The nucleoskeleton as a genome-associated dynamic 'network of networks'.

In the cytosol, actin polymers, intermediate filaments and microtubules can anchor to cell surface adhesions and interlink to form intricate networks. This cytoskeleton is anchored to the nucleus through LINC (links the nucleoskeleton and cytoskeleton) complexes that span the nuclear envelope and in turn anchor to networks of filaments in the nucleus. The metazoan nucleoskeleton includes nuclear pore-linked filaments, A-type and B-type lamin intermediate filaments, nuclear mitotic apparatus (NuMA) networks, spectrins, titin, 'unconventional' polymers of actin and at least ten different myosin and kinesin motors. These elements constitute a poorly understood 'network of networks' that dynamically reorganizes during mitosis and is responsible for genome organization and integrity.

Test Structure Design for Defect Detection during Active Thermal Cycling.

Integrated power ICs acting as smart power switches for automotive or industrial applications are often subjected to active thermal cycling. Consequently, they undergo significant self-heating and are prone to various failure mechanisms related to the electro-thermo-mechanical phenomena that take place in the device metallization. In this article a test structure consisting of a lateral DMOS transistor equipped with several integrated sensors is proposed for metallization fatigue assessment. The design of the test structure is presented in detail, alongside with design considerations drawn from the literature and from simulation results. The testing procedure is then described, and experimental results are discussed. The experimental data provided by the integrated sensors correlated with the electro-thermal simulation results indicate the emergence of a failure mechanism and this is later confirmed by failure analysis. Conclusions are further drawn regarding the feasibility of using the proposed integrated sensors for monitoring defects in power ICs.

Ex ante coherence shifts.

Cushman characterizes rationalization as the inverse of rational reasoning, but this distinction is psychologically questionable. Coherence-based reasoning highlights a subtler form of bidirectionality: By distorting task attributes to make one course of action appear superior to its rivals, a patina of rationality is bestowed on the choice. This mechanism drives choice and action, rather than just following in their wake.

Gradient-Based Multi-Objective Feature Selection for Gait Mode Recognition of Transfemoral Amputees.

One control challenge in prosthetic legs is seamless transition from one gait mode to another. User intent recognition (UIR) is a high-level controller that tells a low-level controller to switch to the identified activity mode, depending on the user's intent and environment. We propose a new framework to design an optimal UIR system with simultaneous maximum performance and minimum complexity for gait mode recognition. We use multi-objective optimization (MOO) to find an optimal feature subset that creates a trade-off between these two conflicting objectives. The main contribution of this paper is two-fold: (1) a new gradient-based multi-objective feature selection (GMOFS) method for optimal UIR design; and (2) the application of advanced evolutionary MOO methods for UIR. GMOFS is an embedded method that simultaneously performs feature selection and classification by incorporating an elastic net in multilayer perceptron neural network training. Experimental data are collected from six subjects, including three able-bodied subjects and three transfemoral amputees. We implement GMOFS and four variants of multi-objective biogeography-based optimization (MOBBO) for optimal feature subset selection, and we compare their performances using normalized hypervolume and relative coverage. GMOFS demonstrates competitive performance compared to the four MOBBO methods. We achieve a mean classification accuracy of 97.14 % ± 1.51 % and 98.45 % ± 1.22 % with the optimal selected subset for able-bodied and amputee subjects, respectively, while using only 23% of the available features. Results thus indicate the potential of advanced optimization methods to simultaneously achieve accurate, reliable, and compact UIR for locomotion mode detection of lower-limb amputees with prostheses.

The molecular basis of emerin-emerin and emerin-BAF interactions.

Emerin is a conserved membrane component of nuclear lamina structure. Here, we report an advance in understanding the molecular basis of emerin function: intermolecular emerin-emerin association. There were two modes: one mediated by association of residues 170-220 in one emerin molecule to residues 170-220 in another, and the second involving residues 170-220 and 1-132. Deletion analysis showed residues 187-220 contain a positive element essential for intermolecular association in cells. By contrast, deletion of residues 168-186 inactivated a proposed negative element, required to limit or control association. Association of GFP-emerin with nuclear BAF in cells required the LEM domain (residues 1-47) and the positive element. Emerin peptide arrays revealed direct binding of residues 170-220 to residues 206-225 (the proposed positive element), residues 147-174 (particularly P(153)MYGRDSAYQSITHYRP(169)) and the LEM domain. Emerin residues 1-132 and 159-220 were each sufficient to bind lamin A or B1 tails in vitro, identifying two independent regions of molecular contact with lamins. These results, and predicted emerin intrinsic disorder, support the hypothesis that there are multiple 'backbone' and LEM-domain configurations in a proposed intermolecular emerin network at the nuclear envelope.

