SAR Patterns Research Articles

How to Obtain a Detailed SAR Pattern of Currents on the Ocean Surface

At present, the generally accepted method for remote measurement of current velocity on the ocean surface is to determine the Doppler centroid, i.e., the position of the maximum of backscattered radar signal Doppler spectrum (see, for example, [1] and the list of references given there). However, this measurement, generally speaking, is not enough to reconstruct a detailed pattern of the curents

240.3: Detection of CMV Mediated Sub-Clinical Rejection by Urine Biomarkers

Methods: Research on early detection of Cytomegalovirus (CMV) mediated sub-clinical rejection (sAR) is in its nascence. This study explores the efficacy of urine-based biomarkers for sAR risk prognostication. Urine samples were serially collected (1 week- 2yrs) across 125 unique renal allograft recipients from UCSF and UCLA. These CMV+ (blood CMV-PCR) patients received valganciclovir therapy until CMV- for 3 consecutive months. Analysis: We computed a machine-learning based rejection prediction score incorporating urine cell-free DNA (cfDNA), methylated cfDNA, total protein, CXCL10, clusterin and creatinine. Rejection was determined between scores of 32-100; higher score associated with biopsy severity (Yang et al, STM 2021). In a cross-sectional analysis, Kruskal-Wallis test was performed on the urine-score distribution, to determine sAR during CMV+. Subsequently UCSF samples were analyzed longitudinally to establish the relationship between CMV and sAR; this was validated independently in UCLA samples. Results: Significant differences were observed in scores >32 between biopsy-confirmed AR vs. stable (p: 0.0034) and CMV vs. stable (p=0.003). Longitudinal analysis yielded 3 primary sAR patterns following CMV infection; (i)persistence of sAR leading to new development of chronic allograft injury; (ii)early sAR (score >32) followed by a further increase in score (>55) with biopsy confirmed cAR; (iii)sAR (>32) followed by recovery of injury with CMV resolution and a decline in score <32). Conclusions: We provide a urine-based method for detecting sAR at the time of CMV infection, and its potential clinical utility for titrating use of anti-viral therapy and recipient immunosuppression load.

Exploring the Chemical Space of Urease Inhibitors to Extract Meaningful Trends and Drivers of Activity.

Blocking the catalytic activity of urease has been shown to have a key role in different diseases as well as in different agricultural applications. A vast array of molecules have been tested against ureases of different species, but the clinical translation of these compounds has been limited due to challenges of potency, chemical and metabolic stability as well as promiscuity against other proteins. The design and development of new compounds greatly benefit from insights from previously tested compounds; however, no large-scale studies surveying the urease inhibitors' chemical space exist that can provide an overview of developed compounds to data. Therefore, given the increasing interest in developing new compounds for this target, we carried out a comprehensive analysis of the activity landscape published so far. To do so, we assembled and curated a data set of compounds tested against urease. To the best of our knowledge, this is the largest data set of urease inhibitors to date, composed of 3200 compounds of diverse structures. We characterized the data set in terms of chemical space coverage, molecular scaffolds, distribution with respect to physicochemical properties, as well as temporal trends of drug development. Through these analyses, we highlighted different substructures and functional groups responsible for distinct activity and inactivity against ureases. Furthermore, activity cliffs were assessed, and the chemical space of urease inhibitors was compared to DrugBank. Finally, we extracted meaningful patterns associated with activity using a decision tree algorithm. Overall, this study provides a critical overview of urease inhibitor research carried out in the last few decades and enabled finding underlying SAR patterns such as under-reported chemical functional groups that contribute to the overall activity. With this work, we propose different rules and practical implications that can guide the design or selection of novel compounds to be screened as well as lead optimization.

Design and Analysis of Compact Diversity Antenna for Wearable Applications

A new compact Ultra-Wideband (UWB) antenna is designed for wearable applications using jeans fabric as the substrate. The proposed antenna has an impedance bandwidth from 3.1 to 11.1 GHz. The antenna footprint is of size 18mm x 26 mm, and the thickness of the substrate is 0.8mm. It is based on a simple patch antenna configuration where the radiator consists of a simple rectangular structure and an ellipse added on top. Circular and elliptical notches are removed from the radiator, and rectangular notches are removed from the feed line for bandwidth enhancement. A partial ground plane of size 18mm x 9mm with a square notch is present on the other side of the antenna. Two such antennas are placed side by side as unit cells, one horizontal and the other vertical, to obtain a 2-port diversity set. The unit cells are placed at a distance such that minimal mutual coupling is present between the cells, and the size is also not compromised. The final diversity set so obtained is of size 44mm x 26 mm. The simulation results for reflection coefficients, SAR, and radiation pattern for both unit cell and diversity port are presented. Diversity parameters like ECC and diversity gain are also simulated for diversity antenna. The results obtained by testing the fabricated prototype are found to be matching reasonably with the simulated results. The antenna is also subjected to bending analysis.

