Miracle-dz/UniFAR-FTUs huggingface dataset:
AcuC, a histone deacetylase, contributes to the pathogenicity of Aeromonas hydrophila

The interactions of pathogens and phagocytes are complex. Our study demonstrated that Aeromonas hydrophila B11 can survive in the macrophagocytes of Tilapia mossambica. To explore the regulatory processes of A. hydrophila survival in the macrophagocytes, we used the mini‐Tn10 transposon mutagenesis system to build a mutant library by mixing Escherichia coli Sm10 (pLOFKm) and A. hydrophila B11. In total, 102 mutant colonies were detected, and 11 of them showed reduced survival in macrophagocytes. The mutant with the most severe phenotype, AM73, was chosen for further research. The ORF interrupted by mini‐Tn10 in AM73 was approximately 960 bp and was deposited in GenBank with the accession number SRP049226. The 319 amino acid protein encoded by the ORF showed a high degree of identity (89%) with proteins in the histone deacetylase/AcuC/AphA family of A. hydrophila subsp. hydrophila ATCC7966. A strain (AC73) in which the acuC mutation was complemented was constructed by generating the recombinant expression plasmid pACYC184‐acuC and introducing it into the AM73 mutant strain. Our experiments revealed that strain AM73 was deficient in biofilm formation, adhesion, survival in macrophagocytes, and virulence compared with A. hydrophila B11, and all of these biological properties were improved in strain AC73. The expression of 10 significant virulence genes was significantly inhibited in strain AM73. The results indicated that AcuC was an important regulatory protein contributing to the pathogenicity of A. hydrophila.
The fluid dynamics of simultaneous irrigation with negative pressure wound therapy

Saline irrigation has been shown to be both experimentally and clinically efficacious in decreasing bacterial contamination as well as decreasing infection rates. The dynamics of irrigation delivery fall into two primary categories: simultaneous and intermittent irrigation. An important component to irrigation therapy is distribution of irrigation solution to hard‐to‐reach areas of a wound bed, including undermining and fissure‐like structures. Here we test the effectiveness of simultaneous irrigation to fill the irregular structures of a wound bed. In order to visualise the dynamic movement of irrigation solution, three‐dimensional wound models were constructed using clear synthetic ballistic gel. Wounds with the aforementioned characteristics were carved into the ballistic gel with varying area, depth and volume. All three wounds were dressed as per manufacturer's instructions. Data demonstrate that simultaneous irrigation is effective in reaching all parts of a wound bed in wound models that have both undermining and tunnelling, and irrigation effectively saturates bridged wounds. Finally, this study shows that there is constant turnover of irrigation solution in the wound that is driven more by administration volume and less by flow rate. These data show that simultaneous irrigation is an effective technique for delivering irrigation solution to both simple and complex wounds.
Highly compact robots for inspection of power plants

This paper reports on a 3 years applied research project dealing with several inspection scenarios of power plants and resulting in many robot prototypes and 3 main achievements. The project is a common effort between industry and university, including ALSTOM together with researchers from the 2 Swiss Federal Institutes of Technology. The goal is to generate knowledge and transfer technology to the industry in the field of robot inspection. The method is to collect commercial scenarios, study them, make some exploratory prototypes, select the best scenarios and develop enhanced prototypes for the most promising applications. The 3 most evolved robots are MagneBike for steam chest, AirGapCrawler for generators and TubeCrawler for boiler tube. The supporting technologies that have been developed are adhesion, locomotion, system integration and localization.
Nusinersen versus Sham Control in Infantile‐Onset Spinal Muscular Atrophy

