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The goal of immunotherapy is to mobilize the immune system to kill cancer cells. Immunotherapy is more effective and, in general, the prognosis is better, when more immune cells infiltrate the tumor. We explore the question of whether the spatial distribution rather than just the density of immune cells in the tumor is important in forecasting whether cancer recurs. After reviewing previous work on this issue, we introduce a novel application of maximum entropy to quantify the spatial distribution of discrete point-like objects. We apply our approach to B and T cells in images of tumor tissue taken from triple negative breast cancer patients. We find that the immune cells are more spatially dispersed in good clinical outcome (no recurrence of cancer within at least 5 years of diagnosis) compared to poor clinical outcome (recurrence within 3 years of diagnosis). Our results highlight the importance of spatial distribution of immune cells within tumors with regard to clinical outcome, and raise new questions on their role in cancer recurrence.

The goal of immunotherapy is to mobilize the immune system to kill cancer cells. Immunotherapy is more effective and, in general, the prognosis is better, when more immune cells infiltrate the tumor. We explore the question of whether the spatial distribution rather than just the density of immune cells in the tumor is important in forecasting whether cancer recurs. After reviewing previous work on this issue, we introduce a novel application of maximum entropy to quantify the spatial distribution of discrete point-like objects. We apply our approach to B and T cells in images of tumor tissue taken from triple negative breast cancer patients. We find that the immune cells are more spatially dispersed in good clinical outcome (no recurrence of cancer within at least 5 years of diagnosis) compared to poor clinical outcome (recurrence within 3 years of diagnosis). Our results highlight the importance of spatial distribution of immune cells within tumors with regard to clinical outcome, and raise new questions on their role in cancer recurrence.

While tumor infiltration by CD8+ T cells is now widely accepted to predict outcomes, the clinical significance of intratumoral B cells is less clear. We hypothesized that spatial distribution rather than density of B cells within tumors may provide prognostic significance. We developed statistical techniques (fractal dimension differences and a box-counting method 'occupancy') to analyze the spatial distribution of tumor-infiltrating lymphocytes (TILs) in human triple-negative breast cancer (TNBC). Our results indicate that B cells in good outcome tumors (no recurrence within 5 years) are spatially dispersed, while B cells in poor outcome tumors (recurrence within 3 years) are more confined. While most TILs are located within the stroma, increased numbers of spatially dispersed lymphocytes within cancer cell islands are associated with a good prognosis. B cells and T cells often form lymphocyte clusters (LCs) identified via density-based clustering. LCs consist either of T cells only or heterotypic mixtures of B and T cells. Pure B cell LCs were negligible in number. Compared to tertiary lymphoid structures (TLS), LCs have fewer lymphocytes at lower densities. Both types of LCs are more abundant and more spatially dispersed in good outcomes compared to poor outcome tumors. Heterotypic LCs in good outcome tumors are smaller and more numerous compared to poor outcome. Heterotypic LCs are also closer to cancer islands in a good outcome, with LC size decreasing as they get closer to cancer cell islands. These results illuminate the significance of the spatial distribution of B cells and LCs within tumors.

Post-translational modification of tubulin provides differential functions to microtubule networks. Here, we address the role of tubulin acetylation on the penetrative capacity of cells undergoing radial intercalation, which is the process by which cells move apically, insert between outer cells, and join an epithelium. There are opposing forces that regulate intercalation, namely, the restrictive forces of the epithelial barrier versus the penetrative forces of the intercalating cell. Positively and negatively modulating tubulin acetylation in intercalating cells alters the developmental timing such that cells with more acetylation penetrate faster. We find that intercalating cells preferentially penetrate higher-order vertices rather than the more prevalent tricellular vertices. Differential timing in the ability of cells to penetrate different vertices reveals that lower-order vertices represent more restrictive sites of insertion. We shift the accessibility of intercalating cells toward more restrictive junctions by increasing tubulin acetylation, and we provide a geometric-based mathematical model that describes our results.

