The unrestricted Skyrme-tensor time-dependent Hartree-Fock and its application to the nuclear response from spherical to triaxial nuclei

The nuclear time-dependent Hartree-Fock model formulated in the three-dimensional space,based on the full Skyrme energy density functional and complemented with the tensor force,is presented for the first time. Full self-consistency is achieved by the model. The application to the isovector giant dipole resonance is discussed in the linear limit, ranging from spherical nuclei (16O, 120Sn) to systems displaying axial or triaxial deformation (24Mg, 28Si, 178Os, 190W, 238U). Particular attention is paid to the spin-dependent terms from the central sector of the functional, recently included together with the tensor. They turn out to be capable of producing a qualitative change on the strength distribution in this channel. The effect on the deformation properties is also discussed. The quantitative effects on the linear response are small and, overall, the giant dipole energy remains unaffected. Calculations are compared to predictions from the (quasi)-particle random phase approximation and experimental data where available, finding good agreement

Finite conductance governs the resonance transmission of thin metal slits at microwave frequencies

James R. Suckling, Alastair P. Hibbins, Matthew J. Lockyear, T. W. Preist, J. Roy Sambles, and Christopher R. Lawrence, Physical Review Letters, Vol. 92, article 147401 (2004). "Copyright © 2004 by the American Physical Society."Fabry-Perot–like resonant transmission of microwave radiation through a single subwavelength slit in a thick aluminum plate is quantified for a range of slit widths. Surprisingly, and in contrast to previous studies [e.g., Y. Takakura, Phys. Rev. Lett. 86, 5601 (2001)], the resonant frequency exhibits a maximum as a function of slit width, decreasing as the slit width is reduced to less than 2% of the incident wavelength. This result accords with a new model based on coupled surface plasmon theory taking into account the finite conductivity, and hence permittivity, of the metal. This is contrary to a common assumption that metals can be treated as infinitely conducting in this regime

Age-related grey matter volume correlates of response inhibition and shifting in Attention Deficit Hyperactivity Disorder

Background Children with attention-deficit hyperactivity disorder (ADHD) have difficulties with executive function and impulse control which may improve with age. Aims To map the brain correlates of executive function in ADHD and determine age-related changes in reaction times and brain volumes. Method Attention-deficit hyperactivity disorder and control groups were compared on the change task measures of response inhibition (stop signal reaction time, SSRT) and shifting (change response reaction time, CRRT). voxel-wise magnetic resonance imaging (MRI) correlations of reaction times and grey matter volume were determined, along with bivariate correlations of reaction times, brain volumes and age.Results Individuals in the ADHD group had longer SSRTs and CRRTs. Anterior cingulate, striatal and medial temporal volumes highly correlated with SSRT. Striatal and cerebellar volumes strongly correlated with CRRT. Older children had faster reaction times and larger regional brain volumes. In controls, orbitofrontal, medial temporal and cerebellar volumes correlated with CRRT but not SSRT. Neither reaction times nor regional brain volumes were strongly age- dependent. Conclusions Our evidence supports delayed brain maturation in ADHD and implies that some features of ADHD improve with age.link_to_subscribed_fulltex

Structure-based design and synthesis of antiparasitic pyrrolopyrimidines targeting pteridine reductase 1

The treatment of Human African Trypanosomiasis remains a major unmet health need in sub-Saharan Africa. Approaches involving new molecular targets are important and pteridine reductase 1 (PTR1), an enzyme that reduces dihydrobiopterin in Trypanosoma spp. has been identified as a candidate target and it has been shown previously that substituted pyrrolo[2,3-d]pyrimidines are inhibitors of PTR1 from T. brucei (J. Med. Chem. 2010, 53, 221-229). In this study, 61 new pyrrolo[2,3-d]pyrimidines have been prepared, designed with input from new crystal structures of 23 of these compounds complexed with PTR1, and evaluated in screens for enzyme inhibitory activity against PTR1 and in vitro antitrypanosomal activity. 8 compounds were sufficiently active in both screens to take forward to in vivo evaluation. Thus although evidence for trypanocidal activity in a stage I disease model in mice was obtained, the compounds were too toxic to mice for further development

Intrinsic excitation-inhibition imbalance affects medial prefrontal cortex differently in autistic men versus women

