Heteroepitaxial growth of ferromagnetic MnSb(0001) films on Ge/Si(111) virtual substrates

Molecular beam epitaxial growth of ferromagnetic MnSb(0001) has been achieved on high quality, fully relaxed Ge(111)/Si(111) virtual substrates grown by reduced pressure chemical vapor deposition. The epilayers were characterized using reflection high energy electron diffraction, synchrotron hard X-ray diffraction, X-ray photoemission spectroscopy, and magnetometry. The surface reconstructions, magnetic properties, crystalline quality, and strain relaxation behavior of the MnSb films are similar to those of MnSb grown on GaAs(111). In contrast to GaAs substrates, segregation of substrate atoms through the MnSb film does not occur, and alternative polymorphs of MnSb are absent

Mechanical properties of Ti-6Al-4V selectively laser melted parts with body-centred-cubic lattices of varying cell size

Significant weight savings in parts can be made through the use of additive manufacture (AM), a process which enables the construction of more complex geometries, such as functionally graded lattices, than can be achieved conventionally. The existing framework describing the mechanical properties of lattices places strong emphasis on one property, the relative density of the repeating cells, but there are other properties to consider if lattices are to be used effectively. In this work, we explore the effects of cell size and number of cells, attempting to construct more complete models for the mechanical performance of lattices. This was achieved by examining the modulus and ultimate tensile strength of latticed tensile specimens with a range of unit cell sizes and fixed relative density. Understanding how these mechanical properties depend upon the lattice design variables is crucial for the development of design tools, such as finite element methods, that deliver the best performance from AM latticed parts. We observed significant reductions in modulus and strength with increasing cell size, and these reductions cannot be explained by increasing strut porosity as has previously been suggested. We obtained power law relationships for the mechanical properties of the latticed specimens as a function of cell size, which are similar in form to the existing laws for the relative density dependence. These can be used to predict the properties of latticed column structures comprised of body-centred-cubic (BCC) cells, and may also be adapted for other part geometries. In addition, we propose a novel way to analyse the tensile modulus data, which considers a relative lattice cell size rather than an absolute size. This may lead to more general models for the mechanical properties of lattice structures, applicable to parts of varying size

On the precipitation hardening of selective laser melted AlSi10Mg

Precipitation hardening of selective laser melted AlSi10Mg was investigated in terms of solution heat treatment and aging duration. The influence on the microstructure and hardness was established, as was the effect on the size and density of Si particles. Although the hardness changes according to the treatment duration, the maximum hardening effect falls short of the hardness of the as-built parts with their characteristic fine microstructure. This is due to the difference in strengthening mechanisms

Role of liraglutide in Alzheimer's disease pathology

Background The described relationship between Alzheimer's disease (AD) and type 2 diabetes (T2D) and the fact that AD has no succesful treatment has led to the study of antidiabetic drugs that may limit or slow down AD pathology. Main body Although T2D treatment has evident limitations, options are increasing including glucagon-like peptide 1 analogs. Among these, liraglutide (LRGT) is commonly used by T2D patients to improve beta cell function and suppress glucagon to restore normoglycaemia. Interestingly, LRGT also counterbalances altered brain metabolism and has anti-inflammatory properties. Previous studies have reported its capacity to reduce AD pathology, including amyloid production and deposition, tau hyperphosphorylation, or neuronal and synaptic loss in animal models of AD, accompanied by cognitive improvement. Given the beneficial effects of LRGT at central level, studies in patients have been carried out, showing modest beneficial effects. At present, the ELAD trial (Evaluating Liraglutide in Alzheimer's Disease NCT01843075) is an ongoing phase IIb study in patients with mild AD. In this minireview, we resume the outcomes of LRGT treatment in preclinical models of AD as well as the available results in patients up to date. Conclusion The effects of LRGT on animal models show significant benefits in AD pathology and cognitive impairment. While studies in patients are limited, ongoing clinical trials will probably provide more definitive conclusions on the role of LRGT in AD patients