Land subsidence from interferometric SAR and groundwater patterns in the Qazvin plain, Iran

ABSTRACTQazvin plain as one of the important plains in northwest Iran in terms of industrial and agricultural activities, reveals evidence of land subsidence in the last decade. We used a descending ENVISAT dataset during 2003–2006 and two ascending and descending Sentinel-1 tracks acquired during 2014–2016 to study the subsidence in the area. Our time-series analysis of the ENVISAT data reveals that the area is subsiding at an average rate of 40 mm yr−1 with a maximum value of 50 mm yr−1 in the line of sight direction. Moreover, our result for the Sentinel-1 ascending and descending tracks shows that the average subsidence rate reaches 65 mm yr−1 in the line of sight direction. Comparing the obtained mean velocity maps of the two datasets indicates the growing subsidence pattern in the northwest-southeast direction inside the plain. The investigation of the water source reveals that the overexploitation of aquifers caused an approximately 17 m decline in the groundwater level from 2001 to 2011. This drastic drop in the groundwater level has resulted in progressive subsidence over time. The comparison between the extent of subsidence from the image processing and the water level depletion contour map in the Qazvin plain depicts that subsidence is occurring in areas with a high decrease in underground water level. This study suggests that, besides decreasing the number of deep wells as well as their outflow water, the types of agricultural production related to water consumption and irrigation methods in an area such as Iran can play an important role in decreasing the stress on aquifers.

Standardization of patient modeling in hyperthermia simulation studies: introducing the Erasmus Virtual Patient Repository

Purpose Thermal dose-effect relations have demonstrated that clinical effectiveness of hyperthermia would benefit from more controlled heating of the tumor. Hyperthermia treatment planning (HTP) is a potent tool to study strategies enabling target conformal heating, but its accuracy is affected by patient modeling approximations. Homogeneous phantoms models are being used that do not match the body shape of patients in treatment position and often have unrealistic target volumes. As a consequence, simulation accuracy is affected, and performance comparisons are difficult. The aim of this study is to provide the first step toward standardization of HTP simulation studies in terms of patient modeling by introducing the Erasmus Virtual Patient Repository (EVPR): a virtual patient model database. Methods Four patients with a tumor in the head and neck or the pelvis region were selected, and corresponding models were created using a clinical segmentation procedure. Using the Erasmus University Medical Center standard procedure, HTP was applied to these models and compared to HTP for commonly used surrogate models. Results Although this study was aimed at presenting the EVPR database, our study illustrates that there is a non-negligible difference in the predicted SAR patterns between patient models and homogeneous phantom-based surrogate models. We further demonstrate the difference between actual and simplified target volumes being used today. Conclusion Our study describes the EVPR for the research community as a first step toward standardization of hyperthermia simulation studies.

Novel Methods for Prioritizing "Close-In" Analogs from Structure-Activity Relationship Matrices.

Here we describe the development of novel methods for compound evaluation and prioritization based on the structure-activity relationship matrix (SARM) framework. The SARM data structure allows automatic and exhaustive extraction of SAR patterns from data sets and their organization into a chemically intuitive scaffold/functional-group format. While SARMs have been used in the retrospective analysis of SAR discontinuity and identifying underexplored regions of chemistry space, there have been only a few attempts to apply SARMs prospectively in the prioritization of "close-in" analogs. In this work, three new ways of prioritizing virtual compounds based on SARMs are described: (1) matrix pattern-based prioritization, (2) similarity weighted, matrix pattern-based prioritization, and (3) analysis of variance based prioritization (ANV). All of these methods yielded high predictive power for six benchmark data sets (prediction accuracy R2 range from 0.63 to 0.82), yielding confidence in their application to new design ideas. In particular, the ANV method outperformed the previously reported SARM based method for five out of the six data sets tested. The impact of various SARM parameters were investigated and the reasons why SARM-based compound prioritization methods provide higher predictive power are discussed.