The Elasticity of Preferences.

We explore how preferences for attributes are constructed when people choose between multiattribute options. As found in prior research, we observed that while people make decisions, their preferences for the attributes in question shift to support the emerging choice, thus enabling confident decisions. The novelty of the studies reported here is that participants repeated the same task 6 to 8 weeks later. We found that between tasks, preferences returned to near their original levels, only to shift again to support the second choice, regardless of which choice participants made. Similar patterns were observed in a free-choice task (Study 1) and when the favorableness of options was manipulated (Study 2). It follows that preferences behave in an elastic manner: In the absence of situational pressures, they rest at baseline levels, but during the process of reaching a decision, they morph to support the chosen options. This elasticity appears to facilitate confident decision making in the face of decisional conflict.

Statistical Mechanics Approximation of Biogeography-Based Optimization.

Biogeography-based optimization (BBO) is an evolutionary algorithm inspired by biogeography, which is the study of the migration of species between habitats. This paper derives a mathematical description of the dynamics of BBO based on ideas from statistical mechanics. Rather than trying to exactly predict the evolution of the population, statistical mechanics methods describe the evolution of statistical properties of the population fitness. This paper uses the one-max problem, which has only one optimum and whose fitness function is the number of 1s in a binary string, to derive equations that predict the statistical properties of BBO each generation in terms of those of the previous generation. These equations reveal the effect of migration and mutation on the population fitness dynamics of BBO. The results obtained in this paper are similar to those for the simple genetic algorithm with selection and mutation. The paper also derives equations for the population fitness dynamics of general separable functions, and we find that the results obtained for separable functions are the same as those for the one-max problem. The statistical mechanics theory of BBO is shown to be in good agreement with simulation.

Partners and post-translational modifications of nuclear lamins.

Nuclear intermediate filament networks formed by A- and B-type lamins are major components of the nucleoskeleton that are required for nuclear structure and function, with many links to human physiology. Mutations in lamins cause diverse human diseases ('laminopathies'). At least 54 partners interact with human A-type lamins directly or indirectly. The less studied human lamins B1 and B2 have 23 and seven reported partners, respectively. These interactions are likely to be regulated at least in part by lamin post-translational modifications. This review summarizes the binding partners and post-translational modifications of human lamins and discusses their known or potential implications for lamin function.

Cancer and the nuclear pore complex.

The nuclear pore complex (NPC) mediates trafficking between the cytoplasm and nucleoplasm. It also plays key roles in other nuclear processes such as chromatin silencing, transcriptional regulation, and DNA damage repair. Nucleoporins, the structural components of the NPC, have been linked to a multitude of cancers through chromosomal translocations generating fusion proteins, changes in protein expression levels, and single point mutations. Only a small number of nucleoporins have been linked to tumorigenesis thus far, and these proteins--Nup62, Nup88, Nup98, Nup214, Nup358/RanBP2, and Tpr--line the trafficking pathway and are particularly associated with mRNA export. Overexpression of several associated nuclear export factors, most also involved in various stages of mRNA export, has been linked to cancers as well. Some oncogenic nucleoporin mutants are mislocalized to either the cytoplasm or nucleoplasm while others are incorporated into the NPC, and in all these cases they are thought to misregulate signaling pathways and transcription through either altered or diminished nucleoporin functionality. Intriguingly, many viruses target the same cancer-linked nucleoporins, often causing their degradation or mislocalization, implying that these viruses exploit some of the same weaknesses as the oncogenic defects.

Toward a General Framework of Biased Reasoning: Coherence-Based Reasoning.

