Universal logic with encoded spin qubits in silicon.

Quantum computation features known examples of hardware acceleration for certain problems, but is challenging to realize because of its susceptibility to small errors from noise or imperfect control. The principles of fault tolerance may enable computational acceleration with imperfect hardware, but they place strict requirements on the character and correlation of errors. For many qubit technologies, some challenges to achieving fault tolerance can be traced to correlated errors arising from the need to control qubits by injecting microwave energy matching qubit resonances.

Thyroid homeostasis in B6C3F1 mice upon sub-chronic exposure to trifluoroiodomethane (CFI).

Trifluoroiodomethane (CFI) is a fire suppressant gas with potential for use in low global-warming refrigerant blends. Data from studies in rats suggest that the most sensitive health effect of CFI is thyroid hormone perturbation, but the rat is a particularly sensitive species for disruption of thyroid homeostasis. Mice appear to be less sensitive than rats but still a conservative model with respect to humans.

Quantifying error and leakage in an encoded Si/SiGe triple-dot qubit.

Quantum computation requires qubits that satisfy often-conflicting criteria, which include long-lasting coherence and scalable control. One approach to creating a suitable qubit is to operate in an encoded subspace of several physical qubits. Although such encoded qubits may be particularly susceptible to leakage out of their computational subspace, they can be insensitive to certain noise processes and can also allow logical control with a single type of entangling interaction while maintaining favourable features of the underlying physical system.

Immunization with a Recombinant, Pseudomonas fluorescens-Expressed, Mutant Form of Bacillus anthracis-Derived Protective Antigen Protects Rabbits from Anthrax Infection.

Protective antigen (PA), one of the components of the anthrax toxin, is the major component of human anthrax vaccine (Biothrax). Human anthrax vaccines approved in the United States and Europe consist of an alum-adsorbed or precipitated (respectively) supernatant material derived from cultures of toxigenic, non-encapsulated strains of Bacillus anthracis. Approved vaccination schedules in humans with either of these vaccines requires several booster shots and occasionally causes adverse injection site reactions.

Biologic comparison of inhaled insulin formulations: Exubera™ and novel spray-dried engineered particles of dextran-10.

Inhaled peptides and proteins have promise for respiratory and systemic disease treatment. Engineered spray-dried powder formulations have been shown to stabilize peptides and proteins and optimize aerosol properties for pulmonary delivery. The current study was undertaken to investigate the in vitro and in vivo inhalation performance of a model spray-dried powder of insulin and dextran 10 in comparison to Exubera™.

Local and systemic tolerability of a 2'O-methoxyethyl antisense oligonucleotide targeting interleukin-4 receptor-α delivery by inhalation in mouse and monkey.

Antisense oligonucleotides (ASOs) bind and facilitate degradation of RNA and inhibit protein expression in pathways not easily targeted with small molecules or antibodies. Interleukin (IL)-4 and IL-13 potentiate signaling through the shared IL-4 receptor-α (IL-4Rα) subunit of their receptors. ASO targeting of IL-4Rα mRNA in a mouse model of asthma led to attenuation of airway hyperactivity, demonstrating potential benefit in asthma patients.

SGI-110 and entinostat therapy reduces lung tumor burden and reprograms the epigenome.

The DNA methyltransferase (DNMT) inhibitor vidaza (5-Azacytidine) in combination with the histone deacetylase inhibitor entinostat has shown promise in treating lung cancer and this has been replicated in our orthotopic lung cancer model. However, the effectiveness of DNMT inhibitors against solid tumors is likely impacted by their limited stability and rapid inactivation by cytidine deaminase (CDA) in the liver. These studies were initiated to test the efficacy of SGI-110, a dinucleotide containing decitabine that is resistant to deamination by CDA, as a single agent and in combination with entinostat.

Challenges for inhaled drug discovery and development: Induced alveolar macrophage responses.

Alveolar macrophage (AM) responses are commonly induced in inhalation toxicology studies, typically being observed as an increase in number or a vacuolated 'foamy' morphology. Discriminating between adaptive AM responses and adverse events during nonclinical and clinical development is a major scientific challenge. When measuring and interpreting induced AM responses, an understanding of macrophage biology is essential; this includes 'sub-types' of AMs with different roles in health and disease and mechanisms of induction/resolution of AM responses to inhalation of pharmaceutical aerosols.

