Miracle-dz/UniFAR-FTUs huggingface dataset:
Settling Velocities of Fractal Aggregates

Aggregates generated in water and wastewater treatment systems and those found in natural systems are fractal and therefore have different scaling properties than assumed in settling velocity calculations using Stokes' law. In order to demonstrate that settling velocity models based on impermeable spheres do not accurately relate aggregate size, porosity and settling velocity for highly porous fractal aggregates, we generated fractal aggregates by coagulation of latex microspheres in paddle mixers and analyzed each aggregate individually for its size, porosity, and settling velocity. Settling velocities of these aggregates were on average 4−8.3 times higher than those predicted using either an impermeable sphere model (Stokes' law) or a permeable sphere model that specified aggregate permeability for a homogeneous distribution of particles within an aggregate. Fractal dimensions (D) derived from size−porosity relationships for the three batches of aggregates were 1.78 ± 0.10, 2.19 ± 0.12 and 2.25 ± 0.10.
Epstein-Barr virus nuclear antigen 3C (EBNA3C) interacts with the metabolism sensing C-terminal binding protein (CtBP) repressor to upregulate host genes

Epstein-Barr virus (EBV) infection is associated with the development of specific types of lymphoma and some epithelial cancers. EBV infection of resting B-lymphocytes in vitro drives them to proliferate as lymphoblastoid cell lines (LCLs) and serves as a model for studying EBV lymphomagenesis. EBV nuclear antigen 3C (EBNA3C) is one of the genes required for LCL growth and previous work has suggested that suppression of the CDKN2A encoded tumor suppressor p16INK4A and possibly p14ARF is central to EBNA3C’s role in this growth transformation. To directly assess whether loss of p16 and/or p14 was sufficient to explain EBNA3C growth effects, we used CRISPR/Cas9 to disrupt specific CDKN2A exons in EBV transformed LCLs. Disruption of p16 specific exon 1α and the p16/p14 shared exon 2 were each sufficient to restore growth in the absence of EBNA3C. Using EBNA3C conditional LCLs knocked out for either exon 1α or 2, we identified EBNA3C induced and repressed genes. By trans-complementing with EBNA3C mutants, we determined specific genes that require EBNA3C interaction with RBPJ or CtBP for their regulation. Unexpectedly, interaction with the CtBP repressor was required not only for repression, but also for EBNA3C induction of many host genes. Contrary to previously proposed models, we found that EBNA3C does not recruit CtBP to the promoters of these genes. Instead, our results suggest that CtBP is bound to these promoters in the absence of EBNA3C and that EBNA3C interaction with CtBP interferes with the repressive function of CtBP, leading to EBNA3C mediated upregulation.
Modulation of a protein-folding landscape revealed by AFM-based force spectroscopy notwithstanding instrumental limitations

Significance Atomic force microscopy (AFM) is widely applied to unfold proteins. Using advanced cantilevers in a commercial AFM to improve stability and precision, we unfolded and then refolded an individual fast-folding, mechanically labile protein—a technically challenging sample—thousands of times. To address concerns that the measured dynamics of such proteins are dominated by the AFM assay, we modulated the protein’s folding rate using pH. Kinetic analysis demonstrated changes in free-energy landscape parameters with pH, despite the reconstructed landscape being dominated by the assay. Hence, AFM using advanced cantilevers can yield biophysical insight into proteins, even if they unfold at low force. Single-molecule force spectroscopy is a powerful tool for studying protein folding. Over the last decade, a key question has emerged: how are changes in intrinsic biomolecular dynamics altered by attachment to μm-scale force probes via flexible linkers? Here, we studied the folding/unfolding of α3D using atomic force microscopy (AFM)–based force spectroscopy. α3D offers an unusual opportunity as a prior single-molecule fluorescence resonance energy transfer (smFRET) study showed α3D’s configurational diffusion constant within the context of Kramers theory varies with pH. The resulting pH dependence provides a test for AFM-based force spectroscopy’s ability to track intrinsic changes in protein folding dynamics. Experimentally, however, α3D is challenging. It unfolds at low force (<15 pN) and exhibits fast-folding kinetics. We therefore used focused ion beam–modified cantilevers that combine exceptional force precision, stability, and temporal resolution to detect state occupancies as brief as 1 ms. Notably, equilibrium and nonequilibrium force spectroscopy data recapitulated the pH dependence measured using smFRET, despite differences in destabilization mechanism. We reconstructed a one-dimensional free-energy landscape from dynamic data via an inverse Weierstrass transform. At both neutral and low pH, the resulting constant-force landscapes showed minimal differences (∼0.2 to 0.5 kBT) in transition state height. These landscapes were essentially equal to the predicted entropic barrier and symmetric. In contrast, force-dependent rates showed that the distance to the unfolding transition state increased as pH decreased and thereby contributed to the accelerated kinetics at low pH. More broadly, this precise characterization of a fast-folding, mechanically labile protein enables future AFM-based studies of subtle transitions in mechanoresponsive proteins.
A retrospective comparison of cognitive performance in individuals with advanced Parkinson’s Disease in Hong Kong and Canada

