Miracle-dz/UniFAR-FTUs huggingface dataset:
Application of CRISPR/Cas9-Based Gene Editing in HIV-1/AIDS Therapy

Despite the fact that great efforts have been made in the prevention and therapy of HIV-1 infection, HIV-1/AIDS remains a major threat to global human health. Highly active antiretroviral therapy (HAART) can suppress virus replication, but it cannot eradicate latent viral reservoirs in HIV-1/AIDS patients. Recently, the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated nuclease 9 (Cas9) system has been engineered as an effective gene-editing technology with the potential to treat HIV-1/AIDS. It can be used to target cellular co-factors or HIV-1 genome to reduce HIV-1 infection and clear the provirus, as well as to induce transcriptional activation of latent virus in latent viral reservoirs for elimination. This versatile gene editing technology has been successfully applied to HIV-1/AIDS prevention and reduction in human cells and animal models. Here, we update the rapid progress of CRISPR/Cas9-based HIV-1/AIDS therapy research in recent years and discuss the limitations and future perspectives of its application.
VIP2 in LNGS - Testing the Pauli Exclusion Principle for electrons with high sensitivity

The VIP2 (VIolation of the Pauli Exclusion Principle) experiment at the Gran Sasso underground laboratory (LNGS) is searching for possible violations of standard quantum mechanics predictions in atoms at very high sensitivity. We investigate atomic transitions with precision X-ray spectroscopy in order to test the Pauli Exclusion Principle (PEP) and therefore the related spin-statistics theorem. We will present our experimental method for the search for “anomalous” (i.e. Pauli-forbidden) X-ray transitions in copper atoms, produced by “new” electrons, which could have tiny probability to undergo Pauli-forbidden transition to the ground state already occupied by two electrons. We will describe the VIP2 experimental setup, which is taking data at LNGS presently. The goal of VIP2 is to test the PEP for electrons with unprecedented accuracy, down to a limit in the probability that PEP is violated at the level of 10−31. We will present current experimental results and discuss implications of a possible violation.
Prophylaxis With Oral Zinc Sulfate Against Radiation Induced Oral Mucositis in Patients With Head and Neck Cancers: A Systematic Review and Meta-Analysis of Four Randomized Controlled Trials

Background: Oral mucositis is an inevitable and distressing adverse event patients, who were treated with irradiation for head and neck cancer, face. Although several studies have investigated the potential of oral zinc sulfate in preventing radiation-induced oral mucositis in patients with head and neck cancers, conclusive results have not yet been found. Objective: The aim of the present study is to determine whether oral zinc sulfate is effective in preventing radiation-induced oral mucositis, in patients with head and neck cancers. Methods: We electronically searched all potential citations in PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL) and EBSCO from their inception to December 2018. After the search and checked literatures, extracted data and appraised risk of bias, RevMan software version 5.3 was used to perform meta-analysis. Results: Four randomized controlled trials (RCTs) involving 162 patients were included. A meta-analysis showed that zinc sulfate did not decrease the incidence (RR [relative risk], 0.97; 95% CI [confidence interval], 0.74–1.28), and did not relieve the moderate and severe grade of radiation induced oral mucositis (moderate and severe oral mucositis: RR, 0.84; 95% CI, 0.14–4.87; severe oral mucositis: RR, 0.43; 95% CI, 0.00–38.98). A qualitative analysis suggested that zinc sulfate was associated with the onset of oral mucositis. Conclusions: Based on limited evidence, zinc sulfate may not have the benefit of prophylaxis against radiation-induced oral mucositis, in patients with head and neck cancers. However, further RCTs with larger sample sizes and more rigorous methodologies are needed to enhance the evidence of these results.
Visbrain: A Multi-Purpose GPU-Accelerated Open-Source Suite for Multimodal Brain Data Visualization

