Miracle-dz/UniFAR-FTUs huggingface dataset:
The role of extracellular matrix stiffness in megakaryocyte and platelet development and function

The extracellular matrix (ECM) is a key acellular structure in constant remodeling to provide tissue cohesion and rigidity. Deregulation of the balance between matrix deposition, degradation, and crosslinking results in fibrosis. Bone marrow fibrosis (BMF) is associated with several malignant and nonmalignant pathologies severely affecting blood cell production. BMF results from abnormal deposition of collagen fibers and enhanced lysyl oxidase‐mediated ECM crosslinking within the marrow, thereby increasing marrow stiffness. Bone marrow stiffness has been recently recognized as an important regulator of blood cell development, notably by modifying the fate and differentiation process of hematopoietic or mesenchymal stem cells. This review surveys the different components of the ECM and their influence on stem cell development, with a focus on the impact of the ECM composition and stiffness on the megakaryocytic lineage in health and disease. Megakaryocyte maturation and the biogenesis of their progeny, the platelets, are thought to respond to environmental mechanical forces through a number of mechanosensors, including integrins and mechanosensitive ion channels, reviewed here.
Heterogeneous Networks With Power-Domain NOMA: Coverage, Throughput, and Power Allocation Analysis

In a heterogeneous cellular network (HetNet), consider that a base station in the HetNet is able to simultaneously schedule and serve <inline-formula> <tex-math notation="LaTeX">$K$ </tex-math></inline-formula> users in the downlink by performing the power-domain non-orthogonal multiple access (NOMA) scheme. This paper aims at the preliminary study on the downlink coverage and throughput performances of the HetNet with the non-coordinated NOMA and the proposed coordinated joint transmission NOMA (JT-NOMA) schemes. First, the coverage probability and link throughput of <inline-formula> <tex-math notation="LaTeX">$K$ </tex-math></inline-formula> users in each cell are studied and their accurate expressions are derived for the non-coordinated NOMA scheme in which no BSs are coordinated to jointly transmit the NOMA signals for a particular user. We show that the coverage and link throughput can be largely reduced if transmit power allocations among the <inline-formula> <tex-math notation="LaTeX">$K$ </tex-math></inline-formula> users do not satisfy the constraint derived. Next, we analyze the coverage and link throughput of <inline-formula> <tex-math notation="LaTeX">$K$ </tex-math></inline-formula> users for the coordinated JT-NOMA scheme in which the void BSs without users are coordinated to enhance the farthest NOMA user in a cell. The derived accurate results show that coordinated JT-NOMA can significantly improve the coverage and link throughput of all users. Finally, we show that there exist optimal power allocation schemes that maximize the average cell coverage and throughput under some derived power allocation constraints and numerical results validate our analytical findings.
Atg13 Is Essential for Autophagy and Cardiac Development in Mice

ABSTRACT Autophagy is a major intracellular degradation system by which cytoplasmic components are enclosed by autophagosomes and delivered to lysosomes. Formation of the autophagosome requires a set of autophagy-related (Atg) proteins. Among these proteins, the ULK1 complex, which is composed of ULK1 (or ULK2), FIP200, Atg13, and Atg101, acts at an initial step. Previous studies showed that ULK1 and FIP200 also function in pathways other than autophagy. However, whether Atg13 and Atg101 act similarly to ULK1 and FIP200 remains unknown. In the present study, we generated Atg13 knockout mice. Like FIP200-deficient mice, Atg13-deficient mice die in utero, which is distinct from most other types of Atg-deficient mice. Atg13-deficient embryos show growth retardation and myocardial growth defects. In cultured fibroblasts, Atg13 deficiency blocks autophagosome formation at an upstream step. In addition, sensitivity to tumor necrosis factor alpha (TNF-α)-induced apoptosis is enhanced by deletion of Atg13 or FIP200, but not by other Atg proteins, as well as by simultaneous deletion of ULK1 and ULK2. These results suggest that Atg13 has both autophagic and nonautophagic functions and that the latter are essential for cardiac development and likely shared with FIP200 but not with ULK1/2.
Fish consumption and cardiovascular disease related biomarkers: A review of clinical trials

