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This article presents a fully analog, signal-to-noise-ratio-based voice-activity detection (VAD) circuit. The circuit is based on an energy-efficient analog implementation with continuous-time nonlinear operation and fully passive switched-capacitor signal processing. The overall chain is composed of a programmable-gain amplifier, a squarer, an integrator, an SC-based signal averaging circuit, and a periodic threshold update circuit for adaptability. This implementation allows the minimization of both power consumption and chip area. The VAD circuit prototype has been fabricated in a 180-nm CMOS technology and occupies an area of 0.14 mm2. The device achieves 99.5% classification accuracy in a domestic environment in the presence of loud ambient noise, consuming 760 nW from a 1.2-V supply.

This paper presents a fully analog, signal-to-noise ratio (SNR) based voice-activity detection circuit, which achieves 99.5 % classification accuracy in a domestic environment in the presence of loud ambient noise, consuming 760 nW from a 1.2 V supply. The circuit exploits an energy-efficient analog implementation with continuous-time non-linear operation and fully-passive switched-capacitor processing, to minimize both the power consumption and the chip area. The VAD circuit prototype, fabricated in a 180 nm CMOS technology, occupies 0.14mm2.

Nel saggio si considera analiticamente la categoria di "esperienza integrale" a partire dalla sua espressione nell'opera di Angelo Campodonico e se ne propone un'analisi critica nel confronto con alcune voci del dibattito internazionale (R. Audi, A. MacIntyre, J. Raz, M. Nussbaum). A tale scopo, la categoria viene discussa a partire da tre aree problematiche: il rapporto fra esperienza assiologica e percezione morale, la presenza della ricerca di senso nelle pratiche sociali, la tensione fra esperienza religiosa ed etica pubblica., The essay analytically considers the category of "integral experience" starting from its expression in the work of Angelo Campodonico and proposes a critical analysis in comparison with some voices of the international debate (R. Audi, A. MacIntyre, J. Raz, M. Nussbaum). To this end, the category is discussed starting from three problematic areas: the relationship between axiological experience and moral perception, the presence of the search for meaning in social practices, the tension between religious experience and public ethics.

A pair of completely integrated capless preamplifiers (not requiring external capacitance) for MEMS microphones are presented. The devices exploit specific circuit solutions to implement a proper dc biasing of the pre-amplifier and a low frequency (< 1 Hz) high-pass pole. The two solutions adopted are a based on a transistor in the off state (OTP) and a switched-resistor (SRP), respectively. Since the devices are supposed to operate with different silicon microphones, the pre-amplifier gain has to be programmable. In spite of the single ended configuration and independently of the gain, both pre-amplifiers achieve a signal to noise ratio (SNR) lower than -100 dB. The total harmonic distortion (THD) is lower than -80 dB for the OTP and lower than -100 dB for the SRP. The devices are implemented in a 0.18-Î1⁄4m CMOS technology, with a supply voltage of 1.8-V. In both cases the power consumption is 230 Î1⁄4W. The bandwidth of interest ranges from 20 Hz to 20 kHz. Both solutions have variable gain configurations [-6, 0, 6, 12, 18] dB.

Anti-PD-1 or anti-PD-L1 blocking monoclonal antibodies (mAbs) have shown potent anti-tumor effects in adult cancer patients and clinical studies have recently been started in pediatric cancers, including high-risk/relapsing neuroblastoma (NB). Therefore, we studied the effects of anti-PD-1/PD-L1 mAbs in two syngeneic models of disseminated NB generated by the injection of either Neuro2a or NXS2 cells, which express PD-L1. In addition, we tested the combination of these agents with the immune-enhancing cytokine IL-21, the Ecto-NTPDase inhibitor POM-1, an anti-CD25 mAb targeting Treg cells, or an anti-CD4 mAb. We previously showed that CD4-transient depletion removes CD4+CD25+ Treg cells and other CD4+CD25- regulatory subsets. Here we show that mono-therapy with anti-PD-1/PD-L1 mAbs had no effect on systemic NB progression in vivo, and also their combination with IL-21, POM-1 or anti-CD25 mAb was ineffective. The combined use of anti-PD-1 with an anti-CD4 mAb mediated a very potent, CD8-dependent, synergistic effect leading to significant elongation of tumor-free survival of mice, complete tumor regression and durable anti-NB immunity. Similar results were obtained by combining the anti-PD-L1 and anti-CD4 mAbs. These findings indicate that both PD-1/PD-L1 and CD4+ T cell-related immune-regulatory mechanisms must be simultaneously blocked to mediate therapeutic effects in these models.

In 2012 an unpublished book by the Austrian legal philosopher Hans Kelsen, Secular Religion, has been posthumously published. This book, written by Kelsen between 1952 and 1964 in the United States, severely criticizes those theories of politics and culture that misinterpret modern social philosophy, science and politics as new religions, mainly adopting the controversial concept of “secular religión.” In the first part of the paper, we reconstruct the genesis of the book and the complex events that led to its final version, and we underline the motives that led Kelsen to write this vehement polemic in defense of the spirit of modernity, and eventually to withdraw it. In the second part of the paper, we investigate some of the main methodological and theoretical contributions that this work, albeit its critical tenor, is able to give to an anthropology of modernity.

