OBJECTIVES/GOALS: In triple negative breast cancer (TNBC), obesity is associated with poor outcomes. Adipose stem cells (ASCs) from obese patients (obASCs) secrete higher levels of adipokines compared to ASCs from lean individuals. Leptin, one of these adipokines, has been implicated in many cancers. This study seeks to examine the role of leptin signaling in TNBC. METHODS/STUDY POPULATION: Previous work in conjunction with a collaborating lab has shown that leptin signaling promotes metastasis and increased expression of epithelial-mesenchymal transition (EMT) markers in triple negative breast cancer cell lines. This project expands upon this work through using both patient-derived cell lines and and patient-derived xenografts (PDX), and examines the role of leptin signaling both in vitro and in vivo. To determine the effects of obesity upon a PDX model of TNBC, a high fat diet was used to induce obesity in vivo. A pharmacological inhibitor of the leptin receptor was used to test the requirement for leptin signaling both in vivo and in vitro. RESULTS/ANTICIPATED RESULTS: Exposure to conditioned media harvested from obASCs increased the percentage of TNBC cells that expressed cancer stem cell markers, whereas exposure to an inhibitor of the leptin receptor decreased the percentage of cells with cancer stem cell markers. PDX tumors implanted into mice with diet-induced obesity had an increased volume compared to tumors implanted into lean controls. Further analysis will be conducted on metastasis, circulating tumor cells, and survival in both lean and obese mice. DISCUSSION/SIGNIFICANCE: Understanding the complex signaling events in the obese tumor microenvironment is essential, as these molecular differences may contribute to different outcomes for obese and lean individuals with triple negative breast cancer. Therefore, study of the crosstalk between obASCs and TNBC cells is critical.

OBJECTIVES/GOALS: Current approaches to drug development for the aggressive triple negative breast cancer rely on current 2D and 3D in vitro models which have limited capabilities. We have developed a translational microphysiological system that can maintain the human breast microenvironment to capture the complex interaction with the tumor microenvironment. METHODS/STUDY POPULATION: Three different TNBC cell lines were seeded in BC-MPS: MDA-MB-231 parental cell line, MDA-MB-231wiht the gene, LKB1 overexpressed, which is a tumor suppressor, and MDA-MB-231 with the enzyme, ERK5, an enzyme associated with increased metastasis and drug resistance, knocked out. These three TNBC cell lines were cultured in a standard 2D 96-well plate and in BC-MPS. Time-lapse videos were taken to track cellular mobility. RNA-sequencing was performed to compare different expression levels of various cancer related genes of the cell lines cultured in standard 2D and BC-MPS. RESULTS/ANTICIPATED RESULTS: The LKB1 overexpressed MDA-MB-231 and the ERK5-ko MDA-MB-231 cell lines are expected to have decreased mobility compared to the parental cells. The cell lines are expected to have increased expression of cancer related genes when cultured in BC-MPS than when cultured in standard 2D due to the presence of human breast tissue. DISCUSSION/SIGNIFICANCE: BC-MPS is a promising new translational MPS that facilitates studying long term interactions between real human breast tissue and cancer cells. The BC-MPS systems ability to support the growth of established cell lines has been demonstrated. Future studies will focus on developing the model for personalized medicine.

Let $N\geq 1$ be squarefree with $(N,6)=1$ . Let $c\phi _N(n)$ denote the number of N-colored generalized Frobenius partitions of n introduced by Andrews in 1984, and $P(n)$ denote the number of partitions of n. We prove

$$ \begin{align*}c\phi_N(n)= \sum_{d \mid N} N/d \cdot P\left( \frac{ N}{d^2}n - \frac{N^2-d^2}{24d^2} \right) + b(n),\end{align*} $$

$C(z) := (q;q)^N_\infty \sum _{n=1}^{\infty } b(n) q^n$

$S_{(N-1)/2} (\Gamma _0(N),\chi _N)$

$c\phi _N(n)$

$P(n)$

We explore the possibility of combining a knowledge-based reduced order model (ROM) with a reservoir computing approach to learn and predict the dynamics of chaotic systems. The ROM is based on proper orthogonal decomposition (POD) with Galerkin projection to capture the essential dynamics of the chaotic system while the reservoir computing approach used is based on echo state networks (ESNs). Two different hybrid approaches are explored: one where the ESN corrects the modal coefficients of the ROM (hybrid-ESN-A) and one where the ESN uses and corrects the ROM prediction in full state space (hybrid-ESN-B). These approaches are applied on two chaotic systems: the Charney–DeVore system and the Kuramoto–Sivashinsky equation and are compared to the ROM obtained using POD/Galerkin projection and to the data-only approach based uniquely on the ESN. The hybrid-ESN-B approach is seen to provide the best prediction accuracy, outperforming the other hybrid approach, the POD/Galerkin projection ROM, and the data-only ESN, especially when using ESNs with a small number of neurons. In addition, the influence of the accuracy of the ROM on the overall prediction accuracy of the hybrid-ESN-B is assessed rigorously by considering ROMs composed of different numbers of POD modes. Further analysis on how hybrid-ESN-B blends the prediction from the ROM and the ESN to predict the evolution of the system is also provided.

