Sickle Cell Disease Erythrocyte Stiffness and Cytoadhesion Investigated via Atomic Force Microscopy

The biomechanical properties of red blood cells (RBCs), including increased stiffness and abnormal cytoadherence, are integral components in the cascade of events resulting to vasoocclusive episodes (VOEs) in sickle cell disease (SCD). VOEs are the main cause of morbidity in SCD and sickle cell trait (SCT). Using experimental techniques based on atomic force microscopy (AFM), we studied the stiffness and adhesion of RBCs from SCD patients and from subjects with SCT. We found that SCD and SCT RBCs are three-fold stiffer than normal RBCs. Further, a ten-fold increase in the stiffness of sickled RBCs was measured upon deoxygenation. In an effort to rectify the increased stiffness of sickle RBCs, mice were fed a diet supplemented with docosahexanoic acid (DHA), an omega-3 fatty acid. A decrease in RBC stiffness was measured suggesting therapeutic benefits of DHA. Cytoadherence of RBCs to subendothelial laminin via the basal cell adhesion molecule/Lutheran (BCAM/Lu) is implicated in vasculopathy, a common condition in SCD patients. We established the in vitro technique of single-molecule force spectroscopy (SMFS) which enables detection of single BCAM/Lu proteins on the RBC surface via measurement of the unbinding force with laminin. It was shown that epinephrine, acting through the cyclic adenosine monophosphate (cAMP) signaling pathway, increases the population of active BCAM/Lu receptors on SCT RBCs, suggesting a role in exercise-induced VOEs. The sensitivity of the SMFS system was validated in a neuronal system to quantitatively map SK channels and then employed to investigate the effects of cAMP pathway targeting on BCAM/Lu receptor expression on normal and SCD RBCs. We illustrated that A-kinase anchoring proteins are crucial for BCAM/Lu receptor activation. To examine the relevance of results based on SMFS in the cytoadhesion of entire RBCs, single-cell force spectroscopy (SCFS) was established to measure the adhesion of whole cells with a functionalized substrate. We established a correspondence between the SMFS and SCFS results. Both techniques were able to detect significant changes in the adhesive response of RBCs to cAMP pathway modulation and variability was measured amongst human subjects, suggesting that RBCs maintain diverse intracellular levels of tonic protein kinase A

Wastewater treatment using artificial wetlands

In the study described in this paper, pilot scale vertical flow wetlands were evaluated as a potential wastewater treatment system for agricultural wastewater exiting from swine farm. The criteria used for evaluation were based on water quality requirements for irrigation

Euclid space mission: a cosmological challenge for the next 15 years

Euclid is the next ESA mission devoted to cosmology. It aims at observing most of the extragalactic sky, studying both gravitational lensing and clustering over $\sim$15,000 square degrees. The mission is expected to be launched in year 2020 and to last six years. The sheer amount of data of different kinds, the variety of (un)known systematic effects and the complexity of measures require efforts both in sophisticated simulations and techniques of data analysis. We review the mission main characteristics, some aspects of the the survey and highlight some of the areas of interest to this meetingComment: to appear in Proceedings IAU Symposium No. 306, 2014, "Statistical Challenges in 21st Century Cosmology", A.F. Heavens, J.-L. Starck & A. Krone-Martins, ed

NISP- CU PDR report

This document presents the NI-­CU PDR report. In particular, it gives: - the review group, the review process and schedule - the documents submitted to review - the review objectives and the success criteria - the list of RID's with their answers by the NI-­‐CU project team - the actions taken during the final meeting - the main findings of the Review Panel and proposes a conclusion on the outcome of this revie

Cellular shear adhesion force measurement and simultaneous imaging by atomic force microscope

This paper presents a sensitive and fast cellular shear adhesion force measurement method using an atomic force microscope (AFM). In the work, the AFM was used both as a tool for the imaging of cells on the nano-scale and as a force sensor for the measurement of the shear adhesion force between the cell and the substrate. After the cell imaging, the measurement of cellular shear adhesion forces was made based on the different positions of the cell on the nano-scale. Moreover, different pushing speeds of probe and various locations of cells were used in experiments to study their influences. In this study, the measurement of the cell adhesion in the upper portion of the cell is different from that in the lower portion. It may reveal that the cancer cells have the metastasis tendency after cultured for 16 to 20 hours, which is significant for preventing metastasis in the patients diagnosed with early cancer lesions. Furthermore, the cellular shear adhesion forces of two types of living cancer cells were obtained based on the measurements of AFM cantilever deflections in the torsional and vertical directions. The results demonstrate that the shear adhesion force of cancer cells is twice as much as the same type of cancer cells with TRAIL. The method can also provide a way for the measurement of the cellular shear adhesion force between the cell and the substrate, and for the simultaneous exploration of cells using the AFM imaging and manipulatio

A conceptual modeling methodology based on niches and granularity

This paper presents a methodology for conceptual modeling which is based on a new modeling primitive, the niche, and associated constructs granularity and reconciliation. A niche is an environment where entities interact for a specific purpose, playing specific roles, and according to the norms and constraints of that environment. Granularity refers to the relative level of power or influence of an entity within a niche. Reconciliation is a relationship from N entities onto one reconciled entity, and represents explicitly a situation where two or more different perspectives of the same entity have been reconciled, by negotiation, into a single consensus view. The methodology we propose provides a systematic method of designing conceptual models along with a process for normalising inappropriate relationships. Normalising is a prescriptive process for identifying and remedying inconsistencies within a model based on granularities. Drawing on a number of case studies, we show how niches and granularity make complexity easier to manage, highlight inaccuracies in a model, identify opportunities for achieving project goals, and reduce semantic heterogeneity

Planck early results I : The Planck mission

Peer reviewe

Planck early results. II. The thermal performance of Planck

The performance of the Planck instruments in space is enabled by their low operating temperatures, 20 K for LFI and 0.1 K for HFI, achieved through a combination of passive radiative cooling and three active mechanical coolers. The scientific requirement for very broad frequency coverage led to two detector technologies with widely different temperature and cooling needs. Active coolers could satisfy these needs; a helium cryostat, as used by previous cryogenic space missions (IRAS, COBE, ISO, Spitzer, AKARI), could not. Radiative cooling is provided by three V-groove radiators and a large telescope baffle. The active coolers are a hydrogen sorption cooler (<20 K), a 4He Joule-Thomson cooler (4.7 K), and a 3He-4He dilution cooler (1.4 K and 0.1 K). The flight system was at ambient temperature at launch and cooled in space to operating conditions. The HFI bolometer plate reached 93 mK on 3 July 2009, 50 days after launch. The solar panel always faces the Sun, shadowing the rest of Planck, and operates at a mean temperature of 384 K. At the other end of the spacecraft, the telescope baffle operates at 42.3 K and the telescope primary mirror operates at 35.9 K. The temperatures of key parts of the instruments are stabilized by both active and passive methods. Temperature fluctuations are driven by changes in the distance from the Sun, sorption cooler cycling and fluctuations in gas-liquid flow, and fluctuations in cosmic ray flux on the dilution and bolometer plates. These fluctuations do not compromise the science data

Planck pre-launch status : The Planck mission

Peer reviewe