Miracle-dz/UniFAR-FTUs huggingface dataset:
Neutrinos from captured dark matter annihilation in a galactic population of neutron stars

Particulate dark matter captured by a population of neutron stars distributed around the galactic center while annihilating through long-lived mediators can give rise to an observable neutrino flux. We examine the prospect of an idealised gigaton detector like IceCube/KM3NeT in probing such scenarios. Within this framework, we report an improved reach in spin-dependent and spin-independent dark matter nucleon cross-section below the current limits for dark matter masses in the TeV-PeV range.
Approximate Computing for Robotic path planning -- Experimentation, Case Study and Practical Implications

Approximate computing is a computation domain which can be used to trade time and energy with quality and therefore is useful in embedded systems. Energy is the prime resource in battery-driven embedded systems, like robots. Approximate computing can be used as a technique to generate approximate version of the control functionalities of a robot, enabling it to ration energy for computation at the cost of degraded quality. Usually, the programmer of the function specifies the extent of degradation that is safe for the overall safety of the system. However, in a collaborative environment, where several sub-systems co-exist and some of the functionality of each of them have been approximated, the safety of the overall system may be compromised. In this paper, we consider multiple identical robots operate in a warehouse, and the path planning function of the robot is approximated. Although the planned paths are safe for individual robots (ı.e. they do not collide with the racks), we show that this leads to a collision among the robots. So, a controlled approximation needs to be carried out in such situations to harness the full power of this new paradigm if it needs to be a mainstream paradigm in future.
The Impact of Parental Presence on their Children during Painful Medical Procedures:A Systematic Review.

OBJECTIVE Whether parental presence during their children's painful medical procedures is advantageous with regard to child's pain-related outcomes is questionable. Research regarding this topic is equivocal and additional questions, such as whether levels of parental involvement may play a role as well, remain to be assessed. The purpose of this systematic review is to summarize and critically appraise the literature regarding the impact of parental presence versus absence during their children's painful medical procedures on the child's pain-related outcomes. METHODS The review protocol was registered on Prospero (ID CRD42018116614). A systematic search in PubMed, Web of Science, and PsycArticles resulted in 22 eligible studies incorporating 2157 participants. Studies were considered eligible if they included children (≤ 18 years old) undergoing a painful medical procedure and compared parental presence and/or involvement with parental absence during the procedure. RESULTS The children's pain-related outcomes included self-reported pain intensity, self-reported fear, anxiety and distress, observed pain-related behavior, and physiological parameters. Overall, evidence points in the direction of beneficial effects of parental presence versus absence with regard to children's self-reported pain intensity and physiological parameters, whereas mixed findings were recorded for children's self-reported fears, anxiety and distress, and observed pain-related behaviors. CONCLUSIONS : In order to provide clear recommendations on how to involve the parent during the procedure, as well as for which type of children and parents parental presence has the best effects, further research is needed, as indicated in this review.
Mechanism and Origins of Stereoinduction in Natural Cinchona Alkaloid Catalyzed Asymmetric Electrophilic Trifluoromethylthiolation of β-Keto Esters with N-Trifluoromethylthiophthalimide as Electrophilic SCF3 Source

The trifluoromethylthio (SCF3) group enjoys a privileged role in the field of drug discovery because its incorporation into a drug molecule often leads to significantly improved pharmacokinetics and efficacy. In spite of its prime importance in drug discovery, the stereospecific introduction of the SCF3 group into target molecules has remained an unmet challenge. A major breakthrough was made in 2013 when Rueping and Shen simultaneously and independently disclosed natural Cinchona alkaloid catalyzed asymmetric electrophilic trifluoromethylthiolation of β-keto esters. However, two key issues remain obscure. (a) What is the preferred mode of catalysis? (b) How is asymmetric induction accomplished? Here we report an in-depth computational exploration into the mechanism and origin of stereoinduction in Cinchona alkaloid catalyzed trifluoromethylthiolation of β-keto esters with N-trifluoromethylthiophthalimide as electrophilic SCF3 source. Three mechanistic possibilities, i.e., (a) the transfer-trifluoromethyl.
Enhanced oxidative stress mediates pathological autophagy and necroptosis in cardiac myocytes in pressure overload induced heart failure in rats

