Fluctuation and localization of acoustic waves in bubbly water

Here the fluctuation properties of acoustic localization in bubbly water is explored. We show that the strong localization can occur in such a system for a certain frequency range and sufficient filling fractions of air-bubbles. Two fluctuating quantities are considered, that is, the fluctuation of transmission and the fluctuation of the phase of acoustic wave fields. When localization occurs, these fluctuations tend to vanish, a feature able to uniquely identify the phenomenon of wave localization.Comment: 10 pages, 4 figure

Rainbow Kaposi's Sarcoma-Associated Herpesvirus Revealed Heterogenic Replication with Dynamic Gene Expression.

Molecular mechanisms of Kaposi's sarcoma-associated herpesvirus (KSHV) reactivation have been studied primarily by measuring the total or average activity of an infected cell population, which often consists of a mixture of both nonresponding and reactivating cells that in turn contain KSHVs at various stages of replication. Studies on KSHV gene regulation at the individual cell level would allow us to better understand the basis for this heterogeneity, and new preventive measures could be developed based on findings from nonresponding cells exposed to reactivation stimuli. Here, we generated a recombinant reporter virus, which we named "Rainbow-KSHV," that encodes three fluorescence-tagged KSHV proteins (mBFP2-ORF6, mCardinal-ORF52, and mCherry-LANA). Rainbow-KSHV replicated similarly to a prototype reporter-KSHV, KSHVr.219, and wild-type BAC16 virus. Live imaging revealed unsynchronized initiation of reactivation and KSHV replication with diverse kinetics between individual cells. Cell fractionation revealed temporal gene regulation, in which early lytic gene expression was terminated in late protein-expressing cells. Finally, isolation of fluorescence-positive cells from nonresponders increased dynamic ranges of downstream experiments 10-fold. Thus, this study demonstrates a tool to examine heterogenic responses of KSHV reactivation for a deeper understanding of KSHV replication.IMPORTANCE Sensitivity and resolution of molecular analysis are often compromised by the use of techniques that measure the ensemble average of large cell populations. Having a research tool to nondestructively identify the KSHV replication stage in an infected cell would not only allow us to effectively isolate cells of interest from cell populations but also enable more precise sample selection for advanced single-cell analysis. We prepared a recombinant KSHV that can report on its replication stage in host cells by differential fluorescence emission. Consistent with previous host gene expression studies, our experiments reveal the highly heterogenic nature of KSHV replication/gene expression at individual cell levels. The utilization of a newly developed reporter-KSHV and initial characterization of KSHV replication in single cells are presented

Quantitative Bioluminescence Tomography-guided System for Conformal Irradiation In Vivo

Although cone-beam CT (CBCT) has been used to guide irradiation for pre-clinical radiotherapy(RT) research, it is limited to localize soft tissue target especially in a low imaging contrast environment. Knowledge of target shape is a fundamental need for RT. Without such information to guide radiation, normal tissue can be irradiated unnecessarily, leading to experimental uncertainties. Recognition of this need led us to develop quantitative bioluminescence tomography (QBLT), which provides strong imaging contrast to localize optical targets. We demonstrated its capability of guiding conformal RT using an orthotopic bioluminescent glioblastoma (GBM) model. With multi-projection and multi-spectral bioluminescence imaging and a novel spectral derivative method, our QBLT system is able to reconstruct GBM with localization accuracy <1mm. An optimal threshold was determined to delineate QBLT reconstructed gross target volume (GTV_{QBLT}), which provides the best overlap between the GTV_{QBLT} and CBCT contrast labeled GBM (GTV), used as the ground truth for the GBM volume. To account for the uncertainty of QBLT in target localization and volume delineation, we also innovated a margin design; a 0.5mm margin was determined and added to GTV_{QBLT} to form a planning target volume (PTV_{QBLT}), which largely improved tumor coverage from 75% (0mm margin) to 98% and the corresponding variation (n=10) of the tumor coverage was significantly reduced. Moreover, with prescribed dose 5Gy covering 95% of PTV_{QBLT}, QBLT-guided 7-field conformal RT can irradiate 99.4 \pm 1.0% of GTV vs. 65.5 \pm 18.5% with conventional single field irradiation (n=10). Our QBLT-guided system provides a unique opportunity for researchers to guide irradiation for soft tissue targets and increase rigorous and reproducibility of scientific discovery

In vivo bioluminescence tomography-guided system for pancreatic cancer radiotherapy research

Recent development of radiotherapy (RT) has heightened the use of radiation in managing pancreatic cancer. Thus, there is a need to investigate pancreatic cancer in a pre-clinical setting to advance our understanding of the role of RT. Widely-used cone-beam CT (CBCT) imaging cannot provide sufficient soft tissue contrast to guide irradiation. The pancreas is also prone to motion. Large collimation is unavoidably used for irradiation, costing normal tissue toxicity. We innovated a bioluminescence tomography (BLT)-guided system to address these needs. We established an orthotopic pancreatic ductal adenocarcinoma (PDAC) mouse model to access BLT. Mice underwent multi-projection and multi-spectral bioluminescence imaging (BLI), followed by CBCT imaging in an animal irradiator for BLT reconstruction and radiation planning. With optimized absorption coefficients, BLT localized PDAC at 1.25 ± 0.19 mm accuracy. To account for BLT localization uncertainties, we expanded the BLT-reconstructed volume with margin to form planning target volume(PTVBLT) for radiation planning, covering 98.7 ± 2.2% of PDAC. The BLT-guided conformal plan can cover 100% of tumors with limited normal tissue involvement across both inter-animal and inter-fraction cases, superior to the 2D BLI-guided conventional plan. BLT offers unique opportunities to localize PDAC for conformal irradiation, minimize normal tissue involvement, and support reproducibility in RT studies.</p

