Comprehensive thermal analysis of a high stability Cu-Zr-Al bulk metallic glass subjected to high-pressure torsion

Bulk metallic glass of Cu38Zr54Al8 nominal composition was synthesized by copper mold casting into 6 mm diameter rods. Disks of the as-cast glass were subjected to severe plastic deformation by high-pressure torsion for different number of revolutions. The microstructure and the thermal behavior of the as-cast, isothermally annealed and deformed glass have been investigated by X-ray diffraction and differential scanning calorimetry, respectively. Continuous heating experiments revealed a two-stage devitrification event with excellent glass forming parameters, such as glass transition (T-g = 671 K), supercooled liquid region ( increment T-x = 80 K), reduced glass transition (T-r = 0.57) and gamma parameter (gamma = 0.41). Power law crystal growth during diffusion-controlled homogeneous nucleation was observed for isothermal annealings. Glassy state was preserved almost in the entire sample volume of the as-cast alloy during the high-pressure torsion process, corresponding to the extreme stability of the Cu38Zr54Al8 alloy against deformation-induced devitrification. This is in accordance with the transition of the reversible specific heat from the glassy to supercooled liquid state measured by modulated calorimetry. It was also concluded that glassy structure is more ordered in the severely deformed state

Landscape-scale connectivity and fragment size determine species composition of grassland fragments

As a consequence of agricultural intensification and habitat fragmentation since the mid-20th century, biological diversity has declined considerably throughout the world, particularly in Europe. We assessed how habitat and landscape-scale heterogeneity, such as variation in fragment size (small vs. large) and landscape configuration (measured as connectivity index), affect plant and arthropod diversity. We focused on arthropods with different feeding behaviour and mobility, spiders (predators, moderate dispersal), true bugs (mainly herbivores and omnivores with moderate dispersal), wild bees (pollinators with good dispersal abilities), and wasps (pollinators, omnivores with good dispersal abilities). We studied 60 dry grassland fragments in the same region (Hungarian Great Plain); 30 fragments were represented by the grassland component of forest-steppe stands, and 30 were situated on burial mounds (kurgans). Forest-steppes are mosaics of dry grasslands with small forests in a matrix of plantation forests. Kurgans are ancient burial mounds with moderately disturbed grasslands surrounded by agricultural fields. The size of fragments ranged between 0.16 6.88 ha (small: 0.16 0.48 ha, large: 0.93 6.88 ha) for forest-steppes and 0.01 0.44 ha (small: 0.01 0.10 ha and large: 0.20 0.44 ha) for kurgans. Fragments also represented an isolation gradient from almost cleared and homogenous landscapes, to landscapes with relatively high compositional heterogeneity. Fragment size, connectivity, and their interaction affected specialist and generalist species abundances of forest-steppes and kurgans. Large fragments had higher species richness of ground-dwelling spiders, and the effect of connectivity was more strongly positive for specialist arthropods and more strongly negative for generalists in large than in small fragments. However, we also found a strong positive impact of connectivity for generalist plants in small kurgans in contrast to larger ones. We conclude that besides the well-known effect of enhancing habitat quality, increasing connectivity between fragments by restoring natural and semi-natural habitat patches would help to maintain grassland biodiversityinfo:eu-repo/semantics/publishedVersio

Vagal Blocking for Obesity Control : a Possible Mechanism-Of-Action

14 September 2016 Erratum to: Vagal Blocking for Obesity Control: a Possible Mechanism-Of-Action Helene Johannessen, David Revesz, Yosuke Kodama, Nikki Cassie, Karolina P Skibicka, Perry Barrett, Suzanne Dickson, Jens Holst, Jens Rehfeld, Geoffrey van der Plasse, Roger Adan, Bård Kulseng, Elinor Ben-Menachem, Chun-Mei Zhao, Duan Chen, 2016, 2016. Obesity surgery. In the original article on page 4 the figures are referred to as (Fig. 1b-d) and (Fig. 1e) in the text. The correct reference is (Fig. 1b-e) and (Fig. 1f), respectively. In the original article on page 5 the figures are referred to as (Fig. 3c) and (Fig. 3d) in the text. The correct reference is (Fig. 3c,d) and (Fig. 3e,f), respectively. Peer reviewedPostprin

Illuminating hydrological processes at the soil-vegetation-atmosphere interface with water stable isotopes

Funded by DFG research project “From Catchments as Organised Systems to Models based on Functional Units” (FOR 1Peer reviewedPublisher PDFPublisher PD

