Endocrine therapy: defining the path of least resistance

One of the best-characterized oncogenic mechanisms in breast cancer is the aberrant activation of phosphatidylinositol-3-kinase, protein kinase B, and mammalian target of rapamycin signaling. In both endocrine-resistant disease and breast cancer stem cells, this is commonly caused by specific genetic lesions or amplification of key pathway components or both. These observations have generated two interesting hypotheses. Firstly, do these genetic anomalies provide clinically significant biomarkers predictive of endocrine resistance? Secondly, do tamoxifen-resistant breast cancer cells emerge from a stem-like cell population? New studies, published in Breast Cancer Research, raise the possibility that these hypotheses are intrinsically linked

Effects of Type 1 Diabetes on the Mechanoreflex in Rats

Mechanical allodynia is present as early as four days post streptozotocin (STZ) injection in type 1 diabetic (T1DM) rats. This is thought to occur through mechanisms affecting the same thin fiber afferents that evoke the mechanoreflex. PURPOSE: In this study, we attempted to determine the effects of T1DM on the mechanoreflex. METHODS: We injected (i.p.) 50 mg/kg of Streptozotocin (STZ) or the vehicle (CTL) in either sex Sprague Dawley rat and waited 1 week (STZ: BW=258±31 g, glucose=448±88 mg/dL, HbA1C=6.4±1.0%; CTL: BW=318±54 g, glucose=175±48 mg/dL, HbA1C=4.3±0.2%). On the day of experiment, the right jugular vein and both carotid arteries were cannulated to inject fluids and to measure blood pressure and heart rate, respectively. The rat was placed in a Kopf stereotaxic frame and spinal unit to perform a precollicular decerebration that allowed for termination of anesthesia. The musculature of the left hindlimb was exposed and the Achilles tendon was attached to a force transducer. The tendon was then stretched for 30 seconds using a rack and pinion and the pressor and cardioaccelerator responses were measured. RESULTS: We found that the pressor (STZ: ΔMAP=42.11±8 mmHg, n=9; CTL: ΔMAP=18.67±4 mmHg, n=6; p=0.02) but not the cardioaccelerator (STZ: ΔHR=13.67±3 bpm, n=9; CTL: ΔHR=9.67±2 bpm, n=6; p=0.22) responses to tendon stretch were exaggerated 1 week after injecting STZ. Both diabetic and control rats developed similar tensions with tendon stretch. CONCLUSION: We conclude that the mechanoreflex is augmented in T1DM rats. Further studies are needed to identify the mechanisms involved in this augmentation

Line tension and structure of smectic liquid crystal multilayers at the air-water interface

At the air/water interface, 4,-8-alkyl[1,1,-biphenyl]-4-carbonitrile (8CB) domains with different thicknesses coexist in the same Langmuir film, as multiple bilayers on a monolayer. The edge dislocation at the domain boundary leads to line tension, which determines the domain shape and dynamics. By observing the domain relaxation process starting from small distortions, we find that the line tension is linearly dependent on the thickness difference between the coexisting phases in the film. Comparisons with theoretical treatments in the literature suggest that the edge dislocation at the boundary locates near the center of the film, which means that the 8CB multilayers are almost symmetric with respect to the air/water interface.Comment: 21 pages, 6 figure

"Socialist Morality" in Sartre's Unpublished 1964 Rome Lecture: A Summary and Commentary

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Nurses\u27 Alumnae Association Bulletin, June 1970

Alumnae President\u27s Message Congratulations Alumni Association Portrait of Samuel D. Gross Officers and Chairmen of Committees Financial Report Progress of Jefferson 1969-1970 School of Nursing Annual Report School of Practical Nursing Report Emergency Department Patient Services Department Annual Luncheon Pictures Committee Reports Progress of the Alumnae Association Crossword Puzzle Missing Graduates Resume of Alumnae Meetings Minutes Class News Student Nurses Section Crossword Puzzle Answers Notice

Nurses\u27 Alumnae Association Bulletin, June 1969

Alumnae President\u27s Message Officers and Chairmen Financial Report Progressive Changes at Jefferson School of Nursing Report Student Activities School of Practical Nursing Report Jefferson Expansion Report Clerk-Typist Report Committee Reports Resume of Alumnae Meetings Class News 1969 CLINIC Correspondence Notice

Determination of Inter-Phase Line Tension in Langmuir Films

A Langmuir film is a molecularly thin film on the surface of a fluid; we study the evolution of a Langmuir film with two co-existing fluid phases driven by an inter-phase line tension and damped by the viscous drag of the underlying subfluid. Experimentally, we study an 8CB Langmuir film via digitally-imaged Brewster Angle Microscopy (BAM) in a four-roll mill setup which applies a transient strain and images the response. When a compact domain is stretched by the imposed strain, it first assumes a bola shape with two tear-drop shaped reservoirs connected by a thin tether which then slowly relaxes to a circular domain which minimizes the interfacial energy of the system. We process the digital images of the experiment to extract the domain shapes. We then use one of these shapes as an initial condition for the numerical solution of a boundary-integral model of the underlying hydrodynamics and compare the subsequent images of the experiment to the numerical simulation. The numerical evolutions first verify that our hydrodynamical model can reproduce the observed dynamics. They also allow us to deduce the magnitude of the line tension in the system, often to within 1%. We find line tensions in the range of 200-600 pN; we hypothesize that this variation is due to differences in the layer depths of the 8CB fluid phases.Comment: See (http://www.math.hmc.edu/~ajb/bola/) for related movie

Effector memory differentiation increases detection of replication-competent HIV-l in resting CD4+ T cells from virally suppressed individuals.

Studies have demonstrated that intensive ART alone is not capable of eradicating HIV-1, as the virus rebounds within a few weeks upon treatment interruption. Viral rebound may be induced from several cellular subsets; however, the majority of proviral DNA has been found in antigen experienced resting CD4+ T cells. To achieve a cure for HIV-1, eradication strategies depend upon both understanding mechanisms that drive HIV-1 persistence as well as sensitive assays to measure the frequency of infected cells after therapeutic interventions. Assays such as the quantitative viral outgrowth assay (QVOA) measure HIV-1 persistence during ART by ex vivo activation of resting CD4+ T cells to induce latency reversal; however, recent studies have shown that only a fraction of replication-competent viruses are inducible by primary mitogen stimulation. Previous studies have shown a correlation between the acquisition of effector memory phenotype and HIV-1 latency reversal in quiescent CD4+ T cell subsets that harbor the reservoir. Here, we apply our mechanistic understanding that differentiation into effector memory CD4+ T cells more effectively promotes HIV-1 latency reversal to significantly improve proviral measurements in the QVOA, termed differentiation QVOA (dQVOA), which reveals a significantly higher frequency of the inducible HIV-1 replication-competent reservoir in resting CD4+ T cells