Numerical investigation of novel microwave applicators based on zero-order mode resonance for hyperthermia treatment of cancer

This paper characterizes three novel microwave applicators based on zero-order mode resonators for use in hyperthermia treatment of cancer. The radiation patterns are studied with numerical simulations in muscle tissue-equivalent model at 434MHz. The relative performance of the applicators is compared in terms of reflection coefficient, current distribution, power deposition (SAR) pattern, effective field size in 2D and 3D tissue volumes, and penetration depth. One particular configuration generated the most uniform SAR pattern, with 25% SAR covering 84% of the treatment volume extending to 1cm depth under the aperture, while remaining above 58% coverage as deep as 3cm under the aperture. Recommendations are made to further optimize this structure.

FEM simulation of tapered cap floating sleeve antenna for hepatocellular carcinoma therapy

ABSTRACTMalignant liver tumors are the sixth most common and deadly cancer in the world and the third most common cause of cancer mortality. Hepatocellular carcinoma (primary liver cancer) is one of the most common malignancies worldwide with one of the highest mortality rates. Microwave ablation (MWA) is a new, promising, and multidisciplinary technology designed to destroy unhealthy tissue of various natures by radiating electromagnetic waves with microwave antennas. The finite element method (FEM) has been used in the present work to generate the simulated models of tapered cap floating sleeve antenna for validation of its design concepts, because FEM allows modeling of complex geometries that cannot be solved by analytical methods or finite difference models. The performances have been evaluated in terms of objective metrics, ablation zone, antenna matching, power absorption and SAR pattern.

SAR Matrices: Automated Extraction of Information-Rich SAR Tables from Large Compound Data Sets

We introduce the SAR matrix data structure that is designed to elucidate SAR patterns produced by groups of structurally related active compounds, which are extracted from large data sets. SAR matrices are systematically generated and sorted on the basis of SAR information content. Matrix generation is computationally efficient and enables processing of large compound sets. The matrix format is reminiscent of SAR tables, and SAR patterns revealed by different categories of matrices are easily interpretable. The structural organization underlying matrix formation is more flexible than standard R-group decomposition schemes. Hence, the resulting matrices capture SAR information in a comprehensive manner.

FDTD analysis of a noninvasive hyperthermia system for brain tumors

BackgroundHyperthermia is considered one of the new therapeutic modalities for cancer treatment and is based on the difference in thermal sensitivity between healthy tissues and tumors. During hyperthermia treatment, the temperature of the tumor is raised to 40–45°C for a definite period resulting in the destruction of cancer cells. This paper investigates design, modeling and simulation of a new non-invasive hyperthermia applicator system capable of effectively heating deep seated as well as superficial brain tumors using inexpensive, simple, and easy to fabricate components without harming surrounding healthy brain tissues.MethodsThe proposed hyperthermia applicator system is composed of an air filled partial half ellipsoidal chamber, a patch antenna, and a head model with an embedded tumor at an arbitrary location. The irradiating antenna is placed at one of the foci of the hyperthermia chamber while the center of the brain tumor is placed at the other focus. The finite difference time domain (FDTD) method is used to compute both the SAR patterns and the temperature distribution in three different head models due to two different patch antennas at a frequency of 915 MHz.ResultsThe obtained results suggest that by using the proposed noninvasive hyperthermia system it is feasible to achieve sufficient and focused energy deposition and temperature rise to therapeutic values in deep seated as well as superficial brain tumors without harming surrounding healthy tissue.ConclusionsThe proposed noninvasive hyperthermia system proved suitable for raising the temperature in tumors embedded in the brain to therapeutic values by carefully selecting the systems components. The operator of the system only needs to place the center of the brain tumor at a pre-specified location and excite the antenna at a single frequency of 915 MHz. Our study may provide a basis for a clinical applicator prototype capable of heating brain tumors.

Synthesis of 2-substituted 17β-hydroxy/17-methylene estratrienes and their in vitro cytotoxicity in human cancer cell cultures

Synthesis of various types of 2-(alkylaminomethyl) and 2-(aroyl) 17β-estradiol analogs are reported. The synthesis of similar types of 2-substituted 17-methylene estratriene analogs was also achieved. Synthesis of chalcone derivatives of 17β-estradiol and 17-methylene estratriene were also realized. All these 2-substituted estratrienes were tested for their antiproliferative activity by using four different cell lines from colon, lung, glioma and breast cancers. Among the various 2-substituted estratrienes, the compounds 10d, 14a– h and 17e were found to have in vitro antiproliferative activity comparable to that of parent analogs 1– 4. Comparison of the SAR pattern of these 2-susbtituted estratriene derivatives confirmed that relatively, 17-methylene estratrienes are more active than that of 17β-estradiol analogs.

