A reduced order model for the study of asymmetries in linear gas chromatography for homogeneous tubular columns.

In gas chromatography, a chemical sample separates into its constituent components as it travels along a long thin column. As the component chemicals exit the column they are detected and identified, allowing the chemical makeup of the sample to be determined. For correct identification of the component chemicals, the distribution of the concentration of each chemical along the length of the column must be nearly symmetric. The prediction and control of asymmetries in gas chromatography has been an active research area since the advent of the technique. In this paper, we develop from first principles a general model for isothermal linear chromatography. We use this model to develop closed-form expressions for terms related to the first, second, and third moments of the distribution of the concentration, which determines the velocity, diffusion rate, and asymmetry of the distribution. We show that for all practical experimental situations, only fronting peaks are predicted by this model, suggesting that a nonlinear chromatography model is required to predict tailing peaks. For situations where asymmetries arise, we analyze the rate at which the concentration distribution returns to a normal distribution. Numerical examples are also provided

Lineage-dependent effects of aryl hydrocarbon receptor agonists contribute to liver tumorigenesis

Rodent cancer bioassays indicate that the aryl hydrocarbon receptor (AHR) agonist, 2,3,7,8-tetracholorodibenzo-p-dioxin (TCDD), causes increases in both hepatocytic and cholangiocytic tumors. Effects of AHR activation have been evaluated on rodent hepatic stem cells (rHpSCs) versus their descendants, hepatoblasts (rHBs), two lineage stages of multipotent, hepatic precursors with overlapping but also distinct phenotypic traits. This was made possible by defining the first successful culture conditions for ex vivo maintenance of rHpScs consisting of a substratum of hyaluronans and Kubota's medium (KM), a serum-free medium designed for endodermal stem/progenitor cells. Supplementation of KM with leukemia inhibitory factor elicited lineage restriction to rHBs. Cultures were treated with various AHR agonists including TCDD, 6-formylindolo-[3,2-b]carbazole (FICZ), and 3-3'-diindolylmethane (DIM) and then analyzed with a combination of immunocytochemistry, gene expression, and high-content image analysis. The AHR agonists increased proliferation of rHpSCs at concentrations producing a persistent AHR activation as indicated by induction of Cyp1a1. By contrast, treatment with TCDD resulted in a rapid loss of viability of rHBs, even though the culture conditions, in the absence of the agonists, were permissive for survival and expansion of rHBs. The effects were not observed with FICZ and at lower concentrations of DIM. Conclusion: Our findings are consistent with a lineage-dependent mode of action for AHR agonists in rodent liver tumorigenesis through selective expansion of rHpSCs in combination with a toxicity-induced loss of viability of rHBs. These lineage-dependent effects correlate with increased frequency of liver tumors. (Hepatology 2015;61:548-560

Non-Native Plant Invasion along Elevation and Canopy Closure Gradients in a Middle Rocky Mountain Ecosystem

Mountain environments are currently among the ecosystems least invaded by non-native species; however, mountains are increasingly under threat of non-native plant invasion. The slow pace of exotic plant invasions in mountain ecosystems is likely due to a combination of low anthropogenic disturbances, low propagule supply, and extreme/steep environmental gradients. The importance of any one of these factors is debated and likely ecosystem dependent.We evaluated the importance of various correlates of plant invasions in the Wallowa Mountain Range of northeastern Oregon and explored whether non-native species distributions differed from native species along an elevation gradient. Vascular plant communities were sampled in summer 2012 along three mountain roads. Transects (n = 20) were evenly stratified by elevation (~70 m intervals) along each road. Vascular plant species abundances and environmental parameters were measured. We used indicator species analysis to identify habitat affinities for non-native species. Plots were ordinated in species space, joint plots and non-parametric multiplicative regression were used to relate species and community variation to environmental variables. Nonnative species richness decreased continuously with increasing elevation. In contrast, native species richness displayed a unimodal distribution with maximum richness occurring at mid–elevations. Species composition was strongly related to elevation and canopy openness. Overlays of trait and environmental factors onto non-metric multidimensional ordinations identified the montane-subalpine community transition and over-story canopy closure exceeding 60% as potential barriers to non-native species establishment. Unlike native species, non-native species showed little evidence for high-elevation or closed-canopy specialization. These data suggest that non-native plants currently found in the Wallowa Mountains are dependent on open canopies and disturbance for establishment in low and mid elevations. Current management objectives including restoration to more open canopies in dry Rocky Mountain forests, may increase immigration pressure of non-native plants from lower elevations into the montane and subalpine zones