In light of the recent advances regarding the role of vascularity in Alzheimer's disease (AD) pathophysiology, the relationship between plasma levels and activities of the major antioxidant molecules and the carotid intima-media thickness (C-IMT) of older persons with no or very mild cognitive impairment was evaluated. The underlying hypothesis is that the IMT may be an indirect index of vascular damage in persons with low levels of plasma antioxidants. Plasma levels of vitamins A, C, E, of uric acid as well as activities of the plasma antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) were measured. Plasma levels of vitamins C and E significantly decreased among participants from the first to the fourth IMT quartile, with a linear slope only for vitamin C. Compared to participants in the lowest vitamin C quartile, the probability to have IMT > 1.2 mm significantly decreased among persons from the second to the fourth quartile independent of confounders. In conclusion, only vitamin C plasma levels appear to be selectively associated with the risk of increasing C-IMT. An adequate vitamin C status might be particularly important for protection against AD and other clinical manifestations of vascular and cognitive ageing.

In light of the recent advances regarding the role of vascularity in Alzheimer's disease (AD) pathophysiology, the relationship between plasma levels and activities of the major antioxidant molecules and the carotid intima-media thickness (C-IMT) of older persons with no or very mild cognitive impairment was evaluated. The underlying hypothesis is that the IMT may be an indirect index of vascular damage in persons with low levels of plasma antioxidants. Plasma levels of vitamins A, C, E, of uric acid as well as activities of the plasma antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) were measured. Plasma levels of vitamins C and E significantly decreased among participants from the first to the fourth IMT quartile, with a linear slope only for vitamin C. Compared to participants in the lowest vitamin C quartile, the probability to have IMT > 1.2 mm significantly decreased among persons from the second to the fourth quartile independent of confounders. In conclusion, only vitamin C plasma levels appear to be selectively associated with the risk of increasing C-IMT. An adequate vitamin C status might be particularly important for protection against AD and other clinical manifestations of vascular and cognitive ageing.

In light of the recent advances regarding the role of vascularity in Alzheimer's disease (AD) pathophysiology, the relationship between plasma levels and activities of the major antioxidant molecules and the carotid intima-media thickness (C-IMT) of older persons with no or very mild cognitive impairment was evaluated. The underlying hypothesis is that the IMT may be an indirect index of vascular damage in persons with low levels of plasma antioxidants. Plasma levels of vitamins A, C, E, of uric acid as well as activities of the plasma antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) were measured. Plasma levels of vitamins C and E significantly decreased among participants from the first to the fourth IMT quartile, with a linear slope only for vitamin C. Compared to participants in the lowest vitamin C quartile, the probability to have IMT > 1.2 mm significantly decreased among persons from the second to the fourth quartile independent of confounders. In conclusion, only vitamin C plasma levels appear to be selectively associated with the risk of increasing C-IMT. An adequate vitamin C status might be particularly important for protection against AD and other clinical manifestations of vascular and cognitive ageing.

In light of the recent advances regarding the role of vascularity in Alzheimer's disease (AD) pathophysiology, the relationship between plasma levels and activities of the major antioxidant molecules and the carotid intima-media thickness (C-IMT) of older persons with no or very mild cognitive impairment was evaluated. The underlying hypothesis is that the IMT may be an indirect index of vascular damage in persons with low levels of plasma antioxidants. Plasma levels of vitamins A, C, E, of uric acid as well as activities of the plasma antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) were measured. Plasma levels of vitamins C and E significantly decreased among participants from the first to the fourth IMT quartile, with a linear slope only for vitamin C. Compared to participants in the lowest vitamin C quartile, the probability to have IMT > 1.2 mm significantly decreased among persons from the second to the fourth quartile independent of confounders. In conclusion, only vitamin C plasma levels appear to be selectively associated with the risk of increasing C-IMT. An adequate vitamin C status might be particularly important for protection against AD and other clinical manifestations of vascular and cognitive ageing.

In light of the recent advances regarding the role of vascularity in Alzheimer's disease (AD) pathophysiology, the relationship between plasma levels and activities of the major antioxidant molecules and the carotid intima-media thickness (C-IMT) of older persons with no or very mild cognitive impairment was evaluated. The underlying hypothesis is that the IMT may be an indirect index of vascular damage in persons with low levels of plasma antioxidants. Plasma levels of vitamins A, C, E, of uric acid as well as activities of the plasma antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) were measured. Plasma levels of vitamins C and E significantly decreased among participants from the first to the fourth IMT quartile, with a linear slope only for vitamin C. Compared to participants in the lowest vitamin C quartile, the probability to have IMT > 1.2 mm significantly decreased among persons from the second to the fourth quartile independent of confounders. In conclusion, only vitamin C plasma levels appear to be selectively associated with the risk of increasing C-IMT. An adequate vitamin C status might be particularly important for protection against AD and other clinical manifestations of vascular and cognitive ageing.

The MUC1 gene is aberrantly overexpressed in approximately 90% of human breast cancers. Several studies have shown that MUC1 overexpression is due to transcriptional regulatory events. However, the importance of gene amplification as a mechanism leading to the increase of MUC1 expression in breast cancer has been poorly characterized. The aim of this study was to evaluate the role of MUC1 gene amplification and protein expression in human breast cancer development. By means of real-time quantitative polymerase chain reaction and immunohistochemical methods, 83 breast tissue samples were analyzed for MUC1 gene amplification and protein expression. This analysis showed MUC1 genomic amplification and a positive association with the histopathological group in 12% (1 out of 8) of benign lesions and 38% (23 out of 60) of primary invasive breast carcinoma samples (P = 0.004). Array-comparative genomic hybridization meta-analysis of 886 primary invasive breast carcinomas obtained from 22 studies showed MUC1 genomic gain in 43.7% (387 out of 886) of the samples. Moreover, we identified a highly statistical significant association between MUC1 gene amplification and MUC1 protein expression assessed by immunohistochemistry and Western blot test (P < 0.0001). In conclusion, this study demonstrated that MUC1 copy number increases from normal breast tissue to primary invasive breast carcinomas in correlation with MUC1 protein expression.