The Law of Scale Independence

Geography and geosciences deal with phenomena that span spatial scales from the molecular to the planetary, and temporal scales from instantaneous to billions of years. A strong reductionist tradition in geosciences and spatial sciences tempts us to seek to apply similar representations and process-based explanations across these vast-scale ranges, usually from a bottom-up perspective. However, the law of scale independence (LSI) states that for any phenomenon that exists across a sufficiently large range of scales, there exists a scale separation distance at which the scales are independent with respect to system dynamics and explanation. The LSI is evaluated here from five independent perspectives: geographic intuition, dynamical systems theory, Kolmogorov entropy, hierarchy theory, and algebraic graph theory. All of these support the LSI. Results indicate that rather than attempting to identify the largest or smallest relevant scales and work down or up from there, the LSI dictates a strategy of focusing directly on the most important or interesting scales. An example is given from a hierarchical state factor model of ecosystem responses to climate change

Maximum Likelihood Estimation of Individual Inbreeding Coefficients and Null Allele Frequencies

In this paper, we developed and compared several expectation-maximization (EM) algorithms to find maximum likelihood estimates of individual inbreeding coefficients using molecular marker information. The first method estimates the inbreeding coefficient for a single individual and assumes that allele frequencies are known without error. The second method jointly estimates inbreeding coefficients and allele frequencies for a set of individuals that have been genotyped at several loci. The third method generalizes the second method to include the case in which null alleles may be present. In particular, it is able to jointly estimate individual inbreeding coefficients and allele frequencies, including the frequencies of null alleles, and accounts for missing data. We compared our methods with several other estimation procedures using simulated data and found that our methods perform well. The maximum likelihood estimators consistently gave among the lowest root-mean-square-error (RMSE) of all the estimators that were compared. Our estimator that accounts for null alleles performed particularly well and was able to tease apart the effects of null alleles, randomly missing genotypes and differing degrees of inbreeding among members of the datasets we analysed. To illustrate the performance of our estimators, we analysed previously published datasets on mice (Mus musculus) and white-tailed deer (Odocoileus virginianus)

Ultra long range plasmonic waveguides using quasi two dimensional metallic layers

We calculate the bound plasmonic modes of a quantum metamaterial slab, comprised of multiple quasi two dimensional electron gas (Q2DEG) layers, whose thickness is much smaller than the optical wavelength. For the first order transverse magnetic (TM) optical and the surface plasmonic modes we find propagation constants which are independent of both the electron density and of the scattering rates in the Q2DEGs. This leads to extremely long propagation distances. In a detailed case study of a structure comprising a slab of GaAs/AlGaAs multiple quantum well (MQW) material, we find propagation lengths of 100s of mm. In addition, the electric field enhancement associated with the plasmonic resonance is found to be sufficient to induce the condition of strong coupling between the slab modes and the intersubband transitions in the MQWs

Cupid, a cell permeable peptide derived from amoeba, capable of delivering GFP into a diverse range of species

Cell permeating peptides (CPPs) are attracting great interest for use as molecular delivery vehicles for the transport of biologically active cargo across the cell membrane. The sequence of a novel CPP sequence, termed ‘Cupid’, was identified from the genome of Dictyostelium discoideum. A Cupid-Green Fluorescent Protein (Cupid-GFP) fusion protein was tested on mammalian, whole plant cells, plant leaf protoplast and fungal cell cultures and observed using confocal microscopy. GFP fluorescence builds up within the cell cytosol in 60 min, demonstrating Cupid-GFP has permeated them and folded correctly into its fluorescent form. Our combined data suggest Cupid can act as a molecular vehicle capable of delivering proteins, such as GFP, into the cytosol of a variety of cells

Accountability in Intervention Research: Developing a Fidelity Checklist of a Mental Health Intervention in Prisons

Adherence to intervention content and delivery protocols is vital in establishing the efficacy of treatment programs for mental illnesses. Using a fidelity tool during interventions can substantially increase the likelihood of clients receiving the most scientifically rigorous treatment. This article outlines the steps taken to develop a fidelity checklist to measure treatment adherence of a two-part intervention delivered in a prison setting. Researchers followed the five-step guide by Feely et al. (Child and Adolescent Social Work Journal, 35(2), 139–152: 2018) and describe the process of developing a fidelity tool to measure treatment adherence to a newly adapted CBT-based intervention designed to maximize uptake for participants with serious mental illnesses. Key decision points are discussed, along with final decisions and contextual considerations. A 26-item checklist was developed to measure treatment adherence related to process, content, and adaptations of the intervention. The checklist follows the structure of the CBT intervention, as well as provides flexibility for the delivery adaptations. Pilot testing of the checklist revealed all sessions were implemented with at least 85% fidelity, and 90% of sessions were implemented with at least 90% fidelity. Raters agreed on the fidelity of a session in 99.6% of sessions. Contextual considerations included the highly secure study setting, reconciling the constant monitoring of a group and creating a treatment environment, the flexibility mandated by the intervention, the relative newness of the intervention, and the limitations based on study aims and resources. These results illustrate how study specific considerations and challenges can be successfully navigated in the development and deployment of a fidelity tool in a real-world setting. The fidelity checklist achieved our goal of measuring treatment adherence for this intervention. In the development of a fidelity tool, we recommend leaving space for raters to note specific considerations that disrupt facilitators’ ability to deploy the intervention precisely. Measuring fidelity is imperative for mental health interventions to ensure that the treatment is responsible for the changes observed in clients

Lung Malignancy in Prostate Cancer: a Report of Both Metastatic and Primary Lung Lesions

Prostate cancer is the most common non-cutaneous malignancy diagnosed in men. When it metastasizes, it usually spreads to bone and/or lymph nodes. A handful of cases have described prostatic metastases to the lung; however, this is usually in the setting of existing bone lesions. Here we describe a unique case in which a patient was found to have both metastatic prostate cancer to the lung and a primary lung cancer in the absence of any other evidence of extra-prostatic disease

Global and Local Conformation of Human IgG Antibody Variants Rationalizes Loss of Thermodynamic Stability.

Immunoglobulin G (IgG) monoclonal antibodies (mAbs) are a major class of medicines, with high specificity and affinity towards targets spanning many disease areas. The antibody Fc (fragment crystallizable) region is a vital component of existing antibody therapeutics, as well as many next generation biologic medicines. Thermodynamic stability is a critical property for the development of stable and effective therapeutic proteins. Herein, a combination of ion-mobility mass spectrometry (IM-MS) and hydrogen/deuterium exchange mass spectrometry (HDX-MS) approaches have been used to inform on the global and local conformation and dynamics of engineered IgG Fc variants with reduced thermodynamic stability. The changes in conformation and dynamics have been correlated with their thermodynamic stability to better understand the destabilising effect of functional IgG Fc mutations and to inform engineering of future therapeutic proteins.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1002/anie.20150722

Enhanced Optical Trapping

Optical tweezers have contributed substantially to the advancement of micro-manipulation. However, they do have restrictions, mainly the limited range of materials that yield to optical trapping. Here we propose a method of employing optically trapped objects to manipulate the surrounding fluid and thus particles freely diffusing within it. We create and investigate a reconfigurable active-feedback system of optically trapped actuators, capable of manipulating translational and rotational motion of one or more nearby free objects