ABSTRACT The purpose of this review is to collect and compare fish intervention studies. Prospective studies have outlined the beneficial effect of frequent fish consumption on cardiovascular incidents that is attributed to n-3 fatty acids incorporated in fish, mainly eicosapentaenoic (EPA), and docosahexaenoic (DHA) acids. This outcome triggered clinical trials to examine the effect of either fish intake or consumption of n-3 fatty acids via capsules on biomarkers related to cardiovascular disease (CVD). The absence of a recent review focusing on clinical trials regarding fish intake and not n-3 fatty acids supplements rendered necessary the composition of this article. In total, 28 studies on healthy volunteers were found to meet the inclusion criteria. With EPA and DHA intake varying between 0.03 to 5 g per day, biomarkers, such as triglycerides, high-density lipoprotein and platelet aggregation, tended to ameliorate when daily intake exceeded 1 g per day, while the most common inflammatory marker, C-reactive protein, was not affected. In all, fish consumption gives promising results; yet fish micronutrients, total diet fat, as well as other dietary habits may also affect biomarkers. Therefore, all these factors should be considered in future clinical trials in order for one to draw more reliable conclusions.
Association of Age with Mortality and Virological and Immunological Response to Antiretroviral Therapy in Rural South African Adults

Objective To assess whether treatment outcomes vary with age for adults receiving antiretroviral therapy (ART) in a large rural HIV treatment cohort. Design Retrospective cohort analysis using data from a public HIV Treatment & Care Programme. Methods Adults initiating ART 1st August 2004 - 31st October 2009 were stratified by age at initiation: young adults (16–24 years) mid-age adults (25–49 years) and older (≥50 years) adults. Kaplan-Meier survival analysis was used to estimate mortality rates and age and person-time stratified Cox regression to determine factors associated with mortality. Changes in CD4 cell counts were quantified using a piecewise linear model based on follow-up CD4 cell counts measured at six-monthly time points. Results 8846 adults were included, 808 (9.1%) young adults; 7119 (80.5%) mid-age adults and 919 (10.4%) older adults, with 997 deaths over 14,778 person-years of follow-up. Adjusting for baseline characteristics, older adults had 32% excess mortality (p = 0.004) compared to those aged 25–49 years. Overall mortality rates (MR) per 100 person-years were 6.18 (95% CI 4.90–7.78); 6.55 (95% CI 6.11–7.02) and 8.69 (95% CI 7.34–10.28) for young, mid-age and older adults respectively. In the first year on ART, for older compared to both young and mid-aged adults, MR per 100 person-years were significantly higher; 0–3 months (MR: 27.1 vs 17.17 and 21.36) and 3–12 months (MR: 9.5 vs 4.02 and 6.02) respectively. CD4 count reconstitution was lower, despite better virological response in the older adults. There were no significant differences in MR after 1year of ART. Baseline markers of advanced disease were independently associated with very early mortality (0–3 months) whilst immunological and virological responses were associated with mortality after 12months. Conclusions Early ART initiation and improving clinical care of older adults are required to reduce high early mortality and enhance immunologic recovery, particularly in the initial phases of ART.
A Millimeter-Wave Fully Integrated Passive Reflection-Type Phase Shifter With Transformer-Based Multi-Resonance Loads for 360° Phase Shifting

This paper presents a millimeter-wave fully differential transformer-based passive reflection-type phase shifter (RTPS) capable of performing full span 360° continuous phase shift from 58 to 64 GHz. It consists of two transformer-based 90° couplers and two transformer-based multi-resonance reflective loads to provide 360° phase shift with low loss and ultra-compact chip size. Our proof-of-concept design is implemented in a standard 130-nm BiCMOS process with a core area of 480 <inline-formula> <tex-math notation="LaTeX">$\mu \text{m} \,\, \times 340~\mu \text{m}$ </tex-math></inline-formula>. It achieves a wide phase shifting range of 367° and a low insertion loss IL (<inline-formula> <tex-math notation="LaTeX">$3.7~\text {dB}<\vert \text {IL}\vert <10.2~\text {dB}$ </tex-math></inline-formula>) at 62 GHz and maintains a full span 360° phase shifting range from 58 to 64 GHz. Moreover, it supports 360° phase shifting with a constant IL, i.e., <inline-formula> <tex-math notation="LaTeX">$\vert \text {IL}\vert =10$ </tex-math></inline-formula>, 11, 12 dB, at an IL variation of less than 0.74 dB at 62 GHz. To the best of our knowledge, this design achieves a first-ever full span 360° phase shifting (up to 367°), the lowest IL, the smallest IL variation, and the best figure-of-merit of 37.1°/dB among reported 60 GHz fully integrated RTPS in silicon.
Formation of anthropogenic secondary organic aerosol (SOA) and its influence on biogenic SOA properties