Excitation-inhibition (E:I) imbalance is theorized as an important pathophysiological mechanism in autism. Autism affects males more frequently than females and sex-related mechanisms (e.g., X-linked genes, androgen hormones) can influence E:I balance. This suggests that E:I imbalance may affect autism differently in males versus females. With a combination of in-silico modeling and in-vivo chemogenetic manipulations in mice, we first show that a time-series metric estimated from fMRI BOLD signal, the Hurst exponent (H), can be an index for underlying change in the synaptic E:I ratio. In autism we find that H is reduced, indicating increased excitation, in the medial prefrontal cortex (MPFC) of autistic males but not females. Increasingly intact MPFC H is also associated with heightened ability to behaviorally camouflage social-communicative difficulties, but only in autistic females. This work suggests that H in BOLD can index synaptic E:I ratio and that E:I imbalance affects autistic males and females differently

Design and Synthesis of Heterocyclic Cations for Specific DNA Recognition: From AT-Rich to Mixed-Base-Pair DNA Sequences

The compounds synthesized in this research were designed with the goal of establishing a new paradigm for mixed-base-pair DNA sequence-specific recognition. The design scheme starts with a cell-permeable heterocyclic cation that binds to AT base pair sites in the DNA minor groove. Modifications were introduced in the original compound to include an Hbond accepting group to specifically recognize the G-NH that projects into the minor groove. Therefore, a series of heterocyclic cations substituted with an azabenzimidazole ring has been designed and synthesized for mixed-base-pair DNA recognition. The most successful compound, 12a, had an azabenzimidazole to recognize G and additional modifications for general minor groove interactions. It binds to the DNA site −AAAGTTT− more strongly than the −AAATTT− site without GC and indicates the design success. Structural modifications of 12a generally weakened binding. The interactions of the new compound with a variety of DNA sequences with and without GC base pairs were evaluated by thermal melting analysis, circular dichroism, fluorescence emission spectroscopy, surface plasmon resonance, and molecular modeling

The short-term effect of high versus moderate protein intake on recovery after strength training in resistance-trained individuals

Background: Dietary protein intakes up to 2.9 g.kg-1.d-1 and protein consumption before and after resistance training may enhance recovery, resulting in hypertrophy and strength gains. However, it remains unclear whether protein quantity or nutrient timing is central to positive adaptations. This study investigated the effect of total dietary protein content, whilst controlling for protein timing, on recovery in resistance trainees. Methods: Fourteen resistance-trained individuals underwent two 10-day isocaloric dietary regimes with a protein content of 1.8 g.kg-1.d-1 (PROMOD) or 2.9 g.kg-1.d-1 (PROHIGH) in a randomised, counterbalanced, crossover design. On days 8-10 (T1-T3), participants undertook resistance exercise under controlled conditions, performing 3 sets of squat, bench press and bent-over rows at 80% 1 repetition maximum until volitional exhaustion. Additionally, participants consumed a 0.4 g.kg-1 whey protein concentrate/isolate mix 30 minutes before and after exercise sessions to standardise protein timing specific to training. Recovery was assessed via daily repetition performance, muscle soreness, bioelectrical impedance phase angle, plasma creatine kinase (CK) and tumor necrosis factor-α (TNF-α). Results: No significant differences were reported between conditions for any of the performance repetition count variables (p>0.05). However, within PROMOD only, squat performance total repetition count was significantly lower at T3 (19.7 ± 6.8) compared to T1 (23.0 ± 7.5; p=0.006). Pre and post-exercise CK concentrations significantly increased across test days (p≤0.003), although no differences were reported between conditions. No differences for TNF-α or muscle soreness were reported between dietary conditions. Phase angle was significantly greater at T3 for PROHIGH (8.26 ± 0.82°) compared with PROMOD (8.08 ± 0.80°; p=0.012). Conclusions: When energy intake and peri-exercise protein intake was controlled for, a short term PROHIGH diet did not improve markers of muscle damage or soreness in comparison to a PROMOD approach following repeated days of intensive training. Whilst it is therefore likely that protein intakes (1.8g.kg-1.d-1) may be sufficient for resistance-trained individuals, it is noteworthy that both lower body exercise performance and bioelectrical phase angle were maintained with PROHIGH. Longer term interventions are warranted to determine whether PROMOD intakes are sufficient during prolonged training periods or when extensive exercise (e.g. training twice daily) is undertaken

