Conventional Probe Research Articles

Multipole resonance probe measurement in plasma

In the study of low-temperature plasma, the plasma parameters such as plasma density and plasma temperature are required. Recently, a multipole resonance probe (MRP) which utilized an active plasma resonance concept was proposed. The probe consists of two hemispheres, insulated by a thin dielectric sheet. The advantages of the probe include simple setup and localized measurements similar to those of the conventional Langmuir probe. The probe does not cause plasma contamination, one of the Langmuir probe disadvantages since the probe conductors are covered in the dielectric. However, it can only determine plasma density. The MRP is usually connected with a Network Analyzer for measuring the reflection coefficient spectrum which can be analyzed to obtain the plasma density. In this experiment, the constructed MRP is used to measure the plasma density comparing to the Langmuir probe. The results of the experiment showed that the plasma density result of the MRP gives a similar tendency as that of the Langmuir probe. However, the plasma density determined by the MRP was deviated when compared with the Langmuir probe. In order to explore the idea that MRP does not need to be constructed in hemisphere shape, MRP in different shapes have been assembled and verified.

Treatment of hepatocellular carcinoma using the Smart Fusion needle navigation system: conversion from real-time 4D-echo data

Advances in ultrasound systems have improved the accuracy of hepatocellular carcinoma (HCC) diagnosis and treatment. We have been treating HCC using real-time 4D and Live 3D-echo technologies. However, these treatment methods have drawbacks such as vibrations during puncture and a limited angle of needle insertion. To overcome these problems, systems that can display ultrasound images simultaneously with computed tomography (CT) and magnetic resonance images in a real-time manner for reference purposes have been reported. These systems have recently been equipped with a needle tip navigation system, making it possible to reliably visualize tumors and determine the needle tip position in a tumor. These developments have enabled the safe treatment of HCC. Treatment using needle navigation is performed as follows: A Canon APLIO800 ultrasound system is used with a conventional convex probe (PVT-375BT) and a micro-convex probe (PVT-382BT). The system function is known as Smart Fusion. Ultrasound images can be displayed with volume data from other modalities, such as CT and magnetic resonance imaging (MRI), in relation to the positional information using a magnetic sensor. This enables the use of CT/MRI data as reference for accurate puncture and treatment of lesions that are difficult to identify by ultrasound alone. Axis alignment is also completed by displaying the xiphoid process on a CT image and having the system learn the orientation of the probe placed perpendicular to the body axis. Then, landmark alignment is performed and fine-adjusted by aligning a target point near the lesion with the same point as displayed on CT (Fig. 1). Case presentation A 7x-year-old woman was found to have elevated tumor markers and a liver tumor identified by regular blood testing and CT performed in August 20xx and was admitted to our hospital for treatment. Abdominal ultrasonography showed a hypoechoic lesion measuring approximately 3 cm in diameter in liver S6, which led to a diagnosis of HCC. For treatment, microwave therapy was selected at the patient’s request. Microwaves were delivered using a Medtronic Emprint ablation system with a 3.0-cm needle for ablation. During treatment, the needle position was confirmed by needle navigation before ablation (Fig. 2) because the tumor needed to be ablated in an overlapping manner (Fig. 3).

Multiphoton Deep-Tissue Imaging of Micrometastases and Disseminated Cancer Cells Using Conjugates of Quantum Dots and Single-Domain Antibodies.

Early detection of malignant tumors, micrometastases, and disseminated tumor cells is one of the effective way of fighting cancer. Among the many existing imaging methods like computed tomography (CT), ultrasound (US), magnetic resonance imaging (MRI), positron emission tomography (PET), and single-photon emission computed tomography (SPECT), optical imaging with fluorescent probes is one of the most promising alternatives because it is fast, inexpensive, safe, sensitive, and specific. However, traditional fluorescent probes, based on organic fluorescent dyes, suffer from the low signal-to-noise ratio. Furthermore, conventional organic fluorescent dyes are unsuitable for deep tissue imaging because of the strong visible light absorption by biological tissues. The use of fluorescent semiconductor nanocrystals, or quantum dots (QDs), may overcome this limitation due to their large multiphoton cross section, which ensures efficient imaging of thick tissue sections inaccessible with conventional fluorescent probes. Moreover, the lower photobleaching and higher brightness of fluorescence signals from QDs ensures a much better discrimination of positive signals from the background. The use of fluorescent nanoprobes based on QDs conjugated to uniformly oriented high-affinity single-domain antibodies (sdAbs) may significantly increase the sensitivity and specificity due to better recognition of analytes and deeper penetration into tissues due to small size of such nanoprobes.Here, we describe a protocol for the fabrication of nanoprobes based on sdAbs and QDs, preparation of experimental xenograft mouse models for quality control, and multiphoton imaging of deep-tissue solid tumors, micrometastases, and disseminated tumor cells.

