850 research outputs found
Granular Flow Impact Forces on Protection Structures: MPM Numerical Simulations with Different Constitutive Models
No full textAbstractFlows of granular materials are among the most destructive of all landslide phenomena. The assessment of the potential damage caused by the granular flow and the design of protection structures require the knowledge of the landslide-structure interaction. Numerical simulations of these phenomena are very complex because large displacements, soil-structure interaction and complex non-linear soil behavior have to be considered. A key issue in the simulation of these phenomena is the definition of a constitutive model able to describe the granular material response under a wide range of strain rates. This study examines and compares the results obtained by different constitutive models, namely the elastic perfectly plastic model with Mohr-Coulomb failure criterion, and the viscoplastic model with Drucker-Prager yielding condition. To this aim, we consider a finite volume of granular material instantaneously released from the top of an inclined channel; the material flows downslope and bumps a rigid wall on which the forces are measured
Structural evolution of the Rieserferner pluton in the framework of the Oligo-Miocene tectonics of the Eastern Alps
No full textThe structural evolution of the Oligocene Rieserferner pluton (Eastern Alps), developed during pluton cooling and exhumation, includes localized deformation structures consisting of: (i) steeply dipping joints, leucocratic dykes and quartz-feldspar veins, and related ductile shear zones (formed at ∼600 °C); (ii) shallowly dipping joints with associated epidote and quartz veins, and related ductile shear zones (∼450 °C); (iii) steeply dipping mafic dykes and calcite + white mica-bearing brittle-ductile faults (∼300 °C); (iv) steeply dipping pseudotachylyte-bearing faults (< 250 °C); and (v) zeolite-bearing faults (< 200 °C). The structures (i-iii) and (iv-v) can be dated to the Oligocene and Early Miocene, respectively. The kinematic analysis suggests a change in local shortening direction from N290°to N350°, interpreted to reflect a change from transtension in the Early Oligocene, associated with a N060°-directed plate divergence, to transpression in the Miocene, associated with a (N)NW-directed plate convergence. This evolution reflects the sequence of transient and long-term geodynamic processes occurring in the Eastern Alps during the Tertiary, including slab break-off of the subducted European slab, the indentation of the Dolomites promontory against the Alpine stack of nappes, and the exhumation and lateral escape tectonics of the Alpine belt
Quantitative histopathology in congenital myopathies
No full textA histo-morphometric analysis has been carried out in 23 muscle biopsies obtained from patients with congenital myopathies (6 nemaline m., 10 centronuclear m., 4 central core m., 3 multicore m.) in order to improve diagnosis and to confirm the data available in literature. No relationship has been found between the severity of the disease and the histo-pathological features as previously described. Nevertheless, the following pathological aspects diverge from previous reports: a) the absence of rods within the nuclei and of mitochondrial abnormalities in nemaline myopathy; b) the presence of type I fiber hypertrophy and of mitochondrial alterations in 30% of the patients with centronuclear myopathy; c) the presence of cores even in type II fibers, mitochondrial abnormalities, nucleosis, inflammatory cellular reaction and fibrosis in addition to the absence of rods in central core myopathy; d) the type I fiber hypertrophy in all patients with multicore myopathy
Frequently Asked Questions in Patients With Adrenal Insufficiency in the Time of COVID-19
No full textAdrenal insufficiency (AI) is a life-threatening disorder, with increased morbidity and mortality, especially in case of an acute illness that can increase the requirement of cortisol. A novel infectious disease, termed Coronavirus Disease 2019 (COVID-19), appeared in 2020. Therefore, AI patients are experiencing a novel challenge: the risk of infection. In our experience, a prompt contact to the Endocrine center (with a telemedicine consultation) and a full awareness of diseases (cortisol deficiency, COVID-19 and the self-management of an adrenal crisis) are important to motivate patients. Vaccine is an effective treatment to prevent hospitalization and aggressive course of COVID-19. Some patients manifest challenges due to inequitable access and vaccine hesitancy, resulting in a delay in the acceptance of vaccines despite the availability of vaccination services. Therefore, an effort of all physicians must be conducted in order to advise patients with AI. In this short review, we try to answer some frequently asked questions regarding the management of patients with AI
Who and how to screen for endogenous hypercortisolism in a high-risk population: a special issue of the journal of endocrinological investigations
No full textSkin-electroretinography patterns in early onset retinal dystrophies
No full textNo abstract availabl
Obfuscating Java Programs by Translating Selected Portions of Bytecode to Native Libraries
No full textode obfuscation is a popular approach to turn program comprehension and analysis harder, with the aim of mitigating threats related to malicious reverse engineering and code tampering. However, programming languages that compile to high level bytecode (e.g., Java) can be obfuscated only to a limited extent. In fact, high level bytecode still contains high level relevant information that an attacker might exploit. In order to enable more resilient obfuscations, part of these programs might be implemented with programming languages (e.g., C) that compile to low level machine-dependent code. In fact, machine code contains and leaks less high level information and it enables more resilient obfuscations. In this paper, we present an approach to automatically translate critical sections of high level Java bytecode to C code, so that more effective obfuscations can be resorted to. Moreover, a developer can still work with a single programming language, i.e., Java
A large study on the effect of code obfuscation on the quality of java code
No full textContext: Obfuscation is a common technique used to protect software against malicious reverse engineering. Obfuscators manipulate the source code to make it harder to analyze and more difficult to understand for the attacker. Although different obfuscation algorithms and implementations are available, they have never been directly compared in a large scale study.
Aim: This paper aims at evaluating and quantifying the effect of several different obfuscation implementations (both open source and commercial), to help developers and project managers to decide which algorithms to use.
Method: In this study we applied 44 obfuscations to 18 subject applications covering a total of 4 millions lines of code. The effectiveness of these source code obfuscations has been measured using 10 code metrics, considering modularity, size and complexity of code.