Comparison of inhalation toxicity studies of gentamicin in rats and dogs.

Nebulized gentamicin solution was administered to rats (nose-only) and dogs (face mask) for 14 days with a 14-day recovery period. Control groups of each were exposed to saline aerosols. Mean estimated inhaled lung doses of gentamicin were 39, 123 and 245 mg/kg for rats (deposited doses 6, 17 and 34 mg/kg) over 30, 90 and 180 min, respectively.

STP position paper: interpreting the significance of increased alveolar macrophages in rodents following inhalation of pharmaceutical materials.

The Scientific and Regulatory Policy Committee of the Society of Toxicologic Pathology (STP) appointed a working group to address risk assessment for increases in alveolar macrophages following inhalation of pharmaceutical materials. This position paper provides recommendations for inhalation study-specific terminology and interpretation based on literature and information from marketed inhaled drugs. Based on a weight-of-the-evidence approach, and with appropriate consideration of the physical and pharmacological characteristics of the compound, uncomplicated increases in the size or number of alveolar macrophages in nonclinical species are interpreted as nonadverse.

Safety assessment of nebulized xylitol in beagle dogs.

Xylitol, a potential cystic fibrosis treatment, lowers the salt concentration of airway surface liquid and enhances innate immunity of human airways. The study objective was to evaluate the potential toxicity/recovery from a 14-consecutive day (7 days/week), facemask inhalation administration of nebulized xylitol solution in Beagle dogs. Aerosolized xylitol was generated through three Aerotech II nebulizers operating at approximately 40 psi driving pressure.

Effects of simulated downwind coal combustion emissions on pre-existing allergic airway responses in mice.

Context: Coal-fired power plant emissions can contribute a significant portion of the ambient air pollution in many parts of the world.

Objective: We hypothesized that exposure to simulated downwind coal combustion emissions (SDCCE) may exacerbate pre-existing allergic airway responses.

Methods: Mice were sensitized and challenged with ovalbumin (OVA).

Health effects of subchronic inhalation exposure to simulated downwind coal combustion emissions.

Context: There have been no animal studies of the health effects of repeated inhalation of mixtures representing downwind pollution from coal combustion. Environmental exposures typically follow atmospheric processing and mixing with pollutants from other sources.

Objective: This was the fourth study by the National Environmental Respiratory Center to create a database for responses of animal models to combustion-derived pollutant mixtures, to identify causal pollutants-regardless of source.

Hypercholesterolemia potentiates aortic endothelial response to inhaled diesel exhaust.

Background: Inhalation of diesel exhaust induces vascular effects including impaired endothelial function and increased atherosclerosis.

Objective: To examine the in vivo effects of subchronic diesel exhaust exposure on endothelial cell transcriptional responses in the presence of hypercholesterolemia.

Methods: ApoE (-/-) and ApoE (+/+) mice inhaled diesel exhaust diluted to particulate matter levels of 300 or 1000 μg/m³ vs.

Inhaled diesel emissions alter atherosclerotic plaque composition in ApoE(-/-) mice.

Recent epidemiological studies suggest that traffic-related air pollution may have detrimental effects on cardiovascular health. Previous studies reveal that gasoline emissions can induce several enzyme pathways involved in the formation and development of atherosclerotic plaques. As a direct comparison, the present study examined the impact of diesel engine emissions on these pathways, and further examined the effects on vascular lesion pathology.

Effects of gasoline engine emissions on preexisting allergic airway responses in mice.

Gasoline-powered vehicle emissions contribute significantly to ambient air pollution. We hypothesized that exposure to gasoline engine emissions (GEE) may exacerbate preexisting allergic airway responses. Male BALB/c mice were sensitized by injection with ovalbumin (OVA) and then received a 10-min aerosolized OVA challenge.

Health effects of inhaled gasoline engine emissions.

Despite their prevalence in the environment, and the myriad studies that have shown associations between morbidity or mortality with proximity to roadways (proxy for motor vehicle exposures), relatively little is known about the toxicity of gasoline engine emissions (GEE). We review the studies conducted on GEE to date, and summarize the findings from each of these studies. While there have been several studies, most of the studies were conducted prior to 1980 and thus were not conducted with contemporary engines, fuels, and driving cycles.

