Biallelic mutations in ) cause a primary immunodeficiency disorder.

CRAC channel regulator 2 A (CRACR2A) is a large Rab GTPase that is expressed abundantly in T cells and acts as a signal transmitter between T cell receptor stimulation and activation of the Ca-NFAT and JNK-AP1 pathways. CRACR2A has been linked to human diseases in numerous genome-wide association studies, however, to date no patient with damaging variants in CRACR2A has been identified. In this study, we describe a patient harboring biallelic variants in [paternal allele c.

B-cell capacity for differentiation changes with age.

Background: Age-related immune deficiencies are thought to be responsible for increased susceptibility to infection in older adults, with alterations in lymphocyte populations becoming more prevalent over time. The loss of humoral immunity in ageing was attributed to the diminished numbers of B cells and the reduced ability to generate immunoglobulin.

Aims: To compare the intrinsic B-cell capacity for differentiation into mature plasma cells (PCs), between young and old donors, using in vitro assays, providing either effective T-cell help or activation via TLR engagement.

Spatial and environmental effects on Coho Salmon life history trait variation.

Adult size, egg size, fecundity, and mass of gonads are affected by trade-offs between reproductive investment and environmental conditions shaping the evolution of life history traits among populations for widely distributed species. Coho salmon have a large geographic distribution, and different environmental conditions are experienced by populations throughout their range. We examined the effect of environmental variables on female size, egg size, fecundity, and reproductive investment of populations of Coho Salmon from across British Columbia using an information theoretic approach.

Assessment of spawning site fidelity in interior Fraser River Coho salmon Oncorhynchus kisutch using otolith microchemistry, in British Columbia, Canada.

Coho Salmon Oncorhynchus kisutch show fidelity to natal spawning watersheds. Fine-scale homing, however, within rivers is not well understood. Interior Fraser Coho (IFC) salmon eggs were incubated at known spawning locations in the Coldwater River, two main stem sites and one-off channel pond site, providing otolith reference data for comparison to otolith signatures for returning adults using laser ablation inductively coupled plasma mass spectrometry.

TLR-mediated activation of Waldenström macroglobulinemia B cells reveals an uncoupling from plasma cell differentiation.

Waldenström macroglobulinemia (WM) is a rare malignancy in which clonal B cells infiltrate the bone marrow and give rise to a smaller compartment of neoplastic plasma cells that secrete monoclonal immunoglobulin M paraprotein. Recent studies into underlying mutations in WM have enabled a much greater insight into the pathogenesis of this lymphoma. However, there is considerably less characterization of the way in which WM B cells differentiate and how they respond to immune stimuli.

Germline TET2 loss of function causes childhood immunodeficiency and lymphoma.

Molecular dissection of inborn errors of immunity can help to elucidate the nonredundant functions of individual genes. We studied 3 children with an immune dysregulation syndrome of susceptibility to infection, lymphadenopathy, hepatosplenomegaly, developmental delay, autoimmunity, and lymphoma of B-cell (n = 2) or T-cell (n = 1) origin. All 3 showed early autologous T-cell reconstitution following allogeneic hematopoietic stem cell transplantation.

Perpetual sedimentation for the continuous delivery of particulate suspensions.

Particle sedimentation is deleterious to a tremendous variety of microfluidic applications. Using an open instrumentation approach we show that syringe rotation retains particles in a suspended state, providing a universal solution for the continuous delivery of particulate samples to microfluidic processors.

Behavioural changes during the parr-smolt transformation in coho salmon Oncorhynchus kisutch: is it better to be cool?

Behavioural changes that occur during the parr-smolt transformation were investigated in juvenile coho salmon Oncorhynchus kisutch. Fish from two populations were examined from the Fraser River catchment in British Columbia, Canada; a short and a long-distance migrating population. Fish showed a significant decrease in condition factor and significant increase in gill Na K -ATPase activity during the spring indicating that they became competent smolts, but no difference between populations.

Tail walking in a bottlenose dolphin community: the rise and fall of an arbitrary cultural 'fad'.

