Miracle-dz/UniFAR-FTUs huggingface dataset:
An Antimicrobial Peptide-Loaded Gelatin/Chitosan Nanofibrous Membrane Fabricated by Sequential Layer-by-Layer Electrospinning and Electrospraying Techniques

Guided bone regeneration (GBR) technique is widely used in the treatment of bone defects caused by peri-implantitis, periodontal disease, etc. However, the GBR membranes commonly used in clinical treatments currently have no antibacterial activity. Therefore, in this study, sequential layer-by-layer electrospinning and electrospraying techniques were utilized to prepare a gelatin (Gln) and chitosan (CS) composite GBR membrane containing hydroxyapatite nanoparticles (nHAp) and antimicrobial peptide (Pac-525)-loaded PLGA microspheres (AMP@PLGA-MS), which was supposed to have osteogenic and antibacterial activities. The scanning electron microscope (SEM) observation showed that the morphology of the nanofibers and microspheres could be successfully produced. The diameters of the electrospun fibers with and without nHAp were 359 ± 174 nm and 409 ± 197 nm, respectively, and the mechanical properties of the membrane were measured according to the tensile stress-strain curve. Both the involvement of nHAp and the chemical crosslinking were able to enhance their tensile strength. In vitro cell culture of rat bone marrow mesenchymal stem cells (rBMSCs) indicated that the Gln/CS composite membrane had an ideal biocompatibility with good cell adhesion, spreading, and proliferation. In addition, the Gln/CS membrane containing nHAp could promote osteogenic differentiation of rBMSCs. Furthermore, according to the in vitro drug release assay and antibacterial experiments, the composite GBR membrane containing AMP@PLGA-MS exhibited a long-term sustained release of Pac-525, which had bactericidal activity within one week and antibacterial activity for up to one month against two kinds of bacteria, S. aureus and E. coli. Our results suggest that the antimicrobial peptide-loaded Gln/CS composite membrane (AMP@PLGA-MS@Gln/CS/nHAp) has a great promise in bone generation-related applications for the unique functions of guiding bone regeneration and inhibiting bacterial infection as well.
Effects of a multi-component nutritional telemonitoring intervention on nutritional status, diet quality, physical functioning and quality of life of community-dwelling older adults

Abstract This study aimed to evaluate the effects of an intervention including nutritional telemonitoring, nutrition education, and follow-up by a nurse on nutritional status, diet quality, appetite, physical functioning and quality of life of Dutch community-dwelling elderly. We used a parallel arm pre-test post-test design with 214 older adults (average age 80 years) who were allocated to the intervention group (n 97) or control group (n 107), based on the municipality. The intervention group received a 6-month intervention including telemonitoring measurements, nutrition education and follow-up by a nurse. Effect measurements took place at baseline, after 4·5 months, and at the end of the study. The intervention improved nutritional status of participants at risk of undernutrition (β (T1)=2·55; 95 % CI 1·41, 3·68; β (T2)=1·77; 95 % CI 0·60, 2·94) and scores for compliance with Dutch guidelines for the intake of vegetables (β=1·27; 95 % CI 0·49, 2·05), fruit (β=1·24; 95 % CI 0·60, 1·88), dietary fibre (β=1·13; 95 % CI 0·70, 1·57), protein (β=1·20; 95 % CI 0·15, 2·24) and physical activity (β=2·13; 95 % CI 0·98, 3·29). The intervention did not have an effect on body weight, appetite, physical functioning and quality of life. In conclusion, this intervention leads to improved nutritional status in older adults at risk of undernutrition, and to improved diet quality and physical activity levels of community-dwelling elderly. Future studies with a longer duration should focus on older adults at higher risk of undernutrition than this study population to investigate whether the impact of the intervention on nutritional and functional outcomes can be improved.
Augmentation of the cytotoxic effects of nitrogen‐containing bisphosphonates in hypoxia

Tumour hypoxia is a major obstacle in cancer therapy that leads to poor prognosis. Therefore, the development of cancer treatments that are effective in hypoxia is necessary. Nitrogen‐containing bisphosphonates (N‐BPs), which are used to treat bone disease, are cytotoxic to several cancer cells in normoxia. Therefore, we investigated the cytotoxicity of N‐BPs in cancer cells in hypoxia.
Updates to Clostridium difficile Spore Germination

