Molecular diagnostics is typically outsourced to well-equipped centralized laboratories, often far from the patient. We developed molecular assays and portable optical imaging designs that permit ...on-site diagnostics with a cost-effective mobile-phone-based multimodal microscope. We demonstrate that targeted next-generation DNA sequencing reactions and in situ point mutation detection assays in preserved tumour samples can be imaged and analysed using mobile phone microscopy, achieving a new milestone for tele-medicine technologies.
Stroke is a major cause of death, disability, and public health problems. Its intervention is limited to early treatment with thrombolytics and/or endovascular clot removal with mechanical ...thrombectomy without any available subacute or chronic neuroprotective treatments. RNS60 has reduced neuroinflammation and increased neuronal survival in several animal models of neurodegeneration and trauma. The aim here was to evaluate whether RNS60 protects the brain and cognitive function in a mouse stroke model.
Male C57BL/6J mice were subjected to sham or ischemic stroke surgery using 60-minute transient middle cerebral artery occlusion (tMCAo). In each group, mice received blinded daily administrations of RNS60 or control fluids (PNS60 or normal saline NS), beginning 2 hours after surgery over 13 days. Multiple neurobehavioral tests were conducted (Neurological Severity Score mNSS, Novel Object Recognition NOR, Active Place Avoidance APA, and the Conflict Variant of APA APAc). On day 14, cortical microvascular perfusion (MVP) was measured, then brains were removed and infarct volume, immunofluorescence of amyloid beta (Aβ), neuronal density, microglial activation, and white matter damage/myelination were measured. SPSS was used for analysis (e.g., ANOVA for parametric data; Kruskal Wallis for non-parametric data; with post-hoc analysis).
Thirteen days of treatment with RNS60 reduced brain infarction, amyloid pathology, neuronal death, microglial activation, white matter damage, and increased MVP. RNS60 reduced brain pathology and resulted in behavioral improvements in stroke compared to sham surgery mice (increased memory-learning in NOR and APA, improved cognitive flexibility in APAc).
RNS60-treated mice exhibit significant protection of brain tissue and improved neurobehavioral functioning after tMCAo-stroke. Additional work is required to determine mechanisms, time-window of dosing, and multiple dosing volumes durations to support clinical stroke research.
Desde su arribo al territorio americano, los españoles emplearon los referentes propios de la realidad monetaria de la que procedían para operar en un contexto económico carente de moneda. Esta ...adecuación derivó en el uso de ciertos conceptos específicos que, en el caso del oro, luego habrían de retomarse de manera oficial tras el establecimiento de las casas de moneda, si bien con nuevas modificaciones y valores. Esto implica la existencia de “pesos de oro” distintos según el momento, aspecto no siempre reconocido en los estudios que dan luz sobre la etapa formativa novohispana. Con base en las cuentas de tesorería y los registros de fundición de Nueva España, este artículo evidencia tal diferencia y ofrece una vía para su dimensión económica.
Ever since their arrival in American territory, the Spaniards utilized references to the monetary reality of their place of origin while operating in an economic context that lacked currency. This situation led to the use of certain specific concepts that, in the case of gold, would have to be officially adapted once mints were established, albeit with new values and modifications. This implied the existence of different “gold pesos” that varied over time, something that hasn’t always been acknowledged in studies on the formative stage in New Spain. Based on treasury account books and records of the founding of New Spain, this article reveals this difference and offers a way toward understanding its economic dimensions.
Traditional histopathologic evaluation of peripheral nerve using brightfield microscopy is resource-intensive, necessitating complex sample preparation. Label-free imaging techniques paired with ...artificial intelligence-based image reconstruction and segmentation may facilitate peripheral nerve histomorphometry.
Herein, the utility of label-free phase contrast techniques paired with artificial intelligence-based image processing for imaging of mammalian peripheral nerve is demonstrated.
Fresh frozen murine sciatic nerve sections were imaged in transmission modalities using differential interference and phase contrast microscopy and in epifluorescent modality following staining with myelin-specific dye. Deep learning was employed to predict epifluorescent images from transmitted phase contrast images, and machine learning employed for automated segmentation of myelinated axons for reporting of axons counts and g-ratios.
Conventional peripheral nerve histomorphometry employs resource intensive resin embedding, ultra-microtome sectioning, and staining steps. Herein we demonstrate feasibility of high-throughput nerve histomorphometry via label-free phase contrast imaging of frozen sections.
Clinical applications of label-free phase contrast microscopy paired with deep learning algorithms are discussed.
