Microscopic Structure of Liquid Nitric Oxide

The microscopic structure of nitric oxide is investigated using neutron scattering experiments. The measurements are performed at various temperatures between 120 and 144 K and at pressures between 1.1 and 9 bar. Using the technique of empirical potential structure refinement (EPSR), our results show that the dimer is the main form, around 80%, of nitric oxide in the liquid phase at 120 K, but the degree of dissociation to monomers increases with increasing temperature. The reported degree of dissociation of dimers, and its trend with increasing temperature, is consistent with earlier measurements and studies. It is also shown that nonplanar dimers are not inconsistent with the diffraction data and that the possibility of nitric oxide molecules forming longer oligomers, consisting of bonded nitrogen atoms along the backbone, cannot be ruled out in the liquid. A molecular dynamics simulation is used to compare the present EPSR simulations with an earlier proposed intermolecular potential for the liquid

Induction of apoptosis in rat peripheral blood lymphocytes by the anticancer drug CI-994 (acetyldinaline)

ABSTRACT: CI-994 (acetyldinaline) is an investigational anticancer drug currently in clinical trials. In preclinical safety studies in rats and dogs, CI-994 resulted in significant toxicity to bone marrow and lymphoid tissue. To determine if apoptosis was involved in CI-994 toxicity, peripheral blood lymphocytes were isolated from untreated male Wistar rats and exposed to CI-994 (1, 3, 10, or 30 μM) in vitro for up to 24 hours. Morphological and biochemical features of apoptosis were evaluated using several techniques, and lactate dehydrogenase (LDH) release was measured as an indicator of cell necrosis. No evidence of apoptosis or necrosis was detected in lymphocytes exposed to CI-994 for 4 hours. After 24 hours, concentration-dependent increases in apoptosis characterized by DNA condensation, DNA fragmentation, and/or externalization of phosphatidyl serine were seen at CI-994 concentrations as low as 1 μM and were statistically significant beginning at 10 μM. Ultrastructural analysis confirmed the presence of DNA condensation, DNA fragmentation, cell shrinkage, and membrane blebbing in cells exposed to 30 μM CI-994. After 24 hours, the percent of maximum LDH release from lymphocytes treated with 10 and 30 μM CI-994 was 7% and 15%, respectively, compared with 0% in the controls. In comparison, morphological changes of apoptosis detected by fluorescent microscopy were observed in 79% of the lymphocytes at these two concentrations. Additionally, apoptosis was seen in more than 24% of lymphocytes exposed to 1 and 3 μM CI-994, whereas maximum LDH release was less than or equal to 1% at these concentrations. These results show that apoptosis is the primary mode of cell death in rat lymphocytes exposed to CI-994 in vitro

Antibody-mediated immunity to the obligate intracellular bacterial pathogen Coxiella burnetii is Fc receptor- and complement-independent

<p>Abstract</p> <p>Background</p> <p>The obligate intracellular bacterial pathogen <it>Coxiella burnetii </it>causes the zoonosis Q fever. The intracellular niche of <it>C. burnetii </it>has led to the assumption that cell-mediated immunity is the most important immune component for protection against this pathogen. However, passive immunization with immune serum can protect naïve animals from challenge with virulent <it>C. burnetii</it>, indicating a role for antibody (Ab) in protection. The mechanism of this Ab-mediated protection is unknown. Therefore, we conducted a study to determine whether Fc receptors (FcR) or complement contribute to Ab-mediated immunity (AMI) to <it>C. burnetii</it>.</p> <p>Results</p> <p>Virulent <it>C. burnetii </it>infects and replicates within human dendritic cells (DC) without inducing their maturation or activation. We investigated the effects of Ab opsonized <it>C. burnetii </it>on human monocyte-derived and murine bone marrow-derived DC. Infection of DC with Ab-opsonized <it>C. burnetii </it>resulted in increased expression of maturation markers and inflammatory cytokine production. Bacteria that had been incubated with naïve serum had minimal effect on DC, similar to virulent <it>C. burnetii </it>alone. The effect of Ab opsonized <it>C. burnetii </it>on DC was FcR dependent as evidenced by a reduced response of DC from FcR knockout (FcR k/o) compared to C57Bl/6 (B6) mice. To address the potential role of FcR in Ab-mediated protection in vivo, we compared the response of passively immunized FcR k/o mice to the B6 controls. Interestingly, we found that FcR are not essential for AMI to <it>C. burnetii </it>in vivo. We subsequently examined the role of complement in AMI by passively immunizing and challenging several different strains of complement-deficient mice and found that AMI to <it>C. burnetii </it>is also complement-independent.</p> <p>Conclusion</p> <p>Despite our data showing FcR-dependent stimulation of DC in vitro, Ab-mediated immunity to <it>C. burnetii </it>in vivo is FcR-independent. We also found that passive immunity to this pathogen is independent of complement.</p