Germination of Clostridium difficile spores is a crucial early requirement for colonization of the gastrointestinal tract. Likewise, C. difficile cannot cause disease pathologies unless its spores germinate into metabolically active, toxin-producing cells. ABSTRACT Germination of Clostridium difficile spores is a crucial early requirement for colonization of the gastrointestinal tract. Likewise, C. difficile cannot cause disease pathologies unless its spores germinate into metabolically active, toxin-producing cells. Recent advances in our understanding of C. difficile spore germination mechanisms indicate that this process is both complex and unique. This review defines unique aspects of the germination pathways of C. difficile and compares them to those of two other well-studied organisms, Bacillus anthracis and Clostridium perfringens. C. difficile germination is unique, as C. difficile does not contain any orthologs of the traditional GerA-type germinant receptor complexes and is the only known sporeformer to require bile salts in order to germinate. While recent advances describing C. difficile germination mechanisms have been made on several fronts, major gaps in our understanding of C. difficile germination signaling remain. This review provides an updated, in-depth summary of advances in understanding of C. difficile germination and potential avenues for the development of therapeutics, and discusses the major discrepancies between current models of germination and areas of ongoing investigation.
In silico prediction of gene expression patterns in Citrus flavedo

Out of the 18,942 flavedo expressed sequences (clusters plus singletons) in Citrus sinensis from the Citrus EST Project (CitEST), 25 were statistically supported to be differentially expressed in this tissue after a double in silico hybridization strategy against leaf-, flower-, and bark-derived ESTs. Five of them, two terpene synthases and three O-methyltransferases, are absent in the other citrus tissues with concomitant 2x2 statistics, supporting the hypothesis that they are putative flavedo-specific expressed sequences. The pattern of these differentially expressed sequences during fruit development suggests that most of them are developmentally regulated. Some expressed gene products, including a putative germin-like protein highly expressed in flavedo, are shown to be promising candidates for further characterization. In addition to promoter seeking, this kind of analysis can lead to gene discovery, tissue-specific and tissue-enriched expression pattern predictions (as shown herein) and can also be adopted as an in silico first, and probably reliable approach, for detecting expression profiles from EST sequencing efforts before experimental validation is available or for heuristically guiding that validation.
When Two Bosses Are Better Than One: Nearly Decomposable Systems and Organizational Adaptation

Organizations, as is true with social systems more generally, tend to be nearly, not fully, decomposable. However, analyses of nearly decomposable systems have tended to be at a single level of analysis and have generally neglected the vertical element of nearly decomposable systems. Critical to the notion of nearly decomposable systems is the property that the details of a particular subproblem may be encapsulated and captured by more aggregate parameters and that those subproblems interact in an aggregate way. We explore these issues in reference to the role of three canonical organizational structures in facilitating adaptation in the presence of near decomposability: a traditional hierarchy in which a subordinate reports to a single boss, an autonomous form in which the subordinate does not have a direct reporting relationship, and a multiauthority structure in which the subordinate reports to multiple bosses. Despite the ubiquity and potential benefits of multiauthority structures in coordinating highly interdependent tasks, our understanding of the mechanisms that determine the performance of those structures is still relatively modest. Scholars have noted conflicting empirical findings and have called for a more rigorous approach to study these organizational forms. To help address these issues, we develop an agent-based computational model that compares the performance of these three canonical types of organizational forms in settings characterized by different degrees of complexity and near decomposability. The online appendix is available at https://doi.org/10.1287/orsc.2017. 1177 .
Blocking of an intronic splicing silencer completely rescues IKBKAP exon 20 splicing in familial dysautonomia patient cells

