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关键词： Tumors  

摘要： The primary treatment of breast cancer is the surgical removal of the tumor with an adequate healthy tissue margin. An intraoperative method for assessing surgical margins could optimize tumor resection. Differential ion mobility spectrometry (DMS) is applicable for tissue analysis and allows for the differentiation of malignant and benign tissues. However, the number of cancer cells necessary for detection remains unknown. We studied the detection threshold of DMS for cancer cell identification with a widely characterized breast cancer cell line (BT-474) dispersed in a human myoma-based tumor microenvironment mimicking matrix (Myogel). Predetermined, small numbers of cultured BT-474 cells were dispersed into Myogel. Pure Myogel was used as a zero sample. All samples were assessed with a DMSbased custom-built device described as "the automated tissue laser analysis system " (ATLAS). We used machine learning to determine the detection threshold for cancer cell densities by training binary classifiers to distinguish the reference level (zero sample) from single predetermined cancer cell density levels. Each classifier (sLDA, linear SVM, radial SVM, and CNN) was able to detect cell density of 3700 cells mL-1 and above. These results suggest that DMS combined with laser desorption can detect low densities of breast cancer cells, at levels clinically relevant for margin detection, from Myogel samples in vitro.(c) 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://***/licenses/by/4.0/).

关键词： Shock   Molecular dynamics   Coarse-grained model   Micro-spallation   Strain rate effects  

摘要： Micro-spallation in metals is a complex dynamic fragmentation process accompanied by shock-induced overheating and melting. However, the damage evolution involved in this process, as well as the underlying mechanism, remain poorly understood. Here, a computationally efficient coarse-grained molecular dynamics (CGMD) method is used to study the micro-spallation of Cu. We demonstrate the capability of this method to reproduce results obtained by the classical molecular dynamics (MD) method in predicting spall damage of solid Cu under shock loading. CGMD simulations, however, give a higher spall strength and a later nucleation time compared with MD simulations, owing to the higher stress required to create collective voids in the former compared with the smaller individual voids in the latter. By contrast, the calculated values (including those of the compressive pressure, strain rate, and spall strength) and the predictions of microstructural evolution during micro-spallation of Cu obtained from CGMD simulations are in good agreement with those from MD simulations. This is attributed to the temperature immediately before spallation being sufficiently high for a strong shock to exist with a dominant effect on spallation, such that the collective motion of voids in CGMD simulations has a negligible effect on spall strength. A dependence of the spall strength on the strain rate of liquid Cu is proposed. This CGMD method allows the investigation of micro-spallation of Cu at the mesoscale.

关键词： Inverse differential quadrature method   Underdetermined system   Structural analysis   Composite plates  

摘要： A novel two-dimensional inverse differential quadrature method is proposed to approximate the solution of high-order system of differential equations. A critical aspect of the proposed scheme is to circumvent the error arising from high sensitivity to noise associated with high-order numerical differentiation oper-ations during direct approximation. A general framework for approximating arbitrary functions from high-order partial derivatives is developed and a comprehensive insight for the implementation of differ-ent orders of the analysis within the context of first-order shear deformation theory kinematical assump-tions governing laminated plates bending and buckling behaviours is presented. Concerning buckling analysis, a Moore-Penrose pseudo-inverse preconditioning procedure is further proposed to formulate the eigenvalue problem, since the developed algebraic expressions constitute an underdetermined sys-tem. According to the numerical tests for bending and buckling analyses of laminated plates under dif-ferent loading and boundary conditions, the accuracy of current solutions compares satisfactorily with Navier's solution, differential quadrature method and commercial finite element analysis models. Furthermore, the developed method demonstrates the potential for improved convergence in comparison with differential quadrature solutions highlighting its computational merits. (c) 2022 The Authors. Published by Elsevier Ltd.

关键词： dorsal horn   fos   interneuron   neuropathic pain   spinal cord injury   TRAP  

摘要： Neuropathic pain (NP) is one of the most common and debilitating comorbidities of spinal cord injury (SCI). Current therapies are often ineffective due in part to an incomplete understanding of underlying pathogenic mechanisms. In particular, it remains unclear how SCI leads to dysfunction in the excitability of nociceptive circuitry. The immediate early gene c-Fos has long been used in pain processing locations as a marker of neuronal activation. We employed a mouse reporter line with fospromoter driven Cre-recombinase to define neuronal activity changes in relevant pain circuitry locations following cervical spinal cord level (C)5/6 contusion (using both females and males), a SCI model that results in multiple forms of persistent NP-related behavior. SCI significantly increased activation of cervical dorsal horn (DH) projection neurons, as well as induced a selective reduction in the activation of a specific DH projection neuron subpopulation that innervates the periaqueductal gray (PAG), an important brain region involved in descending inhibitory modulation of DH pain transmission. SO also increased the activation of both protein kinase C (PKC)gamma and calretinin excitatory DH interneuron populations. Interestingly, SCI promoted a significant decrease in the activation selectively of neuronal nitric oxide synthase (nNOS)-expressing inhibitory interneurons of cervical DH. In addition, SCI altered activation of various supraspinal neuron populations associated with pain processing, including a large increase in thalamus and a significant decrease in PAG. These findings reveal a complex and diverse set of SCI-induced neuron activity changes across the pain circuitry neuraxis. Moving forward, these results can be used to inform therapeutic targeting of defined neuronal populations in NP.