Background Spinal muscular atrophy is an autosomal recessive neuromuscular disorder that is caused by an insufficient level of survival motor neuron (SMN) protein. Nusinersen is an antisense oligonucleotide drug that modifies pre–messenger RNA splicing of the SMN2 gene and thus promotes increased production of full‐length SMN protein. Methods We conducted a randomized, double‐blind, sham‐controlled, phase 3 efficacy and safety trial of nusinersen in infants with spinal muscular atrophy. The primary end points were a motor‐milestone response (defined according to results on the Hammersmith Infant Neurological Examination) and event‐free survival (time to death or the use of permanent assisted ventilation). Secondary end points included overall survival and subgroup analyses of event‐free survival according to disease duration at screening. Only the first primary end point was tested in a prespecified interim analysis. To control the overall type I error rate at 0.05, a hierarchical testing strategy was used for the second primary end point and the secondary end points in the final analysis. Results In the interim analysis, a significantly higher percentage of infants in the nusinersen group than in the control group had a motor‐milestone response (21 of 51 infants [41%] vs. 0 of 27 [0%], P<0.001), and this result prompted early termination of the trial. In the final analysis, a significantly higher percentage of infants in the nusinersen group than in the control group had a motor‐milestone response (37 of 73 infants [51%] vs. 0 of 37 [0%]), and the likelihood of event‐free survival was higher in the nusinersen group than in the control group (hazard ratio for death or the use of permanent assisted ventilation, 0.53; P=0.005). The likelihood of overall survival was higher in the nusinersen group than in the control group (hazard ratio for death, 0.37; P=0.004), and infants with a shorter disease duration at screening were more likely than those with a longer disease duration to benefit from nusinersen. The incidence and severity of adverse events were similar in the two groups. Conclusions Among infants with spinal muscular atrophy, those who received nusinersen were more likely to be alive and have improvements in motor function than those in the control group. Early treatment may be necessary to maximize the benefit of the drug. (Funded by Biogen and Ionis Pharmaceuticals; ENDEAR ClinicalTrials.gov number, NCT02193074.)
The Multifaceted Impact of Peroxiredoxins on Aging and Disease.

SIGNIFICANCE Peroxiredoxins (Prxs), a family of thiol-associated peroxidases, are purported to play a major role in sensing and managing hydrogen peroxide concentrations and transducing peroxide-derived signals. Recent Advances: Prxs can act as detoxifying factors and impart effects to cells that can be either sparing or suicidal. Advances have been made to address the qualitative changes in Prx function in response to quantitative changes in the signal level and to understand how Prx activity could be affected by their own substrates. Here we rationalize the basis for both positive and negative effects on signaling pathways and cell physiology, summarizing data from model organisms, including invertebrates. CRITICAL ISSUES Resolving the relationship between the promiscuous behavior of reactive oxygen species and the specificity of Prxs toward different targets in redox-sensitive signaling pathways is a key area of research. Attempts to understand Prx function and underlying mechanisms were conducted in vitro or in vivo under nonphysiological conditions, leaving the physiological relevance yet to be defined. Other issues: Why despite the high degree of homology and similarities in subcellular and tissue distribution between Prxs do they display differential effects on signaling? How is the specificity of post-translational protein modifications determined? Other than chaperone-like activity, how do hyperoxidized Prxs function? FUTURE DIRECTIONS Genetic models with mutated catalytic and resolving cysteines should be further exploited to dissect the functional significance of individual Prxs in their different states together with their alternative reducing partners. Such an analysis may then be extended to help identify Prx-specific targets.
Double-Q Learning-Based DVFS for Multi-core Real-Time Systems

The Q-learning based DVFS selection algorithm has been used to lower energy consumption for system-level power management. However, this algorithm normally suffers from overestimation since it greedily uses maximum action value to approximate expected value, consequently fails to select the most appropriate DVFS method for real-time systems. In this article, we propose a Double-Q learning based DVFS selection algorithm to reduce energy consumption. In our scheme, instead of approximating actual action values with only one estimator, it implements Double-Q learning that applies two estimators to efficiently reduce overestimation, leading to an energy-aware scheme that can maintain a relatively stable and sufficient performance in action selection. We evaluate the performance of the proposed scheme through simulated data sets. Results demonstrate that our scheme can save more energy than the Q-learning based scheme while adapting to various system conditions and provide a more stable and accurate DVFS policy selection mechanism for multi-core real-time systems.
Differential expression and androgen regulation of microRNAs and metalloprotease 13 in breast cancer cells