In cardiac myocytes in vitro, hydrogen peroxide induces autophagic cell death and necroptosis. Oxidative stress, myocyte autophagy and necroptosis coexist in heart failure (HF). In this study, we tested the hypothesis that excessive oxidative stress mediates pathological autophagy and necroptosis in myocytes in pressure overload‐induced HF. HF was produced by chronic pressure overload induced by abdominal aortic constriction (AAC) in rats. Rats with AAC or sham operation were randomised to orally receive an antioxidant N‐acetylcysteine (NAC) or placebo for 4 weeks. Echocardiography was performed for the assessments of left ventricular (LV) structure and function. AAC rats exhibited decreased LV fractional shortening (FS) at 4 weeks after surgery. NAC treatment attenuated decreased LV FS in AAC rats. In AAC rats, myocardial level of 8‐hydroxydeoxyguanosine assessed by immunohistochemical staining, indicative of oxidative stress, was increased, LC3 II protein, a marker of autophagy, Beclin1 protein and Atg4b, Atg5, Atg7 and Atg12 mRNA expression were markedly increased, RIP1, RIP3 and MLKL expression, indicative of necroptosis, was increased, and all of the alterations in AAC rats were prevented by the NAC treatment. NAC treatment also attenuated myocyte cross‐sectional area and myocardial fibrosis in AAC rats. In conclusion, NAC treatment prevented the increases in oxidative stress, myocyte autophagy and necroptosis and the decrease in LV systolic function in pressure overload‐induced HF. These findings suggest that enhanced oxidative stress mediates pathological autophagy and necroptosis in myocytes, leading to LV systolic dysfunction, and antioxidants may be of value to prevent HF through the inhibition of excessive autophagy and necroptosis.
zmiz1a zebrafish mutants have defective erythropoiesis, altered expression of autophagy genes, and a deficient response to vitamin D

ZMIZ1 is a transcriptional coactivator that is related to members of the protein inhibitor of activated STAT (PIAS) family. ZMIZ1 regulates the activity of various transcription factors including the androgen receptor, p53, and Smad3. ZMIZ1 also interacts with Notch1 and selectively regulates Notch1 target genes relevant for T cell development and leukemogenesis in mammals. Human ZMIZ1 is additionally characterized as a latitude-dependent autoimmune disease (LDAD) risk gene, as it is responsive to vitamin D and has been associated with at least eleven blood cell traits. To address the function of ZMIZ1 in fish, we introduced CRISPR/Cas9 mutations in the zmiz1a gene in zebrafish. We observed that inactivation of zmiz1a in developing zebrafish larvae results in lethality at 15 dpf and delayed erythroid maturation. Differential gene expression analysis indicated that 15 dpf zmiz1a-null larvae had altered expression of autophagy genes, and erythrocytes that lacked Zmiz1a function exhibited an accumulation of mitochondrial DNA. Furthermore, we observed that autophagy gene expression was dysregulated at earlier stages of development, which suggests the involvement of Zmiz1a in the regulation of autophagy genes beyond the process of red blood cell differentiation. Finally, we showed that the loss of Zmiz1a decreased the capacity of the embryos to respond to vitamin D, indicating additional participation of Zmiz1a as a mediator of vitamin D activity.
The use of customer‐ and employee‐based performance measures in The Times top 500 companies

Discusses the degree to which customer‐ and employee‐based measures of performance are used within The Times top 500 companies, as revealed by a postal survey carried out in 1995 and from initial findings from six in‐depth case studies. The inquiry was initiated as a result of the continuing wave of changes resulting from the performance measurement revolution and ongoing developments in the field of total quality management. Investigates the generation and use of the measures and assesses the commonality between management theory and reported practice. Concludes that, although best practice (in academic terms) is apparent in some companies, the use of these measures in the determination of business strategy has not yet become standard practice.
Characterization of Allophane from Gamalama Volcanic Soil, North Maluku, Indonesia

