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A key impediment to studying water-related mechanisms in plants is the inability to non-invasively image water fluxes in cells at high temporal and spatial resolution. Here, we report that Raman microspectroscopy, complemented by hydrodynamic modelling, can achieve this goal - monitoring hydrodynamics within living root tissues at cell- and sub-second-scale resolutions. Raman imaging of water-transporting xylem vessels in Arabidopsis thaliana mutant roots reveals faster xylem water transport in endodermal diffusion barrier mutants. Furthermore, transverse line scans across the root suggest water transported via the root xylem does not re-enter outer root tissues nor the surrounding soil when en-route to shoot tissues if endodermal diffusion barriers are intact, thereby separating ‘two water worlds’.

Large data centers host thousands of tenants and services, and today's data center networks are no longer simple end- to-end transfer fabrics. Tenants desire more functionality like strong performance isolation, latency control, load balancing, middlebox placement, and other services. As tenant performance requirements become more demanding, data center providers wish to increase the set of services they offer in an attempt to meet the demand and attract new customers. Critically, while the promise of cloud computing makes it straightforward to rent compute resources, there is no standard model for tenants to pick and choose the network resources and services they require. Traditionally, a single procedure governs the allocation of resources to tenant services. For efficiency, data center providers multiplex tenants across the physical infrastructure, leveraging end host virtualization to carve out well-specified units of isolated CPU, memory, and storage. In contrast, tenants typically receive loose, qualitative descriptions of network performance with a limited set of available features. This disparity is problematic for today's data centers, which need to satisfy services with a diverse and non-uniform set of networking needs. This dissertation proposes to resolve this contention by provisioning a custom virtual network for each of the data center's clients. It presents task switching, a framework that redefines how tenants interact with and obtain resources from the network by servicing their individual requests for virtual network tasks. It then describes a model with two components, Blender and Omakase, that defines interfaces for the network provider to implement differing features and resource allocation procedures that tenants may choose to adopt for their tasks. Blender focuses on performance isolation, eliminating the either/or balancing act between resource efficiency and performance predictability by allowing data center operators to run multiple perfor

Large data centers host thousands of tenants and services, and today's data center networks are no longer simple end- to-end transfer fabrics. Tenants desire more functionality like strong performance isolation, latency control, load balancing, middlebox placement, and other services. As tenant performance requirements become more demanding, data center providers wish to increase the set of services they offer in an attempt to meet the demand and attract new customers. Critically, while the promise of cloud computing makes it straightforward to rent compute resources, there is no standard model for tenants to pick and choose the network resources and services they require. Traditionally, a single procedure governs the allocation of resources to tenant services. For efficiency, data center providers multiplex tenants across the physical infrastructure, leveraging end host virtualization to carve out well-specified units of isolated CPU, memory, and storage. In contrast, tenants typically receive loose, qualitative descriptions of network performance with a limited set of available features. This disparity is problematic for today's data centers, which need to satisfy services with a diverse and non-uniform set of networking needs. This dissertation proposes to resolve this contention by provisioning a custom virtual network for each of the data center's clients. It presents task switching, a framework that redefines how tenants interact with and obtain resources from the network by servicing their individual requests for virtual network tasks. It then describes a model with two components, Blender and Omakase, that defines interfaces for the network provider to implement differing features and resource allocation procedures that tenants may choose to adopt for their tasks. Blender focuses on performance isolation, eliminating the either/or balancing act between resource efficiency and performance predictability by allowing data center operators to run multiple perfor

Today’s large-scale services generally exploit loosely-coupled architectures that restrict functionality requiring tight cooperation (e.g., leader election, synchronization, and reconfiguration) to a small subset of nodes. In contrast, this work presents a way to scalably deploy tightly-coupled distributed systems that require significant coordination among a large number of nodes in the wide area. Our design relies upon a new reliable group membership abstraction to ensure that either group members are capable of communicating or that new groups form. In particular, we deploy a distributed rate limiting (DRL) service within a global testbed infrastructure. Unlike most distributed services, DRL can safely operate in separate partitions simultaneously, but requires timely snapshots of global state within each. Our DRL implementation leverages our proposed group membership abstraction and a robust gossip-based communication protocol, conjoining the fates of view maintenance and data dissemination. Through local and wide-area experiments, we illustrate that DRL remains accurate and responsive in the face of a variety of failure scenarios.Pre-2018 CSE ID: CS2012-0973

A combination of open data tools and methods, facilitated by data format standardization, has started changing business as usual in the transit industry. The general transit feed specification (GTFS) has become the de facto standard for releasing public transit route and schedule data. This study analyzed this rapidly evolving transit information sector through the Mexico City, Mexico, experience. The case study illustrated that even a megacity with several transit providers could create a fully functional GTFS feed in a few weeks and obtain the benefits of work done elsewhere. Because of the global open data ecosystem, a range of free or low-cost applications—customer-facing applications and planning tools—can immediately capitalize on these data. However, the Mexico experience revealed a limitation of GTFS in its current form: its inability to easily accommodate semi-structured public transit services common in many cities in the developing world. An adaption to GTFS developed in Mexico City to address this limitation is described. The case study revealed significant untapped potential to maximize the value of the open data ecosystem, particularly for planning and regulatory tools., World Bank. Energy Sector Management Assistance Program

A metamaterial based on carbon nanocoil inclusions is suggested as a means to obtain homogenized magnetism. Demonstrated growth techniques for such nanocoils suggest convenient fabrication is possible. The effective permeability of the medium is studied numerically and shown to exhibit a resonance curve in frequency. By fitting the resonance curve to a Lorentzian-based analytic model and exploring its parameter space, the performance of the nanocoil inclusion configuration is evaluated. These results suggest carbon nanocoils should be effective as magnetic materials in the terahertz frequency regime and possibly beyond. (C) 2015 AIP Publishing LLC., QC 20151116

