Miracle-dz/UniFAR-FTUs huggingface dataset:
Suppressor of cytokine signaling 2 (Socs2) deletion protects bone health of mice with DSS-induced inflammatory bowel disease

ABSTRACT Individuals with inflammatory bowel disease (IBD) often present with poor bone health. The development of targeted therapies for this bone loss requires a fuller understanding of the underlying cellular mechanisms. Although bone loss in IBD is multifactorial, the altered sensitivity and secretion of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in IBD is understood to be a critical contributing mechanism. The expression of suppressor of cytokine signaling 2 (SOCS2), a well-established negative regulator of GH signaling, is stimulated by proinflammatory cytokines. Therefore, it is likely that SOCS2 expression represents a critical mediator through which proinflammatory cytokines inhibit GH/IGF-1 signaling and decrease bone quality in IBD. Using the dextran sodium sulfate (DSS) model of colitis, we reveal that endogenously elevated GH function in the Socs2−/− mouse protects the skeleton from osteopenia. Micro-computed tomography assessment of DSS-treated wild-type (WT) mice revealed a worsened trabecular architecture compared to control mice. Specifically, DSS-treated WT mice had significantly decreased bone volume, trabecular thickness and trabecular number, and a resulting increase in trabecular separation. In comparison, the trabecular bone of Socs2-deficient mice was partially protected from the adverse effects of DSS. The reduction in a number of parameters, including bone volume, was less, and no changes were observed in trabecular thickness or separation. This protected phenotype was unlikely to be a consequence of improved mucosal health in the DSS-treated Socs2−/− mice but rather a result of unregulated GH signaling directly on bone. These studies indicate that the absence of SOCS2 is protective against bone loss typical of IBD. This study also provides an improved understanding of the relative effects of GH/IGF-1 signaling on bone health in experimental colitis, information that is essential before these drugs are explored as bone protective agents in children and adults with IBD. Summary: Using a mouse model of inflammatory bowel disease, this article provides an improved understanding of the relative effects of GH/IGF-1 on bone health in experimental colitis.
N‐ethyl‐N‐nitrosourea–Induced Adaptor Protein 2 Sigma Subunit 1 (Ap2s1) Mutations Establish Ap2s1 Loss‐of‐Function Mice

The adaptor protein‐2 sigma subunit (AP2σ), encoded by AP2S1, forms a heterotetrameric complex, with AP2α, AP2β, and AP2μ subunits, that is pivotal for clathrin‐mediated endocytosis, and AP2σ loss‐of‐function mutations impair internalization of the calcium‐sensing receptor (CaSR), a G‐protein–coupled receptor, and cause familial hypocalciuric hypercalcemia type‐3 (FHH3). Mice with AP2σ mutations that would facilitate investigations of the in vivo role of AP2σ, are not available, and we therefore embarked on establishing such mice. We screened >10,000 mice treated with the mutagen N‐ethyl‐N‐nitrosourea (ENU) for Ap2s1 mutations and identified 5 Ap2s1 variants, comprising 2 missense (Tyr20Asn and Ile123Asn) and 3 intronic base substitutions, one of which altered the invariant donor splice site dinucleotide gt to gc. Three‐dimensional modeling and cellular expression of the missense Ap2s1 variants did not reveal them to alter AP2σ structure or CaSR‐mediated signaling, but investigation of the donor splice site variant revealed it to result in an in‐frame deletion of 17 evolutionarily conserved amino acids (del17) that formed part of the AP2σ α1‐helix, α1‐β3 loop, and β3 strand. Heterozygous mutant mice (Ap2s1+/del17) were therefore established, and these had AP2σ haplosufficiency but were viable with normal appearance and growth. Ap2s1+/del17 mice, when compared with Ap2s1+/+ mice, also had normal plasma concentrations of calcium, phosphate, magnesium, creatinine, urea, sodium, potassium, and alkaline phosphatase activity; normal urinary fractional excretion of calcium, phosphate, sodium, and potassium; and normal plasma parathyroid hormone (PTH) and 1,25‐dihydroxyvitamin D (1,25(OH)2) concentrations. However, homozygous Ap2s1del17/del17 mice were non‐viable and died between embryonic days 3.5 and 9.5 (E3.5–9.5), thereby indicating that AP2σ likely has important roles at the embryonic patterning stages and organogenesis of the heart, thyroid, liver, gut, lungs, pancreas, and neural systems. Thus, our studies have established a mutant mouse model that is haplosufficient for AP2σ. © 2017 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.
A Bluetooth Low Energy Indoor Positioning System with Channel Diversity, Weighted Trilateration and Kalman Filtering