Post-translational modification of tubulin provides differential functions to microtubule networks. Here, we address the role of tubulin acetylation on the penetrative capacity of cells undergoing radial intercalation, which is the process by which cells move apically, insert between outer cells, and join an epithelium. There are opposing forces that regulate intercalation, namely, the restrictive forces of the epithelial barrier versus the penetrative forces of the intercalating cell. Positively and negatively modulating tubulin acetylation in intercalating cells alters the developmental timing such that cells with more acetylation penetrate faster. We find that intercalating cells preferentially penetrate higher-order vertices rather than the more prevalent tricellular vertices. Differential timing in the ability of cells to penetrate different vertices reveals that lower-order vertices represent more restrictive sites of insertion. We shift the accessibility of intercalating cells toward more restrictive junctions by increasing tubulin acetylation, and we provide a geometric-based mathematical model that describes our results.

Post-translational modification of tubulin provides differential functions to microtubule networks. Here, we address the role of tubulin acetylation on the penetrative capacity of cells undergoing radial intercalation, which is the process by which cells move apically, insert between outer cells, and join an epithelium. There are opposing forces that regulate intercalation, namely, the restrictive forces of the epithelial barrier versus the penetrative forces of the intercalating cell. Positively and negatively modulating tubulin acetylation in intercalating cells alters the developmental timing such that cells with more acetylation penetrate faster. We find that intercalating cells preferentially penetrate higher-order vertices rather than the more prevalent tricellular vertices. Differential timing in the ability of cells to penetrate different vertices reveals that lower-order vertices represent more restrictive sites of insertion. We shift the accessibility of intercalating cells toward more restrictive junctions by increasing tubulin acetylation, and we provide a geometric-based mathematical model that describes our results.

While tumor infiltration by CD8+ T cells is now widely accepted to predict outcomes, the clinical significance of intratumoral B cells is less clear. We hypothesized that spatial distribution rather than density of B cells within tumors may provide prognostic significance. We developed statistical techniques (fractal dimension differences and a box-counting method 'occupancy') to analyze the spatial distribution of tumor-infiltrating lymphocytes (TILs) in human triple-negative breast cancer (TNBC). Our results indicate that B cells in good outcome tumors (no recurrence within 5 years) are spatially dispersed, while B cells in poor outcome tumors (recurrence within 3 years) are more confined. While most TILs are located within the stroma, increased numbers of spatially dispersed lymphocytes within cancer cell islands are associated with a good prognosis. B cells and T cells often form lymphocyte clusters (LCs) identified via density-based clustering. LCs consist either of T cells only or heterotypic mixtures of B and T cells. Pure B cell LCs were negligible in number. Compared to tertiary lymphoid structures (TLS), LCs have fewer lymphocytes at lower densities. Both types of LCs are more abundant and more spatially dispersed in good outcomes compared to poor outcome tumors. Heterotypic LCs in good outcome tumors are smaller and more numerous compared to poor outcome. Heterotypic LCs are also closer to cancer islands in a good outcome, with LC size decreasing as they get closer to cancer cell islands. These results illuminate the significance of the spatial distribution of B cells and LCs within tumors.

We present a novel view of the standard model of tunneling two level systems (TLSs) to explain the puzzling universal value of a quantity, C∼3×10^{-4}, that characterizes phonon scattering in glasses below 1 K as reflected in thermal conductivity, ultrasonic attenuation, internal friction, and the change in sound velocity. Physical considerations lead to a broad distribution of phonon-TLS couplings that (1) exponentially renormalize tunneling matrix elements, and (2) reduce the TLS density of states through TLS-TLS interactions. We find good agreement between theory and experiment for a variety of individual glasses.