We demonstrate high resonant absorption of visible light with a plasmonic nanocavity chain structure fabricated through resistless nanoimprinting in metal (RNIM). The RNIM approach provides a simple, reproducible, and accurate means to fabricate metallic nanopatterns with high fidelity. The nanocavities are shown to be efficiently excited using normally incident light, and the resonant wavelength can be controlled by either the width or the depth of the cavity. Numerical simulations confirm the experimental observations, and illustrate the behavior of the nanocavity chain waveguide and insensitivity to incident angle. The resonant absorption is due to the excitation of a localized metal-insulator-metal cavity mode. The interacting surface waves allow cavity lengths on the order of ten nanometers for light having a free space wavelength of about four hundred nanometers. Coupling of the cavities with an intervening surface plasmon wave results in a collective excitation and a chain waveguide mode that should prove valuable for more sensitive detection based on surface enhanced Raman scattering. (C) 2013 Optical Society of America

We demonstrate high resonant absorption of visible light with a plasmonic nanocavity chain structure fabricated through resistless nanoimprinting in metal (RNIM). The RNIM approach provides a simple, reproducible, and accurate means to fabricate metallic nanopatterns with high fidelity. The nanocavities are shown to be efficiently excited using normally incident light, and the resonant wavelength can be controlled by either the width or the depth of the cavity. Numerical simulations confirm the experimental observations, and illustrate the behavior of the nanocavity chain waveguide and insensitivity to incident angle. The resonant absorption is due to the excitation of a localized metal-insulator-metal cavity mode. The interacting surface waves allow cavity lengths on the order of ten nanometers for light having a free space wavelength of about four hundred nanometers. Coupling of the cavities with an intervening surface plasmon wave results in a collective excitation and a chain waveguide mode that should prove valuable for more sensitive detection based on surface enhanced Raman scattering. (C) 2013 Optical Society of America

Our focus has been on the design and analysis of metamaterials that will lead to the realization of new classes of devices. In large part, the materials are not defined by lithography, and hence are amenable to inexpensive large-scale manufacture. Nonlinear optimization methods have been used to design structures that are based on anisotropic metamaterials and operate as efficient energy collectors (anti-reflection coatings) and cloaks. Active quantum dot metamaterials have yielded controllable transmission windows, and this material forms the basis of a nanophotonic source. A graphene stack is proposed that appears to be the blackest material, and an experimental effort has started with a collaborator. Magnetism based on carbon nanotube coils is providing new insight into magnetic metamaterials. A study of electromagnetic energy in dispersive materials has produced some surprising results. A rigorous study of electromagnetic forces in positive and negative refractive index materials shows that a negative force occurs in a material with gain. Imaging and antenna opportunities are described for metal-insulator stack lenses, and analytic models are developed for curved stacks that can be used in design. The influence of surface roughness on the homogenized anisotropic response of metal-insulator stacks is evaluated., The original document contains color images.

The calcite-liquid interface is of great importance in many industrial and academic situations. In this paper, this interface is investigated using the powerful method of neutron reflection. Experimental approaches to overcome the challenges of surface roughness, cleanliness and mineral dissolution have been developed. Based on this protocol, the interfaces of calcite with the liquids water, toluene and heptane have been characterised successfully. Hence this study allows the technique of neutron reflection to be expanded to the investigation of mineral surfaces.

The calcite-liquid interface is of great importance in many industrial and academic situations. In this paper, this interface is investigated using the powerful method of neutron reflection. Experimental approaches to overcome the challenges of surface roughness, cleanliness and mineral dissolution have been developed. Based on this protocol, the interfaces of calcite with the liquids water, toluene and heptane have been characterised successfully. Hence this study allows the technique of neutron reflection to be expanded to the investigation of mineral surfaces.

The calcite-liquid interface is of great importance in many industrial and academic situations. In this paper, this interface is investigated using the powerful method of neutron reflection. Experimental approaches to overcome the challenges of surface roughness, cleanliness and mineral dissolution have been developed. Based on this protocol, the interfaces of calcite with the liquids water, toluene and heptane have been characterised successfully. Hence this study allows the technique of neutron reflection to be expanded to the investigation of mineral surfaces.

QC 20211019

Government, medical, financial, and web-based services increasingly depend on the ability to rapidly sift through huge, evolving data sets. These data-intensive applications perform complex multi-step computations over successive generations of data inflows (e.g., weekly web crawls, nightly telescope dumps, or hourly surveillance videos). Because of the data volumes involved, applications must avoid reprocessing old data when new data arrives and instead process incrementally. Unlike in stream-based systems, incoming data does not have to be processed immediately, permitting work to be amortized via bulk processing. Such bulk-incremental processing represents an emerging class of applications whose needs are not fully met by current systems. This paper presents a generalized architecture for bulk-incremental processing systems (BIPS), simplifying the creation of such programs. In contrast with incremental view maintenance in data warehousing, BIPS provides flexible low-level primitives for managing incremental data and processing, upon which both relational and non-relational operations can be implemented. The paper describes the BIPS programming model along with several example applications and examines some key implementation choices. These choices are shown to play a major role in overall system performance, via experiments on a large testbed cluster.Pre-2018 CSE ID: CS2009-0944

Government, medical, financial, and web-based services increasingly depend on the ability to rapidly sift through huge, evolving data sets. These data-intensive applications perform complex multi-step computations over successive generations of data inflows (e.g., weekly web crawls, nightly telescope dumps, or hourly surveillance videos). Because of the data volumes involved, applications must avoid reprocessing old data when new data arrives and instead process incrementally. Unlike in stream-based systems, incoming data does not have to be processed immediately, permitting work to be amortized via bulk processing. Such bulk-incremental processing represents an emerging class of applications whose needs are not fully met by current systems. This paper presents a generalized architecture for bulk-incremental processing systems (BIPS), simplifying the creation of such programs. In contrast with incremental view maintenance in data warehousing, BIPS provides flexible low-level primitives for managing incremental data and processing, upon which both relational and non-relational operations can be implemented. The paper describes the BIPS programming model along with several example applications and examines some key implementation choices. These choices are shown to play a major role in overall system performance, via experiments on a large testbed cluster.Pre-2018 CSE ID: CS2009-0951

