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Purpose: The tumor immune microenvironment plays a crucial role in the development and progression of cancer. Sarcomas are a group of heterogeneous soft tissue malignancies that are often treated with radiotherapy as a part of the treatment concept. There is increasing evidence that radiotherapy leads to alterations in the tumor microenvironment, particularly with respect to the immune infiltrate. This study has been carried out to develop a better understanding of such changes following radiotherapy.Experimental Design: We retrospectively analyzed the expression of 35 immune response-related genes by quantitative reverse transcription PCR analysis and immunohistochemistry on paired formalin-fixed paraffin-embedded tumor samples from 38 sarcoma patients before and after radiotherapy.Results: We observed that radiotherapy results in a significant upregulation of several immune effectors and cancer-testis antigens and a concomitant downregulation of immune suppressors, indicating that radiotherapy may support the immune defense in sarcomas.Conclusions: These novel findings may have implications for the design of therapeutic regimens which exploite the immune system in sarcoma patients by combining standard radiotherapy with immunotherapeutic strategies. Clin Cancer Res; 19(17); 4843–53. ©2013 AACR.

Supplementary Figure S6 - PDF file 594K, Correlation between different immune response-related transcripts following radiotherapy in sarcoma patients: (A) Scatter dot plots demonstrating the significance of a bivariate correlation analysis (2-tailed). Each symbol represents an individual patient. Only correlations with a significant P value are represented in the figure. The solid line represents linear regression

Supplementary Table S1 - PDF file 558K, Patient information: The table summarizes patient diagnosis, survival status and the time of biopsy collection following radiotherapy. All patients received only neo-adjuvant radiotherapy (RT) and underwent surgery as part of their standard treatment regimen. N: number of patients, MPNST: malignant peripheral nerve sheath tumor, NOS: not otherwise specified

Leptin is a cytokine-like hormone that functions as a link between obesity and breast cancer (BC). Leptin treatment induces Epithelial to Mesenchymal Transition (EMT) in BC cell lines. In non-tumoral breast epithelial MCF10A cells, acute leptin treatment induces partial EMT. However, the effect of chronic leptin treatment on EMT in non-tumorigenic breast cells has not been fully explored. This study aimed to evaluate the effect of chronic leptin treatment on the induction of EMT in MCF10A cells. We found that chronic leptin treatment induces a switch from an epithelial to a mesenchymal morphology, partial loss of E-cadherin and gain of vimentin expression. Immunolocalization experiments showed a partial loss of E-cadherin at cell junctions and increased cytoplasmic localization of vimentin in leptin-treated cells. Moreover, chronic leptin treatment increased collective cell migration and invasion. Furthermore, when cultured in non-adherent conditions leptin treated cells exhibited reduced cell aggregation, increased survival, and decreased apoptosis, which correlates with increased FAK and AKT phosphorylation. Finally, bioinformatic analysis in two publicly available RNAseq datasets from normal breast tissue shows that high levels of leptin mRNA correlate positively with the expression of mesenchymal markers, and negatively with epithelial markers. Thus, our results demonstrate that chronic leptin treatment induces EMT in non-tumorigenic MCF10A cells and suggest that high leptin expression in normal breast tissue may induce EMT and contribute to increased risk of breast cancer.

The cerebral cortex contains billions of neurons, and their disorganization or misspecification leads to neurodevelopmental disorders. Understanding how the plethora of projection neuron subtypes are generated by cortical neural stem cells (NSCs) is a major challenge. Here, we focused on elucidating the transcriptional landscape of murine embryonic NSCs, basal progenitors (BPs), and newborn neurons (NBNs) throughout cortical development. We uncover dynamic shifts in transcriptional space over time and heterogeneity within each progenitor population. We identified signature hallmarks of NSC, BP, and NBN clusters and predict active transcriptional nodes and networks that contribute to neural fate specification. We find that the expression of receptors, ligands, and downstream pathway components is highly dynamic over time and throughout the lineage implying differential responsiveness to signals. Thus, we provide an expansive compendium of gene expression during cortical development that will be an invaluable resource for studying neural developmental processes and neurodevelopmental disorders., The EMBO Journal, 41 (24), ISSN:0261-4189, ISSN:1460-2075

This communication presents a framework for cosimulating receiving antenna arrays and receivers using circuit simulators. This framework is based on a recently introduced $\boldsymbol {2M}$ -port electrical model of an $\boldsymbol {M}$ -element antenna array with $\boldsymbol {M}$ physically accessible ports and $\boldsymbol {M}$ “free-space” ports. Based on this framework, we describe analytical and simulator-based approaches to determine receiving-array performance metrics, such as isotropic noise response, beam-equivalent system and receiver noise temperatures, and noise-matching efficiency.