Coaxial Slot Antenna Design for Microwave Hyperthermia using Finite- Difference Time-Domain and Finite Element Method

Hyperthermia also called thermal therapy or thermotherapy is a type of cancer treatment in which body tissue is exposed to high temperatures. Research has shown that high temperatures can damage and kill cancer cells, usually with minimal injury to normal tissues. Otherwise, ablation or high temperature hyperthermia, including lasers and the use of radiofrequency, microwaves, and high-intensity focused ultrasound, are gaining attention as an alternative to standard sur- gical therapies. The electromagnetic microwave irradiation applied to the tumor tissue causes water molecules to vibrate and rotate, resulting in tissue heating and subsequently cell death via thermal-induced protein denaturation. The effective- ness of this technique is related to the temperature achieved during the therapy, as well as the length time of treatment and cell and tissue characteristics. Numerical electromagnetic and thermal simulations are used to optimize the antenna design and predict heating patterns. A computer modeling of a double slot antenna for interstitial hyperthermia was designed us- ing two different numerical methods, the Finite Element Method and a Finite-Difference Time-Domain. The aim of this work is to analyze both numerical methods and finally experiments results are compared to the simulated results generated by a thermal model. Our results show that normalized SAR patterns using FEM and FDTD look broadly similar. Further- more, the computed 60 °C isotherm using FEM and the measured lesion diameter in ex vivo tissue results agree very well.

Extracting SAR Information from a Large Collection of Anti-Malarial Screening Hits by NSG-SPT Analysis.

We combine two graphical SAR analysis methods, Network-like Similarity Graphs (NSGs) and Similarity-Potency Trees (SPTs), to search for SAR information in a large and heterogeneous compound data set containing more than 13,000 antimalarial screening hits that was recently released by GlaxoSmithKline (GSK). The NSG-SPT approach first identifies subsets of compounds inducing local SAR discontinuity in data sets and then extracts available SAR information from these subsets in a graphically intuitive manner. Applying the NSG-SPT analysis scheme, we have identified in the GSK collection compound subsets of high local SAR information content including both known and previously unknown antimalarial chemotypes, which yielded interpretable SAR patterns. This information should be helpful to prioritize and select antimalarial candidate compounds for further chemical exploration. Furthermore, the NSG-SPT tools are publicly available, and our study also shows how to practically apply these SAR analysis methods to study large compound data sets.

Improved hyperthermia treatment control using SAR/temperature simulation and PRFS magnetic resonance thermal imaging

Purpose: This article explores the feasibility of using coupled electromagnetic and thermodynamic simulations to improve planning and control of hyperthermia treatments for cancer. The study investigates the usefulness of preplanning to improve heat localisation in tumour targets in treatments monitored with PRFS-based magnetic resonance thermal imaging (MRTI).Methods: Heating capabilities of a cylindrical radiofrequency (RF) mini-annular phased array (MAPA) applicator were investigated with electromagnetic and thermal simulations of SAR in homogeneous phantom models and two human leg sarcomas. High frequency structure simulator (HFSS) (Ansoft) was used for electromagnetic simulations and SAR patterns were coupled into EPhysics (Ansoft) for thermal modelling with temperature-dependent variable perfusion. Simulations were accelerated by integrating tumour-specific anatomy into a pre-gridded whole body tissue model. To validate this treatment planning approach, simulations were compared with MR thermal images in both homogenous phantoms and heterogeneous tumours.Results: SAR simulations demonstrated excellent agreement with temperature rise distributions obtained with MR thermal imaging in homogeneous phantoms and clinical treatments of large soft-tissue sarcomas. The results demonstrate feasibility of preplanning appropriate relative phases of antennas for localising heat in tumour.Conclusions: Advances in the accuracy of computer simulation and non-invasive thermometry via MR thermal imaging have provided powerful new tools for optimisation of clinical hyperthermia treatments. Simulations agree well with MR thermal images in both homogeneous tissue models and patients with lower leg tumours. This work demonstrates that better quality hyperthermia treatments should be possible when simplified hybrid model simulations are performed routinely as part of the clinical pretreatment plan.

