A stronger topology for the Brownian web

We propose a metric space of coalescing pairs of paths on which we are able to prove (more or less) directly convergence of objects such as the persistence probability in the (one dimensional, nearest neighbor, symmetric) voter model or the diffusively rescaled weight distribution in a silo model (as well as the equivalent output distribution in a river basin model), interpreted in terms of (dual) diffusively rescaled coalescing random walks, to corresponding objects defined in terms of the Brownian web.Comment: 22 page

The Magnetic Field in the central parsec of the Galaxy

We present a polarisation map of the warm dust emission from the minispiral in the central parsec of the Galactic centre. The observations were made at a wavelength of 12.5 microns with CanariCam mounted on the 10.4-m Gran Telescopio Canarias. The magnetic field traced by the polarised emission from aligned dust grains is consistent with previous observations, but the increased resolution of the present data reveals considerably more information on the detailed structure of the B field and its correspondence with the filamentary emission seen in both mid-infrared continuum emission and free-free emission at cm wavelengths. The magnetic field appears to be compressed and pushed by the outflows from luminous stars in the Northern Arm, but it is not disordered by them. We identify some magnetically coherent filaments that cross the Northern Arm at a Position Angle of ~45 degrees, and which may trace orbits inclined to the primary orientation of the Northern Arm and circumnuclear disk. In the East-West bar, the magnetic fields implied by the polarization in the lower intensity regions lie predominantly along the bar at a Position Angle of 130 - 140 degrees. In contrast to the Northern Arm, the brighter regions of the bar tend to have lower degrees of polarization with a greater divergence in position angle compared to the local diffuse emission. It appears that the diffuse emission in the East-West bar traces the underlying field and that the bright compact sources are unrelated objects presumably projected onto the bar and with different field orientationsComment: 12 Pages, 5 figures, 1 Table. To be published in MNRA

Structural optimization of reversible dibromomaleimide peptide stapling

Methods to constrain peptides in a bioactive α‐helical conformation for inhibition of protein‐protein interactions represent an ongoing area of investigation in chemical biology. Recently, the first example of a reversible “stapling” methodology was described which exploits native cysteine or homocysteine residues spaced at the i and i + 4 positions in a peptide sequence together with the thiol selective reactivity of dibromomaleimides (a previous study). This manuscript reports on the optimization of the maleimide based constraint, focusing on the kinetics of macrocyclization and the extent to which helicity is promoted with different thiol containing amino acids. The study identified an optimal stapling combination of X1 = L‐Cys and X5 = L‐hCys in the context of the model peptide Ac‐X1AAAX5‐NH2, which should prove useful in implementing the dibromomaleimide stapling strategy in peptidomimetic ligand discovery programmes

Yrityksen Tekes-rahoitteisen projektin tilintarkastus

Innovaatiorahoituskeskus Tekes rahoitti vuonna 2016 suomalaisten yritysten toteuttamia projekteja noin 467 miljoonalla eurolla. Useimpien Tekesin tarjoamien rahoituspalvelujen ehtona on rahoituksen tilityksen tarkistuttaminen auktorisoidulla tilintarkastajalla. Työn tavoitteena on tuottaa Tekes-rahoitteisten projektien tarkastusta varten osin tarkastusta ohjaava dokumentaatiopohja, tarjota opinnäytetyön raporttiosalla dokumentaatiopohjaa tukeva katsaus Tekes-rahoitteisten projektien tarkastukseen ja syventää kirjoittajan vielä kapeaa osaamista projektitarkastuksista. Opinnäytetyössä keskitytään Tekesin yrityksille tarjoamien rahoitusmuotojen tarkastuksen erityispiirteisiin eikä raporttia tai dokumentaatiopohjaa voida soveltaa julkisten toimijoiden projektien tarkastuksiin. Työ toteutettiin laatien teoriapohja tilintarkastuksen tavoitteista ja eri toimeksiannoista, julkisen rahoituksen ja Tekesin rooleista rahoittajana sekä niistä normeista ja sääntelyistä, jotka koskevat julkisen rahoituksen tilitysten tarkastusta. Teoriapohjan lisäksi tuotettiin luku Tekes-rahoitteisen projektin tarkastuksen teknisestä toteutuksesta osin Tekesin vuoden 2017 yleisten rahoitusehtojen ja tarkastusraporttipohjien sekä auktorisoidun tilintarkastajan ja Tekesin maksatuspalvelujohtajan haastattelujen pohjalta. Tämän osion rinnalla tuotettiin Tekes-rahoitteisten projektien tarkastuksia varten dokumentaatiopohja, joka koottiin kokonaisuudeksi raportin liitteisiin. Tekesin maksatuspalvelujohtaja Anne Kleemolan haastattelun tuloksena todettiin, etteivät Tekesin nykyiset tarkastusraporttipohjat huomioi erityisehtojen tarkastusta yhtä yksityiskohtaisesti, kuin tarkastusraporttipohjalla olevat muut tarkastuksessa huomioitavat seikat on huomioitu. Kleemola totesi tämän olevan hyödyllinen huomio ja tarkastusraporttipohjiin mahdollisesti kehitettävä asia. Koska toimeksiantajalle tuotetusta dokumentaatiopohjasta syntyi selkeä runko Tekes-rahoitteisen projektin tarkastukselle, projektitarkastuksien osalta koettiin oman osaamisen syventyneen ja yhteydenotto Tekesiin koettiin myös heidän osaltaan hyödylliseksi, opinnäytetyön voidaan todeta täyttäneen tavoitteensa