Favorable outcomes have been associated with high densities of tumor infiltrating lymphocytes (TILs) such as cytotoxic ([Formula: see text]) T cells. However, the clinical significance of the spatial distribution of TILs is less well understood. We have developed novel statistical techniques to characterize the spatial distribution of TILs at various length scales. These include a box counting method that we call “occupancy” and novel applications of fractal dimensions. We apply these techniques to the spatial distribution of [Formula: see text] T cells in the tumor microenvironment of tissue resected from 35 triple negative breast cancer patients. We find that there is a distinct difference in the spatial distribution of [Formula: see text] T cells between good clinical outcome (no recurrence within at least 5 years of diagnosis) and poor clinical outcome (recurrence within 3 years of diagnosis). The statistical significance of the difference between good and poor outcome in the occupancy, fractal dimension (FD), and FD difference of [Formula: see text] T cells is comparable to that of the [Formula: see text] T cell density. Even when we randomly exclude some of the cells so that the images have the same cell density, we still find that the fractal dimension at short length scales is correlated with cancer recurrence, implying that the actual spatial distribution of [Formula: see text] cells, and not just the [Formula: see text] cell density, is associated with clinical outcome. The occupancy and FD difference indicate that the [Formula: see text] T cells are more spatially dispersed in good outcome and more aggregated in poor outcome. We discuss possible interpretations.

Favorable outcomes have been associated with high densities of tumor infiltrating lymphocytes (TILs) such as cytotoxic ([Formula: see text]) T cells. However, the clinical significance of the spatial distribution of TILs is less well understood. We have developed novel statistical techniques to characterize the spatial distribution of TILs at various length scales. These include a box counting method that we call “occupancy” and novel applications of fractal dimensions. We apply these techniques to the spatial distribution of [Formula: see text] T cells in the tumor microenvironment of tissue resected from 35 triple negative breast cancer patients. We find that there is a distinct difference in the spatial distribution of [Formula: see text] T cells between good clinical outcome (no recurrence within at least 5 years of diagnosis) and poor clinical outcome (recurrence within 3 years of diagnosis). The statistical significance of the difference between good and poor outcome in the occupancy, fractal dimension (FD), and FD difference of [Formula: see text] T cells is comparable to that of the [Formula: see text] T cell density. Even when we randomly exclude some of the cells so that the images have the same cell density, we still find that the fractal dimension at short length scales is correlated with cancer recurrence, implying that the actual spatial distribution of [Formula: see text] cells, and not just the [Formula: see text] cell density, is associated with clinical outcome. The occupancy and FD difference indicate that the [Formula: see text] T cells are more spatially dispersed in good outcome and more aggregated in poor outcome. We discuss possible interpretations.

We present a novel view of the standard model of tunneling two level systems (TLSs) to explain the puzzling universal value of a quantity, C∼3×10^{-4}, that characterizes phonon scattering in glasses below 1 K as reflected in thermal conductivity, ultrasonic attenuation, internal friction, and the change in sound velocity. Physical considerations lead to a broad distribution of phonon-TLS couplings that (1) exponentially renormalize tunneling matrix elements, and (2) reduce the TLS density of states through TLS-TLS interactions. We find good agreement between theory and experiment for a variety of individual glasses.

Long-distance intracellular axonal transport is predominantly microtubule-based, and its impairment is linked to neurodegeneration. Here we review recent theoretical and experimental evidence that suggest that near the axon boundaries (walls), the effective viscosity can become large enough to impede cargo transport in small (but not large) caliber axons. Theoretical work suggests that this opposition to motion increases rapidly as the cargo approaches the wall. However, having parallel microtubules close enough together to enable a cargo to simultaneously engage motors on more than one microtubule dramatically enhances motor activity, and thus decreases the effects due to such opposition. Experimental evidence supports this hypothesis: in small caliber axons, microtubule density is higher, increasing the probability of having parallel microtubules close enough that they can be used simultaneously by motors on a cargo. For transport toward the minus-end of microtubules, e.g., toward the cell body in an axon, a recently discovered force adaptation system can also contribute to overcoming such opposition to motion.

Long-distance intracellular axonal transport is predominantly microtubule-based, and its impairment is linked to neurodegeneration. Here we review recent theoretical and experimental evidence that suggest that near the axon boundaries (walls), the effective viscosity can become large enough to impede cargo transport in small (but not large) caliber axons. Theoretical work suggests that this opposition to motion increases rapidly as the cargo approaches the wall. However, having parallel microtubules close enough together to enable a cargo to simultaneously engage motors on more than one microtubule dramatically enhances motor activity, and thus decreases the effects due to such opposition. Experimental evidence supports this hypothesis: in small caliber axons, microtubule density is higher, increasing the probability of having parallel microtubules close enough that they can be used simultaneously by motors on a cargo. For transport toward the minus-end of microtubules, e.g., toward the cell body in an axon, a recently discovered force adaptation system can also contribute to overcoming such opposition to motion.

