Compact Ultra-Wideband Wilkinson Power Divider in Parallel Stripline with Modified Isolation Branches.

An efficient design method for a compact and ultra-wideband multi-stage Wilkinson power divider in a parallel stripline (PSL) is proposed. To enhance the frequency bandwidth of the proposed power divider while reducing its size, the isolation branch is modified; that is, two capacitors are connected to both sides of a resistor at each isolation branch. For an efficient design process, the PSL power divider is equivalently represented by two microstrip power dividers, and the design equations are derived. Based on the design equations, an in-house algorithm is utilized to optimally determine the design parameters, including the line impedance, resistance, and capacitance of each stage. For example, a three-stage PSL power divider is designed with three λ/4 transmission lines at a base frequency of 5 GHz. To verify the accuracy of the design procedure, 3D EM simulations and measurements are performed, and the results show good agreement. Compared with the conventional three-stage Wilkinson power divider, the proposed PSL power divider achieves a wider frequency bandwidth of 1.16 to 6.51 GHz (139.5%) and a 23% shorter transmission line length of 207°, while exhibiting an insertion loss of 0.7 to 1.4 dB.

Ultra-Wideband Vertical Transition in Coplanar Stripline for Ultra-High-Speed Digital Interfaces.

A design method for an ultra-wideband coplanar-stripline-based vertical transition that can be used for ultra-high-speed digital interfaces is proposed. A conventional via structure, based on a differential line (DL), inherently possesses performance limitations (<10 GHz) due to difficulties in maintaining constant line impedance and smooth electric field transformation, in addition to the effects of signal skews, FR4 fiber weave, and unbalanced EM interferences. DL-based digital interfaces may not meet the demands of ultra-high-speed digital data transmission required for the upcoming 6G communications. The use of a coplanar stripline (CPS), a type of planar balanced line (BL), for the vertical transition, along with the ultra-wideband DL-to-CPS transition, mostly removes the inherent and unfavorable issues of the DL and enables ultra-high-speed digital data transmission. The design process of the transition is simplified using the analytical design formulas, derived using the conformal mapping method, of the transition. The characteristic line impedances of the transition are calculated and found to be in close agreement with the results obtained from EM simulations. Utilizing these results, the CPS-based vertical transition, maintaining the characteristic line impedance of 100 Ω, is designed and fabricated. The measured results confirm its ultra-wideband characteristics, with a maximum of 1.6 dB insertion loss and more than 10 dB return loss in the frequency range of DC to 30 GHz. Therefore, the proposed CPS-based vertical transition offers a significantly wider frequency bandwidth, i.e., more than three times that of conventional DL-based via structures.

Temporal and spatial distribution of microplastic in the sediment of the Han River, South Korea.

Sediments are sinks for microplastics (MPs) in freshwater environments. It is, therefore, necessary to investigate the occurrence and fate of accumulated MPs in the sediments, which pose a risk to aquatic organisms. We conducted the first comprehensive investigation of MPs in riverine sediment in South Korea to examine the temporal and spatial distribution of MPs in the sediment at the two main branches and downstream of the Han River. The average abundance of MPs over all sites was 0.494 ± 0.280 particles/g. Spatially, the MP abundance at three sites in the North Han River (0.546 ± 0.217 particles/g) was higher than those in the South Han River (0.383 ± 0.145 particles/g) and downstream of the Han River (0.417 ± 0.114 particles/g). The abundances of MPs before dams at two upstream sites were significantly higher than that at other sites because of the slow river flow velocity attributed to the artificial structure. The abundance of MPs after the mosoon season (October, 0.600 ± 0.357 particles/g) was higher than that before the mosoon season (April, 0.389 ± 0.099 particles/g). The most common polymer types observed were polyethylene (>38%) and polypropylene (>24%). Irrespective of the location and season, greater than 93% of MPs identified were fragments, and the remaining were fibers. The concentrations of TOC, TN, and TP in the sediment were positively correlated with MP abundance. MP abundance was also positively correlated with clay and silt fractions of the sediment; however, it was negatively correlated with sand fraction. This study provides a basis for the management of MP pollution by offering findings related to critical factors influencing MP abundance in sediment.

