Dietary alterations modulate the microRNA 29/30 and IGF-1/AKT signaling axis in breast Cancer liver metastasis.

Background: Metastatic cancer is incurable and understanding the molecular underpinnings is crucial to improving survival for our patients. The IGF-1/Akt signaling pathway is often impaired in cancer leading to its progression and metastases. Diet modification is known to alter the IGF-1/Akt pathway and affect the expression of microRNA involved in tumor initiation, growth and metastases. Liver metastases are one of the most common type of metastases in breast and colon cancer. In the present study, we looked at the effect of diet modification on the expression of microRNA in normal liver and liver with breast cancer metastases using in vivo model. Methodology: 6-month-old C57BL/6 J mice were put on either an ad libitum (AL) diet, or 40% calorie restricted (CR) diet or were fasted for 24 h (FA) before sacrifice. MicroRNA array analysis, western blot and qRT-PCR were performed using liver tissue to compare the treatment groups. A breast cancer model was also used to study the changes in microRNA expression in liver of a group of BALB/c mice orthotopically injected with 4 T1 cells in the mammary fat pad, put on either an AL or 30% CR diet. Liver and primary tumor tissues were used to perform qRT-PCR to compare the treatment groups. Results: MicroRNA array analysis showed significant changes in miRNA expression in both CR and FA conditions in normal liver. Expression of miR-29 and miR-30 family members was increased in both CR and FA. Western blot analysis of the normal liver tissue showed that CR and FA downregulated the IGF-1/Akt pathway and qRT-PCR showed that the expression of miR-29b, miR-29c, miR-30a and miR-30b were increased with CR and FA. Liver tissue collected from mice in the breast cancer model showed an increase in expression of miR-29b, miR-29c and miR-30b while tumor tissue showed increased expression of miR-29c, miR-30a and miR-30b. Discussion: Members of the miR-29 family are known to target and suppress IGF-1, while members of the miR-30 family are known to target and suppress both IGF-1 and IGF-1R. In the present study, we observe that calorie restriction increased the expression of miR-29 and miR-30 in both the normal liver as well as the liver with breast cancer metastases. These findings suggest that dietary alterations may play a role in the treatment of liver metastasis, which should be evaluated further

Head-on collision of compact objects in general relativity: comparison of post-newtonian and perturbation approaches

The gravitational-wave energy flux produced during the head-on infall and collision of two compact objects is calculated using two approaches: (i) a post-Newtonian method, carried to second post-Newtonian order beyond the quadrupole formula, valid for systems of arbitrary masses; and (ii) a black-hole perturbation method, valid for a test-body falling radially toward a black hole. In the test-body case, the methods are compared. The post-Newtonian method is shown to converge to the ``exact'' perturbation result more slowly than expected {\it a priori\/}. A surprisingly good approximation to the energy radiated during the infall phase, as calculated by perturbation theory, is found to be given by a Newtonian, or quadrupole, approximation combined with the exact test-body equations of motion in the Schwarzschild spacetime

The Lone Wolf Amendment and the Future of Foreign Intelligence Surveillance Law

In December 2004, Congress adopted an important change to the statutory framework authorizing domestic surveillance of foreign powers and their agents, the Foreign Intelligence Surveillance Act (FISA). The change, directly prompted by the events of September 11, 2001, makes it easier for the government to conduct surveillance of so-called lone wolf terrorists - that is, terrorists who act in sympathy with the aims of an international terrorist group but not on its behalf, or terrorists whose link to an international terrorist group cannot be demonstrated. Although the logic of the lone wolf amendment at first seems quite compelling, the amendment offers a fascinating lens through which to examine the current state of foreign intelligence surveillance law and highlights some of the critical questions facing Congress as the December 31, 2005, sunset date for many of the post-9/11 changes to surveillance law (including the lone wolf amendment itself) approaches. As a substantive matter, the lone wolf change goes to the heart of the constitutional issues that the foreign intelligence surveillance framework presents. More important, the lone wolf amendment underscores the critical need for Congress to rethink not only FISA\u27s scope and substantive standards, but also its information structure - the institutional mechanisms designed to generate the information necessary for evaluation of how FISA is being implemented. This Article argues that maintaining a well-functioning - and publicly acceptable - framework for foreign intelligence gathering in the United States requires a careful focus on the framework\u27s information structure. At the time of FISA\u27s passage, Congress recognized that fact. As the foreign intelligence surveillance framework has shifted and expanded over nearly three decades, however, Congress\u27s attention to FISA\u27s information structure has been haphazard and episodic. This Article presents specific reforms to FISA\u27s information structure that Congress should consider as the sunset date approaches