A considerable amount of experimental research has been devoted to uncovering biased forms of reasoning. Notwithstanding the richness and overall empirical soundness of the bias research, the field can be described as disjointed, incomplete, and undertheorized. In this article, we seek to address this disconnect by offering "coherence-based reasoning" as a parsimonious theoretical framework that explains a sizable number of important deviations from normative forms of reasoning. Represented in connectionist networks and processed through constraint-satisfaction processing, coherence-based reasoning serves as a ubiquitous, essential, and overwhelmingly adaptive apparatus in people's mental toolbox. This adaptive process, however, can readily be overrun by bias when the network is dominated by nodes or links that are incorrect, overweighted, or otherwise nonnormative. We apply this framework to explain a variety of well-established biased forms of reasoning, including confirmation bias, the halo effect, stereotype spillovers, hindsight bias, motivated reasoning, emotion-driven reasoning, ideological reasoning, and more.

Early evaluation of a powered transfemoral prosthesis with force-modulated impedance control and energy regeneration.

Individuals with an above-knee (AK) amputation typically use passive prostheses, whether reactive (microprocessor) or purely mechanical. Though sufficient for walking, these solutions lack the positive power generation observed in able-bodied individuals. Active (powered) prostheses can provide positive power but suffer complex control and limited energy storage capacities. These shortcomings motivate the development of an active prosthesis implementing a novel impedance controller design with energy regeneration. The controller requires only five tuning parameters that are intuitive to adjust in contrast to the current standard-finite state machine impedance scheduling of up to 45 gains. This simplification is uniquely achieved by modulating knee joint impedance by axial shank force. Furthermore, the proposed control approach introduces analytical guidance for impedance tuning to purposely integrate energy regeneration; specifically, a precise amount of negative damping is injected into the joint. A pilot study conducted with a volunteer with an AK amputation walking at three distinct speeds and at continually self-selected varying speeds demonstrated the adaptability of the controller to changes in speed. Self-powered operation was attained for all trials despite low mechanical component efficiencies. These early results suggest the efficacy of simplifying impedance control tuning and fusing control and energy regeneration in transfemoral prostheses.

A probabilistic analysis of a simplified biogeography-based optimization algorithm.

Biogeography-based optimization (BBO) is a population-based evolutionary algorithm (EA) that is based on the mathematics of biogeography. Biogeography is the study of the geographical distribution of biological organisms. We present a simplified version of BBO and perform an approximate analysis of the BBO population using probability theory. Our analysis provides approximate values for the expected number of generations before the population's best solution improves, and the expected amount of improvement. These expected values are functions of the population size. We quantify three behaviors as the population size increases: first, we see that the best solution in the initial randomly generated population improves; second, we see that the expected number of generations before improvement increases; and third, we see that the expected amount of improvement decreases.

Moving a research lab during the COVID-19 pandemic.

The COVID-19 pandemic has created additional challenges for mid-career investigators seeking new academic opportunities. JCB asked scientists to share their experiences of uprooting their research careers and laboratories during the pandemic.

New investigators in the time of the COVID-19 pandemic.

JCB checks in with newly independent cell biologists and learns about their experience running a lab during the COVID-19 pandemic.

Toward Minimal-Sensing Locomotion Mode Recognition for a Powered Knee-Ankle Prosthesis.

OBJECTIVE: Locomotion mode recognition (LMR) enables seamless and natural transitions between low-level control systems in a powered prosthesis. We present a new optimization framework for LMR that eliminates irrelevant or redundant features and measurement signals while still maintaining performance. METHODS: We use multi-objective biogeography-based optimization to find a compromise solution between performance and the minimization of feature set size. Experimental data are collected from four transfemoral users walking with a powered knee-ankle prosthesis. We compare the performance of LMR systems trained with the optimal feature subsets and with the full feature set using a deep neural network classifier across six locomotion modes: standing, flat-ground walking, stair up/down, and ramp up/down. RESULTS: Statistical tests indicate that classifier performance using the optimal feature subsets is statistically equal to that using the full feature set. The LMR trained with an optimal subset results in the 1.98% steady-state and 4.09% transitional error rates, while only using approximately 41% and 53% of the available features and sensors, respectively. CONCLUSION: Results thus indicate the capability of the proposed framework to achieve simultaneously accurate and low-complex LMR systems for transfemoral individuals with powered prostheses. SIGNIFICANCE: This framework would potentially lead to less frequent clinical visits needed for sensor replacement and calibrations, which may save health care costs and the prosthesis user's time and energy.