Occurrence and characteristics of microplastics in fish of the Han River, South Korea: Factors affecting microplastic abundance in fish.

This study examined the abundance of microplastics (MPs) in 106 fish from 22 species inhabiting three sites of the Han River, South Korea. In total, 1753 MPs from 106 fish samples were identified with an average abundance of 15.60 ± 13.45 MPs per individual fish (MPs indiv-1) in the North Han River, 16.35 ± 12.32 MPs indiv-1 in the South Han River, and 20.14 ± 10.01 MPs indiv-1 in downstream of the Han River, indicating that the fish in the downstream of the Han River was the most contaminated by MPs. The dominant size of MPs detected in fish ranged between 0.1 and 0.2 mm, and the most common polymer types found in fish were polypropylene (PP) (≥40%) and polyethylene (PE) (≥23%), followed by polytetrafluoroethylene (PTFE) (≥16%) at all sampling locations. A significant correlation was observed between the log-transformed number of MPs with log-transformed fish length (p < 0.01) and with log-transformed fish weight (p < 0.01). The Kruskal-Wallis test disclosed a significant difference in the number of MPs among the feeding habits (p < 0.01), indicating that omnivorous and insectivorous fish contained more MPs than carnivorous and herbivorous fish. In addition, fish habitat result showed that pelagic fish contained a higher level of MPs than demersal fish, but no significant differences in the number of MPs among fish habitats were observed (p > 0.05).

Dynamic Pore Modulation of Stretchable Electrospun Nanofiber Filter for Adaptive Machine Learned Respiratory Protection.

The recent emergence of highly contagious respiratory disease and the underlying issues of worldwide air pollution jointly heighten the importance of the personal respirator. However, the incongruence between the dynamic environment and nonadaptive respirators imposes physiological and psychological adverse effects, which hinder the public dissemination of respirators. To address this issue, we introduce adaptive respiratory protection based on a dynamic air filter (DAF) driven by machine learning (ML) algorithms. The stretchable elastomer fiber membrane of the DAF affords immediate adjustment of filtration characteristics through active rescaling of the micropores by simple pneumatic control, enabling seamless and constructive transition of filtration characteristics. The resultant DAF-respirator (DAF-R), made possible by ML algorithms, successfully demonstrates real-time predictive adapting maneuvers, enabling personalizable and continuously optimized respiratory protection under changing circumstances.

Pyruvate sensitizes pancreatic tumors to hypoxia-activated prodrug TH-302.

BACKGROUND: Hypoxic niches in solid tumors harbor therapy-resistant cells. Hypoxia-activated prodrugs (HAPs) have been designed to overcome this resistance and, to date, have begun to show clinical efficacy. However, clinical HAPs activity could be improved. In this study, we sought to identify non-pharmacological methods to acutely exacerbate tumor hypoxia to increase TH-302 activity in pancreatic ductal adenocarcinoma (PDAC) tumor models. RESULTS: Three human PDAC cell lines with varying sensitivity to TH-302 (Hs766t > MiaPaCa-2 > SU.86.86) were used to establish PDAC xenograft models. PDAC cells were metabolically profiled in vitro and in vivo using the Seahorse XF system and hyperpolarized (13)C pyruvate MRI, respectively, in addition to quantitative immunohistochemistry. The effect of exogenous pyruvate on tumor oxygenation was determined using electroparamagnetic resonance (EPR) oxygen imaging. Hs766t and MiaPaCa-2 cells exhibited a glycolytic phenotype in comparison to TH-302 resistant line SU.86.86. Supporting this observation is a higher lactate/pyruvate ratio in Hs766t and MiaPaCa xenografts as observed during hyperpolarized pyruvate MRI studies in vivo. Coincidentally, response to exogenous pyruvate both in vitro (Seahorse oxygen consumption) and in vivo (EPR oxygen imaging) was greatest in Hs766t and MiaPaCa models, possibly due to a higher mitochondrial reserve capacity. Changes in oxygen consumption and in vivo hypoxic status to pyruvate were limited in the SU.86.86 model. Combination therapy of pyruvate plus TH-302 in vivo significantly decreased tumor growth and increased survival in the MiaPaCa model and improved survival in Hs766t tumors. CONCLUSIONS: Using metabolic profiling, functional imaging, and computational modeling, we show improved TH-302 activity by transiently increasing tumor hypoxia metabolically with exogenous pyruvate. Additionally, this work identified a set of biomarkers that may be used clinically to predict which tumors will be most responsive to pyruvate + TH-302 combination therapy. The results of this study support the concept that acute increases in tumor hypoxia can be beneficial for improving the clinical efficacy of HAPs and can positively impact the future treatment of PDAC and other cancers.

