Local stabilization and network synchronization: The case of stationary regimes

Relationships between local stability and synchronization in networks of identical dynamical systems are established through the Master Stability Function approach. First, it is shown that stable equilibria of the local dynamics correspond to stable stationary synchronous regimes of the entire network if the coupling among the systems is sufficiently weak or balanced (in other words, stationary synchronous regimes can be unstable only if the coupling is sufficiently large and unbalanced). Then, it is shown that [de]stabilizing factors at local scale are [de]synchronizing at global scale again if the coupling is sufficiently weak or balanced. These results allow one to transfer, with almost no effort, what is known for simple prototypical models in biology and engineering to complex networks composed of these models. This is shown through a series of applications ranging from networks of electrical circuits to various problems in ecology and sociology involving migrations of plants, animal and human populations

Synchronization propensity in networks of dynamical systems: A purely topological indicator

Synchronization in networks of identical dynamical systems is enhanced by the number of manifolds in which synchrony of groups of systems is conserved or reinforced. Since the number of these invariant manifolds depends only on the coupling architecture of the network, it can be proposed as a purely topological indicator of synchronization propensity. The proposal is empirically validated through the detailed study of an ecological application

A conceptual model for the prediction of sexual intercourses in permanent couples

The problem of the frequency of sexual intercourses in permanent couples is investigated for the first time with a purely conceptual model. The model, based on a few axioms involving very simple notions like sexual appetite and erotic potential, is composed of two ordinary differential equations which are exactly the same than those proposed almost one century ago in epidemiology. The model can be used to discuss the possibility of estimating strategic parameters from real data, as well as to criticize the rule of "the beans in the yar" proposed in 1970 by David Martin in The Journal of Sex Research

Multi-Temporal investigation of the Boulder Clay Glacier and Northern Foothills (Victoria Land, Antarctica) by integrated surveying techniques

The paper aims to detect the main changes that occurred in the area surrounding the Mario Zucchelli Station (MZS) through analysis of multi-temporal remote sensing integrated by geophysical measurements. Specific attention was directed at realizing an integrated geomorphological study of the Boulder Clay Glacier, a partially debris-covered glacier belonging to the Northern Foothills (Victoria Land, Antarctica). This area was recently chosen as the location for the construction of a new semi-permanent gravel runway for MZS logistical airfreight operations. Photogrammetric analysis was performed by comparing three historical aerial photogrammetric surveys (carried out in 1956, 1985, and 1993) and Very High Resolution (VHR) GeoEye-1 satellite stereo-image coverage acquired in 2012. The comparison of geo-referenced orthophoto-mosaics allowed the main changes occurring in some particular areas along the coast nearby MZS to be established. Concerning the study of the Boulder Clay Glacier, it has to be considered that glaciers and moraines are not steady-state systems by definition. Several remote sensing and geophysical investigations were carried out with the main aim of determining the general assessment of this glacier: Ground Penetrating Radar (GPR); Geodetic Global Positioning System (GPS) network; multi-temporal satellite Synthetic Aperture Radar (SAR) interferometry. The analysis of Boulder Clay Glacier moraine pointed out a deformation of less than 74 mm y-1 in a time span of 56 years, value that agrees with velocity and deformation data observed by GPS and InSAR methods. The presence of unexpected brine ponds at the ice/bedrock interface and the deformation pattern observed in the central part of the moraine has to be monitored and studied, especially under the long-term maintenance of the future runway

HER2-Enriched Subtype and ERBB2 Expression in HER2-Positive Breast Cancer Treated with Dual HER2 Blockade