Structure-based classification of tauopathies

Ordered assembly of tau protein into filaments characterizes multiple neurodegenerative diseases, which are called tauopathies. We previously reported that by electron cryo-microscopy (cryo-EM), tau filament structures from Alzheimer’s disease (1,2), Pick’s disease (3), chronic traumatic encephalopathy (CTE) (4) and corticobasal degeneration (CBD) (5) are distinct. Here we show that the structures of tau filaments from progressive supranuclear palsy (PSP) define a novel three-layered fold. Moreover, the tau filament structures from globular glial tauopathy (GGT) are similar to those from PSP. The tau filament fold of argyrophilic grain disease (AGD) differs from the above and resembles the four-layered CBD fold. The AGD fold is also observed in aging-related tau astrogliopathy (ARTAG). Tau protofilament structures from inherited cases with mutations +3 or +16 in intron 10 of MAPT, the microtubule-associated protein tau gene, are also identical to those from AGD, suggesting that relative overproduction of four-repeat tau can give rise to the AGD fold. Finally, tau filament structures from cases of familial British dementia (FBD) and familial Danish dementia (FDD) are the same as those from Alzheimer’s disease and primary age-related tauopathy (PART). These findings suggest a hierarchical classification of tauopathies based on their filament folds, which complements clinical diagnosis and neuropathology, and allows identification of new entities, as we show for a case diagnosed as PSP, but with filament structures that are intermediate between those of GGT and PSP

Assessment of β-amyloid deposits in human brain: a study of the BrainNet Europe Consortium

β-Amyloid (Aβ) related pathology shows a range of lesions which differ both qualitatively and quantitatively. Pathologists, to date, mainly focused on the assessment of both of these aspects but attempts to correlate the findings with clinical phenotypes are not convincing. It has been recently proposed in the same way as ι and α synuclein related lesions, also Aβ related pathology may follow a temporal evolution, i.e. distinct phases, characterized by a step-wise involvement of different brain-regions. Twenty-six independent observers reached an 81% absolute agreement while assessing the phase of Aβ, i.e. phase 1 = deposition of Aβ exclusively in neocortex, phase 2 = additionally in allocortex, phase 3 = additionally in diencephalon, phase 4 = additionally in brainstem, and phase 5 = additionally in cerebellum. These high agreement rates were reached when at least six brain regions were evaluated. Likewise, a high agreement (93%) was reached while assessing the absence/presence of cerebral amyloid angiopathy (CAA) and the type of CAA (74%) while examining the six brain regions. Of note, most of observers failed to detect capillary CAA when it was only mild and focal and thus instead of type 1, type 2 CAA was diagnosed. In conclusion, a reliable assessment of Aβ phase and presence/absence of CAA was achieved by a total of 26 observers who examined a standardized set of blocks taken from only six anatomical regions, applying commercially available reagents and by assessing them as instructed. Thus, one may consider rating of Aβ-phases as a diagnostic tool while analyzing subjects with suspected Alzheimer’s disease (AD). Because most of these blocks are currently routinely sampled by the majority of laboratories, assessment of the Aβ phase in AD is feasible even in large scale retrospective studies

Progression of atypical parkinsonian syndromes: PROSPECT-M-UK study implications for clinical trials

The advent of clinical trials of disease-modifying agents for neurodegenerative disease highlights the need for evidence-based endpoint selection. Here we report the longitudinal PROSPECT-M-UK study of progressive supranuclear palsy, corticobasal syndrome, multiple system atrophy and related disorders, to compare candidate clinical trial endpoints. In this multicentre United Kingdom study, participants were assessed with serial questionnaires, motor examination, neuropsychiatric and magnetic resonance imaging assessments at baseline, six and twelve-months. Participants were classified by diagnosis at baseline and study end, into Richardson syndrome, progressive supranuclear palsy-subcortical (progressive supranuclear palsy-parkinsonism and progressive gait freezing subtypes), progressive supranuclear palsy-cortical (progressive supranuclear palsy-frontal, progressive supranuclear palsy-speech-and-language, and progressive supranuclear palsy-corticobasal syndrome subtypes), multiple system atrophy-parkinsonism, multiple system atrophy-cerebellar, corticobasal syndrome with and without evidence of Alzheimer’s disease pathology and indeterminate syndromes. We calculated annual rate of change, with linear mixed modelling, and sample sizes for clinical trials of disease modifying agents, according to group and assessment type. Two hundred forty-three people were recruited (117 progressive supranuclear palsy, 68 corticobasal syndrome, 42 multiple system atrophy and 16 indeterminate; 138 [56.8%] male; age at recruitment 68.7 ± 8.61 years). One hundred fifty-nine completed six-month assessment (82 progressive supranuclear palsy, 27 corticobasal syndrome, 40 multiple system atrophy and 10 indeterminate) and 153 completed twelve-month assessment (80 progressive supranuclear palsy, 29 corticobasal syndrome, 35 multiple system atrophy and 9 indeterminate). Questionnaire, motor examination, neuropsychiatric and neuroimaging measures declined in all groups, with differences in longitudinal change between groups. Neuroimaging metrics would enable lower sample sizes to achieve equivalent power for clinical trials than cognitive and functional measures, often achieving N < 100 required for one-year two-arm trials (with 80% power to detect 50% slowing). However, optimal outcome measures were disease specific. In conclusion, phenotypic variance within progressive supranuclear palsy, corticobasal syndrome and multiple system atrophy is a major challenge to clinical trial design. Our findings provide an evidence base for selection of clinical trial endpoints, from potential functional, cognitive, clinical or neuroimaging measures of disease progression