MicroRNA molecules (miRNAs) play important roles in regulating cell behavior. The expression of certain miRNAs has been shown to be regulated by the androgen receptor (AR), which seems to have a critical role in the tumorigenic process of breast cancer. The differential expression of 84 miRNAs was first examined in three breast cancer cell lines: the luminal MCF‐7 and T47D cells and the molecular apocrine MDA‐MB‐453 cells. Analysis of basal expression of miRNAs revealed that each cell line had distinct miRNA expression where let‐7a and ‐7b were markers of MDA‐MB‐453 cells, whereas miR‐205 was a marker for the luminal cell lines. Treating the cells with the AR agonist, CI‐4AS‐1, resulted in unique alterations in the expression of specific miRNA among the three cell lines. Particularly, the expression of miR‐100 and miR‐125 was reduced in MDA‐MB‐453 cells by five and three folds, respectively. This effect was simultaneous with AR‐induced increase in the expression and extracellular release of metalloprotease‐13 (MMP13). Transfection of cells with either miR‐100 or miR‐125b negated the induction of MMP13 release. Additionally, AR activation induced a morphological alteration of MDA‐MB‐453 cells, which was blocked by miR‐125b only. Collectively, these data indicate that AR may control the biological behavior of breast cancer cells and protein expression via miRNAs.
Digging through the Obstruction: Insight into the Epithelial Cell Response to Respiratory Virus Infection in Patients with Cystic Fibrosis

ABSTRACT Respiratory virus infections are common but generally self-limiting infections in healthy individuals. Although early clinical studies reported low detection rates, the development of molecular diagnostic techniques by PCR has led to an increased recognition that respiratory virus infections are associated with morbidity and acute exacerbations of chronic lung diseases, such as cystic fibrosis (CF). The airway epithelium is the first barrier encountered by respiratory viruses following inhalation and the primary site of respiratory viral replication. Here, we describe how the airway epithelial response to respiratory viral infections contributes to disease progression in patients with CF and other chronic lung diseases, including the role respiratory viral infections play in bacterial acquisition in the CF patient lung.
Multicenter Noninferiority Evaluation of Hain GenoType MTBDRplus Version 2 and Nipro NTM+MDRTB Line Probe Assays for Detection of Rifampin and Isoniazid Resistance

ABSTRACT Less than 30% of multidrug-resistant tuberculosis (MDR-TB) patients are currently diagnosed, due to laboratory constraints. Molecular diagnostics enable rapid and simplified diagnosis. Newer-version line probe assays have not been evaluated against the WHO-endorsed Hain GenoType MTBDRplus (referred to as Hain version 1 [V1]) for the rapid detection of rifampin (RIF) and isoniazid (INH) resistance. A two-phase noninferiority study was conducted in two supranational reference laboratories to allow head-to-head comparisons of two new tests, Hain Genotype MTBDRplus version 2 (referred to as Hain version 2 [V2]) and Nipro NTM+MDRTB detection kit 2 (referred to as Nipro), to Hain V1. In phase 1, the results for 379 test strains were compared to a composite reference standard that used phenotypic drug susceptibility testing (DST) and targeted sequencing. In phase 2, the results for 644 sputum samples were compared to a phenotypic DST reference standard alone. Using a challenging set of strains in phase 1, the values for sensitivity and specificity for Hain V1, Hain V2, and Nipro, respectively, were 90.3%/98.5%, 90.3%/98.5%, and 92.0%/98.5% for RIF resistance detection and 89.1%/99.4%, 89.1%/99.4%, and 89.6%/100.0% for INH resistance detection. Testing of sputa in phase 2 yielded values for sensitivity and specificity of 97.1%/97.1%, 98.2%/97.8%, and 96.5%/97.5% for RIF and 94.4%/96.4%, 95.4%/98.8%, and 94.9%/97.6% for INH. Overall, the rates of indeterminate results were low, but there was a higher rate of indeterminate results with Nipro than with Hain V1 and V2 in samples with low smear grades. Noninferiority of Hain V2 and Nipro to Hain V1 was demonstrated for RIF and INH resistance detection in isolates and sputum specimens. These results serve as evidence for WHO policy recommendations on the use of line probe assays, including the Hain V2 and Nipro assays, for MDR-TB detection.
Kesan penambahan nanotiub karbon berbilang dinding ke atas kekonduksian terma polilaktik asid nanokomposit