ABSTRACT IMPACT: Identifying an important pathway in treatment resistant TNBC will allow for the future development of clinical therapeutics specific for this disease. OBJECTIVES/GOALS: Triple Negative Breast Cancer (TNBC) is a subtype of breast cancer characterized by negative expression of estrogen receptor, progesterone receptor, and HER2/neu amplification. It resists therapies and has a high recurrence rate after resection. The goal of my research is to identify & characterize a TNBC pathway for future development of therapies. METHODS/STUDY POPULATION: The project uses a combination of cell lines, patient derived xenograft (PDX) models, as well as patient databases. Standard cellular and molecular biology techniques will be used including: Cell culture, qPCR, western blotting, and flow cytometry. RESULTS/ANTICIPATED RESULTS: LKB1 is a master kinase that activates 14 possible downstream kinases. The signaling pathway has been demonstrated to play a role in energy homeostasis and metabolism. Mutation of LKB1 signaling results in Peutz-Jeghers Syndrome and is associated with neoplasias of the lung, pancreas, and breast. Based on preliminary analysis, overexpression of LKB1 by shRNA in TNBC cell lines results in suppression of EMT and reduction of the cancer stem cell population. Additional studies show that LKB1 overexpression has no effect on growth rate in 2D culture while significant reduction in 3D mammosphere formations can be seen. Downstream studies using commercially available SIK1 inhibitor HG-9-91-01 is able to induce a larger fraction of CSC from reduced LKB1 overexpression as well as from baseline levels. DISCUSSION/SIGNIFICANCE OF FINDINGS: Overall, our results suggest that LKB1 acts through SIK1 to suppress EMT and the generation of cancer stem cells. This results in reduced cancer functionality, as evidenced by inhibition of mammosphere formation. These results establishes a foundation for future mechanistic studies on the LKB1 axis and its mechanisms in TNBC.

Let $X$ be a finite-dimensional connected compact abelian group equipped with the normalized Haar measure $\unicode[STIX]{x1D707}$. We obtain the following mean ergodic theorem over ‘thin’ phase sets. Fix $k\geq 1$ and, for every $n\geq 1$, let $A_{n}$ be a subset of $\mathbb{Z}^{k}\cap [-n,n]^{k}$. Assume that $(A_{n})_{n\geq 1}$ has $\unicode[STIX]{x1D714}(1/n)$ density in the sense that $\lim _{n\rightarrow \infty }(|A_{n}|/n^{k-1})=\infty$. Let $T_{1},\ldots ,T_{k}$ be ergodic automorphisms of $X$. We have

$$\begin{eqnarray}\frac{1}{|A_{n}|}\mathop{\sum }_{(n_{1},\ldots ,n_{k})\in A_{n}}f_{1}(T_{1}^{n_{1}}(x))\cdots f_{k}(T_{k}^{n_{k}}(x))\stackrel{L_{\unicode[STIX]{x1D707}}^{2}}{\longrightarrow }\int f_{1}\,d\unicode[STIX]{x1D707}\cdots \int f_{k}\,d\unicode[STIX]{x1D707},\end{eqnarray}$$

$f_{1},\ldots ,f_{k}\in L_{\unicode[STIX]{x1D707}}^{\infty }$

$T_{i}$

$A_{n}$

$[0,n]^{k}$

$n$

$A_{i}$

In Canada, recreational use of cannabis was legalized in October 2018. This policy change along with recent publications evaluating the efficacy of cannabis for the medical treatment of epilepsy and media awareness about its use have increased the public interest about this agent. The Canadian League Against Epilepsy Medical Therapeutics Committee, along with a multidisciplinary group of experts and Canadian Epilepsy Alliance representatives, has developed a position statement about the use of medical cannabis for epilepsy. This article addresses the current Canadian legal framework, recent publications about its efficacy and safety profile, and our understanding of the clinical issues that should be considered when contemplating cannabis use for medical purposes.

We show that Hermite’s theorem fails for every integer $n$ of the form $3^{k_{1}}+3^{k_{2}}+3^{k_{3}}$ with integers $k_{1}>k_{2}>k_{3}\geqslant 0$. This confirms a conjecture of Brassil and Reichstein. We also obtain new results for the relative Hermite–Joubert problem over a finitely generated field of characteristic 0.

A 52-year-old woman was referred for a progressive neurological condition which started a year before with continuous irregular twitching of the right facial and arm muscles as well as the tongue and palate, followed by progressive dysphagia, right hemiparesis, ataxia, dysphasia and dysarthria. Though magnetic resonance imaging (MRI) at clinical presentation and a year after were both normal (Figure A1), Rasmussen's encephalitis (RE) was strongly suspected and treatment with corticosteroids and immunoglobulins were begun. A third MRI, two years after onset, revealed mild T2 hyperintense subcortical white matter changes over the left perisylvian region (Figure A) which confirmed our initial suspicion of RE as she now met clinical, electrophysiological and morphological criterias for RE. While waiting for a cerebral biopsy after unsatisfactory response from antiepileptic drugs, corticosteroids and immunoglobulins, her condition markedly worsened less than three years after onset with the sudden occurrence of status epilepticus requiring intubation and continuous infusions of midazolam and propofol.

We prove Zhang’s dynamical Manin–Mumford conjecture and dynamical Bogomolov conjecture for dominant endomorphisms $\unicode[STIX]{x1D6F7}$ of $(\mathbb{P}^{1})^{n}$. We use the equidistribution theorem for points of small height with respect to an algebraic dynamical system, combined with an analysis of the symmetries of the Julia set for a rational function.