On the convex characterisation of the set of unital quantum channels

In this paper, we consider the convex structure of the set of unital quantum channels. To do this, we introduce a novel framework to construct and characterise different families of low-rank unital quantum maps. In this framework, unital quantum maps are represented as a set of complex parameters on which we impose a set of constraints. The different families of unital maps are obtained by mapping those parameters into the operator representation of a quantum map. For these families, we also introduce a scalar measuring their distance to the set of mixed-unitary maps. We consider the particular case of qutrit channels which is the smallest set of maps for which the existence of non-unitary extremal maps is known. In this setting, we show how our framework generalises the description of well-known maps such as the antisymmetric Werner-Holevo map but also novel families of qutrit maps

Prediction of dementia risk in low-income and middle-income countries (the 10/66 Study): an independent external validation of existing models

BackgroundTo date, dementia prediction models have been exclusively developed and tested in high-income countries (HICs). However, most people with dementia live in low-income and middle-income countries (LMICs), where dementia risk prediction research is almost non-existent and the ability of current models to predict dementia is unknown. This study investigated whether dementia prediction models developed in HICs are applicable to LMICs.MethodsData were from the 10/66 Study. Individuals aged 65 years or older and without dementia at baseline were selected from China, Cuba, the Dominican Republic, Mexico, Peru, Puerto Rico, and Venezuela. Dementia incidence was assessed over 3–5 years, with diagnosis according to the 10/66 Study diagnostic algorithm. Discrimination and calibration were tested for five models: the Cardiovascular Risk Factors, Aging and Dementia risk score (CAIDE); the Study on Aging, Cognition and Dementia (AgeCoDe) model; the Australian National University Alzheimer's Disease Risk Index (ANU-ADRI); the Brief Dementia Screening Indicator (BDSI); and the Rotterdam Study Basic Dementia Risk Model (BDRM). Models were tested with use of Cox regression. The discriminative accuracy of each model was assessed using Harrell's concordance (c)-statistic, with a value of 0·70 or higher considered to indicate acceptable discriminative ability. Calibration (model fit) was assessed statistically using the Grønnesby and Borgan test.Findings11 143 individuals without baseline dementia and with available follow-up data were included in the analysis. During follow-up (mean 3·8 years [SD 1·3]), 1069 people progressed to dementia across all sites (incidence rate 24·9 cases per 1000 person-years). Performance of the models varied. Across countries, the discriminative ability of the CAIDE (0·52≤c≤0·63) and AgeCoDe (0·57≤c≤0·74) models was poor. By contrast, the ANU-ADRI (0·66≤c≤0·78), BDSI (0·62≤c≤0·78), and BDRM (0·66≤c≤0·78) models showed similar levels of discriminative ability to those of the development cohorts. All models showed good calibration, especially at low and intermediate levels of predicted risk. The models validated best in Peru and poorest in the Dominican Republic and China.InterpretationNot all dementia prediction models developed in HICs can be simply extrapolated to LMICs. Further work defining what number and which combination of risk variables works best for predicting risk of dementia in LMICs is needed. However, models that transport well could be used immediately for dementia prevention research and targeted risk reduction in LMICs

Target-Oriented Synthesis of Marine Coelenterazine Derivatives with Anticancer Activity by Applying the Heavy-Atom Effect

Photodynamic therapy (PDT) is an anticancer therapeutic modality with remarkable advantages over more conventional approaches. However, PDT is greatly limited by its dependence on external light sources. Given this, PDT would benefit from new systems capable of a light-free and intracellular photodynamic effect. Herein, we evaluated the heavy-atom effect as a strategy to provide anticancer activity to derivatives of coelenterazine, a chemiluminescent single-molecule widespread in marine organisms. Our results indicate that the use of the heavy-atom effect allows these molecules to generate readily available triplet states in a chemiluminescent reaction triggered by a cancer marker. Cytotoxicity assays in different cancer cell lines showed a heavy-atom-dependent anticancer activity, which increased in the substituent order of hydroxyl < chlorine < bromine. Furthermore, it was found that the magnitude of this anticancer activity is also dependent on the tumor type, being more relevant toward breast and prostate cancer. The compounds also showed moderate activity toward neuroblastoma, while showing limited activity toward colon cancer. In conclusion, the present results indicate that the application of the heavy-atom effect to marine coelenterazine could be a promising approach for the future development of new and optimized self-activating and tumor-selective sensitizers for light-free PDT

Area-level deprivation and adiposity in children: is the relationship linear?