Rationale: Advances in the management of cystic fibrosis have led to a significant improvement in survival, although marked differences between individuals are still observed. The value of patient-reported health-related quality of life scores in predicting survival in adults with cystic fibrosis is unknown. Objectives: To evaluate whether patient-reported health-related quality of life could predict survival in cystic fibrosis. Methods: From 1996 to 1997 a consecutive series of 223 patients were recruited to evaluate the Cystic Fibrosis Quality of Life Questionnaire. Demographic (age, sex), clinical (FEV1% predicted, body mass index, diabetes, B. Cepacia complex, intravenous access device, nutritional and lung transplant status) and health-related quality of life variables were recorded (Cystic Fibrosis Quality of Life Questionnaire and the SF-36). These data were used as baseline measures to explore the prognostic association of health-related quality of life and subsequent survival. Measurements and Main Results: At the census date (December 31, 2006) 154 (69.1%) adults were alive, 66 (29.6%) had died, and three (1.3%) were lost to follow-up. Cox proportional hazards models and bootstrapping procedures examined if health-related quality of life domains predicted survival after adjusting for the demographic and clinical factors. The physical functioning domain of the Cystic Fibrosis Quality of Life Questionnaire and the pain domain of the Short Form-36 had the strongest statistical associations with survival. Conclusions: Aspects of patient-reported quality of life serve as prognostic measures of survival beyond a number of previously known factors in cystic fibrosis. This needs to be investigated further in a larger longitudinal study.

The imaging properties of a uniaxial anisotropic slab lens, where the dielectric tensor components are of opposite sign, are studied as a function of the structure parameters. While hypothetical parameters yield various levels of performance, a design principle to achieve good sub-wavelength resolution is suggested. The anisotropy can be implemented with a metal-insulator stack. The influence of material and thickness on the subwavelength imaging performance of a negative dielectric constant slab is studied. Resonance in the plane wave transfer function produces a high spatial frequency ripple that could be useful in fabricating periodic structures. A cost function based on the plane wave transfer function provides a useful metric to evaluate the planar slab lens performance, and using this, the optimal slab dielectric constant can be determined. Prospects for a lossless negative dielectric constant material for optical devices are studied. Simulations show that with sufficient gain, a mixture of two semiconductor quantum dots can produce an isotropic effective dielectric constant that is lossless and negative. Over length scales where homogenization is meaningful, this permits a small-scale optical mode volume and lossless waveguides, major goals in the field of nanophotonics.

We suggest, based on the principle of causality and for a material exhibiting adjacent absorptive and gain resonances, that there can be an intervening frequency where perfect imaging is in theory possible. At this frequency, both the dielectric constant and the permeability are negative, leading to a negative refractive index, and there is no loss. In such a material exhibiting a double resonance, the gain must be at the higher frequency. Through appropriate tuning of the refractive index, all propagating and evanescent fields from the object could then in principle be reconstructed at the image plane, subject to practical implementation limits., QC 20100525Correction in DOI:10.1364/OL.35.001190 ISI:000276861100025

The theory of irregular diffractive optical elements is being developed by means of optimization software that allows wavelength-scale geometries to be synthesized. Structures are being designed for mode conversion and filtering demonstrations using the developed software. Example structures will be fabricated using silicon%based materials an hen tested using near-field optical microscopy. This work will lay the foundation for applications such as VCSEL mod control and compact wavelength division multiplexing elements., The original document contains color images.

Purpose: How individuals cope with aspects of cystic fibrosis (CF) has the potential to influence their self management and the course of their disease. To evaluate how individuals cope with CF, a disease specific coping scale was developed and validated. A second objective of the work was to examine the relationship between coping styles and treatment adherence. Methods: The development of the coping scale constituted a longitudinal design. A cross-sectional questionnaire design was used to examine the coping-adherence relationship. The development and validation of the coping scale comprised three phases: (1) Initially, 60 patients were interviewed to identify CF concerns. From this information a list of 23 concerns were recorded; (2) Eighty-three patients were interviewed to identify CF coping responses. For each concern, they were asked what they did or thought to ease the worry. A list of 24 coping strategies were recorded that formed a comprehensive set of items as to how people with CF act, feel and think about aspects of their disease; and (3) Further development and testing of the questionnaire involved 174 patients completing the measure. Four distinct ways of coping with CF were identified by factor analysis. These were termed optimistic acceptance, hopefulness, distraction and avoidance. The cronbach alpha coefficients were 0.74 (optimistic acceptance), 0.69 (hopefulness), 0.71 (distraction) and 0.76 (avoidance). To evaluate the relationship between coping and treatment adherence 60 patients completed the CF Coping Questionnaire and the Manchester Adult Cystic Fibrosis Compliance Questionnaire. Results: Compared with patients who were non-adherent, those who were adherent scored higher on the optimistic acceptance scale (physiotherapy p < 0.05, enzymes p < 0.003, vitamins p < 0.05) and hopefulness scale (physiotherapy p < 0.002, enzymes p < 0.001). Those who were partially adherent reported using distraction as a way of coping to a greater extent than ad

Purpose : Quality of Life (QoL) is an important outcome measure in health care and pharmacological trials. The trend towards multinational clinical trials may be problematic because it is unclear as to whether, or to what extent, QoL measures are comparable across cultures. This study compared QoL between English and German adolescents with Cystic Fibrosis (CF) and their healthy peers. Method : The study comprised a cross-sectional design. The English subjects formed two groups; 58 adolescents with CF and 49 healthy controls. The German subjects consisted of 26 adolescents with CF and 75 healthy controls. Quality of life was measured using the English and German versions of the SF-36. Demographic (age and gender) and clinical data (FEV 1 % predicted and BMI) were also recorded. Results : The English and German CF groups had similar age-adjusted lung function and body mass index. Both the English CF and control groups reported a poorer quality of life than their respective German counterparts across several domains of the SF-36. These were limitations in activities due to physical health problems and emotional difficulties, social functioning, energy and vitality and pain. Conclusions : The differences in quality of life between English and German adolescents with CF appear to be either culturally determined or due to idiosyncrasies in the translations of the SF-36, rather than a consequence of their disease or its management.

