Molecular Density Functional Theory for water with liquid-gas coexistence and correct pressure

The solvation of hydrophobic solutes in water is special because liquid and gas are almost at coexistence. In the common hypernetted chain approximation to integral equations, or equivalently in the homogenous reference fluid of molecular density functional theory, coexistence is not taken into account. Hydration structures and energies of nanometer-scale hydrophobic solutes are thus incorrect. In this article, we propose a bridge functional that corrects this thermodynamic inconsistency by introducing a metastable gas phase for the homogeneous solvent. We show how this can be done by a third order expansion of the functional around the bulk liquid density that imposes the right pressure and the correct second order derivatives. Although this theory is not limited to water, we apply it to study hydrophobic solvation in water at room temperature and pressure and compare the results to all-atom simulations. With this correction, molecular density functional theory gives, at a modest computational cost, quantitative hydration free energies and structures of small molecular solutes like n-alkanes, and of hard sphere solutes whose radii range from angstroms to nanometers. The macroscopic liquid-gas surface tension predicted by the theory is comparable to experiments. This theory gives an alternative to the empirical hard sphere bridge correction used so far by several authors.Comment: 18 pages, 6 figure

SELF-REGULATION IN OLDER ADULTS: THE PRIORITIZATION OF EMOTION REGULATION

Despite having fewer cognitive resources, older adults regulate their emotions as well as, if not better than, younger adults. This study aimed to (1) test the limits of older adults’ emotion regulation capacity and (2) gain a better understanding of how older adults use their more limited resources to regulate their emotions. Participants included 48 healthy older adults aged 65-85 from the community and 50 healthy younger adults aged 18-25 from the student population. They were randomly assigned to one of four experimental groups involving an initial activity that was high or low in self-regulatory demand followed by a test task of emotion regulation or attention regulation. As expected, older adults performed equally as well as younger adults on the emotion regulation test task, though worse on the attention regulation test task. Using resting heart rate variability (HRV) as a physiological measure of self-regulatory capacity, older adults appeared to allocate more resources toward the emotion regulation task compared to the attention regulation task, and relative to younger adults. The results suggest that older adults maintain their emotion regulation capacity in part by allocating more resources toward emotion regulation goals

"So, Tell Me What Users Want, What They Really, Really Want!"

Equating users' true needs and desires with behavioural measures of 'engagement' is problematic. However, good metrics of 'true preferences' are difficult to define, as cognitive biases make people's preferences change with context and exhibit inconsistencies over time. Yet, HCI research often glosses over the philosophical and theoretical depth of what it means to infer what users really want. In this paper, we present an alternative yet very real discussion of this issue, via a fictive dialogue between senior executives in a tech company aimed at helping people live the life they `really' want to live. How will the designers settle on a metric for their product to optimise

Genome-wide association study for calving performance using high-density genotypes in dairy and beef cattle

peer-reviewedBackground Calving difficulty and perinatal mortality are prevalent in modern-day cattle production systems. It is well-established that there is a genetic component to both traits, yet little is known about their underlying genomic architecture, particularly in beef breeds. Therefore, we performed a genome-wide association study using high-density genotypes to elucidate the genomic architecture of these traits and to identify regions of the bovine genome associated with them. Results Genomic regions associated with calving difficulty (direct and maternal) and perinatal mortality were detected using two statistical approaches: (1) single-SNP (single nucleotide polymorphism) regression and (2) a Bayesian approach. Data included high-density genotypes on 770 Holstein-Friesian, 927 Charolais and 963 Limousin bulls. Several novel or previously identified genomic regions were detected but associations differed by breed. For example, two genomic associations, one each on chromosomes 18 and 2 explained 2.49 % and 3.13 % of the genetic variance in direct calving difficulty in the Holstein-Friesian and Charolais populations, respectively. Imputed Holstein-Friesian sequence data was used to refine the genomic regions responsible for significant associations. Several candidate genes on chromosome 18 were identified and four highly significant missense variants were detected within three of these genes (SIGLEC12, CTU1, and ZNF615). Nevertheless, only CTU1 contained a missense variant with a putative impact on direct calving difficulty based on SIFT (0.06) and Polyphen (0.95) scores. Using imputed sequence data, we refined a genomic region on chromosome 4 associated with maternal calving difficulty in the Holstein-Friesian population and found the strongest association with an intronic variant in the PCLO gene. A meta-analysis was performed across the three breeds for each calving performance trait to identify common variants associated with these traits in the three breeds. Our results suggest that a portion of the genetic variation in calving performance is common to all three breeds. Conclusion The genomic architecture of calving performance is complex and mainly influenced by many polymorphisms of small effect. We identified several associations of moderate effect size but the majority were breed-specific, indicating that breed-specific alleles exist for calving performance or that the linkage phase between genotyped allele and causal mutation varies between breeds

Asteroseismology, standard candles and the Hubble Constant: what is the role of asteroseismology in the era of precision cosmology?

