Role of surface charge and oxidative stress in cytotoxicity of organic monolayer-coated silicon nanoparticles towards macrophage NR8383 cells

Background - Surface charge and oxidative stress are often hypothesized to be important factors in cytotoxicity of nanoparticles. However, the role of these factors is not well understood. Hence, the aim of this study was to systematically investigate the role of surface charge, oxidative stress and possible involvement of mitochondria in the production of intracellular reactive oxygen species (ROS) upon exposure of rat macrophage NR8383 cells to silicon nanoparticles. For this aim highly monodisperse (size 1.6 ± 0.2 nm) and well-characterized Si core nanoparticles (Si NP) were used with a surface charge that depends on the specific covalently bound organic monolayers: positively charged Si NP-NH2, neutral Si NP-N3 and negatively charged Si NP-COOH. Results - Positively charged Si NP-NH2 proved to be more cytotoxic in terms of reducing mitochondrial metabolic activity and effects on phagocytosis than neutral Si NP-N3, while negatively charged Si NP-COOH showed very little or no cytotoxicity. Si NP-NH2 produced the highest level of intracellular ROS, followed by Si NP-N3 and Si NP-COOH; the latter did not induce any intracellular ROS production. A similar trend in ROS production was observed in incubations with an isolated mitochondrial fraction from rat liver tissue in the presence of Si NP. Finally, vitamin E and vitamin C induced protection against the cytotoxicity of the Si NP-NH2 and Si NP-N3, corroborating the role of oxidative stress in the mechanism underlying the cytotoxicity of these Si NP. Conclusion - Surface charge of Si-core nanoparticles plays an important role in determining their cytotoxicity. Production of intracellular ROS, with probable involvement of mitochondria, is an important mechanism for this cytotoxicit

Cancellation of OpAmp virtual ground imperfections by a negative conductance applied to improve RF receiver linearity

High linearity CMOS radio receivers often exploit linear V-I conversion at RF, followed by passive down-mixing and an OpAmp-based Transimpedance Amplifier at baseband. Due to nonlinearity and finite gain in the OpAmp, virtual ground is imperfect, inducing distortion currents. This paper proposes a negative conductance concept to cancel such distortion currents. Through a simple intuitive analysis, the basic operation of the technique is explained. By mathematical analysis the optimum negative conductance value is derived and related to feedback theory. In- and out-of-band linearity, stability and Noise Figure are also analyzed. The technique is applied to linearize an RF receiver, and a prototype is implemented in 65 nm technology. Measurement results show an increase of in-band IIP3 from 9dBm to >20dBm, and IIP2 from 51 to 61dBm, at the cost of increasing the noise figure from 6 to 7.5dB and <10% power penalty. In 1MHz bandwidth, a Spurious-Free Dynamic Range of 85dB is achieved at <27mA up to 2GHz for 1.2V supply voltage

A CMOS spectrum analyzer frontend for cognitive radio achieving +25dBm IIP3 and −169 dBm/Hz DANL

A dual RF-receiver preceded by discrete-step attenuators is implemented in 65nm CMOS and operates from 0.3– 1.0 GHz. The noise of the receivers is reduced by cross-correlating the two receiver outputs in the digital baseband, allowing attenuation of the RF input signal to increase linearity. With this technique a displayed average noise level below -169 dBm/Hz is obtained with +25 dBm IIP3, giving a spurious-free dynamic range of 89 dB in 1 MHz resolution bandwidth

Baseline Functioning and Stress Reactivity in Maltreating Parents and At-Risk Adults: Review and Meta-Analyses of Autonomic Nervous System Studies.