Purpose: How individuals cope with aspects of cystic fibrosis (CF) has the potential to influence their self management and the course of their disease. To evaluate how individuals cope with CF, a disease specific coping scale was developed and validated. A second objective of the work was to examine the relationship between coping styles and treatment adherence. Methods: The development of the coping scale constituted a longitudinal design. A cross-sectional questionnaire design was used to examine the coping-adherence relationship. The development and validation of the coping scale comprised three phases: (1) Initially, 60 patients were interviewed to identify CF concerns. From this information a list of 23 concerns were recorded; (2) Eighty-three patients were interviewed to identify CF coping responses. For each concern, they were asked what they did or thought to ease the worry. A list of 24 coping strategies were recorded that formed a comprehensive set of items as to how people with CF act, feel and think about aspects of their disease; and (3) Further development and testing of the questionnaire involved 174 patients completing the measure. Four distinct ways of coping with CF were identified by factor analysis. These were termed optimistic acceptance, hopefulness, distraction and avoidance. The cronbach alpha coefficients were 0.74 (optimistic acceptance), 0.69 (hopefulness), 0.71 (distraction) and 0.76 (avoidance). To evaluate the relationship between coping and treatment adherence 60 patients completed the CF Coping Questionnaire and the Manchester Adult Cystic Fibrosis Compliance Questionnaire. Results: Compared with patients who were non-adherent, those who were adherent scored higher on the optimistic acceptance scale (physiotherapy p < 0.05, enzymes p < 0.003, vitamins p < 0.05) and hopefulness scale (physiotherapy p < 0.002, enzymes p < 0.001). Those who were partially adherent reported using distraction as a way of coping to a greater extent than ad

Purpose : Quality of Life (QoL) is an important outcome measure in health care and pharmacological trials. The trend towards multinational clinical trials may be problematic because it is unclear as to whether, or to what extent, QoL measures are comparable across cultures. This study compared QoL between English and German adolescents with Cystic Fibrosis (CF) and their healthy peers. Method : The study comprised a cross-sectional design. The English subjects formed two groups; 58 adolescents with CF and 49 healthy controls. The German subjects consisted of 26 adolescents with CF and 75 healthy controls. Quality of life was measured using the English and German versions of the SF-36. Demographic (age and gender) and clinical data (FEV 1 % predicted and BMI) were also recorded. Results : The English and German CF groups had similar age-adjusted lung function and body mass index. Both the English CF and control groups reported a poorer quality of life than their respective German counterparts across several domains of the SF-36. These were limitations in activities due to physical health problems and emotional difficulties, social functioning, energy and vitality and pain. Conclusions : The differences in quality of life between English and German adolescents with CF appear to be either culturally determined or due to idiosyncrasies in the translations of the SF-36, rather than a consequence of their disease or its management.

Purpose: How individuals cope with aspects of cystic fibrosis (CF) has the potential to influence their self management and the course of their disease. To evaluate how individuals cope with CF, a disease specific coping scale was developed and validated. A second objective of the work was to examine the relationship between coping styles and treatment adherence. Methods: The development of the coping scale constituted a longitudinal design. A cross-sectional questionnaire design was used to examine the coping-adherence relationship. The development and validation of the coping scale comprised three phases: (1) Initially, 60 patients were interviewed to identify CF concerns. From this information a list of 23 concerns were recorded; (2) Eighty-three patients were interviewed to identify CF coping responses. For each concern, they were asked what they did or thought to ease the worry. A list of 24 coping strategies were recorded that formed a comprehensive set of items as to how people with CF act, feel and think about aspects of their disease; and (3) Further development and testing of the questionnaire involved 174 patients completing the measure. Four distinct ways of coping with CF were identified by factor analysis. These were termed optimistic acceptance, hopefulness, distraction and avoidance. The cronbach alpha coefficients were 0.74 (optimistic acceptance), 0.69 (hopefulness), 0.71 (distraction) and 0.76 (avoidance). To evaluate the relationship between coping and treatment adherence 60 patients completed the CF Coping Questionnaire and the Manchester Adult Cystic Fibrosis Compliance Questionnaire. Results: Compared with patients who were non-adherent, those who were adherent scored higher on the optimistic acceptance scale (physiotherapy p < 0.05, enzymes p < 0.003, vitamins p < 0.05) and hopefulness scale (physiotherapy p < 0.002, enzymes p < 0.001). Those who were partially adherent reported using distraction as a way of coping to a greater extent than ad

Purpose : Quality of Life (QoL) is an important outcome measure in health care and pharmacological trials. The trend towards multinational clinical trials may be problematic because it is unclear as to whether, or to what extent, QoL measures are comparable across cultures. This study compared QoL between English and German adolescents with Cystic Fibrosis (CF) and their healthy peers. Method : The study comprised a cross-sectional design. The English subjects formed two groups; 58 adolescents with CF and 49 healthy controls. The German subjects consisted of 26 adolescents with CF and 75 healthy controls. Quality of life was measured using the English and German versions of the SF-36. Demographic (age and gender) and clinical data (FEV 1 % predicted and BMI) were also recorded. Results : The English and German CF groups had similar age-adjusted lung function and body mass index. Both the English CF and control groups reported a poorer quality of life than their respective German counterparts across several domains of the SF-36. These were limitations in activities due to physical health problems and emotional difficulties, social functioning, energy and vitality and pain. Conclusions : The differences in quality of life between English and German adolescents with CF appear to be either culturally determined or due to idiosyncrasies in the translations of the SF-36, rather than a consequence of their disease or its management.

