High-Precision Viral Detection Using Electrochemical Kinetic Profiling of Aptamer-Antigen Recognition in Clinical Samples and Machine Learning.

High-precision viral detection at point of need with clinical samples plays a pivotal role in the diagnosis of infectious diseases and the control of a global pandemic. However, the complexity of clinical samples that often contain very low viral concentrations makes it a huge challenge to develop simple diagnostic devices that do not require any sample processing and yet are capable of meeting performance metrics such as very high sensitivity and specificity. Herein we describe a new single-pot and single-step electrochemical method that uses real-time kinetic profiling of the interaction between a high-affinity aptamer and an antigen on a viral surface. This method generates many data points per sample, which when combined with machine learning, can deliver highly accurate test results in a short testing time. We demonstrate this concept using both SARS-CoV-2 and Influenza A viruses as model viruses with specifically engineered high-affinity aptamers. Utilizing this technique to diagnose COVID-19 with 37 real human saliva samples results in a sensitivity and specificity of both 100 % (27 true negatives and 10 true positives, with 0 false negative and 0 false positive), which showcases the superb diagnostic precision of this method.

Targeting metabolic sensing switch GPR84 on macrophages for cancer immunotherapy.

INTRODUCTION: As one of the major components of the tumor microenvironment, tumor-associated macrophages (TAMs) possess profound inhibitory activity against T cells and facilitate tumor escape from immune checkpoint blockade therapy. Converting this pro-tumorigenic toward the anti-tumorigenic phenotype thus is an important strategy for enhancing adaptive immunity against cancer. However, a plethora of mechanisms have been described for pro-tumorigenic differentiation in cancer, metabolic switches to program the anti-tumorigenic property of TAMs are elusive. MATERIALS AND METHODS: From an unbiased analysis of single-cell transcriptome data from multiple tumor models, we discovered that anti-tumorigenic TAMs uniquely express elevated levels of a specific fatty acid receptor, G-protein-coupled receptor 84 (GPR84). Genetic ablation of GPR84 in mice leads to impaired pro-inflammatory polarization of macrophages, while enhancing their anti-inflammatory phenotype. By contrast, GPR84 activation by its agonist, 6-n-octylaminouracil (6-OAU), potentiates pro-inflammatory phenotype via the enhanced STAT1 pathway. Moreover, 6-OAU treatment significantly retards tumor growth and increases the anti-tumor efficacy of anti-PD-1 therapy. CONCLUSION: Overall, we report a previously unappreciated fatty acid receptor, GPR84, that serves as an important metabolic sensing switch for orchestrating anti-tumorigenic macrophage polarization. Pharmacological agonists of GPR84 hold promise to reshape and reverse the immunosuppressive TME, and thereby restore responsiveness of cancer to overcome resistance to immune checkpoint blockade.

Effect of Substrate Negative Bias on the Microstructural, Optical, Mechanical, and Laser Damage Resistance Properties of HfO2 Thin Films Grown by DC Reactive Magnetron Sputtering.

Hafnium oxide thin films have attracted great attention as promising materials for applications in the field of optical thin films and microelectronic devices. In this paper, hafnium oxide thin films were prepared via DC magnetron sputtering deposition on a quartz substrate. The influence of various negative biases on the structure, morphology, and mechanical and optical properties of the obtained films were also evaluated. XRD results indicated that (1¯11)-oriented thin films with a monoclinic phase could be obtained under the non-bias applied conditions. Increasing the negative bias could refine the grain size and inhibit the grain preferred orientation of the thin films. Moreover, the surface quality and mechanical and optical properties of the films could be improved significantly along with the increase in the negative bias and then deteriorated as the negative bias voltage arrived at -50 V. It is evident that the negative bias is an effective modulation means to modify the microstructural, mechanical, and optical properties of the films.

Widespread and complex drought effects on vegetation physiology inferred from space.