关键词： ABC transporters   Bacillus thuringiensis   cadherins   cotton bollworm   protoxins  

摘要： Better understanding of the mode of action of Bacillus thuringiensis toxins is beneficial for the sustainable application of Bt crops. It is generally accepted that Cry-protoxins need to be activated by proteases to bind with midgut cell proteins and exert toxicity against insects. Bacillus thuringiensis Cry proteins are used worldwide for insect control. It was proposed that Cry-protoxins must be converted into activated toxin by proteases to bind midgut cell proteins to kill insects. However, Cry-protoxins also bind to midgut proteins and kill insects that have evolved resistance to activated toxins suggesting an independent toxicity pathway. Cadherin (CAD) and ABCC transporters are recognized as important receptors for Cry proteins. Here we constructed different Helicoverpa armigera mutations in these receptors by CRISPR/Cas9. HaCAD-KO mutant showed much higher resistance to Cry1Ac activated toxin than to Cry1Ac protoxin. In contrast, the HaABCC2-M and HaABCC3-M mutants showed higher resistance to Cry1Ac-protoxin than to activated toxin. However, in the double HaABCC2/3-KO mutant, very high levels of resistance were observed to both Cry1Ac protoxin and activated toxin, supporting that both ABC transporters have redundant functions for these two proteins. In addition, Hi5 cells transfected with HaCAD were susceptible only to the activated toxin but not to protoxin. In contrast, both forms of Cry1Ac were similarly toxic to Hi5 cells expressing HaABCC2 or HaABCC3. Co-expression of HaCAD with HaABCC2 or HaABCC3 revealed a more important synergistic effect for activated toxin compared to protoxin. Overall, our results show that toxicity of Cry1Ac activated toxin involves synergistic interplay of HaCAD with ABCC transporters, while the Cry1Ac protoxin toxicity is mainly mediated by ABCC transporters with little participation of HaCAD. These data help to understand the mode of action of Cry proteins that will be relevant to enhance efficacy and durability of Bt-crops. I

关键词： Microcirculation  

摘要： Characterization of blood flow rheology in hematological disorders is critical for understanding disease pathophysiology. Existing methods to measure blood rheological parameters are limited in their physiological relevance, and there is a need for new tools that focus on the microcirculation and extract properties at finer resolution than overall flow resistance. Herein, we present a method that combines microfluidic systems and powerful object-tracking computational technologies with mathematical modeling to separate the red blood cell flow profile into a bulk component and a wall component. We use this framework to evaluate differential contributions of effective viscosity and wall friction to the overall resistance in blood from patients with sickle cell disease (SCD) under a range of oxygen tensions. Our results demonstrate that blood from patients with SCD exhibits elevated frictional and viscous resistances at all physiologic oxygen tensions. Additionally, the viscous resistance increases more rapidly than the frictional resistance as oxygen tension decreases, which may confound analyses that extract only flow velocities or overall flow resistances. Furthermore, we evaluate the impact of transfusion treatments on the components of the resistance, revealing patient variability in blood properties that may improve our understanding of the heterogeneity of clinical responses to such treatments. Overall, our system provides a new method to analyze patient-specific blood properties and can be applied to a wide range of hematological and vascular disorders.

关键词： Freeform surfaces   Optical systems   Precision metrology   Shearing interferometry   Surface roughness measurement   Wavefront distortions  

摘要： To meet the need for the high-precision contactless measurement of the freeform surface profile during the manufacturing, we propose a high-precision measurement method that combines the laser differential confocal trigger sensor (LDCTS) and the real-time comparison method using reference planes (RCMRP). LDCTS is used to measure the freeform surface under test (FSUT), which enables the high-precision measurement of the surface profile with the large roughness and local inclination. Through the real-time comparisons of the coordinate changes of the reference planes and FSUT, the dominant straightness and rotation errors can be separated based on the error model and thus the spatial motion errors can be significantly reduced along all three axes. Combing these two strategies, we find that the inclination measurement capacity becomes larger than 25 degrees and the repeated measurement accuracy is improved to be better than 10 nm within the horizontal scanning range of 150 mm x 150 mm. Compared with the non-RCMRP method, the repeated measurement accuracy is improved by at least 5 times. We believe the proposed method provides a strategy for the high-precision measurement of freeform surface profile with large local inclination and roughness during different manufacturing periods. (C) 2022 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement

关键词： Shot noise  

摘要： We report a method to measure the size of single dielectric nanoparticles with high accuracy and precision using quantitative differential interference contrast (DIC) microscopy. Dielectric nanoparticles are detected optically by the conversion of the optical phase change into an intensity change using DIC. Phase images of individual nanoparticles were retrieved from DIC by Wiener filtering, and a quantitative methodology to extract nanoparticle sizes was developed. Using polystyrene beads of 100 nm radius as size standard, we show that the method determines this radius within a few nm accuracy. The smallest detectable polystyrene bead is limited by background and shot-noise, which depend on acquisition and analysis parameters, including the objective numerical aperture, the DIC phase offset, and the refractive index contrast between particles and their surrounding. Measurements on small beads of 15 nm nominal radius are shown, and a sensitivity limit potentially reaching down to 1.8 nm radius was inferred. As application example, individual nanodiamonds with nominal sizes below 50 nm were measured, and were found to have a nearly exponential size distribution with 28 nm mean value. Considering the importance of dielectric nanoparticles in many fields, from naturally occurring virions to polluting nanoplastics, the proposed method could offer a powerful quantitative tool for nanoparticle analysis, combining accuracy, sensitivity and high-throughput with widely available and easy-to-use DIC microscopy.