Development of a high-time/spatial resolution self-impedance probe for measurements in laboratory and space plasmas.

Plasma impedance probes are often used in laboratory experiments as well as in space to make measurements of important plasma parameters such as the electron density. Conventional impedance probe methods involve sweeping the frequency applied to the probe through a range containing the plasma frequency, which can take on the order of a second to complete. This acquisition time leads to very low spatial resolution when making measurements from sounding rockets in the ionosphere. A high-time resolution impedance probe is under development at the U.S. Naval Research Laboratory with the goal of increasing the spatial resolution of measurements in space. To achieve this, a short-time Gaussian monopulse with a center frequency of 40MHz and containing a full spectrum of frequencies is applied to an electrically short dipole antenna. Laboratory experiments were performed with the Gaussian monopulse triggered once every 10 µs and averaged over ten shots, equating to a spatial resolution of 13cm for a typical sounding rocket speed. This paper discusses the development of the new high-time/spatial resolution self-impedance probe and illustrates that the short-time pulse method yields results that match well with data taken using conventional methods. It is shown that plasma parameters such as the electron density, sheath frequency, and electron-neutral collision frequency can also be derived from the data. In addition, data from the high-time/spatial resolution impedance probe are shown to compare well with those from theoretical impedance models.

Aggregation-induced emission materials for protein fibrils imaging.

Protein fibrillation is linked to many devastating diseases including neurodegenerative disorders. Fluorescence probes play a significant role in the detection of amyloid aggregates, monitoring amyloid kinetics, and in the development of amyloid inhibitors. Despite the considerable progress in this area, the mechanism of amyloid fibril formation in vivo is not completely understood. Recent studies in amyloidosis indicate that oligomers and prefibrillar species are more cytotoxic than the fibrils. Hence, early diagnosis of fibrillation has high therapeutical relevance. The gold standard for amyloid staining is thioflavin-T and its major drawbacks are aggregation caused quenching and inability in the detection of oligomers. New amyloid staining probes with novel properties are highly desirable as they can give valuable insights into the complicated process and can replace conventional probes. Aggregation-induced emission probes (AIE-probes) with desirable features are promising candidates in protein fibrils imaging. AIE probes in staining different amyloid fibrils, monitoring amyloid kinetics, and early-stage conformers are reported. Other remarkable features are they can be modified as NIR probes, multifunctional probes, theranostic probes, and super-resolution imaging probes. We aim to provide a broad perspective on the progress attained with AIE probes in protein fibrils imaging and thereby emphasizing the scope of these smart probes in translative research.

Harnessing α-l-fucosidase for in vivo cellular senescence imaging.

Precise detection of cellular senescence may allow its role in biological systems to be evaluated more effectively, while supporting studies of therapeutic candidates designed to evade its detrimental effect on physical function. We report here studies of α-l-fucosidase (α-fuc) as a biomarker for cellular senescence and the development of an α-fuc-responsive aggregation induced emission (AIE) probe, termed QM-NHαfuc designed to complement more conventional probes based on β-galactosidase (β-gal). Using QM-NHαfuc, the onset of replicative-, reactive oxygen species (ROS)-, ultraviolet A (UVA)-, and drug-induced senescence could be probed effectively. QM-NHαfuc also proved capable of identifying senescent cells lacking β-gal expression. The non-invasive real-time senescence tracking provided by QM-NHαfuc was validated in an in vivo senescence model. The results presented in this study lead us to suggest that the QM-NHαfuc could emerge as a useful tool for investigating senescence processes in biological systems.