Purpose: How individuals cope with aspects of cystic fibrosis (CF) has the potential to influence their self management and the course of their disease. To evaluate how individuals cope with CF, a disease specific coping scale was developed and validated. A second objective of the work was to examine the relationship between coping styles and treatment adherence. Methods: The development of the coping scale constituted a longitudinal design. A cross-sectional questionnaire design was used to examine the coping-adherence relationship. The development and validation of the coping scale comprised three phases: (1) Initially, 60 patients were interviewed to identify CF concerns. From this information a list of 23 concerns were recorded; (2) Eighty-three patients were interviewed to identify CF coping responses. For each concern, they were asked what they did or thought to ease the worry. A list of 24 coping strategies were recorded that formed a comprehensive set of items as to how people with CF act, feel and think about aspects of their disease; and (3) Further development and testing of the questionnaire involved 174 patients completing the measure. Four distinct ways of coping with CF were identified by factor analysis. These were termed optimistic acceptance, hopefulness, distraction and avoidance. The cronbach alpha coefficients were 0.74 (optimistic acceptance), 0.69 (hopefulness), 0.71 (distraction) and 0.76 (avoidance). To evaluate the relationship between coping and treatment adherence 60 patients completed the CF Coping Questionnaire and the Manchester Adult Cystic Fibrosis Compliance Questionnaire. Results: Compared with patients who were non-adherent, those who were adherent scored higher on the optimistic acceptance scale (physiotherapy p < 0.05, enzymes p < 0.003, vitamins p < 0.05) and hopefulness scale (physiotherapy p < 0.002, enzymes p < 0.001). Those who were partially adherent reported using distraction as a way of coping to a greater extent than ad

Purpose : Quality of Life (QoL) is an important outcome measure in health care and pharmacological trials. The trend towards multinational clinical trials may be problematic because it is unclear as to whether, or to what extent, QoL measures are comparable across cultures. This study compared QoL between English and German adolescents with Cystic Fibrosis (CF) and their healthy peers. Method : The study comprised a cross-sectional design. The English subjects formed two groups; 58 adolescents with CF and 49 healthy controls. The German subjects consisted of 26 adolescents with CF and 75 healthy controls. Quality of life was measured using the English and German versions of the SF-36. Demographic (age and gender) and clinical data (FEV 1 % predicted and BMI) were also recorded. Results : The English and German CF groups had similar age-adjusted lung function and body mass index. Both the English CF and control groups reported a poorer quality of life than their respective German counterparts across several domains of the SF-36. These were limitations in activities due to physical health problems and emotional difficulties, social functioning, energy and vitality and pain. Conclusions : The differences in quality of life between English and German adolescents with CF appear to be either culturally determined or due to idiosyncrasies in the translations of the SF-36, rather than a consequence of their disease or its management.

Although the functionality of the lens water channels aquaporin 1 (AQP1; epithelium) and AQP0 (fiber cells) is well established, less is known about the role of AQP5 in the lens. Since in other tissues AQP5 functions as a regulated water channel with a water permeability (PH2O) some 20 times higher than AQP0, AQP5 could function to modulate PH2O in lens fiber cells. To test this possibility, a fluorescence dye dilution assay was used to calculate the relative PH2O of epithelial cells and fiber membrane vesicles isolated from either the mouse or rat lens, in the absence and presence of HgCl2, an inhibitor of AQP1 and AQP5. Immunolabeling of lens sections and fiber membrane vesicles from mouse and rat lenses revealed differences in the subcellular distributions of AQP5 in the outer cortex between species, with AQP5 being predominantly membranous in the mouse but predominantly cytoplasmic in the rat. In contrast, AQP0 labeling was always membranous in both species. This species-specific heterogeneity in AQP5 membrane localization was mirrored in measurements of PH2O, with only fiber membrane vesicles isolated from the mouse lens, exhibiting a significant Hg2+-sensitive contribution to PH2O. When rat lenses were first organ cultured, immunolabeling revealed an insertion of AQP5 into cortical fiber cells, and a significant increase in Hg2+-sensitive PH2O was detected in membrane vesicles. Our results show that AQP5 forms functional water channels in the rodent lens, and they suggest that dynamic membrane insertion of AQP5 may regulate water fluxes in the lens by modulating PH2O in the outer cortex.

We describe a rapid one-step method to biotinylate virtually any biological or non-biological surface. Contacting a solution of biotin-spacer-lipid constructs with a surface will form a coating within seconds on non-biological surfaces or within minutes on most biological membranes including membrane viruses. The resultant biotinylated surface can then be used to interact with avidinylated conjugates, beads, vesicles, surfaces or cells.

Silicon nanomembrane technologies (NPN, pnc-Si, and others) have been used commercially as electron microscopy (EM) substrates, and as filters with nanometer-resolution size cut-offs. Combined with EM, these materials provide a platform for catching or suspending nanoscale-size structures for analysis. Usefully, the nanomembrane itself can be manufactured to achieve a variety of nanopore topographies. The size, shapes, and surfaces of nanopores will influence transport, fouling, sieving, and electrical behavior. Electron tomography (ET) techniques used to recreate nanoscale-sized structures would provide an excellent way to capture this variation. Therefore, we modified a sample holder to accept our standardized 5.4 mm × 5.4 mm silicon nanomembrane chips and imaged NPN nanomembranes (50–100 nm thick, 10–100 nm nanopore diameters) using transmission electron microscopy (TEM). After imaging and ET reconstruction using a series of freely available tools (ImageJ, TomoJ, SEG3D2, Meshlab), we used COMSOL Multiphysics™ to simulate fluid flow inside a reconstructed nanopore. The results show flow profiles with significantly more complexity than a simple cylindrical model would predict, with regions of stagnation inside the nanopores. We expect that such tomographic reconstructions of ultrathin nanopores will be valuable in elucidating the physics that underlie the many applications of silicon nanomembranes.

This paper describes theoretical and experimental study of the fundamentals of using surface plasmon resonance (SPR) for label-free detection of voltage. Plasmonic voltage sensing relies on the capacitive properties of metal-electrolyte interface that are governed by electrostatic interactions between charge carriers in both phases. Externally-applied voltage leads to changes in the free electron density in the surface of the metal, shifting the SPR position. The study shows the effects of the applied voltage on the shape of the SPR curve. It also provides a comparison between the theoretical and experimental response to the applied voltage. The response is presented in a universal term that can be used to assess the voltage sensitivity of different SPR instruments. Finally, it demonstrates the capacity of the SPR system in resolving dynamic voltage signals; a detection limit of 10mV with a temporal resolution of 5ms is achievable. These findings pave the way for the use of SPR systems in the detection of electrical activity of biological cells.

