Miracle-dz/UniFAR-FTUs huggingface dataset:
Statistical physics of bulk and confined ionic liquids

Room temperature ionic liquids are molten salts at ambient temperature. This thesis is concerned with the structure of room temperature ionic liquids both in the bulk and in confinement. A particular theme is the rich statistical physics of such systems, which is primarily due to strong Coulomb correlations. We begin by examining the structure of ionic liquids in the bulk. One of the most important questions in understanding the structure of ionic liquids is whether ions are truly "free" and mobile (a concentrated ionic solution), or are rather bundled up as ion pairs (a dilute solution of free ions dissolved in a sea of ion pairs). We propose a mathematical model for the thermodynamics and kinetics of ion pairing in ionic liquids. Our model reveals that roughly 2/3 of ions are free, whilst those ion pairs that do exist are short- lived. We conclude that ionic liquids ought to be considered to be concentrated, rather than dilute, electrolytes. We then examine the structure of ionic liquids confined between charged surfaces. Motivated by surface force balance experiments, we use a 1D Coulomb gas model to study ionic liquids confined between charged mica surfaces. We show that the disjoining pressure– surface separation curve depends on the fugacity (the bulk cohesive energy) of the ionic liquid, and the electrostatic interaction energy of ions at closest approach. The model shows good qualitative agreement with experimental data, with all parameters independently estimated without fitting. We then turn our attention to a single layer of ionic liquid ions confined between metal surfaces, and develop a mean field model for equilibrium charge storage in a nanoporous supercapacitor. The development of nanoporous supercapacitors is hindered by the perceived tradeoff between capacitance, power delivery and reversible charging - a trilemma. Our model identifies the affinity of ions to the pore wall as a key parameter that controls charging behaviour. From this, we elucidate a region of "ionophilicity" in which the capacitance-power-hysteresis trilemma can be avoided. The non-equilibrium physics of ion transport in ionic liquids is then considered. We derive a novel system of continuum electrokinetic equations for ionic liquids that is based ￼on coarse graining a simple exclusion process defined on a lattice. The resulting dynamical equations are written as a gradient flow with a degenerate mobility function. This form of the mobility function gives rise to novel charging behaviours that are qualitatively different to those known in electrolytic solutions. Finally, we consider active non-equilibrium fluids, in which energy is continuously consumed from the surrounding environment. Those systems are inherently far from thermo- dynamic equilibrium. By developing a top-down description for non-equilibrium systems with the fluctuation spectrum as the central quantity, we show that the form of the disjoin- ing force may reveal crucial elements of the microscopic physics. Our framework explains the long-ranged force observed in recent molecular dynamics simulation of active Brownian particles.
Barriers to treatment adjustment within a treat to target strategy in rheumatoid arthritis: a secondary analysis of the TRACTION trial

Objectives Adherence to a treat to target (TTT) strategy is a recommended paradigm for RA; however, research shows there are many barriers to implementation. We conducted a trial to improve TTT implementation, and herein examine barriers to treatment adjustment within TTT among patient visits not in agreement with the TTT paradigm. Methods Chart review assessed TTT implementation based on documentation of four items: designation of a treatment target, recording a disease activity measure, shared-decision making when applicable and adjusting treatment when disease activity was not at target. A treatment decision not in agreement with the TTT paradigm was defined as lack of treatment adjustment when disease activity was not at the pre-determined treatment target. Providers were encouraged to report the barriers to treatment change; these were categorized and analysed by study staff. Multiple barriers were possible for one visit. Results Eighty-three visits not in agreement with the TTT strategy were observed in 74 patients, during which 90 reported barriers to treatment adjustment were noted. Common barriers to adjusting treatment included patient preference in 37.1% of visits and elevated disease activity measure despite no objective evidence of active RA in 38.6% of visits. Conclusion An elevated disease activity measure not reflective of RA disease activity and patient preference are the two leading barriers to treatment adjustment to TTT in RA. Understanding barriers to adherence should guide interventions aimed at using better markers of disease activity and improving alignment with patient preference, with the overarching goal of enhancing TTT adherence.
Boosting of Mucosal Immunity After Fractional-Dose Inactivated Poliovirus Vaccine