Temperature response of laser heated emissive probe materials under vacuum and free atmospheric conditions

Precise temporal and spatial knowledge of plasma potential has been a challenging task for decades. Gradient in values of plasma potential govern local electric fields providing insight into many other bulk plasma properties like particle drifts, confinement, transport barriers etc and plays a crucial role in determining stability of magnetically confined high temperature plasmas. In high temperature devices like tokamaks, plasma tends to develop edge bifurcations and results in edge transport barriers, which are a key tool for enhancing the plasma confinement properties in magnetic fusion devices, which in turn requires knowledge of plasma potential. Conventional emissive probes (CEPs) in high temperature magnetically confined plasmas are not advisable owing to their inherent properties and tokamak parameters like high magnetic field, ultra-high vacuum pressure etc as well as tokamak geometry. A new type of emissive probe is becoming popular in recent times in such devices called the laser heated emissive probe (LHEP). Mostly, LaB6 and graphite are used as a LHEP tip owing to their inherent properties of thermal conductivity, low work function, high emissivity, higher lifetime etc. Similar with LaB6 in its mechanical and electrical properties, CeB6 is emerging as a promising candidate for LHEP. CeB6 is a better electron emitter than graphite and LaB6 at comparatively low power due to its lower work function. In this work, the heating dynamics of LaB6 and CeB6 heated by a CW CO2 laser with maximum power of 55 W have been reported. Theoretical and simulation models using Matlab and ANSYS have been developed to understand and explain the temperature gaining process of the probes. Simulation results are further validated by comparing them with experimentally measured data using an infrared camera.

Monitoring of high-moisture content particle drying in a fluidized bed by microwave and capacitance tomographic sensors

Particle drying in fluidized beds is a common and important process in food and pharmaceutical industry. However, the fluidization characteristic is complex due to the moisture content change in the process and it is a challenge to monitor the flow characteristics by conventional measurement approach, likes pressure and thermal probes. In this research, process tomography including capacitance and microwave tomographic systems are used to investigate the flow characteristics in a fluidized bed dryer with high-moisture content particles. Static tests were firstly carried out to investigate the image characteristics based on microwave tomography (MWT) and electrical capacitance tomography (ECT). The imaging ability was compared between MWT and ECT. In the dynamic tests, the drying process for particles with high-moisture content was monitored on-line by MWT and ECT separately. The static test results show that the high calibration for ECT is critical and particles with low moisture content should be used for high calibration of an ECT system to achieve high quality images for the dynamic tests. For the high calibration of ECT, there is an upper limit for the moisture content. With a fixed calibration background, the moisture content of particles should not exceed this upper limit value. MWT basically has no limitation on the moisture content both for high calibration and measurement. Dynamic test results illustrate that MWT is a good option to monitor high-moisture content particles drying in a fluidized bed and it is possible to combine ECT together to identify the gas–solids flow regime transit and to determine the moisture content by MWT in a fluidized bed drying process.

Individualized Brain Tissue Oxygen-Monitoring Probe Placement Helps to Guide Therapy and Optimizes Outcome in Neurocritical Care

Background/ObjectiveIn order to monitor tissue oxygenation in patients with acute neurological disorders, probes for measurement of brain tissue oxygen tension (ptO2) are often placed non-specifically in a right frontal lobe location. To improve the value of ptO2 monitoring, placement of the probe into a specific area of interest is desirable. We present a technique using CT-guidance to place the ptO2 probe in a particular area of interest based on the individual patient’s pathology.MethodsIn this retrospective cohort study, we analyzed imaging and clinical data from all patients who underwent CT-guided ptO2 probe placement at our institution between October 2017 and April 2019. Primary endpoint was successful placement of the probe in a particular area of interest rated by two independent reviewers. Secondary outcomes were complications from probe insertion, clinical consequences from ptO2 measurements, clinical outcome according to the modified Rankin Scale (mRS) as well as development of ischemia on follow-up imaging. A historical control group was selected from patients who underwent conventional ptO2 probe placement between January 2010 and October 2017.ResultsEleven patients had 16 CT-guided probes inserted. In 15 (93.75%) probes, both raters agreed on the correct placement in the area of interest. Each probe triggered on average 0.48 diagnostic or therapeutic adjustments per day. Only one infarction within the vascular territory of a probe was found on follow-up imaging. Eight out of eleven patients (72.73%) reached a good outcome (mRS ≤ 3). In comparison, conventionally placed probes triggered less diagnostic and therapeutic adjustment per day (p = 0.007). Outcome was worse in the control group (p = 0.024).ConclusionCT-guided probe insertion is a reliable and easy technique to place a ptO2 probe in a particular area of interest in patients with potentially reduced cerebral oxygen supply. By adjusting treatment aggressively according to this individualized monitoring data, clinical outcome may improve.

