Review of Pedestrian Load Models for Vibration Serviceability Assessment of Floor Structures

This is the final version. Available on open access from MDPI via the DOI in this recordInnovative design and technological advancements in the construction industry have resulted in an increased use of large, slender and lightweight floors in contemporary office buildings. Compounded by an ever-increasing use of open-plan layouts with few internal partitions and thus lower damping, floor vibration is becoming a governing limit state in the modern structural design originating from dynamic footfall excitations. This could cause annoyance and discomfort to building occupants as well as knock-on management and financial consequences for facility owners. This article presents a comprehensive review pertinent to walking-induced dynamic loading of low-frequency floor structures. It is intended to introduce and explain key walking parameters in the field as well as summarise the development of previous walking models and methods for vibration serviceability assessment. Although a number of walking models and design procedures have been proposed, the literature survey highlights that further work is required in the following areas; (1) the development of a probabilistic multi-person loading model which accounts for inter- and intra-subject variabilities, (2) the identification of walking paths (routes accounting for the effect of occupancy patterns on office floors) coupled with spatial distribution of pedestrians and (3) the production of a statistical spatial response approach for vibration serviceability assessment. A stochastic approach, capable of taking into account uncertainties in loading model and vibration responses, appears to be a more reliable way forward compared to the deterministic approaches of the past and there is a clear need for further research in this areaEngineering and Physical Sciences Research Council (EPSRC)Qatar National Research Foundatio

Phase relations in K_xFe_{2-y}Se_2 and the structure of superconducting K_xFe_2Se_2 via high-resolution synchrotron diffraction

Superconductivity in iron selenides has experienced a rapid growth, but not without major inconsistencies in the reported properties. For alkali-intercalated iron selenides, even the structure of the superconducting phase is a subject of debate, in part because the onset of superconductivity is affected much more delicately by stoichiometry and preparation than in cuprate or pnictide superconductors. If high-quality, pure, superconducting intercalated iron selenides are ever to be made, the intertwined physics and chemistry must be explained by systematic studies of how these materials form and by and identifying the many coexisting phases. To that end, we prepared pure K_2Fe_4Se_5 powder and superconductors in the K_xFe_{2-y}Se_2 system, and examined differences in their structures by high-resolution synchrotron and single-crystal x-ray diffraction. We found four distinct phases: semiconducting K_2Fe_4Se_5, a metallic superconducting phase K_xFe_2Se_2 with x ranging from 0.38 to 0.58, an insulator KFe_{1.6}Se_2 with no vacancy ordering, and an oxidized phase K_{0.51(5)}Fe_{0.70(2)}Se that forms the PbClF structure upon exposure to moisture. We find that the vacancy-ordered phase K_2Fe_4Se_5 does not become superconducting by doping, but the distinct iron-rich minority phase K_xFe_2Se_2 precipitates from single crystals upon cooling from above the vacancy ordering temperature. This coexistence of metallic and semiconducting phases explains a broad maximum in resistivity around 100 K. Further studies to understand the solubility of excess Fe in the K_xFe_{2-y}Se_2 structure will shed light on the maximum fraction of superconducting K_xFe_2Se_2 that can be obtained by solid state synthesis.Comment: 12 pages, 16 figures, supplemental materia

Role of cell adhesion molecule DM-GRASP in growth and orientation of retinal ganglion cell axons

AbstractThe cell adhesion molecule (CAM) DM-GRASP was investigated with respect to a role for axonal growth and navigation in the developing visual system. Expression analysis reveals that DM-GRASP's presence is highly spatiotemporally regulated in the chick embryo retina. It is restricted to the optic fiber layer (OFL) and shows an expression maximum in a phase when the highest number of retinal ganglion cell (RGC) axons extend. In the developing retina, axons grow between the DM-GRASP-displaying OFL and the Laminin-rich basal lamina. We show that DM-GRASP enhances RGC axon extension and growth cone size on Laminin substrate in vitro. Preference assays reveal that DM-GRASP-containing lanes guide RGC axons, partially depending on NgCAM in the axonal membrane. Inhibition of DM-GRASP in organ-cultured eyes perturbs orientation of RGC axons at the optic fissure. Instead of leaving the retina, RGC axons cross the optic fissure and grow onto the opposite side of the retina. RGC axon extension per se and navigation from the peripheral retina towards the optic fissure, however, is not affected. Our results demonstrate a role of DM-GRASP for axonal pathfinding in an early phase of the formation of the higher vertebrate central nervous system