Mechanical aspects of microtubule bundling in taxane-treated circulating tumor cells.

Microtubules play an important role in many cellular processes, including mitotic spindle formation and cell division. Taxane-based anticancer treatments lead to the stabilization of microtubules, thus preventing the uncontrolled proliferation of tumor cells. One of the striking physical features of taxane-treated cells is the localization of their microtubules, which can be observed via fluorescent microscopy as an intense fluorescent band and are referred to as a microtubule bundle. With the recent advances in capturing and analyzing tumor cells circulating in a patient's blood system, there is increasing interest in using these cells to examine a patient's response to treatment. This includes taxanes that are used routinely in clinics to treat prostate, breast, lung, and other cancers. Here, we have used a computational model of microtubule mechanics to investigate self-arrangement patterns of stabilized microtubules, which allowed for the identification of specific combinations of three physical parameters: microtubule stiffness, intracellular viscosity, and cell shape, that can prevent the formation of microtubule bundles in cells with stabilized microtubules, such as taxane-treated cells. We also developed a method to quantify bundling in the whole microtubule aster structure and a way to compare the simulated results to fluorescent images from experimental data. Moreover, we investigated microtubule rearrangement in both suspended and attached cells and showed that the observed final microtubule patterns depend on the experimental protocol. The results from our computational studies can explain the heterogeneous bundling phenomena observed via fluorescent immunostaining from a mechanical point of view without relying on heterogeneous cellular responses to the microtubule-stabilizing drug.

The formation of tight tumor clusters affects the efficacy of cell cycle inhibitors: a hybrid model study.

Cyclin-dependent kinases (CDKs) are vital in regulating cell cycle progression, and, thus, in highly proliferating tumor cells CDK inhibitors are gaining interest as potential anticancer agents. Clonogenic assay experiments are frequently used to determine drug efficacy against the survival and proliferation of cancer cells. While the anticancer mechanisms of drugs are usually described at the intracellular single-cell level, the experimental measurements are sampled from the entire cancer cell population. This approach may lead to discrepancies between the experimental observations and theoretical explanations of anticipated drug mechanisms. To determine how individual cell responses to drugs that inhibit CDKs affect the growth of cancer cell populations, we developed a spatially explicit hybrid agent-based model. In this model, each cell is equipped with internal cell cycle regulation mechanisms, but it is also able to interact physically with its neighbors. We model cell cycle progression, focusing on the G1 and G2/M cell cycle checkpoints, as well as on related essential components, such as CDK1, CDK2, cell size, and DNA damage. We present detailed studies of how the emergent properties (e.g., cluster formation) of an entire cell population depend on altered physical and physiological parameters. We analyze the effects of CDK1 and CKD2 inhibitors on population growth, time-dependent changes in cell cycle distributions, and the dynamic evolution of spatial cell patterns. We show that cell cycle inhibitors that cause cell arrest at different cell cycle phases are not necessarily synergistically super-additive. Finally, we demonstrate that the physical aspects of cell population growth, such as the formation of tight cell clusters versus dispersed colonies, alter the efficacy of cell cycle inhibitors, both in 2D and 3D simulations. This finding may have implications for interpreting the treatment efficacy results of in vitro experiments, in which treatment is applied before the cells can grow to produce clusters, especially because in vivo tumors, in contrast, form large masses before they are detected and treated.

