Geometric Hamilton-Jacobi Theory

The Hamilton-Jacobi problem is revisited bearing in mind the consequences arising from a possible bi-Hamiltonian structure. The problem is formulated on the tangent bundle for Lagrangian systems in order to avoid the bias of the existence of a natural symplectic structure on the cotangent bundle. First it is developed for systems described by regular Lagrangians and then extended to systems described by singular Lagrangians with no secondary constraints. We also consider the example of the free relativistic particle, the rigid body and the electron-monopole system.Comment: 40 page

Electron acceleration by turbulent plasmoid reconnection

In space and astrophysical plasmas, like in planetary magnetospheres, as that of Mercury,energetic electrons are often found near current sheets (CSs), which hints at electron acceleration by magnetic reconnection. Unfortunately, electron acceleration by reconnection is not well understood, yet. In particular, acceleration by turbulent plasmoid reconnection. We have investigated electron acceleration by turbulent plasmoid reconnection, described by MHD simulations, via test particle calculations. In order to avoid resolving all relevant turbulence scales down to the dissipation scales, a mean-field turbulence model is used to describe the turbulence of sub-grid scales (SGS) and their effects via a turbulent electromotive force (EMF). The mean-field model describes the turbulent EMF as a function of the mean values of current density, vorticity, magnetic field as well as of the energy, cross-helicity and residual helicity of the turbulence. We found that, mainly around X-points of turbulent reconnection, strongly enhanced localized EMFs most efficiently accelerated electrons and caused the formation of power-law spectra. Magnetic-field-aligned EMFs, caused by the turbulence, dominate the electron acceleration process. Scaling the acceleration processes to parameters of the Hermean magnetotail, electron energies up to 60 keV can be reached by turbulent plasmoid reconnection through the thermal plasma.Comment: 2018PhPl...25d2904

Therapeutic potential of delivering arsenic trioxide into HPV-infected cervical cancer cells using liposomal nanotechnology

Arsenic trioxide (ATO) has been used successfully to treat acute promyelocytic leukaemia, and since this discovery, it has also been researched as a possible treatment for other haematological and solid cancers. Even though many positive results have been found in the laboratory, wider clinical use of ATO has been compromised by its toxicity at higher concentrations. The aim of this study was to explore an improved method for delivering ATO using liposomal nanotechnology to evaluate whether this could reduce drug toxicity and improve the efficacy of ATO in treating human papillomavirus (HPV)-associated cancers. HeLa, C33a, and human keratinocytes were exposed to 5 μm of ATO in both free and liposomal forms for 48 h. The stability of the prepared samples was tested using inductively coupled plasma optical emission spectrometer (ICP-OES) to measure the intracellular arsenic concentrations after treatment. Fluorescent double immunocytochemical staining was carried out to evaluate the protein expression levels of HPV-E6 oncogene and caspase-3. Cell apoptosis was analysed by flow cytometry. Results showed that liposomal ATO was more effective than free ATO in reducing protein levels of HPV-E6 and inducing cell apoptosis in HeLa cells. Moreover, lower toxicity was observed when liposomal-delivered ATO was used. This could be explained by lower intracellular concentrations of arsenic. The slowly accumulated intracellular ATO through liposomal delivery might act as a reservoir which releases ATO gradually to maintain its anti-HPV effects. To conclude, liposome-delivered ATO could protect cells from the direct toxic effects induced by higher concentrations of intracellular ATO. Different pathways may be involved in this process, depending on local architecture of the tissues and HPV status

Capillarity-like growth of protein folding nuclei

We analyzed folding routes predicted by a variational model in terms of a generalized formalism of the capillarity scaling theory for 28 two-state proteins. The scaling exponent ranged from 0.2 to 0.45 with an average of 0.33. This average value corresponds to packing of rigid objects.That is, on average the folded core of the nucleus is found to be relatively diffuse. We also studied the growth of the folding nucleus and interface along the folding route in terms of the density or packing fraction. The evolution of the folded core and interface regions can be classified into three patterns of growth depending on how the growth of the folded core is balanced by changes in density of the interface. Finally, we quantified the diffuse versus polarized structure of the critical nucleus through direct calculation of the packing fraction of the folded core and interface regions. Our results support the general picture of describing protein folding as the capillarity-like growth of folding nuclei.Comment: 16 pages,6 figures. Submitted to Proc.Natl.Acad.Sc

