The stability of Cl-, Br-, and I-passivated Si(100)-(2 × 1) in ambient environments for atomically-precise pattern preservation.

Atomic precision advanced manufacturing (APAM) leverages the highly reactive nature of Si dangling bonds relative to H- or Cl-passivated Si to selectively adsorb precursor molecules into lithographically defined areas with sub-nanometer resolution. Due to the high reactivity of dangling bonds, this process is confined to ultra-high vacuum (UHV) environments, which currently limits its commercialization and broad-based appeal. In this work, we explore the use of halogen adatoms to preserve APAM-derived lithographic patterns outside of UHV to enable facile transfer into real-world commercial processes. Specifically, we examine the stability of H-, Cl-, Br-, and I-passivated Si(100) in inert N2and ambient environments. Characterization with scanning tunneling microscopy and x-ray photoelectron spectroscopy (XPS) confirmed that each of the fully passivated surfaces were resistant to oxidation in 1 atm of N2for up to 44 h. Varying levels of surface degradation and contamination were observed upon exposure to the laboratory ambient environment. Characterization byex situXPS after ambient exposures ranging from 15 min to 8 h indicated the Br- and I-passivated Si surfaces were highly resistant to degradation, while Cl-passivated Si showed signs of oxidation within minutes of ambient exposure. As a proof-of-principle demonstration of pattern preservation, a H-passivated Si sample patterned and passivated with independent Cl, Br, I, and bare Si regions was shown to maintain its integrity in all but the bare Si region post-exposure to an N2environment. The successful demonstration of the preservation of APAM patterns outside of UHV environments opens new possibilities for transporting atomically-precise devices outside of UHV for integrating with non-UHV processes, such as other chemistries and commercial semiconductor device processes.

STM-Induced Desorption and Lithographic Patterning of Cl-Si(100)-(2 × 1).

A scanning tunneling microscope (STM) was used to investigate tip-induced chlorine desorption and lithographic patterning of Cl-terminated Si(100)-(2 × 1) surfaces from 4 to 600 K in ultrahigh vacuum. Until now, STM lithography has exclusively focused on hydrogen-based chemistry for donor device fabrication. As the initial step in developing halogen-based chemistries for STM fabrication of acceptor-based devices, we substituted the hydrogen resist with chlorine. We found that chlorine can be selectively desorbed by the STM tip using both electron and hole injection. Observations show that targeted chlorine was not driven into the surface but desorbed completely as both individual and pairs of atoms. Chlorine depassivation lithography is demonstrated using both field-emission patterning to desorb chlorine from large areas with high efficiency (0.83(1)) and atomic-precision patterning to desorb one to two dimer rows at a time, resulting in 1.5 nm wide lines. Further, varying the experimental parameters for lithography revealed a positive correlation between pattern line widths and both positive sample bias voltage (1.7(2) nm/V) and total electron dose (0.15(2) nm/(mC/cm)), demonstrating that the energy and total number of electrons play a role in desorption from multiple sites.

[Guides to chemical risk assessment in the construction industry]. / Percorsi di valutazione del rischio chimico in edilizia.

The presence of chemical agents in construction is certainly relevant in terms of quality, quantity and toxicity. Their manipulation can result in potential exposure as inhaled and/or through the skin. It is therefore possible and necessary to identify a list of substances to be considered relevant for the risk assessment and the possible environmental monitoring to verify the adequacy of the estimate made. The many variables inherent in construction make it extremely difficult to apply the usual methods of the industrial hygiene because it would not very significant conclusions in terms of space-time representation. SIMLII in one of its guidelines have proposed a "indexes" method that can provide useful information to the figures of prevention for the actions of their competence. The subsequent introduction of the REACH Regulation and exposure scenarios may help to further sharpening the assessment of chemical hazards in construction.

Holoprosencephaly in clomiphene-induced pregnancy: a possible association? A case report and literature review.

Clomiphene is widely used for inducing ovulation. Evidence for congenital abnormalities, in particular central nervous system defects (CNS-D) and in babies born from clomiphene-induced pregnancies is conflicting. The authors report a case of holoprosencephalia (HPE) in a fetus delivered from a mother receiving clomiphene.