OBJECTIVE: It has been suggested that childhood obesity is inversely associated with deprivation, such that the prevalence is higher in more deprived groups. However, comparatively few studies actually use an area-level measure of deprivation, limiting the scope to assess trends in the association with obesity for this indicator. Furthermore, most assume a linear relationship. Therefore, the aim of this study was to investigate associations between area-level deprivation and three measures of adiposity in children: body mass index (BMI), waist circumference (WC) and waist-to-height ratio (WHtR). DESIGN: This is a cross-sectional study in which data were collected on three occasions a year apart (2005-2007). SUBJECTS: Data were available for 13,333 children, typically aged 11-12 years, from 37 schools and 542 lower super-output areas (LSOAs). MEASURES: Stature, mass and WC. Obesity was defined as a BMI and WC exceeding the 95th centile according to British reference data. WHtR exceeding 0.5 defined obesity. The Index of Multiple Deprivation affecting children (IDACI) was used to determine area-level deprivation. RESULTS: Considerable differences in the prevalence of obesity exist between the three different measures. However, for all measures of adiposity the highest probability of being classified as obese is in the middle of the IDACI range. This relationship is more marked in girls, such that the probability of being obese for girls living in areas at the two extremes of deprivation is around half that at the peak, occurring in the middle. CONCLUSION: These data confirm the high prevalence of obesity in children and suggest that the relationship between obesity and residential area-level deprivation is not linear. This is contrary to the 'deprivation theory' and questions the current understanding and interpretation of the relationship between obesity and deprivation in children. These results could help make informed decisions at the local level

Inflammatory markers in depression: a meta-analysis of mean differences and variability in 5,166 patients and 5,083 controls

Importance The magnitude and variability of cytokine alterations in depression are not clear. Objective To perform an up to date meta-analysis of mean differences of immune markers in depression, and to quantify and test for evidence of heterogeneity in immune markers in depression by conducting a meta-analysis of variability to ascertain whether only a sub-group of patients with depression show evidence of inflammation. Data Sources Studies that reported immune marker levels in peripheral blood in patients with depression and matched healthy controls in the MEDLINE database from inception to August 29th 2018 were examined. Study Selection Case-control studies that reported immune marker levels in peripheral blood in patients with depression and healthy controls were selected. Data Extraction and Synthesis Means and variances (SDs) were extracted for each measure to calculate effect sizes, which were combined using multivariate meta-analysis. Main Outcomes and Measures Hedges g was used to quantify mean differences. Relative variability of immune marker measurements in patients compared with control groups as indexed by the coefficient of variation ratio (CVR). Results A total of 107 studies that reported measurements from 5,166 patients with depression and 5,083 controls were included in the analyses. Levels of CRP (g=0.71; 95%CI: 0.50-0.92; p<0.0001); IL-3 (g=0.60; 95%CI: 0.31-0.89; p<0.0001); IL-6 (g=0.61; 95%CI: 0.39-0.82; p<0.0001); IL-12 (g=1.18; 95%CI: 0.74-1.62; p<0.0001); IL-18 (g=1.97; 95%CI: 1.00-2.95; p<0.0001); sIL-2R (g=0.71; 95%CI: 0.44-0.98; p<0.0001); and TNFα (g=0.54; 95%CI: 0.32-0.76; p<0.0001) were significantly higher in patients with depression. These findings were robust to a range of potential confounds and moderators. Mean-scaled variability, measured as CVR, was significantly lower in patients with depression for CRP (CVR=0.85; 95%CI: 0.75-0.98; p=0.02); IL-12 (CVR=0.61; 95%CI: 0.46-0.80; p<0.01); and sIL-2R (CVR=0.85; 95%CI: 0.73-0.99; p=0.04), while it was unchanged for IL-3, IL-6, IL-18, and TNF α. Conclusions and Relevance Acute depression is confirmed as a pro-inflammatory state. Some of the inflammatory markers elevated in depression, including CRP and IL-12, show reduced variability in patients with depression, therefore supporting greater homogeneity in terms of an inflammatory phenotype in depression. Some inflammatory marker elevations in depression do not appear due to an inflamed sub-group, but rather to a right shift of the immune marker distribution