Segmental aging underlies the development of a Parkinson phenotype in the AS/AGU rat

There is a paucity of information on the molecular biology of aging processes in the brain. We have used biomarkers of aging (SA β-Gal, p16Ink4a, Sirt5, Sirt6, and Sirt7) to demonstrate the presence of an accelerated aging phenotype across different brain regions in the AS/AGU rat, a spontaneous Parkinsonian mutant of PKCγ derived from a parental AS strain. P16INK4a expression was significantly higher in AS/AGU animals compared to age-matched AS controls (p < 0.001) and displayed segmental expression across various brain regions. The age-related expression of sirtuins similarly showed differences between strains and between brain regions. Our data clearly show segmental aging processes within the rat brain, and that these are accelerated in the AS/AGU mutant. The accelerated aging, Parkinsonian phenotype, and disruption to dopamine signalling in the basal ganglia in AS/AGU rats, suggests that this rat strain represents a useful model for studies of development and progression of Parkinson's disease in the context of biological aging and may offer unique mechanistic insights into the biology of aging

Changes in women’s facial skin color over the ovulatory cycle are not detectable by the human visual system

Human ovulation is not advertised, as it is in several primate species, by conspicuous sexual swellings. However, there is increasing evidence that the attractiveness of women’s body odor, voice, and facial appearance peak during the fertile phase of their ovulatory cycle. Cycle effects on facial attractiveness may be underpinned by changes in facial skin color, but it is not clear if skin color varies cyclically in humans or if any changes are detectable. To test these questions we photographed women daily for at least one cycle. Changes in facial skin redness and luminance were then quantified by mapping the digital images to human long, medium, and shortwave visual receptors. We find cyclic variation in skin redness, but not luminance. Redness decreases rapidly after menstrual onset, increases in the days before ovulation, and remains high through the luteal phase. However, we also show that this variation is unlikely to be detectable by the human visual system. We conclude that changes in skin color are not responsible for the effects of the ovulatory cycle on women’s attractiveness

Low-Temperature Phase Transitions in a Soluble Oligoacene and Their Effect on Device Performance and Stability

The use of organic semiconductors in high-performance organic field-effect transistors requires a thorough understanding of the effects that processing conditions, thermal, and bias-stress history have on device operation. Here, we evaluate the temperature dependence of the electrical properties of transistors fabricated with 2,8-difluoro-5,11-bis(triethylsilylethynyl)anthradithiophene, a material that has attracted much attention recently due to its exceptional electrical properties. We have discovered a phase transition at T = 205 K and discuss its implications on device performance and stability. We examined the impact of this low-temperature phase transition on the thermodynamic, electrical, and structural properties of both single crystals and thin films of this material. Our results show that while the changes to the crystal structure are reversible, the induced thermal stress yields irreversible degradation of the devices

Quantitative Analysis of the Density of Trap States at the Semiconductor-Dielectric Interface in Organic Field-Effect Transistors

The electrical properties of organic field-effect transistors are governed by the quality of the constituting layers, and the resulting interfaces. We compare the properties of the same organic semiconductor film, 2,8-difluoro- 5,11-bis (triethylsilylethynyl) anthradithiophene, with bottom SiO2 dielectric and top Cytop dielectric and find a 10× increase in charge carrier mobility, from 0.17 ± 0.19 cm2 V−1 s−1 to 1.5 ± 0.70 cm2 V−1 s−1, when the polymer dielectric is used. This results from a significant reduction of the trap density of states in the semiconductor band-gap, and a decrease in the contact resistance

HopScotch - a low-power renewable energy base station network for rural broadband access

The provision of adequate broadband access to communities in sparsely populated rural areas has in the past been severely restricted. In this paper, we present a wireless broadband access test bed running in the Scottish Highlands and Islands which is based on a relay network of low-power base stations. Base stations are powered by a combination of renewable sources creating a low cost and scalable solution suitable for community ownership. The use of the 5~GHz bands allows the network to offer large data rates and the testing of ultra high frequency ``white space'' bands allow expansive coverage whilst reducing the number of base stations or required transmission power. We argue that the reliance on renewable power and the intelligent use of frequency bands makes this approach an economic green radio technology which can address the problem of rural broadband access

Solution-Printed Organic Semiconductor Blends Exhibiting Transport Properties on Par with Single Crystals

Solution-printed organic semiconductors have emerged in recent years as promising contenders for roll-to-roll manufacturing of electronic and optoelectronic circuits. The stringent performance requirements for organic thin-film transistors (OTFTs) in terms of carrier mobility, switching speed, turn-on voltage and uniformity over large areas require performance currently achieved by organic single-crystal devices, but these suffer from scale-up challenges. Here we present a new method based on blade coating of a blend of conjugated small molecules and amorphous insulating polymers to produce OTFTs with consistently excellent performance characteristics (carrier mobility as high as 6.7 cm2V−1s−1, low threshold voltages of \u3c1V and low sub threshold swings \u3c0.5Vdec−1). Our findings demonstrate that careful control over phase separation and crystallization can yield solution-printed polycrystalline organic semiconductor films with transport properties and other figures of merit on par with their single-crystal counterparts