We present Visbrain, a Python open-source package that offers a comprehensive visualization suite for neuroimaging and electrophysiological brain data. Visbrain consists of two levels of abstraction: (1) objects which represent highly configurable neuro-oriented visual primitives (3D brain, sources connectivity, etc.) and (2) graphical user interfaces for higher level interactions. The object level offers flexible and modular tools to produce and automate the production of figures using an approach similar to that of Matplotlib with subplots. The second level visually connects these objects by controlling properties and interactions through graphical interfaces. The current release of Visbrain (version 0.4.2) contains 14 different objects and three responsive graphical user interfaces, built with PyQt: Signal, for the inspection of time-series and spectral properties, Brain for any type of visualization involving a 3D brain and Sleep for polysomnographic data visualization and sleep analysis. Each module has been developed in tight collaboration with end-users, i.e., primarily neuroscientists and domain experts, who bring their experience to make Visbrain as transparent as possible to the recording modalities (e.g., intracranial EEG, scalp-EEG, MEG, anatomical and functional MRI). Visbrain is developed on top of VisPy, a Python package providing high-performance 2D and 3D visualization by leveraging the computational power of the graphics card. Visbrain is available on Github and comes with a documentation, examples, and datasets (http://visbrain.org).
Moderately severe and severe acute pancreatitis : a systematic review of the outcomes in the USA and European Union-5

Background and objectives The global incidence of hospitalisation due to acute pancreatitis (AP) has been rising in the recent decades. In the USA alone, there was a 13.2% increase between 2009 and 2012 compared with 2002–2005. There remains a lack of approved treatments to prevent disease progression, leaving many liable to developing complications that include multisystem organ failure (OF) and death. This therapeutic deficit raises questions about the scale of the current burden of illness (BOI) associated with severe forms of AP. The aim of the systematic literature review (SLR) was to assess clinical, humanistic, and economic outcomes associated with moderately severe AP (MSAP) and severe AP (SAP) in the USA and the European Union-5 (EU-5). Methods Systematic searches were conducted in MEDLINE and Embase to identify studies published in English (between 2007 and 2017) that reported on the BOI of MSAP and/or SAP. Manual searches of ‘grey’ literature sources were also conducted. Results The SLR identified 19 studies which indicated that 15%–20% of patients with AP progress to more severe forms of the disease, up to 10.5% of those with SAP require surgery for complications, and up to 40% die during hospitalisation. By contrast, there appears to be a lack of data on the extent to which SAP affects patients’ quality of life. Conclusion The available evidence clearly demonstrates that the current management for MSAP and SAP in the USA and EU-5 does not adequately meet patients’ needs. Early identification and intervention for AP is crucial, given the evidence of high rates of morbidity and an associated economic burden that is considerable. Since many patients with the condition present to hospitals at a point when multisystem OF or death is highly likely, there is a particularly urgent need for effective treatment options to prevent disease progression.
Development of an antimicrobial peptide-loaded mineralized collagen bone scaffold for infective bone defect repair

Abstract The repair of infective bone defects is a great challenge in clinical work. It is of vital importance to develop a kind of bone scaffold with good osteogenic properties and long-term antibacterial activity for local anti-infection and bone regeneration. A porous mineralized collagen (MC) scaffold containing poly(d,l-lactide-co-glycolic acid) (PLGA) microspheres loaded with two antibacterial synthetic peptides, Pac-525 or KSL-W was developed and characterized via scanning electron microscopy (SEM), porosity measurement, swelling and mechanical tests. The results showed that the MC scaffold embedded with smooth and compact PLGA microspheres had a positive effect on cell growth and also had antibacterial properties. Through toxicity analysis, cell morphology and proliferation analysis and alkaline phosphatase evaluation, the antibacterial scaffolds showed excellent biocompatibility and osteogenic activity. The antibacterial property evaluated with Staphylococcus aureus and Escherichia coli suggested that the sustained release of Pac-525 or KSL-W from the scaffolds could inhibit the bacterial growth aforementioned in the long term. Our results suggest that the antimicrobial peptides-loaded MC bone scaffold has good antibacterial and osteogenic activities, thus providing a great promise for the treatment of infective bone defects.
Convergence analysis for parallel‐in‐time solution of hyperbolic systems

