A diagonally inverted LU implicit multigrid scheme

A new Diagonally Inverted LU Implicit scheme is developed within the framework of the multigrid method for the 3-D unsteady Euler equations. The matrix systems that are to be inverted in the LU scheme are treated by local diagonalizing transformations that decouple them into systems of scalar equations. Unlike the Diagonalized ADI method, the time accuracy of the LU scheme is not reduced since the diagonalization procedure does not destroy time conservation. Even more importantly, this diagonalization significantly reduces the computational effort required to solve the LU approximation and therefore transforms it into a more efficient method of numerically solving the 3-D Euler equations

Rotating strings

Analytical expressions are provided for the configurations of an inextensible, flexible, twistable inertial string rotating rigidly about a fixed axis. Solutions with trivial radial dependence are helices of arbitrary radius and pitch. Non-helical solutions are governed by a cubic equation whose roots delimit permissible values of the squared radial coordinate. Only curves coplanar with the axis of rotation make contact with it.Comment: added to discussion and made small revisions to tex

The effects of feed restriction, time of day and time since feeding on behavioral and physiological indicators of hunger in broiler breeder hens

Broiler breeder chickens are commercially feed restricted to slow their growth and improve their health and production, however, there is research demonstrating that this leads to chronic hunger resulting in poor welfare. A challenge in these studies is to account for possible daily rhythms or the effects of time since last meal on measures relating hunger. To address this, we used 3 feed treatments: AL (ad libitum fed), Ram (restricted, fed in the morning), and Rpm (restricted, fed in the afternoon) to control for diurnal effects. We then conducted foraging motivation tests and collected home pen behavior and physiological samples at 4 times relative to feeding throughout a 24-h period. The feed treatment had the largest influence on the data, with AL birds weighing more, having lower concentrations of plasma NEFA, and mRNA expression of AGRP and NPY alongside higher expression of POMC in the basal hypothalamus than Ram or Rpm birds (P &lt; 0.001). R birds were more successful at and had a shorter latency to complete the motivation test, and did more walking and less feeding than AL birds in the home pen (P &lt; 0.01). There was little effect of time since last meal on many measures (P &gt; 0.05) but AGRP expression was highest in the basal hypothalamus shortly after a meal (P &lt; 0.05), blood plasma NEFA was higher in R birds just before feeding (P &lt; 0.001) and glucose was higher in Ram birds just after feeding (P &lt; 0.001), and the latency to complete the motivation test was shortest before the next meal (P &lt; 0.05). Time of day effects were mainly found in the difference in activity levels in the home pen when during lights on and lights off periods. In conclusion, many behavioral and physiological hunger measures were not significantly influenced by time of day or time since the last meal. For the measures that do change, future studies should be designed so that sampling is balanced in such a way as to minimize bias due to these effects.</p

Functional Amyloid Formation within Mammalian Tissue

Amyloid is a generally insoluble, fibrous cross-β sheet protein aggregate. The process of amyloidogenesis is associated with a variety of neurodegenerative diseases including Alzheimer, Parkinson, and Huntington disease. We report the discovery of an unprecedented functional mammalian amyloid structure generated by the protein Pmel17. This discovery demonstrates that amyloid is a fundamental nonpathological protein fold utilized by organisms from bacteria to humans. We have found that Pmel17 amyloid templates and accelerates the covalent polymerization of reactive small molecules into melanin—a critically important biopolymer that protects against a broad range of cytotoxic insults including UV and oxidative damage. Pmel17 amyloid also appears to play a role in mitigating the toxicity associated with melanin formation by sequestering and minimizing diffusion of highly reactive, toxic melanin precursors out of the melanosome. Intracellular Pmel17 amyloidogenesis is carefully orchestrated by the secretory pathway, utilizing membrane sequestration and proteolytic steps to protect the cell from amyloid and amyloidogenic intermediates that can be toxic. While functional and pathological amyloid share similar structural features, critical differences in packaging and kinetics of assembly enable the usage of Pmel17 amyloid for normal function. The discovery of native Pmel17 amyloid in mammals provides key insight into the molecular basis of both melanin formation and amyloid pathology, and demonstrates that native amyloid (amyloidin) may be an ancient, evolutionarily conserved protein quaternary structure underpinning diverse pathways contributing to normal cell and tissue physiology

Transonic small-disturbance theory for lightly loaded cascades

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76863/1/AIAA-7841-736.pd

Million-fold sensitivity enhancement in proteopathic seed amplification assays for biospecimens by Hofmeister ion comparisons

Recent work with prion diseases and synucleinopathies indicates that accurate diagnostic methods for protein-folding diseases can be based on the ultrasensitive, amplified measurement of pathological aggregates in biospecimens. A better understanding of the physicochemical factors that control the seeded polymerization of such aggregates, and their amplification in vitro, should allow improvements in existing assay platforms, as well as the development of new assays for other proteopathic aggregates. Here, we systematically investigated the effects of the ionic environment on the polymerization of tau, α-synuclein, and the prion protein (PrP) induced by aggregates in biospecimens. We screened salts of the Hofmeister series, a relative ordering of strongly and weakly hydrated salts that tend to precipitate or solubilize proteins. We found that sensitivities of tau-based assays for Alzheimer’s seeds and PrP-based assays for prions were best in weakly hydrated anions. In contrast, we saw an inverse trend with different tau-based assays, improving detection sensitivity for progressive supranuclear palsy seeds by ≈106. Hofmeister analysis also improved detection of sporadic Creutzfeldt–Jakob disease prions in human nasal brushings and chronic wasting disease prions in deer-ear homogenates. Our results demonstrate strong and divergent influences of ionic environments on the amplification and detection of proteopathic seeds as biomarkers for protein-folding diseases