Mucosal-associated invariant T (MAIT) cells are activated in the gastrointestinal tissue of patients with combination ipilimumab and nivolumab therapy-related colitis in a pathology distinct from ulcerative colitis

The aim of this study was to investigate the pathogenesis of combination ipilimumab and nivolumab-associated colitis (IN-COL) by measuring gut-derived and peripheral blood mononuclear cell (GMNC; PBMC) profiles. We studied GMNC and PBMC from patients with IN-COL, IN-treated with no adverse-events (IN-NAE), ulcerative colitis (UC) and healthy volunteers using flow cytometry. In the gastrointestinal-derived cells we found high levels of activated CD8+ T cells and mucosal-associated invariant T (MAIT) cells in IN-COL, changes that were not evident in IN-NAE or UC. UC, but not IN-C, was associated with a high proportion of regulatory T cells (Treg). We sought to determine if local tissue responses could be measured in peripheral blood. Peripherally, checkpoint inhibition instigated a rise in activated memory CD4+ and CD8+ T cells, regardless of colitis. Low circulating MAIT cells at baseline was associated with IN-COL patients compared with IN-NAE in one of two cohorts. UC, but not INCOL, was associated with high levels of circulating plasmablasts. In summary, the alterations in T cell subsets measured in IN-COL-affected tissue, characterized by high levels of activated CD8+ T cells and MAIT cells and a low proportion of Treg, reflected a pathology distinct from UC. These tissue changes differed from the periphery, where T cell activation was a widespread on-treatment effect, and circulating MAIT cell count was low but not reliably predictive of colitis

Effect of 18F-fluciclovine positron emission tomography on the management of patients with recurrence of prostate cancer: Results from the FALCON Trial

Purpose: Early and accurate localization of lesions in patients with biochemical recurrence (BCR) of prostate cancer may guide salvage therapy decisions. The present study, 18F-Fluciclovine PET/CT in biochemicAL reCurrence Of Prostate caNcer (FALCON; NCT02578940), aimed to evaluate the effect of 18F-fluciclovine on management of men with BCR of prostate cancer. Methods and Materials: Men with a first episode of BCR after curative-intent primary therapy were enrolled at 6 UK sites. Patients underwent 18F-fluciclovine positron emission tomography/computed tomography (PET/CT) according to standardized procedures. Clinicians documented management plans before and after scanning, recording changes to treatment modality as major and changes within a modality as other. The primary outcome measure was record of a revised management plan postscan. Secondary endpoints were evaluation of optimal prostate specific antigen (PSA) threshold for detection, salvage treatment outcome assessment based on 18F-fluciclovine-involvement, and safety. Results: 18F-Fluciclovine was well tolerated in the 104 scanned patients (median PSA = 0.79 ng/mL). Lesions were detected in 58 out of 104 (56%) patients. Detection was broadly proportional to PSA level; ≤1 ng/mL, 1 out of 3 of scans were positive, and 93% scans were positive at PSA >2.0 ng/mL. Sixty-six (64%) patients had a postscan management change (80% after a positive result). Major changes (43 out of 66; 65%) were salvage or systemic therapy to watchful waiting (16 out of 66; 24%); salvage therapy to systemic therapy (16 out of 66; 24%); and alternative changes to treatment modality (11 out of 66, 17%). The remaining 23 out of 66 (35%) management changes were modifications of the prescan plan: most (22 out of 66; 33%) were adjustments to planned brachytherapy/radiation therapy to include a 18F-fluciclovine-guided boost. Where 18F-fluciclovine guided salvage therapy, the PSA response rate was higher than when 18F-fluciclovine was not involved (15 out of 17 [88%] vs 28 out of 39 [72%]). Conclusions: 18F-Fluciclovine PET/CT located recurrence in the majority of men with BCR, frequently resulting in major management plan changes. Incorporating 18F-fluciclovine PET/CT into treatment planning may optimize targeting of recurrence sites and avoid futile salvage therapy

Harnessing genetic potential of wheat germplasm banks through impact-oriented-prebreeding for future food and nutritional security

The value of exotic wheat genetic resources for accelerating grain yield gains is largely unproven and unrealized. We used next-generation sequencing, together with multi-environment phenotyping, to study the contribution of exotic genomes to 984 three-way-cross-derived (exotic/elite1//elite2) pre-breeding lines (PBLs). Genomic characterization of these lines with haplotype map-based and SNP marker approaches revealed exotic specific imprints of 16.1 to 25.1%, which compares to theoretical expectation of 25%. A rare and favorable haplotype (GT) with 0.4% frequency in gene bank identified on chromosome 6D minimized grain yield (GY) loss under heat stress without GY penalty under irrigated conditions. More specifically, the ‘T’ allele of the haplotype GT originated in Aegilops tauschii and was absent in all elite lines used in study. In silico analysis of the SNP showed hits with a candidate gene coding for isoflavone reductase IRL-like protein in Ae. tauschii. Rare haplotypes were also identified on chromosomes 1A, 6A and 2B effective against abiotic/biotic stresses. Results demonstrate positive contributions of exotic germplasm to PBLs derived from crosses of exotics with CIMMYT’s best elite lines. This is a major impact-oriented pre-breeding effort at CIMMYT, resulting in large-scale development of PBLs for deployment in breeding programs addressing food security under climate change scenarios