Social learning of adaptive behaviour is widespread in animal populations, but the spread of arbitrary behaviours is less common. In this paper, we describe the rise and fall of a behaviour called tail walking, where a dolphin forces the majority of its body vertically out of the water and maintains the position by vigourously pumping its tail, in a community of Indo-Pacific bottlenose dolphins (). The behaviour was introduced into the wild following the rehabilitation of a wild female individual, Billie, who was temporarily co-housed with trained dolphins in a dolphinarium.

Temporal and spatial differences in smolting among Oncorhynchus nerka populations throughout fresh and seawater migration.

Physiological changes that occur in the spring are preparatory for salmonid smolts to successfully enter seawater, but variation is likely to exist within species with a wide geographic distribution. Whether differences in development of seawater tolerance exist among populations that differ in distance to the ocean, temporally during the spring, or as fish migrate downstream is not known. Juvenile sockeye salmon Oncorhynchus nerka from four regions in the Fraser River catchment, British Columbia, were intercepted to assess physiological differences among populations and at different times during migration to characterize the parr-smolt transformation.

Is the duration of the smolt window related to migration distance in coho salmon Oncorhynchus kisutch?

Physiological changes during the parr-smolt transformation were investigated in short distance (Chilliwack River) and long-distance (Salmon River) migrating coho salmon Oncorhynchus kisutch populations in British Columbia, Canada. Biochemical and molecular indicators were used to monitor smolt development for fish reared at 10 °C throughout the spring. Fish grew well and developed the physical appearance of competent smolts.

The effect of substrate rearing on growth, aerobic scope and physiology of larval white sturgeon Acipenser transmontanus.

The effect of substratum on growth and metabolic rate was assessed in larval white sturgeon Acipenser transmontanus. Yolk-sac larvae (YSL) were reared in bare tanks or tanks with gravel as substratum from hatch until approximately 16 days post hatch (dph). The effect of an artificial substratum was also evaluated on growth alone.

Studying the limits of production rate and yield for the volume manufacturing of hollow core photonic band gap fibers.

Hollow core photonic band gap fibers have great potential in low latency data transmission and power delivery applications, but they are currently only fabricated in research scale fabrication facilities, with km-scale lengths. To drive cost reduction and volume manufacturing it is essential to be able to upscale the preform size, but before embarking on costly experimental attempts it is useful to apply fluid dynamics models to study how the fiber drawing dynamics would be affected by such a change. In this work we use a fluid dynamics model to virtually draw increasingly longer lengths of the same fiber from preforms of identical length but different diameters.

MicroStructure Element Method (MSEM): viscous flow model for the virtual draw of microstructured optical fibers.

We propose a new method to accurately model the structural evolution of a microstructured fiber (MOF) during its drawing process, given its initial preform structure and draw conditions. The method, applicable to a broad range of MOFs with high air-filling fraction and thin glass membranes, is an extension of the Discrete Element Method; it determines forces on the nodes in the microstructure to progressively update their position along the neck-down region, until the fiber reaches a final frozen state. The model is validated through simulation of 6 Hollow Core Photonic Band Gap Fibers (HC-PBGFs) and is shown to predict accurately the final fiber dimensions and cross-sectional distortions.

Freshwater movement patterns by juvenile Pacific salmon Oncorhynchus spp. before they migrate to the ocean: Oh the places you'll go!

Juvenile movement patterns for coho salmon Oncorhynchus kisutch and Chinook salmon Oncorhynchus tshawytscha from two large interior rivers of British Columbia, Canada, were examined. Otoliths from post-spawned fishes were collected on spawning grounds and elemental signatures were determined through transects from sectioned otoliths using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). Large variations in otolith elemental signatures were found during the freshwater life stage indicative of movement downstream to rivers and tributaries that differed in elemental signature.

Whole cell quenched flow analysis.

This paper describes a microfluidic quenched flow platform for the investigation of ligand-mediated cell surface processes with unprecedented temporal resolution. A roll-slip behavior caused by cell-wall-fluid coupling was documented and acts to minimize the compression and shear stresses experienced by the cell. This feature enables high-velocity (100-400 mm/s) operation without impacting the integrity of the cell membrane.

Effect of expansion chamber geometry on atomization and spray dispersion characters of a flashing mixture containing inerts. Part II: High speed imaging measurements.