Levers and leverage points for pathways to sustainability

Humanity is on a deeply unsustainable trajectory. We are exceeding planetary boundaries and unlikely to meet many international sustainable development goals and global environmental targets. Until recently, there was no broadly accepted framework of interventions that could ignite the transformations needed to achieve these desired targets and goals. As a component of the IPBES Global Assessment, we conducted an iterative expert deliberation process with an extensive review of scenarios and pathways to sustainability, including the broader literature on indirect drivers, social change and sustainability transformation. We asked, what are the most important elements of pathways to sustainability? Applying a social–ecological systems lens, we identified eight priority points for intervention (leverage points) and five overarching strategic actions and priority interventions (levers), which appear to be key to societal transformation. The eight leverage points are: (1) Visions of a good life, (2) Total consumption and waste, (3) Latent values of responsibility, (4) Inequalities, (5) Justice and inclusion in conservation, (6) Externalities from trade and other telecouplings, (7) Responsible technology, innovation and investment, and (8) Education and knowledge generation and sharing. The five intertwined levers can be applied across the eight leverage points and more broadly. These include: (A) Incentives and capacity building, (B) Coordination across sectors and jurisdictions, (C) Pre-emptive action, (D) Adaptive decision-making and (E) Environmental law and implementation. The levers and leverage points are all non-substitutable, and each enables others, likely leading to synergistic benefits. Transformative change towards sustainable pathways requires more than a simple scaling-up of sustainability initiatives—it entails addressing these levers and leverage points to change the fabric of legal, political, economic and other social systems. These levers and leverage points build upon those approved within the Global Assessment's Summary for Policymakers, with the aim of enabling leaders in government, business, civil society and academia to spark transformative changes towards a more just and sustainable world. A free Plain Language Summary can be found within the Supporting Information of this article.Fil: Chan, Kai M. A.. University of British Columbia; CanadáFil: Boyd, David R.. University of British Columbia; CanadáFil: Gould, Rachelle. University of Vermont; Estados UnidosFil: Jetzkowitz, Jens. Staatliches Museum fur Naturkunde Stuttgart; AlemaniaFil: Liu, Jianguo. Michigan State University; Estados UnidosFil: Muraca, Bárbara. University of Oregon; Estados UnidosFil: Naidoo, Robin. University of British Columbia; CanadáFil: Beck, Paige. University of British Columbia; CanadáFil: Satterfield, Terre. University of British Columbia; CanadáFil: Selomane, Odirilwe. Stellenbosch University; SudáfricaFil: Singh, Gerald G.. University of British Columbia; CanadáFil: Sumaila, Rashid. University of British Columbia; CanadáFil: Ngo, Hien T.. Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services; AlemaniaFil: Boedhihartono, Agni Klintuni. University of British Columbia; CanadáFil: Agard, John. The University Of The West Indies; Trinidad y TobagoFil: de Aguiar, Ana Paula D.. Stockholms Universitet; SueciaFil: Armenteras, Dolors. Universidad Nacional de Colombia; ColombiaFil: Balint, Lenke. BirdLife International; Reino UnidoFil: Barrington-Leigh, Christopher. Mcgill University; CanadáFil: Cheung, William W. L.. University of British Columbia; CanadáFil: Díaz, Sandra Myrna. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Driscoll, John. University of British Columbia; CanadáFil: Esler, Karen. Stellenbosch University; SudáfricaFil: Eyster, Harold. University of British Columbia; CanadáFil: Gregr, Edward J.. University of British Columbia; CanadáFil: Hashimoto, Shizuka. The University Of Tokyo; JapónFil: Hernández Pedraza, Gladys Cecilia. The World Economy Research Center; CubaFil: Hickler, Thomas. Goethe Universitat Frankfurt; AlemaniaFil: Kok, Marcel. PBL Netherlands Environmental Assessment Agency; Países BajosFil: Lazarova, Tanya. PBL Netherlands Environmental Assessment Agency; Países BajosFil: Mohamed, Assem A. A.. Central Laboratory for Agricultural Climate; EgiptoFil: Murray-Hudson, Mike. University Of Botswana; BotsuanaFil: O'Farrell, Patrick. University of Cape Town; SudáfricaFil: Palomo, Ignacio. Basque Centre for Climate Change; EspañaFil: Saysel, Ali Kerem. Boğaziçi University; TurquíaFil: Seppelt, Ralf. Martin-universität Halle-wittenberg; AlemaniaFil: Settele, Josef. German Centre for Integrative Biodiversity Research-iDiv; AlemaniaFil: Strassburg, Bernardo. International Institute for Sustainability, Estrada Dona Castorina; BrasilFil: Xue, Dayuan. Minzu University Of China; ChinaFil: Brondízio, Eduardo S.. Indiana University; Estados Unido