A cell wall reference profile for Miscanthus bioenergy crops highlights compositional and structural variations associated with development and organ origin

Miscanthus spp. are promising lignocellulosic energy crops, but cell wall recalcitrance to deconstruction still hinders their widespread use as bioenergy and biomaterial feedstocks. Identification of cell wall characteristics desirable for biorefining applications is crucial for lignocellulosic biomass improvement. However, the task of scoring biomass quality is often complicated by the lack of a reference for a given feedstock. A multidimensional cell wall analysis was performed to generate a reference profile for leaf and stem biomass from several miscanthus genotypes harvested at three developmentally distinct time points. A comprehensive suite of 155 monoclonal antibodies was used to monitor changes in distribution, structure and extractability of noncellulosic cell wall matrix glycans. Glycan microarrays complemented with immunohistochemistry elucidated the nature of compositional variation, and in situ distribution of carbohydrate epitopes. Key observations demonstrated that there are crucial differences in miscanthus cell wall glycomes, which may impact biomass amenability to deconstruction. For the first time, variations in miscanthus cell wall glycan components were comprehensively characterized across different harvests, organs and genotypes, to generate a representative reference profile for miscanthus cell wall biomass. Ultimately, this portrait of the miscanthus cell wall will help to steer breeding and genetic engineering strategies for the development of superior energy crops

Pancreatic Cancer Malnutrition and Pancreatic Exocrine Insufficiency in the Course of Chemotherapy in Unresectable Pancreatic Cancer

Background: Malnutrition and cachexia are common in patients with advanced pancreatic ductal adenocarcinoma (PDAC) and have a significant influence on the tolerance and response to treatments. If timely identified, malnourished PDAC patients could be treated to increase their capacity to complete the planned treatments and, therefore, possibly, improve their efficacy. Aims: The aim of this study is to assess the impact of nutritional status, pancreatic exocrine insufficiency (PEI), and other clinical factors on patient outcomes in patients with advanced PDAC. Methods: PAncreatic Cancer MAlnutrition and Pancreatic Exocrine INsufficiency in the Course of Chemotherapy in Unresectable Pancreatic Cancer (PAC-MAIN) is an international multicenter prospective observational cohort study. The nutritional status will be determined by means of Mini-Nutritional Assessment score and laboratory blood tests. PEI will be defined by reduced fecal elastase levels. MAIN OUTCOME: adherence to planned chemotherapy in the first 12 weeks following the diagnosis, according to patients' baseline nutritional status and quantified and reported as "percent of standard chemotherapy dose delivered." SECONDARY OUTCOMES: rate of chemotherapy-related toxicity, progression-free survival, survival at 6 months, overall survival, quality of life, and the number of hospitalizations. ANALYSIS: chemotherapy dosing over the first 12 weeks of therapy (i.e., percent of chemotherapy received in the first 12 weeks, as defined above) will be compared between well-nourished and malnourished patients. SAMPLE SIZE: based on an expected percentage of chemotherapy delivered of 70% in well-nourished patients, with a type I error of 0.05 and a type II error of 0.20, a sample size of 93 patients per group will be required in case of a percentage difference of chemotherapy delivered of 20% between well-nourished and malnourished patients, 163 patients per group in case of a difference of 15% between the groups, and 356 patients per group in case of a 10% difference. Centers from Russia, Romania, Turkey, Spain, Serbia, and Italy will participate in the study upon Local Ethics Committee approval. Discussion: PAC-MAIN will provide insights into the role of malnutrition and PEI in the outcomes of PDAC. The study protocol was registered at clinicaltrials.gov as NCT04112836

