High-resolution imaging of depth filter structures using X-ray computed tomography

A multiple length scale approach to the imaging and measurement of depth filters using X-ray computed tomography is described. Three different filter grades of varying nominal retention ratings were visualized in 3D and compared quantitatively based on porosity, pore size and tortuosity. Positional based analysis within the filters revealed greater voidage and average pore sizes in the upstream quartile before reducing progressively through the filter from the center to the downstream quartile, with these results visually supported by voidage distance maps in each case. Flow simulation to display tortuous paths that flow may take through internal voidage were examined. Digital reconstructions were capable of identifying individual constituents of voidage, cellulose and perlite inside each depth filter grade, with elemental analysis on upstream and downstream surfaces confirming perlite presence. Achieving an appropriate pixel size was of particular importance when optimizing imaging conditions for all grades examined. A 3 µm pixel size was capable of representing internal macropores of each filter structure; however, for the finest grade, an improvement to a 1 µm pixel size was required in order to resolve micropores and small perlite shards. Enhancing the pixel size resulted in average porosity measurements of 70% to 80% for all grades. Graphical abstract: [Figure not available: see fulltext.

Packed bed compression visualisation and flow simulation using an erosion-dilation approach

X-ray computed tomography has been demonstrated to be capable of imaging 1 mL (5 mm diameter, 50 mm height) chromatography packed beds under compression, visualising the 3D structure and measuring changes to geometry of the packing. 1 mL pre-packed columns did not exhibit any structural changes at vendor specified flow rate limits, however cellulose beds did compress at higher flow rates that were imaged before, during and after flow. This was used to visualise and quantitate changes to porosity, tortuosity and permeability based on simulation of flow through the packed bed structure using the imaging data. When using a high flow rate it was found that a decrease in porosity could be measured during compression before reverting after flow had ceased, with corresponding changes to tortuosity and permeability also occurring. X-ray CT imaging of packed beds and individual beads exposed to foulant-rich process streams resulted in considerable image quality loss, associated with residual biological material. In order to address this, digital processing using an erosion-dilation method was applied at bead and bed scales to computationally alter the porosity by adding or removing material from the existing surface to calculate the impact upon tortuosity factor. The eroded and dilated bead volumes of agarose, cellulose and ceramic materials were used to simulate diffusivity whilst mimicking internal bead pore constriction and blocking mechanisms

Loss of anion transport without increased sodium absorption characterizes newborn porcine cystic fibrosis airway epithelia

Defective transepithelial electrolyte transport is thought to initiate cystic fibrosis (CF) lung disease. Yet, how loss of CFTR affects electrolyte transport remains uncertain. CFTR -/- pigs spontaneously develop lung disease resembling human CF. At birth, their airways exhibit a bacterial host defense defect, but are not inflamed. Therefore, we studied ion transport in newborn nasal and tracheal/bronchial epithelia in tissues, cultures, and in vivo. CFTR -/- epithelia showed markedly reduced Cl - and HCO 3 - transport. However, in contrast to a widely held view, lack of CFTR did not increase transepithelial Na + or liquid absorption or reduce periciliary liquid depth. Like human CF, CFTR -/- pigs showed increased amiloride-sensitive voltage and current, but lack of apical Cl - conductance caused the change, not increased Na + transport. These results indicate that CFTR provides the predominant transcellular pathway for Cl - and HCO 3 - in porcine airway epithelia, and reduced anion permeability may initiate CF airway disease. © 2010 Elsevier Inc.published_or_final_versio

Evaluation of two high-throughput proteomic technologies for plasma biomarker discovery in immunotherapy-treated melanoma patients

