Miracle-dz/UniFAR-FTUs huggingface dataset:
Quantized Dehydration and the Determinants of Selectivity in the NaChBac Bacterial Sodium Channel

A discrete electrostatic/diffusion model has been developed to describe the selective permeation of ion channels, based on ionic Coulomb blockade (ICB) and quantised dehydration (QD). It has been applied to describe selectivity phenomena measured in the bacterial NaChBac sodium channel and some of its mutants. Site-directed mutagenesis and the whole-cell patch-clamp technique were used to investigate how the value $Q_f$ of the fixed charge at the selectivity filter (SF) affected both valence and alike-charge selectivity. The new ICB/QD model predicts that increasing ${Q_f}$ should lead to a shift of selectivity sequences towards larger ion sizes and charges, a result that agrees with the present experiments and with earlier work. Comparison of the model with experimental data provides evidence for an {\it effective charge} $Q_f^*$ at the SF that is smaller in magnitude than the nominal $Q_f$ corresponding to the charge on the isolated protein residues. Furthermore, $Q_f^*$ was different for aspartate and glutamate charged rings and also depended on their position within the SF. It is suggested that protonation of the residues within the restricted space is an important factor in significantly reducing the effective charge of the EEEE ring. Values of $Q_f^*$ derived from experiments on the anomalous mole fraction effect (AMFE) agree well with expectations based on the ICB/QD model and have led to the first clear demonstration of the expected ICB oscillations in Ca$^{2+}$ conduction as a function of the fixed charge. Pilot studies of the dependence of Ca$^{2+}$ conduction on pH are consistent with the predictions of the model. \\
Behavioral, transcriptomic and epigenetic responses to social challenge in honey bees

Understanding how social experiences are represented in the brain and shape future responses is a major challenge in the study of behavior. We addressed this problem by studying behavioral, transcriptomic and epigenetic responses to intrusion in honey bees. Previous research showed that initial exposure to an intruder provokes an immediate attack; we now show that this also leads to longer‐term changes in behavior in the response to a second intruder, with increases in the probability of responding aggressively and the intensity of aggression lasting 2 and 1 h, respectively. Previous research also documented the whole‐brain transcriptomic response; we now show that in the mushroom bodies (MBs) there are 2 waves of gene expression, the first highlighted by genes related to cytoskeleton remodeling, and the second highlighted by genes related to hormones, stress response and transcription factors (TFs). Overall, 16 of 37 (43%) of the TFs whose cis‐motifs were enriched in the promoters of the differentially expressed genes (DEGs) were also predicted from transcriptional regulatory network analysis to regulate the MB transcriptional response, highlighting the strong role played by a relatively small subset of TFs in the MB's transcriptomic response to social challenge. Whole brain histone profiling showed few changes in chromatin accessibility in response to social challenge; most DEGs were ‘ready’ to be activated. These results show how biological embedding of a social challenge involves temporally dynamic changes in the neurogenomic state of a prominent region of the insect brain that are likely to influence future behavior.
Improving Health Care Management in Primary Care for Homeless People: A Literature Review

Background: Homeless people have poorer health status than the general population. They need complex care management, because of associated medical troubles (somatic and psychiatric) and social difficulties. We aimed to describe the main characteristics of the primary care programs that take care of homeless people, and to identify which could be most relevant. Methods: We performed a literature review that included articles which described and evaluated primary care programs for homeless people. Results: Most of the programs presented a team-based approach, multidisciplinary and/or integrated care. They often proposed co-located services between somatic health services, mental health services and social support services. They also tried to answer to the specific needs of homeless people. Some characteristics of these programs were associated with significant positive outcomes: tailored primary care organizations, clinic orientation, multidisciplinary team-based models which included primary care physicians and clinic nurses, integration of social support, and engagement in the community’s health. Conclusions: Primary health care programs that aimed at taking care of the homeless people should emphasize a multidisciplinary approach and should consider an integrated (mental, somatic and social) care model.
Improving Transferability of Adversarial Examples With Input Diversity