Background Inactivated poliovirus vaccine (IPV) boosts mucosal immunity in persons previously vaccinated with oral poliovirus vaccine (OPV). We assessed whether fractional-dose IPV (fIPV, 1/5th of full dose) administered intradermally also boosts mucosal immunity. Methods Children 10-12 years old were enrolled in Sri Lanka and randomized to receive one dose IPV, fIPV, or no IPV vaccine. One month later, they received OPV challenge. Blood was collected at enrolment and before challenge; stool was collected at 3, 7, and 14 days post-challenge. Sera were analysed for presence of poliovirus neutralizing antibodies; stool was analysed for poliovirus. Results We analysed 304/309 (98%) enrolled subjects. There were 16/97 (16%), 9/99 (9%), and 72/95 (76%) subjects excreting poliovirus after challenge in the IPV, fIPV and "No IPV Vaccine" study arms, respectively (P < .001 for comparison of IPV [or fIPV] vs "No IPV Vaccine"; P = .1 for comparisons of fIPV vs IPV). Relative decrease in excretion prevalence was 80% and 88% to IPV and fIPV, respectively, compared with the "No IPV Vaccine" control arm. Conclusions Single fIPV dose boosted mucosal immunity to a similar degree as single full dose of IPV. This finding provides further evidence in support of fIPV for poliovirus outbreak response at the time of IPV global supply shortage. Clinical trials registration Australia New Zealand Clinical Trial Registry ACTRN12616000124437p.
The Man in the Shadows Has Something to Say.

REFERENCES 1. Sehgal A: Haemodynamically unstable preterm infant: An unresolved management conundrum. Eur J Pediatr 2011; 170:1237–1245 2. Vogt W, Läer S: Treatment for paediatric low cardiac output syndrome: Results from the European EuLoCOS-Paed survey. Arch Dis Child 2011; 96:1180–1186 3. Vogt W, Läer S: Prevention for pediatric low cardiac output syndrome: Results from the European survey EuLoCOS-Paed. Paediatr Anaesth 2011; 21:1176–1184 4. Cavigelli-Brunner A, Hug MI, Dave H, et al: Prevention of Low Cardiac Output Syndrome After Pediatric Cardiac Surgery: A Double Blind Randomized Clinical Pilot Study Comparing Dobutamine and Milrinone. Pediatr Crit Care Med 2018; 19:619–625 5. Burkhardt BE, Rucker B, Fau Stiller G, et al: Prophylactic milrinone for the prevention of low cardiac output syndrome and mortality in children undergoing surgery for congenital heart disease. Cochrane Database Syst Rev 2015; (3):CD009515 6. Samiee-Zafarghandy S, Raman SR, van den Anker JN, et al; Best Pharmaceuticals for Children Act—Pediatric Trials Network Administrative Core Committee: Safety of milrinone use in neonatal intensive care units. Early Hum Dev 2015; 91:31–35 7. Majure DT, Greco T, Greco M, et al: Meta-analysis of randomized trials of effect of milrinone on mortality in cardiac surgery: An update. J Cardiothorac Vasc Anesth 2013; 27:220–229 8. Hoffman TM, Wernovsky G, Atz AM, et al: Prophylactic intravenous use of milrinone after cardiac operation in pediatrics (PRIMACORP) study. Prophylactic intravenous use of milrinone after cardiac operation in pediatrics. Am Heart J 2002; 143:15–21 9. Hoffman TM, Wernovsky G, Atz AM, et al: Efficacy and safety of milrinone in preventing low cardiac output syndrome in infants and children after corrective surgery for congenital heart disease. Circulation 2003; 107:996–1002
Extending IoT/M2M system scalability by network slicing

In this research, we have extended our initial effort in cloud-based IoT/M2M system scalability and developed a more robust solution by considering diverse QoS requirements from various IoT/M2M traffic patterns. Though our initial effort created a highly scalable architecture for IoT/M2M platforms based on OpenStack, it treated all IoT/M2M traffic without any discrepancy in the same underlying network (i.e. in the same network slice). Now, by leveraging software-defined networking in OpenStack and by using our traffic-slice optimal matching algorithm, we can direct different types of IoT traffic to feasible network slices in terms of QoS. Our experiments show that when compared with a system without network slicing, our scalability system performs better in terms of response time, power consumption, and computational cost.
Clarin-1 gene transfer rescues auditory synaptopathy in model of Usher syndrome