In developing tissues, cell polarization and proliferation are regulated by morphogens and signaling pathways. Cells throughout the Drosophila wing primordium typically show subcellular localization of the unconventional myosin Dachs on the distal side of cells (nearest the center of the disc). Dachs localization depends on the spatial distribution of bonds between the protocadherins Fat (Ft) and Dachsous (Ds), which form heterodimers between adjacent cells; and the Golgi kinase Four-jointed (Fj), which affects the binding affinities of Ft and Ds. The Fj concentration forms a linear gradient while the Ds concentration is roughly uniform throughout most of the wing pouch with a steep transition region that propagates from the center to the edge of the pouch during the third larval instar. Although the Fj gradient is an important cue for polarization, it is unclear how the polarization is affected by cell division and the expanding Ds transition region, both of which can alter the distribution of Ft-Ds heterodimers around the cell periphery. We have developed a computational model to address these questions. In our model, the binding affinity of Ft and Ds depends on phosphorylation by Fj. We assume that the asymmetry of the Ft-Ds bond distribution around the cell periphery defines the polarization, with greater asymmetry promoting cell proliferation. Our model predicts that this asymmetry is greatest in the radially-expanding transition region that leaves polarized cells in its wake. These cells naturally retain their bond distribution asymmetry after division by rapidly replenishing Ft-Ds bonds at new cell-cell interfaces. Thus we predict that the distal localization of Dachs in cells throughout the pouch requires the movement of the Ds transition region and the simple presence, rather than any specific spatial pattern, of Fj.

In developing tissues, cell polarization and proliferation are regulated by morphogens and signaling pathways. Cells throughout the Drosophila wing primordium typically show subcellular localization of the unconventional myosin Dachs on the distal side of cells (nearest the center of the disc). Dachs localization depends on the spatial distribution of bonds between the protocadherins Fat (Ft) and Dachsous (Ds), which form heterodimers between adjacent cells; and the Golgi kinase Four-jointed (Fj), which affects the binding affinities of Ft and Ds. The Fj concentration forms a linear gradient while the Ds concentration is roughly uniform throughout most of the wing pouch with a steep transition region that propagates from the center to the edge of the pouch during the third larval instar. Although the Fj gradient is an important cue for polarization, it is unclear how the polarization is affected by cell division and the expanding Ds transition region, both of which can alter the distribution of Ft-Ds heterodimers around the cell periphery. We have developed a computational model to address these questions. In our model, the binding affinity of Ft and Ds depends on phosphorylation by Fj. We assume that the asymmetry of the Ft-Ds bond distribution around the cell periphery defines the polarization, with greater asymmetry promoting cell proliferation. Our model predicts that this asymmetry is greatest in the radially-expanding transition region that leaves polarized cells in its wake. These cells naturally retain their bond distribution asymmetry after division by rapidly replenishing Ft-Ds bonds at new cell-cell interfaces. Thus we predict that the distal localization of Dachs in cells throughout the pouch requires the movement of the Ds transition region and the simple presence, rather than any specific spatial pattern, of Fj.

We show that charge noise $S_Q$ in Josephson qubits can be produced by fluctuating two level systems (TLS) with electric dipole moments in the substrate using a flat density of states. At high frequencies the frequency and temperature dependence of the charge noise depends on the ratio $J/J_c$ of the electromagnetic flux $J$ to the critical flux $J_c$. It is not widely appreciated that TLS in small qubits can easily be strongly saturated with $J/J_c\gg 1$. Our results are consistent with experimental conclusions that $S_Q\sim 1/f$ at low frequencies and $S_Q\sim f$ at high frequencies.

We show that charge noise $S_Q$ in Josephson qubits can be produced by fluctuating two level systems (TLS) with electric dipole moments in the substrate using a flat density of states. At high frequencies the frequency and temperature dependence of the charge noise depends on the ratio $J/J_c$ of the electromagnetic flux $J$ to the critical flux $J_c$. It is not widely appreciated that TLS in small qubits can easily be strongly saturated with $J/J_c\gg 1$. Our results are consistent with experimental conclusions that $S_Q\sim 1/f$ at low frequencies and $S_Q\sim f$ at high frequencies.