Indoor Positioning Systems (IPS) using Bluetooth Low Energy (BLE) technology are currently becoming real and available, which has made them grow in popularity and use. However, there are still plenty of challenges related to this technology, especially in terms of Received Signal Strength Indicator (RSSI) fluctuations due to the behaviour of the channels and the multipath effect, that lead to poor precision. In order to mitigate these effects, in this paper we propose and implement a real Indoor Positioning System based on Bluetooth Low Energy, that improves accuracy while reducing power consumption and costs. The three main proposals are: frequency diversity, Kalman filtering and a trilateration method what we have denominated “weighted trilateration”. The analysis of the results proves that all the proposals improve the precision of the system, which goes up to 1.82 m 90% of the time for a device moving in a middle-size room and 0.7 m for static devices. Furthermore, we have proved that the system is scalable and efficient in terms of cost and power consumption. The implemented approach allows using a very simple device (like a SensorTag) on the items to locate. The system enables a very low density of anchor points or references and with a precision better than existing solutions.
Protein phosphatase 1 regulates huntingtin exon 1 aggregation and toxicity

Huntington’s disease (HD) is neurodegenerative disorder caused by a polyglutamine expansion in the N-terminal region of the huntingtin protein (N17). Here, we analysed the relative contribution of each phosphorylatable residue in the N17 region (T3, S13 and S16) towards huntingtin exon 1 (HTTex1) oligomerization, aggregation and toxicity in human cells and Drosophila neurons. We used bimolecular fluorescence complementation (BiFC) to show that expression of single phosphomimic mutations completely abolished HTTex1 aggregation in human cells. In Drosophila, Mimicking phosphorylation at T3 decreased HTTex1 aggregation both in larvae and adult flies. Interestingly, pharmacological or genetic inhibition of protein phosphatase 1 (PP1) prevented HTTex1 aggregation in both human cells and Drosophila while increasing neurotoxicity in flies. Our findings suggest that PP1 modulates HTTex1 aggregation by regulating phosphorylation on T3. In summary, our study suggests that modulation of HTTex1 single phosphorylation events by PP1 could constitute an efficient and direct molecular target for therapeutic interventions in HD.
Experimental and numerical treatment of delamination in laminated glass plate structures

This paper aims to investigate the delamination issues of laminated glass plates and the effect of boundary conditions on the delamination of laminated glass plates. Delamination of laminated glass which may be defined as reduction or total loss in the perfect bond between the glass sheets and the PVB interlayer is one of the most important failure modes. Due to delamination, the load-carrying capacity and structural stiffness of laminated glass unit can change significantly. The author conducted experimental and numerical studies about the delamination of laminated glass plate problem based on the results of digital image processing.
Comprehensive Review of Keloid Formation