Abstract. Secondary organic aerosol (SOA) formation from mixed anthropogenic and biogenic precursors has been studied exposing reaction mixtures to natural sunlight in the SAPHIR chamber in Julich, Germany. In this study aromatic compounds served as examples of anthropogenic volatile organic compound (VOC) and a mixture of α-pinene and limonene as an example for biogenic VOC. Several experiments with exclusively aromatic precursors were performed to establish a relationship between yield and organic aerosol mass loading for the atmospheric relevant range of aerosol loads of 0.01 to 10 μg m−3. The yields (0.5 to 9%) were comparable to previous data and further used for the detailed evaluation of the mixed biogenic and anthropogenic experiments. For the mixed experiments a number of different oxidation schemes were addressed. The reactivity, the sequence of addition, and the amount of the precursors influenced the SOA properties. Monoterpene oxidation products, including carboxylic acids and dimer esters were identified in the aged aerosol at levels comparable to ambient air. OH radicals were measured by Laser Induced Fluorescence, which allowed for establishing relations of aerosol properties and composition to the experimental OH dose. Furthermore, the OH measurements in combination with the derived yields for aromatic SOA enabled application of a simplified model to calculate the chemical turnover of the aromatic precursor and corresponding anthropogenic contribution to the mixed aerosol. The estimated anthropogenic contributions were ranging from small (a8%) up to significant fraction (>50%) providing a suitable range to study the effect of aerosol composition on the aerosol volatility (volume fraction remaining (VFR) at 343 K: 0.86–0.94). The aromatic aerosol had higher oxygen to carbon ratio O/C and was less volatile than the biogenic fraction. However, in order to produce significant amount of aromatic SOA the reaction mixtures needed a higher OH dose that also increased O/C and provided a less volatile aerosol. The SOA yields, O/C, and f44 (the mass fraction of CO2+ ions in the mass spectra which can be considered as a measure of carboxylic groups) in the mixed photo-chemical experiments could be described as linear combinations of the corresponding properties of the pure systems. For VFR there was in addition an enhancement effect, making the mixed aerosol significantly less volatile than what could be predicted from the pure systems. A strong positive correlation was found between changes in volatility and O/C with the exception during dark hours where the SOA volatility decreased while O/C did not change significantly. Thus, this change in volatility under dark conditions as well as the anthropogenic enhancement is due to chemical or morphological changes not affecting O/C.
Microscopic texture characterisation in piezoceramics

In polycrystalline piezoelectric ceramics, ferroelectric domain texture is the most important parameter influencing the attainable electromechanical performance. High piezoelectric properties are obtained when the maximum poling of the material is achieved. This condition can be favoured by modifying material composition, poling routes or by proper grain texturing. Hence, it is necessary to characterise domain texture, in order to develop piezoceramics with improved performance. In this review, an outline of the methods for ferroelectric domain texture determination will be given, with focus on microscopic techniques. The advantages and complementarity of methods like X-ray and neutron diffraction, electron diffraction, and Raman spectroscopy will be highlighted.
Effect of Changing Work Stressors and Coping Resources on Psychological Distress

Objectives: We examined whether or not changing work stressors and coping resources affect the risk of psychological distress. Method: A baseline evaluation of work stressors and coping resources and mental health was assessed for 4362 petroleum industry workers after 12 years. Results: Increased task and organizational stressors were associated with an elevated risk of psychological distress. Decreased task stressors, increased job control, and increased coping resources were associated with a reduced risk of psychological distress. Increased coping also had a buffering effect on increased work stressors and psychological distress. Gender-specific differences were observed in the factors influencing mental health. Conclusions: The findings indicated that reducing gender-specific task and organizational stressors, and promoting coping resources at work may help prevent the onset of psychological distress.
Disturbed sleep and activity in toddlers with early signs of attention deficit hyperactivity disorder (ADHD)

