Techniques for high speed and low power digital to analog converters

Obiettivo principale di questa tesi consiste nella definizione e nello sviluppo di nuove tecniche e metodologie di progetto per la realizzazione di convertitori digitale-analogici ad alta velocità ed elevate prestazioni, adatti all'implementazione in tecnologie CMOS super-scalate ed in grado di superare i fondamentali trade-offs che ne limitano le prestazioni. In particolare, al centro della tesi si pone l'introduzione di una nuova tecnica digitale di linearizzazione della caratteristica statica di un DAC, basata sull'uso estensivo di tecniche di filtraggio adattivo. La cancellazione delle non-linearità statiche dovute alle imperfezioni dei circuiti analogici è effettuata completamente nel dominio digitale, consentendo in questo modo una progettazione esclusivamente finalizzata all'ottimizzazione delle prestazioni ad alta frequenza. Inoltre, il metodo digitale proposto si presta in particolar modo all'integrazione in processi CMOS nanometrici, beneficiandone ulteriormente in termini di consumo di potenza ed area. Al fine di dimostarne l'efficiacia, la tecnica proposta è stata applicata al progetto di un DAC current-steering con 10-bit di risoluzione e frequenza di sampling di 2.5GS/s in tecnologia CMOS 28nm. Le simulazioni circuitali del DAC progettato indicano un SFDR maggiore di 65dB su tutta la banda di Nyquist, con un consumo di potenza di 36mW (da una tensione di alimentazione di 1V) e una potenza d'uscita erogata al carico di -2dBm.The essential objective of this thesis is the definition and the development of new design methodologies and techniques for the realization of high-speed high performance Digital-to-Analog Converters suitable for the integration in ultra-scaled CMOS technologies, which allow overcoming the fundamental trade-offs limiting performances. In particular, the thesis core is the introduction of a new digital technique for the linearization of DAC static characteristic, which is based on the extensive use of digital adaptive filtering. As static non-linearity due to analog circuits impairments is canceled out in digital domain, a design full-oriented at optimizing high-frequency performances is allowed. Furthermore, the digital style of the proposed method particularly fits into integration in nanometer CMOS processes, further benefiting in terms of area and power consumption. To demonstrate its effectiveness, the proposed technique has been applied to the design of a 10-bit 2.5GS/s current-steering DAC in 28nm CMOS. Simulations of the overall design show a DAC SFDR greater than 65dB across the entire Nyquist bandwidth, while consuming 36mW analog power from a 1V supply voltage and delivering a maximum −2dBm power to the load.DIPARTIMENTO DI ELETTRONICA, INFORMAZIONE E BIOINGEGNERIAElectronics26GERACI, ANGELOFIORINI, CARLO ETTOR

A peculiar formula of essential amino acids prevents rosuvastatin myopathy in mice

Aims: Myopathy, characterized by mitochondrial oxidative stress, occurs in ∼10% of statin-treated patients, and a major risk exists with potent statins such as rosuvastatin (Rvs). We sought to determine whether a peculiar branched-chain amino acid-enriched mixture (BCAAem), found to improve mitochondrial function and reduce oxidative stress in muscle of middle-aged mice, was able to prevent Rvs myopathy. Results: Dietary supplementation of BCAAem was able to prevent the structural and functional alterations of muscle induced by Rvs in young mice. Rvs-increased plasma 3-methylhistidine (a marker of muscular protein degradation) was prevented by BCAAem. This was obtained without changes of Rvs ability to reduce cholesterol and triglyceride levels in blood. Rather, BCAAem promotes de novo protein synthesis and reduces proteolysis in cultured myotubes. Morphological alterations of C2C12 cells induced by statin were counteracted by amino acids, as were the Rvs-increased atrogin-1 mRNA and protein levels. Moreover, BCAAem maintained mitochondrial mass and density and citrate synthase activity in skeletal muscle of Rvs-treated mice beside oxygen consumption and ATP levels in C2C12 cells exposed to statin. Notably, BCAAem assisted Rvs to reduce oxidative stress and to increase the anti-reactive oxygen species (ROS) defense system in skeletal muscle. Innovation and Conclusions: The complex interplay between proteostasis and antioxidant properties may underlie the mechanism by which a specific amino acid formula preserves mitochondrial efficiency and muscle health in Rvs-treated mice. Strategies aimed at promoting protein balance and controlling mitochondrial ROS level may be used as therapeutics for the treatment of muscular diseases involving mitochondrial dysfunction, such as statin myopathy

