Breast Cancer Advocacy and Public Policy

The issue of breast cancer, and women’s health generally, is a political issue and requires an expanded approach to public interest law. Decisions that affect how individual women are treated—such as how much and what research is performed, whether the environmental connections to breast cancer are understood and dealt with, whether all women will have access to quality health care—are made at the political level. Appropriations for breast cancer research come from Congress. Congress tells the Food and Drug Administration (FDA) what to do, and the FDA approves drugs and devices. Government-regulated programs, such as Medicaid and Medicare, provide access to health care for many individuals in this country. Even private insurance companies are regulated by the states. As a lawyer, I recognize that to have a significant impact on breast cancer—not just for individual women but on the systems that affect all women—the usual public interest law approach is not enough. Necessary, overarching change will not likely come about through the judicial system, a system that is bound by tradition and precedent. What breast cancer advocates realized in the early 1990s was the need to make new law to change the systems that affect everyone— the systems of research, access to care and regulation. Fortunately, my background and education equipped me to meet the challenges of forging new law and refusing to settle for the status quo in the name of precedent

The LArase Satellites Spin mOdel Solutions (LASSOS): a comprehensive model for the spin evolution of the LAGEOS and LARES satellites

The two LAGEOS and LARES are laser-ranged satellites tracked with the best accuracy ever achieved. Using their range measurements many geophysical parameters were calculated and some General Relativity effects were directly observed. To obtain precise and refined measurements of the effects due to the predictions of General Relativity on the orbit of these satellites, it is mandatory to model with high precision and accuracy all other forces, reducing the free parameters introduced in the orbit determination. A main category of non-gravitational forces to be considered are those of thermal origin, whose fine modeling strongly depends on the knowledge of the evolution of the spin vector. We present a complete model, named LASSOS, to describe the evolution of the spin of the LAGEOS and LARES satellites. In particular, we solved Euler equations of motion considering not-averaged torques. This is the most general case, and the predictions of the model well fit the available observations of the satellites spin. We also present the predictions of our model in the fast-spin limit, based on the application of averaged equations. The results are in good agreement with those already published, but with our approach we have been able to highlight small errors within these previous works. LASSOS was developed within the LARASE research program. LARASE aims to improve the dynamical model of the two LAGEOS and LARES satellites to provide very precise and accurate measurements of relativistic effects on their orbit, and also to bring benefits to geophysics and space geodesy

Activity driven fluctuations in living cells

We propose a model for the dynamics of a probe embedded in a living cell, where both thermal fluctuations and nonequilibrium activity coexist. The model is based on a confining harmonic potential describing the elastic cytoskeletal matrix, which undergoes random active hops as a result of the nonequilibrium rearrangements within the cell. We describe the probe's statistics and we bring forth quantities affected by the nonequilibrium activity. We find an excellent agreement between the predictions of our model and experimental results for tracers inside living cells. Finally, we exploit our model to arrive at quantitative predictions for the parameters characterizing nonequilibrium activity, such as the typical time scale of the activity and the amplitude of the active fluctuations.Comment: 6 pages, 4 figure

First test of a BAE transducing scheme on a Resonant Gravitational-Wave Antenna

We present the results obtained with a resonant capacitive transducer, suitable for Back Action Evasion (BAE) measurements, coupled for the first time to a gravitational-wave antenna. This scheme was developed in collaboration with the Group of the University of Rome La Sapienza. The antenna is a 270 kg aluminum 5056 alloy cylinder, with a resonant frequency of 1805 Hz, operating at 4.2K in the ALTAIR cryostat, located in Frascati (Italy) at the IFSI-CNR laboratory. The apparatus was able to work continuously for periods as long as days, both in up-conversion and BAE configurations, with good stability. The behaviour of the system is in reasonable Agreement with a proposed model of a double harmonic oscillator in a BAE readout scheme. The limits on the sensitivity of this set-up are discussed as well as the possible future improvements

Exact solution of a model DNA-inversion genetic switch with orientational control

DNA inversion is an important mechanism by which bacteria and bacteriophage switch reversibly between phenotypic states. In such switches, the orientation of a short DNA element is flipped by a site-specific recombinase enzyme. We propose a simple model for a DNA inversion switch in which recombinase production is dependent on the switch state (orientational control). Our model is inspired by the fim switch in Escherichia coli. We present an exact analytical solution of the chemical master equation for the model switch, as well as stochastic simulations. Orientational control causes the switch to deviate from Poissonian behaviour: the distribution of times in the on state shows a peak and successive flip times are correlated.Comment: Revised version, accepted for publicatio

BCL-W has a fundamental role in B cell survival and lymphomagenesis.

Compromised apoptotic signaling is a prerequisite for tumorigenesis. The design of effective therapies for cancer treatment depends on a comprehensive understanding of the mechanisms that govern cell survival. The antiapoptotic proteins of the BCL-2 family are key regulators of cell survival and are frequently overexpressed in malignancies, leading to increased cancer cell survival. Unlike BCL-2 and BCL-XL, the closest antiapoptotic relative BCL-W is required for spermatogenesis, but was considered dispensable for all other cell types. Here, however, we have exposed a critical role for BCL-W in B cell survival and lymphomagenesis. Loss of Bcl-w conferred sensitivity to growth factor deprivation-induced B cell apoptosis. Moreover, Bcl-w loss profoundly delayed MYC-mediated B cell lymphoma development due to increased MYC-induced B cell apoptosis. We also determined that MYC regulates BCL-W expression through its transcriptional regulation of specific miR. BCL-W expression was highly selected for in patient samples of Burkitt lymphoma (BL), with 88.5% expressing BCL-W. BCL-W knockdown in BL cell lines induced apoptosis, and its overexpression conferred resistance to BCL-2 family-targeting BH3 mimetics. Additionally, BCL-W was overexpressed in diffuse large B cell lymphoma and correlated with decreased patient survival. Collectively, our results reveal that BCL-W profoundly contributes to B cell lymphoma, and its expression could serve as a biomarker for diagnosis and aid in the development of better targeted therapies

Dark Matter searches using gravitational wave bar detectors: quark nuggets and newtorites

Many experiments have searched for supersymmetric WIMP dark matter, with null results. This may suggest to look for more exotic possibilities, for example compact ultra-dense quark nuggets, widely discussed in literature with several different names. Nuclearites are an example of candidate compact objects with atomic size cross section. After a short discussion on nuclearites, the result of a nuclearite search with the gravitational wave bar detectors Nautilus and Explorer is reported. The geometrical acceptance of the bar detectors is 19.5 $\rm m^2$ sr, that is smaller than that of other detectors used for similar searches. However, the detection mechanism is completely different and is more straightforward than in other detectors. The experimental limits we obtain are of interest because, for nuclearites of mass less than $10^{-5}$ g, we find a flux smaller than that one predicted considering nuclearites as dark matter candidates. Particles with gravitational only interactions (newtorites) are another example. In this case the sensitivity is quite poor and a short discussion is reported on possible improvements.Comment: published on Astroparticle Physics Sept 25th 2016 replaced fig 1

Relevance of initial and final conditions for the Fluctuation Relation in Markov processes

Numerical observations on a Markov chain and on the continuous Markov process performed by a granular tracer show that the ``usual'' fluctuation relation for a given observable is not verified for finite (but arbitrarily large) times. This suggests that some terms which are usually expected to be negligible, i.e. ``border terms'' dependent only on initial and final states, in fact cannot be neglected. Furthermore, the Markov chain and the granular tracer behave in a quite similar fashion.Comment: 23 pages, 5 figures, submitted to JSTA