This study investigated whether early signs of attention deficit hyperactivity disorder (ADHD) in toddlers aged 2–3 years are associated with disturbed sleep and activity levels. Participants were recruited from the Odense Child Cohort, and children scoring above the 93rd percentile on the ADHD scale of the Child Behaviour Checklist 1½–5 were categorised as cases and compared with age‐ and gender‐matched normal‐scoring controls. Daytime and nocturnal activity for 24 children with ADHD traits (cases) and 25 healthy controls was assessed through 7 days of actigraphy, and parents completed the Children's Sleep Habits Questionnaire (CSHQ) and the ADHD Rating Scale IV Preschool Version (ADHD‐RS). Cases differed significantly on actigraphic parameters by having fewer minutes of moderate‐to‐vigorous physical activity (MVPA), prolonged total sleep time, fewer sleep interruptions, and increased night‐to‐night variability. A significant association was found between fewer minutes of MVPA and higher parent‐reported motor activity on the ADHD‐RS. Furthermore, increased night‐to‐night variability was significantly associated with higher total scores on both CSHQ and ADHD‐RS. The findings show that early signs of ADHD are associated with an irregular sleep pattern and lower daytime activity, as illustrated by actigraphy. Studies investigating early ADHD risk factors could lead to a preschool ADHD risk index to help guide future early intervention.
Mutations in Protocadherin 15 and Cadherin 23 Affect Tip Links and Mechanotransduction in Mammalian Sensory Hair Cells

Immunocytochemical studies have shown that protocadherin-15 (PCDH15) and cadherin-23 (CDH23) are associated with tip links, structures thought to gate the mechanotransducer channels of hair cells in the sensory epithelia of the inner ear. The present report describes functional and structural analyses of hair cells from Pcdh15av3J (av3J), Pcdh15av6J (av6J) and Cdh23v2J (v2J) mice. The av3J and v2J mice carry point mutations that are predicted to introduce premature stop codons in the transcripts for Pcdh15 and Cdh23, respectively, and av6J mice have an in-frame deletion predicted to remove most of the 9th cadherin ectodomain from PCDH15. Severe disruption of hair-bundle morphology is observed throughout the early-postnatal cochlea in av3J/av3J and v2J/v2J mice. In contrast, only mild-to-moderate bundle disruption is evident in the av6J/av6J mice. Hair cells from av3J/av3J mice are unaffected by aminoglycosides and fail to load with [3H]-gentamicin or FM1-43, compounds that permeate the hair cell's mechanotransducer channels. In contrast, hair cells from av6J/av6J mice load with both FM1-43 and [3H]-gentamicin, and are aminoglycoside sensitive. Transducer currents can be recorded from hair cells of all three mutants but are reduced in amplitude in all mutants and have abnormal directional sensitivity in the av3J/av3J and v2J/v2J mutants. Scanning electron microscopy of early postnatal cochlear hair cells reveals tip-link like links in av6J/av6J mice, substantially reduced numbers of links in the av3J/av3J mice and virtually none in the v2J/v2J mice. Analysis of mature vestibular hair bundles reveals an absence of tip links in the av3J/av3J and v2J/v2J mice and a reduction in av6J/av6J mice. These results therefore provide genetic evidence consistent with PCDH15 and CDH23 being part of the tip-link complex and necessary for normal mechanotransduction.
Social Information Is Integrated into Value and Confidence Judgments According to Its Reliability

How much we like something, whether it be a bottle of wine or a new film, is affected by the opinions of others. However, the social information that we receive can be contradictory and vary in its reliability. Here, we tested whether the brain incorporates these statistics when judging value and confidence. Participants provided value judgments about consumer goods in the presence of online reviews. We found that participants updated their initial value and confidence judgments in a Bayesian fashion, taking into account both the uncertainty of their initial beliefs and the reliability of the social information. Activity in dorsomedial prefrontal cortex tracked the degree of belief update. Analogous to how lower-level perceptual information is integrated, we found that the human brain integrates social information according to its reliability when judging value and confidence. SIGNIFICANCE STATEMENT The field of perceptual decision making has shown that the sensory system integrates different sources of information according to their respective reliability, as predicted by a Bayesian inference scheme. In this work, we hypothesized that a similar coding scheme is implemented by the human brain to process social signals and guide complex, value-based decisions. We provide experimental evidence that the human prefrontal cortex's activity is consistent with a Bayesian computation that integrates social information that differs in reliability and that this integration affects the neural representation of value and confidence.
6‐Methoxyethylamino‐numonafide inhibits hepatocellular carcinoma xenograft growth as a single agent and in combination with sorafenib