Perinatal Parenting Stress, Anxiety, and Depression Outcomes in First-Time Mothers and Fathers: A 3- to 6-Months Postpartum Follow-Up Study

Objective: Although there is an established link between parenting stress, postnatal depression, and anxiety, no study has yet investigated this link in first-time parental couples. The specific aims of this study were 1) to investigate whether there were any differences between first-time fathers’ and mothers’ postnatal parenting stress, anxiety, and depression symptoms and to see their evolution between three and 6 months after their child’s birth; and 2) to explore how each parent’s parenting stress and anxiety levels and the anxiety levels and depressive symptoms of their partners contributed to parental postnatal depression. Method: The sample included 362 parents (181 couples; mothers’ MAge = 35.03, SD = 4.7; fathers’ MAge = 37.9, SD = 5.6) of healthy babies. At three (T1) and 6 months (T2) postpartum, both parents filled out, in a counterbalanced order, the Parenting Stress Index-Short Form, the Edinburgh Postnatal Depression Scale, and the State- Trait Anxiety Inventory. Results: The analyses showed that compared to fathers, mothers reported higher scores on postpartum anxiety, depression, and parenting stress. The scores for all measures for both mothers and fathers decreased from T1 to T2. However, a path analysis suggested that the persistence of both maternal and paternal postnatal depression was directly influenced by the parent’s own levels of anxiety and parenting stress and by the presence of depression in his/her partner. Discussion: This study highlights the relevant impact and effects of both maternal and paternal stress, anxiety, and depression symptoms during the transition to parenthood. Therefore, to provide efficacious, targeted, early interventions, perinatal screening should be directed at both parents

Lymphatic endothelial cells are a replicative niche for Mycobacterium tuberculosis

In extrapulmonary tuberculosis, the most common site of infection is within the lymphatic system, and there is growing recognition that lymphatic endothelial cells (LECs) are involved in immune function. Here, we identified LECs, which line the lymphatic vessels, as a niche for Mycobacterium tuberculosis in the lymph nodes of patients with tuberculosis. In cultured primary human LECs (hLECs), we determined that M. tuberculosis replicates both in the cytosol and within autophagosomes, but the bacteria failed to replicate when the virulence locus RD1 was deleted. Activation by IFN-γ induced a cell-autonomous response in hLECs via autophagy and NO production that restricted M. tuberculosis growth. Thus, depending on the activation status of LECs, autophagy can both promote and restrict replication. Together, these findings reveal a previously unrecognized role for hLECs and autophagy in tuberculosis pathogenesis and suggest that hLECs are a potential niche for M. tuberculosis that allows establishment of persistent infection in lymph nodes

Ischemic Neuroprotection by Insulin with Down-Regulation of Divalent Metal Transporter 1 (DMT1) Expression and Ferrous Iron-Dependent Cell Death

Background: The regulation of divalent metal transporter-1 (DMT1) by insulin has been previously described in Langerhans cells and significant neuroprotection was found by insulin and insulin-like growth factor 1 treatment during experimental cerebral ischemia in acute ischemic stroke patients and in a rat 6-OHDA model of Parkinson's disease, where DMT1 involvement is described. According to the regulation of DMT1, previously described as a target gene of NF-kB in the early phase of post-ischemic neurodegeneration, both in vitro and in vivo, and because insulin controls the NFkB signaling with protection from ischemic cell death in rat cardiomyocytes, we evaluated the role of insulin in relation to DMT1 expression and function during ischemic neurodegeneration. Methods: Insulin neuroprotection is evaluated in differentiated human neuroblastoma cells, SK-N-SH, and in primary mouse cortical neurons exposed to oxygen glucose deprivation (OGD) for 8 h or 3 h, respectively, with or without 300 nM insulin. The insulin neuroprotection during OGD was evaluated in both cellular models in terms of cell death, and in SK-N-SH for DMT1 protein expression and acute ferrous iron treatment, performed in acidic conditions, known to promote the maximum DMT1 uptake as a proton co-transporter; and the transactivation of 1B/DMT1 mouse promoter, already known to be responsive to NF-kB, was analyzed in primary mouse cortical neurons. Results: Insulin neuroprotection during OGD was concomitant to the down-regulation of both DMT1 protein expression and 1B/DMT1 mouse promoter transactivation. We also showed the insulin-dependent protection from cell death after acute ferrous iron treatment. In conclusion, although preliminary, this evaluation highlights the peculiar role of DMT1 as a possible pharmacological target, involved in neuroprotection by insulin during in vitro neuronal ischemia and acute ferrous iron uptake