North Maluku is a province in Indonesia in which there are five active volcanoes. The fifth of the volcano is Mount Gamalama in Ternate, Gamkonora in Halmahera Barat, Ibu and Dukono in North Halmahera and Kiebesi in South Halmahera. Mount Gamalama, which located adjacent to the Khairun University, Ternate, has erupted 60 times since 1538. The eruption has produced millions of tons of volcanic soil which contains a variety of very useful materials. One of the materials contained in the volcanic soil is allophane particles that are formed naturally in volcanic soil weathering processes [1,2]. The existence of allophane in the volcanic soil of Mount Gamalama has not been studied previously. This led to the use of volcanic soil of Mount Gamalama until now is limited to the agricultural sector or simply as an adsorbent pollutants. In this study, allophane from the volcanic soil of Mount Gamalama North Maluku was isolated and characterized by using FTIR, XRD, TEM and SEM-EDX. Allophane is a noncrystalline mineral aluminosilicate with Si/Al ratio between 0.5-2 and 3.5-5.0 nm in particle size [3-5].
The surname structure of Trentino (Italy) and its relationship with dialects and genes

Abstract Background Thanks to the availability of rich surname, linguistic and genetic information, together with its geographic and cultural complexity, Trentino (North-Eastern Italy) is an ideal place to test the relationships between genetic and cultural traits. Aim We provide a comprehensive study of population structures based on surname and dialect variability and evaluate their relationships with genetic diversity in Trentino. Subjects and methods Surname data were collected for 363 parishes, linguistic data for 57 dialects and genetic data for different sets of molecular markers (Y-chromosome, mtDNA, autosomal) in 10 populations. Analyses relied on different multivariate methods and correlation tests. Results Besides the expected isolation-by-distance-like patterns (with few local exceptions, likely related to sociocultural instances), we detected a significant and geography-independent association between dialects and surnames. As for molecular markers, only Y-chromosomal STRs seem to be associated with the dialects, although no significant result was obtained. No evidence for correlation between molecular markers and surnames was observed. Conclusion Surnames act as cultural markers as do other words, although in this context they cannot be used as reliable proxies for genetic variability at a local scale.
Insights into Punic genetic signatures in the southern necropolis of Tharros (Sardinia)

Abstract Background Phoenician and Punic expansions have been protagonists of intense trade networks and settlements in the Mediterranean Sea. Aims The maternal genetic variability of ancient Punic samples from the Sardinian necropolis of Tharros was analysed, with the aim to explore genetic interactions and signatures of past population events. Subjects and methods The mtDNA HVS-I and coding region SNPs were analysed in 14 Punic samples and 74 modern individuals from Cabras and Belvì (for which the HVS-II region was also analysed). The results were compared with 5,590 modern Euro-Mediterranean sequences and 127 ancient samples. Results While contemporary groups fall within the genetic variability of other modern Sardinians, our Punic samples reveal proximity to present-day North-African and Iberian populations. Furthermore, Cabras and Belvì cluster mainly with pre-Phoenician groups, while samples from Tharros project with other Punic Sardinian individuals. Conclusion This study provides the first preliminary insights into the population dynamics of the Punic site of Tharros. While the number of currently available samples does not allow definitive investigation of the connection with indigenous Sardinian groups, our results seem to confirm internal migratory phenomena in the central-western Mediterranean and female participation in the Punic mobility.
Lattice Boltzmann method investigation of a reactive electro-kinetic flow in porous media: towards a phenomenological model

A model based on the Lattice Boltzmann method is developed to study the flow of reactive electro-kinetic fluids in porous media. The momentum, concentration and electric/potential fields are simulated via the Navier–Stokes, advection–diffusion/Nernst–Planck and Poisson equations, respectively. With this model, the total density and velocity fields, the concentration of reactants and reaction products, including neutral and ionized species, the electric potential and the interaction forces between the fields can be studied, and thus we provide an insight into the interplay between chemistry, flow and the geometry of the porous medium. The results show that the conversion efficiency of the reaction can be strongly influenced by the fluid velocity, reactant concentration and by porosity of the porous medium. The fluid velocity determines how long the reactants stay in the reaction areas, the reactant concentration controls the amount of the reaction material and with different dielectric constant, the porous medium can distort the electric field differently. All these factors make the reaction conversion efficiency display a non-trivial and non-monotonic behaviour as a function of the flow and reaction parameters. To better illustrate the dependence of the reaction conversion efficiency on the control parameters, based on the input from a number of numerical investigations, we developed a phenomenological model of the reactor. This model is capable of capturing the main features of the causal relationship between the performance of the reactor and the main test parameters. Using this model, one could optimize the choice of reaction and flow parameters in order to improve the performance of the reactor and achieve higher production rates. This article is part of the theme issue ‘Progress in mesoscale methods for fluid dynamics simulation’.
Structure and dynamics of water confined in cylindrical nanopores with varying hydrophobicity