Though CNNs have achieved the state-of-the-art performance on various vision tasks, they are vulnerable to adversarial examples --- crafted by adding human-imperceptible perturbations to clean images. However, most of the existing adversarial attacks only achieve relatively low success rates under the challenging black-box setting, where the attackers have no knowledge of the model structure and parameters. To this end, we propose to improve the transferability of adversarial examples by creating diverse input patterns. Instead of only using the original images to generate adversarial examples, our method applies random transformations to the input images at each iteration. Extensive experiments on ImageNet show that the proposed attack method can generate adversarial examples that transfer much better to different networks than existing baselines. By evaluating our method against top defense solutions and official baselines from NIPS 2017 adversarial competition, the enhanced attack reaches an average success rate of 73.0%, which outperforms the top-1 attack submission in the NIPS competition by a large margin of 6.6%. We hope that our proposed attack strategy can serve as a strong benchmark baseline for evaluating the robustness of networks to adversaries and the effectiveness of different defense methods in the future. Code is available at https://github.com/cihangxie/DI-2-FGSM.
Quadruplet Network With One-Shot Learning for Fast Visual Object Tracking

In the same vein of discriminative one-shot learning, Siamese networks allow recognizing an object from a single exemplar with the same class label. However, they do not take advantage of the underlying structure of the data and the relationship among the multitude of samples as they only rely on the pairs of instances for training. In this paper, we propose a new quadruplet deep network to examine the potential connections among the training instances, aiming to achieve a more powerful representation. We design a shared network with four branches that receive a multi-tuple of instances as inputs and are connected by a novel loss function consisting of pair loss and triplet loss. According to the similarity metric, we select the most similar and the most dissimilar instances as the positive and negative inputs of triplet loss from each multi-tuple. We show that this scheme improves the training performance. Furthermore, we introduce a new weight layer to automatically select suitable combination weights, which will avoid the conflict between triplet and pair loss leading to worse performance. We evaluate our quadruplet framework by model-free tracking-by-detection of objects from a single initial exemplar in several visual object tracking benchmarks. Our extensive experimental analysis demonstrates that our tracker achieves superior performance with a real-time processing speed of 78 frames/s. Our source code is available.
Stable Finite Element Algorithms for Analysing the Vertebral Artery

The research described in this thesis began with a single long-term objective: modelling of the vertebral artery during chiropractic manipulation of the cervical spine. Although chiropractic treatment has become prevalent, the possible correlation between neck manipulation and subsequent stroke in patients has been the subject of debate without resolution. Past research has been qualitative or statistical, whereas resolution demands a fundamental understanding of the associated mechanics. Analysis in the thesis begins with a study of the anatomy and properties pertinent to the chiropractic problem. This indicates that the complexity of the problem will necessitate a long-term multidisciplinary effort including a nonlinear finite element formulation effective in analysing image data for soft tissue modelled as nearly incompressible. This leads to an assessment of existing finite element methods and the conclusion that new equation solving techniques are needed to ensure numerical stability. Three techniques for effectively eliminating the source of numerical instability are developed and demonstrated with the aid of original finite element codes. Two of the methods are derived as modifications of matrix decomposition algorithms, while the third method constitutes a new finite element formulation. In addition, the understanding gained in developing these methods is used to produce a theorem for assessing a different but related problem: deformation of a nearly incompressible material subjected to a single concentrated force. Throughout the thesis, an interdisciplinary path from chiropractic problem to numerical algorithms is outlined, and results are in the form of mathematical proofs and derivations of both existing and new methods. ii
Anti-proteinuric and anti-coagulatory effects of camostat mesilate in azotemic diabetics.