The response of vegetation physiology to drought at large spatial scales is poorly understood due to a lack of direct observations. Here, we study vegetation drought responses related to photosynthesis, evaporation, and vegetation water content using remotely sensed data, and we isolate physiological responses using a machine learning technique. We find that vegetation functional decreases are largely driven by the downregulation of vegetation physiology such as stomatal conductance and light use efficiency, with the strongest downregulation in water-limited regions. Vegetation physiological decreases in wet regions also result in a discrepancy between functional and structural changes under severe drought. We find similar patterns of physiological drought response using simulations from a soil-plant-atmosphere continuum model coupled with a radiative transfer model. Observation-derived vegetation physiological responses to drought across space are mainly controlled by aridity and additionally modulated by abnormal hydro-meteorological conditions and vegetation types. Hence, isolating and quantifying vegetation physiological responses to drought enables a better understanding of ecosystem biogeochemical and biophysical feedback in modulating climate change.

Microenvironmental control of hematopoietic stem cell fate via CXCL8 and protein kinase C.

Altered hematopoietic stem cell (HSC) fate underlies primary blood disorders but microenvironmental factors controlling this are poorly understood. Genetically barcoded genome editing of synthetic target arrays for lineage tracing (GESTALT) zebrafish were used to screen for factors expressed by the sinusoidal vascular niche that alter the phylogenetic distribution of the HSC pool under native conditions. Dysregulated expression of protein kinase C delta (PKC-δ, encoded by prkcda) increases the number of HSC clones by up to 80% and expands polyclonal populations of immature neutrophil and erythroid precursors. PKC agonists such as cxcl8 augment HSC competition for residency within the niche and expand defined niche populations. CXCL8 induces association of PKC-δ with the focal adhesion complex, activating extracellular signal-regulated kinase (ERK) signaling and expression of niche factors in human endothelial cells. Our findings demonstrate the existence of reserve capacity within the niche that is controlled by CXCL8 and PKC and has significant impact on HSC phylogenetic and phenotypic fate.

Widespread increasing vegetation sensitivity to soil moisture.

Global vegetation and associated ecosystem services critically depend on soil moisture availability which has decreased in many regions during the last three decades. While spatial patterns of vegetation sensitivity to global soil water have been recently investigated, long-term changes in vegetation sensitivity to soil water availability are still unclear. Here we assess global vegetation sensitivity to soil moisture during 1982-2017 by applying explainable machine learning with observation-based leaf area index (LAI) and hydro-climate anomaly data. We show that LAI sensitivity to soil moisture significantly increases in many semi-arid and arid regions. LAI sensitivity trends are associated with multiple hydro-climate and ecological variables, and strongest increasing trends occur in the most water-sensitive regions which additionally experience declining precipitation. State-of-the-art land surface models do not reproduce this increasing sensitivity as they misrepresent water-sensitive regions and sensitivity strength. Our sensitivity results imply an increasing ecosystem vulnerability to water availability which can lead to exacerbated reductions in vegetation carbon uptake under future intensified drought, consequently amplifying climate change.

Modulation of the spatial distribution of crystallizable emulsifiers in Pickering double emulsions.

The unique role of the spatial distribution of crystallizable emulsifiers in regulating the structure and properties of double emulsions has been gradually recognized. Herein, we utilized crystallizable monoglycerides of different carbon chain length (GMS/GMP/GML) to "structuring" the intermediate oil phase of double emulsions during a two-stage emulsification process followed by a cooling treatment. A ternary eigenvector (I, M, E) based on the numerical processing of polarization images was invented to quantitatively characterize the distribution pattern of monoglycerides. Crystallization kinetics analysis and dissipative particle dynamic simulation were then employed to reveal the regulatory mechanism for the site-specific interface distribution behavior. Results suggested that the distribution pattern of monoglycerides could be pricesly tuned as the internal interface-, external interface- or oil-phase dominated one in double emulsions. The surface activity as well as crystallization rates of monoglycerides dominated the interfacial distribution kinetics, and the cooling gradient along the interface region further regulated their interfacial distribution potential. Specificly, shorter crystallization time (t1/2) made GMP molecules rapidly solidified in oil phase, leading to the oil phase domninate crystallization (0, M, 0), whereas, slow crystallization rate rendered GML and GMS with sufficient time to diffuse to the interface, thus forming interfacial crystals ((I, 0, 0) and (0, 0, E)). The sensitivity of GML to cooling gradient along the interface region led to its preferential external interface distribution under cooling treatment. The presented study explored novel strategies that can be used in characterizing and manipulating the distribution pattern of crystallizable emulsifiers in multi-interface emulsion systems.

