Design of a five-axis ultra-precision micro-milling machine—UltraMill. Part 2: Integrated dynamic modelling, design optimisation and analysis

Using computer models to predict the dynamic performance of ultra-precision machine tools can help manufacturers to substantially reduce the lead time and cost of developing new machines. However, the use of electronic drives on such machines is becoming widespread, the machine dynamic performance depending not only on the mechanical structure and components but also on the control system and electronic drives. Bench-top ultra-precision machine tools are highly desirable for the micro-manufacturing of high-accuracy micro-mechanical components. However, the development is still at the nascent stage and hence lacks standardised guidelines. Part 2 of this two-part paper proposes an integrated approach, which permits analysis and optimisation of the entire machine dynamic performance at the early design stage. Based on the proposed approach, the modelling and simulation process of a novel five-axis bench-top ultra-precision micro-milling machine tool—UltraMill—is presented. The modelling and simulation cover the dynamics of the machine structure, the moving components, the control system and the machining process and are used to predict the entire machine performance of two typical configurations

Safe Trajectory Sampling in Model-Based Reinforcement Learning

Model-based reinforcement learning aims to learn a policy to solve a target task by leveraging a learned dynamics model. This approach, paired with principled handling of uncertainty allows for data-efficient policy learning in robotics. However, the physical environment has feasibility and safety constraints that need to be incorporated into the policy before it is safe to execute on a real robot. In this work, we study how to enforce the aforementioned constraints in the context of model-based reinforcement learning with probabilistic dynamics models. In particular, we investigate how trajectories sampled from the learned dynamics model can be used on a real robot, while fulfilling user-specified safety requirements. We present a model-based reinforcement learning approach using Gaussian processes where safety constraints are taken into account without simplifying Gaussian assumptions on the predictive state distributions. We evaluate the proposed approach on different continuous control tasks with varying complexity and demonstrate how our safe trajectory-sampling approach can be directly used on a real robot without violating safety constraints

5D gravity and the discrepant G measurements

It is shown that 5D Kaluza-Klein theory stabilized by an external bulk scalar field may solve the discrepant laboratory G measurements. This is achieved by an effective coupling between gravitation and the geomagnetic field. Experimental considerations are also addressed.Comment: 13 pages, to be published in: Proceedings of the 18th Course of the School on Cosmology and Gravitation: The gravitational Constant. Generalized gravitational theories and experiments (30 April-10 May 2003, Erice). Ed. by G. T. Gillies, V. N. Melnikov and V. de Sabbata, (Kluwer), 13pp. (in print) (2003

3D Printed Franz cells - update on optimization of manufacture and evaluation

The evaluation of permeation profiles from cosmetic formulations is considered to be a crucial component in both the development and quality assurance of any new product [1, 2]. Data gathered from such studies allow researchers to assess the viability of delivering different materials to and through biological membranes. To date, laboratory in vitro permeation processes require the use of modified Franz type diffusion cells, conventionally fabricated from glass, which are available in different formats that can be customised to experimental requirements [3]

Attribution of the Hemispheric Asymmetries in Trends of Stratospheric Trace Gases Inferred From Microwave Limb Sounder (MLS) Measurements

Using Microwave Limb Sounder (MLS) satellite observations, ERA‐Interim reanalysis data, and a chemistry transport model simulation, we analyze and investigate the causes of the asymmetric hemispheric trends of N2O, CH4, and HCl in the stratosphere during the period 2004–2012. We find significant hemispheric asymmetries in the trends of these trace gases in the midlatitude middle and lower stratosphere. With regard to N2O and CH4, the enhanced downwelling branch of the residual circulation in the Northern Hemisphere (NH) middle and upper stratosphere transports more N2O/CH4‐poor air from the upper stratosphere to the lower stratosphere. The enhanced poleward meridional branch of the residual circulation in the Southern Hemisphere (SH) stratosphere brings more N2O/CH4‐rich air from lower to middle latitudes. These processes therefore contribute to the negative trends of N2O and CH4 in the NH lower stratosphere and the positive trends in the SH middle stratosphere. A corresponding positive trend is found for HCl in the NH, where the deep branch of the residual circulation located in the middle and upper stratosphere strengthens, bringing more HCl‐rich air downward to the lower stratosphere, while the shallow branch of the residual circulation in the lower stratosphere weakens and leads to enhanced conversion of chlorine‐containing source gases of different lifetimes to HCl. A reversed picture emerges in the SH, where the deep branch of the residual circulation in the middle and upper stratosphere weakens, while the shallow branch in the lower stratosphere strengthens, resulting in less HCl there. In addition, the southward shift of the upwelling branch of the residual circulation in recent decades can partly explain trace gas trends above 20 hPa, while the eddy mixing has a small effect on the trends. Understanding these contributions from different processes to the hemispheric asymmetries in trends of these trace gases can help us to evaluate more accurately future changes in stratospheric composition