Classical Cepheids form one of the foundations of modern cosmology and the extragalactic distance scale, however, cosmic microwave background observations measure cosmological parameters and indirectly the Hubble Constant, H0, to unparalleled precision. The coming decade will provide opportunities to measure H0 to 2% uncertainty thanks to the GAIA satellite, JWST, ELTs and other telescopes using Cepheids and other standard candles. In this work, we discuss the upcoming role for variable stars and asteroseismology in calibrating the distance scale and measuring H0 and what problems exist in understanding these stars that will feedback on these measurements.Comment: 8 pages, summary of splinter session at IAU Symposium 301, Precision Asteroseismology, August 2013, Wroclaw, Polan

Multifocal versus monofocal intraocular lenses after cataract extraction.

BACKGROUND: Good unaided distance visual acuity is now a realistic expectation following cataract surgery and intraocular lens (IOL) implantation. Near vision, however, still requires additional refractive power, usually in the form of reading glasses. Multiple optic (multifocal) IOLs are available which claim to allow good vision at a range of distances. It is unclear whether this benefit outweighs the optical compromises inherent in multifocal IOLs. OBJECTIVES: The objective of this review was to assess the effects of multifocal IOLs, including effects on visual acuity, subjective visual satisfaction, spectacle dependence, glare and contrast sensitivity, compared to standard monofocal lenses in people undergoing cataract surgery. METHODS: SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register), The Cochrane Library 2012, Issue 2, MEDLINE (January 1946 to March 2012), EMBASE (January 1980 to March 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 6 March 2012. We searched the reference lists of relevant articles and contacted investigators of included studies and manufacturers of multifocal IOLs for information about additional published and unpublished studies. SELECTION CRITERIA: All randomised controlled trials comparing a multifocal IOL of any type with a monofocal IOL as control were included. Both unilateral and bilateral implantation trials were included. DATA COLLECTION AND ANALYSIS: Two authors collected data and assessed trial quality. Where possible, we pooled data from the individual studies using a random-effects model, otherwise we tabulated data. MAIN RESULTS: Sixteen completed trials (1608 participants) and two ongoing trials were identified. All included trials compared multifocal and monofocal lenses but there was considerable variety in the make and model of lenses implanted. Overall we considered the trials at risk of performance and detection bias because it was difficult to mask patients and outcome assessors. It was also difficult to assess the role of reporting bias. There was moderate quality evidence that similar distance acuity is achieved with both types of lenses (pooled risk ratio, RR for unaided visual acuity worse than 6/6: 0.98, 95% confidence interval, CI 0.91 to 1.05). There was also evidence that people with multifocal lenses had better near vision but methodological and statistical heterogeneity meant that we did not calculate a pooled estimate for effect on near vision. Total freedom from use of glasses was achieved more frequently with multifocal than monofocal IOLs. Adverse subjective visual phenomena, particularly haloes, or rings around lights, were more prevalent and more troublesome in participants with the multifocal IOL and there was evidence of reduced contrast sensitivity with the multifocal lenses

Genetic investigation of Mendelian disorders in the founder populations of Newfoundland & Labrador

