Parameterized thermal macromodeling for fast and effective design of electronic components and systems

We present a parameterized macromodeling approach to perform fast and effective dynamic thermal simulations of electronic components and systems where key design parameters vary. A decomposition of the frequency-domain data samples of the thermal impedance matrix is proposed to improve the accuracy of the model and reduce the number of the computationally costly thermal simulations needed to build the macromodel. The methodology is successfully applied to analyze the impact of layout variations on the dynamic thermal behavior of a state-of-the-art 8-finger AlGaN/GaN HEMT grown on a SiC substrate

REMOVABLE SETS FOR LIPSCHITZ HARMONIC FUNCTIONS ON CARNOT GROUPS

Abstract. Let G be a Carnot group with homogeneous dimension Q ≥ 3 and let L be a sub-Laplacian on G. We prove that the critical dimension for removable sets of Lipschitz L-harmonic functions is (Q − 1). Moreover we construct self-similar sets with positive and finite H Q−1 measure which are removable. 1

Nicastrin and Notch4 drive endocrine therapy resistance and epithelial to mesenchymal transition in MCF7 breast cancer cells

Introduction Resistance to anti-estrogen therapies is a major cause of disease relapse and mortality in estrogen receptor alpha (ERα)-positive breast cancers. Tamoxifen or estrogen withdrawal increases the dependence of breast cancer cells on Notch signalling. Here, we investigated the contribution of Nicastrin and Notch signalling in endocrine-resistant breast cancer cells. Methods We used two models of endocrine therapies resistant (ETR) breast cancer: tamoxifen-resistant (TamR) and long-term estrogen-deprived (LTED) MCF7 cells. We evaluated the migratory and invasive capacity of these cells by Transwell assays. Expression of epithelial to mesenchymal transition (EMT) regulators as well as Notch receptors and targets were evaluated by real-time PCR and western blot analysis. Moreover, we tested in vitro anti-Nicastrin monoclonal antibodies (mAbs) and gamma secretase inhibitors (GSIs) as potential EMT reversal therapeutic agents. Finally, we generated stable Nicastrin overexpessing MCF7 cells and evaluated their EMT features and response to tamoxifen. Results We found that ETR cells acquired an epithelial to mesenchymal transition (EMT) phenotype and displayed increased levels of Nicastrin and Notch targets. Interestingly, we detected higher level of Notch4 but lower levels of Notch1 and Notch2 suggesting a switch to signalling through different Notch receptors after acquisition of resistance. Anti-Nicastrin monoclonal antibodies and the GSI PF03084014 were effective in blocking the Nicastrin/Notch4 axis and partially inhibiting the EMT process. As a result of this, cell migration and invasion were attenuated and the stem cell-like population was significantly reduced. Genetic silencing of Nicastrin and Notch4 led to equivalent effects. Finally, stable overexpression of Nicastrin was sufficient to make MCF7 unresponsive to tamoxifen by Notch4 activation. Conclusions ETR cells express high levels of Nicastrin and Notch4, whose activation ultimately drives invasive behaviour. Anti-Nicastrin mAbs and GSI PF03084014 attenuate expression of EMT molecules reducing cellular invasiveness. Nicastrin overexpression per se induces tamoxifen resistance linked to acquisition of EMT phenotype. Our finding suggest that targeting Nicastrin and/or Notch4 warrants further clinical evaluation as valid therapeutic strategies in endocrine-resistant breast cancer

Importance of Sexual Function Assessment in Multidimensional Evaluation of AGHD Patients: Results from the MAGHD Study.

Background: Adult growth hormone deficiency (AGHD) is a debilitating clinical condition leading to decreased quality of life (QoL). The impact of reduced muscle mass, weakening and loss of vitality on QoL have been well characterized in AGHD. The impact of AGHD on sexual function, a recognized factor able to modify well-being, has never been investigated. Aim: To investigate the prevalence of sexual dysfunction in AGHD patients referring to a single endocrinological center and grouped according to their his- tory of r-hGH therapy.Methods: The Management of Adult Growth Hormone Deficiency (MAGHD) Study is a pro- spective, real-life trial aiming to improve management of AGHD patients through a smartphone app (MAGHD App)and a wearable device. The 83 AGHD enrolled patients (31 Females, 52 Males, mean age 56.27 + 14.68 years) were divided in 3 groups (G) according to r-hGH therapy: on long-term r-hGH therapy (G1, n=32), previously treated with r-hGH (G2, n=20), never treated (G3, n=31). Within the first phase of the study, a large database was created collecting clinical, biochemical and psychological data. In addition to QLS-H and QoL-AGHDA routinely used to as- sess QoL, IIEF-15 and FSFI were employed to evaluate sexual function in males and females, respectively. The nonparametric Kruskal-Wallis test was used for compar- ison among 3 groups.Results: Here only baseline data of the MAGHD Study are presented.According to IIEF-15 results, the prevalence of erectile dysfunction (ED) in male AGHD cohort was 60%. Erectile function (EF) score was signifi- cantly higher in G1 compared to both G2 and G3 (p < 0.05) with an ED prevalence of 35% in G1, 75% in G2 and 75% in G3. Even excluding patients with serum testosterone lower than 2 ng/ml and older than 65 years, ED prevalence did not change significantly in the 3 groups. Moreover, EF do- main was inversely and directly correlated to age (R20.130, β-0.360) and IGF1 levels (R20.156, β0.395), respectively. The prevalence of female sexual dysfunction according to FSFI was 89.3%. Even though desire, arousal, lubrication and overall scores were significantly higher (better results) in G1 compared to G2 and G3 (p < 0.05), no correlation resulted between FSFI domains and IGF1 levels. Instead an inverse correlation resulted between desire domain and age.Conclusions: This study, performed in a real-life clinical setting, demonstrates a high prevalence of sexual dysfunc- tion in AGHD patients and that r-hGH treatment seems to be associated to better sexual outcomes. These results suggest that the evaluation of sexual function should be in- tegrated in the global assessment of AGHD patients since sexual activity is a fundamental domain able to influence both well-being and QoL