We report a detailed study of the main structural and dynamical features of water confined in model Lennard–Jones nanopores with tunable hydrophobicity and finite length (L=26 Å). The generic model of cylindrical confinement used is able to reproduce the wetting features of a large class of technologically and biologically relevant systems spanning from crystalline nanoporous materials, to mesoporous silica and ion channels. The aim of this work is to discuss the influence of parameters such as wall hydrophobicity, temperature, and pore size on the structural and dynamical features of confined water. Our simulation campaign confirmed the existence of a core domain in which water displays bulk-like structural features even in extreme (R=7.0 Å) confinement, while dynamical properties were shown to depend non-trivially on the size and hydrophobicity of the pores. This article is part of the theme issue ‘Progress in mesoscale methods for fluid dynamics simulation’.
Fully Autonomous Vehicles for People with Visual Impairment

A significant number of individuals in the United States report a disability that limits their ability to travel, including many people who are blind or visually impaired (BVI). The implications of restricted transportation result in negative impacts related to economic security, physical and mental health, and overall quality of life. Fully autonomous vehicles (FAVs) present a means to mitigate travel barriers for this population by providing new, safe, and independent travel opportunities. However, current policies governing interactions with the artificial intelligence (AI) ‘at the wheel’ of FAVs do not reflect the accessibility needs articulated by BVI people in the extant literature, failing to encourage use cases that would result in life changing mobility. By reviewing the legislative and policy efforts surrounding FAVs, we argue that the heart of this problem is due to a disjointed, laissez-faire approach to FAV accessibility that has yet to actualize the full benefits of this new transportation mode, not only for BVI people, but also for all users. We outline the necessity for a policy framework that guides the design of FAVs to include the concerns of BVI people and then propose legislative and design recommendations aimed to promote enhanced accessibility, transparency, and fairness during FAV travel.
24-nt phasiRNAs move from tapetal to meiotic cells in maize anthers

In maize, 24-nt phased, secondary small interfering RNAs (phasiRNAs) are abundant in meiotic stage anthers, but their distribution and functions are not precisely known. Using laser capture microdissection, we analyzed tapetal cells, meiocytes, and other somatic cells at several stages of anther development to establish the timing of 24-PHAS precursor transcripts and the 24-nt phasiRNA products. By integrating RNA and small RNA profiling plus single-molecule and small RNA FISH (smFISH or sRNA-FISH) spatial detection, we demonstrate that the tapetum is the primary site of 24-PHAS precursor and Dcl5 transcripts and the resulting 24-nt phasiRNAs. Interestingly, 24-nt phasiRNAs accumulate in all cell types, with the highest levels in meiocytes, followed by tapetum. Our data support the conclusion that 24-nt phasiRNAs are mobile from tapetum to meiocytes and to other somatic cells. We discuss possible roles for 24-nt phasiRNAs in anther cell types.
Spatially resolved in silico modeling of NKG2D signaling kinetics suggests a key role of NKG2D and Vav1 Co-clustering in generating natural killer cell activation