Abstract A deeper understanding of the cross-cultural applicability of cognitive tests across countries and cultures is needed to better equip neuropsychologists for the assessment of patients from diverse backgrounds. Our study compared cognitive test scores in patients with advanced Parkinson’s disease (PD) at the Prince of Wales Hospital (n = 63; Hong Kong) and the Foothills Medical Center (n = 20; Calgary, Canada). The groups did not differ in age or sex (p > .05), but Western patients had significantly more years of education (M = 14.2, SD = 2.7) than Asian patients (M = 10.33, SD = 4.4). Cognitive tests administered to both groups included: digit span, verbal fluency (animals), the Boston Naming Test, and verbal memory (California Verbal Learning Test or Chinese Auditory Verbal Learning Test). Testing was completed before and 12 months after deep brain stimulation surgery. Results showed cognitive performance was similar across time, but significant group differences were found on digit span forward (longer among patients from Hong Kong; F(1, 75) = 44.155, p < . 001) and the Boston Naming Test (higher percent spontaneous correct among patients from Canada; F(1, 62) = 7.218, p = . 009, η 2 = 0.104), after controlling for age, sex, and years of education. In conclusion, our findings provide preliminary support for the similarity of Chinese versions of tests originally developed for Western populations. Also, we caution that some aspects of testing may be susceptible to cultural bias and therefore warrant attention in clinical practice and refinement in future test development for Asian patients.
Cellular and molecular changes that predispose skin in chronic spinal cord injury to pressure ulcer formation

Patients with spinal cord injury have a predisposition to develop pressure ulcers. Specific characteristics of the patients' skin potentially involved have not yet been identified. The purpose of this investigation was to determine whether loss of neuronal control affects cellular and molecular homeostasis in the skin. Intact afflicted skin, wound edge of pressure ulcers, and control skin were analysed. Platelets, transforming growth factor‐β1, and activin A were identified by immunohistochemistry. Transforming growth factor‐β‐like activity was determined by bioassay, and gene expression by DNA microarray analysis or RT‐PCR. In afflicted skin, enhanced platelet extravasation was detected. Transforming growth factor‐β1 and activin A accumulated in the dermal‐epidermal junction zone. Transforming growth factor‐β‐like activity and activin A expression were increased in intact afflicted skin (compared to control skin) and were further enhanced in pressure ulcers. In vitro, activity was generated by fibroblast‐epithelial cell interactions, which also induced activin A. Thus, loss of neuronal control in spinal cord injury appears to trigger inappropriate wound healing processes in the patients' skin. Plasma leakage and increased transforming growth factor‐β‐like activity combined with shear forces potentially enhance the risk for pressure ulcer formation.
Evidence supporting a time-limited hippocampal role in retrieving autobiographical memories