Bioimpedance modeling to monitor astrocytic response to chronically implanted electrodes.

The widespread adoption of neural prosthetic devices is currently hindered by our inability to reliably record neural signals from chronically implanted electrodes. The extent to which the local tissue response to implanted electrodes influences recording failure is not well understood. To investigate this phenomenon, impedance spectroscopy has shown promise for use as a non-invasive tool to estimate the local tissue response to microelectrodes. Here, we model impedance spectra from chronically implanted rats using the well-established Cole model, and perform a correlation analysis of modeled parameters with histological markers of astroglial scar, including glial fibrillary acid protein (GFAP) and 4',6-diamidino-2- phenylindole (DAPI). Correlations between modeled parameters and GFAP were significant for three parameters studied: Py value, R(o) and |Z|(1 kHz), and in all cases were confined to the first 100 microm from the interface. Py value was the only parameter also correlated with DAPI in the first 100 microm. Our experimental results, along with computer simulations, suggest that astrocytes are a predominant cellular player affecting electrical impedance spectra. The results also suggest that the largest contribution from reactive astrocytes on impedance spectra occurs in the first 100 microm from the interface, where electrodes are most likely to record electrical signals. These results form the basis for future approaches where impedance spectroscopy can be used to evaluate neural implants, evaluate strategies to minimize scar and potentially develop closed-loop prosthetic devices.

Cl insertion on Si(100)-(2x1): etching under conditions of supersaturation.

We use scanning tunneling microscopy to show that Cl2 dosing of Cl-saturated Si(100)-(2x1) surfaces at elevated temperature leads to uptake beyond "saturation" and allows access to a new etching pathway. This process involves Cl insertion in Si-Si dimer bonds or backbonds, diffusion of the inserted Cl, and ultimately desorption of SiCl2. Investigations into the etch kinetics reveal that insertion occurs via a novel form of Cl2 dissociative chemisorption that is mediated by dangling bond sites. Upon dissociation, one Cl atom adsorbs at the dangling bond while the other can insert.

Intrinsic bursters increase the robustness of rhythm generation in an excitatory network.

The pre-Botzinger complex (pBC) is a vital subcircuit of the respiratory central pattern generator. Although the existence of neurons with pacemaker-like bursting properties in this network is not questioned, their role in network rhythmogenesis is unresolved. Modeling is ideally suited to address this debate because of the ease with which biophysical parameters of individual cells and network architecture can be manipulated. We modeled the parameter variability of experimental data from pBC bursting pacemaker and nonpacemaker neurons using a modified version of our previously developed pBC neuron and network models. To investigate the role of pacemakers in networkwide rhythmogenesis, we simulated networks of these neurons and varied the fraction of the population made up of pacemakers. For each number of pacemaker neurons, we varied the amount of tonic drive to the network and measured the frequency of synchronous networkwide bursting produced. Both excitatory networks with all-to-all coupling and sparsely connected networks were explored for several levels of synaptic coupling strength. Networks containing only nonpacemakers were able to produce networkwide bursting, but with a low probability of bursting and low input and output ranges. Our results indicate that inclusion of pacemakers in an excitatory network increases robustness of the network by more than tripling the input and output ranges compared with networks containing no pacemakers. The largest increase in dynamic range occurs when the number of pacemakers in the network is greater than 20% of the population. Experimental tests of our model predictions are proposed.

Web-based antidotes management: evaluation of an Italian experience.

Antidotes (ANT) are lifesaving drugs that must be timely administered in case of poisoning, but their availability when and where needed is often a problem. The experience of setting up a web-based national network aimed at sharing ANT availability information is described, together with the steps followed to make it be an effective solution.

Weak phase-resetting in neural oscillators.