Abstract Familial dysautonomia (FD) is a severe genetic disorder causing sensory and autonomic dysfunction. It is predominantly caused by a c.2204+6T>C mutation in the IKBKAP gene. This mutation decreases the 5′ splice site strength of IKBKAP exon 20 leading to exon 20 skipping and decreased amounts of full-length IKAP protein. We identified a binding site for the splicing regulatory protein hnRNP A1 downstream of the IKBKAP exon 20 5′-splice site. We show that hnRNP A1 binds to this splicing regulatory element (SRE) and that two previously described inhibitory SREs inside IKBKAP exon 20 are also bound by hnRNP A1. Knockdown of hnRNP A1 in FD patient fibroblasts increases IKBKAP exon 20 inclusion demonstrating that hnRNP A1 is a negative regulator of IKBKAP exon 20 splicing. Furthermore, by mutating the SREs in an IKBKAP minigene we show that all three SREs cause hnRNP A1-mediated exon repression. We designed splice switching oligonucleotides (SSO) that blocks the intronic hnRNP A1 binding site, and demonstrate that this completely rescues splicing of IKBKAP exon 20 in FD patient fibroblasts and increases the amounts of IKAP protein. We propose that this may be developed into a potential new specific treatment of FD.
Pedestrian Detectability Estimation Considering Visual Adaptation to Drastic Illumination Change

SUMMARY We propose an estimation method of pedestrian de-tectability considering the driver’s visual adaptation to drastic illumination change, which has not been studied in previous works. We assume that driver’s visual characteristics change in proportion to the elapsed time after illumination change. In this paper, as a solution, we construct multiple estimators corresponding to di ﬀ erent elapsed periods, and estimate the detectability by switching them according to the elapsed period. To evaluate the proposed method, we construct an experimental setup to present a participant with illumination changes and conduct a preliminary simulated experiment to measure and estimate the pedestrian detectability according to the elapsed period. Results show that the proposed method can actually estimate the detectability accurately after a drastic illumination change.
Differential Roles of LTβR in Endothelial Cell Subsets for Lymph Node Organogenesis and Maturation

Cellular cross-talk mediated by lymphotoxin αβ–lymphotoxin β receptor (LTβR) signaling plays a critical role in lymph node (LN) development. Although the major role of LTβR signaling has long been considered to occur in mesenchymal lymphoid tissue organizer cells, a recent study using a VE-cadherincreLtbrfl/fl mouse model suggested that endothelial LTβR signaling contributes to the formation of LNs. However, the detailed roles of LTβR in different endothelial cells (ECs) in LN development remain unknown. Using various cre transgenic mouse models (Tekcre, a strain targeting ECs, and Lyve1cre, mainly targeting lymphatic ECs), we observed that specific LTβR ablation in Tekcre+ or Lyve1cre+ cells is not required for LN formation. Moreover, double-cre–mediated LTβR depletion does not interrupt LN formation. Nevertheless, TekcreLtbrfl/fl mice exhibit reduced lymphoid tissue inducer cell accumulation at the LN anlagen and impaired LN maturation. Interestingly, a subset of ECs (VE-cadherin+Tekcre-low/neg ECs) was found to be enriched in transcripts related to hematopoietic cell recruitment and transendothelial migration, resembling LN high ECs in adult animals. Furthermore, endothelial Tek was observed to negatively regulate hematopoietic cell transmigration. Taken together, our data suggest that although Tekcre+ endothelial LTβR is required for the accumulation of hematopoietic cells and full LN maturation, LTβR in VE-cadherin+Tekcre-low/neg ECs in embryos might represent a critical portal-determining factor for LN formation.
The Biotechnological and Seafood Potential of Stichopus regalis

Sea cucumbers are highly used not only for the production of the beche-de-mer, but also recent studies have been showing the high potential of these marine invertebrates on the pharmaceutical industry, as they are rich in bioactive compounds with important functions. Stichopus regalis extracts (1 mg·mL-1) were used in antioxidant, antimicrobial and antitumor assays. The lipid profile was also evaluated. No significant antioxidant activity was detected in both methanolic and dichloromethane extracts. The methanolic fraction showed the highest antimicrobial potential against Candida albicans with an IC50 of 475.4 μg·mL-1. In the antitumor assays, the dichloromethane fraction showed a high potential for both cell lines, as revealed by the MTT method. The total fat content was 3.63% ± 0.11% and the fatty acid profile revealed the highest amount in C16:0 (9.43% ± 0.77%), C18:0 (12.43% ± 0.83%), C18:1 ω7 (5.63% ± 0.33%), EPA (12.49% ± 0.15%), DHA (7.35% ± 0.02%), ARA (19.29% ± 0.14%) and a ω3/ω6 ratio of 1.078. These findings led us to suggest the potential use of S. regalis as a new source of bioactive compounds with pharmacological potential and its nutritional benefits for human health.
Tracers Reveal Recharge Elevations, Groundwater Flow Paths and Travel Times on Mount Shasta, California