The proposed design pursues an applicator that can survive deployment into deep hydrocarbon deposits. To ensure mechanical robustness, the design must be supported by a contiguous metal pipe, and to this end, the applicator uses a single-bare conductor transmission line excited bidirectionally with two coaxial discontinuities. These two discontinuities create a virtual impedance boundary through field superposition, where, ideally, the virtual boundary is a termination for a tuning stub formed in the surrounding material. As the material around the applicator changes, so does the impedance of the stub, engendering a degree of self-tuning behavior. The applicator concept was validated at 2.45 GHz, where the double discontinuity gave an $S_{11}$ of less than −10 dB in three different material cases and the measured electric field magnitude around the applicator was similar to simulation.

An antenna can be modeled as a two-port network using S-parameters. However, having individual antenna S-parameters is not sufficient for modeling an array of antennas as antennas exhibit mutual coupling. This article proposes a network model to represent an antenna array with mutual coupling. Using the proposed model, an $N$ -element antenna array is modeled as a combination of two-port networks representing each element and an $N$ -port network representing mutual coupling. Two techniques to calculate mutual coupling S-parameters are presented: a primary method using numerical solutions and an approximate method using approximate expressions. The proposed model was validated using four monopole arrays having different interelement spacings, the number of elements, and nonidentical antennas.

A power combined high-efficiency oscillator is proposed using a hybrid class E and class F tuning, where the odd harmonics are shorted: the class E/Fodd. The oscillator is achieved by adding a high-pass feedback network to a class E/Fodd amplifier, where the output’s odd harmonics are used to construct the required square-like wave at the input. Furthermore, two class E/Fodd oscillators can be power combined using a distributed active transformer, where magnetic coupling to the high-pass feedback network can be realized using a third transformer winding. Two power combined class E/Fodd oscillators designed using this method have an oscillation frequency of 10.1 MHz, a total output power of 324 W and dc-to-RF conversion efficiency of 75%.

A variant of the finite-difference time-domain (FDTD) algorithm—the Lebedev FDTD method—is augmented to allow for the simulation of electromagnetic waves in general dispersive anisotropic materials. Distinct dispersions may be applied to each of the principal axes of the anisotropic medium. The method is based on the auxiliary differential equation and is simple to implement. Because of the collocated nature of the algorithm, multiterm dispersions necessary in previous implementations are avoided. Lebedev grid has previously been studied in detail by different research groups for the simulation of anisotropy. In this paper, we specifically focus on extending frequency-dispersive materials to this method and provide multiple examples to demonstrate the accuracy, validity, and stability of the method.

The Lebedev grid is an alternative to Yee grid where, because the discretized fields lie at the same location in space, there is no need for further field interpolations when modeling anisotropic materials. In this letter, we focus on accurately implementing perfect electric conductors with planar interfaces, as well as 90° and 270° corners. Simulations are provided to demonstrate the overall improvements and also the second-order accuracy of the proposed methods.

Noise correlation matrices and noise parameters are useful for low-noise amplifier designers seeking to achieve the best noise performance out of their circuits. In some applications, such as radio astronomy, antennas and antenna arrays are part of receivers and, thus, modeling of the antenna noise is useful. Currently, antenna noise is modeled through antenna efficiency. A more accurate information on the highest-possible antenna efficiency is obtained from its $S$ -parameters or noise parameters. In this letter, we show how the two-port $S$ -parameters of an antenna can be determined by measuring its reflection coefficients inside two specifically sized Wheeler caps, in addition to a free-space measurement. We use the measurement to determine the noise correlation matrices and noise parameters of an antenna. The challenges of constructing appropriately sized Wheeler caps are discussed, and a new way of constructing a Wheeler cap is shown.