Significance The hippocampus is central to healthy memory function, yet its necessity for remembering events from the distant past remains unclear. Prominent hypotheses alternatively suggest a time-limited or an indefinite role. fMRI evidence, typically based on silent in-scanner recall, has been equivocal, possibly because it provides sparse information of the content being remembered. Here, we asked fMRI participants to verbally describe recent and remote memories. After accounting for neural activity associated with the moment-to-moment memory content of recalled memories, we observed a temporally graded pattern of activity within the posterior hippocampus and found that recent—but not remote—event recall significantly activated the hippocampus relative to a non-autobiographical control task. Our findings support a time-limited hippocampal role in autobiographical memory. The necessity of the human hippocampus for remote autobiographical recall remains fiercely debated. The standard model of consolidation predicts a time-limited role for the hippocampus, but the competing multiple trace/trace transformation theories posit indefinite involvement. Lesion evidence remains inconclusive, and the inferences one can draw from functional MRI (fMRI) have been limited by reliance on covert (silent) recall, which obscures dynamic, moment-to-moment content of retrieved memories. Here, we capitalized on advances in fMRI denoising to employ overtly spoken recall. Forty participants retrieved recent and remote memories, describing each for approximately 2 min. Details associated with each memory were identified and modeled in the fMRI time-series data using a variant of the Autobiographical Interview procedure, and activity associated with the recall of recent and remote memories was then compared. Posterior hippocampal regions exhibited temporally graded activity patterns (recent events > remote events), as did several regions of frontal and parietal cortex. Consistent with predictions of the standard model, recall-related hippocampal activity differed from a non-autobiographical control task only for recent, and not remote, events. Task-based connectivity between posterior hippocampal regions and others associated with mental scene construction also exhibited a temporal gradient, with greater connectivity accompanying the recall of recent events. These findings support predictions of the standard model of consolidation and demonstrate the potential benefits of overt recall in neuroimaging experiments.
Compensating Local Magnifications in Atom Probe Tomography for Accurate Analysis of Nano-Sized Precipitates

Abstract Abstract Local magnification artifacts in atom probe tomography (APT) caused by multiphase materials with heterogeneous evaporation behavior are a well-known problem. In particular, the analysis of the exact size, shape, and composition of small precipitates is, therefore, not trivial. We performed numerical simulations of APT measurements to predict the reconstructed morphology of precipitates with contrasting evaporation thresholds. Based on a statistical approach that avoids coarse graining, the simulated data are evaluated to develop a model for the calculation of the original size of the precipitates. The model is tested on experimental APT data of precipitates with a higher and lower evaporation field in a ferritic alloy. Accurate sizes, proven by a complementary investigation by transmission electron microscopy, are obtained. We show further, how the size information can be used to obtain compositional information of the smallest precipitates and present a new methodology to determine a correct in-depth scaling of the APT reconstruction in case no complementary geometric information about the specimen exists or if no lattice planes are visible in the reconstruction.
Targeted Therapies for Metabolic Myopathies Related to Glycogen Storage and Lipid Metabolism: a Systematic Review and Steps Towards a ‘Treatabolome’

Background: Metabolic myopathies are a heterogenous group of muscle diseases typically characterized by exercise intolerance, myalgia and progressive muscle weakness. Effective treatments for some of these diseases are available, but while our understanding of the pathogenesis of metabolic myopathies related to glycogen storage, lipid metabolism and β-oxidation is well established, evidence linking treatments with the precise causative genetic defect is lacking. Objective: The objective of this study was to collate all published evidence on pharmacological therapies for the aforementioned metabolic myopathies and link this to the genetic mutation in a format amenable to databasing for further computational use in line with the principles of the “treatabolome” project. Methods: A systematic literature review was conducted to retrieve all levels of evidence examining the therapeutic efficacy of pharmacological treatments on metabolic myopathies related to glycogen storage and lipid metabolism. A key inclusion criterion was the availability of the genetic variant of the treated patients in order to link treatment outcome with the genetic defect. Results: Of the 1,085 articles initially identified, 268 full-text articles were assessed for eligibility, of which 87 were carried over into the final data extraction. The most studied metabolic myopathies were Pompe disease (45 articles), multiple acyl-CoA dehydrogenase deficiency related to mutations in the ETFDH gene (15 articles) and systemic primary carnitine deficiency (8 articles). The most studied therapeutic management strategies for these diseases were enzyme replacement therapy, riboflavin, and carnitine supplementation, respectively. Conclusions: This systematic review provides evidence for treatments of metabolic myopathies linked with the genetic defect in a computationally accessible format suitable for databasing in the treatabolome system, which will enable clinicians to acquire evidence on appropriate therapeutic options for their patient at the time of diagnosis.
Trans-generational viral transmission and immune priming are dose-dependent.

