Mathematical modelling of the pathogenesis of multiple myeloma-induced bone disease

Multiple myeloma (MM) is the second most common haematological malignancy and results in destructive bone lesions. The interaction between MM cells and the bone microenvironment plays an important role in the development of the tumour cells and MM-induced bone disease and forms a 'vicious cycle' of tumour development and bone destruction, intensified by suppression of osteoblast activity and promotion of osteoclast activity. In this paper, a mathematical model is proposed to simulate how the interaction between MM cells and the bone microenvironment facilitates the development of the tumour cells and the resultant bone destruction. It includes both the roles of inhibited osteoblast activity and stimulated osteoclast activity. The model is able to mimic the temporal variation of bone cell concentrations and resultant bone volume after the invasion and then removal of the tumour cells and explains why MM-induced bone lesions rarely heal even after the complete removal of MM cells. The behaviour of the model compares well with published experimental data. The model serves as a first step to understand the development of MM-induced bone disease and could be applied further to evaluate the current therapies against MM-induced bone disease and even suggests new potential therapeutic targets

The Link between Environmental Toxicant Exposure and Endometriosis Re-Examined

Endometriosis is widely acknowledged to be an estrogen dependent disease or unknown etiology. Recognition that environmental toxicants can bind with and activate the estrogen receptor, dysregulate steroid metabolism and, in some cases, act as anti-androgenic substances (phthalate esters) has led to proposal that exposure to environmental toxicants are associated with increased risk of endometriosis. Since our last review of the subject in 2008, the literature has expanded with several epidemiological and biomonitoring studies suggesting a potential association, whereas others have been unable to demonstrate a link between exposure and enhanced risk. Therefore, we carried out a systematic review and critical appraisal of the literature published over the past decade (2009–2019). The majority of studies found dealt with exposure to polychlorinated biphenyls (PCBs), dioxins, dioxin-like and non-dioxin-like compounds, bisphenol A and phthalate esters. Several studies suggest a potential association between exposure to environmental toxicants; however, important weaknesses in study design, methodology, and analysis together with many contradictory studies weaken confidence in these associations. Consequently, we conclude that despite a growing literature, evidence for an association between exposure to environmental toxicants and risk of endometriosis remains weak

Transition from ion-coupled to electron-only reconnection: Basic physics and implications for plasma turbulence

Using kinetic particle-in-cell (PIC) simulations, we simulate reconnection conditions appropriate for the magnetosheath and solar wind, i.e., plasma beta (ratio of gas pressure to magnetic pressure) greater than 1 and low magnetic shear (strong guide field). Changing the simulation domain size, we find that the ion response varies greatly. For reconnecting regions with scales comparable to the ion Larmor radius, the ions do not respond to the reconnection dynamics leading to ''electron-only'' reconnection with very large quasi-steady reconnection rates. The transition to more traditional ''ion-coupled'' reconnection is gradual as the reconnection domain size increases, with the ions becoming frozen-in in the exhaust when the magnetic island width in the normal direction reaches many ion inertial lengths. During this transition, the quasi-steady reconnection rate decreases until the ions are fully coupled, ultimately reaching an asymptotic value. The scaling of the ion outflow velocity with exhaust width during this electron-only to ion-coupled transition is found to be consistent with a theoretical model of a newly reconnected field line. In order to have a fully frozen-in ion exhaust with ion flows comparable to the reconnection Alfv\'en speed, an exhaust width of at least several ion inertial lengths is needed. In turbulent systems with reconnection occurring between magnetic bubbles associated with fluctuations, using geometric arguments we estimate that fully ion-coupled reconnection requires magnetic bubble length scales of at least several tens of ion inertial lengths

Exploiting cross-channel quantizer error correlation in time-interleaved analog-to-digital converters

