The ability of proteins to sense and transmit mechanical forces underlies many biological processes, but characterizing these forces in biological systems remains a challenge. Existing genetically encoded force sensors typically rely on fluorescence or bioluminescence resonance energy transfer (FRET or BRET) to visualize tension. However, these force sensing modules are relatively large, and interpreting measurements requires specialized image analysis and careful control experiments. Here, we report a compact molecular tension sensor that generates a bioluminescent signal in response to tension. This sensor (termed PILATeS) makes use of the split NanoLuc luciferase and consists of the H. sapiens titin I10 domain with the insertion of a 10–15 amino acid tag derived from the C-terminal β-strand of NanoLuc. Mechanical load across PILATeS mediates exposure of this tag to recruit the complementary split NanoLuc fragment, resulting in force-dependent bioluminescence. We demonstrate the ability of PILATeS to report biologically meaningful forces by visualizing forces at the interface between integrins and extracellular matrix substrates. We further use PILATeS as a genetically encoded sensor of tension experienced by the mechanosensing protein vinculin. We anticipate that PILATeS will provide an accessible means of visualizing molecular-scale forces in biological systems.
PURPOSE: The aim of this study is to discuss the diagnosis and treatment of intracranial frontotemporal dermoid cyst with cutaneous sinus tract. METHODS: The history and process of clinical treatment of 2 cases were analyzed and the relative literatures were reviewed. RESULTS: Case 1,a girl aged 3 years presented with intracranial abscesses. Case 2, a 5-year old boy suffered from temporal space abscess. After control of infection, a combined intra-and extracranial approach was performed. There was cutaneous sinus of frontotemporal skin and fibrous sheet of dermoid extended down to the dura mater. Dermoid cyst was confirmed by pathology. No recurrence was noted after 14 months and 3 months of follow-up period, respectively. CONCLUSIONS: Intracranial frontotemporal dermoid cyst is rare and could cause severe complications such as meningitis and cerebral abscess. Successful treatment can be obtained through localization with CT scan or MRI, and combined intra-and extracranial operation.
The Northwest China(NWC) drought region is a part of the middle Asian drought region, it is a important study region of the geography, life and environment sciences. In this paper, 3 experiments as DE (changing the NWC surface type to desert), FE (changing the NWC surface type to cold defoliation broad forest) and CTL (control experiment) are made by using CCM3. By analyzing the balance of the radiation on the top of the atmosphere, the balance of the surface energy, the temperature change, the precipitation change and the CO (2 ) fluxes of the vegetation physiologicalprocess, the influence of the drought environment over the NWC region on the global change is primarily studied. The results show that if the drought environment is developed or reformed, it could affect the global energy balance process and its spatial distribution, and then it would affect the global and the regional climate and its distribution. These characters are obviously behaved by global temperature and precipitation regional change. The variation of the land surface type of the NWC can also affect the global climate change by the biology-geochemistry feedback process. And this influence might be long-term and more important. By all the analysis, it is known that the formation and evolvement of the drought climate and environment over the NWC are important part of the global change. So the study of the NWC drought region must be bring into the global climate and environment study. And then the influence and response of the drought region on the global change can be general understand.
In this paper, we propose a novel design of dielectric laser-driven accelerator (DLA) utilizing evanescent electric field of racetrack ring resonator structures. Driven by laser light with the correctly designed optical phase window, sustained acceleration of electrons with controlled deflection is shown. Based on this design, we calculate an acceleration from 30 keV to 148.312 keV in 104.655 μm using a cascaded 11-stage racetrack ring resonators. This new idea poses a solution for on-chip integration of many DLA stages, while maintains high average accelerating gradients, providing a potential practical realization for "accelerator on a chip".
The rapid and accurate detection of bacteria resistance to β-lactam antibiotics is critical to inform optimal treatment and prevent overprescription of potent antibiotics. Here, we present a fast, culture-independent method for the detection of extended-spectrum β-lactamases (ESBLs) using surface-enhanced Raman scattering (SERS). The method uses Raman probes that release sulfur-based Raman active molecules in the presence of β-lactamases. The released thiol molecules can be captured by gold nanoparticles, leading to amplified Raman signals. A broad-spectrum cephalosporin probe R1G and an ESBL-specific probe R3G are designed to enable duplex detection of bacteria expressing broad-spectrum β-lactamases or ESBLs with a detection limit of 103 cfu/mL in 1 h incubation. Combined with a portable Raman microscope, our culturing-free SERS assay has reduced screening time to 1.5 h without compromising sensitivity and specificity.
A monolayer of MGITC molecules in a gold nanosphere-plane junction is excited by focusing a radially polarized laser beam. A record electromagnetic enhancement factor of 1010 for deterministic SERS experiments has been obtained.
Abstract Serology has provided valuable diagnostic and epidemiological data on antibody responses to SARS-CoV-2 in diverse patient cohorts. Deployment of high content, multiplex serology platforms across the world, including in low and medium income countries, can accelerate longitudinal epidemiological surveys. Here we report multiSero, an open platform to enable multiplex serology with up to 48 antigens in a 96-well format. The platform consists of three components: ELISA-array of printed proteins, a commercial or home-built plate reader, and modular python software for automated analysis (pysero). We validate the platform by comparing antibody titers against the SARS-CoV-2 Spike, receptor binding domain (RBD), and nucleocapsid (N) in 114 sera from COVID-19 positive individuals and 87 pre-pandemic COVID-19 negative sera. We report data with both a commercial plate reader and an inexpensive, open plate reader (nautilus). Receiver operating characteristic (ROC) analysis of classification with single antigens shows that Spike and RBD classify positive and negative sera with the highest sensitivity at a given specificity. The platform distinguished positive sera from negative sera when the reactivity of the sera was equivalent to the binding of 1 ng mL −1 RBD-specific monoclonal antibody. We developed normalization and classification methods to pool antibody responses from multiple antigens and multiple experiments. Our results demonstrate a performant and accessible pipeline for multiplexed ELISA ready for multiple applications, including serosurveillance, identification of viral proteins that elicit antibody responses, differential diagnosis of circulating pathogens, and immune responses to vaccines.
Polarization dependence of supercontinuum and third-harmonic generations in silicon-nitride waveguides is mapped from 350-1750 nm. We identify parameters suited for generating coherent signals near 500 and 1000 nm for optical atomic clocks.
Dengue virus (DENV) is a mosquito-borne disease that poses a public health threat to sub/tropical areas worldwide. Vaccination drives require differential diagnosis of serotype-specific DENV exposure to reduce severe dengue risks, yet state-of-the-art DENV serology relies upon short-lived serotype-specific IgM or labor intensive neutralization assays. The need for high-throughput differential diagnosis is met with our multiSero platform (Byrum et al.), a screening technique capable of detecting 48 antigen-antibody pairs simultaneously, demonstrating utility for population-wide screening. Through machine-vision techniques, we quantify and classify antibody-response signals with high sensitivity to develop automated analysis pipelines capable of diagnosing serotype-specific DENV exposure.
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