Charge Solitons in 1-D Arrays of Serially Coupled Josephson Junctions

We study a 1-D array of Josephson coupled superconducting grains with kinetic inductance which dominates over the Josephson inductance. In this limit the dynamics of excess Cooper pairs in the array is described in terms of charge solitons, created by polarization of the grains. We analyze the dynamics of these topological excitations, which are dual to the fluxons in a long Josephson junction, using the continuum sine-Gordon model. We find that their classical relativistic motion leads to saturation branches in the I-V characteristic of the array. We then discuss the semi-classical quantization of the charge soliton, and show that it is consistent with the large kinetic inductance of the array. We study the dynamics of a quantum charge soliton in a ring-shaped array biased by an external flux through its center. If the dephasing length of the quantum charge soliton is larger than the circumference of the array, quantum phenomena like persistent current and coherent current oscillations are expected. As the characteristic width of the charge soliton is of the order of 100 microns, it is a macroscopic quantum object. We discuss the dephasing mechanisms which can suppress the quantum behaviour of the charge soliton.Comment: 26 pages, LaTex, 7 Postscript figure

A model for control of HIV/AIDS with parental care

In this study we investigate the HIV/AIDS epidemic in a population which experiences a significant flow of immigrants. We derive and analyze a mathematical model that describes the dynamics of HIV infection among the immigrant youths and how parental care can minimize or prevent the spread of the disease in the population. We analyze the model with both screening control and parental care, then investigate its stability and sensitivity behavior. We also conduct both qualitative and quantitative analyses. It is observed that in the absence of infected youths, disease-free equilibrium is achievable and is globally asymptotically stable. We establish optimal strategies for the control of the disease with screening and parental care, and provide numerical simulations to illustrate the analytic results.Web of Scienc

Compressed Sensing for Multidimensional Spectroscopy Experiments

Compressed sensing is a processing method that significantly reduces the number of measurements needed to accurately resolve signals in many fields of science and engineering. We develop a two-dimensional variant of compressed sensing for multidimensional spectroscopy and apply it to experimental data. For the model system of atomic rubidium vapor, we find that compressed sensing provides an order-of-magnitude (about 10-fold) improvement in spectral resolution along each dimension, as compared to a conventional discrete Fourier transform, using the same data set. More attractive is that compressed sensing allows for random undersampling of the experimental data, down to less than 5% of the experimental data set, with essentially no loss in spectral resolution. We believe that by combining powerful resolution with ease of use, compressed sensing can be a powerful tool for the analysis and interpretation of ultrafast spectroscopy data.Chemistry and Chemical Biolog

Search algorithms as a framework for the optimization of drug combinations

Combination therapies are often needed for effective clinical outcomes in the management of complex diseases, but presently they are generally based on empirical clinical experience. Here we suggest a novel application of search algorithms, originally developed for digital communication, modified to optimize combinations of therapeutic interventions. In biological experiments measuring the restoration of the decline with age in heart function and exercise capacity in Drosophila melanogaster, we found that search algorithms correctly identified optimal combinations of four drugs with only one third of the tests performed in a fully factorial search. In experiments identifying combinations of three doses of up to six drugs for selective killing of human cancer cells, search algorithms resulted in a highly significant enrichment of selective combinations compared with random searches. In simulations using a network model of cell death, we found that the search algorithms identified the optimal combinations of 6-9 interventions in 80-90% of tests, compared with 15-30% for an equivalent random search. These findings suggest that modified search algorithms from information theory have the potential to enhance the discovery of novel therapeutic drug combinations. This report also helps to frame a biomedical problem that will benefit from an interdisciplinary effort and suggests a general strategy for its solution.Comment: 36 pages, 10 figures, revised versio

Concurrent Validity and Reliability of Average Heart Rate and Energy Expenditure of Identical Garmin Instinct Watches During Low Intensity Resistance Training

ABSTRACT Wearable technology and resistance training are two of the top five worldwide fitness trends for 2022 as determined by ACSM. Many devices, such as Garmin’s Instinct, have functions to track various physiological aspects during resistance training. However, to our knowledge, independent verification of the validity and reliability of these devices for estimating average heart rate (HR) and energy expenditure (EE) during resistance training are nonexistent. PURPOSE: To determine the concurrent validity and reliability of identical Garmin Instinct watches during resistance training. METHODS: Twenty subjects (n=10 female and male; age: 23.2±7.7 years; height: 169.7±11.1; weight: 76.3±15.7 kg) completed this study. Two Garmin Instinct watches were evaluated, along with the Polar H10 chest strap and Cosmed K5 portable metabolic unit as the criterion devices for average HR and EE, respectively. Subjects completed 4 circuits of 4 exercises (front squat, reverse lunge, push-ups, and shoulder press) using dumbbells at a light intensity with 1 set of 10 repetitions per exercise, 30 seconds rest between exercises, and 1-1.5 min. rest between circuits. Data were analyzed for validity (Mean Absolute Percent Error [MAPE] and Lin’s Concordance Coefficient [CCC]) and reliability (Coefficient of Variation [CV]), with predetermined thresholds of MAPE0.70, and CVRESULTS: Garmin Instinct 1 and Instinct 2 were significantly (