Parallel‐in‐time algorithms have been successfully employed for reducing time‐to‐solution of a variety of partial differential equations, especially for diffusive (parabolic‐type) equations. A major failing of parallel‐in‐time approaches to date, however, is that most methods show instabilities or poor convergence for hyperbolic problems. This paper focuses on the analysis of the convergence behavior of multigrid methods for the parallel‐in‐time solution of hyperbolic problems. Three analysis tools are considered that differ, in particular, in the treatment of the time dimension: (a) space–time local Fourier analysis, using a Fourier ansatz in space and time; (b) semi‐algebraic mode analysis, coupling standard local Fourier analysis approaches in space with algebraic computation in time; and (c) a two‐level reduction analysis, considering error propagation only on the coarse time grid. In this paper, we show how insights from reduction analysis can be used to improve feasibility of the semi‐algebraic mode analysis, resulting in a tool that offers the best features of both analysis techniques. Following validating numerical results, we investigate what insights the combined analysis framework can offer for two model hyperbolic problems, the linear advection equation in one space dimension and linear elasticity in two space dimensions.
Interplanetary spread of solar energetic protons near a high-speed solar wind stream

Aims. We study how a fast solar wind stream embedded in a slow solar wind influences the spread of solar energetic protons in interplanetary space. In particular, we aim at understanding how the particle intensity and anisotropy vary along interplanetary magnetic field (IMF) lines that encounter changing solar wind conditions such as the shock waves bounding a corotating interaction region (CIR). Moreover, we study how the intensities and anisotropies vary as a function of the longitudinal and latitudinal coordinate, and how the width of the particle intensities evolves with the heliographic radial distance. Furthermore, we study how cross-field diffusion may alter these spatial profiles. Methods. To model the energetic protons, we used a recently developed particle transport code that computes particle distributions in the heliosphere by solving the focused transport equation (FTE) in a stochastic manner. The particles are propagated in a solar wind containing a CIR, which was generated by the heliospheric model, EUHFORIA. We study four cases in which we assume a delta injection of 4 MeV protons spread uniformly over different regions at the inner boundary of the model. These source regions have the same size and shape, yet are shifted in longitude from each other, and are therefore magnetically connected to different solar wind conditions. Results. The intensity and anisotropy profiles along selected IMF lines vary strongly according to the different solar wind conditions encountered along the field line. The IMF lines crossing the shocks bounding the CIR show the formation of accelerated particle populations, with the reverse shock wave being a more efficient accelerator than the forward shock wave. The longitudinal intensity profiles near the CIR are highly asymmetric in contrast to the profiles obtained in a nominal solar wind. For the injection regions that do not cross the transition zone between the fast and slow solar wind, we observe a steep intensity drop of several orders of magnitude near the stream interface (SI) inside the CIR. Moreover, we demonstrate that the longitudinal width of the particle intensity distribution can increase, decrease, or remain constant with heliographic radial distance, reflecting the underlying IMF structure. Finally, we show how the deflection of the IMF at the shock waves and the compression of the IMF in the CIR deforms the three-dimensional shape of the particle distribution in such a way that the original shape of the injection profile is lost.
Characteristic temperatures of a triplon system of dimerized quantum magnets

Exploiting the analogy between ultracold atomic gases and the system of triplons, we study magneto-thermodynamic properties of dimerized quantum magnets in the framework of Bose–Einstein condensation (BEC). Particularly, introducing the inversion (or Joule–Thomson) temperature [Formula: see text] as the point where Joule–Thomson coefficient of an isenthalpic process changes its sign, we show that for a simple paramagnet, this temperature is infinite, while for three-dimensional (3D) dimerized quantum magnets it is finite and always larger than the critical temperature [Formula: see text] of BEC. Below the inversion temperature [Formula: see text], the system of triplons may be in a liquid phase, which undergoes a transition into a superfluid phase at [Formula: see text]. The dependence of the inversion temperature on the external magnetic field [Formula: see text] has been calculated for quantum magnets of TlCuCl3 and Sr3Cr2O8.
Latent Simplex Position Model: High Dimensional Multi-view Clustering with Uncertainty Quantification