A practical guide to unbiased quantitative morphological analyses of the gills of rainbow trout (Oncorhynchus mykiss) in ecotoxicological studies.

Rainbow trout (Oncorhynchus mykiss) are frequently used as experimental animals in ecotoxicological studies, in which they are experimentally exposed to defined concentrations of test substances, such as heavy metals, pesticides, or pharmaceuticals. Following exposure to a broad variety of aquatic pollutants, early morphologically detectable toxic effects often manifest in alterations of the gills. Suitable methods for an accurate and unbiased quantitative characterization of the type and the extent of morphological gill alterations are therefore essential prerequisites for recognition, objective evaluation and comparison of the severity of gill lesions. The aim of the present guidelines is to provide practicable, standardized and detailed protocols for the application of unbiased quantitative stereological analyses of relevant morphological parameters of the gills of rainbow trout. These gill parameters inter alia include the total volume of the primary and secondary gill lamellae, the surface area of the secondary gill lamellae epithelium (i.e., the respiratory surface) and the thickness of the diffusion barrier. The featured protocols are adapted to fish of frequently used body size classes (300–2000 g). They include well-established, conventional sampling methods, probes and test systems for unbiased quantitative stereological analyses of light- and electron microscopic 2-D gill sections, as well as the application of modern 3-D light sheet fluorescence microscopy (LSFM) of optically cleared gill samples as an innovative, fast and efficient quantitative morphological analysis approach. The methods shown here provide a basis for standardized and representative state-of-the-art quantitative morphological analyses of trout gills, ensuring the unbiasedness and reproducibility, as well as the intra- and inter-study comparability of analyses results. Their broad implementation will therefore significantly contribute to the reliable identification of no observed effect concentration (NOEC) limits in ecotoxicological studies and, moreover, to limit the number of experimental animals by reduction of unnecessary repetition of experiments.

In Cellulo Generation of Fluorescent Probes for Live-Cell Imaging of Cylooxygenase-2.

Live-cell imaging with fluorescent probes is an essential tool in chemical biology to visualize the dynamics of biological processes in real-time. Intracellular disease biomarker imaging remains a formidable challenge due to the intrinsic limitations of conventional fluorescent probes and the complex nature of cells. This work reports the in cellulo assembly of a fluorescent probe to image cyclooxygenase-2 (COX-2). We developed celecoxib-azide derivative 14, possessing favorable biophysical properties and excellent COX-2 selectivity profile. In cellulo strain-promoted fluorogenic click chemistry of COX-2-engaged compound 14 with non/weakly-fluorescent compounds 11 and 17 formed fluorescent probes 15 and 18 for the detection of COX-2 in living cells. Competitive binding studies, biophysical, and comprehensive computational analyses were used to describe protein-ligand interactions. The reported new chemical toolbox enables precise visualization and tracking of COX-2 in live cells with superior sensitivity in the visible range.