Multi walled carbon nanotubes (MWCNT) hold the increasing interest in many different fields. To employ MWCNT as an effective reinforcement in order to enhance the thermal conductivity of polylactic acid (PLA) modified with liquid natural rubber (LNR), proper dispersion and appropriate interfacial adhesion between MWCNT and PLA/LNR have to be guaranteed. This paper used ultrasonic technique as the method to help to improve the dispersion of MWCNT in PLA/LNR matrix. The result shown that the sample with 3.5 wt. % of MWCNT provided higher thermal conductivity which is believe to be the optimum loading due to better dispersion of MWCNT in PLA/LNR matrix. The 4 wt. % of MWCNT shows decreasing of thermal conductivity due to the presence of agglomeration of MWCNT. The results confirmed by Scanning Electron Microscopy (SEM) micrograph. Fourier Transform Infrared (FTIR) spectra shown that there were no chemical changes happen.
Reversal agents: do we need to administer with neuromuscular monitoring – an observational study

Background and Aims: In clinical practice, in the majority of patients, recovery from the effect of muscle relaxants is assessed using subjective methods such as head lift, eye-opening, or by sustained hand grip after giving anticholinesterases (neostigmine) at the end of surgery. We planned a prospective observational cohort study to test the hypothesis that objective neuromuscular monitoring can help us in avoiding the use of anticholinesterases for reversal. Methods: The patients posted for surgery of <2 h duration were included in the study. The cohort of patients was formed on the basis of those who were exposed to objective neuromuscular monitoring of recovery (train-of-four [TOF] ratio of 0.9 or more; exposed group) and the patients who were not exposed to objective neuromuscular monitoring (non-exposed group) acting as a control. Using objective neuromuscular monitoring, the time required for recovery from muscle relaxation when neostigmine was not given for reversal was noted and it was then compared with that of the control group. Results: A total of 190 patients were enrolled over a period of 3 years. With the use of TOF ratio of 0.9 for extubation, patients safely recovered from neuromuscular blockade, without using neostigmine, with no difference in the mean recovery time (14.48 ± 1.138 min) as compared to the control group (12.14 ± 1.067 min, P = 0.139). There was no incidence of reintubation in post-operative period. Conclusion: With objective neuromuscular monitoring, we can ensure complete recovery from the neuromuscular blockade while avoiding the use of anticholinesterases.
Visual cue-specific craving is diminished in stressed smokers

