Moment-Based Estimation of State-Switching Rates in Cell Populations

In isogenic cell populations, cells can switch back and forth between different gene expression states. These expression states can be biologically relevant. For example, a certain expression state may cause a tumor cell to be resistant to treatment, while another state may leave it vulnerable to treatment. However, estimating the rates of state-switching can be difficult, because experimentally measuring a cell's transcriptome often involves destroying the cell, so it can only be measured once. In this paper, we propose a computational method to estimate the rate of switching between expression states, given data from a Luria-Delbrück style fluctuation test that is experimentally simple and feasible. We then benchmark this method using simulated data to test its efficacy, with varying assumptions made about cell cycle timing distribution in the simulations.

A LARGE SCALP MYXOID NEUROFIBROMA AN UNUSUAL PRESENTATION IN A MIDDLE- AGED PATIENT: A RARE CASE REPORT

The transformed cells in a neoplasm, whether benign or malignant, often resemble each other, as though all had been derived from a single progenitor, consistent with the monoclonal origin of the tumor. Myxoid neurobroma (MN) is a benign tumor of perineural origin, which is demonstrated by positive immunohistochemical staining for S100 protein. The most common locations are the face, shoulder, anus, periungual, and feet. To our knowledge, this is the first report of an MN in the scalp, which is a very rare location that has been reported earlier. The differential diagnosis of the tumor at this location MN should be kept in mind. This 56 years old male who presented with a large swelling in the scalp (occipital region) which extended to the nape of nack for last 3 years which is gradually increasing in size along with heaviness, intermittent severe pain in the head. Clinically (25x20) cm size swelling in the occipital area and extending to the nape of the neck. The swelling is nontender. It is ovoid in shape . Soft cystic in consistency, the surface is smooth, margins are well dened, the mobility is absent. Fluctuation test is negative but the swelling is brilliantly transilluminant. CONCLUSION: We report this case because of the rarity of both the tumor and its scalp location and also a giant size and to provide a review of the literature. This case study illustrates that any slowly progressing swelling in an unusual location should have been properly investigated and complete surgical excision is the preferred choice of treatment for future recurrence. The MN should be included in the differential diagnosis of tumors at this location.

A modified fluctuation test for elucidating drug resistance in microbial and cancer cells

Clonal populations of microbial and cancer cells are often driven into a drug-tolerant persister state in response to drug therapy, and these persisters can subsequently adapt to the new drug environment via genetic and epigenetic mechanisms. Estimating the frequency with which drug-tolerance states arise, and its transition to drug-resistance, is critical for designing efficient treatment schedules. Here we study a stochastic model of cell proliferation where drug-tolerant persister cells transform into a drug-resistant state with a certain adaptation rate, and the resistant cells can then proliferate in the presence of the drug. Assuming a random number of persisters to begin with, we derive an exact analytical expression for the statistical moments and the distribution of the total cell count (i.e., colony size) over time. Interestingly, for Poisson initial conditions the noise in the colony size (as quantified by the Fano factor) becomes independent of the initial condition and only depends on the adaptation rate. Thus, experimentally quantifying the fluctuations in the colony sizes provides an estimate of the adaptation rate, which then can be used to infer the starting persister numbers from the mean colony size. Overall, our analysis introduces a modification of the classical Luria–Delbrück experiment, also called the “Fluctuation Test”, providing a valuable tool to quantify the emergence of drug resistance in cell populations.

“A transient heritable memory regulates HIV reactivation from latency”

Reactivation of human immunodeficiency virus 1 (HIV-1) from latently infected T cells is a critical barrier to successfully eradicate HIV-1 from patients. Latency models in Jurkat T-cells reveal that individual cells reactivate in an all-or-none fashion when exposed to latency reversal agents (LRAs). Remarkably, this heterogeneity arises within a clonal cell population of genetically identical cells containing a single copy of the provirus integrated at the same genomic site. To characterize these single-cell responses, we leverage the classical Luria-Delbrück fluctuation test where single cells are isolated from a clonal population, and exposed to LRAs after a period of colony expansion. If cellular responses are purely random, then the fraction of reactivating cells should have minimal colony-to-colony fluctuations given the large number of cells present after weeks of colony growth. In contrast, data shows considerable colony-to-colony fluctuations with the fraction of reactivating cells following a skewed distribution. Systematic measurements of fluctuations over time in combination with mathematical modeling uncovers the existence of a heritable memory that regulates HIV-1 reactivation, where single cells are in a LRA-responsive state for a few weeks before switching back to an irresponsive state. These results have enormous implications for designing therapies to purge the latent reservoir and illustrate the utility of fluctuation-based assays to uncover hidden transient cellular states underlying phenotypic heterogeneity.

Design of Temperature Fluctuation Test Platform Based on Radiation Heat Transfer

The optical characteristics of the space science detectors are very sensitive to the temperature fluctuation. In order to study the effect of it, a method to simulate the temperature fluctuation was put forward in this paper, and the feasibility of this method was verified numerically. A radiation disturbance was artificially applied at a certain distance from the test platform, so that the surface temperature of the platform changed periodically with the radiation heater. The results show that the radiation heat transfer disturbance could produce a temperature fluctuation on the test platform, which provides a reliable theoretical support for the time-varying temperature control system.