Mechanical characterisation and imaging of biological tissue has piqued interest in the applicability to cell and tissue biology. One method, based on detection of Brillouin oscillations, has already lead to demonstrations on biological cells using ultrasound in the GHz range. In this paper we present a technique to extend this picosecond laser ultrasound technique from point measurements and line scans into high resolution acoustic imaging. Our technique uses a three layered metal-dielectric-metal film under the cell as a transducer for the generation of ultrasound. The design of this transducer and measuring system is optimised to address a limiting SNR factor related to the cell fragility; its sensitivity to laser light. Our approach shields the cell from laser radiation while having acoustic generation, optical detection and aiding heat dissipation. For that, Brillouin detection is performed in transmission rather than reflection. The conditions necessary to perform successfully this kind of detection are discussed and experimental results on phantom, fixed and living cells are presented.

Mechanical imaging and characterisation of biological cells has been a subject of interest for the last twenty years. Ultrasonic imaging based on the scanning acoustic microscope (SAM) and mechanical probing have been extensively reported. Large acoustic attenuation at high frequencies and the use of conventional piezo-electric transducers limit the operational frequency of a SAM. This limitation results in lower resolution compared to an optical microscope. Direct mechanical probing in the form of applied stress by contacting probes causes stress to cells and exhibits poor depth resolution. More recently, laser ultrasound has been reported to detect ultrasound in the GHz range via Brillouin oscillations on biological cells. This technique offers a promising new high resolution acoustic cell imaging technique. In this work, we propose, design and apply a thin-film based opto-acoustic transducer for the detection in transmission of Brillouin oscillations on cells. The transducer is used to generate acoustic waves, protect the cells from laser radiation and enhance signal-to-noise ratio (SNR). Experimental traces are presented in water films as well as images of the Brillouin frequency of phantom and fixed 3T3 fibroblast cells.

Surface plasmon resonance is used for the sensitive measurement of minute concentrations of bio-analytes and probing of electrochemical processes. Typical refractive index sensitivity, for the intensity approach, is around 10−6 refractive index units (RIUs). A better sensitivity has been suggested by developing a differential-intensity detection method. This method relies on the excitation of surface plasmons using a weakly focused beam with the average angle of incidence equal to the resonance angle, while the reflected light is detected using a bi-cell photodiode. The Bi-cell signal is processed by calculating the difference between its two units, normalized to their sum. This ratio estimates the shift in the resonance angle using a model that represents the resonance curve with a quadratic function. However, this model does not explain the effects of parameters such as the angular width of the excitation beam and the specifications of the sensing structure on the system’s response. This paper presents a detailed evaluation of the responsivity using experimental and theoretical approaches, which can predict the effect of the different parameters, paving the way towards the investigation of a better sensitivity and the optimization of the system’s design for different applications.

Phase contrast microscopy allows the study of highly transparent yet detail-rich specimens by producing intensity contrast from phase objects within the sample. Presented here is a generalized phase contrast illumination schema in which condenser optics are entirely abrogated, yielding a condenser- free yet highly effective method of obtaining phase contrast in transmitted-light microscopy. A ring of light emitting diodes (LEDs) is positioned within the light-path such that observation of the objective back focal plane places the il- luminating ring in appropriate conjunction with the phase ring. It is demonstrated that true Zernike phase contrast is obtained, whose geometry can be flexibly manipulated to provide an arbitrary working distance between illuminator and sample. Condenser-free phase contrast is demonstrated across a range of magnifications (4–100×), numerical apertures (0.13–1.65NA) and conventional phase positions. Also demonstrated is condenser-free darkfield microscopy as well as combinatorial contrast including Rheinberg illumination and simultaneous, colour-contrasted, brightfield, darkfield and Zernike phase contrast. By providing enhanced and arbitrary working space above the preparation, a range of concurrent imaging and electrophysiological techniques will be technically facilitated. Condenser-free phase contrast is demonstrated in conjunction with scanning ion conductance microscopy (SICM), using a notched ring to admit the scanned probe. The compact, versatile LED illumination schema will further lend itself to novel next-generation transmitted-light microscopy designs. The condenser-free illumination method, using rings of independent or radially-scanned emitters, may be exploited in future in other electromagnetic wavebands, including X-rays or the infrared.

In order to work at higher ultrasonic frequencies, for instance, to increase the resolution, it is necessary to fabricate smaller and higher frequency transducers. This paper presents an ultrasonic transducer capable of being made at a very small size and operated at GHz frequencies. The transducers are activated and read optically using pulsed lasers and without physical contact between the instrumentation and the transducer. This removes some of the practical impediments of traditional piezoelectric architectures (such as wiring) and allows the devices to be placed immediately on or within samples, reducing the significant effect of attenuation which is very strong at frequencies above 1 GHz. The transducers presented in this paper exploit simultaneous optical and mechanical resonances to couple the optical input into ultrasonic waves and vice versa. This paper discusses the mechanical and optical design of the devices at a modest scale (a few lm) and explores the scaling of the transducers toward the sub-micron scale. Results are presented that show how the transducers response changes depending on its local environment and how the resonant frequency shifts when the transducer is loaded by a printed protein sample.

We describe a rapid one-step method to biotinylate virtually any biological or non-biological surface. Contacting a solution of biotin-spacer-lipid constructs with a surface will form a coating within seconds on non-biological surfaces or within minutes on most biological membranes including membrane viruses. The resultant biotinylated surface can then be used to interact with avidinylated conjugates, beads, vesicles, surfaces or cells.