Current advances in mathematical modeling of anti-cancer drug penetration into tumor tissues.

Delivery of anti-cancer drugs to tumor tissues, including their interstitial transport and cellular uptake, is a complex process involving various biochemical, mechanical, and biophysical factors. Mathematical modeling provides a means through which to understand this complexity better, as well as to examine interactions between contributing components in a systematic way via computational simulations and quantitative analyses. In this review, we present the current state of mathematical modeling approaches that address phenomena related to drug delivery. We describe how various types of models were used to predict spatio-temporal distributions of drugs within the tumor tissue, to simulate different ways to overcome barriers to drug transport, or to optimize treatment schedules. Finally, we discuss how integration of mathematical modeling with experimental or clinical data can provide better tools to understand the drug delivery process, in particular to examine the specific tissue- or compound-related factors that limit drug penetration through tumors. Such tools will be important in designing new chemotherapy targets and optimal treatment strategies, as well as in developing non-invasive diagnosis to monitor treatment response and detect tumor recurrence.

Catheter-based treatment in patients with critical pulmonary stenosis or pulmonary atresia with intact ventricular septum: a single institute experience with comparison between patients with and without additional procedure for pulmonary flow.

OBJECTIVES: We report a single institute experience of transcatheter pulmonary valvotomy using the soft end of a guidewire followed or not by a systemic-pulmonary shunt in patients with pulmonary atresia with intact ventricular septum (PAIVS) or critical pulmonary stenosis (CPS). In addition, we compare patients with or without an additional source of flow to support the pulmonary circulation after successful pulmonary valvotomy. METHODS: All neonates with PAIVS or CPS who underwent primary transcatheter pulmonary valvotomy between January 2004 and December 2010 were reviewed retrospectively. Some of them needed an additional source of flow to support the pulmonary circulation. We performed a comparison between those who required an additional source of pulmonary flow and those who did not. RESULTS: The initial procedure was successful in 20 out of 22 patients (seven of nine with PAIVS; all of 13 with CPS), but 10 of them needed an additional source of flow to support the pulmonary circulation: nine had arterial duct stenting and one had surgical Blalock-Taussig shunt. There were no deaths or major acute complications, except for femoral artery occlusion in three patients. The bipartite right ventricular morphology, the tricuspid z-score of ≤-0.74, the tricuspid to mitral valve ratio of ≤ 0.9, and the z-score of the diastolic interventricular septal thickness ≥ 2.37 in preprocedural examination showed more tendency of needing shunt placement. CONCLUSION: Transcatheter pulmonary valvotomy using the soft end of a guidewire followed or not by the arterial duct stent implantation was an effective approach in those patients. The angiographic distinction between CPS and PAIVS did not affect anything in this study including the procedural method, success, and odds for reintervention. The degree of right ventricle cavity hypoplasia provided the main restriction to forward flow after pulmonary valvotomy.

Association study of the candidate gene for knee osteoarthritis in Koreans.

The aim of this study was to examine a single-nucleotide polymorphism (SNP) rs7639618 of double von Willebrand factor (DVWA) gene for the association with osteoarthritis (OA) susceptibility in Korean cohort. The study was a part of the Korean cohort study. Two thousand four hundred sixty-two subjects aged 50 years and older who were derived from the cohort and who were assessed for OA at the knee were genotyped. The anteroposterior extended-view weight-bearing radiographs of the knees were obtained. Of the subjects, 725 subjects had radiographic OA. Genomic DNA was extracted from peripheral blood using a QIAamp DNA Blood Mini Kit (Qiagen, Valencia, CA). Genotyping was performed using High Resolution Melt or the Taq-Man allelic discrimination assay and the Rotor-Gene 6000 (Corbett Research, Sydney,Australia). Associations were tested by calculating the odds ratios (ORs) and 95% confidence intervals (95% CIs), using logistic regression analysis with adjustments for age, gender, and body mass index (BMI). The mean age of the OA patients (females: 554 subjects, 76.4%) was 67.4 (7.9) years. The intraobserver agreement was high for the identification of osteophytes (κ: 0.80) and joint space narrowing (κ: 0.70). There was no significant difference (all P values > 0.05) in the genotype or allele frequencies between the patients with OA and healthy controls. There was also no significant difference when the cases were adjusted by age, gender, and BMI. The associations of DVWA SNPs with OA were noted in previous studies and were not found in the Korean OA cohort.