The present study was conducted on 8 patients with advanced diabetic nephropathy who showed a significant reduction of proteinuria through ACE inhibition. Camostat mesilate, one of the most potent protease inhibitors developed for oral use, was administered to these patients at a daily dose of 600 mg starting after 4 weeks of ACE inhibitor administration. Laboratory data were obtained 1) just before the ACE inhibition, 2) after 4 weeks of the ACE inhibitor single treatment, and 3) after another 4 weeks of the additional treatment with camostat mesilate. The urinary protein excretion decreased from 1) 10.1 +/- 1.3 to 2) 7.3 +/- 1.1, and 3) 4.6 +/- 0.9 g/day [mean +/- SEM; significance of difference 1)-2), p less than 0.05; 2)-3), p less than 0.01], and the serum total protein values increased from 1) 5.0 +/- 0.3 to 2) 5.2 +/- 0.2, and 3) 5.4 +/- 0.3 g/dl [1)-3), p less than 0.05]. The plasma levels of fibrinogen, and of E fragment and D-dimer of FDP changed from 1) 476 +/- 43 to 2) 477 +/- 41, and 3) 374 +/- 33 mg/dl [2)-3), p less than 0.01], from 1) 125 +/- 19 to 2) 147 +/- 27, and 3) 104 +/- 30 ng/ml [2)-3), p less than 0.05], and from 1) 261 +/- 60 to 2) 272 +/- 86, and 3) 185 +/- 56 ng/ml [2)-3), p less than 0.05], respectively. (ABSTRACT TRUNCATED AT 250 WORDS)
Genomic Selection Outperforms Marker Assisted Selection for Grain Yield and Physiological Traits in a Maize Doubled Haploid Population Across Water Treatments

To increase genetic gain for tolerance to drought, we aimed to identify environmentally stable QTL in per se and testcross combination under well-watered (WW) and drought stressed (DS) conditions and evaluate the possible deployment of QTL using marker assisted and/or genomic selection (QTL/GS-MAS). A total of 169 doubled haploid lines derived from the cross between CML495 and LPSC7F64 and 190 testcrosses (tester CML494) were evaluated in a total of 11 treatment-by-population combinations under WW and DS conditions. In response to DS, grain yield (GY) and plant height (PHT) were reduced while time to anthesis and the anthesis silking interval (ASI) increased for both lines and hybrids. Forty-eight QTL were detected for a total of nine traits. The allele derived from CML495 generally increased trait values for anthesis, ASI, PHT, the normalized difference vegetative index (NDVI) and the green leaf area duration (GLAD; a composite trait of NDVI, PHT and senescence) while it reduced trait values for leaf rolling and senescence. The LOD scores for all detected QTL ranged from 2.0 to 7.2 explaining 4.4 to 19.4% of the observed phenotypic variance with R2 ranging from 0 (GY, DS, lines) to 37.3% (PHT, WW, lines). Prediction accuracy of the model used for genomic selection was generally higher than phenotypic variance explained by the sum of QTL for individual traits indicative of the polygenic control of traits evaluated here. We therefore propose to use QTL-MAS in forward breeding to enrich the allelic frequency for a few desired traits with strong additive QTL in early selection cycles while GS-MAS could be used in more mature breeding programs to additionally capture alleles with smaller additive effects.
Morphological and physicochemical evaluation of the propranolol HCl–Eudragit® RS100 electrosprayed nanoformulations

Abstract The aim of this study was to fabricate propranolol hydrochloride (Prop. HCl) (as a water-soluble drug):Eudragit® RS100 (Eud) nanobeads and nanofibres applying the electrospraying method as an economical and one-step technique. Different ratios of Prop. HCl:Eud (i.e. 1:5 and 1:10) at total solution concentrations of 10–20% W/V were investigated. The FE-SEM studies revealed that morphology and size of the samples were highly affected by the solution concentration; so that, the nanobeads (a mean diameter of 82.9 nm) were formed in low concentration and at the highest concentration of the solution, nanofibres (a mean diameter of 232.3 nm) were resulted. Besides the morphological changes, the size of processed nanoformulations was increased with an increment of the solution concentrations. X-ray diffraction results as well as DSC thermograms clearly indicated that the drug crystallinity decreased in the electrosprayed samples. Furthermore, in vitro dissolution test showed that the electrosprayed samples had relatively slower release patterns toward the pure drug and physical mixtures, where the samples with the drug:polymer ratio of 1:10 indicated a faster release rate toward 1:5 ratio; nevertheless, the concentration of the injected formulations did not remarkably impressed the release behaviours. The current study established the suitability of electrospraying method in the fabrication of the water-soluble drugs nanobeads/nanofibres; however, in vivo effectiveness of the prepared nanoformulations should be meticulously considered.
A General Method to Simulate the Electromagnetic Characteristics of HTS Maglev Systems by Finite Element Software