RETRACTED: Research on inversion of ecosystem dynamics model parameters based on improved Neural Network algorithm

Bayesian probability reversal and Markov chain Monte Carlo (MCMC) techniques were used in the regional environmental model to evaluate carbon (C) conversion coefficient and simulate carbon pool size uncertainty. Six data sets of C were used on soil respiration, tree biology, bio-leaves, litter, bed layer C, mineral soil measured under CO 2 (350 ppm) in these two contexts, and six data levels and liter height. Go 2 (550 ppm) curve. Increasing and better understanding of carbon dioxide levels in the Earth's atmosphere and the global carbon cycle. Web-based time-series models are based on the environment and climate parameters and create deep learning. To avoid a large part of the research and hard data downloads, the Google Earth Engine platform, based on this model can generate, and all input data will be published on the Internet. Variation method of numerical simulation, the global ocean ecosystem dynamics is used. Data Degradation Cycle Current measurement is a useful tool for extracting quantitative information from environmental information. However, to estimate the parameter value in terms of time inversion, it has been reduced that the sample factor can control the amount of spiral data as in the conventional reverse probe model. This research aims to increase the number of data degradation and increase the number of parameters.

Luminescent Nanomaterials Doped with Rare Earth Ions and Prospects for Their Biomedical Applications (A Review)

A review of recent advances in the development of luminescent inorganic nanoparticles doped with rare earth ions, which can be used for biomedical applications, is presented. Luminescent nanomaterials doped with rare earth ions are characterized by physicochemical properties such as long luminescence time, large Stokes and/or anti-Stokes shifts, narrow luminescence bands, high photostability, and low toxicity. These materials can be considered to be a new generation of biosensors along with conventional molecular probes such as organic dyes, quantum dots, and lanthanide labels based on organic chelates.

Exploiting the unique specialty of hydrazone functionality: Synthesis of a highly sensitive UV–Vis active solvatochromic probe

The unique physico-chemical attributes of the hydrazone functionality have been extensively studied for a diverse range of chemical, biological and analytical applications. The synthesis of a highly sensitive hydrazone based UV–Vis active solvatochromic probe that exhibits excellent sensitivity toward sensing of solvent polarity, microstructural changes and onset of micellization in aqueous systems was carried out. Specifically, synthesis of 2,4-dinitrophenyl-2-(2-nitrobenzylidene)hydrazone (DNPNBH), through an easy to carry, atom economical, one-pot single step approach via use of low-cost precursors viz. ortho-nitrobenzaldehyde and 2,4-dinitrophenyl hydrazine is presented. The UV–Vis absorption features of the synthesized hydrazone exhibit excellent sensitivity toward the polarity of its immediate microenvironment. The microenvironment polarity sensing potential of DNPNBH is demonstrated for some single solvent systems and DMF-Water mixture as a model binary solvent system and the results are supported by quantum mechanical calculations. Use of the DNPNBH as a probe (at concentrations many orders lower than required for conventional probes) to precisely reflect the onset of micellization and estimation of critical micelle concentration (CMC) of amphiphilic molecules (5.25 mM for SDS, 1.53 mM for CTAB and 0.055 mM for Brij56) in aqueous solutions is also demonstrated. The results clearly qualify the synthesized hydrazone as a highly sensitive UV–Vis probe that can be employed for reliable sensing of solvent polarity, composition dependence of physicochemical attributes in mixed solvent systems and the estimation of CMC of surfactant systems via spectrophotometry.

A simplified and open-source approach for multiple-valued water surface measurements in 2D hydrodynamic experiments

Water elevation measurements in 2D hydrodynamic experiments are widely used for validating analytical and numerical models. Experimental research has shown that some phenomena can present multiple-valued water surfaces. However, conventional wave probe sensors do not provide measurements of these surfaces, which is required for appropriate model comparisons. This paper aims to propose a simplified and open-source image-based methodology to measure the spatio-temporal evolution of multiple-valued water surface elevations observed in two-dimensional hydrodynamic experiments, considering the problem of shipping water on a fixed structure as the topic of application. This approach examines the stages of image processing and analysis through morphological operations, which have been implemented in plugins for free use in the open-source ImageJ software. Measurements performed in two experimental study cases of shipping water on the deck of a fixed structure, due to single and multiple incident waves, were compared with measurements taken by conventional wave probe sensors and manual tracking to verify the performance of the methodology. The results obtained give the time series of elevation of multiple-valued water surfaces, which can be obtained at any desired position over the horizontal domain of the images, at low cost and high computational efficiency. The present approach has been made available for its free use and can be adapted to analyze the spatio-temporal flow evolution in a wide range of 2D hydrodynamic experiments.