Mount Shasta (4322 m) is famous for its spring water. Water for municipal, domestic and industrial use is obtained from local springs and wells, fed by annual snow melt and sustained perennially by the groundwater flow system. We examined geochemical and isotopic tracers in samples from wells and springs on Mount Shasta, at the headwaters of the Sacramento River, in order to better understand the hydrologic system. The topographic relief in the study area imparts robust signatures of recharge elevation to both stable isotopes of the water molecule (δ18O and δD) and to dissolved noble gases, offering tools to identify recharge areas and delineate groundwater flow paths. Recharge elevations determined using stable isotopes and noble gas recharge temperatures are in close agreement and indicate that most snowmelt infiltrates at elevations between 2000 m and 2900 m, which coincides with areas of thin soils and barren land cover. Large springs in Mt Shasta City discharge at an elevation more than 1600 m lower. High elevation springs (>2000 m) yield very young water (<2 years) while lower elevation wells (1000–1500 m) produce water with a residence time ranging from 6 years to over 60 years, based on observed tritium activities. Upslope movement of the tree line in the identified recharge elevation range due to a warming climate is likely to decrease infiltration and recharge, which will decrease spring discharge and production at wells, albeit with a time lag dependent upon the length of groundwater flow paths.
TensOrMachine: Probabilistic Boolean Tensor Decomposition

Boolean tensor decomposition approximates data of multi-way binary relationships as product of interpretable low-rank binary factors, following the rules of Boolean algebra. Here, we present its first probabilistic treatment. We facilitate scalable sampling-based posterior inference by exploitation of the combinatorial structure of the factor conditionals. Maximum a posteriori decompositions feature higher accuracies than existing techniques throughout a wide range of simulated conditions. Moreover, the probabilistic approach facilitates the treatment of missing data and enables model selection with much greater accuracy. We investigate three real-world data-sets. First, temporal interaction networks in a hospital ward and behavioural data of university students demonstrate the inference of instructive latent patterns. Next, we decompose a tensor with more than 10 billion data points, indicating relations of gene expression in cancer patients. Not only does this demonstrate scalability, it also provides an entirely novel perspective on relational properties of continuous data and, in the present example, on the molecular heterogeneity of cancer. Our implementation is available on GitHub: this https URL.
Method to estimate the approximate samples size that yield a certain number of significant GWAS signals in polygenic traits

To argue for increased sample collection for disorders without significant findings, researchers retorted to plotting, for multiple traits, the number of significant findings as a function of the sample size. However, for polygenic traits, the prevalence of the disorder confounds the relationship between the number of significant findings and the sample size. To adjust the number of significant findings for prevalence, we develop a method that uses the expected noncentrality of the contrast between liabilities of cases and controls. We empirically find that, when compared to the sample size, this measure is a better predictor of number of significant findings. Even more, we show that the sample size effect on the number of signals is explained by the noncetrality measure. Finally, we provide an R script to estimate the required sample size (non-centrality) needed to yield a pre-specified number of significant findings.
Application of EMI and FDR sensors to assess the fraction of transpirable soil water over an olive grove