Silicon nanomembrane technologies (NPN, pnc-Si, and others) have been used commercially as electron microscopy (EM) substrates, and as filters with nanometer-resolution size cut-offs. Combined with EM, these materials provide a platform for catching or suspending nanoscale-size structures for analysis. Usefully, the nanomembrane itself can be manufactured to achieve a variety of nanopore topographies. The size, shapes, and surfaces of nanopores will influence transport, fouling, sieving, and electrical behavior. Electron tomography (ET) techniques used to recreate nanoscale-sized structures would provide an excellent way to capture this variation. Therefore, we modified a sample holder to accept our standardized 5.4 mm × 5.4 mm silicon nanomembrane chips and imaged NPN nanomembranes (50–100 nm thick, 10–100 nm nanopore diameters) using transmission electron microscopy (TEM). After imaging and ET reconstruction using a series of freely available tools (ImageJ, TomoJ, SEG3D2, Meshlab), we used COMSOL Multiphysics™ to simulate fluid flow inside a reconstructed nanopore. The results show flow profiles with significantly more complexity than a simple cylindrical model would predict, with regions of stagnation inside the nanopores. We expect that such tomographic reconstructions of ultrathin nanopores will be valuable in elucidating the physics that underlie the many applications of silicon nanomembranes.

Although the functionality of the lens water channels aquaporin 1 (AQP1; epithelium) and AQP0 (fiber cells) is well established, less is known about the role of AQP5 in the lens. Since in other tissues AQP5 functions as a regulated water channel with a water permeability (PH2O) some 20 times higher than AQP0, AQP5 could function to modulate PH2O in lens fiber cells. To test this possibility, a fluorescence dye dilution assay was used to calculate the relative PH2O of epithelial cells and fiber membrane vesicles isolated from either the mouse or rat lens, in the absence and presence of HgCl2, an inhibitor of AQP1 and AQP5. Immunolabeling of lens sections and fiber membrane vesicles from mouse and rat lenses revealed differences in the subcellular distributions of AQP5 in the outer cortex between species, with AQP5 being predominantly membranous in the mouse but predominantly cytoplasmic in the rat. In contrast, AQP0 labeling was always membranous in both species. This species-specific heterogeneity in AQP5 membrane localization was mirrored in measurements of PH2O, with only fiber membrane vesicles isolated from the mouse lens, exhibiting a significant Hg2+-sensitive contribution to PH2O. When rat lenses were first organ cultured, immunolabeling revealed an insertion of AQP5 into cortical fiber cells, and a significant increase in Hg2+-sensitive PH2O was detected in membrane vesicles. Our results show that AQP5 forms functional water channels in the rodent lens, and they suggest that dynamic membrane insertion of AQP5 may regulate water fluxes in the lens by modulating PH2O in the outer cortex.

This paper describes theoretical and experimental study of the fundamentals of using surface plasmon resonance (SPR) for label-free detection of voltage. Plasmonic voltage sensing relies on the capacitive properties of metal-electrolyte interface that are governed by electrostatic interactions between charge carriers in both phases. Externally-applied voltage leads to changes in the free electron density in the surface of the metal, shifting the SPR position. The study shows the effects of the applied voltage on the shape of the SPR curve. It also provides a comparison between the theoretical and experimental response to the applied voltage. The response is presented in a universal term that can be used to assess the voltage sensitivity of different SPR instruments. Finally, it demonstrates the capacity of the SPR system in resolving dynamic voltage signals; a detection limit of 10mV with a temporal resolution of 5ms is achievable. These findings pave the way for the use of SPR systems in the detection of electrical activity of biological cells.

Mechanical characterisation and imaging of biological tissue has piqued interest in the applicability to cell and tissue biology. One method, based on detection of Brillouin oscillations, has already lead to demonstrations on biological cells using ultrasound in the GHz range. In this paper we present a technique to extend this picosecond laser ultrasound technique from point measurements and line scans into high resolution acoustic imaging. Our technique uses a three layered metal-dielectric-metal film under the cell as a transducer for the generation of ultrasound. The design of this transducer and measuring system is optimised to address a limiting SNR factor related to the cell fragility; its sensitivity to laser light. Our approach shields the cell from laser radiation while having acoustic generation, optical detection and aiding heat dissipation. For that, Brillouin detection is performed in transmission rather than reflection. The conditions necessary to perform successfully this kind of detection are discussed and experimental results on phantom, fixed and living cells are presented.

Mechanical imaging and characterisation of biological cells has been a subject of interest for the last twenty years. Ultrasonic imaging based on the scanning acoustic microscope (SAM) and mechanical probing have been extensively reported. Large acoustic attenuation at high frequencies and the use of conventional piezo-electric transducers limit the operational frequency of a SAM. This limitation results in lower resolution compared to an optical microscope. Direct mechanical probing in the form of applied stress by contacting probes causes stress to cells and exhibits poor depth resolution. More recently, laser ultrasound has been reported to detect ultrasound in the GHz range via Brillouin oscillations on biological cells. This technique offers a promising new high resolution acoustic cell imaging technique. In this work, we propose, design and apply a thin-film based opto-acoustic transducer for the detection in transmission of Brillouin oscillations on cells. The transducer is used to generate acoustic waves, protect the cells from laser radiation and enhance signal-to-noise ratio (SNR). Experimental traces are presented in water films as well as images of the Brillouin frequency of phantom and fixed 3T3 fibroblast cells.

Surface plasmon resonance is used for the sensitive measurement of minute concentrations of bio-analytes and probing of electrochemical processes. Typical refractive index sensitivity, for the intensity approach, is around 10−6 refractive index units (RIUs). A better sensitivity has been suggested by developing a differential-intensity detection method. This method relies on the excitation of surface plasmons using a weakly focused beam with the average angle of incidence equal to the resonance angle, while the reflected light is detected using a bi-cell photodiode. The Bi-cell signal is processed by calculating the difference between its two units, normalized to their sum. This ratio estimates the shift in the resonance angle using a model that represents the resonance curve with a quadratic function. However, this model does not explain the effects of parameters such as the angular width of the excitation beam and the specifications of the sensing structure on the system’s response. This paper presents a detailed evaluation of the responsivity using experimental and theoretical approaches, which can predict the effect of the different parameters, paving the way towards the investigation of a better sensitivity and the optimization of the system’s design for different applications.

