On fiber diameters of continuous maps

We present a surprisingly short proof that for any continuous map $f : \mathbb{R}^n \rightarrow \mathbb{R}^m$, if $n>m$, then there exists no bound on the diameter of fibers of $f$. Moreover, we show that when $m=1$, the union of small fibers of $f$ is bounded; when $m>1$, the union of small fibers need not be bounded. Applications to data analysis are considered.Comment: 6 pages, 2 figure

Resistance is futile: overcoming resistance to targeted therapies in lung adenocarcinoma.

The advent of genomics has led to the identification of specific "driver" mutations in oncogenic kinases, and the development of targeted small molecule inhibitors to block their tumor-driving functions. These specific inhibitors have been a clinical success, and often significantly prolong the lives of individuals with cancer. Inevitably, however, the treated tumors recur as resistance to these targeted therapies develops. Here, we review the major mechanisms by which a cancer cell can evade targeted therapy, focusing on mechanisms of resistance to kinase inhibitors in lung cancer. We discuss the promising concept of rational upfront polytherapy in lung cancer, which involves concurrently targeting multiple proteins in critical signaling pathways in a cancer cell to prevent or delay resistance

Chaser: A Modern Film Noir

Chaser is a story about Devin, a city detective who has been investigating the kidnapping of the police captain???s wife, Melissa Florek. Devin???s search takes him to a seedy bar that is suspected to be a front for other illicit activities by the city???s biggest crime lord, Vincent. Although Devin???s job requires him to be a symbol of justice and good his struggles with his own demons are revealed through the subtext of his dialogue and his actions. Chaser is an homage to the independent style of neo-noir. Noir???s dramatic style of shadows, moral ambiguity, and cynicism is often seen as its own genre, when truly it is a style that can be applied to various other genres. This project paper will explore the various stylistic techniques of neo-noir as well as other movie making aesthetics. More specifically, it will elaborate on the significance of their presence within this short film and how they will make it similar to that of a modern noi

An Engineered Calmodulin-Based Allosteric Switch for Peptide Biosensing

This work describes the development of a new platform for allosteric protein engineering that takes advantage of the ability of calmodulin to change conformation upon binding to peptide and protein ligands. The switch we have developed consists of a fusion protein in which calmodulin is genetically inserted into the sequence of TEM1 β-lactamase. In this approach, calmodulin acts as the input domain, whose ligand-dependent conformational changes control the activity of the β-lactamase output domain. The new allosteric enzyme exhibits up to 120 times higher catalytic activity in the activated (peptide bound) state compared to the inactive (no peptide bound) state in vitro. Activation of the enzyme is ligand-dependent-peptides with higher affinities for wild-type calmodulin exhibit increased switch activity. Calmodulin's ability to "turn on" the activity of β-lactamase makes this a potentially valuable scaffold for the directed evolution of highly specific biosensors for detecting toxins and other clinically relevant biomarkers.Chemistry and Chemical Biolog

Efficiency tests on gasoline engine

Citation: Stauffer, Arthur S., Matthews, Vernon, and Blair, Otis Neel. Efficiency tests on gasoline engine. Senior thesis, Kansas State Agricultural College, 1904.Morse Department of Special CollectionsIntroduction: This is a horizontal, ten horse power engine of the usual four cycle type, ignition taking place every fourth stroke and the speed being governed by cutting out charges of gasoline, (commonly called the “hit and miss" method) The following tests were made to determine the mechanical efficiency and the amount of gasoline required. The cylinder is cooled by city water direct from the hydrant. The temperatures of the cooling water were not taken as no attempt was made to determine the thermal efficiency of the engine. In the first two tests the load was applied by means of the ordinary prony brake, but as there was no provision for cooling the brake it, heated too badly for satisfactory results. In place of this was substituted a brake as shown in the frontispiece. This is a leather strap passing part way around the flywheel, the pull being recorded on a platform scale. By varying the arc of contract, the operator is enabled to maintain a steady load upon the engine

The ULK3 Kinase Is Critical for Convergent Control of Cancer-Associated Fibroblast Activation by CSL and GLI.

The connection between signaling pathways activating cancer-associated fibroblasts (CAFs) remains to be determined. Metabolic alterations linked to autophagy have also been implicated in CAF activation. CSL/RBPJ, a transcriptional repressor that mediates Notch signaling, suppresses the gene expression program(s), leading to stromal senescence and CAF activation. Deregulated GLI signaling can also contribute to CAF conversion. Here, we report that compromised CSL function depends on GLI activation for conversion of human dermal fibroblasts into CAFs, separately from cellular senescence. Decreased CSL upregulates the expression of the ULK3 kinase, which binds and activates GLI2. Increased ULK3 also induces autophagy, which is unlinked from GLI and CAF activation. ULK3 upregulation occurs in the CAFs of several tumor types, and ULK3 silencing suppresses the tumor-enhancing properties of these cells. Thus, ULK3 links two key signaling pathways involved in CAF conversion and is an attractive target for stroma-focused anti-cancer intervention

Memory in nanomagnetic systems: Superparamagnetism versus Spinglass behavior

The slow dynamics and concomitant memory (aging) effects seen in nanomagnetic systems are analyzed on the basis of two separate paradigms : superparamagnets and spinglasses. It is argued that in a large class of aging phenomena it suffices to invoke superparamagnetic relaxation of individual single domain particles but with a distribution of their sizes. Cases in which interactions and randomness are important in view of distinctive experimental signatures, are also discussed.Comment: 11 pages and 19 figure

Evidence for a multipotent mammary progenitor with pregnancy-specific activity

Introduction: The mouse mammary gland provides a powerful model system for studying processes involved in epithelial tissue development. Although markers that enrich for mammary stem cells and progenitors have been identified, our understanding of the mammary developmental hierarchy remains incomplete. Methods: We used the MMTV promoter linked to the reverse tetracycline transactivator to induce H2BGFP expression in the mouse mammary gland. Mammary epithelial cells (MECs) from virgin mice were sorted by flow cytometry for expression of the mammary stem cell/progenitor markers CD24 and CD29, and H2BGFP. Sorted populations were analyzed for in vivo repopulation ability, expression of mammary lineage markers, and differential gene expression. Results: The reconstituting activity of CD24+/CD29+ cells in cleared fat pad transplantation assays was not distinguished in GFP+ compared to GFP- subpopulations. However, within the CD24+/CD29lo luminal progenitor-enriched population, H2BGFP+, but not H2BGFP-, MECs formed mammary structures in transplantation assays; moreover, this activity was dramatically enhanced in pregnant recipients. These outgrowths contained luminal and myoepithelial mammary lineages and produced milk, but lacked the capacity for serial transplantation. Transcriptional microarray analysis revealed that H2BGFP+/CD24+/CD29lo MECs are distinct from H2BGFP-/CD24+/CD29lo MECs and enriched for gene expression signatures with both the stem cell (CD24+/CD29+) and luminal progenitor (CD24+/CD29lo/CD61+) compartments. Conclusions: We have identified a population of MECs containing pregnancy-activated multipotent progenitors that are present in the virgin mammary gland and contribute to the expansion of the mammary gland during pregnancy