Epithelial chemokine CXCL14 synergizes with CXCL12 via allosteric modulation of CXCR4

The chemokine receptor, CXC chemokine receptor 4 (CXCR4), is selective for CXC chemokine ligand 12 (CXCL12), is broadly expressed in blood and tissue cells, and is essential during embryogenesis and hematopoiesis. CXCL14 is a homeostatic chemokine with unknown receptor selectivity and preferential expression in peripheral tissues. Here, we demonstrate that CXCL14 synergized with CXCL12 in the induction of chemokine responses in primary human lymphoid cells and cell lines that express CXCR4. Combining subactive concentrations of CXCL12 with 100–300 nM CXCL14 resulted in chemotaxis responses that exceeded maximal responses that were obtained with CXCL12 alone. CXCL14 did not activate CXCR4-expressing cells (i.e., failed to trigger chemotaxis and Ca2+ mobilization, as well as signaling via ERK1/2 and the small GTPase Rac1); however, CXCL14 bound to CXCR4 with high affinity, induced redistribution of cell-surface CXCR4, and enhanced HIV-1 infection by >3-fold. We postulate that CXCL14 is a positive allosteric modulator of CXCR4 that enhances the potency of CXCR4 ligands. Our findings provide new insights that will inform the development of novel therapeutics that target CXCR4 in a range of diseases, including cancer, autoimmunity, and HIV.—Collins, P. J., McCully, M. L., Mart´ınez-Muñoz, L., Santiago, C.,Wheeldon, J., Caucheteux, S., Thelen, S., Cecchinato, V., Laufer, J.M., Purvanov, V.,Monneau, Y. R., Lortat-Jacob, H., Legler, D. F., Uguccioni, M., Thelen, M., Piguet, V., Mellado, M., Moser, B. Epithelial chemokine CXCL14 synergizes with CXCL12 via allosteric modulation of CXCR4. FASEB J. 31, 000–000 (2017). www.fasebj.or

Hydra: A mixture modeling framework for subtyping pediatric cancer cohorts using multimodal gene expression signatures.

Precision oncology has primarily relied on coding mutations as biomarkers of response to therapies. While transcriptome analysis can provide valuable information, incorporation into workflows has been difficult. For example, the relative rather than absolute gene expression level needs to be considered, requiring differential expression analysis across samples. However, expression programs related to the cell-of-origin and tumor microenvironment effects confound the search for cancer-specific expression changes. To address these challenges, we developed an unsupervised clustering approach for discovering differential pathway expression within cancer cohorts using gene expression measurements. The hydra approach uses a Dirichlet process mixture model to automatically detect multimodally distributed genes and expression signatures without the need for matched normal tissue. We demonstrate that the hydra approach is more sensitive than widely-used gene set enrichment approaches for detecting multimodal expression signatures. Application of the hydra analysis framework to small blue round cell tumors (including rhabdomyosarcoma, synovial sarcoma, neuroblastoma, Ewing sarcoma, and osteosarcoma) identified expression signatures associated with changes in the tumor microenvironment. The hydra approach also identified an association between ATRX deletions and elevated immune marker expression in high-risk neuroblastoma. Notably, hydra analysis of all small blue round cell tumors revealed similar subtypes, characterized by changes to infiltrating immune and stromal expression signatures

Evaluation of Average and Maximum Heart Rate of Wrist-worn Wearable Technology Devices During Trail Running