Quantitative bioluminescence tomography using spectral derivative data

Bioluminescence imaging (BLI) is a non-contact, optical imaging technique based on measurement of emitted light due to an internal source, which is then often directly related to cellular activity. It is widely used in pre-clinical small animal imaging studies to assess the progression of diseases such as cancer, aiding in the development of new treatments and therapies. For many applications, the quantitative assessment of accurate cellular activity and spatial distribution is desirable as it would enable direct monitoring for prognostic evaluation. This requires quantitative spatially-resolved measurements of bioluminescence source strength inside the animal to be obtained from BLI images. This is the goal of bioluminescence tomography (BLT) in which a model of light propagation through tissue is combined with an optimization algorithm to reconstruct a map of the underlying source distribution. As most models consider only the propagation of light from internal sources to the animal skin surface, an additional challenge is accounting for the light propagation from the skin to the optical detector (e.g. camera). Existing approaches typically use a model of the imaging system optics (e.g. ray-tracing, analytical optical models) or approximate corrections derived from calibration measurements. However, these approaches are typically computationally intensive or of limited accuracy. In this work, a new approach is presented in which, rather than directly using BLI images acquired at several wavelengths, the spectral derivative of that data (difference of BLI images at adjacent wavelengths) is used in BLT. As light at similar wavelengths encounters a near-identical system response (path through the optics etc.) this eliminates the need for additional corrections or system models. This approach is applied to BLT with simulated and experimental phantom data and shown that the error in reconstructed source intensity is reduced from 49% to 4%. Qualitatively, the accuracy of source localization is improved in both simulated and experimental data, as compared to reconstruction using the standard approach. The outlined algorithm can widely be adapted to all commercial systems without any further technological modifications

A universal bioluminescence tomography system for pre-clinical image-guided radiotherapy research

CBCT-guided small animal irradiators encounter challenges in localizing soft-tissue targets due to low imaging contrast. Bioluminescence tomography (BLT) offers a promising solution, but they have largely remained in laboratorial development, limiting accessibility for researchers. In this work, we develop a universal, commercial-graded BLT-guided system (MuriGlo) designed to seamlessly integrate with commercial irradiators and empower researchers for translational studies. We demonstrate its capabilities in supporting in vitro and in vivo studies. The MuriGlo comprises detachable mouse bed, thermostatic control, mirrors, filters, and CCD, enabling multi-projection and multi-spectral imaging. We evaluate that the thermostatic control effectively sustains animal temperature at 37{\deg}C throughout imaging, and quantify that the system can detect as few as 61 GL261-AkaLuc cells in vitro. To illustrate how the MuriGlo can be utilized for in vivo image-guided research, we present 3 strategies, BLT-guided 5-arc, 2-field box, and BLI-guided single-beam, ranging from complicated high-conformal to simplest high-throughput plans. The high conformal BLT-guided 5-arc plan fully covers the gross tumor volume (GTV) at prescribed dose with minimal normal tissue exposure (3.9%), while the simplified, high-throughput BLT-guided 2-field box achieves 100% GTV coverage but results in higher normal tissue exposure (13.1%). Moreover, we demonstrate that the localization accuracy of MuriGlo for both widely-used SARRP and SmART irradiators is within1 mm, and the tumor coverage reaches over 97% with 0.75mm margin. The universal BLT-guided system offers seamless integration with commercial irradiators, achieving comparable localization accuracy, expected to supporting high-precision radiation research

Diffusive and localization behavior of electromagnetic waves in a two-dimensional random medium

In this paper, we discuss the transport phenomena of electromagnetic waves in a two-dimensional random system which is composed of arrays of electrical dipoles, following the model presented earlier by Erdogan, et al. (J. Opt. Soc. Am. B {\bf 10}, 391 (1993)). A set of self-consistent equations is presented, accounting for the multiple scattering in the system, and is then solved numerically. A strong localization regime is discovered in the frequency domain. The transport properties within, near the edge of and nearly outside the localization regime are investigated for different parameters such as filling factor and system size. The results show that within the localization regime, waves are trapped near the transmitting source. Meanwhile, the diffusive waves follow an intuitive but expected picture. That is, they increase with travelling path as more and more random scattering incurs, followed by a saturation, then start to decay exponentially when the travelling path is large enough, signifying the localization effect. For the cases that the frequencies are near the boundary of or outside the localization regime, the results of diffusive waves are compared with the diffusion approximation, showing less encouraging agreement as in other systems (Asatryan, et al., Phys. Rev. E {\bf 67}, 036605 (2003).)Comment: 8 pages 9 figure

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Combined searches for the production of supersymmetric top quark partners in proton-proton collisions at root s=13 TeV

A combination of searches for top squark pair production using proton-proton collision data at a center-of-mass energy of 13 TeV at the CERN LHC, corresponding to an integrated luminosity of 137 fb(-1) collected by the CMS experiment, is presented. Signatures with at least 2 jets and large missing transverse momentum are categorized into events with 0, 1, or 2 leptons. New results for regions of parameter space where the kinematical properties of top squark pair production and top quark pair production are very similar are presented. Depending on themodel, the combined result excludes a top squarkmass up to 1325 GeV for amassless neutralino, and a neutralinomass up to 700 GeV for a top squarkmass of 1150 GeV. Top squarks with masses from 145 to 295 GeV, for neutralino masses from 0 to 100 GeV, with a mass difference between the top squark and the neutralino in a window of 30 GeV around the mass of the top quark, are excluded for the first time with CMS data. The results of theses searches are also interpreted in an alternative signal model of dark matter production via a spin-0 mediator in association with a top quark pair. Upper limits are set on the cross section for mediator particle masses of up to 420 GeV