Doxycycline, an inhibitor of mitochondrial biogenesis, effectively reduces cancer stem cells (CSCs) in early breast cancer patients : a clinical pilot study

Background and objectives: Cancer stem cells (CSCs) have been implicated in tumor initiation, recurrence, metastatic spread and poor survival in multiple tumor types, breast cancers included. CSCs selectively overexpress key mitochondrial-related proteins and inhibition of mitochondrial function may represent a new potential approach for the eradication of CSCs. Because mitochondria evolved from bacteria, many classes of FDA-approved antibiotics, including doxycycline, actually target mitochondria. Our study aimed to determine whether short-term pre-operative treatment with oral doxycycline results in reduction of CSCs in early breast cancer patients. Methods: Doxycycline was administered orally for 14 days before surgery for a daily dose of 200 mg. Immuno-histochemical analysis of formalin-fixed paraffin-embedded (FFPE) samples from 15 patients, of which 9 were treated with doxycycline and 6 controls (no treatment), was performed with known biomarkers of “stemness” (CD44, ALDH1), mitochondrial mass (TOMM20), cell proliferation (Ki67, p27), apoptosis (cleaved caspase-3) and neo-angiogenesis (CD31). For each patient, the analysis was performed both on pre-operative specimens (core-biopsies) and surgical specimens. Changes from baseline to post-treatment were assessed with MedCalc 12 (unpaired t-test). Results: Post-doxycycline tumor samples demonstrated a statistically significant decrease in the stemness marker CD44 (p-value < 0.005), when compared to pre-doxycycline tumor samples. More specifically, CD44 levels were reduced between 17.65% and 66.67%, in 8 out of 9 patients treated with doxycycline. In contrast, only one patient showed a rise in CD44, by 15%. Overall, this represents a positive response rate of nearly 90%. Similar results were also obtained with ALDH1, another marker of stemness. In contrast, markers of mitochondrial mass, proliferation, apoptosis and neo-angiogenesis, were all similar between the two groups. Conclusions: Quantitative decreases in CD44 and ALDH1 expression are consistent with pre-clinical experiments and suggest that doxycycline can selectively eradicate CSCs in breast cancer patients in vivo. Future studies (with larger numbers of patients) will be conducted to validate these promising pilot studies

Identifying relationship patterns inside communities

Community detection is an important problem for Computer and other sciences. Following Agarwal and Kempe one of the most important reasons to make clustering over a network is to identify the function/role of each element in a community. If the communities have hundreds or thousands of elements, it is important to understand the functions of internal elements, but that will require an automatic process. In this context, we propose to develop a model, capable to identify elements with common features in different communities, based on the connection between elements and communities, agreeing with Newman and Girvan model features. (Párrafo extraído del texto a modo de resumen)Sociedad Argentina de Informática e Investigación Operativa (SADIO

Diffusion and wave behaviour in linear Voigt model

A boundary value problem related to a third- order parabolic equation with a small parameter is analized. This equation models the one-dimensional evolution of many dissipative media as viscoelastic fluids or solids, viscous gases, superconducting materials, incompressible and electrically conducting fluids. Moreover, the third-order parabolic operator regularizes various non linear second order wave equations. In this paper, the hyperbolic and parabolic behaviour of the solution is estimated by means of slow time and fast time. As consequence, a rigorous asymptotic approximation for the solution is established

A systematically coarse-grained model for DNA, and its predictions for persistence length, stacking, twist, and chirality

We introduce a coarse-grained model of DNA with bases modeled as rigid-body ellipsoids to capture their anisotropic stereochemistry. Interaction potentials are all physicochemical and generated from all-atom simulation/parameterization with minimal phenomenology. Persistence length, degree of stacking, and twist are studied by molecular dynamics simulation as functions of temperature, salt concentration, sequence, interaction potential strength, and local position along the chain, for both single- and double-stranded DNA where appropriate. The model of DNA shows several phase transitions and crossover regimes in addition to dehybridization, including unstacking, untwisting, and collapse which affect mechanical properties such as rigidity and persistence length. The model also exhibits chirality with a stable right-handed and metastable left-handed helix.Comment: 30 pages, 20 figures, Supplementary Material available at http://www.physics.ubc.ca/~steve/publications.htm

From attosecond to zeptosecond coherent control of free-electron wave functions using semi-infinite light fields

Light-electron interaction in empty space is the seminal ingredient for free-electron lasers and also for controlling electron beams to dynamically investigate materials and molecules. Pushing the coherent control of free electrons by light to unexplored timescales, below the attosecond, would enable unprecedented applications in light-assisted electron quantum circuits and diagnostics at extremely small timescales, such as those governing intramolecular electronic motion and nuclear phenomena. We experimentally demonstrate attosecond coherent manipulation of the electron wave function in a transmission electron microscope, and show that it can be pushed down to the zeptosecond regime with existing technology. We make a relativistic pulsed electron beam interact in free space with an appropriately synthesized semi-infinite light field generated by two femtosecond laser pulses reflected at the surface of a mirror and delayed by fractions of the optical cycle. The amplitude and phase of the resulting coherent oscillations of the electron states in energymomentum space are mapped via momentum-resolved ultrafast electron energy-loss spectroscopy. The experimental results are in full agreement with our theoretical framework for light-electron interaction, which predicts access to the zeptosecond timescale by combining semi-infinite X-ray fields with free electrons.Comment: 22 pages, 6 figure

The complete catalogue of gamma-ray bursts observed by the Wide Field Cameras on board BeppoSAX

We present the complete on-line catalogue of gamma-ray bursts observed by the two Wide Field Cameras on board \sax in the period 1996-2002. Our aim is to provide the community with the largest published data set of GRB's prompt emission X-ray light curves and other useful data. This catalogue (BS-GRBWFCcat) contains data on 77 bursts and a collection of the X-ray light curves of 56 GRB discovered or noticed shortly after the event and of other additional bursts detected in subsequent searches. Light curves are given in the three X-ray energy bands (2-5, 5-10, 10-26 keV). The catalogue can be accessed from the home web page of the ASI Science Data Center-ASDC (http://www.asdc.asi.it)Comment: 4 pages, 3 figure

Entropy Production in a Persistent Random Walk

We consider a one-dimensional persisent random walk viewed as a deterministic process with a form of time reversal symmetry. Particle reservoirs placed at both ends of the system induce a density current which drives the system out of equilibrium. The phase space distribution is singular in the stationary state and has a cumulative form expressed in terms of generalized Takagi functions. The entropy production rate is computed using the coarse-graining formalism of Gaspard, Gilbert and Dorfman. In the continuum limit, we show that the value of the entropy production rate is independent of the coarse-graining and agrees with the phenomenological entropy production rate of irreversible thermodynamics.Comment: 21 pages, 8 figures, to appear in Physica