Background: Selective kinase and immune checkpoint inhibitors, and their combinations, have significantly improved the survival of patients with advanced metastatic melanoma. Not all patients will respond to treatment however, and some patients will present with significant toxicities. Hence, the identification of biomarkers is critical for the selection and management of patients receiving treatment. Biomarker discovery often involves proteomic techniques that simultaneously profile multiple proteins but few studies have compared these platforms. Methods: In this study, we used the multiplex bead-based Eve Technologies Discovery assay and the aptamer-based SomaLogic SOMAscan assay to identify circulating proteins predictive of response to immunotherapy in melanoma patients treated with combination immune checkpoint inhibitors. Expression of four plasma proteins were further validated using the bead-based Millipore Milliplex assay. Results: Both the Discovery and the SOMAscan assays detected circulating plasma proteins in immunotherapy-treated melanoma patients. However, these widely used assays showed limited correlation in relative protein quantification, due to differences in specificity and the dynamic range of protein detection. Protein data derived from the Discovery and Milliplex bead-based assays were highly correlated. Conclusions: Our study highlights significant limitations imposed by inconsistent sensitivity and specificity due to differences in the detection antibodies or aptamers of these widespread biomarker discovery approaches. Our findings emphasize the need to improve these technologies for the accurate identification of biomarkers

Reverberation Mapping and the Physics of Active Galactic Nuclei

Reverberation-mapping campaigns have revolutionized our understanding of AGN. They have allowed the direct determination of the broad-line region size, enabled mapping of the gas distribution around the central black hole, and are starting to resolve the continuum source structure. This review describes the recent and successful campaigns of the International AGN Watch consortium, outlines the theoretical background of reverberation mapping and the calculation of transfer functions, and addresses the fundamental difficulties of such experiments. It shows that such large-scale experiments have resulted in a ``new BLR'' which is considerably different from the one we knew just ten years ago. We discuss in some detail the more important new results, including the luminosity-size-mass relationship for AGN, and suggest ways to proceed in the near future.Comment: Review article to appear in Astronomical Time Series, Proceedings of the Wise Observatory 25th Ann. Symposium. 24 pages including 7 figure

Three dimensional characterisation of chromatography bead internal structure using X-ray computed tomography and focused ion beam microscopy

X-ray computed tomography (CT) and focused ion beam (FIB) microscopy were used to generate three dimensional representations of chromatography beads for quantitative analysis of important physical characteristics including tortuosity factor. Critical-point dried agarose, cellulose and ceramic beads were examined using both methods before digital reconstruction and geometry based analysis for comparison between techniques and materials examined. X-ray ‘nano’ CT attained a pixel size of 63 nm and 32 nm for respective large field of view and high resolution modes. FIB improved upon this to a 15 nm pixel size for the more rigid ceramic beads but required compromises for the softer agarose and cellulose materials, especially during physical sectioning that was not required for X-ray CT. Digital processing of raw slices was performed using software to produce 3D representations of bead geometry. Porosity, tortuosity factor, surface area to volume ratio and pore diameter were evaluated for each technique and material, with overall averaged simulated tortuosity factors of 1.36, 1.37 and 1.51 for agarose, cellulose and ceramic volumes respectively. Results were compared to existing literature values acquired using established imaging and non-imaging techniques to demonstrate the capability of tomographic approaches used here

Regional Endothermy in a Coral Reef Fish?

Although a few pelagic species exhibit regional endothermy, most fish are regarded as ectotherms. However, we document significant regional endothermy in a benthic reef fish. Individual steephead parrotfish, Chlorurus microrhinos (Labridae, formerly Scaridae) were tagged and their internal temperatures were monitored for a 24 h period using active acoustic telemetry. At night, on the reef, C. microrhinos were found to maintain a consistent average peritoneal cavity temperature 0.16±0.005°C (SE) warmer than ambient. Diurnal internal temperatures were highly variable for individuals monitored on the reef, while in tank-based trials, peritoneal cavity temperatures tracked environmental temperatures. The mechanisms responsible for a departure of the peritoneal cavity temperature from environmental temperature occurred in C. microrhinos are not yet understood. However, the diet and behavior of the species suggests that heat in the peritoneal cavity may result primarily from endogenous thermogenesis coupled with physiological heat retention mechanisms. The presence of limited endothermy in C. microrhinos indicates that a degree of uncertainty may exist in the manner that reef fish respond to their thermal environment. At the very least, they do not always appear to respond to environmental temperatures as neutral thermal vessels and do display limited, but significant, visceral warming

Transit Timing and Duration Variations for the Discovery and Characterization of Exoplanets