Keloid is a benign fibrous growth, which presents in scar tissue of predisposed individuals. Although the pathogenesis of keloid disease is not well understood, it is considered to be the end product of an abnormal healing process. There are several molecules and cells implicated in keloid mechanism in relation to the normal wound healing process. However, it is possible that several factors such as age of onset, sex, cause of scarring, blood groups, anatomical site, presence of family history, number of injured sites (multiple/ single), and modifiable factors like delayed healing, and hypertension have an important role in keloid formation and consequentially in predicting keloid’s behavior in response to treatment and prognosis. Keloids appear as firm, mildly tender, bosselated tumors with a shiny surface. The main differential diagnosis of keloid is hypertrophic scar, also called pseudokeloid, which not only a clinical challenges, but also histological challenge. No single therapeutic modality is best for all keloids. The location, size, and depth of the lesion; the age of the patient; and the past response to treatment determine the type of therapy used, so there are several options in keloid treatment. Prevention is the first rule in keloid therapy, so we must take special care in treating patients with a history of keloids. This review gives a comprehensive view of keloid formation (pathogenesis, risk factors, diagnosis, different diagnosis, histopathology, treatment and prevention) and this is the object of this review.
The functional impact of amblyopia

Amblyopia is the most common disorder managed in paediatric ophthalmic practice in industrialised countries. Reports on the impact of amblyopia on tasks relevant to the activities of children, or on skills pertinent to their education and quality of life, is leading to greater understanding of the functional disabilities associated with the condition. This review considers the extent to which amblyopia affects the ability to carry out everyday tasks, with particular attention to studies of motor skills and reading proficiency in children. Collectively, these studies show that amblyopia results in poorer outcomes on tests of skills required for proficiency in everyday tasks and which relate to childhood academic performance. However, the relative contributions that the documented vision anomalies inherent in amblyopia contribute to various functional disabilities is not fully determined. Recent reports have demonstrated improvement following treatment in standardised measures of fine motor skills involved in practical, everyday tasks. Including measurement of functional performance skills in amblyopia treatment trials is desirable to show treatment effect on crucial, real‐world activities.
A study on energy management controller of EDLC for batteries and capacitors hybrid electric vehicles

There are still technical issues with batteries for electric vehicles(EVs), such as less driving distance, and their short life. Then, there is an idea providing a more highly efficient and longer life energy storage system by hybridizing batteries and EDLCs (Electric Double Layer Capacitors). The purpose of choosing EDLCs is to cut the peak power of the battery. However, EDLC cannot be utilized without managing the energy properly since the energy capacity of EDLC is low. For this reason, a control system has been proposed to keep the energy of EDLC within the limits. This paper describes a design criteria of the proposed controller and experimentally validates that the control system is effective.
Climate Change Helplessness and the (De)moralization of Individual Energy Behavior

Although most people understand the threat of climate change, they do little to modify their own energy conservation behavior. One reason for this gap between belief and behavior may be that individual actions seem unimpactful and therefore are not morally relevant. This research investigates how climate change helplessness—belief that one’s actions cannot affect climate change—can undermine the moralization of climate change and personal energy conservation. In Study 1, climate change efficacy predicted both moralization of energy use and energy conservation intentions beyond individual belief in climate change. In Studies 2 and 3, participants read information about climate change that varied in efficacy message, that is, whether individual actions (e.g., using less water, turning down heat) make a difference in the environment. Participants who read that their behavior made no meaningful impact reported weaker moralization and intentions (Study 2), and reported more energy consumption 1 week later (Study 3). Moreover, effects on intentions and actions were mediated by changes in moralization. We discuss ways to improve climate change messages to foster environmental efficacy and moralization of personal energy use.
Free-electron-driven nanoscale light sources: from Hertzian antennas to metamaterials