The Jlab Upgrade - Studies of the Nucleon with CLAS12

An overview is presented on the program to study the nucleon structure at the 12 GeV JLab upgrade using the CLAS12 detector. The focus is on deeply virtual exclusive processes to access the generalized parton distributions, semni-inclusive processes to study transverse momentum dependent distribution functions, and inclusive spin structure functions and resonance transition form factors at high Q^2 and with high precision.Comment: 7 pages, 12 figures, NSTAR 2007 conference, Bonn, September 5-8, 200

Immobilisation of electrochemically active bacteria on screen-printed electrodes for rapid in situ toxicity biosensing

Microbial biosensors can be an excellent alternative to classical methods for toxicity monitoring, which are time-consuming and not sensitive enough. However, bacteria typically connect to electrodes through biofllm formation, leading to problems due to lack of uniformity or long device production times. A suitable immobilisation technique can overcome these challenges. Still, they may respond more slowly than biofllm-based electrodes because bacteria gradually adapt to electron transfer during biofllm formation. In this study, we propose a controlled and reproducible way to fabricate bacteria-modified electrodes. The method consists of an immobilisation step using a cellulose matrix, followed by an electrode polarization in the presence of ferricyanide and glucose. Our process is short, reproducible and led us to obtain ready-to-use electrodes featuring a high-current response. An excellent shelf-life of the immobilised electrochemically active bacteria was demonstrated for up to one year. After an initial 50% activity loss in the first month, no further declines have been observed over the following 11 months. We implemented our bacteria-modified electrodes to fabricate a lateral flow platform for toxicity monitoring using formaldehyde (3%). Its addition led to a 59% current decrease approximately 20 min after the toxic input. The methods presented here offer the ability to develop a high sensitivity, easy to produce, and long shelf life bacteria-based toxicity detectors. (C) 2020 The Author(s). Published by Elsevier B.V. on behalf of Chinese Society for Environmental Sciences, Harbin Institute of Technology, Chinese Research Academy of Environmental Sciences

The structure of a polyketide synthase bimodule core

Polyketide synthases (PKSs) are predominantly microbial biosynthetic enzymes. They assemble highly potent bioactive natural products from simple carboxylic acid precursors. The most versatile families of PKSs are organized as assembly lines of functional modules. Each module performs one round of precursor extension and optional modification, followed by directed transfer of the intermediate to the next module. While enzymatic domains and even modules of PKSs are well understood, the higher-order modular architecture of PKS assembly lines remains elusive. Here, we visualize a PKS bimodule core using cryo-electron microscopy and resolve a two-dimensional meshwork of the bimodule core formed by homotypic interactions between modules. The sheet-like organization provides the framework for efficient substrate transfer and for sequestration of trans-acting enzymes required for polyketide production

Visual Acuity Loss and Associated Risk Factors in the Retrospective Progression of Stargardt Disease Study (ProgStar Report No. 2)

PURPOSE: To examine the association between characteristics of Stargardt disease and visual acuity (VA), to estimate the longitudinal rate of VA loss, and to identify risk factors for VA loss. DESIGN: Retrospective, multicenter cohort study. PARTICIPANTS: A total of 176 patients (332 eyes) with molecularly and clinically confirmed Stargardt disease enrolled from the United States and Europe. METHODS: Standardized data report forms were used to collect retrospective data on participants' characteristics and best-corrected or presenting VA from medical charts. Linear models with generalized estimating equations were used to estimate the cross-sectional associations, and linear mixed effects models were used to estimate the longitudinal VA loss. MAIN OUTCOME MEASURES: Yearly change in VA. RESULTS: The median duration of observation was 3.6 years. At baseline, older age of symptom onset was associated with better VA, and a longer duration of symptoms was associated with worse VA. Longitudinal analysis estimated an average of 0.3 lines loss (P 30 years showed 0.4 lines slower change of VA per year (P = 0.01) compared with patients with onset age ≤14 years. CONCLUSIONS: Given the overall slow rate of VA loss, VA is unlikely to be a sensitive outcome measure for treatment trials of Stargardt disease. However, given the faster decline in younger patients and those with no or mild visual impairment, VA may be a potential outcome measure for trials targeting such subgroups of patients. These observations will need to be assessed in a prospective study bearing in mind the inherent limitations of retrospective datasets