Der Schuleffekt auf die Mathematikleistung in PISA 2012: ein Vergleich zwischen zwei Kantonen in der Schweiz

Through this research, we explored the relationship between student achievement and school environment. We compared mathematics scores from the PISA test in Ticino and Geneva. We discovered that in both cantons there is a significant but moderate school effect on student mathematics performance (around 7% of the variance is attributable to school affiliation). Based on our results, we rejected the hypothesis that the context effect was a social and/or academic compositional one. We identified other factors, related to the teaching staff (seniority) and to the organization (class size), which may partly explain the between-school variance. However, we did not identify a systematic effect, since none of the variables analyzed were found to be statistically significant in both cantons. (DIPF/Orig.)In dieser Studie haben wir den Zusammenhang zwischen Erfolg und Schulumfeld untersucht. Wir haben die Mathematikergebnisse im PISA-Test in den Kantonen Tessin und Genf verglichen. In beiden Kantonen besteht ein signifikanter, aber gemäßigter institutioneller Einfluss auf die Mathematikleistung (etwa 7% der Abweichung sind auf die Schule zurückzuführen). Aufgrund unserer Ergebnisse haben wir die Hypothese abgelehnt, dass der Kontext-Effekt ein Effekt der sozialen und/oder akademischen Zusammensetzung ist. Wir haben andere Faktoren in Bezug auf Lehrpersonal und Organisation identifiziert, die zum Teil die Unterschiede zwischen den Institutionen erklären können. Wir konnten jedoch keinen systematischen Effekt finden; keine der Variablen waren in beiden Kantonen statistisch signifikant. (DIPF/Orig.

On the relations between historical epistemology and students’ conceptual developments in mathematics

There is an ongoing discussion within the research field of mathematics education regarding the utilization of the history of mathematics within mathematics education. In this paper we consider problems that may emerge when the historical epistemology of mathematics is paralleled to students’ conceptual developments in mathematics. We problematize this attempt to link the two fields on the basis of Grattan-Guinness’ distinction between “history” and “heritage”. We argue that when parallelism claims are made, history and heritage are often mixed up, which is problematic since historical mathematical definitions must be interpreted in its proper historical context and conceptual framework. Furthermore, we argue that cultural and local ideas vary at different time periods, influencing conceptual developments in different directions regardless of whether historical or individual developments are considered, and thus it may be problematic to uncritically assume a platonic perspective. Also, we have to take into consideration that an average student of today and great mathematicians of the past are at different cognitive levels

Worldwide prevalence of tocophobia in pregnant women: systematic review and meta-analysis

Introduction: Tocophobia is defined as a severe fear of pregnancy and childbirth. There is increasing evidence that tocophobia may have short-term and long-term adverse effects on mother and baby. We performed a systematic review and meta-analysis to determine the global prevalence of tocophobia in pregnancy. Material and methods: Relevant articles were identified through searching six relevant databases: MEDLINE, CINAHL, Pubmed, PsycINFO, Maternity & Infant Care and Scopus between 1946 and April 2016. We used search terms for tocophobia prevalence in pregnant women that we agreed with a medical librarian. There were no language restrictions. Two review authors independently assessed data for inclusion, extracted data and assessed quality using a standardized appraisal tool. Meta-analysis was performed to determine the overall pooled-prevalence of tocophobia. Several subgroup and sensitivity analyses were conducted. Results: Thirty-three studies were included in the systematic review from 18 countries of which data from 29 studies were used in the meta-analysis of 853 988 pregnant women. Definition of tocophobia varied, whereas prevalence rates ranged between 3.7 and 43%. The overall pooled prevalence of tocophobia, using a random-effects model, was 14% (95% CI 0.12â 0.16). Significant heterogeneity was observed (I2 = 99.25%, p = 0.00), which was not explained in subgroup analyses including tocophobia definition used, screening trimester and parity. Conclusion: The prevalence of tocophobia is estimated at 14% and appears to have increased in recent years (2000 onwards). Considerable heterogeneity (99.25%) was noted that may be attributed to lack of consensus on the definition of tocophobia, so our results should be interpreted with caution