Day to Day Variability of Dynamic Knee Joint Stability in Healthy Individuals

The cause of osteoarthritis remains unknown; however abnormal joint mechanics are speculated to be an initiating factor [1]. Relating the Finite Helical Axis (FHA) to joint health may provide a means of predicting risk of joint degeneration [2]. To study dynamic knee joint stability using FHA and electromyography (EMG), it is valuable to quantify the day to day variance of these measures in a healthy population. It was hypothesized that there would be no statistically significant differences in FHA parameters or muscle patterns between days for healthy individuals. Three healthy females with intact anterior cruciate ligaments were recruited and tested 3 times during one week. Three-dimensional data for FHA determination was collected from reflective skin markers placed on each lower extremity (3 markers/segment) using an 8-camera (120 Hz) video motion capture system (Motion Analysis Corp.). A 16-channel EMG system recorded muscle activation patterns from 6 major muscles of the leg. Each subject performed two dynamic tasks: unconstrained knee flexion and extension while seated, and a single leg squat and rise. Data was analyzed using in house programs written in Matlab 7.1 (Mathworks Inc.). Four FHA parameters were described: location, translation, orientation and dispersion [2]. Muscle activity patterns were quantified using a wavelet analysis approach [3]. Due to the small sample size, a non-parametric Friedman’s test was used to detect differences in dynamic knee joint stability between days (p=0.05). Significant differences (p=0.028) were found for the extension phase of the squat in the contra lateral legs for location y, which describes the anterior/posterior location of the FHA in the knee. No significant differences were detected for any other FHA or EMG parameters. This finding suggests that the y location of the FHA during the extension phase of the squat task changes across days, and must be carefully interpreted in future studies

MRI-Based Knee Joint Laxity Measure in Healthy Individuals

A functional MRI based knee joint laxity device was developed by the current research group to enable three-dimensional (3D) evaluation of change in ligament length as a function of loading [1]. Previous studies have used the knee loading apparatus (KLA) to quantify knee joint laxity in the dominant leg of healthy individuals [1]; however anterior laxity of the knee is reported clinically as a left-right difference, and not absolute values [2]. Therefore, the purpose of this study was to quantify side-to-side differences in knee joint laxity using the KLA in a healthy population. It was hypothesized that there would be no statistically significant differences in knee joint laxity between legs for healthy individuals. One healthy female with an intact anterior cruciate ligament was recruited and tested 3 times during the span of 10 days. Magnetic Resonance (MR) imaging was used in conjunction with the KLA to obtain images of the knee joint geometry during an unloaded state and at an anterior load of 133 N. Sagittal images of the knee were manually digitized using SliceOmatic (Tomovision) to obtain 3D volumes of the femur and tibia. The displacement of the tibia at 133N was obtained from the 3D joint position of the femur relative to the tibia, specifically anterior displacement of the tibia [1]. Due to complications with data collection, results are only available for day 2 for the right leg, and days 1 and 3 for the left leg. The anterior displacement of the tibia under an anterior load of 133N was 1.29 mm for the right leg, and 0.62 ± 0.42 mm for the left leg. Due to the sample size of 1, statistical analysis was not performed. This is preliminary data; future studies will increase the number of subjects and collect data at multiple load levels

On the motion of a classical charged particle

We show that the Lorentz-Dirac equation is not an unavoidable consequence of energy-momentum conservation for a point charge. What follows solely from conservation laws is a less restrictive equation already obtained by Honig and Szamosi. The latter is not properly an equation of motion because, as it contains an extra scalar variable, it does not determine the future evolution of the charge. We show that a supplementary constitutive relation can be added so that the motion is determined and free from the troubles that are customary in Lorentz-Dirac equation, i. e. preacceleration and runaways

Post COP26: does the 1.5°C climate target remain alive?

One of the COP26 aims was to keep 1.5°C within reach by asking countries to come forward with ambitious year 2030 emission reductions targets to further pursue the necessary action to meet the Paris climate targets. We assess the mean global temperature rise given the updated year 2030 emission pledges in the context of future emission pathways considered by the international scientific community. Overall, we find current pledges are not consistent with a likely meeting of 1.5°C this century without overshoot. Meeting the 1.5°C goal in 2100 post overshoot given the pledges remains feasible, but urgent action is required to ensure pledges are met and policies are in place for the very deep and rapid emission reductions that are required post 2030

Lars Hætta’s miniature world: Sámi prison op-art autoethnography

This article examines a collection of miniature objects, now held in museum collections, which were originally made by a Sámi political prisoner in Norway during the mid-19th century as part of an educational programme. The author draws on recent developments in the theory of miniaturization to consider these miniatures as examples of prison op-art autoethnography: communicative devices which seek to address broad and complex social issues through the process of the creation and distribution of semiophorically functionless mimetic objects of reduced scale and complexity, and which reflect the restrictions of incarcerated artistic expression and the questions this raises regarding authenticity and hybridity

NF-κB-inducing kinase regulates selected gene expression in the Nod2 signaling pathway