It is becoming increasingly apparent that trans-generational immune priming (i.e. the transfer of the parental immunological experience to its progeny resulting in offspring protection from pathogens that persist across generations) is a common phenomenon not only in vertebrates, but also invertebrates. Likewise, it is known that covert pathogenic infections may become 'triggered' into an overt infection by various stimuli, including exposure to heterologous infections. Yet rarely have both phenomena been explored in parallel. Using as a model system the African armyworm (Spodoptera exempta), an eruptive agricultural pest, and its endemic dsDNA virus (Spodoptera exempta nucleopolyhedrovirus, SpexNPV), the aim of this study was to explore the impact of parental inoculating-dose on trans-generational pathogen transmission and immune priming (in its broadest sense). Larvae were orally-challenged with one of five doses of SpexNPV and survivors from these treatments were mated and their offspring monitored for viral mortality. Offspring from parents challenged with low viral doses showed evidence of 'immune priming' (i.e. enhanced survival following SpexNPV challenge); in contrast, offspring from parents challenged with higher viral doses exhibited greater susceptibility to viral challenge. Most offspring larvae died of the virus they were orally-challenged with; in contrast, most offspring from parents that had been challenged with the highest doses were killed by the vertically-transmitted virus (90%) and not the challenge virus. These results demonstrate that the outcome of a potentially lethal virus challenge is critically dependent on the level of exposure to virus in the parental generation - either increasing resistance at very low parental viral doses (consistent with trans-generational immune-priming) or increasing susceptibility at higher parental doses (consistent with virus triggering). We discuss the implications of these findings for understanding both natural epizootics of baculoviruses and for using them as biological control agents.
Use of antimicrobials for food animals in New Zealand: updated estimates to identify a baseline to measure targeted reductions

ABSTRACT Aim To describe the use of antimicrobial drugs for food animals in New Zealand, based on sales data reported to government for 2005–2018, to provide a baseline to determine the success of measures to reduce antimicrobial use for food animals and to compare usage to selected European countries. Methods Data were sourced from official government and industry reports to update previous estimates of use (as amount sold) of antimicrobial products applied to animals in New Zealand. The data included antimicrobial sales and animal populations, weighted where appropriate by breed and age class. Antimicrobial use was estimated based on the amount of active ingredient sold, per kg of animal biomass standardised to the probable weight at time of treatment or lifetime average but not slaughter weight (population correction unit; PCU). New Zealand data for 2017 and 2018 were adjusted to account only for antimicrobials used for farm animals by discounting horticulture use, companion animal use and export. Results Between 2014 and 2018 the estimated usage of antimicrobials in animals flattened to a 5-year rolling average of 10.40 mg/PCU. New data on use for companion animals and on exports of zinc bacitracin and tylosin, included previously in the gross New Zealand values, allow a more refined estimate of use of antimicrobials in food animals of 10.21 mg/PCU in 2018, the third lowest rate of use for countries reporting by the same methodology. The intensive industries of pigs and poultry combined use more than 500 mg/PCU whereas the extensive red meat and dairy industries use an estimated 6.25 mg/PCU. New Zealand uses proportionally more cephalosporins and macrolides, two of the critically important antimicrobial groups, when compared with European countries, but less quinolones. The most obvious difference is the extensive use of zinc bacitracin and tylosin fed to pigs and poultry in New Zealand but not in the European Union. Conclusions Use of antimicrobials in food animals has stabilised to a rate of approximately 10.2 mg/PCU. This baseline should be used by the animal health industry to measure future success in its efforts to reduce and make more refined use of antimicrobial drugs as New Zealand works to deliver the government’s Antimicrobial Resistance Action Plan. High rates of use of zinc bacitracin and some critically important macrolides represent clear targets in attempts to reduce usage.
Illness Perception, Perceived Social Support and Quality of Life in Patients with Pemphigus Vulgaris: What Should Dermatologists Know?