The collocated Lebedev grid has previously been proposed as an alternative to the Yee grid for electromagnetic finite-difference time-domain (FDTD) simulations. While it performs better in anisotropic media, it performs poorly in isotropic media because it is equivalent to four overlapping, uncoupled Yee grids. We propose to couple the four Yee grids and fix the Lebedev method using discrete exterior calculus (DEC) with higher-order Hodge duals. We find that higher-order Hodge duals do improve the performance of the Lebedev grid, but they also improve the Yee grid by a similar amount. The effectiveness of coupling overlapping Yee grids with a higher-order Hodge dual is thus questionable. However, the theoretical foundations developed to derive these methods may be of interest in other problems.

It is difficult to elucidate the transcriptional history of a cell using current experimental approaches, as they are destructive in nature and therefore describe only a moment in time. To overcome these limitations, we recently established Record-seq, a technology that enables transcriptional recording by CRISPR spacer acquisition from RNA. The recorded transcriptomes are recovered by SENECA, a method that selectively amplifies expanded CRISPR arrays, followed by deep sequencing. The resulting CRISPR spacers are aligned to the host genome, thereby enabling transcript quantification and associated analyses. Here, we describe the experimental procedures of the Record-seq workflow as well as subsequent data analysis. Beginning with the experimental design, Record-seq data can be obtained and analyzed within 1-2 weeks.

A broadside-scanning half-mode substrate integrated waveguide periodic leaky-wave antenna architecture with antipodal tapered slots is presented. The antenna builds upon a previously proposed architecture by introducing a periodic phase-reversal of radiating elements. This enables the antenna to operate with a comparatively low substrate permittivity while maintaining grating-lobe-free scanning from reverse to forward endfire.

A design of a 460 GHz substrate-integrated-waveguide (SIW) slot antenna in a 65-nm CMOS process is presented in thisarticle. The size of the antenna is 380 μm × 224 μm. An inductor identification layer is placed in the layout to reduce the internal metal density requirements significantly. The proposed antenna, which includes metal dummy fill to be compliant with the 65 nm process design rules, was simulated using HFSS. The antenna simulated with a 0.5 mm Si substrate has a maximum gain of 0.09 dBi and a radiation efficiency of 29.1%. The bandwidth of S11 below −10 dB is 25.3 GHz. © 2016 Wiley Periodicals, Inc. Microwave Opt Technol Lett 58:347–351, 2016

Microwave radar imaging is promising as a complementary medical imaging modality. However, the unique nature of the images means interpretation can be difficult. As a result, it is important to understand the sources of image differences, and how much variability is inherent in the imaging system itself. To address this issue, we compare the effectiveness of six different measures of image similarity for quantifying the similarity (or difference) between two microwave radar images. The structural similarity index has become the de facto standard for image comparison, but we propose that useful information can be acquired from a measure known as the Modified Hausdorff Distance. We apply each measure to image pairs from sequential scans of both phantoms and volunteers. We find that rather than using a single value to quantify the image similarity, by computing a number of values that are designed to capture different image aspects, we can better assess the ways in which the images differ.

The numerical evaluation of dielectric heating in a heavy oil containing sand is presented using a shaped dipole antenna under static (no oil production) and dynamic (with oil production) conditions. The electromagnetic simulator AxREMS™ was coupled to the commercial reservoir simulator STARS™ to model RF heating using three different shaped antenna designs (Straight dipole, Concave, and Convex design). The static simulations showed that the Concave design offers more uniform radiation pattern and temperature profile than the Straight and Convex counterparts. A conceptual model with seven sands (over- and under-burden and five oil-containing sands) was utilized for the dynamic simulation of downhole RF dielectric heating. The results indicated that all the RF heating cases had accelerated oil production than that found for the Base Case (cold production). Modeling shows that peak production is increased if RF heating is initiated before the start of production. However, all cases studied converged to approximately equal cumulative incremental oil above the Base Case, after about 700 days after the initiation of RF heating.