Estimation of the right atrial pressure by ultrasound-assessed internal jugular vein in patients with advanced chronic heart failure

Abstract Background In patients with systolic chronic heart failure (CHF) clinical signs of congestion cannot always be evident at clinical examination. Right atrial pressure (RAP) measured by right heart catheterization (RHC) is an accurate and reproducible marker of blood volume. A non-invasive accurate tool to identify CHF patients with normal RAP would be desirable to tailor therapy. Purpose To validate an ultrasound (US)-assessed internal jugular vein distensibility (JVD) ratio to identify patients with normal mean RAP (defined as 7 mmHg or less) measured by RHC. Methods We first identify the JVD ratio that allows the most accurate identification of patients with normal RAP in a prospective calibration cohort of 100 patients with systolic CHF. Then, we tested the JVD ratio threshold to identify patients with normal RAP in a validation cohort of 101 consecutive patients with systolic CHF. All patients had a left ventricular ejection fraction (LVEF)<50% and underwent RHC in the setting of heart transplant work-up. At the time of jugular vein puncture, we recorded the internal jugular vein diameter by conventional linear probes. JVD ratio was calculated as the ratio between maximum diameter (during Valsalva maneuver) and rest diameter of the vein (FIGURE). Finally, we assessed the prognostic value of the JVD ratio in the follow up of the first 100 patients. Results In the calibration cohort (mean age 53 years, 13% female; median LVEF 25%, 81% in NYHA class III/IV) we define the best threshold of the JVD ratio to identify patients with normal RAP that has 1.6 with an area under the curve (AUC of 0.74; p<0.0001). Based on this JVD ratio threshold we defined patients with low JVD ratio (≤1.6; n=58; median RAP 8 mmHg) and patients with high JVD ratio (>1.6, n=42; median RAP 4 mmHg). High JVD ratio and low JVD ratio groups had similar clinical and laboratory characteristics. In the validation cohort (mean age 55 years, 13% female; median LVEF 25%; 56% in NYHA class III/IV) using the previously defined 1.6 JVD ratio threshold, we identified 51 patients with low JVD ratio (median RAP 8 mmHg) and 50 patients with high JVD ratio (median RAP 3 mmHg; p<0.0001) The JVD ratio threshold has an accuracy to identify patients with a normal RAP with an AUC of 0.82 (p<0.0001); a predictive positive value of 0.94, negative predictive value of 0.51, specificity of 0.90, and sensitivity of 0.65. Finally, in the calibration cohort, the CHF patients with low JVD ratio (≤1.6) had a higher cumulative incidence of overall death, heart transplant, or left ventricular assist device (42.7% vs. 16.1% in the high JVD ratio group, p log-rank 0.006) at a median of 13-month follow-up. Conclusions We found that US-assessed JVD ratio is a convenient and accurate diagnostic tool to identify patients with advanced systolic CHF with normal vs. increased RAP. This tool could be tested in the ambulatory setting to modulate therapies, particularly diuretics and vasodilators. Figure 1 Funding Acknowledgement Type of funding source: None

3D ultrasonic reconstruction of contour node represented voids and cracks

Although the 2D imaging technology was widely used, it cannot provide enough information for protecting cultural relics. Base on the homogeneous material assumption, 3D contour node is therefore proposed to represent defects of different shapes inside the cultural relics. This paper describes a novel algorithm to reconstruct 3D image of defects inside cultural relics combined with dynamic chain technology and two algorithms: Simultaneous Iterative Reconstruct Technique (SIRT) and Adaptive Moment Estimation(Adam). And the latter is used to improve the former. Meanwhile, a detection scheme is designed like this : Firstly, rough position of defects will be searched, and then precise reconstruction is made for defective areas. The algorithm proposed is verified by simulation experiments. With application of the algorithm, 3D images of defects of different shapes and quantities can be obtained and the errors of reconstruction, in most cases, are lower than 10%, even the maximum error is lower than 22%. Finally, the laboratory experiment also tests the ability of the proposed algorithm. The reconstruction is done by using conventional ultrasonic probes instead of array probes which can reduce the detection cost.

