160 research outputs found
Radial-orbit instability in modified Newtonian dynamics
The stability of radially anisotropic spherical stellar systems in modified
Newtonian dynamics (MOND) is explored by means of numerical simulations
performed with the N-body code N-MODY. We find that Osipkov-Merritt MOND models
require for stability larger minimum anisotropy radius than equivalent
Newtonian systems (ENSs) with dark matter, and also than purely baryonic
Newtonian models with the same density profile. The maximum value for stability
of the Fridman-Polyachenko-Shukhman parameter in MOND models is lower than in
ENSs, but higher than in Newtonian models with no dark matter. We conclude that
MOND systems are substantially more prone to radial-orbit instability than ENSs
with dark matter, while they are able to support a larger amount of kinetic
energy stored in radial orbits than purely baryonic Newtonian systems. An
explanation of these results is attempted, and their relevance to the MOND
interpretation of the observed kinematics of globular clusters, dwarf
spheroidal and elliptical galaxies is briefly discussed.Comment: 9 pages, 4 figures, accepted for publication in MNRA
The research on the immuno-modulatory defect of Mesenchymal Stem Cell from Chronic Myeloid Leukemia patients
Overwhelming evidence from leukemia research has shown that the clonal population of neoplastic cells exhibits marked heterogeneity with respect to proliferation and differentiation. There are rare stem cells within the leukemic population that possess extensive proliferation and self-renewal capacity not found in the majority of the leukemic cells. These leukemic stem cells are necessary and sufficient to maintain the leukemia. While the hematopoietic stem cell (HSC) origin of CML was first suggested over 30 years ago, recently CML-initiating cells beyond HSCs are also being investigated. We have previously isolated fetal liver kinase-1-positive (Flk1+) cells carrying the BCR/ABL fusion gene from the bone marrow of Philadelphia chromosome-positive (Ph+) patients with hemangioblast property. Here, we showed that CML patient-derived Flk1+CD31-CD34-MSCs had normal morphology, phenotype and karyotype but appeared impaired in immuno-modulatory function. The capacity of patient Flk1+CD31-CD34- MSCs to inhibit T lymphocyte activation and proliferation was impaired in vitro. CML patient-derived MSCs have impaired immuno-modulatory functions, suggesting that the dysregulation of hematopoiesis and immune response may originate from MSCs rather than HSCs. MSCs might be a potential target for developing efficacious cures for CML
Reduced Apaf-1 expression in human cutaneous melanomas
Malignant melanoma is a life-threatening skin cancer due to its highly metastatic character and resistance to radio- and chemotherapy. It is believed that the ability to evade apoptosis is the key mechanism for the rapid growth of cancer cells. However, the exact mechanism for failure in the apoptotic pathway in melanoma cells is unclear. p53, the most frequently mutated tumour suppressor gene in human cancers, is a key apoptosis inducer. However, p53 mutation is only found in 15–20% of melanoma biopsies. Recently, it was found that Apaf-1, a downstream target of p53, is inactivated in metastatic melanoma. Specifically, loss of heterozygosity (LOH) of the Apaf-1 gene was found in 40% of metastatic melanoma. To determine if loss of Apaf-1 expression is indeed involved in melanoma progression, we employed the tissue microarray technology and examined Apaf-1 expression in 70 human primary malignant melanoma biopsies by immunohistochemistry. Our data showed that Apaf-1 expression is significantly reduced in melanoma cells compared with normal nevi (χ2=6.02, P=0.014). Our results also revealed that loss of Apaf-1 was not associated with the tumour thickness, ulceration or subtype, patient's gender, age and 5-year survival. In addition, our in vitro apoptosis assay revealed that overexpression of Apaf-1 can sensitise melanoma cells to anticancer drug treatment. Taken together, our data indicate that Apaf-1 expression is significantly reduced in human melanoma and that Apaf-1 may serve as a therapeutic target in melanoma
Tumour-draining axillary lymph nodes in patients with large and locally advanced breast cancers undergoing neoadjuvant chemotherapy (NAC): the crucial contribution of immune cells (effector, regulatory) and cytokines (TH1, TH2) to immune-mediated tumour cell death induced by NAC
Background
The tumour microenvironment consists of malignant cells, stroma and immune cells. In women with large and locally advanced breast cancers (LLABCs) undergoing neoadjuvant chemotherapy (NAC), tumour-infiltrating lymphocytes (TILs), various subsets (effector, regulatory) and cytokines in the primary tumour play a key role in the induction of tumour cell death and a pathological complete response (pCR) with NAC. Their contribution to a pCR in nodal metastases, however, is poorly studied and was investigated.