A breath activated, pressurized metered dose inhaler (pMDI) device (Oxette(®)) has been developed to replace the traditional cigarette. In this paper, internal and external spray characters are measured by high speed imaging along with sizing the residual droplets at the distance from the discharge orifice where the human oropharynx locates. Two different formulations with 95% and 98% mass fraction of HFA 134a and two prototype cigarette alternatives with different expansion chamber volumes have been analyzed.

Effect of expansion chamber geometry on atomization and spray dispersion characters of a flashing mixture containing inerts. Part I. Numerical predictions and dual laser measurements.

A cigarette alternative is designed to deliver a dose of medicinal nicotine within a timeframe comparable to that of a cigarette, and gives much of what smokers expect from a cigarette without the risks of smoking tobacco. The design concept is the same as a pressurized metered dose inhaler (pMDI), but is a breath actuated device (Oxette(®)). This work predicts the residual mass median diameter (MMD) of the spray issuing from early stage Oxette(®) prototypes by using an evaporation model of multi-component liquid droplets with the help of a numerical multi-component two-phase actuation model (developed by the authors) to quantify the sprays.

Physiological and molecular endocrine changes in maturing wild sockeye salmon, Oncorhynchus nerka, during ocean and river migration.

Maturing adult sockeye salmon Oncorhynchus nerka were intercepted while migrating in the ocean and upstream in freshwater over a combined distance of more than 1,300 km to determine physiological and endocrine changes associated with ionoregulation. Sockeye migrating through seawater and freshwater showed consistent declines in gill Na+/K+ -ATPase (NKA) activity, plasma osmolality and plasma chloride concentration. In contrast, plasma sodium concentration became elevated in seawater as fish approached the river mouth and was then restored after sockeye entered the river.

Genetic versus rearing-environment effects on phenotype: hatchery and natural rearing effects on hatchery- and wild-born coho salmon.

With the current trends in climate and fisheries, well-designed mitigative strategies for conserving fish stocks may become increasingly necessary. The poor post-release survival of hatchery-reared Pacific salmon indicates that salmon enhancement programs require assessment. The objective of this study was to determine the relative roles that genotype and rearing environment play in the phenotypic expression of young salmon, including their survival, growth, physiology, swimming endurance, predator avoidance and migratory behaviour.

Physiological condition differentially affects the behavior and survival of two populations of sockeye salmon during their freshwater spawning migration.

Recently, a segment of the Adams-Shuswap sockeye salmon (Oncorhynchus nerka) population initiated freshwater migration several weeks earlier than historically recorded, resulting in high mortality rates. The comigrating Chilko population maintained their historic river entry timing and did not experience elevated mortality. To test the hypothesis that population-specific differences in physiological condition would differentially influence behavior and survival when exposed to fisheries capture stress, we physiologically sampled individuals from both populations at the onset of the freshwater phase of their reproductive migration and tracked the remainder of their migrations using radio telemetry.

Effects of experimental manipulations of salinity and maturation status on the physiological condition and mortality of homing adult sockeye salmon held in a laboratory.

Relatively little is known about the physiological response and mortality consequences of the return of anadromous fish to freshwater (FW). We explored the consequences of the return to FW by collecting maturing sockeye salmon from the marine waters off the mouth of the Fraser River and holding approximately 50 sockeye in each of five treatments: saltwater (SW; salinity = 28 ppt), iso-osmotic water (ISO; 13 ppt), FW (0 ppt), SW + gonadotropin-releasing hormone (SW + GnRH), and FW + GnRH. Exogenous GnRH treatments were intended to accelerate maturation.

The effect of reduction of propellant mass fraction on the injection profile of metered dose inhalers.

In order to provide an improved understanding of the flow in pressurized-metered dose inhalers (pMDIs), especially monitoring the output temperature and mass flow rate to obtain maximum atomization efficiency from the available energy, a numerical model for a two phases, multi-component compressible flow in a pressurized-metered dose inhaler is presented and validated. It is suitable for testing with various formulations and different geometries for a range of pMDI devices. We validated the model against available data in the literature for a single component HFA 134a propellant, and then investigated the response of the model to other formulations containing non-volatile components.