We reviewed and meta-analyzed 10 studies ( N = 492) that examined the association between (risk for) child maltreatment perpetration and basal autonomic activity, and 10 studies ( N = 471) that examined the association between (risk for) child maltreatment and autonomic stress reactivity. We hypothesized that maltreating parents/at-risk adults would show higher basal levels of heart rate (HR) and skin conductance (SC) and lower levels of HR variability (HRV) and would show greater HR and SC stress reactivity, but blunted HRV reactivity. A narrative review showed that evidence from significance testing within and across studies was mixed. The first set of meta-analyses revealed that (risk for) child maltreatment was associated with higher HR baseline activity ( g = 0.24), a possible indication of allostatic load. The second set of meta-analyses yielded no differences in autonomic stress reactivity between maltreating/at-risk participants and nonmaltreating/low-risk comparison groups. Cumulative meta-analyses showed that positive effects for sympathetic stress reactivity as a risk factor for child maltreatment were found in a few early studies, whereas each subsequently aggregated study reduced the combined effect size to a null effect, an indication of the winner's curse. Most studies were underpowered. Future directions for research are suggested.The study was supported by the Netherlands Organization for Scientific Research (LRAA: VIDI grant; MHvIJ: NWO SPINOZA prize; MJBK: VICI grant), and the Wellcome Trust (WT103343MA).This is the final version of the article. It first appeared from SAGE Publications via http://dx.doi.org/10.1177/1077559516659937

Estimation of conditional laws given an extreme component

Let $(X,Y)$ be a bivariate random vector. The estimation of a probability of the form $P(Y\leq y \mid X >t)$ is challenging when $t$ is large, and a fruitful approach consists in studying, if it exists, the limiting conditional distribution of the random vector $(X,Y)$, suitably normalized, given that $X$ is large. There already exists a wide literature on bivariate models for which this limiting distribution exists. In this paper, a statistical analysis of this problem is done. Estimators of the limiting distribution (which is assumed to exist) and the normalizing functions are provided, as well as an estimator of the conditional quantile function when the conditioning event is extreme. Consistency of the estimators is proved and a functional central limit theorem for the estimator of the limiting distribution is obtained. The small sample behavior of the estimator of the conditional quantile function is illustrated through simulations.Comment: 32 pages, 5 figur

Predicting growth curves of early childhood externalizing problems: Differential susceptibility of children with difficult temperament

Using an accelerated longitudinal design, the development of externalizing problems from age 2 to 5 years was investigated in relation to maternal psychopathology, maternal parenting, gender, child temperament, and the presence of siblings. The sample consisted of 150 children selected at age 2-3 years for having high levels of externalizing problems. Parenting was measured using observational methods, and maternal reports were used for the other variables. Overall, mean levels of externalizing problems decreased over time, and higher initial levels (intercept) were related to a stronger decrease (negative slope) in externalizing problems. Results showed that higher levels of maternal psychopathology were related to less decrease in early childhood externalizing problems. Parental sensitive behavior predicted a stronger decrease in externalizing problems, but only for children with difficult temperaments. A stronger decrease of externalizing problems in children with older siblings also pertained only to children with difficult temperaments. Thus, temperamentally difficult children appear to be more susceptible to environmental influences on the development of externalizing behaviors. Our results indicate that the role of siblings in early childhood externalizing problems deserves more research attention, and that intervention efforts need to take into account temperamental differences in children's susceptibility to environmental influences. © 2009 Springer Science+Business Media, LLC

A receiver with in-band IIP3&gt;20dBm, exploiting cancelling of OpAmp finite-gain-induced distortion via negative conductance

Highly linear CMOS radio receivers increasingly exploit linear RF V-I conversion and passive down-mixing, followed by an OpAmp based Transimpedance Amplifier at baseband. Due to the finite OpAmp gain in wideband receivers operating with large signals, virtual ground is imperfect, inducing distortion currents. We propose to apply a negative conductance to cancel this distortion. In an RF receiver, this increases In-Band IIP3 from 9dBm to >20dBm, at the cost of 1.5dB extra NF and <10% power penalty. In 1MHz bandwidth, a Spurious-Free Dynamic Range of 85dB is achieved at <27mA up to 2GHz for 1.2V supply voltage