Gender Differences in Heart Rate Variability Among Individuals Undergoing Regular Resistance Training : Preliminary observations

Objectives: Frequency-domain analysis of heart rate variability (HRV) is an effective tool to evaluate autonomic balance. This study aimed to investigate gender differences in HRV among individuals undergoing regular resistance training. Methods: This preliminary cross-sectional study was conducted from April to September 2016 in João Pessoa, Paraíba, Brazil. The low-frequency (LF), high-frequency (HF) and LF/HF ratio components of HRV spectral analysis were analysed among 22 men and 27 women undergoing regular resistance training. Results: Among the male participants, the LF component was significantly increased compared to females in both the supine (1,171 ± 192 versus 545 ± 74 ms2; P = 0.0067) and upright (1,824 ± 260 versus 738 ± 133; P = 0.0011) positions. The LF/HF ratio was also significantly increased in both positions among male participants (P <0.0500 each). Conclusion: These preliminary data suggest a possible gender difference in the HRV of individuals undergoing resistance training

Serotonin Trasporter Tracks Similarities Between Sids And Idiopathic Alte

Polymorphisms in the serotonin transporter (5HTT) (SLC6A4 encoding 5HTT) as a predisposing factor in infant death. Considering stric corrispondence between 5HTT and MAOA genotypic and allelic data inIALTE and SIDS, we hypothesize that the two syndromes are different expression of a common ethiopathogenesis

Alternative antibody for the detection of CA19-9 antigen: a European multicenter study for the evaluation of the analytical and clinical performance of the Access (R) GI Monitor assay on the UniCel (R) Dxl 800 Immunoassay System

Background: Gastrointestinal cancer antigen CA19-9 is known as a valuable marker for the management of patients with pancreatic cancer. Methods: The analytical and clinical performance of the Access(R) GI Monitor assay (Beckman Coulter) was evaluated on the UniCel(R) Dxl 800 Immunoassay System at five different European sites and compared with a reference method, defined as CA19-9 on the Elecsys System (Roche Diagnostics). Results: Total imprecision (%CV) of the GI Monitor ranged between 3.4% and 7.7%, and inter-laboratory reproducibility between 3.6% and 4.0%. Linearity upon dilution showed a mean recovery of 97.4% (SD+7.2%). Endogenous interferents had no influence on GI Monitor levels (mean recoveries: hemoglobin 103%, bilirubin 106%, triglycerides 106%). There was no high-dose hook effect up to 115,000 kU/L. Clinical performance investigated in sera from 1811 individuals showed a good correlation between the Access' GI Monitor and Elecsys CA19-9 (R = 0.959, slope = 1.004, intercept +0.17). GI Monitor serum levels were low in healthy individuals (n = 267, median = 6.0 kU/L, 95th percentile = 23.1 kU/L), higher in individuals with various benign diseases (n = 550, medians = 5.8-13.4 kU/L, 95th percentiles = 30.1-195.5 kU/L) and even higher in individuals suffering from various cancers (n = 995, medians = 8.4-233.8 kU/L, 95th percentiles = 53.7-13,902 kU/L). Optimal diagnostic accuracy for cancer detection against the relevant benign control group by the GI Monitor was found for pancreatic cancer {[}area under the curve (AUC) 0.83]. Results for the reference CA19-9 assay were comparable (AUC 0.85). Conclusions: The Access(R) GI Monitor provides very good methodological characteristics and demonstrates an excellent analytical and clinical correlation with the Elecsys CA19-9. The GI Monitor shows the best diagnostic accuracy in pancreatic cancer. Our results also suggest a clinical value of the GI Monitor in other cancers

Time domain dynamic electrothermal macromodeling for thermally aware integrated system design

Time domain identification of reduced dynamic thermal models is pursued with well established macromodeling techniques, providing electrical equivalents to be integrated in standard circuit simulators. Self and mutual thermal impedances of electronic structures, preliminarily evaluated through accurate 3-D FEM thermal simulations, are directly identified with Time Domain Vector Fitting and synthesised in a lumped PSPICE circuit. Two relevant examples of dynamic electrothermal co-simulation are given, the results of which exhibit significant differences with respect to their isothermal counterpart