Notes

Magnetic Nanoparticles Used in Oncology.
Electron cryo-microscopy (Cryo-EM) is a powerful method for visualizing biological objects with up to near-angstrom resolution. Instead of chemical fixation, the method relies on very rapid freezing to immobilize the sample. Under these conditions, crystalline ice does not have time to form and distort structure. For many practical applications, the rate of cooling is fast enough to consider sample immobilization instantaneous, but in some cases, a more rigorous analysis of structure relaxation during freezing could be essential. This difficult yet important problem has been significantly under-reported in the literature, despite spectacular recent developments in Cryo-EM. Here we use Brownian dynamics modeling to examine theoretically the possible effects of cryo-immobilization on the apparent shapes of biological polymers. The main focus of our study is on tubulin protofilaments. These structures are integral parts of microtubules, which in turn are key elements of the cellular skeleton, essential for intracellular transport, maintenance of cell shape, cell division and migration. We theoretically examine the extent of protofilament relaxation within the freezing time as a function of the cooling rate, the filament's flexural rigidity, and the effect of cooling on water's viscosity. Our modeling suggests that practically achievable cooling rates are not rapid enough to capture tubulin protofilaments in conformations that are incompletely relaxed, suggesting that structures seen by cryo-EM are good approximations to physiological shapes. This prediction is confirmed by our analysis of curvatures of tubulin protofilaments, using samples, prepared and visualized with a variety of methods. We find, however, that cryofixation may capture incompletely relaxed shapes of more flexible polymers, and it may affect Cryo-EM-based measurements of their persistence lengths. This analysis will be valuable for understanding of structures of different types of biopolymers, observed with Cryo-EM.Intratumour heterogeneity is increasingly recognized as a frequent problem for cancer treatment as it allows for the evolution of resistance against treatment. While cancer genotyping becomes more and more established and allows to determine the genetic heterogeneity, less is known about the phenotypic heterogeneity among cancer cells. We investigate how phenotypic differences can impact the efficiency of therapy options that select on this diversity, compared to therapy options that are independent of the phenotype. We employ the ecological concept of trait distributions and characterize the cancer cell population as a collection of subpopulations that differ in their growth rate. We show in a deterministic model that growth rate-dependent treatment types alter the trait distribution of the cell population, resulting in a delayed relapse compared to a growth rate-independent treatment. Whether the cancer cell population goes extinct or relapse occurs is determined by stochastic dynamics, which we investigate using a stochastic model. Again, we find that relapse is delayed for the growth rate-dependent treatment type, albeit an increased relapse probability, suggesting that slowly growing subpopulations are shielded from extinction. Sequential application of growth rate-dependent and growth rate-independent treatment types can largely increase treatment efficiency and delay relapse. Interestingly, even longer intervals between decisions to change the treatment type may achieve close-to-optimal efficiencies and relapse times. Monitoring patients at regular check-ups may thus provide the temporally resolved guidance to tailor treatments to the changing cancer cell trait distribution and allow clinicians to cope with this dynamic heterogeneity.Collective behavior is an emergent property of numerous complex systems, from financial markets to cancer cells to predator-prey ecological systems. Characterizing modes of collective behavior is often done through human observation, training generative models, or other supervised learning techniques. Each of these cases requires knowledge of and a method for characterizing the macro-state(s) of the system. This presents a challenge for studying novel systems where there may be little prior knowledge. Rimiducid mw Here, we present a new unsupervised method of detecting emergent behavior in complex systems, and discerning between distinct collective behaviors. We require only metrics, d(1), d(2), defined on the set of agents, X, which measure agents' nearness in variables of interest. We apply the method of diffusion maps to the systems (X, d(i)) to recover efficient embeddings of their interaction networks. Comparing these geometries, we formulate a measure of similarity between two networks, called the map alignment statistic (MAS). A large MAS is evidence that the two networks are codetermined in some fashion, indicating an emergent relationship between the metrics d(1) and d(2). Additionally, the form of the macro-scale organization is encoded in the covariances among the two sets of diffusion map components. Using these covariances we discern between different modes of collective behavior in a data-driven, unsupervised manner. This method is demonstrated on a synthetic flocking model as well as empirical fish schooling data. We show that our state classification subdivides the known behaviors of the school in a meaningful manner, leading to a finer description of the system's behavior.
We explored the association between influenza epidemic and suicide mortality rates in a large population using a time-series regression of 13-year mortality data in South Korea.

Weekly suicide mortalities and influenza-like illness (ILI) were analyzed using time series regression. Regression coefficient for suicide mortality based on percentage change of ILI was calculated using a quasi-Poisson regression. Non-linear distributed lag models with quadratic function up to 24 weeks were constructed.

The association between ILI and suicide mortality increased significantly up to 8 weeks post-influenza diagnosis. A significant positive association between ILI and suicide mortality was observed from 2009, when a novel influenza A(H1N1)pdm09 virus provoked a worldwide pandemic. No meaningful association between these factors was observed before 2009.

There was a significant positive relationship between ILI and suicide mortality after 2009, when a novel influenza A(H1N1)pdm09 virus provoked a worldwide pandemic.
Website: https://www.selleckchem.com/products/rimiducid-ap1903.html