•Fast myelin histomorphometry using DIC and phase contrast microscopy is demonstrated.•Deep learning is used to predict myelin fluorescent images from label-free images.•Machine learning is employed for automated myelinated axon counts.•Machine learning is employed for semi-automated g-ratio measurements.
Significance: Means for quantitation of myelinated fibers in peripheral nerve may guide diagnosis and clinical decision making in management of peripheral nerve disorders. Multiphoton microscopy ...techniques such as the third-harmonic generation enable label-free in vivo imaging of peripheral nerves.
Aim: Develop a multiphoton microscope based on a custom high-power infrared fiber laser for label-free imaging of peripheral nerve.
Approach: A cost-effective multiphoton microscope employing a single fiber laser source at 1300 nm was designed and used for stain-free multicolor imaging of murine and human peripheral nerve.
Results: Second-harmonic generation signal from collagen centered about 650-nm delineated neural connective tissue, whereas third-harmonic general signal centered about 433-nm delineated myelin and other lipids. In sciatic nerve from transgenic reporter mice expressing yellow fluorescent protein within peripheral neurons, three-photon-excitation with emission peak at 527-nm delineated axoplasm. The signal obtained from unlabeled axially sectioned samples was adequate for segmentation of myelinated fibers using commercial image processing software. In unlabeled whole mount specimens, imaging depths over 100-μm were achieved.
Conclusions: A multiphoton microscope powered by a fiber laser enables stain-free histomorphometry of mammalian peripheral nerve. The simplicity of the microscope design carries potential for clinical translation to inform decision making in peripheral nerve disorders.
The challenge of increasing the spatial resolution of an optical microscope beyond the diffraction limit can be reduced to a spectroscopy task by proper manipulation of the molecular states. The ...nanoscale spatial distribution of the molecules inside the detection volume of a scanning microscope can be encoded within the fluorescence dynamics and decoded by resolving the signal into its dynamics components. Here we present a robust and general method to decode this information using phasor analysis. As an example of the application of this method, we optically generate spatially controlled gradients in the fluorescence lifetime by stimulated emission. Spatial resolution can be increased indefinitely by increasing the number of resolved dynamics components up to a maximum determined by the amount of noise. We demonstrate that the proposed method provides nanoscale imaging of subcellular structures, opening new routes in super-resolution microscopy based on the encoding/decoding of spatial information through manipulation of molecular dynamics.
Building roofs are sources of unwanted heat for buildings situated in zones with a warm climate. Thus, reflective coatings have emerged as an alternative to reject a fraction of the solar energy ...received by roofs. In this research, the thermal behavior of concrete slab roofs with traditional and solar reflective coatings was simulated using a computational tool. The studied slab configurations belong to two groups, non-insulated and insulated roofs. In the second group, the thermal insulation thickness complies with the value recommended by a national building energy standard. Weather data from four cities in Mexico with a warm climate were used as boundary conditions for the exterior surface of the roofs. The computational tool consisted of a numerical model based on the finite volume method, which was validated with experimental data. A series of comparative simulations was developed, taking a gray roof as the control case. The results demonstrated that white roofs without insulation had an exterior surface temperature between 11 and 16 °C lower than the gray roof without insulation. Thus, the daily heat gain of these white roofs was reduced by a factor ranging between 41 and 54%. On the other hand, white roofs with insulation reduced the exterior surface temperature between 17 and 21 °C compared to the gray roof with insulation. This temperature reduction caused insulated white roofs to have a daily heat gain between 37 and 56% smaller than the control case. Another contribution of this research is the assessment of two retrofitting techniques when they are applied at once. In other words, a comparison between a non-insulated gray roof and an insulated white roof revealed that the latter roof had a daily heat gain up to 6.4-times smaller than the first.
This article deals with the design and real-time implementation of three second order sliding mode controllers for the altitude tracking of a quadrotor aircraft. A comparative study based on the ...analysis of the tracking error was performed in order to determine the controller presenting the best performance in a real-time application at outdoors environments. The compared strategies were the Classical First Order Sliding Mode Controller, the Super Twisting Sliding Mode Controller, the Modified Super Twisting Sliding Mode Controller and the Nonsingular Terminal Super Twisting Sliding Mode Controller. The last three controllers are based on the second order sliding mode technique, and they ensure robustness with respect to modeling errors even under external disturbances while reducing the chattering phenomenon in comparison with first order sliding mode controllers. Lyapunov stability theory is used to prove convergence in finite time of the altitude tracking error in the different proposed control laws. In order to demonstrate the effectiveness of the proposed solutions, an extensive set of simulation and real-time experimental results are presented.
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