Fresh gasoline emissions, not paved road dust, alter cardiac repolarization in ApoE-/- mice.

Fresh vehicular emissions potentially represent a ubiquitous environmental concern for cardiovascular health. We compared electrocardiographic effects of fresh gasoline engine emissions with resuspended paved road dust in a mouse model of coronary insufficiency. Apolipoprotein E (ApoE)-/- mice on a high fat diet were exposed by whole-body inhalation to either gasoline emissions at 60 microg/m3 particulate matter (PM), an equivalent atmosphere with particles filtered out of the whole exhaust, or paved road dust at 0.

Effects of hardwood smoke exposure on allergic airway inflammation in mice.

Hardwood smoke (HWS) from wood burning stoves and fireplaces can be a significant contributor to the composition of ambient air pollution. We hypothesize that the inhalation of HWS by ovalbumin (OVA)-sensitized mice with preexisting lung inflammation leads to the exacerbation of allergic airway responses. Two different models were employed to characterize the effects of inhaled wood smoke on allergic airway inflammation.

Low-level subchronic exposure to wood smoke exacerbates inflammatory responses in allergic rats.

Epidemiological studies have implicated wood smoke as a risk factor for exacerbating asthma. However, comparisons of findings in animal models with those in humans are currently not possible, because detailed clinically relevant measurements of pulmonary function are not available in animal studies. Brown Norway rats were immunized with ovalbumin and exposed to either filtered air or wood smoke at 1 mg particulate matter/m(3) for 70 days and challenged with allergen during the last 4 days of exposure.

Responses to subchronic inhalation of low concentrations of diesel exhaust and hardwood smoke measured in rat bronchoalveolar lavage fluid.

Air pollution exposure is associated with adverse health effects, but the causal components and mechanisms are unclear. We compared effects of daily exposure for 6 mo to diesel exhaust (DE) or hardwood smoke (HWS) at 4 concentrations between 30 and 1000 microg/(3) of total particulate matter, or filtered air, in male and female rats. Lung lavage fluid was assayed for toxicity indicators, cytokines, and glutathione.

Hardwood smoke alters murine splenic T cell responses to mitogens following a 6-month whole body inhalation exposure.

The purpose of these studies was to assess the effects of hardwood smoke (HWS) inhalation (30-1000 microg/m3) on the systemic immune responses of A/J mice evaluated after 6 months of daily exposures. Spleen cells obtained from mice were assessed for changes in cell number, cell surface marker expression [B, T, macrophage, and natural killer (NK) cells], and responses to B cell (LPS, endotoxin) and T cell (Con A) mitogens. Results showed that HWS smoke increased T cell proliferation in the 100 microg/m3 exposure group and produced a concentration-dependent suppression of T cell proliferation at concentrations >300 microg/m3.

Inhaled diesel engine emissions reduce bacterial clearance and exacerbate lung disease to Pseudomonas aeruginosa infection in vivo.

Despite experimental evidence supporting an adverse role for air pollution in models of human disease, little has been done in the way of assessing the health effects of inhalation of whole mixtures from defined sources at exposure levels relevant to ambient environmental exposures. The current study assessed the impact of inhaled diesel engine emissions (DEE) in modulating clearance of Pseudomonas aeruginosa (P.a.

Systemic immunotoxicity in AJ mice following 6-month whole body inhalation exposure to diesel exhaust.

The purpose of these studies was to determine the effects of subchronic diesel exposure on indicators of systemic immunity in mice. AJ mice were exposed daily for 6 months (6 h/day) to atmospheres containing one of four concentrations (30, 100, 300, and 1000 microg/m(3)) of diluted diesel exhaust (DE) in whole body exposure chambers. The effects of DE were compared to chamber exposure controls receiving fresh air.

Cardiovascular effects of inhaled diesel exhaust in spontaneously hypertensive rats.

Particulate matter air pollution is associated with increased cardiovascular mortality. The present study examined the cardiac effects of diesel exhaust exposure in spontaneously hypertensive rats. These rats (4 mo old, n = 6 males and 4-6 females/concentration) were exposed to one of five diesel exhaust levels (0, 30, 100, 300, and 1000 micrograms particles/m3) for 6 h per day for 7 d.