Hepatocellular carcinoma (HCC) is the third leading form of cancer worldwide, and its incidence is increasing rapidly in the United States, tripling over the past 3 decades. The current chemotherapeutic strategies against localized and metastatic HCC are ineffective. Here we report that 6‐methoxyethylamino‐numonafide (MEAN) is a potent growth inhibitor of murine xenografts of 2 human HCC cell lines. At the same dose and with the same treatment strategies, MEAN was more efficacious in inhibiting tumor growth in mice than sorafenib, the only approved drug for HCC. Treatment by MEAN at an effective dose for 6 wk was well tolerated by animals. Combined therapy using both sorafenib and MEAN enhanced tumor growth inhibition over monotherapy with either agent. Additional experiments revealed that MEAN inhibited tumor growth through mechanisms distinct from those of either its parent compound, amonafide, or sorafenib. MEAN suppressed C‐MYC expression and increased expression of several tumor suppressor genes, including Src homology region 2 domain‐containing phosphatase‐1 (SHP‐1) and TXNIP (thioredoxin‐interacting protein). As an encouraging feature for envisioned clinical application, the IC50 of MEAN was not significantly changed in several drug‐resistant cell lines with activated P‐glycoprotein drug efflux pumps compared to drug‐sensitive parent cells, demonstrating the ability of MEAN to be effective in cells resistant to existing chemotherapy regimens. MEAN is a promising candidate for clinical development as a single‐agent therapy or in combination with sorafenib for the management of HCC. —Liu, Y. , Lou, G. , Norton, J.T. , Wang, C. , Kandela, I. , Tang, S. , Shank, N.I. , Gupta, P., Huang, M. , Avram, M.J., Green, R. , Mazar, A. , Appella, D. , Chen, Z. , Huang, S. 6‐Methoxyethylamino‐numonafide inhibits hepatocellular carcinoma xenograft growth as a single agent and in combination with sorafenib. FASEB J. 31, 5453–5465 (2017). www.fasebj. org
Structural, electronic, optical and elastic properties of the complex K2PtCl6-structure hydrides ARuH6 (A = Mg, Ca, Sr and Ba): first-principles study

Abstract We report a systematic study of the structural, electronic, optical and elastic properties of the ternary ruthenium-based hydrides A2RuH6 (A = Mg, Ca, Sr and Ba) within two complementary first-principles approaches. We describe the properties of the A2RuH6 systems looking for trends on different properties as a function of the A sublattice. Our results are in agreement with experimental ones when the latter are available. In particular, our theoretical lattice parameters obtained using the GGA-PBEsol to include the exchange-correlation functional are in good agreement with experiment. Analysis of the calculated electronic band structure diagrams suggests that these hydrides are wide nearly direct band semiconductors, with a very slight deviation from the ideal direct-band gap behaviour and they are expected to have a poor hole-type electrical conductivity. The TB-mBJ potential has been used to correct the deficiency of the standard GGA for predicting the optoelectronic properties. The calculated TB-mBJ fundamental band gaps are about 3.53, 3.11, 2.99 and 2.68 eV for Mg2RuH6, Ca2RuH6, Sr2RuH6 and Ba2RuH6, respectively. Calculated density of states spectra demonstrates that the topmost valence bands consist of d orbitals of the Ru atoms, classifying these materials as d-type hydrides. Analysis of charge density maps tells that these systems can be classified as mixed ionic-covalent bonding materials. Optical spectra in a wide energy range from 0 to 30 eV have been provided and the origin of the observed peaks and structures has been assigned. Optical spectra in the visible range of solar spectrum suggest these hydrides for use as antireflection coatings. The single-crystal and polycrystalline elastic moduli and their related properties have been numerically estimated and analysed for the first time.