Effects of the Distribution Site of Crystallizable Emulsifiers on the Gastrointestinal Digestion Behavior of Double Emulsions.

Double emulsions (DEs) are promising delivery vehicles for the protective and programmed release of bioactive compounds. Herein, DEs with monoglycerides crystallized at the internal- or external interface or oil phase were fabricated. The results suggested that the crystallization site of monoglycerides exerts a significant role in retarding the structural degradation and lipid digestion of DEs by affecting the available contact area of lipase. At the initial stage of intestinal digestion, compared with noncrystalline DEs (82.1%, 3.7 min), the burst release of internal markers in the internal interface crystallized emulsions was decreased by 42.4% and the lag time of free fatty acid (FFA) release was delayed by 5.8 min in the external interface crystallized emulsions. The structural integrity and digestion kinetics of the external interface crystallized DEs were synchronized with the retention time of the interfacial crystals. Therefore, crystallizable emulsifiers exhibit unique and fine regulatory effects on the digestive properties of emulsions.

NeuroSim Simulator for Compute-in-Memory Hardware Accelerator: Validation and Benchmark.

Compute-in-memory (CIM) is an attractive solution to process the extensive workloads of multiply-and-accumulate (MAC) operations in deep neural network (DNN) hardware accelerators. A simulator with options of various mainstream and emerging memory technologies, architectures, and networks can be a great convenience for fast early-stage design space exploration of CIM hardware accelerators. DNN+NeuroSim is an integrated benchmark framework supporting flexible and hierarchical CIM array design options from a device level, to a circuit level and up to an algorithm level. In this study, we validate and calibrate the prediction of NeuroSim against a 40-nm RRAM-based CIM macro post-layout simulations. First, the parameters of a memory device and CMOS transistor are extracted from the foundry's process design kit (PDK) and employed in the NeuroSim settings; the peripheral modules and operating dataflow are also configured to be the same as the actual chip implementation. Next, the area, critical path, and energy consumption values from the SPICE simulations at the module level are compared with those from NeuroSim. Some adjustment factors are introduced to account for transistor sizing and wiring area in the layout, gate switching activity, post-layout performance drop, etc. We show that the prediction from NeuroSim is precise with chip-level error under 1% after the calibration. Finally, the system-level performance benchmark is conducted with various device technologies and compared with the results before the validation. The general conclusions stay the same after the validation, but the performance degrades slightly due to the post-layout calibration.

Dielectric Analysis of Microcapsule-Immobilized Composite Capsules Suspension: Substances Release.

Dielectric spectroscopy has unique advantages in monitoring drug release. In this work, a dielectric measurement was carried out on the release of the substances of microcapsule-immobilized composite capsules, which were fabricated by encapsulating the Perinereis aibuhitensis extract-loaded gum Arabic/gelatin microcapsules (PaE: GA/GE-MCs) in calcium alginate hydrogel (PaE: CA/GA/GE-CCs). We established the dielectric model of PaE: CA/GA/GE-CCs and got in-depth information on the systems. There are two relaxations in the dielectric spectroscopy, both of which are caused by interfacial polarization. The relaxation mechanisms correspond to the interfacial polarization of the PaE-loading core/calcium alginate shell interface and the calcium alginate shell/solution interface, respectively. Besides, the swelling of composite capsules and substance migration in the composite capsules were observed by analyzing phase parameters. Finally, the characteristic release of calcium alginate composite capsules was confirmed, and the substance release mechanism of composite capsules, namely, the swelling-diffusion mechanism, was obtained.

