Pancreatic cancer 3D cell line organoids (CLOs) maintain the phenotypic characteristics of organoids and accurately reflect the cellular architecture and heterogeneity In vivo

Pancreatic cancer is a highly lethal disease. Therapeutic resistance to chemotherapy is a major cause of treatment failure and recurrence in pancreatic cancer. Organoids derived from cancer stem cells (CSC) are promising models for the advancement of personalised therapeutic responses to inform clinical decisions. However, scaling-up of 3D organoids for high-throughput screening is time-consuming and costly. Here, we successfully developed organoid-derived cell lines (2.5D) from 3D organoids; the cells were then expanded and recapitulated back into organoids known as cell line organoids (CLOs). The 2.5D lines were cultured long term into 2D established cell lines for downstream comparison analysis. Experimental characterisation of the models revealed that the proliferation of CLOs was slightly faster than that of parental organoids. The therapeutic response to chemotherapeutic agents in 3D CLOs and organoids showed a similar responsive profile. Compared to 3D CLOs and organoids, 2D cell lines tended to be less responsive to all the drugs tested. Stem cell marker expression was higher in either 3D CLOs or organoids compared to 2D cell lines. An in vivo tumorigenicity study found CLOs form tumours at a similar rate to organoids and retain enhanced CSC marker expression, indicating the plasticity of CSCs within the in vivo microenvironment

Particulate matter exposure during pregnancy is associated with birth weight, but not gestational age, 1962-1992: a cohort study

<p>Abstract</p> <p>Background</p> <p>Exposure to air pollutants is suggested to adversely affect fetal growth, but the evidence remains inconsistent in relation to specific outcomes and exposure windows.</p> <p>Methods</p> <p>Using birth records from the two major maternity hospitals in Newcastle upon Tyne in northern England between 1961 and 1992, we constructed a database of all births to mothers resident within the city. Weekly black smoke exposure levels from routine data recorded at 20 air pollution monitoring stations were obtained and individual exposures were estimated via a two-stage modeling strategy, incorporating temporally and spatially varying covariates. Regression analyses, including 88,679 births, assessed potential associations between exposure to black smoke and birth weight, gestational age and birth weight standardized for gestational age and sex.</p> <p>Results</p> <p>Significant associations were seen between black smoke and both standardized and unstandardized birth weight, but not for gestational age when adjusted for potential confounders. Not all associations were linear. For an increase in whole pregnancy black smoke exposure, from the 1^st(7.4 μg/m³) to the 25^th(17.2 μg/m³), 50^th(33.8 μg/m³), 75^th(108.3 μg/m³), and 90^th(180.8 μg/m³) percentiles, the adjusted estimated decreases in birth weight were 33 g (SE 1.05), 62 g (1.63), 98 g (2.26) and 109 g (2.44) respectively. A significant interaction was observed between socio-economic deprivation and black smoke on both standardized and unstandardized birth weight with increasing effects of black smoke in reducing birth weight seen with increasing socio-economic disadvantage.</p> <p>Conclusions</p> <p>The findings of this study progress the hypothesis that the association between black smoke and birth weight may be mediated through intrauterine growth restriction. The associations between black smoke and birth weight were of the same order of magnitude as those reported for passive smoking. These findings add to the growing evidence of the harmful effects of air pollution on birth outcomes.</p

Mending a torn world : Women in interreligious dialogue

New Yorkxv, 158 p.; 21 c

Women speaking, women listening : Women in interreligious dialogue

Maryknoll, New Yorkx, 131 p.; 21 c

DESIGN, MANUFACTURING, AND CHARACTERIZATION OF SOFT, CAPACITIVE ACTUATORS AND ARCHITECTED DIELECTRIC ELASTOMERS

145 pagesSupplemental file(s) description: Supplemental Video for Chapter 2.Elastomeric, dielectric architectures exhibit versatile functionality. Depending on their material properties and geometric structure, dielectric architectures can facilitate the transformation of an object’s shape, sense local deformation, or even alter the transmission of electromagnetic waves in the surrounding envi- ronment. This work develops and characterizes soft material systems and fab- rication frameworks for multi-dimensional mobility and topological morphing. A comprehensive material system is introduced for the additive manufactur- ing of soft, electrohydraulic tentacle actuators. A photo-curable, elastomeric silicone-urethane with strong dielectric properties (εr ≈ 8.8 at 1 kHz) serves as the encapsulating material for ionically-conductive hydrogel and silver paint electrodes that displace a vegetable-based liquid dielectric under an applied electric field. A fully-encapsulated and 3D printed electrohydraulic tentacle actuator—containing a three-dimensional array of 30 actuators—demonstrates the use of this material system in a synthetic hydrostat with multi-dimensional motion. This technology is extended to toplogical morphing with dual-phase capacitive actuators to design conformable reflectarray antennas with beam- steering capabilities. A silicone-urethane membrane with carbon and copper electrodes encapsulates a dual gas-liquid working fluid (N2 gas and Envirotemp FR3 liquid, εr = 3.2) to create a lightweight and rapid reconfiguration mech-anism. A pair of the capacitive actuators can exhibit a free displacement of ∆d ≈ 1.4 mm with only 0.34 g of working fluid (46wt% N2 gas). This work also introduces a numerical and experimental study of dielec- tric elastomer architectures that can serve as flexible metamaterials for adaptive electronics. The unit cell design and porosity of two dielectric elastomeric archi- tectures provides a tuning mechanism for the onset of a mechanical instability in the structure; a shift in effective permittivity is observed due to the increase in matrix volume and the rearrangement of the electric field distribution in the cells. Additive fabrication allows rapid customization of the unit cell geome- try and scale for tuning the matrices’ electromechanical response. We observed effective permittivity shifts ∆ε2 > 0.7 under compressive strains γ 110 MHz under compression.2023-01-0

Crystal structure of the Pseudomonas aeruginosa cytoplasmic heme binding protein, Apo-PhuS

Iron is an essential element to all living organisms and is an important determinant of bacterial virulence. Bacteria have evolved specialized systems to sequester and transport iron from the environment or host. Pseudomonas aeruginosa, an opportunistic pathogen, uses two outer membrane receptor mediated systems (Phu and Has) to utilize host heme as a source of iron. PhuS is a 39 kDa soluble cytoplasmic heme binding protein which interacts and transports heme from the inner membrane heme transporter to the cytoplasm where it is degraded by heme oxygenase thus releasing iron. PhuS is unique among other cytoplasmic heme transporter proteins owing to the presence of three histidines in the heme binding pocket which can potentially serve as heme ligands. Out of the three histidine residues on the heme binding helix, His 209 is conserved among heme trafficking proteins while His 210 and His 212 are unique to PhuS. Here we report the crystal structure of PhuS at 1.98 Å resolution which shows a unique heme binding pocket and oligomeric structure compared to other known cytoplasmic heme transporter and accounts for some of the unusual biochemical properties of PhuS