Development of a clinical decision model for thyroid nodules

<p>Abstract</p> <p>Background</p> <p>Thyroid nodules represent a common problem brought to medical attention. Four to seven percent of the United States adult population (10–18 million people) has a palpable thyroid nodule, however the majority (>95%) of thyroid nodules are benign. While, fine needle aspiration remains the most cost effective and accurate diagnostic tool for thyroid nodules in current practice, over 20% of patients undergoing FNA of a thyroid nodule have indeterminate cytology (follicular neoplasm) with associated malignancy risk prevalence of 20–30%. These patients require thyroid lobectomy/isthmusectomy purely for the purpose of attaining a definitive diagnosis. Given that the majority (70–80%) of these patients have benign surgical pathology, thyroidectomy in these patients is conducted principally with diagnostic intent. Clinical models predictive of malignancy risk are needed to support treatment decisions in patients with thyroid nodules in order to reduce morbidity associated with unnecessary diagnostic surgery.</p> <p>Methods</p> <p>Data were analyzed from a completed prospective cohort trial conducted over a 4-year period involving 216 patients with thyroid nodules undergoing ultrasound (US), electrical impedance scanning (EIS) and fine needle aspiration cytology (FNA) prior to thyroidectomy. A Bayesian model was designed to predict malignancy in thyroid nodules based on multivariate dependence relationships between independent covariates. Ten-fold cross-validation was performed to estimate classifier error wherein the data set was randomized into ten separate and unique train and test sets consisting of a training set (90% of records) and a test set (10% of records). A receiver-operating-characteristics (ROC) curve of these predictions and area under the curve (AUC) were calculated to determine model robustness for predicting malignancy in thyroid nodules.</p> <p>Results</p> <p>Thyroid nodule size, FNA cytology, US and EIS characteristics were highly predictive of malignancy. Cross validation of the model created with Bayesian Network Analysis effectively predicted malignancy [AUC = 0.88 (95%CI: 0.82–0.94)] in thyroid nodules. The positive and negative predictive values of the model are 83% (95%CI: 76%–91%) and 79% (95%CI: 72%–86%), respectively.</p> <p>Conclusion</p> <p>An integrated predictive decision model using Bayesian inference incorporating readily obtainable thyroid nodule measures is clinically relevant, as it effectively predicts malignancy in thyroid nodules. This model warrants further validation testing in prospective clinical trials.</p

Mathematical modelling and numerical simulation of the morphological development of neurons

BACKGROUND: The morphological development of neurons is a very complex process involving both genetic and environmental components. Mathematical modelling and numerical simulation are valuable tools in helping us unravel particular aspects of how individual neurons grow their characteristic morphologies and eventually form appropriate networks with each other. METHODS: A variety of mathematical models that consider (1) neurite initiation (2) neurite elongation (3) axon pathfinding, and (4) neurite branching and dendritic shape formation are reviewed. The different mathematical techniques employed are also described. RESULTS: Some comparison of modelling results with experimental data is made. A critique of different modelling techniques is given, leading to a proposal for a unified modelling environment for models of neuronal development. CONCLUSION: A unified mathematical and numerical simulation framework should lead to an expansion of work on models of neuronal development, as has occurred with compartmental models of neuronal electrical activity

Autocatalytic Loop, Amplification and Diffusion: A Mathematical and Computational Model of Cell Polarization in Neural Chemotaxis

The chemotactic response of cells to graded fields of chemical cues is a complex process that requires the coordination of several intracellular activities. Fundamental steps to obtain a front vs. back differentiation in the cell are the localized distribution of internal molecules and the amplification of the external signal. The goal of this work is to develop a mathematical and computational model for the quantitative study of such phenomena in the context of axon chemotactic pathfinding in neural development. In order to perform turning decisions, axons develop front-back polarization in their distal structure, the growth cone. Starting from the recent experimental findings of the biased redistribution of receptors on the growth cone membrane, driven by the interaction with the cytoskeleton, we propose a model to investigate the significance of this process. Our main contribution is to quantitatively demonstrate that the autocatalytic loop involving receptors, cytoplasmic species and cytoskeleton is adequate to give rise to the chemotactic behavior of neural cells. We assess the fact that spatial bias in receptors is a precursory key event for chemotactic response, establishing the necessity of a tight link between upstream gradient sensing and downstream cytoskeleton dynamics. We analyze further crosslinked effects and, among others, the contribution to polarization of internal enzymatic reactions, which entail the production of molecules with a one-to-more factor. The model shows that the enzymatic efficiency of such reactions must overcome a threshold in order to give rise to a sufficient amplification, another fundamental precursory step for obtaining polarization. Eventually, we address the characteristic behavior of the attraction/repulsion of axons subjected to the same cue, providing a quantitative indicator of the parameters which more critically determine this nontrivial chemotactic response

3D-Printed Stationary Phases with Ordered Morphology: State of the Art and Future Development in Liquid Chromatography Chromatographia