A broadband, high-gain substrate-integrated waveguide (SIW) slot antenna fabricated on a PCB is presented in this article. Measured return loss reaches 25 dB at 45 GHz with the bandwidth of 4.72 GHz. The simulated gain is 9.6 dBi at 46.2 GHz and the efficiency is 96%. The measured gain is 7.8 dBi at 46.2 GHz. Good agreement is achieved between measured and simulated antenna patterns and return losses. It is shown that the antenna behavior can be enhanced by oversizing the bottom ground and properly selecting dimensions of top metal. © 2015 Wiley Periodicals, Inc. Microwave Opt Technol Lett 57:1370–1374, 2015

The challenge of calculating the radiation efficiency of each antenna in a system/device, consisting of multiple non-identical antennas, is addressed in this paper. A model, which accounts for mutual coupling between antennas is proposed and subsequently the radiation efficiency of each individual antenna was calculated. The proposed model was validated using simulations and experimental outcomes.

The Lebedev method is a collocated scheme which makes it more suitable for modelling anisotropic materials compared to Yee method as it removes the need for interpolation since all the field components exist at one location. In this work, we accurately realize planar perfect electric conductors (PEC) and also PEC corners on Lebedev grid. To show the accuracy of the proposed method, a rectangular resonator filled with anisotropic material will be simulated, and the results will be compared with the previous method and HFSS.

The S-parameters of an electrically small antenna, modeled as a 2-port device can be calculated using specifically sized Wheeler caps. However, having antenna S-parameters are not sufficient for modeling S-parameters of an array of antennas as that does not model mutual antenna coupling. This paper proposes a model, which accounts for mutual coupling, and permits the calculation of array S-parameters. It is achieved by modeling mutual coupling as a 2-port device connecting the antenna element 2-port devices. In this paper, a two-element antenna array was used to demonstrate the operation of the model. Signal flow diagram of the model is presented and equations to calculate the radiation efficiency were derived. A two-element antenna array prototype was fabricated with two identical monopoles positioned greater than λ/2 apart at all frequencies of interest. The proposed model was verified using experimental outcomes and simulations for four frequency points. Derived equations can be applied directly to determine the radiation efficiency of a two-element antenna array. This model can be extended to a larger antenna arrays as well.

Many of the existing antennas described in current literature utilize PIN diodes to achieve switchable polarization. In realizing more elaborate reconfigurable antennas, the biasing structures for these DC-controlled components become more complex, which leads to limitations in the RF design as well as losses and undesired radiation. Other reconfigurable technologies, such as MEMS switches and liquid crystals, could be chosen for a particular application depending on various trade-offs, for example efficiency and ease of implementation. An alternative system is a recently developed scheme of using pneumatically controlled solid dielectric slugs, which is low-loss and immune to RF distortion, and eliminates the need for DC biasing structures. To demonstrate the viability of this system, it was incorporated in the design of a reconfigurable ring slot antenna capable of three polarization states (LP/LHCP/RHCP) at 2.4 GHz. The measured axial-ratio bandwidth was 5%, which is comparable to similar low-profile antennas. The simulated and measured antenna performance at all three states showed strong correlation. The pneumatic actuation of four slugs inside a channel to realize the three different states was successfully implemented, demonstrating that pneumatic slug control technology is suitable for inclusion in reconfigurable antennas.

A multi-arm spiral antenna, of N arms, can have N modes of operation. The integer n represents the operating mode which is determined by the signal phase increment between adjacent arms as fed from the antenna terminals. For the antenna to radiate effectively, the active region must be enclosed by a circumference of mode number (n) times the operating wavelength. Each mode generates a different radiation pattern. Modes, with n between 2 and N-2, are capable of forming radiation pattern nulls. This paper shows a way to excite noninteger modes along with integer modes of radiation, which combined, can create a null which can be steered away from the antenna vertical bore sight. Furthermore, variable reactive loading of spiral arm ends offers additional steering control and positioning of nulls in a 2D angular hemispherical space.

We outline a method for simultaneous optimization of multiple imaging parameters for microwave-radar imaging. Arguably, the most important parameter to determine is the effective permittivity to use for image reconstruction. The accuracy and reliability of the final image depends strongly on the ability to accurately estimate the effective permittivity. We demonstrate that our method is capable of estimating the correct effective permittivity, thereby reconstructing reliable images, by applying it to data collected with the Tissue Sensing Adaptive Radar system being developed at the University of Calgary.