A Light-Adjustable Hand-Held Probe for Photoacoustic Tomography in vivo

A light-adjustable illumination scheme for hand-held probe for photoacoustic tomography is presented in this paper. The overall size of the probe is 120 × 60 × 40 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> , which is easy to be held. Compared with traditional photoacoustic probe design, it has the following advantages: (1) Different excitation modes, that is, the different relative position between laser illumination area and ultrasonic detection area, can be selected as needed by tuning control parameters. (2) The spot-adjustable unit (SAU) specifically designed for beam expansion. (3) Angle Adjustment Unit (AAU) based on gear drive is proposed with single power input and bilateral output. Just by adjusting the motor parameters, the purpose of adjusting the incident angle can be precisely achieved. We built a PAT system based on our newly designed apparatus. Phantom and in vivo experimental results show that a variety of lighting schemes can be quickly generated according to requirements without changing the external settings, compared with the conventional probe.

Metabolic precision labeling enables selective probing of O-linked N-acetylgalactosamine glycosylation

Protein glycosylation events that happen early in the secretory pathway are often dysregulated during tumorigenesis. These events can be probed, in principle, by monosaccharides with bioorthogonal tags that would ideally be specific for distinct glycan subtypes. However, metabolic interconversion into other monosaccharides drastically reduces such specificity in the living cell. Here, we use a structure-based design process to develop the monosaccharide probe N-(S)-azidopropionylgalactosamine (GalNAzMe) that is specific for cancer-relevant Ser/Thr(O)-linked N-acetylgalactosamine (GalNAc) glycosylation. By virtue of a branched N-acylamide side chain, GalNAzMe is not interconverted by epimerization to the corresponding N-acetylglucosamine analog by the epimerase N-acetylgalactosamine-4-epimerase (GALE) like conventional GalNAc-based probes. GalNAzMe enters O-GalNAc glycosylation but does not enter other major cell surface glycan types including Asn(N)-linked glycans. We transfect cells with the engineered pyrophosphorylase mut-AGX1 to biosynthesize the nucleotide-sugar donor uridine diphosphate (UDP)-GalNAzMe from a sugar-1-phosphate precursor. Tagged with a bioorthogonal azide group, GalNAzMe serves as an O-glycan-specific reporter in superresolution microscopy, chemical glycoproteomics, a genome-wide CRISPR-knockout (CRISPR-KO) screen, and imaging of intestinal organoids. Additional ectopic expression of an engineered glycosyltransferase, "bump-and-hole" (BH)-GalNAc-T2, boosts labeling in a programmable fashion by increasing incorporation of GalNAzMe into the cell surface glycoproteome. Alleviating the need for GALE-KO cells in metabolic labeling experiments, GalNAzMe is a precision tool that allows a detailed view into the biology of a major type of cancer-relevant protein glycosylation.

New Screening Method For Cervical Cancer- Polar Probe

Objective: Although extensive screening methods had been developed, cervical cancer remains to be an essential health problem. Early detection and administration of appropriate therapy is still a lifesaving procedure, especially for cervical cancer. The most common screening method for cervical cancer is still the cervical cytology (Pap-test). We aim to find out the advantages and disadvantages of a recently developed method, which is called as Polar Probe.&#x0D; Methods: Two different approaches had been used (conventional Pap test and Polar Probe), and 1438 patients were included in the study. Of these, 819 had been screened with Polar Probe. All eligible patients were firstly screened using Polar Probe and then using the Pap test. Each patient with an abnormal Polar Probe result was referred to colposcopy room, where she was re-evaluated using colposcopy.&#x0D; Results: The rate of abnormal smear result was 1.04%, and the corresponding percentage was calculated as 0.62% in LSIL, 0.34% in ASCUS, and 0.069% in HSIL. A total of 819 patients underwent Polar Probe, and the results were abnormal in 261 patients and normal in 558 patients. Abnormality rate was 1% in Pap test and 31.9% in Polar Probe. Although the positive predictive value was 27% for Polar Probe test and 16% for Pap test, as the colposcopy was indicated only for the patients with abnormal results in Polar Probe. The need for colposcopy dramatically increased with the use of Polar Probe.&#x0D; Conclusion: Use of Polar Probe alone was not found to be cost effective. Combination with other methods of screening would decrease the cost of the process.