It has been estimated that there are 20 million people who participate in trail running, and these numbers are expected to increase by 15% each year. Our laboratory group has conducted studies on the validity of wearable technology watches and heart rate (HR) during trail running. The previous generation devices were mostly inaccurate, and a limitation was that reliability was not measured. PURPOSE: To determine both validity and reliability in newer models of wearable devices during trail running. METHODS: Seventeen participants (F = 7) ran on the Thunderbird Gardens Lightning Switch trail in Cedar City, UT. Demographic characteristics: Age = 25 (9) years (mean [standard deviation]), ht = 168 (9) cm, mass = 72 (14) kg. Two Garmin Instincts and two Polar Vantage M2s were evaluated, along with the Polar H10 chest strap as the criterion measure. Participants ran out on the trail for 10-minutes, and then returned to the trailhead. Maximum HR and average HR were measured during the run. Data were analyzed for validity (Mean Absolute Percent Error [MAPE] and Lin’s Concordance [CCC]) and reliability (Coefficient of Variation [CV] and Intraclass Correlation Coefficient [ICC]). Predetermined thresholds were: MAPE0.70, CV0.70. RESULTS: The Garmin Instinct met the threshold for both reliability tests for average and maximum HR (see table). The Garmin Instinct and Polar Vantage met the threshold for both validity tests for maximum HR. CONCLUSION: In order for a device to be considered valid, it must meet the predetermined thresholds for both validity and reliability. These results indicate that only the Garmin Instinct is valid and reliable, but only for measuring maximum HR. This is challenging for those who wish to track their HR while trail running, because neither of the studied devices were valid and reliable for maximum and average HR

Average Heart Rate and Energy Expenditure Validity of Garmin Vivoactive 3 and Fenix 6 Wrist Watches During Light Circuit Resistance Training

Our laboratory recently found wrist-worn wearable technology devices to be valid for measuring average heart rate (HR), but not valid for estimated energy expenditure (EE) compared to criterion devices, during steady state aerobic training (walking, running, biking). However, the validity of wrist-worn devices for HR and EE measures during resistance training is largely unknown. PURPOSE: The purpose of this study was to determine if two wrist-worn devices, Garmin Vivoactive 3 and Garmin Fenix 6 Pro, record valid measures of average HR and EE while performing circuit resistance training. METHODS: Twenty participants (n=10 female, n=10 male; age: 23.2 ± 7.7 years) completed this study. The Garmin Vivoactive 3 and Garmin Fenix 6 Pro were tested along with the Polar H10 chest strap and Cosmed K5 portable metabolic unit as the criterions for average HR and EE, respectively. Participants completed 4 circuits of 4 exercises (front squat, reverse lunge, push-ups, and shoulder press) using dumbbells at a light intensity with 1 set of 10 repetitions per exercise and 30 seconds rest between exercises and 1-1.5 min. rest between circuits. Mean absolute percent error (MAPE, ≤10%) and Lin’s Concordance (ρ≥0.7) were used to validate the device’s average HR (in bpm) and estimated EE (in kcals) compared to criterion reference devices. Dependent T-tests determined differences (p≤0.05). RESULTS: Average HR for Garmin Vivoactive 3 and Fenix 6 Pro were significantly different (p\u3c0.01) than the Polar H10 (115.0±23.9 and 124.5±15.4 vs 128.9±19.0 bpm, respectively), and were not considered valid (MAPE: 44.8% and 25.1%; Lin’s Concordance: 0.50 and 0.63, respectively). Estimated EE for Garmin Vivoactive 3 and Fenix 6 Pro were significantly different (p\u3c0.0001) than the Cosmed K5 (31.7±12.3 and 39.7±13.1 vs 20.3±5.5 kcals, respectively), and were not considered valid (MAPE: 309.7% and 322.1%; Lin’s Concordance: 0.04 and 0.15, respectively). CONCLUSION: Anyone involved in any resistance training aspect should be aware of the limitations of these wrist-worn devices in measuring average HR or EE

Elite control of HIV is associated with distinct functional and transcriptional signatures in lymphoid tissue CD8+ T cells

The functional properties of circulating CD8+ T cells have been associated with immune control of HIV. However, viral replication occurs predominantly in secondary lymphoid tissues, such as lymph nodes (LNs). We used an integrated single-cell approach to characterize effective HIV-specific CD8+ T cell responses in the LNs of elite controllers (ECs), defined as individuals who suppress viral replication in the absence of antiretroviral therapy (ART). Higher frequencies of total memory and follicle-homing HIV-specific CD8+ T cells were detected in the LNs of ECs compared with the LNs of chronic progressors (CPs) who were not receiving ART. Moreover, HIV-specific CD8+ T cells potently suppressed viral replication without demonstrable cytolytic activity in the LNs of ECs, which harbored substantially lower amounts of CD4+ T cell–associated HIV DNA and RNA compared with the LNs of CPs. Single-cell RNA sequencing analyses further revealed a distinct transcriptional signature among HIV-specific CD8+ T cells from the LNs of ECs, typified by the down-regulation of inhibitory receptors and cytolytic molecules and the up-regulation of multiple cytokines, predicted secreted factors, and components of the protein translation machinery. Collectively, these results provide a mechanistic framework to expedite the identification of novel antiviral factors, highlighting a potential role for the localized deployment of noncytolytic functions as a determinant of immune efficacy against HIV