Transiting exoplanets in multi-planet systems have non-Keplerian orbits which can cause the times and durations of transits to vary. The theory and observations of transit timing variations (TTV) and transit duration variations (TDV) are reviewed. Since the last review, the Kepler spacecraft has detected several hundred perturbed planets. In a few cases, these data have been used to discover additional planets, similar to the historical discovery of Neptune in our own Solar System. However, the more impactful aspect of TTV and TDV studies has been characterization of planetary systems in which multiple planets transit. After addressing the equations of motion and parameter scalings, the main dynamical mechanisms for TTV and TDV are described, with citations to the observational literature for real examples. We describe parameter constraints, particularly the origin of the mass/eccentricity degeneracy and how it is overcome by the high-frequency component of the signal. On the observational side, derivation of timing precision and introduction to the timing diagram are given. Science results are reviewed, with an emphasis on mass measurements of transiting sub-Neptunes and super-Earths, from which bulk compositions may be inferred.Comment: Revised version. Invited review submitted to 'Handbook of Exoplanets,' Exoplanet Discovery Methods section, Springer Reference Works, Juan Antonio Belmonte and Hans Deeg, Eds. TeX and figures may be found at https://github.com/ericagol/TTV_revie

Identification of Genetic and Epigenetic Variations in a Rat Model for Neurodevelopmental Disorders

A combination of genetic variations, epimutations and environmental factors may be involved in the etiology of complex neurodevelopmental disorders like schizophrenia. To study such disorders, we use apomorphine-unsusceptible (APO-UNSUS) Wistar rats and their phenotypic counterpart apomorphine-susceptible (APO-SUS) rats that display a complex phenotype remarkably similar to that of schizophrenic patients. As the molecular basis of the APO-SUS/UNSUS rat model, we recently identified a genomic rearrangement of the Aph-1b gene. Here, we discovered between the two rat lines differences other than the Aph-1b gene defect, including a remarkable cluster of genetic variations, two variants corresponding to topoisomerase II-based recombination hot spots and an epigenetic (DNA methylation) difference in cerebellum and (hypo)thalamic but not hippocampal genomic DNA. Furthermore, genetic variations were found to correlate with the degree of apomorphine susceptibility in unselected Wistar rats. Together, the results show that a number of genetic and epigenetic differences exist between the APO-SUS and -UNSUS rat genomes, raising the possibility that in addition to the Aph-1b gene defect the newly identified variations may also contribute to the complex APO-SUS phenotype

Subanesthetic ketamine treatment promotes abnormal interactions between neural subsystems and alters the properties of functional brain networks

Acute treatment with subanesthetic ketamine, a non-competitive N-methyl-D-aspartic acid (NMDA) receptor antagonist, is widely utilized as a translational model for schizophrenia. However, how acute NMDA receptor blockade impacts on brain functioning at a systems level, to elicit translationally relevant symptomatology and behavioral deficits, has not yet been determined. Here, for the first time, we apply established and recently validated topological measures from network science to brain imaging data gained from ketamine-treated mice to elucidate how acute NMDA receptor blockade impacts on the properties of functional brain networks. We show that the effects of acute ketamine treatment on the global properties of these networks are divergent from those widely reported in schizophrenia. Where acute NMDA receptor blockade promotes hyperconnectivity in functional brain networks, pronounced dysconnectivity is found in schizophrenia. We also show that acute ketamine treatment increases the connectivity and importance of prefrontal and thalamic brain regions in brain networks, a finding also divergent to alterations seen in schizophrenia. In addition, we characterize how ketamine impacts on bipartite functional interactions between neural subsystems. A key feature includes the enhancement of prefrontal cortex (PFC)-neuromodulatory subsystem connectivity in ketamine-treated animals, a finding consistent with the known effects of ketamine on PFC neurotransmitter levels. Overall, our data suggest that, at a systems level, acute ketamine-induced alterations in brain network connectivity do not parallel those seen in chronic schizophrenia. Hence, the mechanisms through which acute ketamine treatment induces translationally relevant symptomatology may differ from those in chronic schizophrenia. Future effort should therefore be dedicated to resolve the conflicting observations between this putative translational model and schizophrenia