Starting a lab during the COVID-19 pandemic.

JCB asks early career investigators to share their experience launching a lab during the COVID-19 pandemic.

Interviewing for a PI position-the pandemic way.

JCB asks early career researchers to share their experience interviewing for academic faculty positions and becoming independent PIs during the COVID-19 pandemic.

A Generalized Unscented Transformation for Probability Distributions.

The unscented transform uses a weighted set of samples called sigma points to propagate the means and covariances of nonlinear transformations of random variables. However, unscented transforms developed using either the Gaussian assumption or a minimum set of sigma points typically fall short when the random variable is not Gaussian distributed and the nonlinearities are substantial. In this paper, we develop the generalized unscented transform (GenUT), which uses 2n+1 sigma points to accurately capture up to the diagonal components of the skewness and kurtosis tensors of most probability distributions. Constraints can be analytically enforced on the sigma points while guaranteeing at least second-order accuracy. The GenUT uses the same number of sigma points as the original unscented transform while also being applicable to non-Gaussian distributions, including the assimilation of observations in the modeling of infectious diseases such as coronavirus (SARS-CoV-2) causing COVID-19.

Starting and Operating a Public Cardiac Catheterization Laboratory in a Low Resource Setting: The Eight-Year Story of the Uganda Heart Institute Catheter Laboratory.

Background: Low- and-middle-income-countries (LMICs) currently bear 80% of the world's cardiovascular disease (CVD) mortality burden. The same countries are underequipped to handle the disease burden due to critical shortage of resources. Functional cardiac catheterization laboratories (cath labs) are central in the diagnosis and management of CVDs. Yet, most LMICs, including Uganda, fall remarkably below the minimum recommended standards of cath lab:population ratio due to a host of factors including the start-up and recurring costs. Objectives: To review the performance, challenges and solutions employed, lessons learned, and projections for the future for a single cath lab that has been serving the Ugandan population of 40 million people in the past eight years. Methods: A retrospective review of the Uganda Heart Institute cath lab clinical database from 15 February 2012 to 31 December 2019 was performed. Results: In the initial two years, this cath lab was dependent on skills transfer camps by visiting expert teams, but currently, Ugandan resident specialists independently operate this lab. 3,542 adult and pediatric procedures were conducted in 8 years, including coronary angiograms and percutaneous coronary interventions, device implantations, valvuloplasties, and cardiac defect closures, among others. There was a consistent expansion of the spectrum of procedures conducted in this cath lab each year. The initial lack of technical expertise and sourcing for equipment, as well as the continual need for sundries present(ed) major roadblocks. Government support and leveraging existing multi-level collaborations has provided a platform for several solutions. Sustainability of cath lab services remains a significant challenge especially in relation to the high cost of sundries and other consumables amidst a limited budget. Conclusion: A practical example of how centers in LMIC can set up and sustain a public cardiac catheterization laboratory is presented. Government support, research, and training collaborations, if present, become invaluable leverage opportunities.

An Extensive Set of Kinematic and Kinetic Data for Individuals with Intact Limbs and Transfemoral Prosthesis Users.

This paper introduces an extensive human motion data set for typical activities of daily living. These data are crucial for the design and control of prosthetic devices for transfemoral prosthesis users. This data set was collected from seven individuals, including five individuals with intact limbs and two transfemoral prosthesis users. These data include the following types of movements: (1) walking at three different speeds; (2) walking up and down a 5-degree ramp; (3) stepping up and down; (4) sitting down and standing up. We provide full-body marker trajectories and ground reaction forces (GRFs) as well as joint angles, joint velocities, joint torques, and joint powers. This data set is publicly available at the website referenced in this paper. Data from flexion and extension of the hip, knee, and ankle are presented in this paper. However, the data accompanying this paper (available on the internet) include 46 distinct measurements and can be useful for validating or generating mathematical models to simulate the gait of both transfemoral prosthesis users and individuals with intact legs.