This corrects the article DOI: 10.1103/PhysRevLett.115.077002.

This corrects the article DOI: 10.1103/PhysRevLett.115.077002.

Long-distance intracellular axonal transport is predominantly microtubule-based, and its impairment is linked to neurodegeneration. In this study, we present theoretical arguments that suggest that near the axon boundaries (walls), the effective viscosity can become large enough to impede cargo transport in small (but not large) caliber axons. Our theoretical analysis suggests that this opposition to motion increases rapidly as the cargo approaches the wall. We find that having parallel microtubules close enough together to enable a cargo to simultaneously engage motors on more than one microtubule dramatically enhances motor activity, and thus minimizes the effects of any opposition to transport. Even if microtubules are randomly placed in axons, we find that the higher density of microtubules found in small-caliber axons increases the probability of having parallel microtubules close enough that they can be used simultaneously by motors on a cargo. The boundary effect is not a factor in transport in large-caliber axons where the microtubule density is lower.

The spatial patterns of cell proliferation and polarization in developing organisms depend on, yet differ from, the profiles of related signaling molecules. A classic case is the fruit fly wing primordium, a developing tissue whose cells demonstrate a consistent polarization despite depending on proteins with fairly uniform concentration profiles. Although the profiles of the Fat (Ft) pathway components Four-jointed (Fj) and Dachsous (Ds) are typically viewed as smoothly graded with uniform slope stretching across the wing pouch, this is not the case. Rather, the protocadherin Ds is expressed at high levels outside the wing pouch and low, roughly uniform levels within it, with a steep transition region at the border of the wing pouch. The Golgi kinase Fj has a complementary profile with uniformly high expression levels within the pouch, low levels in the periphery of the wing disc, and a steep concentration gradient in the transition region. However, the Fj and Ds profiles are not static; Ds-expressing cells are gradually recruited into the Fj-expressing wing pouch. We present a computational model that incorporates these profiles and their dynamics. Ft and Ds are protocadherins that form heterodimers between adjacent cells with a binding affinity that depends on Fj. In our model the asymmetry of the Ft-Ds bond distribution around the periphery of a cell defines the polarization. This asymmetry is greatest in the transition region. The transition region expands radially outwards with time, leaving in its wake polarized cells that retain their asymmetric bond distributions and direction of polarization, even after cell division. Similarly, the cells of the pouch proliferate roughly uniformly despite nonuniform profiles of proteins involved in growth signaling, such as Decapentaplegic (Dpp) and Wingless (Wg). In our model, cells grow and proliferate in response to the asymmetry of their Ft-Ds bond distributions as well as to the local morphogen (Dpp and Wg) concentrat

The spatial patterns of cell proliferation and polarization in developing organisms depend on, yet differ from, the profiles of related signaling molecules. A classic case is the fruit fly wing primordium, a developing tissue whose cells demonstrate a consistent polarization despite depending on proteins with fairly uniform concentration profiles. Although the profiles of the Fat (Ft) pathway components Four-jointed (Fj) and Dachsous (Ds) are typically viewed as smoothly graded with uniform slope stretching across the wing pouch, this is not the case. Rather, the protocadherin Ds is expressed at high levels outside the wing pouch and low, roughly uniform levels within it, with a steep transition region at the border of the wing pouch. The Golgi kinase Fj has a complementary profile with uniformly high expression levels within the pouch, low levels in the periphery of the wing disc, and a steep concentration gradient in the transition region. However, the Fj and Ds profiles are not static; Ds-expressing cells are gradually recruited into the Fj-expressing wing pouch. We present a computational model that incorporates these profiles and their dynamics. Ft and Ds are protocadherins that form heterodimers between adjacent cells with a binding affinity that depends on Fj. In our model the asymmetry of the Ft-Ds bond distribution around the periphery of a cell defines the polarization. This asymmetry is greatest in the transition region. The transition region expands radially outwards with time, leaving in its wake polarized cells that retain their asymmetric bond distributions and direction of polarization, even after cell division. Similarly, the cells of the pouch proliferate roughly uniformly despite nonuniform profiles of proteins involved in growth signaling, such as Decapentaplegic (Dpp) and Wingless (Wg). In our model, cells grow and proliferate in response to the asymmetry of their Ft-Ds bond distributions as well as to the local morphogen (Dpp and Wg) concentrat