Phase-resetting experiments have frequently been employed to understand the input/output dynamics of oscillatory physiological systems, such as the respiratory and cardiovascular systems. Analogous techniques based on phase-oscillator models have often been used in computational studies of neuronal networks. These models are often simplified by assuming weak coupling between neurons. This assumption has powerful ramifications for both experimental and theoretical studies, yet it has never been demonstrated in living neurons. Here we examine phase response curves (PRCs) for neurons with different stimulus waveforms. Focusing on amplitude, we show that weak amplitude stimuli create PRCs that scale linearly with amplitude, while strong do not. This is the first step in demonstrating that weak coupling occurs in living neurons. We also show that this notion of weak coupling is more stringent than the geometric classification of weak coupling frequently associated with experimental PRC analysis.

Genetic algorithm for optimization and specification of a neuron model.

We present a novel approach for neuron model specification using a Genetic Algorithm (GA) to develop simple firing neuron models consisting of a single compartment with one inward and one outward current. The GA not only chooses the model parameters, but also chooses the formulation of the ionic currents (i.e. single-variable, two-variable, instantaneous, or leak). The fitness function of the GA compares the frequency output of the GA generated models to an I-F curve of a nominal Morris-Lecar (ML) model. Initially, several different classes of models compete among the population. Eventually, the GA converges to a population containing only ML-type firing models with an instantaneous inward and single-variable outward current. Simulations where ML-type models are restricted from the population are also investigated. This GA approach allows the exploration of a universe of feasible model classes that is less constrained by model formulation assumptions than traditional parameter estimation approaches. While we use a simple model, this technique is scalable to much larger and more complex formulations.

A simple model of dynamic interactions between respiratory centers.

There is a general consensus that neurons responsible for the generation of a respiratory rhythm are located in the rostral ventrolateral medulla. However, there is still controversy regarding the necessary components for respiratory rhythm generation. Both inspiratory neurons in the preBotzinger Complex (preBOtC) and pre-inspiratory neurons located more rostrally to this anatomical structure referred to as the parafacial respiratory group (pFRG) have been proposed to be essential for respiratory rhythmogenesis. To study the dynamical interactions between preBOtC and pFRG neurons, we use a canonical model that describes each neuron population as a phase oscillator. We assume that the oscillators are weakly coupled with pFRG neurons providing stimulation to preBOtC neurons and preBOtC neurons providing inhibitory drive to pFRG neurons. In our mathematical study, we explore plausible mechanisms that may account for the complex interactions between I and pre-I neuron. In particular, we show that reduced excitability of inspiratory in preBOtC may lead to the phenomena known as "quantal slowing".

An implementation of a simple neuron model in field programmable analog arrays.

A minimal neuron model, the Morris-Lecar model, is implemented on field programmable analog arrays (FPAAs). Our approach is to solve the differential equation describing the model in a similar way a computer solves the same problem: numerically integrate the differential equation by making arithmetic operations on voltage mode circuits of the FPAAs. The results demonstrate that biologically relevant dynamics can be observed from the electronic neuron despite limitations on the configurability of the FPAAs. Such models can be run accurately in real-time or many orders of magnitude faster than real-time. FPAAs are feasible candidates for implementation of neuron models using off-the-shelf software-reconfigurable analog circuit elements.

Models of respiratory rhythm generation in the pre-Bötzinger complex. III. Experimental tests of model predictions.

We used the testable predictions of mathematical models proposed by Butera et al. to evaluate cellular, synaptic, and population-level components of the hypothesis that respiratory rhythm in mammals is generated in vitro in the pre-Bötzinger complex (pre-BötC) by a heterogeneous population of pacemaker neurons coupled by fast excitatory synapses. We prepared thin brain stem slices from neonatal rats that capture the pre-BötC and maintain inspiratory-related motor activity in vitro. We recorded pacemaker neurons extracellularly and found: intrinsic bursting behavior that did not depend on Ca(2+) currents and persisted after blocking synaptic transmission; multistate behavior with transitions from quiescence to bursting and tonic spiking states as cellular excitability was increased via extracellular K(+) concentration ([K(+)](o)); a monotonic increase in burst frequency and decrease in burst duration with increasing [K(+)](o); heterogeneity among different cells sampled; and an increase in inspiratory burst duration and decrease in burst frequency by excitatory synaptic coupling in the respiratory network. These data affirm the basis for the network model, which is composed of heterogeneous pacemaker cells having a voltage-dependent burst-generating mechanism dominated by persistent Na(+) current (I(NaP)) and excitatory synaptic coupling that synchronizes cell activity. We investigated population-level activity in the pre-BötC using local "macropatch" recordings and confirmed these model predictions: pre-BötC activity preceded respiratory-related motor output by 100-400 ms, consistent with a heterogeneous pacemaker-cell population generating inspiratory rhythm in the pre-BötC; pre-BötC population burst amplitude decreased monotonically with increasing [K(+)](o) (while frequency increased), which can be attributed to pacemaker cell properties; and burst amplitude fluctuated from cycle to cycle after decreasing bilateral synaptic coupling surgically as predicted from stability analyses of the model. We conclude that the pacemaker cell and network models explain features of inspiratory rhythm generation in vitro.