Exploring the genetic basis of monogenic disorders imparts fundamental insights into human molecular biology. Moreover, cataloguing and describing pathogenic mutations offers new genetic tests to diagnose and identify mutation carriers worldwide. Sometimes, reaching a genetic diagnosis provides long sought-after answers for patients and their families. Likewise, comprehending the genetic and clinical spectrum of rare disorders aids clinicians in managing their patients. Further, clinical knowledge obtained from genetic studies allows clinicians to anticipate and screen for potential complications. Founder populations experience higher burdens of certain Mendelian disorders and thereby provide unique circumstances to conduct genetic studies. Several founder populations exist in the Canadian province of Newfoundland & Labrador. These have proven instrumental for genetic discoveries. My thesis investigated the genetic basis of three Mendelian disorders in families from Newfoundland. These disorders include retinitis pigmentosa, Weill-Marchesani Syndrome and hereditary colorectal cancer. First, whole exome sequencing and linkage analyses were employed to investigate retinitis pigmentosa in a large kindred living on the Great Northern Peninsula of Newfoundland. This identified a linked region on chromosome 2 (logarithm of the odds 4.89 [θ = 0]) encompassing a novel pathogenic 25 kb deletion (c.845-1450del; p.Ala282_His483del) in MERTK, which segregated in the family. The molecular features and clinical manifestations of the deletion were characterized and study findings were explained to family members. Next, Weill-Marchesani Syndrome was investigated in a Newfoundland family using whole exome sequencing and homozygosity mapping. This identified a novel homozygous pathogenic missense variant (c.3068G>A, p.C1023Y) in ADAMTS17. Transfection of ADAMTS17 p.C1023Y expression plasmids into HEK293T cells revealed significantly reduced secretion of ADAMTS17 into the extracellular matrix. The clinical and molecular consequences of the variant were characterized and the family members were counselled. Finally, candidate gene screening of GALNT12 in a cohort of 479 colorectal cancer cases from Newfoundland identified eight rare variants (p.Asp303Asp; p.Arg297Trp; p.His101Gln; p.Ile142Thr; p.Glu239Gln; p.Thr286Met; p.Val290Phe; c.732-8G>T), which were overrepresented in cases compared to controls (N=400) (P=0.0381). Six of eight variants showed reduced GALNT12 enzyme activity, providing supportive evidence of a role for this gene in colorectal cancer. In summary, each study above imparted novel insights into genetic disorders in Newfoundland

Genomic Epidemiology of Horizontal Plasmid Transfer Among Healthcare-Associated Bacterial Pathogens in a Tertiary Hospital

Healthcare-associated bacterial pathogens frequently carry plasmids that contribute to antibiotic resistance and virulence. The horizontal transfer of plasmids between pathogens within hospitals has been previously documented, but the epidemiology and clinical burden of nosocomial plasmid transfer remains poorly understood. Our primary objective was to systematically resolve plasmids from whole-genome sequences of nosocomial bacterial isolates, using thresholds of sequence similarity that were indicative of horizontal transfer. Our secondary objective was to identify potential routes and assess the clinical burden of horizontal plasmid transfer. Whole-genome sequencing was performed on 3,074 nosocomial bacterial isolates from 2,322 hospitalizations of 1,960 patients, using the Illumina platform. Seventy-eight strains were also sequenced by long-read Oxford Nanopore technology, and hybrid genome assemblies were generated using Unicycler. Plasmids were resolved from Illumina-sequenced genomes by alignment using BLASTn. Single nucleotide polymorphisms (SNPs) were identified using Snippy. De-identified patient data associated with bacterial isolates – including length of hospital stay and Charlson comorbidity index – were collected using Theradoc. Ninety-five percent of analyzed strains maintained at least 95% of the sequence content of reference plasmids, with SNPs occurring at rates of fewer than 1 per 5000bp of reference plasmid sequence. Using these thresholds, we identified 41 plasmid lineages that were potentially horizontally transferred among non-clonal bacterial strains. Of these lineages, 28 (68.2%) were significantly associated with at least one medical procedure, room, or hospital ward. Hospitalizations involving the 41 plasmid lineages were significantly longer (+3 days; 95% CI +1 to +4; p < 0.001) than hospitalizations not involving those plasmids. Patients infected with strains carrying transferred plasmids had significantly greater overall comorbidity (Charlson comorbidity index +1, 95% CI +1 to +2; p < 0.0001) than patients whose infections did not involve plasmids in lineages. Our findings show that the horizontal transfer of plasmids among bacterial isolates causing nosocomial infections is frequent, and that this phenomenon may impose an unappreciated clinical burden by exacerbating infections by isolates carrying these plasmids. Future directions will include more detailed analyses of comorbidity and mortality, as well as sequencing of additional samples to confirm or refute hypothesized routes of plasmid transfer

From Lyapunov modes to the exponents for hard disk systems

We demonstrate the preservation of the Lyapunov modes by the underlying tangent space dynamics of hard disks. This result is exact for the zero modes and correct to order $\epsilon$ for the transverse and LP modes where $\epsilon$ is linear in the mode number. For sufficiently large mode numbers the dynamics no longer preserves the mode structure. We propose a Gram-Schmidt procedure based on orthogonality with respect to the centre space that determines the values of the Lyapunov exponents for the modes. This assumes a detailed knowledge of the modes, but from that predicts the values of the exponents from the modes. Thus the modes and the exponents contain the same information