For practical maglev systems, the mutual effects among the bulk superconductor and the permanent magnet are primarily investigated to provide useful implications for the design. This paper proposed a general simulation method to demonstrate the electromagnetic behaviors of a levitation system. The basics properties including the distributions of the induced current and the levitation/guidance force of a bulk superconductor have been calculated while moving in the nonuniform magnetic field generated by a permanent magnet guideway. This numerical method is based on solving the partial differential equations time dependently and adapted to the commercial finite element software COMSOL Multiphysics 5.3. It is worth mentioning that relative movements are solved to simulate more real test scenarios with the moving mesh and automatic remeshing in COMSOL. Simulation results are intuitive for the generation of electromagnetic behaviors and show a good consistency with previous experimental data. We conclude that this simulation method can be a powerful tool for researchers and engineers to investigate analogous problems with a greater level of flexibility and expandability.
Molecular Phylogeography and Evolutionary History of Poropuntius huangchuchieni (Cyprinidae) in Southwest China

Background The evolution of the Yunnan Plateau’s drainages network during the Pleistocene was dominated by the intense uplifts of the Qinghai-Tibetan Plateau. In the present study, we investigated the association between the evolutionary histories of three main drainage systems and the geographic patterns of genetic differentiation of Poropuntius huangchuchieni. Methodology/Principal Findings We sequenced the complete sequences of mitochondrial control region for 304 specimens and the sequences of Cytochrome b gene for 15 specimens of the species P. huangchuchieni and 5 specimens of Poropuntius opisthoptera. Phylogenetic analysis identified five major lineages, of which lineages MK-A and MK-B constrained to the Mekong River System, lineages RL and LX to the Red River System, and lineage SW to the Salween River System. The genetic distance and network analysis detected significant divergences among these lineages. Mismatch distribution analysis implied that the population of P. huangchuchieni underwent demographic stability and the lineage MK-B, sublineages MK-A1 and LX-1 underwent a recent population expansion. The divergence of the 5 major lineages was dated back to 0.73–1.57 MYA. Conclusions/Significance Our results suggest that P. opisthoptera was a paraphyletic group of P. huangchuchieni. The phylogenetic pattern of P. huangchuchieni was mostly associated with the drainage’s structures and the geomorphological history of the Southwest Yunnan Plateau. Also the differentiation of the major lineages among the three drainages systems coincides with the Kunlun-Yellow River Movement (1.10–0.60 MYA). The genetic differentiation within river basins and recent demographical expansions that occurred in some lineages and sublineages are consistent with the palaeoclimatic oscillations during the Pleistocene. Additionally, our results also suggest that the populations of P. huangchuchieni had keep long term large effective population sizes and demographic stability in the recent evolutionary history, which may be responsible for the high genetic diversity and incomplete lineages sorting of Poropuntius huangchuchieni.
Assembly and activation of dynein–dynactin by the cargo adaptor protein Hook3

Metazoan cytoplasmic dynein moves processively along microtubules with the aid of dynactin and an adaptor protein that joins dynein and dynactin into a stable ternary complex. Here, we have examined how Hook3, a cargo adaptor involved in Golgi and endosome transport, forms a motile dynein-dynactin complex. We show that the conserved Hook domain interacts directly with the dynein light intermediate chain 1 (LIC1). By solving the crystal structure of the Hook domain and using structure-based mutagenesis, we identify two conserved surface residues that are each critical for LIC1 binding. Hook proteins with mutations in these residues fail to form a stable dynein-dynactin complex, revealing a crucial role for LIC1 in this interaction. We also identify a region of Hook3 specifically required for an allosteric activation of processive motility. Our work reveals the structural details of Hook3’s interaction with dynein and offers insight into how cargo adaptors form processive dynein-dynactin motor complexes.
Parallel comparative proteomics and phosphoproteomics reveal that cattle myostatin regulates phosphorylation of key enzymes in glycogen metabolism and glycolysis pathway