Uniform quantizers are often modeled as additive uncorrelated noise sources. This paper explores the validity of the additive noise model in the environment of time-interleaved A/D converters. Cross-channel quantizer error correlation is an important discrepancy that arises for channel time delays in close proximity. It is demonstrated through simulation that negative error correlation occurs for different granularity quantizers in close proximity. Statistical analysis is presented to characterize error correlation between quantizers with different granularity. A technique exploiting this correlation often yields significant performance gains above the optimal additive noise model solution.Fullbright FellowshipIrwin Mark Jacobs and Joan Klein Jacobs Presidential FellowshipTexas Instruments Incorporated. Leadership University Consortium ProgramBAE SystemsAnalog Devices, inc.Lincoln Laborator

Planar Double Bubbles on Flat Walls

In this paper, we investigate some properties of planar soap bubbles on a straight wall with a single corner. We show that when a wall has a single corner and a bubble consists of two connected regions, the perimeter minimizing bubble must be one of the types, two concentric circular arcs or a truncated standard double bubble, depending on the angle of the corner and areas of the regions

Observation of Macroscopic Structural Fluctuations in bcc Solid 4He

We report neutron diffraction studies of low density bcc and hcp solid 4He. In the bcc phase, we observed a continuous dynamical behaviour involving macroscopic structural changes of the solid. The dynamical behaviour takes place in a cell full of solid, and therefore represents a solidsolid transformation. The structural changes are consistent with a gradual rotation of macroscopic grains separated by low angle grain boundaries. We suggest that these changes are triggered by random momentary vibrations of the experimental system. An analysis of Laue diffraction patterns indicates that in some cases these structural changes, once initiated by a momentary impulse, seem to proceed at a constant rate over times approaching an hour. The energy associated with these macroscopic changes appears to be on the order of kT. Under similar conditions (temperature and pressure), these effects were absent in the hcp phase.Comment: 14 pages, 6 figure, accepted for PR

Persistent Transport Barrier on the West Florida Shelf

Analysis of drifter trajectories in the Gulf of Mexico has revealed the existence of a region on the southern portion of the West Florida Shelf (WFS) that is not visited by drifters that are released outside of the region. This so-called ``forbidden zone'' (FZ) suggests the existence of a persistent cross-shelf transport barrier on the southern portion of the WFS. In this letter a year-long record of surface currents produced by a Hybrid-Coordinate Ocean Model simulation of the WFS is used to identify Lagrangian coherent structures (LCSs), which reveal the presence of a robust and persistent cross-shelf transport barrier in approximately the same location as the boundary of the FZ. The location of the cross-shelf transport barrier undergoes a seasonal oscillation, being closer to the coast in the summer than in the winter. A month-long record of surface currents inferred from high-frequency (HF) radar measurements in a roughly 60 km $\times$ 80 km region on the WFS off Tampa Bay is also used to identify LCSs, which reveal the presence of robust transient transport barriers. While the HF-radar-derived transport barriers cannot be unambiguously linked to the boundary of the FZ, this analysis does demonstrate the feasibility of monitoring transport barriers on the WFS using a HF-radar-based measurement system. The implications of a persistent cross-shelf transport barrier on the WFS for the development of harmful algal blooms on the shoreward side of the barrier are considered.Comment: Submitted to Geophysical Research Letter

Evaluability Assessment of “Growing Healthy Communities,” a Mini-grant Program to Improve Access to Healthy Foods and Places for Physical Activity

Mini-grants have been used to stimulate multisector collaboration in support of public health initiatives by funding non-traditional partners, such as economic development organizations. Such mini-grants have the potential to increase access to healthy foods and places for physical activity through built environment change, especially in small and rural towns in the United States. Although a promising practice, few mini-grant evaluations have been done. Therefore, our purpose was to conduct an Evaluability Assessment (EA), which is a process that can help promising programs that lack evidence advance toward full-scale evaluation. Specifically, we conducted an Evaluability Assessment of a statewide mini-grant program, called “Growing Healthy Communities” (GHC), to determine if this program was ready for evaluation and identify any changes needed for future implementation and evaluation that could also inform similar programs