiency and reliability with low production costs; it consists indeed of discrete cheap components. The communication system described in this paper implements the technique of transporting digital information over existing power lines, avoiding the issue of installing new cables. Digitized signals can use power line cables through the amplitude voltage and current modulation. The solution proposed is more advantageous compared to communication techniques currently on the market which are essentially two types, power line carrier (modem for high-voltage lines) or radio (zig-Bee transceiver)

Tomographic cluster clustering as a cosmological probe

The spatial distribution of galaxy clusters is a valuable probe for inferring fundamental cosmological parameters. We measured the clustering properties of dark matter haloes from the PINOCCHIO simulations in the redshift range 0.2 &lt; z &lt; 1.0 and with virial masses Mvir &gt; 1014 M⊙ h-1, which reproduce the expected mass selection of galaxy cluster samples. The past light cones we analysed have an angular size of 60 degrees, which approximately corresponds to one-quarter of the sky. We adopted a linear power spectrum model, accounting for non-linear corrections at the scale of baryon acoustic oscillations, to perform a comparative study between 3D and 2D tomographic clustering. For this purpose, we modelled the multipoles of the 3D two-point correlation function, ξ(s); the angular correlation function, w(θ); and the angular power spectrum, Cl. We considered observational effects such as redshift-space distortions produced by the peculiar velocities of tracers, and redshift errors. We found that photo-z errors have a more severe consequence on 3D clustering than on 2D clustering, as they affect only the radial separation between haloes and not the angular separation, with a relevant impact on the 3D multipoles. Using a Bayesian analysis, we explored the posterior distributions of the considered probes with different tomographic strategies, in the Ωm - σ8 plane, focusing on the summary parameter S8 ≡ σ8 √Ωm/0.3. Our results show that in the presence of large photo-z errors the 2D clustering can provide competitive cosmological constraints with respect to the full 3D clustering statistics, and can be successfully applied to analyse the galaxy cluster catalogues from the ongoing and forthcoming Stage III and Stage IV photometric redshift surveys

Saccharomyces cerevisiae Peroxiredoxins in Biological Processes: Antioxidant Defense, Signal Transduction, Circadian Rhythm, and More

The yeast Saccharomyces cerevisiae is a model organism for biochemical and genetic studies, and several very important discoveries of fundamental biological processes have been conducted using this yeast as an experimental organism. An emerging concept, which is validated by several works using this organism, relies on the biological importance of oxidant species, specially the hydroperoxides. These molecules were formed during aerobic biological process and control several intracellular mechanisms such as a range of signaling pathways, cell cycle, programmed cell death, circadian rhythm, aging, and lifespan extension. Thereby, cellular homeostasis depends on a refined control of hydroperoxides levels and low-molecular-weight molecules in combination with antioxidant enzymes playing a role in this equilibrium. This proposal is focused on the S. cerevisiae peroxiredoxins and their role in peroxide decomposition, signal transduction, circadian clocks, and aging as model enzymes for the study and comprehension of these biological processes in living organisms, including humans

Deficient nitric oxide signalling impairs skeletal muscle growth and performance : involvement of mitochondrial dysregulation

Background: Nitric oxide (NO), generated in skeletal muscle mostly by the neuronal NO synthases (nNOS mu), has profound effects on both mitochondrial bioenergetics and muscle development and function. The importance of NO for muscle repair emerges from the observation that nNOS signalling is defective in many genetically diverse skeletal muscle diseases in which muscle repair is dysregulated. How the effects of NO/nNOS mu on mitochondria impact on muscle function, however, has not been investigated yet. Methods: In this study we have examined the relationship between the NO system, mitochondrial structure/activity and skeletal muscle phenotype/growth/functions using a mouse model in which nNOS mu is absent. Also, NO-induced effects and the NO pathway were dissected in myogenic precursor cells. Results: We show that nNOS mu deficiency in mouse skeletal muscle leads to altered mitochondrial bioenergetics and network remodelling, and increased mitochondrial unfolded protein response (UPRmt) and autophagy. The absence of nNOS mu is also accompanied by an altered mitochondrial homeostasis in myogenic precursor cells with a decrease in the number of myonuclei per fibre and impaired muscle development at early stages of perinatal growth. No alterations were observed, however, in the overall resting muscle structure, apart from a reduced specific muscle mass and cross sectional areas of the myofibres. Investigating the molecular mechanisms we found that nNOS mu deficiency was associated with an inhibition of the Akt-mammalian target of rapamycin pathway. Concomitantly, the Akt-FoxO3-mitochondrial E3 ubiquitin protein ligase 1 (Mul-1) axis was also dysregulated. In particular, inhibition of nNOS/NO/cyclic guanosine monophosphate (cGMP)/cGMP-dependent-protein kinases induced the transcriptional activity of FoxO3 and increased Mul-1 expression. nNOS mu deficiency was also accompanied by functional changes in muscle with reduced muscle force, decreased resistance to fatigue and increased degeneration/damage post-exercise. Conclusions: Our results indicate that nNOS mu/NO is required to regulate key homeostatic mechanisms in skeletal muscle, namely mitochondrial bioenergetics and network remodelling, UPRmt and autophagy. These events are likely associated with nNOS mu-dependent impairments of muscle fibre growth resulting in a deficit of muscle performance

Health care's response to climate change: a carbon footprint assessment of the NHS in England

Background: Climate change threatens to undermine the past 50 years of gains in public health. In response, the National Health Service (NHS) in England has been working since 2008 to quantify and reduce its carbon footprint. This Article presents the latest update to its greenhouse gas accounting, identifying interventions for mitigation efforts and describing an approach applicable to other health systems across the world. Methods: A hybrid model was used to quantify emissions within Scopes 1, 2, and 3 of the Greenhouse Gas Protocol, as well as patient and visitor travel emissions, from 1990 to 2019. This approach complements the broad coverage of top-down economic modelling with the high accuracy of bottom-up data wherever available. Available data were backcasted or forecasted to cover all years. To enable the identification of measures to reduce carbon emissions, results were disaggregated by organisation type. Findings: In 2019, the health service's emissions totalled 25 megatonnes of carbon dioxide equivalent, a reduction of 26% since 1990, and a decrease of 64% in the emissions per inpatient finished admission episode. Of the 2019 footprint, 62% came from the supply chain, 24% from the direct delivery of care, 10% from staff commute and patient and visitor travel, and 4% from private health and care services commissioned by the NHS. Interpretation: This work represents the longest and most comprehensive accounting of national health-care emissions globally, and underscores the importance of incorporating bottom-up data to improve the accuracy of top-down modelling and enabling detailed monitoring of progress as health systems act to reduce emissions. Funding: Wellcome Trust