Dynamics of an epidemic model with advection and free boundaries.

This paper deals with the propagation dynamics of an epidemic model, which is modeled by a partially degenerate reaction-diffusion-advection system with free boundaries and sigmoidal function. We focus on the effect of small advection on the propagation dynamics of the epidemic disease. At first, the global existence and uniqueness of solution are obtained. And then, the spreading-vanishing dichotomy and the criteria for spreading and vanishing are given. Our results imply that the small advection make the disease spread more difficult.

The variation of vegetation productivity and its relationship to temperature and precipitation based on the GLASS-LAI of different African ecosystems from 1982 to 2013.

In recent years, many studies have focused on the changes of partial or single African ecosystems and the drivers of those changes. However, focusing only on partial or single ecosystems has limited the understanding of the relationships between the vegetation and climate changes in all of the African ecosystems. In this study, the temporal trends of the satellite-derived annual mean leaf area index (GLASS-LAI) were analyzed, and the inter-annual relationships were developed between the annual mean LAI and the climate variables (precipitation and temperature) for the time period ranging from 1982 to 2013. Additionally, this study applied seasonal curves and step-wise multiple regression methods to investigate the relationships between intra-annual LAI and climate changes. It was found that the GLASS-LAI over half of Africa had shown general significant greening or browning trends during the period from 1982 to 2013. From the results of inter-annual analysis, with mean annual precipitation lower than 600 mm, the greening of the savannas and grasslands in the Sahel was found to highly correspond with the increased precipitation. In contrast, the evergreen broadleaf forests in the Gulf of Guinea and Congo Basin showed strongly positive responses to the annual temperature when the mean annual temperature was below 25 °C. In regard to the intra-annual responses, the precipitation with 1-month lags was found to be helpful for the vegetation growth, with the exception of the evergreen broadleaf. The results of this research study indicated that the different land-covers in Africa had displayed clear differences in their annual trends during the examined 32-year period and had responded differently to the inter- and intra-annual climate drivers. This difference was evident by the characteristics of the vegetation covers and the geographic distributions. Therefore, further examinations of these differences can potentially improve the understanding of the land surface-atmosphere interactions among the different African ecosystems.

Dielectric Behavior and Phase Behavior of Block Copolymer PEO13-PPO30-PEO13 Aqueous Solution.

Dielectric spectroscopy can be applied to study the structure and dynamics of block polymer. In this work, dielectric measurements of block copolymer Pluronic L64 solution are carried out in the frequency range between 40 Hz and 110 MHz with variable temperatures and concentrations. We analyze the phase behavior of the PEO13-PPO30-PEO13 (Pluronic L64) aqueous system according to the concentration/temperature-dependence of direct current conductivity. The result indicates the sensitivity of the phase behavior and conductivity of the Pluronic L64 solution to temperature. Besides, two relaxations were observed: relaxation 1 (0.5 MHz) is related to the gelation process, while relaxation 2 (5 MHz) is caused by the interface polarization. On the basis of relaxation 2, the volume fraction and permittivity of the particle were calculated. The formations of the block copolymer micelle and gel are monitored successfully by the temperature/concentration-dependence of the dielectric parameters and the volume fraction.

Invasion entire solutions in a time periodic Lotka-Volterra competition system with diffusion.

This paper is concerned with invasion entire solutions of a monostable time periodic Lotka-Volterra competition-diffusion system. We first give the asymptotic behaviors of time periodic traveling wave solutions at infinity by a dynamical approach coupled with the two-sided Laplace transform. According to these asymptotic behaviors, we then obtain some key estimates which are crucial for the construction of an appropriate pair of sub-super solutions. Finally, using the sub-super solutions method and comparison principle, we establish the existence of invasion entire solutions which behave as two periodic traveling fronts with different speeds propagating from both sides of x-axis. In other words, we formulate a new invasion way of the superior species to the inferior one in a time periodic environment.