This thesis reports on the development of new types of nanoscale optical light sources driven by free-electrons and on the investigation of the underpinning physical phenomena. It is focused on three types of nanoscale light sources with increasing degree of complexity: a nanoscale antenna, an undulator-based tuneable nanoscale light source and a metamaterial-based spatially coherent light source. I have demonstrated for the first time that a nanoscale Hertzian antenna can be driven by free-electrons. The studied nano-antennas consisting of pair of gold nano-rods spaced by a gap resemble conventional radio dipole antennas. Nanoantennas, driven by electron beam produce emission in the visible part of the spectrum. I show that these nanoantennas are most efficiently fed in the region of closest proximity between their two elements, in particular, where the light density of states reaches a maximum. I have developed for the first time a tuneable nanoscale light source driven by free-electrons, the light-well. Alike a free-electron laser that exploits magnet-based undulators, the light-well is based on a nanoscale undulator, a cylindrical channel through alternating metal-dielectric nano-layers. A fast electron propagating through the channel emit light at the wavelength linked to the electron energy and the period of the undulator, thus allowing for a continuous tuning of the output radiation. It has been achieved a 200 nm tunability range in the vis-NIR range at wavelengths between 750 and 950 nm with light at the level of 200W/cm2. Furthermore, I have performed a comprehensive numerical analysis of the light-well by modeling a free electron propagating in the undulator which has lead to a deeper understanding of its physical mechanisms. I demonstrate for the first time an electron-beam driven metamaterial light source that converts the kinetic energy of tree-electrons into spatially coherent optical radiation. It is based on a fundamentally new radiation phenomenon: the injection of free electrons into the metamaterial leads to a directed light emission that comes from synchronized plasmonic oscillations of the ensemble of metamolecules, the individual building blocks of the nanostructure. The effect results from the synchronizing interactions between the metamolecules leading to the spectrum narrowing with the increasing number of metamolecules involved. Depending on the type of metamaterial used I observed emission of narrow-divergent radiation in the visible range from 640 to 760 nm. These results - in principle - demonstrate an alternative to the laser, a threshold-free way of generating spatially coherent and spectrally narrow electromagnetic radiation.
Mobility Management for TCP in mmWave Networks

Communication at millimeter wave (mmWave) frequencies will likely be a cornerstone for next generation 5G cellular networks. However, providing mobility support for end-to-end applications in mmWave cellular systems is challenging due to the relatively small coverage area of individual cells, and rapid channel dynamics caused by blockage and beam-tracking. This paper presents a comprehensive performance evaluation of TCP on top of mmWave cellular systems with mobility management, detailed modeling of the channel dynamics, and end-to-end network architectures. We show how an efficient mobility management scheme in a dense network deployment can dramatically improve the performance of TCP in terms of both throughput and latency in mobile scenarios with blocking. The study also reveals that, even with fast mobility management, TCP throughput is extremely sensitive to the end-to-end delay with implications on both core network and server location.
Decentralized power control for random access with iterative multi-user detection

This paper is concerned with the application of iterative multi-user detection (MUD) in ALOHA-type random access systems. We focus on a random-power transmission scheme, in which the transmission power level of each user is randomly selected according to a certain distribution f. We aim at designing f to maximize the system throughput given an average power constraint for each user. We adopt a suboptimal scheme, in which only type-2 collisions (collisions involving two packets) are resolved. We first prove that, the support (i.e., the smallest closed set whose complement has zero probability) of the optimal f in this case is a discrete set for systems with certain feasible regions (the set of power profiles that can support reliable communications). The related discrete set can be easily obtained according to the boundaries of the feasible region. We then apply this finding to the design of f. Numerical results show that with iterative MUD, the proposed scheme can achieve noticeable performance improvement compared with the conventional ALOHA and offer flexible tradeoff between the system throughput and power consumption.
Optimizing over a Restricted Policy Class in Markov Decision Processes

We address the problem of finding an optimal policy in a Markov decision process under a restricted policy class defined by the convex hull of a set of base policies. This problem is of great interest in applications in which a number of reasonably good (or safe) policies are already known and we are only interested in optimizing in their convex hull. We show that this problem is NP-hard to solve exactly as well as to approximate to arbitrary accuracy. However, under a condition that is akin to the occupancy measures of the base policies having large overlap, we show that there exists an efficient algorithm that finds a policy that is almost as good as the best convex combination of the base policies. The running time of the proposed algorithm is linear in the number of states and polynomial in the number of base policies. In practice, we demonstrate an efficient implementation for large state problems. Compared to traditional policy gradient methods, the proposed approach has the advantage that, apart from the computation of occupancy measures of some base policies, the iterative method need not interact with the environment during the optimization process. This is especially important in complex systems where estimating the value of a policy can be a time consuming process.
Nonasymptotic Gaussian Approximation for Linear Systems with Stable Noise [Preliminary Version]