Diagnosis Across the Spectrum of Progressive Supranuclear Palsy and Corticobasal Syndrome

IMPORTANCE: Patients with atypical parkinsonian syndromes (APS), including progressive supranuclear palsy (PSP), corticobasal syndrome (CBS) and multiple system atrophy (MSA), may be difficult to distinguish in early stages and are often misdiagnosed as Parkinson’s disease (PD). The diagnostic criteria for PSP have been updated to encompass a range of clinical subtypes, but have not been prospectively studied. OBJECTIVE: To define the distinguishing features of PSP and CBS, and to assess their usefulness in facilitating early diagnosis and separation from PD. DESIGN, SETTING, PARTICIPANTS: Cohort study which recruited APS and PD patients from movement disorder clinics across the UK from September 2015 to December 2018, and will follow up patients over 5 years. APS patients were stratified into PSP-Richardson syndrome, PSP-subcortical (including PSP-parkinsonism and PSP-progressive gait freezing cases), PSP-cortical (including PSP-frontal and PSP/CBS overlap cases), MSA-parkinsonism, MSA-cerebellar, CBS-Alzheimer’s and CBS-non-Alzheimer’s groups. MAIN OUTCOME MEASURES: Baseline group comparisons were conducted using: 1) Clinical trajectory; 2) Cognitive screening scales; 3) Serum neurofilament light chain (NF-L); 4) TRIM11, ApoE and MAPT genotypes; 5) Volumetric MRI. RESULTS: 222 APS cases (101 PSP, 55 MSA, 40 CBS and 26 indeterminate) were recruited (58% male; mean age at recruitment, 68.3 years). Age-matched controls (n=76) and PD cases (n=1967) were also included. Concordance between the ante-mortem clinical diagnosis and pathological diagnosis was achieved in 12/13 (92%) of PSP and CBS cases coming to post-mortem. Applying the MDS PSP diagnostic criteria almost doubled the number of patients diagnosed with PSP. 49/101 (49%) of reclassified PSP patients did not have classical PSP-Richardson syndrome. PSP-subcortical patients had a longer diagnostic latency and a more benign clinical trajectory than PSP-Richardson syndrome and PSP-cortical (p<0.05). PSP-subcortical was distinguished from PSP-cortical and PSP-Richardson syndrome by cortical volumetric MRI measures (AUC 0.84-0.89), cognitive profile (AUC 0.80-0.83), serum NF-L (AUC 0.75-0.83) and TRIM11 rs564309 genotype. Midbrain atrophy was a common feature of all PSP subtypes. 8/17 (47%) of CBS patients with CSF analysis were identified as having CBS-Alzheimer’s. CBS-Alzheimer’s patients had a longer diagnostic latency, relatively benign clinical trajectory, greater cognitive impairment and higher APOE-ε4 allele frequency than CBS-non-Alzheimer’s (p<0.05, AUC 0.80-0.87). Serum NF-L levels distinguished PD from PSP and CBS (p<0.05, AUC 0.80). CONCLUSIONS AND RELEVANCE: Clinical, therapeutic and epidemiological studies focusing on PSP-Richardson syndrome are likely to miss a large number of patients with underlying PSP-tau pathology. CSF analysis defines a distinct CBS-Alzheimer’s subgroup. PSP and CBS subtypes have distinct characteristics that may enhance their early diagnosis