A broadband beam-shifter is designed based on the well-known transformation optics technique. The beam-shifter can be also used as a polarization splitter if it is designed to only affect one polarization. The required material parameters are then realized by highly anisotropic metamaterial cells. Finally, the design is verified through simulation.

Travelling waves for real and complex reference impedance are reviewed. New power waves are defined and their behavior on a lossy transmission line are examined.

The noise correlation matrix and noise parameters are parameters of interest for antennas, and antenna arrays, particularly in the radio-astronomy context. For a passive network, such as an antenna, 2-port scattering parameters can be used to establish a noise correlation matrix and consequently the antenna noise parameters. In this paper we show how the 2-port scattering parameters of an antenna can be completely determined by measuring its reflection coefficient inside two specifically sized Wheeler caps, in addition to a free space measurement. We use the measurement to determine the noise correlation matrices and noise parameters of an antenna.

We present preliminary results from a method for estimating the optimal effective permittivity for reconstructing microwave-radar images. Using knowledge of how microwave-radar images are formed, we identify characteristics that are typical of good images, and define a fitness function to measure the relative image quality. We build a polynomial interpolant of the fitness function in order to identify the most likely permittivity values of the tissue. To make the estimation process more efficient, the polynomial interpolant is constructed using a locally and dimensionally adaptive sampling method that is a novel combination of stochastic collocation and polynomial chaos. Examples, using a series of simulated, experimental and patient data collected using the Tissue Sensing Adaptive Radar system, which is under development at the University of Calgary, are presented. These examples show how, using our method, accurate images can be reconstructed starting with only a broad estimate of the permittivity range.

Cerro Chajnantor Atacama Telescope (CCAT) will be a next-generation submillimeter telescope performing a broad range of submillimeter wave astronomical observations. Currently, the development of CCAT is undertaken by universities from USA, Canada, and Germany with others expressing interest in the project. This paper gives a brief overview of CCAT and its first-light Heterodyne Array Instrument (CHAI). The development of a CHAI receiver conducted at the University of Calgary is discussed.

A pneumatically controlled patch antenna with resonant frequency that can be switched to either 3.05 GHz or 5 GHz is introduced. The resonant frequency of the device is determined by the dimension of the patch that is excited. To select a particular frequency, a pneumatically-operated copper-plated swinging arm is moved to cover one of two orthogonal slots on the ground plane. The uncovered slot allows energy to be coupled from the microstrip feedline to the corresponding dimension of the patch. Simulated results from HFSS are provided.

The standard Yee grid, though simple and robust, is not well suited to modeling anisotropic media. In contrast, the Lebedev grid is well suited, but is computationally more expensive. A methodology is presented to use the classical Yee grid in isotropic regions and take advantage of the Lebedev method as a subgridded region for anisotropic materials only. Two methods to couple the two regions are proposed and described in detail. The proposed methods show low reflection in a scenario where a normally incident plane wave hits a Yee–Lebedev interface. Also, the two techniques are shown to be both accurate and stable.

In this paper, we introduce an ultra-wideband transmission system for detecting heart volume variation. We characterize our proposed system using a semi-dynamic heart model. Our analysis shows multiple propagation paths in the thorax, involving both surface modes around the heart and refraction of the microwave signal by the heart. The results show a strong sensitivity of the signal quality to the placement of the sensors. With correct alignment, our analysis shows 4 dB magnitude variation over the cardiac cycle, a significant improvement on previously reported continuous wave monitors (0.5 dB signal change at 915 MHz).

In this paper, we present a simplified semi-dynamic heart model for investigation of microwave transmission heart monitoring systems between 1.5 and 4 GHz in both simulation and measurement. We aim to validate that our proposed heart model is able to represent the heart structure at microwave frequencies by comparing our model to an accurate numerical heart model (anHM) from the ITIS foundation virtual population. Our simple numerical heart model (snHM) (simulation) and physical heart model (pHM) (measurement) are evaluated in a simplified human chest model using an UWB biomedical sensor. In simulation, the transmission parameter shows agreement with the time domain peak of −94.5 dB for the snHM and −96.4 dB in the anHM. The anHM and pHM transmission signal characteristics were then compared showing good agreement. Our heart model is able to represent the heart between 1.5 and 4.0 GHz and represents a step toward a real time dynamic heart model for hardware evaluation.