High dimensional data often contain multiple facets, and several clustering patterns can co-exist under different variable subspaces, also known as the views. While multi-view clustering algorithms were proposed, the uncertainty quantification remains difficult --- a particular challenge is in the high complexity of estimating the cluster assignment probability under each view, and sharing information among views. In this article, we propose an approximate Bayes approach --- treating the similarity matrices generated over the views as rough first-stage estimates for the co-assignment probabilities; in its Kullback-Leibler neighborhood, we obtain a refined low-rank matrix, formed by the pairwise product of simplex coordinates. Interestingly, each simplex coordinate directly encodes the cluster assignment uncertainty. For multi-view clustering, we let each view draw a parameterization from a few candidates, leading to dimension reduction. With high model flexibility, the estimation can be efficiently carried out as a continuous optimization problem, hence enjoys gradient-based computation. The theory establishes the connection of this model to a random partition distribution under multiple views. Compared to single-view clustering approaches, substantially more interpretable results are obtained when clustering brains from a human traumatic brain injury study, using high-dimensional gene expression data. KEY WORDS: Co-regularized Clustering, Consensus, PAC-Bayes, Random Cluster Graph, Variable Selection
The role of identity in parental support for physical activity and healthy eating among overweight and obese children

ABSTRACT Introduction: Parental support behaviors are established predictors of children's physical activity and healthy eating. However, little is known about predictors of these parental support behaviors. Identity (i.e. a component of the self-concept) has been hypothesized to be an influential construct that may be associated with a variety of behavioral antecedents and behavior itself. Specifically, research suggests healthy eating or physical activity parental support affective attitude may predict parental identity, and that identity may predict support behavior directly and indirectly through support self-regulation (e.g. planning). Thus, this study expands on past literature by exploring these antecedents and outcomes of parental identity in the context of parental support for physical activity and healthy eating among overweight and obese children. Methods: Using a cross-sectional survey design, 83 parents (61.4% female) with at least one overweight or obese child completed measures assessing parental support affective attitude, parental identity, support self-regulation, and actual support behaviors. Path analysis was conducted to examine model fit and hypothesized relationships between variables for eating and physical activity separately. Results: For both behavioral domains, the model fit was good. Parental support affective attitude predicted parental identity, parental identity predicted support self-regulation, and support self-regulation predicted support behavior. Further, for both behaviors, support self-regulation mediated the relationship between parental identity and support behavior. Finally, parental identity also directly predicted support behavior for physical activity but not eating. Conclusions: The results demonstrate the importance of identity in parental support behaviors. These results also show that fostering enjoyable experiences for parents while supporting their children may strengthen their supportive identities.
Surface evolution of the Anhur region on comet 67P/Churyumov-Gerasimenko from high-resolution OSIRIS images

Context. The southern hemisphere of comet 67P/Churyumov-Gerasimenko (67P) became observable by the Rosetta mission in March 2015, a few months before cometary southern vernal equinox. The Anhur region in the southern part of the comet’s larger lobe was found to be highly eroded, enriched in volatiles, and highly active. Aims. We analyze high-resolution images of the Anhur region pre- and post-perihelion acquired by the OSIRIS imaging system on board the Rosetta mission. The Narrow Angle Camera is particularly useful for studying the evolution in Anhur in terms of morphological changes and color variations. Methods. Radiance factor images processed by the OSIRIS pipeline were coregistered, reprojected onto the 3D shape model of the comet, and corrected for the illumination conditions. Results. We find a number of morphological changes in the Anhur region that are related to formation of new scarps; removal of dust coatings; localized resurfacing in some areas, including boulders displacements; and vanishing structures, which implies localized mass loss that we estimate to be higher than 50 million kg. The strongest changes took place in and nearby the Anhur canyon-like structure, where significant dust cover was removed, an entire structure vanished, and many boulders were rearranged. All such changes are potentially associated with one of the most intense outbursts registered by Rosetta during its observations, which occurred one day before perihelion passage. Moreover, in the niche at the foot of a new observed scarp, we also see evidence of water ice exposure that persisted for at least six months. The abundance of water ice, evaluated from a linear mixing model, is relatively high (>20%). Our results confirm that the Anhur region is volatile-rich and probably is the area on 67P with the most pristine exposures near perihelion.
Discrete fuzzy de Sitter cosmology