Data regarding the impact of psychological factors in patients with pemphigus is sparse. This study evaluated the correlation of demographic, clinical, and psychological parameters with quality of life in 58 patients with pemphigus. Illness perception showed a realistic view, with the highest scores for cyclical course (3.35 ± 0.09) and treatment control (3.08 ± 0.06). Mean scores for perceived social support were relatively high from family and significant others (5.89 ± 0.18 and 5.66 ± 0.23, accordingly), and relatively low from friends (4.55 ± 0.24). There were no correlations between demographic, clinical parameters, perceived social support, and Dermatology Life Quality Index. Beliefs in cyclical course, emotional influence, psychological cause, and treatment control correlated significantly with quality of life. Stronger beliefs in self-control, chronicity, and accidental cause predicted higher quality of life, while stronger beliefs in cyclical course, psychological cause, and risk factors predicted lower quality of life. In order to enhance QoL, dermatologists should deliver the message to the patients that pemphigus is a chronic disease rather than cyclical and unexpected, and stress the patients’ role in controlling it.
N‐acetyl cysteine co‐treatment abates perfluorooctanoic acid‐induced reproductive toxicity in male rats

Perfluorooctanoic acid is a synthetic perfluoroalkyl—persistent in the environment and toxic to humans. N‐acetylcysteine is a pro‐drug of both amino acid l‐cysteine and glutathione—a non‐enzymatic antioxidant. N‐acetylcysteine serves as an antidote for paracetamol poisoning and alleviates cellular oxidative and inflammatory stressors. We investigated N‐acetylcysteine role against reproductive toxicity in male Wistar rats (weight: 140–220 g; 10 weeks old) posed by perfluorooctanoic acid exposure. Randomised rat cohorts were dosed both with perfluorooctanoic acid (5 mg/kg; p.o) or co‐dosed with N‐acetylcysteine (25 and 50 mg/kg p.o) for 28 days. Sperm physiognomies, biomarkers of testicular function and reproductive hormones, oxidative stress and inflammation were evaluated. Co‐treatment with N‐acetylcysteine significantly (p < .05) reversed perfluorooctanoic acid‐mediated decreases in reproductive enzyme activities, and adverse effect on testosterone, luteinising and follicle‐stimulating hormone concentrations. N‐acetylcysteine treatment alone, improved sperm motility, count and viability, and reduced total sperm abnormalities. Co‐treatment with N‐acetylcysteine mitigated perfluorooctanoic acid‐induced alterations in sperm function parameters. N‐acetylcysteine abated (p < .05) perfluorooctanoic acid‐induced oxidative stress in experimental rats testes and epididymis, and generally improved antioxidant enzyme activities and cellular thiol levels. Furthermore, N‐acetylcysteine suppressed inflammatory responses and remedied perfluorooctanoic acid‐mediated histological injuries in rat. Cooperatively, N‐acetylcysteine enhanced reproductive function in perfluorooctanoic acid dosed rats, by lessening oxidative and nitrative stressors and mitigated inflammatory responses in the examined organ.
Development of biliary stent applying the antibacterial activity of silver: A literature review.

BACKGROUND Endoscopic transpapillary stenting is commonly performed in patients with obstructive jaundice caused by a biliary stricture. Although the plastic stent (PS) is widely used for biliary drainage because of the low-cost and easy procedure, patency is short after placement in the bile duct because of the small diameter. Dysfunction of PS is primarily caused by biliary sludge that forms as a result of bacterial adhesion and subsequent biofilm formation on the inner surface of the stent. It is well known that silver ions have excellent antibacterial activity against a wide range of microorganisms. OBJECTIVE This review provides an overview and perspective of the significance of silver-coated biliary stents. METHODS We collected literature regarding silver-coated biliary stents, and reviewed the current research/development status and discussed their possible usefulness. RESULTS To date, several in vivo/vitro studies evaluated the patency of silver-blended or silver-coated biliary stents. These studies suggested that the silver coating on a PS was likely to prolong the patency period. CONCLUSION The development of biliary stents using silver is expected to prolong stent patency and prevent frequent stent replacement.