First and second variation formulae for the sub-Riemannian area in three-dimensional pseudo-hermitian manifolds

We calculate the first and the second variation formula for the sub-Riemannian area in three dimensional pseudo-hermitian manifolds. We consider general variations that can move the singular set of a C^2 surface and non-singular variation for C_H^2 surfaces. These formulas enable us to construct a stability operator for non-singular C^2 surfaces and another one for C2 (eventually singular) surfaces. Then we can obtain a necessary condition for the stability of a non-singular surface in a pseudo-hermitian 3-manifold in term of the pseudo-hermitian torsion and the Webster scalar curvature. Finally we classify complete stable surfaces in the roto-traslation group RT .Comment: 36 pages. Misprints corrected. Statement of Proposition 9.8 slightly changed and Remark 9.9 adde

A reversible system based on hybrid toggle radius-4 cellular automata and its application as a block cipher

The dynamical system described herein uses a hybrid cellular automata (CA) mechanism to attain reversibility, and this approach is adapted to create a novel block cipher algorithm called HCA. CA are widely used for modeling complex systems and employ an inherently parallel model. Therefore, applications derived from CA have a tendency to fit very well in the current computational paradigm where scalability and multi-threading potential are quite desirable characteristics. HCA model has recently received a patent by the Brazilian agency INPI. Several evaluations and analyses performed on the model are presented here, such as theoretical discussions related to its reversibility and an analysis based on graph theory, which reduces HCA security to the well-known Hamiltonian cycle problem that belongs to the NP-complete class. Finally, the cryptographic robustness of HCA is empirically evaluated through several tests, including avalanche property compliance and the NIST randomness suite.Comment: 34 pages, 12 figure

pH Switchable Water Dispersed Photocatalytic Nanoparticles

Photogeneration of Reactive Oxygen Species (ROS) finds applications in fields as different as nanomedicine, art preservation, air and water depollution and surface decontamination. Here we present photocatalytic nanoparticles (NP) that are active only at acidic pH while they do not show relevant ROS photo-generation at neutral pH. This dual responsivity (to light and pH) is achieved by stabilizing the surface of TiO2 NP with a specific organic shell during the synthesis and it is peculiar of the achieved core shell-structure, as demonstrated by comparison with commercial photocatalytic TiO2 NP. For the investigation of the photocatalytic activity, we developed two methods that allow real time detection of the process preventing any kind of artifact arising from post-treatments and delayed analysis. The reversibility of the pH response was also demonstrated as well as the selective photo-killing of cancer cells at acidic pH

Baseline serum TSH levels predict the absence of thyroid dysfunction in cancer patients treated with immunotherapy

Purpose Immunotherapy against immune checkpoints has significantly improved survival both in metastatic and adjuvant setting in several types of cancers. Thyroid dysfunction is the most common endocrine adverse event reported. Patients who are at risk of developing thyroid dysfunction remain to be defined. We aimed to identify predictive factors for the develop- ment of thyroid dysfunction during immunotherapy. Methods This is a retrospective study including a total of 68 patients who were treated with immune checkpoint inhibi- tors (ICIs) for metastatic or unresectable advanced cancers. The majority of patients were treated with anti-PD1 drugs in monotherapy or in combination with anti-CTLA4 inhibitors. Thyroid function and anti-thyroid antibodies, before starting immunotherapy and during treatment, were evaluated. Thyroid ultrasound was also performed in a subgroup of patients at the time of enrolment in the study. Results Eleven out of 68 patients (16.1%) developed immune-related overt thyroid dysfunction. By ROC curve analysis, we found that a serum TSH cut-off of 1.72 mUI/l, at baseline, had a good diagnostic accuracy in identifying patients without overt thyroid dysfunction (NPV = 100%, p = 0.0029). At multivariate analysis, both TSH and positive anti-thyroid antibod- ies (ATAbs) levels, before ICIs treatment, were independently associated with the development of overt thyroid dysfunction during immunotherapy (p = 0.0001 and p = 0.009, respectively). Conclusions Pre-treatment serum TSH and ATAbs levels may help to identify patients at high risk for primary thyroid dysfunction. Our study suggests guidance for an appropriate timely screening and for a tailored management of thyroid dysfunctions in patients treated with ICIs

Clinical experience with ipilimumab 10 mg/kg in patients with melanoma treated at Italian centres as part of a European expanded access programme

Background: Patients with advanced melanoma are faced with a poor prognosis and, until recently, limited treatment options. Ipilimumab, a novel immunotherapy that blocks cytotoxic T-lymphocyte-associated antigen-4, was the first agent to improve survival of patients with advanced melanoma in a randomised, controlled phase 3 trial. We used data from an expanded access programme (EAP) at Italian centres to evaluate the clinical activity and safety profile of ipilimumab 10 mg/kg in patients with advanced melanoma in a setting more similar to that of daily practice. Methods. Data were collected from patients enrolled in an ipilimumab EAP across eight participating Italian centres. As per the EAP protocol, patients had life-threatening, unresectable stage III/IV melanoma, had failed or did not tolerate previous treatments and had no other therapeutic option available. Treatment comprised ipilimumab 10 mg/kg every 3 weeks for a total of four doses. If physicians believed patients would continue to derive benefit from ipilimumab treatment, maintenance therapy with ipilimumab 10 mg/kg was provided every 12 weeks. Tumour responses were assessed every 12 weeks using modified World Health Organization criteria and safety continuously monitored. Results: Seventy-four pretreated patients with advanced melanoma were treated with ipilimumab 10 mg/kg. Of these, 9 (13.0%) had an objective response, comprising 3 patients with a complete response and 6 with a partial response. Median overall survival was 7.0 months (95% confidence interval, 5.3-8.7) and 16.6% of patients were alive after 3 years. Forty-five patients (60.8%) reported treatment-related adverse events of any grade, which were most commonly low-grade pruritus, pain, fever and diarrhoea. Grade 3 or 4 treatment-related AEs were reported in 8 patients (10.8%). Conclusions: The clinical activity and safety profile of ipilimumab 10 mg/kg in the EAP was similar to that seen in previous clinical trials of ipilimumab in pretreated patient populations. © 2013 Altomonte et al.; licensee BioMed Central Ltd

Modifications of the Fine Structure of the Incisor Pulp of the Guinea Pig during Fxperimental Scurvy

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68076/2/10.1177_00220345660450030301.pd

Local behavior of p-harmonic Green's functions in metric spaces

We describe the behavior of p-harmonic Green's functions near a singularity in metric measure spaces equipped with a doubling measure and supporting a Poincar\'e inequality

Almost exponential maps and integrability results for a class of horizontally regular vector fields

We show a higher order integrability theorem for distributions generated by a family of vector fields under a horizontal regularity assumption on their coefficients. We use as chart a class of almost exponential maps which we discuss in detailsComment: arXiv admin note: material from arXiv:1106.2410v1, now three separate articles arXiv:1106.2410v2, arXiv:1201.5228, arXiv:1201.520