Phase contrast microscopy allows the study of highly transparent yet detail-rich specimens by producing intensity contrast from phase objects within the sample. Presented here is a generalized phase contrast illumination schema in which condenser optics are entirely abrogated, yielding a condenser- free yet highly effective method of obtaining phase contrast in transmitted-light microscopy. A ring of light emitting diodes (LEDs) is positioned within the light-path such that observation of the objective back focal plane places the il- luminating ring in appropriate conjunction with the phase ring. It is demonstrated that true Zernike phase contrast is obtained, whose geometry can be flexibly manipulated to provide an arbitrary working distance between illuminator and sample. Condenser-free phase contrast is demonstrated across a range of magnifications (4–100×), numerical apertures (0.13–1.65NA) and conventional phase positions. Also demonstrated is condenser-free darkfield microscopy as well as combinatorial contrast including Rheinberg illumination and simultaneous, colour-contrasted, brightfield, darkfield and Zernike phase contrast. By providing enhanced and arbitrary working space above the preparation, a range of concurrent imaging and electrophysiological techniques will be technically facilitated. Condenser-free phase contrast is demonstrated in conjunction with scanning ion conductance microscopy (SICM), using a notched ring to admit the scanned probe. The compact, versatile LED illumination schema will further lend itself to novel next-generation transmitted-light microscopy designs. The condenser-free illumination method, using rings of independent or radially-scanned emitters, may be exploited in future in other electromagnetic wavebands, including X-rays or the infrared.

In order to work at higher ultrasonic frequencies, for instance, to increase the resolution, it is necessary to fabricate smaller and higher frequency transducers. This paper presents an ultrasonic transducer capable of being made at a very small size and operated at GHz frequencies. The transducers are activated and read optically using pulsed lasers and without physical contact between the instrumentation and the transducer. This removes some of the practical impediments of traditional piezoelectric architectures (such as wiring) and allows the devices to be placed immediately on or within samples, reducing the significant effect of attenuation which is very strong at frequencies above 1 GHz. The transducers presented in this paper exploit simultaneous optical and mechanical resonances to couple the optical input into ultrasonic waves and vice versa. This paper discusses the mechanical and optical design of the devices at a modest scale (a few lm) and explores the scaling of the transducers toward the sub-micron scale. Results are presented that show how the transducers response changes depending on its local environment and how the resonant frequency shifts when the transducer is loaded by a printed protein sample.

We describe a rapid one-step method to biotinylate virtually any biological or non-biological surface. Contacting a solution of biotin-spacer-lipid constructs with a surface will form a coating within seconds on non-biological surfaces or within minutes on most biological membranes including membrane viruses. The resultant biotinylated surface can then be used to interact with avidinylated conjugates, beads, vesicles, surfaces or cells.

Silicon nanomembrane technologies (NPN, pnc-Si, and others) have been used commercially as electron microscopy (EM) substrates, and as filters with nanometer-resolution size cut-offs. Combined with EM, these materials provide a platform for catching or suspending nanoscale-size structures for analysis. Usefully, the nanomembrane itself can be manufactured to achieve a variety of nanopore topographies. The size, shapes, and surfaces of nanopores will influence transport, fouling, sieving, and electrical behavior. Electron tomography (ET) techniques used to recreate nanoscale-sized structures would provide an excellent way to capture this variation. Therefore, we modified a sample holder to accept our standardized 5.4 mm × 5.4 mm silicon nanomembrane chips and imaged NPN nanomembranes (50–100 nm thick, 10–100 nm nanopore diameters) using transmission electron microscopy (TEM). After imaging and ET reconstruction using a series of freely available tools (ImageJ, TomoJ, SEG3D2, Meshlab), we used COMSOL Multiphysics™ to simulate fluid flow inside a reconstructed nanopore. The results show flow profiles with significantly more complexity than a simple cylindrical model would predict, with regions of stagnation inside the nanopores. We expect that such tomographic reconstructions of ultrathin nanopores will be valuable in elucidating the physics that underlie the many applications of silicon nanomembranes.

Although the functionality of the lens water channels aquaporin 1 (AQP1; epithelium) and AQP0 (fiber cells) is well established, less is known about the role of AQP5 in the lens. Since in other tissues AQP5 functions as a regulated water channel with a water permeability (PH2O) some 20 times higher than AQP0, AQP5 could function to modulate PH2O in lens fiber cells. To test this possibility, a fluorescence dye dilution assay was used to calculate the relative PH2O of epithelial cells and fiber membrane vesicles isolated from either the mouse or rat lens, in the absence and presence of HgCl2, an inhibitor of AQP1 and AQP5. Immunolabeling of lens sections and fiber membrane vesicles from mouse and rat lenses revealed differences in the subcellular distributions of AQP5 in the outer cortex between species, with AQP5 being predominantly membranous in the mouse but predominantly cytoplasmic in the rat. In contrast, AQP0 labeling was always membranous in both species. This species-specific heterogeneity in AQP5 membrane localization was mirrored in measurements of PH2O, with only fiber membrane vesicles isolated from the mouse lens, exhibiting a significant Hg2+-sensitive contribution to PH2O. When rat lenses were first organ cultured, immunolabeling revealed an insertion of AQP5 into cortical fiber cells, and a significant increase in Hg2+-sensitive PH2O was detected in membrane vesicles. Our results show that AQP5 forms functional water channels in the rodent lens, and they suggest that dynamic membrane insertion of AQP5 may regulate water fluxes in the lens by modulating PH2O in the outer cortex.

This paper describes theoretical and experimental study of the fundamentals of using surface plasmon resonance (SPR) for label-free detection of voltage. Plasmonic voltage sensing relies on the capacitive properties of metal-electrolyte interface that are governed by electrostatic interactions between charge carriers in both phases. Externally-applied voltage leads to changes in the free electron density in the surface of the metal, shifting the SPR position. The study shows the effects of the applied voltage on the shape of the SPR curve. It also provides a comparison between the theoretical and experimental response to the applied voltage. The response is presented in a universal term that can be used to assess the voltage sensitivity of different SPR instruments. Finally, it demonstrates the capacity of the SPR system in resolving dynamic voltage signals; a detection limit of 10mV with a temporal resolution of 5ms is achievable. These findings pave the way for the use of SPR systems in the detection of electrical activity of biological cells.