We analyze the spectrum of time observable in noncommutative cosmological model introduced in [5], defined by $(\rho, s=\frac 12)\,$ representation of the de Sitter group. We find that time has peculiar property: it is not self-adjoint, but appropriate restrictions to the space of physical states give self-adjoint extensions. Extensions have discrete spectrum with logarithmic distribution of eigenvalues, $\,t_n \sim \ell\, \log\, n$+const, where $\ell$ characterizes noncommutativity and the usual assumption is $\,\ell=\ell_{Planck}$. When calculated on physical states, radius of the universe is bounded below by $\, \ell\, \sqrt{\frac 34\, \left( \frac 14 +\rho^2\right)}\, $, which resolves the big bang singularity. An immediate consequence of the model is a specific breaking of the original symmetry at the Planck scale.
Catching Latrophilin With Lasso: A Universal Mechanism for Axonal Attraction and Synapse Formation

Latrophilin-1 (LPHN1) was isolated as the main high-affinity receptor for α-latrotoxin from black widow spider venom, a powerful presynaptic secretagogue. As an adhesion G-protein-coupled receptor, LPHN1 is cleaved into two fragments, which can behave independently on the cell surface, but re-associate upon binding the toxin. This triggers intracellular signaling that involves the Gαq/phospholipase C/inositol 1,4,5-trisphosphate cascade and an increase in cytosolic Ca2+, leading to vesicular exocytosis. Using affinity chromatography on LPHN1, we isolated its endogenous ligand, teneurin-2/Lasso. Both LPHN1 and Ten2/Lasso are expressed early in development and are enriched in neurons. LPHN1 primarily resides in axons, growth cones and presynaptic terminals, while Lasso largely localizes on dendrites. LPHN1 and Ten2/Lasso form a trans-synaptic receptor pair that has both structural and signaling functions. However, Lasso is proteolytically cleaved at multiple sites and its extracellular domain is partially released into the intercellular space, especially during neuronal development, suggesting that soluble Lasso has additional functions. We discovered that the soluble fragment of Lasso can diffuse away and bind to LPHN1 on axonal growth cones, triggering its redistribution on the cell surface and intracellular signaling which leads to local exocytosis. This causes axons to turn in the direction of spatio-temporal Lasso gradients, while LPHN1 knockout blocks this effect. These results suggest that the LPHN1-Ten2/Lasso pair can participate in long- and short-distance axonal guidance and synapse formation.
Enhanced effects of footwarmer by wearing sandals in winter office: A Swedish case study

Human-centred thermal environment conditioning can guarantee thermal comfort needs of human occupants in their micro-environments by using localized heating/cooling devices. Meanwhile, less intensified thermal conditioning of unoccupied surrounding environments can achieve heating/cooling energy efficiency. The concept was originated from task/ambient conditioning, which was developed for personal comfort systems. Most of the localized heating/cooling devices are workstation based or chair based. Task conditioning would become more closely to targets (human bodies) by using special clothing materials or thermoelectric elements. From thermal physiological viewpoints, thermal stimulus to thermally sensitive body parts may generate better results for not only local thermal comfort but also for whole body thermal comfort. Thermal stimulus to the extremities (feet) has demonstrated good thermal comfort effects. Scandinavians are accustomed to outdoor harsh environments and prefer wearing heavy shoes' outdoors in winter. They have the habit of changing heavy shoes to sandals when entering offices, which give the opportunity to enhance localized heating effects of footwarmers by reducing shoes’ thermal resistance. Climatic chamber tests with 32 Nordic subjects were performed under different indoor ambient heating temperatures with/without the aid of footwarmers. With footwarmers and sandals, indoor heating temperature at 16°C was acceptable, which achieved energy efficient thermal comfort.