Piperidinyl-nicotinamides as potent and selective somatostatin receptor subtype 5 antagonists

Nicotinamides of benzyl-substituted 4-aminopiperidines and their seven-membered analogs of generic structure 2 and 2′ have been discovered as potent and selective SST5 antagonists. The activity (Ki) ranges from 2.4 to 436nM. Most compounds exhibit decent physicochemical properties and follow a clear SAR pattern. Interestingly enough, the receptor is strongly enantiodiscriminating and binds in the amino-azepane-series only the (R)-enantiomer.

Dosimetry of a set-up for the exposure of newborn mice to 2.45-GHZ WiFi frequencies

This work describes the dosimetry of a two waveguide cell system designed to expose newborn mice to electromagnetic fields associated with wireless fidelity signals in the frequency band of 2.45 GHz. The dosimetric characterisation of the exposure system was performed both numerically and experimentally. Specific measures were adopted with regard to the increase in both weight and size of the biological target during the exposure period. The specific absorption rate (SAR, W kg(-1)) for 1 W of input power vs. weight curve was assessed. The curve evidenced an SAR pattern varying from <1 W kg(-1) to >6 W kg(-1) during the first 5 weeks of the life of mice, with a peak resonance phenomenon at a weight around 5 g. This curve was used to set the appropriate level of input power during experimental sessions to expose the growing mice to a defined and constant dose.

PARAMETRIC STUDY OF POWER ABSORPTION PATTERNS INDUCED IN ADULT AND CHILD HEAD MODELS BY SMALL HELICAL ANTENNAS

A comparative assessment of power absorption in adult and child heads exposed to a small helical antenna at 1710MHz, is presented, emphasizing the efiect of age related parameters. Finite Difierence Time Domain simulations are employed to study the interaction between MRI-based head models and a mobile communication terminal equipped with a small helical monopole. A semi-analytical method, based on Green's function theory and the Method of Moments, is used to study the absorption in three- layer spherical head models exposed to a small helical dipole. SAR patterns in child head models derived by non-uniform scaling of adult ones were assessed against SAR patterns computed in child heads derived by uniform downscaling procedures. In both realistic and canonical exposure scenarios, comparable levels of absorbed power

Characteristics and performance evaluation of the capacitive Contact Flexible Microstrip Applicator operating at 70 MHz for external hyperthermia

Purpose: To characterise and evaluate the capacitive Contact Flexible Microstrip Applicator operating at 70 MHz, CFMA-70. This applicator is introduced for the treatment of superficial tumours with extension in depth beyond the range of regular superficial applicators.Methods: E-field measurements were performed in an elliptical phantom filled with a saline solution using an E-field vector probe. E-field distributions and SAR patterns are compared to those of the CFMA-434 and of 70 MHz waveguides. The applicator has been used for the treatment of 6 patients with breast cancer with a tumour depth exceeding 4 cm.Results: The effective heating depth of the CFMA-70 is 50% larger than for the CFMA-434. Its effective field size is 26 × 20 cm (aperture 29 × 20 cm), larger than for an equally sized CFMA-434. In contrast to the CFMA-434 the SAR pattern of this applicator is insensitive to the bolus thickness. Comparison to 70 MHz waveguides shows that the E-field component normal to the applicator is 100% larger for the CFMA-70. During clinical applications acceptable temperatures were realised for individual sessions (also at depth), but in many cases treatment limiting hot spots occurred close to superficial bony structures near the applicator edge. Both surface irregularities and the normal field component may be responsible.Conclusions: The CFMA-70 has adequate penetration depth for the treatment of superficial tumours exceeding a depth of 4 cm. However, the relatively large normal E-field component may induce treatment-limiting hot spots at tissue interfaces in the direction normal to the applicator's surface.

Modification of the furan ring of salvinorin A: Identification of a selective partial agonist at the kappa opioid receptor

In an effort to find novel agents which selectively target the kappa opioid receptor (KOPR), we modified the furan ring of the highly potent and selective KOPR agonist salvinorin A. Introduction of small substituents at C-16 was well tolerated. 12- epi-Salvinorin A, synthesized in four steps from salvinorin A, was a selective partial agonist at the KOPR. No clear SAR patterns were observed for C-13 aryl ketones. Introducing a hydroxymethylene group between C-12 and the furan ring was tolerated. Small C-13 esters and ethers gave weak KOPR agonists, while all C-13 amides were inactive. Finally, substitution of oxadiazoles for the furan ring abolished affinity for the KOPR. None of the compounds displayed any KOPR antagonism or any affinity for mu or delta opioid receptors.