The results of a series of theoretical studies are reported, examining the convergence rate for different approximate representations of $\alpha$-stable distributions. Although they play a key role in modelling time-series with jumps and discontinuities, the use of $\alpha$-stable distributions in inference often leads to analytically intractable problems. The infinite series representation employed in this work transforms an intractable, infinite-dimensional inference problem into a finite-dimensional (conditionally Gaussian) parametric problem. The main gist of our approach is the approximation of the tail of this series by a Gaussian random variable. Standard statistical techniques, such as Expectation-Maximization, Markov chain Monte Carlo, and Particle Filtering, can then be readily applied. In addition to the asymptotic normality of the tail of this series, here we establish explicit, nonasymptotic bounds on the approximation error. Their proofs follow classical Fourier-analytic arguments, typically employing Ess\'{e}en's smoothing lemma. Specifically, we consider the distance between the distributions of: $(i)$~the tail of the series and an appropriate Gaussian; $(ii)$~the full series and the truncated series; and $(iii)$~the full series and the truncated series with an added Gaussian term. In all three cases, sharp bounds are established, and the theoretical results are compared with the actual distances (computed numerically) in specific examples of symmetric $\alpha$-stable distributions. This analysis facilitates the selection of appropriate truncations in practice and offers theoretical guarantees for the accuracy of the resulting estimates. One of the main conclusions obtained is that the use of a truncated series together with an approximately Gaussian error term has superior statistical properties and is probably preferable for inference tasks.
A randomised trial on platelet function-guided de-escalation of antiplatelet treatment in ACS patients undergoing PCI

Summary Outcomes of acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) have been significantly improved with the use of potent P2Y12 receptor inhibitors like prasugrel. While most of the ischaemic risk reduction for prasugrel versus clopidogrel was demonstrated in the early treatment period, the risk of bleeding became particularly prominent during the chronic course of therapy. It may therefore be a valid approach to substitute prasugrel for clopidogrel in the early phase of chronic antiplatelet treatment after PCI. In the Testing Responsiveness To Platelet Inhibition On Chronic Antiplatelet Treatment For Acute Coronary Syndromes (TROPICAL-ACS) trial, we aim to compare standard prasugrel therapy with a de-escalating antiplatelet treatment approach guided by platelet function testing (PFT). The study is an investigator-initiated European multicentre, randomised clinical trial in biomarker-positive ACS patients after successful PCI. Two thousand six hundred patients will be randomised prior to hospital discharge in a 1:1 fashion to either receive standard prasugrel therapy (control group) or de-escalating therapy (one-week prasugrel followed by one-week clopidogrel and PFT-guided maintenance therapy from day 14 after hospital discharge, monitoring group). Patients of the monitoring group with high on-clopidogrel platelet reactivity (HPR) based on Multiplate analyzer testing (HPR: ≥ 46U per consensus definition) will be switched back to prasugrel, whereas those without HPR (<46 U) will continue clopidogrel treatment. The overall study treatment duration will be one year in both groups. The primary endpoint of the study is net clinical benefit (combined incidence of cardiovascular death, myocardial infarction, stroke and bleeding ≥ grade 2 according to BARC criteria) one-year after randomisation. TROPICAL-ACS is the first large-scale, randomised controlled trial assessing the clinical value of a PFT-guided de-escalation of antiplatelet treatment in biomarker positive ACS patients undergoing PCI. ClinicalTrials.gov Identifier: NCT01959451