A laplace type problem for three lattices with non-convex cell

In this paper we consider three lattices with cells represented in Fig. 1, 3 and 5 and we determine the probability that a random segment of constant length intersects a side of lattic

Optimality Conditions for Nondifferentiable Multiobjective Semi-Infinite Programming Problems

We have considered a multiobjective semi-infinite programming problem with a feasible set defined by inequality constraints. First we studied a Fritz-John type necessary condition. Then, we introduced two constraint qualifications and derive the weak and strong Karush-Kuhn-Tucker (KKT in brief) types necessary conditions for an efficient solution of the considered problem. Finally an extension of a Caristi-Ferrara-Stefanescu result for the (Φ,ρ)-invexity is proved, and some sufficient conditions are presented under this weak assumption. All results are given in terms of Clark subdifferential

The Risk of Toxicities from Trastuzumab, Alone or in Combination, in an Elderly Breast Cancer Population

Abstract Background: Breast cancer in the elderly is associated with high recurrence and death rates, due mostly to undertreatment. Human epidermal growth factor receptor type 2 (HER2) overexpression is infrequent in older patients. Trastuzumab- based chemotherapy is often withheld from elderly patients because of its cardiotoxicity. Patients and Methods: Medical records of consecutive HER2-positive breast cancer patients aged 65 70 years old treated between 2005 and 2010 in the participating centers were retrospectively reviewed. All patients underwent multidimensional geriatric assessment (MGA). Results: Among 59 patients identified, 51 patients were evaluable (median age 76 years). The rate of any adverse event was 20% (10/51). The most relevant cardiac adverse event consisted of symptomatic congestive heart failure (CHF; n = 1, 2%) followed by asymptomatic decreases of left ventricular ejection fraction (LVEF; n = 6, 12%). Other toxicities included moderate hypersensitivity reactions during trastuzumab infusions (n = 3, 6%). Hypertension, obesity, prior anthracyclines exposure and concurrent chemotherapy were associated with a higher incidence of toxic events. Previous radiotherapy, concurrent endocrine therapy and different trastuzumab-based regimens did not seem to influence toxicity. Conclusions: Our data suggest that trastuzumab has a good safety profile in nonfrail women aged 70 years and older. These favorable findings may be related to a limited number of anthracycline pretreatments, patient selection and a close cardiologic monitoring

Polymerogenic neuroserpin causes mitochondrial alterations and activates NFκB but not the UPR in a neuronal model of neurodegeneration FENIB

The neurodegenerative condition FENIB (familiar encephalopathy with neuroserpin inclusion bodies) is caused by heterozygous expression of polymerogenic mutant neuroserpin (NS), with polymer deposition within the endoplasmic reticulum (ER) of neurons. We generated transgenic neural progenitor cells (NPCs) from mouse fetal cerebral cortex stably expressing either the control protein GFP or human wild type, polymerogenic G392E or truncated (delta) NS. This cellular model makes it possible to study the toxicity of polymerogenic NS in the appropriated cell type by in vitro differentiation to neurons. Our previous work showed that expression of G392E NS in differentiated NPCs induced an adaptive response through the upregulation of several genes involved in the defence against oxidative stress, and that pharmacological reduction of the antioxidant defences by drug treatments rendered G392E NS neurons more susceptible to apoptosis than control neurons. In this study, we assessed mitochondrial distribution and found a higher percentage of perinuclear localisation in G392E NS neurons, particularly in those containing polymers, a phenotype that was enhanced by glutathione chelation and rescued by antioxidant molecules. Mitochondrial membrane potential and contact sites between mitochondria and the ER were reduced in neurons expressing the G392E mutation. These alterations were associated with a pattern of ER stress that involved the ER overload response but not the unfolded protein response. Our results suggest that intracellular accumulation of NS polymers affects the interaction between the ER and mitochondria, causing mitochondrial alterations that contribute to the neuronal degeneration seen in FENIB patients

Perturbed nonlocal fourth order equations of Kirchhoff type with Navier boundary conditions

Abstract We investigate the existence of multiple solutions for perturbed nonlocal fourth-order equations of Kirchhoff type under Navier boundary conditions. We give some new criteria for guaranteeing that the perturbed fourth-order equations of Kirchhoff type have at least three weak solutions by using a variational method and some critical point theorems due to Ricceri. We extend and improve some recent results. Finally, by presenting two examples, we ensure the applicability of our results

Multiple solutions for a class of perturbed second-order differential equations with impulses

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Optimality conditions in convex multiobjective SIP

The purpose of this paper is to characterize the weak efficient solutions, the efficient solutions, and the isolated efficient solutions of a given vector optimization problem with finitely many convex objective functions and infinitely many convex constraints. To do this, we introduce new and already known data qualifications (conditions involving the constraints and/or the objectives) in order to get optimality conditions which are expressed in terms of either Karusk–Kuhn–Tucker multipliers or a new gap function associated with the given problem.This research was partially cosponsored by the Ministry of Economy and Competitiveness (MINECO) of Spain, and by the European Regional Development Fund (ERDF) of the European Commission, Project MTM2014-59179-C2-1-P