The innate immune system surveys the extra- and intracellular environment for the presence of microbes. Among the intracellular sensors is a protein known as Nod2, a cytosolic protein containing a leucine-rich repeat domain. Nod2 is believed to play a role in determining host responses to invasive bacteria. A key element in upregulating host defense involves activation of the NF-κB pathway. It has been suggested through indirect studies that NF-κB-inducing kinase, or NIK, may be involved in Nod2 signaling. Here we have used macrophages derived from primary explants of bone marrow from wild-type mice and mice that either bear a mutation in NIK, rendering it inactive, or are derived from NIK(−/−) mice, in which the NIK gene has been deleted. We show that NIK binds to Nod2 and mediates induction of specific changes induced by the specific Nod2 activator, muramyl dipeptide, and that the role of NIK occurs in settings where both the Nod2 and TLR4 pathways are activated by their respective agonists. Specifically, we have linked NIK to the induction of the B-cell chemoattractant known as BLC and suggest that this chemokine may play a role in processes initiated by Nod2 activation that lead to improved host defense

Description and evaluation of the JULES-ES set-up for ISIMIP2b

Global studies of climate change impacts that use future climate model projections also require projections of land surface changes. Simulated land surface performance in Earth system models is often affected by the atmospheric models' climate biases, leading to errors in land surface projections. Here we run the Joint UK Land Environment Simulator Earth System configuration (JULES-ES) land surface model with the Inter-Sectoral Impact Model Intercomparison Project second-phase future projections (ISIMIP2b) bias-corrected climate model data from four global climate models (GCMs). The bias correction reduces the impact of the climate biases present in individual models. We evaluate the performance of JULES-ES against present-day observations to demonstrate its usefulness for providing required information for impacts such as fire and river flow. We include a standard JULES-ES configuration without fire as a contribution to ISIMIP2b and JULES-ES with fire as a potential future development. Simulations for gross primary productivity (GPP), evapotranspiration (ET) and albedo compare well against observations. Including fire improves the simulations, especially for ET and albedo and vegetation distribution, with some degradation in shrub cover and river flow. This configuration represents some of the most current Earth system science for land surface modelling. The suite associated with this configuration provides a basis for past and future phases of ISIMIP, providing a simulation set-up, postprocessing and initial evaluation, using the International Land Model Benchmarking (ILAMB) project. This suite ensures that it is as straightforward, reproducible and transparent as possible to follow the protocols and participate fully in ISIMIP using JULES.</p

Hydrogen Epoch of Reionization Array (HERA)

The Hydrogen Epoch of Reionization Array (HERA) is a staged experiment to measure 21 cm emission from the primordial intergalactic medium (IGM) throughout cosmic reionization ($z=6-12$), and to explore earlier epochs of our Cosmic Dawn ($z\sim30$). During these epochs, early stars and black holes heated and ionized the IGM, introducing fluctuations in 21 cm emission. HERA is designed to characterize the evolution of the 21 cm power spectrum to constrain the timing and morphology of reionization, the properties of the first galaxies, the evolution of large-scale structure, and the early sources of heating. The full HERA instrument will be a 350-element interferometer in South Africa consisting of 14-m parabolic dishes observing from 50 to 250 MHz. Currently, 19 dishes have been deployed on site and the next 18 are under construction. HERA has been designated as an SKA Precursor instrument. In this paper, we summarize HERA's scientific context and provide forecasts for its key science results. After reviewing the current state of the art in foreground mitigation, we use the delay-spectrum technique to motivate high-level performance requirements for the HERA instrument. Next, we present the HERA instrument design, along with the subsystem specifications that ensure that HERA meets its performance requirements. Finally, we summarize the schedule and status of the project. We conclude by suggesting that, given the realities of foreground contamination, current-generation 21 cm instruments are approaching their sensitivity limits. HERA is designed to bring both the sensitivity and the precision to deliver its primary science on the basis of proven foreground filtering techniques, while developing new subtraction techniques to unlock new capabilities. The result will be a major step toward realizing the widely recognized scientific potential of 21 cm cosmology.Comment: 26 pages, 24 figures, 2 table

Deep computational phenotyping of genomic variants impacting the SET domain of KMT2C reveal molecular mechanisms for their dysfunction

Introduction: Kleefstra Syndrome type 2 (KLEFS-2) is a genetic, neurodevelopmental disorder characterized by intellectual disability, infantile hypotonia, severe expressive language delay, and characteristic facial appearance, with a spectrum of other distinct clinical manifestations. Pathogenic mutations in the epigenetic modifier type 2 lysine methyltransferase KMT2C have been identified to be causative in KLEFS-2 individuals.Methods: This work reports a translational genomic study that applies a multidimensional computational approach for deep variant phenotyping, combining conventional genomic analyses, advanced protein bioinformatics, computational biophysics, biochemistry, and biostatistics-based modeling. We use standard variant annotation, paralog annotation analyses, molecular mechanics, and molecular dynamics simulations to evaluate damaging scores and provide potential mechanisms underlying KMT2C variant dysfunction.Results: We integrated data derived from the structure and dynamics of KMT2C to classify variants into SV (Structural Variant), DV (Dynamic Variant), SDV (Structural and Dynamic Variant), and VUS (Variant of Uncertain Significance). When compared with controls, these variants show values reflecting alterations in molecular fitness in both structure and dynamics.Discussion: We demonstrate that our 3D models for KMT2C variants suggest distinct mechanisms that lead to their imbalance and are not predictable from sequence alone. Thus, the missense variants studied here cause destabilizing effects on KMT2C function by different biophysical and biochemical mechanisms which we adeptly describe. This new knowledge extends our understanding of how variations in the KMT2C gene cause the dysfunction of its methyltransferase enzyme product, thereby bearing significant biomedical relevance for carriers of KLEFS2-associated genomic mutations