Long-distance intracellular axonal transport is predominantly microtubule-based, and its impairment is linked to neurodegeneration. In this study, we present theoretical arguments that suggest that near the axon boundaries (walls), the effective viscosity can become large enough to impede cargo transport in small (but not large) caliber axons. Our theoretical analysis suggests that this opposition to motion increases rapidly as the cargo approaches the wall. We find that having parallel microtubules close enough together to enable a cargo to simultaneously engage motors on more than one microtubule dramatically enhances motor activity, and thus minimizes the effects of any opposition to transport. Even if microtubules are randomly placed in axons, we find that the higher density of microtubules found in small-caliber axons increases the probability of having parallel microtubules close enough that they can be used simultaneously by motors on a cargo. The boundary effect is not a factor in transport in large-caliber axons where the microtubule density is lower.

Planar cell polarization represents the ability of cells to orient within the plane of a tissue orthogonal to the apical basal axis. The proper polarized function of multiciliated cells requires the coordination of cilia spacing and cilia polarity as well as the timing of cilia beating during metachronal synchrony. The planar cell polarity pathway and hydrodynamic forces have been shown to instruct cilia polarity. In this paper, we show how intracellular effectors interpret polarity to organize cellular morphology in accordance with asymmetric cellular function. We observe that both cellular actin and microtubule networks undergo drastic reorganization, providing differential roles during the polarized organization of cilia. Using computational angular correlation analysis of cilia orientation, we report a graded cellular organization downstream of cell polarity cues. Actin dynamics are required for proper cilia spacing, global coordination of cilia polarity, and coordination of metachronic cilia beating, whereas cytoplasmic microtubule dynamics are required for local coordination of polarity between neighboring cilia.

The spatial organization of the cell depends upon intracellular trafficking of cargos hauled along microtubules and actin filaments by the molecular motor proteins kinesin, dynein, and myosin. Although much is known about how single motors function, there is significant evidence that cargos in vivo are carried by multiple motors. While some aspects of multiple motor function have received attention, how the cargo itself - and motor organization on the cargo-affects transport has not been considered. To address this, we have developed a three-dimensional Monte Carlo simulation of motors transporting a spherical cargo, subject to thermal fluctuations that produce both rotational and translational diffusion. We found that these fluctuations could exert a load on the motor(s), significantly decreasing the mean travel distance and velocity of large cargos, especially at large viscosities. In addition, the presence of the cargo could dramatically help the motor to bind productively to the microtubule: the relatively slow translational and rotational diffusion of moderately sized cargos gave the motors ample opportunity to bind to a microtubule before the motor/cargo ensemble diffuses out of range of that microtubule. For rapidly diffusing cargos, the probability of their binding to a microtubule was high if there were nearby microtubules that they could easily reach by translational diffusion. Our simulations found that one reason why motors may be approximately 100 nm long is to improve their 'on' rates when attached to comparably sized cargos. Finally, our results suggested that to efficiently regulate the number of active motors, motors should be clustered together rather than spread randomly over the surface of the cargo. While our simulation uses the specific parameters for kinesin, these effects result from generic properties of the motors, cargos, and filaments, so they should apply to other motors as well.