Methods
Axillary lymph nodes (ALNs) (24 with and 9 without metastases) from women with LLABCs undergoing NAC were immunohistochemically assessed for TILs, T effector and regulatory cell subsets, NK cells and cytokine expression using labelled antibodies, employing established semi-quantitative methods. IBM SPSS statistical package (21v) was used. Non-parametric (paired and unpaired) statistical analyses were performed. Univariate and multivariate regression analyses were carried out to establish the prediction of a pCR and Spearman’s Correlation Coefficient was used to determine the correlation of immune cell infiltrates in ALN metastatic and primary breast tumours.
Results
In ALN metastases high levels of TILs, CD4+ and CD8+ T and CD56+ NK cells were significantly associated with pCRs.. Significantly higher levels of Tregs (FOXP3+, CTLA-4+) and CD56+ NK cells were documented in ALN metastases than in the corresponding primary breast tumours. CD8+ T and CD56+ NK cells showed a positive correlation between metastatic and primary tumours. A high % CD8+ and low % FOXP3+ T cells and high CD8+: FOXP3+ ratio in metastatic ALNs (tumour-free para-cortex) were associated with pCRs. Metastatic ALNs expressed high IL-10, low IL-2 and IFN-ϒ.
Conclusions
Our study has provided new data characterising the possible contribution of T effector and regulatory cells and NK cells and T helper1 and 2 cytokines to tumour cell death associated with NAC in ALNs
Analogue Transformations in Physics and their Application to Acoustics
Transformation optics has shaped up a revolutionary electromagnetic design paradigm, enabling scientists
to build astonishing devices such as invisibility cloaks. Unfortunately, the application of transformation
techniques to other branches of physics is often constrained by the structure of the field equations. We
develop here a complete transformation method using the idea of analogue spacetimes. The method is
general and could be considered as a new paradigm for controlling waves in different branches of physics, from acoustics in quantum fluids to graphene electronics. As an application, we derive an analogue transformation acoustics formalism that naturally allows the use of transformations mixing space and time or involving moving fluids, both of which were impossible with the standard approach. To demonstrate the power of our method, we give explicit designs of a dynamic compressor, a spacetime cloak for acoustic waves and a carpet cloak for a moving aircraft.This work was developed under the framework of the ARIADNA contract 4000104572/11/NL/KML of the European Space Agency. A. M. and J. S.-D. also acknowledge support from Consolider EMET project (CSD2008-00066), A. M. from project TEC2011-28664-C02-02, J.S.-D. from US Office of Naval Research, and C. B. and G. J. from the project FIS2008-06078-C03-01. We thank Reme Miralles for her help with Fig. 2.García Meca, C.; Carloni, S.; Barcelo, C.; Jannes, G.; Sánchez-Dehesa Moreno-Cid, J.; Martínez Abietar, AJ. (2013). Analogue Transformations in Physics and their Application to Acoustics. Scientific Reports. 3(2009):1-5. https://doi.org/10.1038/srep02009S1532009Pendry, J. B., Schurig, D. & Smith, D. R. Controlling electromagnetic fields. Science 312, 1780–1782 (2006).Leonhardt, U. Optical conformal mapping. Science 312, 1777–1780 (2006).Schurig, D. et al. Metamaterial Electromagnetic Cloak at Microwave Frequencies. Science 314, 977–980 (2006).Shalaev, V. M. Transforming Light. Science 322, 384–386 (2008).Greenleaf, A., Kurylev, Y., Lassas, M. & Uhlmann, G. Invisibility and inverse problems. B. Am. Math. Soc. 46, 55–97 (2009).Genov, D. A., Zhang, S. & Zhang, X. Mimicking celestial mechanics in metamaterials. Nat. Phys. 5, 687–692 (2009).Chen, H., Chan, C. T. & Sheng, P. Transformation optics and metamaterials. Nat. Mater. 