Structure and Metal Binding Properties of Chlamydia trachomatis YtgA

Copyright © 2019 American Society for Microbiology. All Rights Reserved. The obligate intracellular pathogen Chlamydia trachomatis is a globally significant cause of sexually transmitted bacterial infections and the leading etiological agent of preventable blindness. The first-row transition metal iron (Fe) plays critical roles in chlamydial cell biology, and acquisition of this nutrient is essential for the survival and virulence of the pathogen. Nevertheless, how C. trachomatis acquires Fe from host cells is not well understood, since it lacks genes encoding known siderophore biosynthetic pathways, receptors for host Fe storage proteins, and the Fe acquisition machinery common to many bacteria. Recent studies have suggested that C. trachomatis directly acquires host Fe via the ATP-binding cassette permease YtgABCD. Here, we characterized YtgA, the periplasmic solute binding protein component of the transport pathway, which has been implicated in scavenging Fe(III) ions. The structure of Fe(III)-bound YtgA was determined at 2.0-Å resolution with the bound ion coordinated via a novel geometry (3 Ns, 2 Os [3N2O]). This unusual coordination suggested a highly plastic metal binding site in YtgA capable of interacting with other cations. Biochemical analyses showed that the metal binding site of YtgA was not restricted to interaction with only Fe(III) ions but could bind all transition metal ions examined. However, only Mn(II), Fe(II), and Ni(II) ions bound reversibly to YtgA, with Fe being the most abundant cellular transition metal in C. trachomatis. Collectively, these findings show that YtgA is the metal-recruiting component of the YtgABCD permease and is most likely involved in the acquisition of Fe(II) and Mn(II) from host cells. Importance: Chlamydia trachomatis is the most common bacterial sexually transmitted infection in developed countries, with an estimated global prevalence of 4.2% in the 15- to 49-year age group. Although infection is asymptomatic in more than 80% of infected women, about 10% of cases result in serious disease. Infection by C. trachomatis is dependent on the ability to acquire essential nutrients, such as the transition metal iron, from host cells. In this study, we show that iron is the most abundant transition metal in C. trachomatis and report the structural and biochemical properties of the iron-recruiting protein YtgA. Knowledge of the highresolution structure of YtgA will provide a platform for future structure-based antimicrobial design approaches

Molecular Cloning, Expression Profile and 5′ Regulatory Region Analysis of Two Chemosensory Protein Genes from the Diamondback Moth, Plutella xylostella

Chemosensory proteins play an important role in transporting chemical compounds to their receptors on dendrite membranes. In this study, two full-length cDNA codings for chemosensory proteins of Plutella xylostella (Lepidoptera: Plutellidae) were obtained by RACE-PCR. PxylCSP3 and Pxyl-CSP4, with GenBank accession numbers ABM92663 and ABM92664, respectively, were cloned and sequenced. The gene sequences both consisted of three exons and two introns. RT-PCR analysis showed that Pxyl-CSP3 and Pxyl-CSP4 had different expression patterns in the examined developmental stages, but were expressed in all larval stages. Phylogenetic analysis indicated that lepidopteran insects consist of three branches, and Pxyl-CSP3 and Pxyl-CSP4 belong to different branches. The 5′regulatory regions of Pxyl-CSP3 and Pxyl-CSP4 were isolated and analyzed, and the results consist of not only the core promoter sequences (TATA-box), but also several transcriptional elements (BR-C Z4, Hb, Dfd, CF2-II, etc.). This study provides clues to better understanding the various physiological functions of CSPs in P. xylostella and other insects

Higher expression of human kallikrein 10 in breast cancer tissue predicts tamoxifen resistance

The human tissue kallikreins are secreted serine proteases, encoded by a group of homologous genes clustered in tandem on chromosome 19q13.3-4. Human kallikrein 6 and human kallikrein 10 are two new members of this family. Recently, we developed highly sensitive and specific immunofluorometric assays for human kallikrein 6 and human kallikrein 10, which allow for their quantification in tissue extracts and biological fluids. Both human kallikrein 6 and human kallikrein 10 are found to be down-regulated in breast cancer cell lines, suggesting that they may be involved in breast cancer pathogenesis and progression. In this study, we investigated the potential value of human kallikrein 6 and human kallikrein 10 as prognostic and predictive factors in breast cancer. We quantified human kallikrein 6 and human kallikrein 10 protein levels in 749 breast tumour cytosolic extracts and correlated this data with various clinicopathological variables and patient outcomes. Human kallikrein 6 and human kallikrein 10 are positively correlated with each other. Higher human kallikrein 6 and human kallikrein 10 protein levels are associated with younger age, pre-menopausal, status and tumours which are negative for oestrogen and progesterone receptors. No correlation was found between human kallikrein 6 and human kallikrein 10 levels and tumour size, grade, and nodal status. Survival analysis showed that neither human kallikrein 6 nor human kallikrein 10 are related to the rate of relapse-free and overall survival. In the analysis with respect to response to tamoxifen therapy, although human kallikrein 6 levels were not associated with tamoxifen responsiveness, higher levels of human kallikrein 10 were significantly associated with a poor response rate. This association remained significant in the multivariate analysis. Furthermore, higher human kallikrein 10 levels were significantly related with a short progression-free and post-relapse overall survival after start of tamoxifen treatment for advanced disease. Taken together, our results suggest that although human kallikrein 6 and human kallikrein 10 are not prognostic markers for breast cancer, human kallikrein 10 is an independent predictive marker for response of tamoxifen therapy

Intra- and inter-individual genetic differences in gene expression

Genetic variation is known to influence the amount of mRNA produced by a gene. Given that the molecular machines control mRNA levels of multiple genes, we expect genetic variation in the components of these machines would influence multiple genes in a similar fashion. In this study we show that this assumption is correct by using correlation of mRNA levels measured independently in the brain, kidney or liver of multiple, genetically typed, mice strains to detect shared genetic influences. These correlating groups of genes (CGG) have collective properties that account for 40-90% of the variability of their constituent genes and in some cases, but not all, contain genes encoding functionally related proteins. Critically, we show that the genetic influences are essentially tissue specific and consequently the same genetic variations in the one animal may up-regulate a CGG in one tissue but down-regulate the same CGG in a second tissue. We further show similarly paradoxical behaviour of CGGs within the same tissues of different individuals. The implication of this study is that this class of genetic variation can result in complex inter- and intra-individual and tissue differences and that this will create substantial challenges to the investigation of phenotypic outcomes, particularly in humans where multiple tissues are not readily available.

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