Natural Killer (NK) cells provide key resistance against viral infections and tumors. A diverse set of activating and inhibitory NK cell receptors (NKRs) interact with cognate ligands presented by target host cells, where integration of dueling signals initiated by the ligand-NKR interactions determines NK cell activation or tolerance. Imaging experiments over decades have shown micron and sub-micron scale spatial clustering of activating and inhibitory NKRs. The mechanistic roles of these clusters in affecting downstream signaling and activation are often unclear. To this end, we developed a predictive in silico framework by combining spatially resolved mechanistic agent based modeling, published TIRF imaging data, and parameter estimation to determine mechanisms by which formation and spatial movements of activating NKG2D microclusters affect early time NKG2D signaling kinetics in a human cell line NKL. We show co-clustering of NKG2D and the guanosine nucleotide exchange factor Vav1 in NKG2D microclusters plays a dominant role over ligand (ULBP3) rebinding in increasing production of phospho-Vav1(pVav1), an activation marker of early NKG2D signaling. The in silico model successfully predicts several scenarios of inhibition of NKG2D signaling and time course of NKG2D spatial clustering over a short (∼3 min) interval. Modeling shows the presence of a spatial positive feedback relating formation and centripetal movements of NKG2D microclusters, and pVav1 production offers flexibility towards suppression of activating signals by inhibitory KIR ligands organized in inhomogeneous spatial patterns (e.g., a ring). Our in silico framework marks a major improvement in developing spatiotemporal signaling models with quantitatively estimated model parameters using imaging data.
CD72-semaphorin3A axis; a possible new player in immune regulation

Semaphorin3A (sema3A) inhibits the activity of B and T cells in autoimmune diseases such as Systemic Lupus Erythematosus (SLE). We have now found that CD72 functions as a novel sema3A binding and signal-transducing receptor. These functions of CD72 are independent of the known sema3A receptor neuropilin-1 (NRP-1). We find that sema3A induces the phosphorylation of CD72 on tyrosine residues and the association of CD72 with SHP-1 and SHP-2. In contrast, sema4D/CD100 inhibits these functions. sema3A signals mediated by CD72, inhibit the phosphorylation of STAT-4 and HDAC-1 and induce the phosphorylation of p38-MAPK and PKC-theta in B-cells derived B-lymphoblastoid (BLCL) cells lacking NRP-1 expression, and in primary B-cells isolated from either healthy donors or SLE (Systemic Lupus Erythematosus) patients. We have also generated a modified truncated sema3A (T-sema3A) which cannot signal via NRP-1 yet still activates inhibitory CD72 signaling. We propose that T-sema3A may have potential as a possible therapeutic for autoimmune diseases such as SLE. One Sentence Summary CD72 found as a novel sema3A receptor transduces inhibitory signals in Bcells. A modified sema3A can be used to treat autoimmunity.
BldD-based bimolecular fluorescence complementation for in vivo detection of the second messenger cyclic di-GMP

The widespread bacterial second messenger bis-(3’-5’)-cyclic diguanosine monophosphate (c-di-GMP) is an important regulator of biofilm formation, virulence and cell differentiation. C-di-GMP-specific biosensors that allow detection and visualization of c-di-GMP levels in living cells are key to our understanding of how c-di-GMP fluctuations drive cellular responses. Here, we describe a novel c-di-GMP biosensor, CensYBL, that is based on c-di-GMP-induced dimerization of the effector protein BldD from Streptomyces resulting in bimolecular fluorescence complementation of split-YPet fusion proteins. As a proof-of-principle, we demonstrate that CensYBL is functional in detecting fluctuations in intracellular c-di-GMP levels in the Gram-negative model bacteria Escherichia coli and Salmonella enterica serovar Typhimurium. Using deletion mutants of c-di-GMP diguanylate cyclases and phosphodiesterases, we show that c-di-GMP dependent dimerization of CBldD-YPet results in fluorescence complementation reflecting intracellular c-di-GMP levels. Overall, we demonstrate that the CensYBL biosensor is a user-friendly and versatile tool that allows to investigate c-di-GMP variations using single-cell and population-wide experimental set-ups. Importance The second messenger c-di-GMP controls various bacterial functions including development of resistant biofilm communities and transition into dormant spores. In vivo detection of c-di-GMP levels is therefore crucial for a better understanding of how intracellular c-di-GMP levels induce changes of bacterial physiology. Here, we describe the design of a novel c-di-GMP biosensor and demonstrate its effective application in investigating fluctuations in intracellular c-di-GMP levels in Escherichia coli and Salmonella enterica serovar Typhimurium on a population-based and single-cell level.