Prevalence and Trends in Obesity and Severe Obesity Among Children in the United States, 1999-2012

IMPORTANCE: Childhood obesity is the focus of public health efforts and accurate estimates of the prevalence and severity of obesity are needed for policy decisions and directions for future research. OBJECTIVE: To examine the prevalence of obesity and severe obesity over time for 14 years of the continuous National Health and Nutrition Examination Survey, 1999 to 2012, and to examine differences in the trends by age, race/ethnicity, and sex. DESIGN, SETTING, AND PARTICIPANTS: Representative sample (N = 26 690) of children in the United States, ages 2 to 19 years, in repeated cross-sections of the National Health and Nutrition Examination Survey, 1999 to 2012. MAIN OUTCOMES AND MEASURES: Prevalence of overweight (body mass index [BMI] ≥ 85th percentile), obesity (BMI ≥ 95th percentile for age and sex), class 2 obesity (BMI ≥ 120% of the 95th percentile or BMI ≥ 35), and class 3 obesity (BMI ≥ 140% of the 95th percentile or BMI ≥ 40). RESULTS: From 2011 to 2012, 17.3% (95% CI, 15.3-19.3) of children in the United States aged 2 to 19 years were obese. Additionally, 5.9% (95% CI, 4.4-7.4) of children met criteria for class 2 obesity and 2.1% (95% CI, 1.6-2.7) met criteria for class 3 obesity. Although these rates were not significantly different from 2009 to 2010, all classes of obesity have increased over the last 14 years. CONCLUSIONS AND RELEVANCE: Nationally representative data do not show any significant changes in obesity prevalence in the most recently available years, although the prevalence of obesity may be stabilizing. Continuing research is needed to determine which, if any, public health interventions can be credited with this stability. Unfortunately, there is an upward trend of more severe forms of obesity and further investigations into the causes of and solutions to this problem are needed

Experimental and modelling evidence for structural crossover in supercritical CO₂

Physics of supercritical state is understood to a much lesser degree compared to subcritical liquids. Carbon dioxide in particular has been intensely studied, yet little is known about the supercritical part of its phase diagram. Here, we combine neutron scattering experiments and molecular dynamics simulations and demonstrate the structural crossover at the Frenkel line. The crossover is seen at pressures as high as 14 times the critical pressure and is evidenced by changes of the main features of the structure factor and pair distribution functions

Lithium isotopes within the ab intio no-core full configuration approach

We perform no-core full configuration calculations for the Lithium isotopes, 6Li, 7Li, and 8Li with the realistic nucleon-nucleon interaction JISP16. We obtain a set of observables, such as spectra, radii, multipole moments, transition rates, etc., and compare with experiment where available. We also present one-body density distributions for selected states. Convergence properties of these density distributions shed light on the convergence properties of one-body observables. We obtain underbinding by 0.5 MeV, 0.7 MeV, and 1.0 MeV for 6Li, 7Li, 8Li respectively. Magnetic moments are well-converged and agree with experiment to within 20%.Comment: 16 pages, 25 eps figures; typos corrected and added referenc