The spatial organization of the cell depends upon intracellular trafficking of cargos hauled along microtubules and actin filaments by the molecular motor proteins kinesin, dynein, and myosin. Although much is known about how single motors function, there is significant evidence that cargos in vivo are carried by multiple motors. While some aspects of multiple motor function have received attention, how the cargo itself - and motor organization on the cargo-affects transport has not been considered. To address this, we have developed a three-dimensional Monte Carlo simulation of motors transporting a spherical cargo, subject to thermal fluctuations that produce both rotational and translational diffusion. We found that these fluctuations could exert a load on the motor(s), significantly decreasing the mean travel distance and velocity of large cargos, especially at large viscosities. In addition, the presence of the cargo could dramatically help the motor to bind productively to the microtubule: the relatively slow translational and rotational diffusion of moderately sized cargos gave the motors ample opportunity to bind to a microtubule before the motor/cargo ensemble diffuses out of range of that microtubule. For rapidly diffusing cargos, the probability of their binding to a microtubule was high if there were nearby microtubules that they could easily reach by translational diffusion. Our simulations found that one reason why motors may be approximately 100 nm long is to improve their 'on' rates when attached to comparably sized cargos. Finally, our results suggested that to efficiently regulate the number of active motors, motors should be clustered together rather than spread randomly over the surface of the cargo. While our simulation uses the specific parameters for kinesin, these effects result from generic properties of the motors, cargos, and filaments, so they should apply to other motors as well.

Planar cell polarization represents the ability of cells to orient within the plane of a tissue orthogonal to the apical basal axis. The proper polarized function of multiciliated cells requires the coordination of cilia spacing and cilia polarity as well as the timing of cilia beating during metachronal synchrony. The planar cell polarity pathway and hydrodynamic forces have been shown to instruct cilia polarity. In this paper, we show how intracellular effectors interpret polarity to organize cellular morphology in accordance with asymmetric cellular function. We observe that both cellular actin and microtubule networks undergo drastic reorganization, providing differential roles during the polarized organization of cilia. Using computational angular correlation analysis of cilia orientation, we report a graded cellular organization downstream of cell polarity cues. Actin dynamics are required for proper cilia spacing, global coordination of cilia polarity, and coordination of metachronic cilia beating, whereas cytoplasmic microtubule dynamics are required for local coordination of polarity between neighboring cilia.

Fiona CM Ling, Rich SW Masters, Clare CW Yu, Alison M McManusInstitute of Human Performance, The University of Hong Kong, Pokfulam, Hong KongBackground: There is increasing evidence that continuous activation of the hypothalamic-pituitary adrenal axis and the central sympathetic nervous system contributes to the pathogenesis of central adiposity via increased psychological stress. The purpose of this study was to examine the link between central adiposity and the propensity for Chinese children to rehearse emotionally upsetting events, a dimension of psychological stress. Additionally, gender differences in this relationship were explored.Methods: Waist circumference, which is a marker of central adiposity and associated risks of developing cardiovascular disease, was measured and the propensity for rehearsal was assessed twice over two consecutive years in Hong Kong Chinese children (n = 194, aged 7–9 years), using a psychometric tool.Results: Children with waist circumference indicative of a risk of cardiovascular disease displayed higher rehearsal scores than children categorized as “not at risk”, as did boys compared with girls. Our results suggest that central adiposity and the propensity for rehearsal of emotionally upsetting events may be linked in Chinese children.Conclusion: Future prospective studies examining the direction of causality between central adiposity and rehearsal can potentially have valuable clinical implications.Keywords: obesity, abdominal, stress, psychological, Hong Kong, child

The Josephson junction (JJ) qubit is a leading candidate in the design of a quantum computer. A significant advantage of this approach is scalability, as these qubits may be readily fabricated in large numbers using integrated-circuit technology. A major obstacle to the realization of quantum computers with Josephson junction qubits is decoherence. The goal of our research was to elucidate the microscopic sources of this decoherence and to suggest ways to eliminate or reduce these culprits. We focused on the decoherence produced by two level systems in the insulating barrier of a Josephson junction as well as in the insulating dielectric material (e.g., SiO2) typically used to fabricate integrated circuit (IC) chips. Two level systems consist of an atom or group of atoms that can sit in one of two places. We worked with John Martinis' group (UCSB/NIST) which found that two level states are a dominant source of decoherence in superconducting qubits. One reason for this is that two level systems can resonantly absorb microwaves that are used to probe and manipulate the qubit. Once there are enough microwaves to saturate the two level systems, the rest of the microwaves can go through resulting in attenuation that decreases with increasing microwave power. Another mechanism for qubit decoherence is due to two level systems in the junction barrier which couple to the qubit. We explored two models in which a two level system couples to a qubit.