Clarin-1, a tetraspan-like membrane protein defective in Usher syndrome type IIIA (USH3A), is essential for hair bundle morphogenesis in auditory hair cells. We report a new synaptic role for clarin-1 in mouse auditory hair cells elucidated by characterization of Clrn1 total (Clrn1ex4–/–) and postnatal hair cell–specific conditional (Clrn1ex4fl/fl Myo15-Cre+/–) knockout mice. Clrn1ex4–/– mice were profoundly deaf, whereas Clrn1ex4fl/fl Myo15-Cre+/– mice displayed progressive increases in hearing thresholds, with, initially, normal otoacoustic emissions and hair bundle morphology. Inner hair cell (IHC) patch-clamp recordings for the 2 mutant mice revealed defective exocytosis and a disorganization of synaptic F-actin and CaV1.3 Ca2+ channels, indicative of a synaptopathy. Postsynaptic defects were also observed, with an abnormally broad distribution of AMPA receptors associated with a loss of afferent dendrites and defective electrically evoked auditory brainstem responses. Protein-protein interaction assays revealed interactions between clarin-1 and the synaptic CaV1.3 Ca2+ channel complex via the Cav&bgr;2 auxiliary subunit and the PDZ domain–containing protein harmonin (defective in Usher syndrome type IC). Cochlear gene therapy in vivo, through adeno-associated virus–mediated Clrn1 transfer into hair cells, prevented the synaptic defects and durably improved hearing in Clrn1ex4fl/fl Myo15-Cre+/– mice. Our results identify clarin-1 as a key organizer of IHC ribbon synapses, and suggest new treatment possibilities for USH3A patients.
Autologous Adoptive T-cell Therapy for Recurrent or Drug-resistant Cytomegalovirus Complications in Solid Organ Transplant Recipients: A Single-arm Open-label Phase I Clinical Trial

Background Opportunistic infections including cytomegalovirus (CMV) are a major cause of morbidity and mortality in solid organ transplant (SOT) recipients. The recurrent and protracted use of antiviral drugs with eventual emergence of drug resistance represents a significant constraint to therapy. Although adoptive T-cell therapy has been successfully used in hematopoietic stem cell transplant recipients, its extension to the SOT setting poses a considerable challenge because of the inhibitory effects of immunosuppressive drugs on the virus-specific T-cell response in vivo and the perceived risk of graft rejection. Methods In this prospective study, 22 SOT recipients (13 renal and 8 lung and 1 heart transplants) with recurrent or ganciclovir-resistant CMV infection were recruited, and 13 of them were treated with in vitro-expanded autologous CMV-specific T cells. These patients were monitored for safety, clinical symptoms, and immune reconstitution. Results Autologous CMV-specific T-cell manufacture was attempted for 21 patients, and was successful in 20. The use of this adoptive immunotherapy was associated with no therapy-related serious adverse events. Eleven (84%) of the 13 treated patients showed improvement in symptoms, including complete resolution or reduction in DNAemia and CMV-associated end-organ disease and/or the cessation or reduced use of antiviral drugs. Furthermore, four of these patients showed coincident increased frequency of CMV-specific T cells in peripheral blood after completion of T-cell therapy. Conclusions The data presented here demonstrate for the first time the clinical safety of CMV-specific adoptive T-cell therapy and its potential therapeutic benefit for SOT recipients with recurrent and/or drug-resistant CMV infection or disease. Clinical Trials Registration ACTRN12613000981729.
What the brain ‘Likes’: neural correlates of providing feedback on social media