Dynamical characteristics of bacteria clustering by self-generated attractants.

Motivated by the recent work on Escherichia coli bacteria clustering [Park, S., Wolanin, P.M., Yuzbashyan, E.A., Lin, H., Darnton, N.C., Stock, J.B., Silberzan, P., Austin, R., 2003. Proc. Natl. Acad. Sci. U.S.A. 100 (24), 13910], we have conducted a computer simulation of E. coli chemotaxis induced by a self-excreted attractant and investigated how bacteria clusters interact through a self-excreted attractant. By modeling the variation of tumbling frequency in the context of phosphorylation rate change, we have investigated the dependency of clustering behavior on the sensitivity of cells to the attractant. We have found that there exists an optimal sensitivity leading to bigger clusters and that the geometry surrounding the cells also plays an important role in localizing the cluster formation. This result suggests that bacterial cluster formation can be reduced by making bacteria more sensitive to attractants, which is opposite to an instinctive way (making them retarded to attractants). In addition, we have studied the effect of an initial cell distribution on clustering.

Deformation of a helical filament by flow and electric or magnetic fields.

Motivated by recent advances in the real-time imaging of fluorescent flagellar filaments in living bacteria [Turner, Ryu, and Berg, J. Bacteriol. 82, 2793 (2000)], we compute the deformation of a helical elastic filament due to flow and external magnetic or high-frequency electric fields. Two cases of deformation due to hydrodynamic drag are considered: the compression of a filament rotated by a stationary motor and the extension of a stationary filament due to flow along the helical axis. We use Kirchhoff rod theory for the filament, and work to linear order in the deflection. Hydrodynamic forces are described first by resistive-force theory, and then for comparison by the more accurate slender-body theory. For helices with a short pitch, the deflection in axial flow predicted by slender-body theory is significantly smaller than that computed with resistive-force theory. Therefore, our estimate of the bending stiffness of a flagellar filament is smaller than that of previous workers. In our calculation of the deformation of a polarizable helix in an external field, we show that the problem is equivalent to the classical case of a helix deformed by forces applied only at the ends.

Hydrodynamic interactions between rotating helices.

Escherichia coli bacteria use rotating helical flagella to swim. At this scale, viscous effects dominate inertia, and there are significant hydrodynamic interactions between nearby helices. These interactions cause the flagella to bundle during the "runs" of bacterial chemotaxis. Here we use slender-body theory to solve for the flow fields generated by rigid helices rotated by stationary motors. We determine how the hydrodynamic forces and torques depend on phase and phase difference, show that rigid helices driven at constant torque do not synchronize, and solve for the flows. We also use symmetry arguments based on kinematic reversibility to show that for two rigid helices rotating with zero phase difference, there is no time-averaged attractive or repulsive force between the helices.

A macroscopic scale model of bacterial flagellar bundling.

Escherichia coli and other bacteria use rotating helical filaments to swim. Each cell typically has about four filaments, which bundle or disperse depending on the sense of motor rotation. To study the bundling process, we built a macroscopic scale model consisting of stepper motor-driven polymer helices in a tank filled with a high-viscosity silicone oil. The Reynolds number, the ratio of viscous to elastic stresses, and the helix geometry of our experimental model approximately match the corresponding quantities of the full-scale E. coli cells. We analyze digital video images of the rotating helices to show that the initial rate of bundling is proportional to the motor frequency and is independent of the characteristic relaxation time of the filament. We also determine which combinations of helix handedness and sense of motor rotation lead to bundling.