Selection of aptamers against triple negative breast cancer cells using high throughput sequencing

Triple-negative breast cancer is the most aggressive subtype of invasive breast cancer with a poor prognosis and no approved targeted therapy. Hence, the identification of new and specific ligands is essential to develop novel targeted therapies. In this study, we aimed to identify new aptamers that bind to highly metastatic breast cancer MDA-MB-231 cells using the cell-SELEX technology aided by high throughput sequencing. After 8 cycles of selection, the aptamer pool was sequenced and the 25 most frequent sequences were aligned for homology within their variable core region, plotted according to their free energy and the key nucleotides possibly involved in the target binding site were analyzed. Two aptamer candidates, Apt1 and Apt2, binding specifically to the target cells with Kd values of 44.3 ± 13.3 nM and 17.7 ± 2.7 nM, respectively, were further validated. The binding analysis clearly showed their specificity to MDA-MB-231 cells and suggested the targeting of cell surface receptors. Additionally, Apt2 revealed no toxicity in vitro and showed potential translational application due to its affinity to breast cancer tissue sections. Overall, the results suggest that Apt2 is a promising candidate to be used in triple-negative breast cancer treatment and/or diagnosis. © 2021, The Author(s).Tis study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UIDB/04469/2020 unit and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020—Programa Operacional Regional do Norte. Débora Ferreira (DF) is the recipient of a fellowship supported by a doctoral advanced training (call NORTE-69-2015-15) funded by the European Social Fund under the scope of Norte2020—Programa Operacional Regional do Norte. Joaquim Barbosa (JB) and Diana A. Sousa (DAS) acknowledge FCT for the Grants SFRH/BD/51109/2010 and PD/BD/139083/2018, respectively.info:eu-repo/semantics/publishedVersio

Roadmap on ferroelectric hafnia- and zirconia-based materials and devices

Ferroelectric hafnium and zirconium oxides have undergone rapid scientific development over the last decade, pushing them to the forefront of ultralow-power electronic systems. Maximizing the potential application in memory devices or supercapacitors of these materials requires a combined effort by the scientific community to address technical limitations, which still hinder their application. Besides their favorable intrinsic material properties, HfO2–ZrO2 materials face challenges regarding their endurance, retention, wake-up effect, and high switching voltages. In this Roadmap, we intend to combine the expertise of chemistry, physics, material, and device engineers from leading experts in the ferroelectrics research community to set the direction of travel for these binary ferroelectric oxides. Here, we present a comprehensive overview of the current state of the art and offer readers an informed perspective of where this field is heading, what challenges need to be addressed, and possible applications and prospects for further development

In-vivo monitoring of infectious diseases in living animals using bioluminescence imaging

Traditional methods of localizing and quantifying the presence of pathogenic microorganisms in living experimental animal models of infections have mostly relied on sacrificing the animals, dissociating the tissue and counting the number of colony forming units. However, the discovery of several varieties of the light producing enzyme, luciferase, and the genetic engineering of bacteria, fungi, parasites and mice to make them emit light, either after administration of the luciferase substrate, or in the case of the bacterial lux operon without any exogenous substrate, has provided a new alternative. Dedicated bioluminescence imaging (BLI) cameras can record the light emitted from living animals in real time allowing non-invasive, longitudinal monitoring of the anatomical location and growth of infectious microorganisms as measured by strength of the BLI signal. BLI technology has been used to follow bacterial infections in traumatic skin wounds and burns, osteomyelitis, infections in intestines, Mycobacterial infections, otitis media, lung infections, biofilm and endodontic infections and meningitis. Fungi that have been engineered to be bioluminescent have been used to study infections caused by yeasts (Candida) and by filamentous fungi. Parasitic infections caused by malaria, Leishmania, trypanosomes and toxoplasma have all been monitored by BLI. Viruses such as vaccinia, herpes simplex, hepatitis B and C and influenza, have been studied using BLI. This rapidly growing technology is expected to continue to provide much useful information, while drastically reducing the numbers of animals needed in experimental studies. © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group