Abstract Evidence increasingly suggests that neural structures that respond to primary and secondary rewards are also implicated in the processing of social rewards. The ‘Like’—a popular feature on social media—shares features with both monetary and social rewards as a means of feedback that shapes reinforcement learning. Despite the ubiquity of the Like, little is known about the neural correlates of providing this feedback to others. In this study, we mapped the neural correlates of providing Likes to others on social media. Fifty-eight adolescents and young adults completed a task in the MRI scanner designed to mimic the social photo-sharing app Instagram. We examined neural responses when participants provided positive feedback to others. The experience of providing Likes to others on social media related to activation in brain circuity implicated in reward, including the striatum and ventral tegmental area, regions also implicated in the experience of receiving Likes from others. Providing Likes was also associated with activation in brain regions involved in salience processing and executive function. We discuss the implications of these findings for our understanding of the neural processing of social rewards, as well as the neural processes underlying social media use.
Revisiting bacterial volatile-mediated plant growth promotion: lessons from the past and objectives for the future

Abstract Background Bacterial volatile compounds (BVCs) are important mediators of beneficial plant–bacteria interactions. BVCs promote above-ground plant growth by stimulating photosynthesis and sugar accumulation and by modulating phytohormone signalling. These compounds also improve below-ground mineral uptake and modify root system architecture. Scope We review advances in our understanding of the mode of action and practical applications of BVCs since the discovery of BVC-mediated plant growth promotion in 2003. We also discuss unanswered questions about the identity of plant receptors, the effectiveness of combination of two or more BVCs on plant growth, and the potential side effects of these compounds for human and animal health. Conclusion BVCs have good potential for use as biostimulants and protectants to improve plant health. Further advances in the development of suitable technologies and preparing standards and guidelines will help in the application of BVCs in crop protection and health.
Prevalence of Methicillin Resistant Staphylococcus aureus and Antibiotic Susceptibility Pattern in a Tertiary Hospital in Nepal.

BACKGROUND Methicillin resistant Staphylococcus aureus is a global health challenge nowadays creating problem in antibiotic therapy. This study was aimed to generate resistance pattern of Methicillin resistant Staphylococcus aureus to various antibiotics in order to formulate antibiotic policy for control of Methicillin resistant Staphylococcus aureus in Nepal. METHODS This was a cross-sectional study conducted at the department of Clinical Microbiology, Nepal Medical College Teaching Hospital, from April 2015 to March 2016. A total of 142 S. aureus isolated from various clinical specimens. were screened for Methicillin resistant Staphylococcus aureus by cefoxitin disc method according to Clinical and Laboratory Standards Institute guidelines. RESULTS Out of 142 S. aureus isolates, 30 (21.1%) were detected as Methicillin resistant Staphylococcus aureus by cefoxitin disc method. Most of the Methicillin resistant Staphylococcus aureus (25/30) were isolated from pus which were collected from OPD patients. Antibiotic sensitivity pattern showed all Methicillin resistant Staphylococcus aureus isolates were sensitive to vancomycin. CONCLUSIONS Prevalence of Methicillin resistant Staphylococcus aureus was found to be 21.1%, and all Methicillin resistant Staphylococcus aureus appear 100% sensitive to vancomycin.
SAG12, a Major Cysteine Protease Involved in Nitrogen Allocation during Senescence for Seed Production in Arabidopsis thaliana

SAG12 is the most widely used senescence-associated reference gene for characterizing leaf senescence, and the increase in SAG12 protein during leaf senescence is remarkable. However, the role of this cysteine protease in N remobilization and the leaf senescence process remains unclear. The role of SAG12 has been poorly investigated and the few reports dealing with this are somewhat controversial. Indeed, sag12 Arabidopsis mutants have not shown any phenotype, while OsSAG12-1 and OsSAG12-2 overexpression in rice moderates senescence progression. Therefore, this study aims at clarifying the role of the SAG12 cysteine protease during the entire plant life span and during leaf senescence. Arabidopsis thaliana plants knocked-out for the SAG12 gene (sag12) did not exhibit any special phenotypic traits when grown under optimal nitrogen supply (HN), suggesting that other cysteine proteases could provide compensatory effects. Moreover, for the first time, this study shows that aspartate protease activity is significantly increased in sag12. Among the putative aspartate proteases involved, a CND41-like aspartate protease has been identified. Under low nitrogen (LN) availability, when inducible proteolytic systems are not sufficient to cope with SAG12 depletion, a decrease in yield is observed. Altogether, these results show that SAG12 (and perhaps also aspartate proteases) could be involved in RuBisCO degradation during the leaf senescence associated with seed filling.
Are serum concentrations of vitamin B-12 causally related to cardiometabolic risk factors and disease? A Mendelian randomization study.