Cardiac damage in pediatric carbon monoxide poisoning.

BACKGROUND: Cardiovascular disorders including myocardial ischemia and heart failure have been described in both laboratory animals and humans following carbon monoxide poisoning. Carbon monoxide cardiotoxicity may be clinically occult and often remains undiagnosed because of the lack of overt symptoms and specific ischemic changes in the electrocardiogram. Routine myocardial necrosis markers have low diagnostic efficiency, particularly in patients with concomitant skeletal muscle necrosis or multiple organ failure complicating carbon monoxide poisoning. Carbon monoxide-induced cardiotoxicity has been investigated rarely in children. CASE REPORT: This paper describes carbon monoxide poisoning in a 12-year-old child who suffered from occult cardiac damage despite mild symptoms and low carboxy hemoglobin concentrations. Myocardial and mitral valve dysfunctions were observed, suggesting an ischemia-like syndrome. Cardiac damage was completely reversible within 1 month. CONCLUSION: This case report supports that a prolonged carbon monoxide exposure can cause cardiac damage in children even in the absence of specific symptoms, cerebral failure and high carboxyhemoglobin concentrations.

Carbon monoxide cardiotoxicity.

Cardiac dysfunction including arrhythmias and myocardial ischemia have often been reported in carbon monoxide poisoning; scattered punctiform hemorrhages throughout the heart have been documented in autopsy samples. An appropriate diagnostic approach is crucial to assess carbon monoxide cardiac damage. This evaluation may be confounded by several factors, including the absence of overt symptoms and of specific ischemic changes in the electrocardiogram. In experimental studies, laboratory animals can develop cardiac changes similar to those seen in humans and therefore proved to be useful models to study the effects and the mechanisms of cardiac damage due to carbon monoxide. These investigations, as well as others performed in vitro, provide support for a direct action of carbon monoxide on the heart, in addition to systemic hypoxia produced by carboxyhemoglobin formation. This review focuses on the diagnostic aspects of carbon monoxide cardiotoxicity. Experimental results obtained in animals and in vitro models are also discussed.

A methodology for achieving high-speed rates for artificial conductance injection in electrically excitable biological cells.

We present a novel approach to implementing the dynamic-clamp protocol (Sharp et al., 1993), commonly used in neurophysiology and cardiac electrophysiology experiments. Our approach is based on real-time extensions to the Linux operating system. Conventional PC-based approaches have typically utilized single-cycle computational rates of 10 kHz or slower. In thispaper, we demonstrate reliable cycle-to-cycle rates as fast as 50 kHz. Our system, which we call model reference current injection (MRCI); pronounced merci is also capable of episodic logging of internal state variables and interactive manipulation of model parameters. The limiting factor in achieving high speeds was not processor speed or model complexity, but cycle jitter inherent in the CPU/motherboard performance. We demonstrate these high speeds and flexibility with two examples: 1) adding action-potential ionic currents to a mammalian neuron under whole-cell patch-clamp and 2) altering a cell's intrinsic dynamics via MRCI while simultaneously coupling it via artificial synapses to an internal computational model cell. These higher rates greatly extend the applicability of this technique to the study of fast electrophysiological currents such fast a currents and fast excitatory/inhibitory synapses.