The role of extracellular vesicles in bone metastasis

Multiple types of cancer have the specific ability to home to the bone microenvironment and cause metastatic lesions. Despite being the focus of intense investigation, the molecular and cellular mechanisms that regulate the metastasis of disseminated tumor cells still remain largely unknown. Bone metastases severely impact quality of life since they are associated with pain, fractures, and bone marrow aplasia. In this review, we will summarize the recent discoveries on the role of extracellular vesicles (EV) in the regulation of bone remodeling activity and bone metastasis occurrence. Indeed, it was shown that extracellular vesicles, including exosomes and microvesicles, released from tumor cells can modify the bone microenvironment, allowing the formation of osteolytic, osteosclerotic, and mixed mestastases. In turn, bone-derived EV can stimulate the proliferation of tumor cells. The inhibition of EV-mediated crosstalk between cancer and bone cells could represent a new therapeutic target for bone metastasis

The Probability Density of the Higgs Boson Mass

The LEP Collaborations have reported a small excess of events in their combined Higgs boson analysis at center of mass energies up to about 208 GeV. In this communication, I present the result of a calculation of the probability distribution function of the Higgs boson mass which can be rigorously obtained if the validity of the Standard Model is assumed. It arises from the combination of the most recent set of precision electroweak data and the current results of the Higgs searches at LEP 2.Comment: 3 pages, 2 figure

Gravity Dual for a Model of Perception

One of the salient features of human perception is its invariance under dilatation in addition to the Euclidean group, but its non-invariance under special conformal transformation. We investigate a holographic approach to the information processing in image discrimination with this feature. We claim that a strongly coupled analogue of the statistical model proposed by Bialek and Zee can be holographically realized in scale invariant but non-conformal Euclidean geometries. We identify the Bayesian probability distribution of our generalized Bialek-Zee model with the GKPW partition function of the dual gravitational system. We provide a concrete example of the geometric configuration based on a vector condensation model coupled with the Euclidean Einstein-Hilbert action. From the proposed geometry, we study sample correlation functions to compute the Bayesian probability distribution.Comment: 21 pages, v2: condition on conformal invariance of a free vector model correcte

Fitting Parton Distribution Data with Multiplicative Normalization Uncertainties

We consider the generic problem of performing a global fit to many independent data sets each with a different overall multiplicative normalization uncertainty. We show that the methods in common use to treat multiplicative uncertainties lead to systematic biases. We develop a method which is unbiased, based on a self--consistent iterative procedure. We demonstrate the use of this method by applying it to the determination of parton distribution functions with the NNPDF methodology, which uses a Monte Carlo method for uncertainty estimation.Comment: 33 pages, 5 figures: published versio

A case report of thyroid carcinoma confined to ovary and concurrently occult in the thyroid. Is conservative treatment always advised?

Introduction: Struma ovarii is an ovarian teratoma, represented in more than 50% by thyroid tissue. Five percent of struma ovarii cases have been proven to be malignant and, as in the thyroid gland, papillary thyroid carcinoma is the most common histotype arising in struma ovarii. Because of the unusual occurrence of this tumor, its management and follow-up after pelvic surgery is still controversial. Usually, total thyroidectomy followed by radioiodine treatment is the choice treatment in metastatic malignant struma ovarii, while these procedures are still controversial in non-metastatic thyroid cancer arising in struma ovarii. Case Presentation: We report a female with follicular variant of papillary thyroid carcinoma arising in struma ovarii. After pelvic surgery, thyroid morphofunctional examinations were performed and a single nodular lesion in the left lobe was discovered. The patient underwent total thyroidectomy and histological examination showed a papillary carcinoma. Radioiodine-ablation of residual thyroid tissue was performed and levothyroxine mildly-suppressive treatment was started. Conclusions: A more aggressive treatment should not be denied for malignant struma ovarii without any evidence, even when apparently confined into the ovary. However, in selected cases, aggressive treatment may be advisable to decrease the risk of recurrence and to allow an accurate follow-up

L’agency de Juliette Adam (1836-1936)

Grâce à ses rôles d’hôtesse de salon et de directrice de revue, et avec ses combats épiques pour la République et pour la Patrie, Juliette Adam a joué un rôle important dans la vie politique française de la seconde moitié du XIXe siècle. Elle a notamment contribué à la fabrication d’une nouvelle classe dirigeante et conditionné l’adoption de certains choix de politique étrangère. Dans cet article, nous reconstruisons le parcours de cette « femme politique » en focalisant notre attention sur sa capacité d’agir au sein de la vie politique française. Notre objectif est d’illustrer le processus à travers lequel cette capacité d’agir (agency) a été rendue possible et a pu se perpétuer dans le temps.Juliette Adam was a great figure in France during the second half of the nineteenth century. She held a famous literary salon and she edited a political review. She took part in the fight for the instauration of the Republic and, later, she contributed to the achievement of a diplomatic alliance between Russia and France. Through these roles, and within these fights, she succeeded in exercising her agency on French political life. This article describes the political route of this woman focalizing attention on her agency. Its purpose is to elucidate the process that lead to agency in this particular case and to give an illustration of it

Testing for rational speculative bubbles in the Brazilian residential real-estate market

Speculative bubbles have been occurring periodically in local or global real estate markets and are considered a potential cause of economic crises. In this context, the detection of explosive behaviors in the financial market and the implementation of early warning diagnosis tests are of critical importance. The recent increase in Brazilian housing prices has risen concerns that the Brazilian economy may have a speculative housing bubble. In the present paper, we employ a recently proposed recursive unit root test in order to identify possible speculative bubbles in data from the Brazilian residential real-estate market. The empirical results show evidence for speculative price bubbles both in Rio de Janeiro and Sao Paulo, the two main Brazilian cities

In Silico Tools to Extract the Drug Design Information Content of Degradation Data: The Case of PROTACs Targeting the Androgen Receptor

Proteolysis-Targeting Chimeras (PROTACs) have recently emerged as a promising technology in the drug discovery landscape. Large interest in the degradation of the androgen receptor (AR) as a new anti-prostatic cancer strategy has resulted in several papers focusing on PROTACs against AR. This study explores the potential of a few in silico tools to extract drug design information from AR degradation data in the format often reported in the literature. After setting up a dataset of 92 PROTACs with consistent AR degradation values, we employed the Bemis–Murcko method for their classification. The resulting clusters were not informative in terms of structure–degradation relationship. Subsequently, we performed Degradation Cliff analysis and identified some key aspects conferring a positive contribution to activity, as well as some methodological limits when applying this approach to PROTACs. Linker structure degradation relationships were also investigated. Then, we built and characterized ternary complexes to validate previous results. Finally, we implemented machine learning classification models and showed that AR degradation for VHL-based but not CRBN-based PROTACs can be predicted from simple permeability-related 2D molecular descriptors