9, 387–396 (2010).Leonhardt, U. & Philbin, T. Geometry and light. The science of invisibility (Dover Publications, 2010).Pendry, J. B., Aubry, A., Smith, D. R. & Maier, S. A. Transformation Optics and Subwavelength Control of Light. Science 337, 549 (2012).Post, E. G. Formal Structure of Electromagnetics: General Covariance and Electromagnetics (Interscience Publishers, New York, 1962).Cummer, S. A. & Schurig, D. One path to acoustic cloaking. New J. Phys. 9, 45 (2007).Chen, H. & Chan, C. T. Acoustic cloaking in three dimensions using acoustic metamaterials. Appl. Phys. Lett. 91, 183518 (2007).Norris, A. N. Acoustic metafluids. J. Acoust. Soc. Am. 125, 839 (2009).Chen, H. & Chan, C. T. Acoustic cloaking and transformation acoustics. J. Phys. D: Appl. Phys. 43, 113001 (2010).Zhang, S., Genov, D. A., Sun, C. & Zhang, X. Cloaking of Matter Waves. Phys. Rev. Lett. 100, 123002 (2008).McCall, M. W., Favaro, A., Kinsler, P. & Boardman, A. A spacetime cloak, or a history editor. J. Opt. 13, 024003 (2011).Fridman, M., Farsi, A., Okawachi, Y. & Gaeta, A. L. Demonstration of temporal cloaking. Nature 481, 62–65 (2012).Cummer, S. A. & Thompson, R. T. Frequency conversion by exploiting time in transformation optics. J. Opt. 13, 024007 (2011).Barceló, C., Liberati, S. & Visser, M. Analogue Gravity. Living Rev. Relativity 14, 3 (2011).Visser, M. Acoustic black holes: Horizons, ergospheres and Hawking radiation. Class. Quant. Grav. 15, 1767 (1998).Barceló, C. & Jannes, G. A Real Lorentz-FitzGerald contraction. Found. Phys. 38, 191 (2008).Bergmann, P. G. The Wave Equation in a Medium with a Variable Index of Refraction. J. Acoust. Soc. Am. 17, 329 (1946).Torrent, D., Håkansson, A., Cervera, F. & Sánchez-Dehesa, J. Homogenization of two-dimensional clusters of rigid rods in air. Phys. Rev. Lett. 96, 204302 (2006).Torrent, D. & Sánchez-Dehesa, J. Effective parameters of clusters of cylinders embedded in a nonviscous fluid or gas. Phys. Rev. B 74, 224305 (2006).Unruh, W. G. Experimental black hole evaporation? Phys. Rev. Lett. 46, 1351 (1981).Li, J. & Pendry, J. B. Hiding under the Carpet: A New Strategy for Cloaking. Phys. Rev. Lett. 101, 203901 (2008).Popa, B. I., Zigoneanu, L. & Cummer, S. A. Experimental acoustic ground cloak in air. Phys. Rev. Lett. 106, 253901 (2011).Garay, L. J., Anglin, J. R., Cirac, J. I. & Zoller, P. Black holes in Bose-Einstein condensates. Phys. Rev. Lett. 85, 4643 (2000).Lahav, O., Itah, A., Blumkin, A., Gordon, C. & Steinhauer, J. Realization of a sonic black hole analogue in a Bose-Einstein condensate. Phys. Rev. Lett. 105, 240401 (2010).Castro Neto, A. H., Guinea, F., Peres, N. M. R., Novoselov, K. S. & Geim, A. K. The electronic properties of graphene. Rev. Mod. Phys. 81, 109 (2009).Cortijo, A. & Vozmediano, M. A. H. Electronic properties of curved graphene sheets. Europhys. Lett. 77, 47002 (2007).Vakil, A. & Engheta, N. Transformation optics using graphene. Science 332, 1291 (2011)
Pseudoneoplastic lesions of the testis and paratesticular structures
Pseudotumors or tumor-like proliferations (non-neoplastic masses) and benign mimickers (non-neoplastic cellular proliferations) are rare in the testis and paratesticular structures. Clinically, these lesions (cysts, ectopic tissues, and vascular, inflammatory, or hyperplastic lesions) are of great interest for the reason that, because of the topography, they may be relevant as differential diagnoses. The purpose of this paper is to present an overview of the pseudoneoplasic entities arising in the testis and paratesticular structures; emphasis is placed on how the practicing pathologist may distinguish benign mimickers and pseudotumors from true neoplasia. These lesions can be classified as macroscopic or microscopic mimickers of neoplasia
Emerging concepts in biomarker discovery; The US-Japan workshop on immunological molecular markers in oncology
Supported by the Office of International Affairs, National Cancer Institute (NCI), the "US-Japan Workshop on Immunological Biomarkers in Oncology" was held in March 2009. The workshop was related to a task force launched by the International Society for the Biological Therapy of Cancer (iSBTc) and the United States Food and Drug Administration (FDA) to identify strategies for biomarker discovery and validation in the field of biotherapy. The effort will culminate on October 28th 2009 in the "iSBTc-FDA-NCI Workshop on Prognostic and Predictive Immunologic Biomarkers in Cancer", which will be held in Washington DC in association with the Annual Meeting. The purposes of the US-Japan workshop were a) to discuss novel approaches to enhance the discovery of predictive and/or prognostic markers in cancer immunotherapy; b) to define the state of the science in biomarker discovery and validation. The participation of Japanese and US scientists provided the opportunity to identify shared or discordant themes across the distinct immune genetic background and the diverse prevalence of disease between the two Nations
- …