Background Several observational studies have shown that low serum vitamin B-12 is associated with increased body mass index (BMI) and adverse cardiometabolic outcomes. However, it is unclear if these associations reflect a causal effect of vitamin B-12 on cardiometabolic risk factors and diseases, latent confounding, or reverse causality. Objectives The aims of this study were to investigate 1) the possible causal relation between vitamin B-12 and indicators of body fat, lipid, and glucose variables; type 2 diabetes (T2D); and cardiovascular disease by using a 2-sample Mendelian randomization (MR) method and 2) the possible pleiotropic role of fucosyltransferase 2 (FUT2). Design We selected 11 single nucleotide polymorphisms (SNPs) robustly associated with serum concentrations of vitamin B-12 in a previous genomewide association study (GWAS) in 45,576 individuals. We performed 2-sample MR analyses of the relation between vitamin B-12 and cardiometabolic risk factors and diseases with the use of publicly available GWAS summary statistics for 15 outcomes in ≤339,224 individuals. The robustness of results was tested with sensitivity analyses by using MR Egger regression and weighted-median estimation, and by performing additional analyses excluding a variant in the FUT2 gene, which may be pleiotropic. Results We found a suggestive causal relation between vitamin B-12 and fasting glucose and β cell function [homeostatic model assessment (HOMA) of β cell function (HOMA-B)]. However, we found no evidence that serum concentrations of vitamin B-12 were causally related to BMI, waist-to-hip ratio, plasma leptin, body fat, fasting insulin, insulin resistance (from HOMA of insulin resistance), glycated hemoglobin, triglycerides, T2D, coronary artery disease, or HDL, LDL, or total cholesterol. Conclusions We found no evidence that serum concentrations of vitamin B-12 are causally related to body weight or the majority of cardiometabolic outcomes investigated. However, vitamin B-12 may have a causal effect on fasting glucose and HOMA-B, although these results will require replication in large independent data sets. This trialwas registered at http://www.isrctn. com/ISRCTN47414943 as ISRCTN47414943.
Developmental Exposure to Low Concentrations of Organophosphate Flame Retardants Causes Life-Long Behavioral Alterations in Zebrafish

As the older class of brominated flame retardants (BFRs) are phased out of commercial use because of findings of neurotoxicity with developmental exposure, a newer class of flame retardants have been introduced, the organophosphate flame retardants (OPFRs). Presently, little is known about the potential for developmental neurotoxicity or the behavioral consequences of OPFR exposure. Our aim was to characterize the life-long neurobehavioral effects of 4 widely used OPFRs using the zebrafish model. Zebrafish embryos were exposed to 0.1% DMSO (vehicle control); or one of the following treatments; isopropylated phenyl phosphate (IPP) (0.01, 0.03, 0.1, 0.3 µM); butylphenyl diphenyl phosphate (BPDP) (0.003, 0.03, 0.3, 3 µM); 2-ethylhexyl diphenyl phosphate (EHDP) (0.03, 0.3, 1 µM); isodecyl diphenyl phosphate (IDDP) (0.1, 0.3, 1, 10 µM) from 0- to 5-days postfertilization. On Day 6, the larvae were tested for motility under alternating dark and light conditions. Finally, at 5-7 months of age the exposed fish and controls were tested on a battery of behavioral tests to assess emotional function, sensorimotor response, social interaction and predator evasion. These tests showed chemical-specific short-term effects of altered motility in larvae in all of the tested compounds, and long-term impairment of anxiety-related behavior in adults following IPP, BPDP, or EHDP exposures. Our results show that OPFRs may not be a safe alternative to the phased-out BFRs and may cause behavioral impacts throughout the lifespan. Further research should evaluate the risk to mammalian experimental models and humans.