Results: Results show that some of the considered obfuscations are effective in making code metrics change substantially from original to obfuscated code, although this change (called potency of the obfuscation) is different on different metrics. In the paper we recommend which obfuscations to select, given the security requirements of the software to be protected
Personalized medical treatment for pituitary adenoma
No full textIntroduction and Aim: Pituitary adenomas are common neoplasms, with a reported prevalence of about one case in 1000 subjects. Patients with pituitary adenomas show significant morbidity due to pituitary hormone hypersecretion or deficiencies, mass effects and infiltration of the surrounding tissues. Although trans-sphenoidal surgery and radiotherapy are largely used to treat patients with pituitary adenomas, the overall long-term remission rate is not complete, beside side effects of surgery or brain irradiation. Therefore, medical treatments with pituitary-directed drugs are increasingly used in patients with secreting pituitary adenomas, especially when surgery fails or is not indicated, or awaiting for effects of radiotherapy. Somatostatin analogues (SSA) have been the mainstay of the medical treatment of GH-secreting adenomas, and nowadays are also used to treat ACTH-secreting pituitary adenomas, since these tumours express several types of somatostatin receptors (SSTR), with the prevalence of SSTR type 2 in the GH-secreting PA and of SSTR type 5 in the ACTH-secreting. Regrettably, 50% of patients with GH- secreting and 60% with ACTH- secreting pituitary adenomas do not respond to medical treatment with pituitary-directed drugs, or present only a partial hormonal reduction. Receptor desensitization, internalization and intra-cellular trafficking of SSTR could explain at least partially the lack of response, hence more data and knowledge about these cellular processes are urgently needed. Moreover, pituitary adenomas are not always benignant: some aggressive cases (up to 15-20% in all series) are characterized by rapid regrowth after first surgery, invasion of the surrounding structure, resistance to medical therapy, therefore the term Pituitary Neuroendocrine Tumor (PitNET) should be actually used.
The aims of this PhD project are to describe the role of medical treatment in patients with PitNET, in order to study the efficacy of available compounds; applicate the combination of medical treatment in clinical practice; analyse the differential effects (if existing) of medical treatment compared to surgery (considered the best curative treatment).
Materials and methods: Among our cohort of patients (120 with GH-, 134 with ACTH-, 171 with PRL-, 6 with TSH- secreting PitNET, 150 with non-secreting PitNET), we retrospectively and prospectively analysed clinical, radiological and pathological features of patient. Considering the treatment of aggressive PitNET or patients with Cushing’s Syndrome, we focused our attention to everolimus, temozolomide (TMZ) and metyrapone (MET) treatment. In some case, primary cell culture were used to study the effect of medical treatment.
Results: Regarding medical treatment, we considered the use of everolimus, TMZ, cabergoline and MET.
1. In a patient with tuberous sclerosis complex (TSC) and silent gonadotroph PitNET we tested the efficacy of everolimus, observing a reduction of cell viability after an in vitro treatment of PitNET’s derived primary cells. TSC analysis retrieved no disease-associated variants with the exception of the heterozygous intronic variant c.4006-71C>T found in TSC2: the computational tools predicted a gain of a new splice site with consequent intron retention, not confirmed by an in-vitro analysis of patient’s lymphocyte derived RNA.
2. Regarding TMZ in aggressive PitNET, we conducted an Italian survey on 31 patients: 11 patients (35.5%) had reduction of the tumor during TMZ treatment, while 6 patients (19.4%) had progression of disease. Median follow-up after start of TMZ was 18 months. Seven patients presented disease progression. The 2-yr recurrence-free survival was 62% (95% C.I., 34 -99%). Seven patients died of progressive disease. The 2-yr and 4-yr survival rates were 90% (95% C.I., 77-100%) and 56% (95% C.I., 26-85%). Moreover, we treated a patient with a combined cabergoline+TMZ treatment, achieving excellent results.
3. Considering MET in patients with Cushing’s Syndrome, patients were treated with a median dose of 1000 mg for 9 months. UFC and LNSC decreased quickly after the first month of treatment (-67% and -57% from baseline), with sustained UFC normalization up to 12 and 24 months (in 13 and 6 patients, respectively). UFC and LNSC normalized later (after 3-6 months) in patients with severe hypercortisolism (>5-fold baseline UFC). Regarding last visit, 70% and 37% of patients normalized UFC and LNSC, respectively. Body weight reduction (-4kg) was observed after UFC normalization. Severe side-effects were not reported, half female patients complained hirsutism, and blood pressure was not increased.
4. In patients with acromegaly, a significant proportion of patients developed Central Adrenal Insufficiency (CA) over time: while primary or secondary medical treatment did not contribute to the risk of CAI, repeated surgery or radiotherapy affected pituitary-adrenal axis. CAI was diagnosed in 18% of patients (10/57) after surgery, and in 53% (9/17) after radiotherapy (p=0.01).
Considering those aspects related to predict the effects of medical treatment with SSA in acromegaly, we studied the role of AIP-AHR and GIPR pathway. Considering AIP-AHR axis, involved in the detoxification of endocrine disruptors and chemical pollutants, we observed that acromegaly is more biochemically severe and resistant to SSA treatment in patients living in highly polluted areas, especially if they also carry specific AHR and/or AIP gene variants. Moreover, we found a stimulatory effect of IGF-1 on GIP promoter support in GIPR-expressing somatotropinomas, suggesting a novel molecular pathway able to induce GH-secreting PitNET.
Conclusions: In this complex scenario, understanding the physio-pathology of PitNET is the beginning of personalized treatment. In clinical practice, a multidisciplinary team for the management of patients is fundamental, to suggest the correct treatment plan, tailored to the patient
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