ABSTRACT Background: Craving among smokers is increased by stress and exposure to smoking-related visual cues. However, few experimental studies have tested both elicitors concurrently and considered how exposures may interact to influence craving. Objective: The current study examined craving in response to stress and visual cue exposure, separately and in succession, in order to better understand the relationship between craving elicitation and the elicitor. Method: Thirty-nine smokers (21 males) who forwent smoking for 30 minutes were randomized to complete a stress task and a visual cue task in counterbalanced orders (creating the experimental groups); for the cue task, counterbalanced blocks of neutral, motivational control, and smoking images were presented. Self-reported craving was assessed after each block of visual stimuli and stress task, and after a recovery period following each task. Results: As expected, the stress and smoking images generated greater craving than neutral or motivational control images (p < .001). Interactions indicated craving in those who completed the stress task first differed from those who completed the visual cues task first (p < .05), such that stress task craving was greater than all image type craving (all p’s < .05) only if the visual cue task was completed first. Conversely, craving was stable across image types when the stress task was completed first. Conclusions: Findings indicate when smokers are stressed, visual cues have little additive effect on craving, and different types of visual cues elicit comparable craving. These findings may imply that once stressed, smokers will crave cigarettes comparably notwithstanding whether they are exposed to smoking image cues.
Aggregation landscapes of Huntingtin exon 1 protein fragments and the critical repeat length for the onset of Huntington’s disease

Significance Formation of inclusion bodies is the pathological hallmark of Huntington’s disease. Huntingtin exon 1-encoded protein fragments aggregate in inclusion bodies, causing disease onset in a length-dependent manner. Using energy landscape theory, the critical length for disease onset is predicted to be between 30 and 40. Huntington’s disease (HD) is a neurodegenerative disease caused by an abnormal expansion in the polyglutamine (polyQ) track of the Huntingtin (HTT) protein. The severity of the disease depends on the polyQ repeat length, arising only in patients with proteins having 36 repeats or more. Previous studies have shown that the aggregation of N-terminal fragments (encoded by HTT exon 1) underlies the disease pathology in mouse models and that the HTT exon 1 gene product can self-assemble into amyloid structures. Here, we provide detailed structural mechanisms for aggregation of several protein fragments encoded by HTT exon 1 by using the associative memory, water-mediated, structure and energy model (AWSEM) to construct their free energy landscapes. We find that the addition of the N-terminal 17-residue sequence (NT17) facilitates polyQ aggregation by encouraging the formation of prefibrillar oligomers, whereas adding the C-terminal polyproline sequence (P10) inhibits aggregation. The combination of both terminal additions in HTT exon 1 fragment leads to a complex aggregation mechanism with a basic core that resembles that found for the aggregation of pure polyQ repeats using AWSEM. At the extrapolated physiological concentration, although the grand canonical free energy profiles are uphill for HTT exon 1 fragments having 20 or 30 glutamines, the aggregation landscape for fragments with 40 repeats has become downhill. This computational prediction agrees with the critical length found for the onset of HD and suggests potential therapies based on blocking early binding events involving the terminal additions to the polyQ repeats.
Vitamin C promotes wound healing through novel pleiotropic mechanisms

Vitamin C (VitC) or ascorbic acid (AscA), a cofactor for collagen synthesis and a primary antioxidant, is rapidly consumed post‐wounding. Parenteral VitC administration suppresses pro‐inflammatory responses while promoting anti‐inflammatory and pro‐resolution effects in human/murine sepsis. We hypothesised that VitC could promote wound healing by altering the inflammatory, proliferative and remodelling phases of wound healing. Mice unable to synthesise VitC (Gulo−/−) were used in this study. VitC was provided in the water (sufficient), withheld from another group (deficient) and supplemented by daily intra‐peritoneal infusion (200 mg/kg, deficient + AscA) in a third group. Full thickness excisional wounds (6 mm) were created and tissue collected on days 7 and 14 for histology, quantitative polymerase chain reaction (qPCR) and Western blotting. Human neonatal dermal fibroblasts (HnDFs) were used to assess effects of In conclusion, VitC favorably on proliferation. Histological analysis showed improved wound matrix deposition and organisation in sufficient and deficient +AscA mice. Wounds from VitC sufficient and deficient + AscA mice had reduced expression of pro‐inflammatory mediators and higher expression of wound healing mediators. Supplementation of HnDF with AscA induced the expression of self‐renewal genes and promoted fibroblast proliferation. VitC favourably impacts the spatiotemporal expression of transcripts associated with early resolution of inflammation and tissue remodelling.