Accurate soil water status measurements across spatial and temporal scales are still a challenging task, specifically at intermediate spatial (0.1–10 ha) and temporal (minutes to days) scales. Consequently, a gap in knowledge limits our understanding of the reliability of the spatial measurements and its practical applicability in agricultural water management. This paper compares the cumulative EM38 (Geonics Ltd., Mississauga, ON, Canada) response collected by placing the sensor above ground with the corresponding soil water content obtained by integrating the values measured with an FDR (frequency domain reflectometry) sensor. In two field areas, characterized by different soil clay content, two Diviner 2000 access tubes (1.2 m) were installed and used to quantify the dimensionless fraction of transpirable soil water (FTSW). After the calibration, the work proposes the combined use of the FDR and electromagnetic induction (EMI) sensors to measure and map FTSW. A strong correlation (R2 = 0.86) between FTSW and EM38 bulk electrical conductivity was found. As a result, field changes of FTSW are due to the variability of soil water content and soil texture. As with the data acquired in the field, more structured patterns occurred after a wetting event, indicating the presence of subsurface flow or root water uptake paths. After assessing the relationship between the soil and crop water status, the FTSW domain includes a critical value, estimated around 0.38, below which a strong reduction of relative transpiration can be recognized.
Reinforced Adversarial Neural Computer for de Novo Molecular Design

In silico modeling is a crucial milestone in modern drug design and development. Although computer-aided approaches in this field are well-studied, the application of deep learning methods in this research area is at the beginning. In this work, we present an original deep neural network (DNN) architecture named RANC (Reinforced Adversarial Neural Computer) for the de novo design of novel small-molecule organic structures based on the generative adversarial network (GAN) paradigm and reinforcement learning (RL). As a generator RANC uses a differentiable neural computer (DNC), a category of neural networks, with increased generation capabilities due to the addition of an explicit memory bank, which can mitigate common problems found in adversarial settings. The comparative results have shown that RANC trained on the SMILES string representation of the molecules outperforms its first DNN-based counterpart ORGANIC by several metrics relevant to drug discovery: the number of unique structures, passing medicinal chemistry filters (MCFs), Muegge criteria, and high QED scores. RANC is able to generate structures that match the distributions of the key chemical features/descriptors (e.g., MW, logP, TPSA) and lengths of the SMILES strings in the training data set. Therefore, RANC can be reasonably regarded as a promising starting point to develop novel molecules with activity against different biological targets or pathways. In addition, this approach allows scientists to save time and covers a broad chemical space populated with novel and diverse compounds.
Space qualification of the optical filter assemblies for the ICESat-2/ATLAS instrument

The Advanced Topographic Laser Altimeter System (ATLAS) will be the only instrument on the Ice, Cloud, and Land Elevation Satellite -2 (ICESat-2). ICESat-2 is the 2nd-generation of the orbiting laser altimeter ICESat, which will continue polar ice topography measurements with improved precision laser-ranging techniques. In contrast to the original ICESat design, ICESat-2 will use a micro-pulse, multi-beam approach that provides dense cross-track sampling to help scientists determine a surface's slope with each pass of the satellite. The ATLAS laser will emit visible, green laser pulses at a wavelength of 532 nm and a rate of 10 kHz and will be split into 6 beams. A set of six identical, thermally tuned optical filter assemblies (OFA) will be used to remove background solar radiation from the collected signal while transmitting the laser light to the detectors. A seventh assembly will be used to monitor the laser center wavelength during the mission. In this paper, we present the design and optical performance measurements of the ATLAS OFA in air and in vacuum prior to their integration on the ATLAS instrument.
Psychological Flexibility as a Moderator of the Relationships between Job Demands and Resources and Occupational Well-being

Abstract The aim of this study was to identify the relations of job demands (work overload) and job resources (social support and autonomy) with subjective job well-being (job satisfaction, positive affects, negative affects), as well as the moderating role of personal resources (psychological flexibility at work) in such relationships. The sample consisted of 4,867 Brazilian workers, of both sexes, with ages ranging from 18 to 67 years. Structural equation modelling showed that the work overload was negatively associated with job satisfaction (β = –.06; p < .001) and positively with negative affects (β = .24; p < .001); autonomy was positively associated with satisfaction (β = .08; p < .001) and negative affects (β = .08; p < .001); social support was positively associated with satisfaction (β = .17; p < .001) and positive affects (β = .20; p < .001), and negatively with negative affects (β = –.21; p < .001); psychological flexibility moderated the relationships of overload with satisfaction (β = .04; p < .05) and negative affects (β = .08; p < .001); autonomy with positive affects (β = –.06; p < .001) and social support with negative affects (β = .08; p < .001). These results are discussed from perspective of a job demands-resources theory, especially with respect to the relevance of personal resources for the promotion of occupational well-being.