Stationary phases with precisely ordered morphology have the potential to drastically 9 improve the performance of chromatographic operations, both in the analytical and in the 10 preparative/industrial fields. The recent wave of additive manufacturing, aka 3D printing, 11 gives the unprecedented ability to fabricate such stationary phases and to experimentally 12 prove theoretical principles of ordered chromatographic beds. The manufacture of highly 13 efficient chromatographic columns is becoming a reality as 3D printers become more 14 affordable and accessible, and their resolution, speed and material flexibility continue to 15 grow. This brings fresh ideas to the design of chromatographic beds, moving away from 16 stereotypical “packed” beds with spherical particles to bespoke monolithic structures to suit 17 a range of specific applications. This review aims to cover the state of the art of ordered 18 beds for liquid chromatography applications, drawing analogies between the well-19 established pillar-array columns in two-dimensions to their three-dimensional counterparts. 20 The potential use of 3D printing to create entirely new column formats and cartridge 21 designs such as microchip columns will also be discussed. Finally, key opportunities and 22 challenges which remain in the field of 3D-printed chromatography are summarised, with 23 the hope that 3D printed chromatographic columns will soon become the standard

Effect of repurposed simvastatin on disability progression in secondary progressive multiple sclerosis (MS-STAT2): a phase 3, randomised, double-blind, placebo-controlled trial

Background Despite the success of immune modulation in the treatment of relapsing multiple sclerosis, disability progression is a major problem driven by multiple mechanisms. Comorbidities (eg, vascular risk) and ageing are thought to augment these neurodegenerative pathologies. In the phase 2b MS-STAT trial of simvastatin (80 mg) versus placebo in secondary progressive multiple sclerosis (SPMS), the adjusted difference in brain atrophy rate between groups was −0·254% per year: a 43% reduction. In this phase 3 MS-STAT2 trial, we aimed to assess the efficacy of simvastatin versus placebo in slowing the progression of disability in SPMS. Methods This phase 3, randomised, double-blind, parallel group, placebo-controlled clinical trial was conducted at 31 neuroscience centres and district general hospitals in the UK. Participants aged 18–65 years with a diagnosis of SPMS and an Expanded Disability Status Scale (EDSS) of between 4·0 and 6·5 were eligible and randomly assigned (1:1) to oral simvastatin (80 mg) or matched placebo for up to 4·5 years, based on a minimisation algorithm within an independent and secure online randomisation service. All participants, site investigators, and the trial coordinating team were masked to treatment allocation. The primary outcome was time to 6-month EDSS confirmed disability progression (an increase of at least 1 point if EDSS score at baseline visit was less than 6·0 or an increase of 0·5 point if EDSS score at baseline visit was 6·0 or more) assessed in all randomly assigned participants (intention-to-treat analysis) without imputation. This study is registered with ClinicalTrials.gov (NCT03387670) and is on the ISRCTN registry (ISRCTN82598726). The study is completed. Findings Between May 10, 2018, and July 26, 2024, 1079 patients were screened for eligibility and 964 participants were randomly assigned, with 482 (50%) in the placebo group and 482 (50%) in the simvastatin group. Of all 964 participants, 704 (73%) were female and 260 (27%) were male, with a mean age of 54 years (SD 7). 173 (36%) of 482 participants in the placebo group and 192 (40%) of 482 participants in the simvastatin group had 6-month confirmed disability progression (adjusted hazard ratio 1·13 [95% CI 0·91 to 1·39], p=0·26). Although no emergent safety issues were seen, there was one serious adverse reaction (rhabdomyolysis) in the simvastatin group. 12 (2%) of 482 participants in the placebo group and five (1%) of 482 participants in the simvastatin group had a cardiovascular serious adverse event. Interpretation The MS-STAT2 trial did not show a treatment effect of simvastatin in slowing disability progression in SPMS. Simvastatin use in multiple sclerosis should be confined to existing vascular indications. Funding National Institute for Health and Care Research Health Technology Assessment Programme, UK Multiple Sclerosis Society, and the US National Multiple Sclerosis Society

Cubic MnSb : epitaxial growth of a predicted room temperature half-metal

Epitaxial films including bulklike cubic and wurtzite polymorphs of MnSb have been grown by molecular beam epitaxy on GaAs via careful control of the Sb4/Mn flux ratio. Nonzero-temperature density functional theory was used to predict ab initio the half-metallicity of the cubic polymorph and compare its spin polarization as a function of reduced magnetization with that of the well known half-metal NiMnSb. In both cases, half-metallicity is lost at a threshold magnetization reduction, corresponding to a temperature T*350 K, making epitaxial cubic MnSb a promising candidate for efficient room temperature spin injection into semiconductors