MSTN-encoded myostatin is a negative regulator of skeletal muscle development. Here, we utilized the gluteus tissues from MSTN gene editing and wild type Luxi beef cattle which are native breed of cattle in China, performed tandem mass tag (TMT) -based comparative proteomics and phosphoproteomics analyses to investigate the regulatory mechanism of MSTN related to cellular metabolism and signaling pathway in muscle development. Out of 1,315 proteins, 69 differentially expressed proteins (DEPs) were found in global proteomics analysis. Meanwhile, 149 differentially changed phosphopeptides corresponding to 76 unique phosphorylated proteins (DEPPs) were detected from 2,600 identified phosphopeptides in 702 phosphorylated proteins. Bioinformatics analyses suggested that majority of DEPs and DEPPs were closely related to glycolysis, glycogenolysis, and muscle contractile fibre processes. The global discovery results were validated by Multiple Reaction Monitoring (MRM)-based targeted peptide quantitation analysis, western blotting, and muscle glycogen content measurement. Our data revealed that increase in abundance of key enzymes and phosphorylation on their regulatory sites appears responsible for the enhanced glycogenolysis and glycolysis in MSTN−/−. The elevated glycogenolysis was assocaited with an enhanced phosphorylation of Ser1018 in PHKA1, and Ser641/Ser645 in GYS1, which were regulated by upstream phosphorylated AKT-GSK3β pathway and highly consistent with the lower glycogen content in gluteus of MSTN−/−. Collectively, this study provides new insights into the regulatory mechanisms of MSTN involved in energy metabolism and muscle growth.
Clinical Aspects of Foot Health in Individuals with Alzheimer’s Disease

Alzheimer’s disease (AD) shows a marked presence of physiologic changes and the start or aggravation of underlying diseases such as physical frailty in diverse anatomical regions. It is believed to have a particularly harmful effect on the health of the foot. We examined the foot health status in older persons with AD, with a specific focus on the extent to which people with AD may be using inadequate footwear in old age. Seventy-three community-dwelling people with probable, mild to moderate AD aged 65–95 years were recruited from a center of excellence for AD. A single trained physician evaluated health status and foot conditions. Current shoe and foot length and width measurements were taken using a calibrated Brannock device. The results indicate that sixty-five participants (89.04%) suffered from feet problems. Also, only twenty-two subjects (30.14%) used the correct shoes in width and size related with the morphology of their feet. Fifty-one participants (69.86%) were using incorrect shoes in length or width. The present study revealed that peoples with AD had a high presence of foot health problems. Also, the use of inappropriate shoes revealed measurable differences of association between shoe size and the morphology of the foot.
TorsinA controls TAN line assembly and the retrograde flow of dorsal perinuclear actin cables during rearward nuclear movement

The nucleus is positioned toward the rear of most migratory cells. In fibroblasts and myoblasts polarizing for migration, retrograde actin flow moves the nucleus rearward, resulting in the orientation of the centrosome in the direction of migration. In this study, we report that the nuclear envelope–localized AAA+ (ATPase associated with various cellular activities) torsinA (TA) and its activator, the inner nuclear membrane protein lamina-associated polypeptide 1 (LAP1), are required for rearward nuclear movement during centrosome orientation in migrating fibroblasts. Both TA and LAP1 contributed to the assembly of transmembrane actin-associated nuclear (TAN) lines, which couple the nucleus to dorsal perinuclear actin cables undergoing retrograde flow. In addition, TA localized to TAN lines and was necessary for the proper mobility of EGFP-mini–nesprin-2G, a functional TAN line reporter construct, within the nuclear envelope. Furthermore, TA and LAP1 were indispensable for the retrograde flow of dorsal perinuclear actin cables, supporting the recently proposed function for the nucleus in spatially organizing actin flow and cytoplasmic polarity. Collectively, these results identify TA as a key regulator of actin-dependent rearward nuclear movement during centrosome orientation.