The e+ e- -> P1 P2 gamma processes close to the Phi peak: toward a model-independent analysis

We discuss the general decomposition and possible general parameterizations of the processes $e^+ e^- \to \gamma^* \to P_1 P_2 \gamma$, where $P_1 P_2=\pi^0 \pi^0$, $\pi^0\eta$, or $\pi^+\pi^-$, for $\sqrt{s}\approx M_\Phi$. Particular attention is devoted to the amplitude where the two pseudoscalar mesons are in a $J^{CP}= 0^{++}$ state, where we propose a general parameterization which should help to shed light on the nature of light scalar mesons.Comment: 12 pages, Late

Gravitational waves from binary systems in circular orbits: Convergence of a dressed multipole truncation

The gravitational radiation originating from a compact binary system in circular orbit is usually expressed as an infinite sum over radiative multipole moments. In a slow-motion approximation, each multipole moment is then expressed as a post-Newtonian expansion in powers of v/c, the ratio of the orbital velocity to the speed of light. The bare multipole truncation of the radiation consists in keeping only the leading-order term in the post-Newtonian expansion of each moment, but summing over all the multipole moments. In the case of binary systems with small mass ratios, the bare multipole series was shown in a previous paper to converge for all values v/c < 2/e, where e is the base of natural logarithms. In this paper, we extend the analysis to a dressed multipole truncation of the radiation, in which the leading-order moments are corrected with terms of relative order (v/c)^2 and (v/c)^3. We find that the dressed multipole series converges also for all values v/c < 2/e, and that it coincides (within 1%) with the numerically ``exact'' results for v/c < 0.2.Comment: 9 pages, ReVTeX, 1 postscript figur

Expert-Augmented Machine Learning

Machine Learning is proving invaluable across disciplines. However, its success is often limited by the quality and quantity of available data, while its adoption by the level of trust that models afford users. Human vs. machine performance is commonly compared empirically to decide whether a certain task should be performed by a computer or an expert. In reality, the optimal learning strategy may involve combining the complementary strengths of man and machine. Here we present Expert-Augmented Machine Learning (EAML), an automated method that guides the extraction of expert knowledge and its integration into machine-learned models. We use a large dataset of intensive care patient data to predict mortality and show that we can extract expert knowledge using an online platform, help reveal hidden confounders, improve generalizability on a different population and learn using less data. EAML presents a novel framework for high performance and dependable machine learning in critical applications

Theory of continuum percolation II. Mean field theory

I use a previously introduced mapping between the continuum percolation model and the Potts fluid to derive a mean field theory of continuum percolation systems. This is done by introducing a new variational principle, the basis of which has to be taken, for now, as heuristic. The critical exponents obtained are $\beta= 1$, $\gamma= 1$ and $\nu = 0.5$, which are identical with the mean field exponents of lattice percolation. The critical density in this approximation is \rho_c = 1/\ve where \ve = \int d \x \, p(\x) \{ \exp [- v(\x)/kT] - 1 \}. p(\x) is the binding probability of two particles separated by \x and v(\x) is their interaction potential.Comment: 25 pages, Late

Ophthalmic manifestations of cat scratch disease

Cat scratch disease (CSD) is a worldwide distributed zoonosis caused by Bartonella henselae and other Bartonella spp. The reservoirs of Bartonella are domestic animals, especially cats, and the transmission to humans is thought to occur from a cat scratch or even through the cat flea Ctenocephalides felix. With more and more pet owners, the physicians should keep in mind signs and symptoms of CSD. A widespread infection may occur in 5-14% of cases, and ocular involvement, called ocular bartonellosis, is a quite common consequence of disseminated CSD. Although the most typical manifestations of ocular Bartonellosis are Parinaud's oculoglandular syndrome, neuroretinitis and retinochoroiditis, many other ophthalmic conditions have been reported. The diagnosis of CSD is often based on history of contact with a cat and high serum titers of immunoglobulin G antibodies against B. henselae. Polymerase chain reaction could be helpful for CSD diagnosis when serology is negative but clinical findings are suggestive for the disease. Multimodal imaging, including fundus autofluorescence, fluorescein and indocyanine green angiography, optical coherence tomography (OCT) and OCT angiography, can be used for diagnosis and monitoring of ocular Bartonellosis. Since CSD is more often a self-limited infection in immunocompetent individuals, no antibiotic treatment is usually needed. However, when a therapy is prescribed, doxycycline is the most used antibiotic. The aim of this article is to review the current literature relating to epidemiology, systemic and ocular manifestations, diagnosis, treatment and prognosis of bartonellosis, in order to give the ophthalmologists a useful tool for daily practice