Construction of tissue-engineered laryngeal cartilage with a hollow, semi-flared shape using poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) as a scaffold.

The aim of the present study was to construct tissue-engineered laryngeal cartilage with a hollow, semi-flared shape using a poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHH) scaffold. Porous PHBHH was prepared and formed into a hollow, semi-flared shape, and the cell-material composites were cultured for one week in vitro prior to implantation in vivo. Cells of the nine rabbits of the experimental group were filled and encapsulated in the myofascial flap-shaping material composite for in situ implantation. The three rabbits in the control group were treated with the shaping material without the chondrocytes. Cartilage regeneration was assessed at six, 12 and 18 weeks after surgery. In the experimental group, the shape and porosity of the material were ideal, the cells exhibited good adhesion with the material and the myofascial flap blood supply was rich. The engineered laryngeal cartilage with the hollow, semi-flared shape was ideally formed, and the cartilage formed at six weeks after the surgery. Further maturation of the cartilage was observed at 12 and 18 weeks after the surgery. PHBHH was a suitable material for the formation of a hollow, semi-flared shape with good cellular compatibility. Myofascial flap filling and wrapping can be used to build tissue-engineered laryngeal cartilage with a hollow, semi-flared shape.

Spreading speeds and traveling waves in competitive recursion systems.

This paper is concerned with the spreading speeds and traveling wave solutions of discrete time recursion systems, which describe the spatial propagation mode of two competitive invaders. We first establish the existence of traveling wave solutions when the wave speed is larger than a given threshold. Furthermore, we prove that the threshold is the spreading speed of one species while the spreading speed of the other species is distinctly slower compared to the case when the interspecific competition disappears. Our results also show that the interspecific competition does affect the spread of both species so that the eventual population densities at the coexistence domain are lower than the case when the competition vanishes.

[Fabrication of larynx-shape tissue engineered cartilage by means of filling together with wrapping with pedicle myofascial flap].

OBJECTIVE: To explore the method of fabricating larynx-shape tissue engineered cartilage by means of filling together with wrapping with pedicle myofascial flap. METHODS: Serial steps of solution casting, extrusion molding and particulate leaching were used to make larynx-shape [poly (3-hydroxybutyrate-co-3-hydroxyhexanoate), PHBHH] biomaterial models. The chondrocytes were seeded onto PHBHH models to form cell-PHBHH composites for culture in vitro for one week and then to fill and wrap larynx-shape composites with pedicle myofascial flap. After that to implant larynx-shape composites in situ on the back of adult New Zealand white rabbits (experimental groups n = 9). Control groups (n = 3) were the same measure as experimental groups but without chondrocytes on PHBHH models. Finally, morphological observation, HE & special staining and immunohistochemical test were conducted to evaluate the cartilage regeneration and its shape at 6, 8 and 12 weeks following implantation. RESULTS: The PHBHH models appeared to be hollow half-trumpet with edges and corners of larynx-shape and its porosity > 90%. Pedicle myofascial flap using fascia as lining presented rich blood supply and had enough to fill and wrap larynx-shape composites. Tissue engineered larynx-shape cartilage specimens could be harvested at different period. It was demonstrated that the cartilaginous tissue formed in 6 weeks after implantation through histological and immunohistochemical examination and further maturity in 12 weeks and 18 weeks. But no cartilaginous tissue showed without chondrocytes on PHBHH as control groups to implant at the same time. CONCLUSION: It seems that pedicled myofascial flap showed sufficient blood supply and that the filling together with wrapping method with pedicled myofascial flap is appropriate for fabricating larynx-shape tissue engineered cartilage.