Comparison of registered and published outcomes in randomized controlled trials: a systematic review

Abstract Background Clinical trial registries can improve the validity of trial results by facilitating comparisons between prospectively planned and reported outcomes. Previous reports on the frequency of planned and reported outcome inconsistencies have reported widely discrepant results. It is unknown whether these discrepancies are due to differences between the included trials, or to methodological differences between studies. We aimed to systematically review the prevalence and nature of discrepancies between registered and published outcomes among clinical trials. Methods We searched MEDLINE via PubMed, EMBASE, and CINAHL, and checked references of included publications to identify studies that compared trial outcomes as documented in a publicly accessible clinical trials registry with published trial outcomes. Two authors independently selected eligible studies and performed data extraction. We present summary data rather than pooled analyses owing to methodological heterogeneity among the included studies. Results Twenty-seven studies were eligible for inclusion. The overall risk of bias among included studies was moderate to high. These studies assessed outcome agreement for a median of 65 individual trials (interquartile range [IQR] 25–110). The median proportion of trials with an identified discrepancy between the registered and published primary outcome was 31 %; substantial variability in the prevalence of these primary outcome discrepancies was observed among the included studies (range 0 % (0/66) to 100 % (1/1), IQR 17–45 %). We found less variability within the subset of studies that assessed the agreement between prospectively registered outcomes and published outcomes, among which the median observed discrepancy rate was 41 % (range 30 % (13/43) to 100 % (1/1), IQR 33–48 %). The nature of observed primary outcome discrepancies also varied substantially between included studies. Among the studies providing detailed descriptions of these outcome discrepancies, a median of 13 % of trials introduced a new, unregistered outcome in the published manuscript (IQR 5–16 %). Conclusions Discrepancies between registered and published outcomes of clinical trials are common regardless of funding mechanism or the journals in which they are published. Consistent reporting of prospectively defined outcomes and consistent utilization of registry data during the peer review process may improve the validity of clinical trial publications

Real time quaking-induced conversion analysis of cerebrospinal fluid in sporadic Creutzfeldt-Jakob disease

OBJECTIVE: Current cerebrospinal fluid (CSF) tests for sporadic Creutzfeldt-Jakob disease (sCJD) are based on the detection of surrogate markers of neuronal damage such as CSF 14-3-3 which are not specific for sCJD. A number of prion protein conversion assays have been developed, including real-time quaking induced conversion (RT-QuIC). The objective of this study is to investigate whether CSF RT-QuIC analysis could be used as a diagnostic test in sCJD. METHODS: An exploratory study was undertaken which analysed 108 CSF samples from patients with neuropathologically confirmed sCJD or from control patients. Of the 108 CSF samples 56 were from sCJD patients (30 female, 26 male, aged 31–84 years; 62.3 ± 13.5 years) and 52 were from control patients (26 female, 26 male, aged 43–84 years; 67.8 ± 10.4 years). A confirmatory group of 118 patients were subsequently examined which consisted of 67 cases of neuropathologically confirmed sCJD (33 female, 34 male, aged 39–82 years; 67.5 ± 9.0 years) and 51 control cases (26 female, 25 male, aged 36–87 years; 63.5 ± 11.6 years). RESULTS: The exploratory study showed that RT-QuIC analysis had a sensitivity of 91% and a specificity of 98% for the diagnosis of sCJD. These results were confirmed in the confirmatory study which showed that CSF RT-QuIC analysis had a sensitivity and specificity of 87% and 100% respectively. INTERPRETATION: This study shows that CSF RT-QuIC analysis has the potential to be a more specific diagnostic test for sCJD than current CSF tests

Evolution of the Surface Science of Catalysis from Single Crystals to Metal Nanoparticles under Pressure

Vacuum studies of metal single crystal surfaces using electron and molecular beam scattering revealed that the surface atoms relocate when the surface is clean (reconstruction) and when it is covered by adsorbates (adsorbate induced restructuring). It was also discovered that atomic steps and other low coordination surface sites are active for breaking chemical bonds (H-H, O=O, C-H, C=O and C-C) with high reaction probability. Investigations at high reactant pressures using sum frequency generation (SFG)--vibrational spectroscopy and high pressure scanning tunneling microscopy (HPSTM) revealed bond breaking at low reaction probability sites on the adsorbate-covered metal surface, and the need for adsorbate mobility for continued turnover. Since most catalysts (heterogeneous, enzyme and homogeneous) are nanoparticles, colloid synthesis methods were developed to produce monodispersed metal nanoparticles in the 1-10 nm range and controlled shapes to use them as new model catalyst systems in two-dimensional thin film form or deposited in mesoporous three-dimensional oxides. Studies of reaction selectivity in multipath reactions (hydrogenation of benzene, cyclohexene and crotonaldehyde) showed that reaction selectivity depends on both nanoparticle size and shape. The oxide-metal nanoparticle interface was found to be an important catalytic site because of the hot electron flow induced by exothermic reactions like carbon monoxide oxidation