Background: Identification of HER2-positive breast cancers with high anti-HER2 sensitivity could help de-escalate chemotherapy. Here, we tested a clinically applicable RNA-based assay that combines ERBB2 and the HER2-enriched (HER2-E) intrinsic subtype in HER2-positive disease treated with dual HER2-blockade without chemotherapy. Methods: A research-based PAM50 assay was applied in 422 HER2-positive tumors from five II-III clinical trials (SOLTI-PAMELA, TBCRC023, TBCRC006, PER-ELISA, EGF104090). In SOLTI-PAMELA, TBCRC023, TBCRC006, and PER-ELISA, all patients had early disease and were treated with neoadjuvant lapatinib or pertuzumab plus trastuzumab for 12-24 weeks. Primary outcome was pathological complete response (pCR). In EGF104900, 296 women with advanced disease were randomized to receive either lapatinib alone or lapatinib plus trastuzumab. Progression-free survival (PFS), overall response rate (ORR), and overall survival (OS) were evaluated. Results: A total of 305 patients with early and 117 patients with advanced HER2-positive disease were analyzed. In early disease, HER2-E represented 83.8% and 44.7% of ERBB2-high and ERBB2-low tumors, respectively. Following lapatinib and trastuzumab, the HER2-E and ERBB2 (HER2-E/ERBB2)-high group showed a higher pCR rate compared to the rest (44.5%, 95% confidence interval [CI] = 35.4% to 53.9% vs 11.6%, 95% CI = 6.9% to 18.0%; adjusted odds ratio [OR] = 6.05, 95% CI = 3.10 to 11.80, P <. 001). Similar findings were observed with neoadjuvant trastuzumab and pertuzumab (pCR rate of 66.7% in HER2-E/ERBB2-high, 95% CI = 22.3% to 95.7% vs 14.7% in others, 95% CI = 4.9% to 31.1%; adjusted OR = 11.60, 95% CI = 1.66 to 81.10, P =. 01). In the advanced setting, the HER2-E/ERBB2-high group was independently associated with longer PFS (hazard ratio [HR] = 0.52, 95% CI = 0.35 to 0.79, P <. 001); higher ORR (16.3%, 95% CI = 8.9% to 26.2% vs 3.7%, 95% CI = 0.8% to 10.3%, P =. 02); and longer OS (HR = 0.66, 95% CI = 0.44 to 0.97, P =. 01). Conclusions: Combining HER2-E subtype and ERBB2 mRNA into a single assay identifies tumors with high responsiveness to HER2-targeted therapy. This biomarker could help de-escalate chemotherapy in approximately 40% of patients with HER2-positive breast cancer

Indagini Geofisiche

Nell'ambito del progetto per la Microzonazione sismica dell'area aquilana, coordinata dal DPC, il Gruppo di Lavoro ha condotto le indagini di MS nella Conca di Roio.Published336-3854T. Sismologia, geofisica e geologia per l'ingegneria sismic

RAD51 foci as a functional biomarker of homologous recombination repair and PARP inhibitor resistance in germline BRCA-mutated breast cancer.

BACKGROUND: BRCA1 and BRCA2 (BRCA1/2)-deficient tumors display impaired homologous recombination repair (HRR) and enhanced sensitivity to DNA damaging agents or to poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi). Their efficacy in germline BRCA1/2 (gBRCA1/2)-mutated metastatic breast cancers has been recently confirmed in clinical trials. Numerous mechanisms of PARPi resistance have been described, whose clinical relevance in gBRCA-mutated breast cancer is unknown. This highlights the need to identify functional biomarkers to better predict PARPi sensitivity. PATIENTS AND METHODS: We investigated the in vivo mechanisms of PARPi resistance in gBRCA1 patient-derived tumor xenografts (PDXs) exhibiting differential response to PARPi. Analysis included exome sequencing and immunostaining of DNA damage response proteins to functionally evaluate HRR. Findings were validated in a retrospective sample set from gBRCA1/2-cancer patients treated with PARPi. RESULTS: RAD51 nuclear foci, a surrogate marker of HRR functionality, were the only common feature in PDX and patient samples with primary or acquired PARPi resistance. Consistently, low RAD51 was associated with objective response to PARPi. Evaluation of the RAD51 biomarker in untreated tumors was feasible due to endogenous DNA damage. In PARPi-resistant gBRCA1 PDXs, genetic analysis found no in-frame secondary mutations, but BRCA1 hypomorphic proteins in 60% of the models, TP53BP1-loss in 20% and RAD51-amplification in one sample, none mutually exclusive. Conversely, one of three PARPi-resistant gBRCA2 tumors displayed BRCA2 restoration by exome sequencing. In PDXs, PARPi resistance could be reverted upon combination of a PARPi with an ataxia-telangiectasia mutated (ATM) inhibitor. CONCLUSION: Detection of RAD51 foci in gBRCA tumors correlates with PARPi resistance regardless of the underlying mechanism restoring HRR function. This is a promising biomarker to be used in the clinic to better select patients for PARPi therapy. Our study also supports the clinical development of PARPi combinations such as those with ATM inhibitors