An Autoreactive Antibody from an SLE/HIV-1 Individual Broadly Neutralizes HIV-1

Broadly HIV-1–neutralizing antibodies (BnAbs) display one or more unusual traits, including a long heavy chain complementarity-determining region 3 (HCDR3), polyreactivity, and high levels of somatic mutations. These shared characteristics suggest that BnAb development might be limited by immune tolerance controls. It has been postulated that HIV-1–infected individuals with autoimmune disease and defective immune tolerance mechanisms may produce BnAbs more readily than those without autoimmune diseases. In this study, we identified an HIV-1–infected individual with SLE who exhibited controlled viral load (\u3c5,000 copies/ml) in the absence of controlling HLA phenotypes and developed plasma HIV-1 neutralization breadth. We collected memory B cells from this individual and isolated a BnAb, CH98, that targets the CD4 binding site (CD4bs) of HIV-1 envelope glycoprotein 120 (gp120). CH98 bound to human antigens including dsDNA, which is specifically associated with SLE. Anti-dsDNA reactivity was also present in the patient’s plasma. CH98 had a mutation frequency of 25% and 15% nt somatic mutations in the heavy and light chain variable domains, respectively, a long HCDR3, and a deletion in the light chain CDR1. The occurrence of anti-dsDNA reactivity by a HIV-1 CD4bs BnAb in an individual with SLE raises the possibility that some BnAbs and SLE-associated autoantibodies arise from similar pools of B cells

Outcomes in patients with gunshot wounds to the brain.

Introduction:Gunshot wounds to the brain (GSWB) confer high lethality and uncertain recovery. It is unclear which patients benefit from aggressive resuscitation, and furthermore whether patients with GSWB undergoing cardiopulmonary resuscitation (CPR) have potential for survival or organ donation. Therefore, we sought to determine the rates of survival and organ donation, as well as identify factors associated with both outcomes in patients with GSWB undergoing CPR. Methods:We performed a retrospective, multicenter study at 25 US trauma centers including dates between June 1, 2011 and December 31, 2017. Patients were included if they suffered isolated GSWB and required CPR at a referring hospital, in the field, or in the trauma resuscitation room. Patients were excluded for significant torso or extremity injuries, or if pregnant. Binomial regression models were used to determine predictors of survival/organ donation. Results:825 patients met study criteria; the majority were male (87.6%) with a mean age of 36.5 years. Most (67%) underwent CPR in the field and 2.1% (n=17) survived to discharge. Of the non-survivors, 17.5% (n=141) were considered eligible donors, with a donation rate of 58.9% (n=83) in this group. Regression models found several predictors of survival. Hormone replacement was predictive of both survival and organ donation. Conclusion:We found that GSWB requiring CPR during trauma resuscitation was associated with a 2.1% survival rate and overall organ donation rate of 10.3%. Several factors appear to be favorably associated with survival, although predictions are uncertain due to the low number of survivors in this patient population. Hormone replacement was predictive of both survival and organ donation. These results are a starting point for determining appropriate treatment algorithms for this devastating clinical condition. Level of evidence:Level II

Single-Molecule Conductance of Pyridine-Terminated Dithienylethene Switch Molecules

We have investigated the conductance of individual optically switchable dithienylethene molecules in both their conducting closed configuration and nonconducting open configuration, using the technique of repeatedly formed break-junctions. We employed pyridine groups to link the molecules to gold electrodes in order to achieve relatively well-defined molecular contacts and stable conductance. For the closed form of each molecule, we observed a peak in the conductance histogram constructed without any data selection, allowing us to determine the conductance of the fully stretched molecules. For two different dithienylethene derivatives, these closed-configuration conductances were (3.3 ± 0.5) × 10^(–5)G_0 and (1.5 ± 0.5) × 10^(–6)G_0, where G_0 is the conductance quantum. For the open configuration of the molecules, the existence of electrical conduction via the molecule was evident in traces of conductance versus junction displacement, but the conductance of the fully stretched molecules was less than the noise floor of our measurement. We can set a lower limit of 30 for the on/off ratio for the simplest dithienylethene derivative we have investigated. Density functional theory calculations predict an on/off ratio consistent with this result

Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500

Tunneling Spectra of Individual Magnetic Endofullerene Molecules

The manipulation of single magnetic molecules may enable new strategies for high-density information storage and quantum-state control. However, progress in these areas depends on developing techniques for addressing individual molecules and controlling their spin. Here we report success in making electrical contact to individual magnetic N@C60 molecules and measuring spin excitations in their electron tunneling spectra. We verify that the molecules remain magnetic by observing a transition as a function of magnetic field which changes the spin quantum number and also the existence of nonequilibrium tunneling originating from low-energy excited states. From the tunneling spectra, we identify the charge and spin states of the molecule. The measured spectra can be reproduced theoretically by accounting for the exchange interaction between the nitrogen spin and electron(s) on the C60 cage.Comment: 7 pages, 4 figures. Typeset in LaTeX, updated text of previous versio

Purification of Reversibly Oxidized Proteins (PROP) Reveals a Redox Switch Controlling p38 MAP Kinase Activity

Oxidation of cysteine residues of proteins is emerging as an important means of regulation of signal transduction, particularly of protein kinase function. Tools to detect and quantify cysteine oxidation of proteins have been a limiting factor in understanding the role of cysteine oxidation in signal transduction. As an example, the p38 MAP kinase is activated by several stress-related stimuli that are often accompanied by in vitro generation of hydrogen peroxide. We noted that hydrogen peroxide inhibited p38 activity despite paradoxically increasing the activating phosphorylation of p38. To address the possibility that cysteine oxidation may provide a negative regulatory effect on p38 activity, we developed a biochemical assay to detect reversible cysteine oxidation in intact cells. This procedure, PROP, demonstrated in vivo oxidation of p38 in response to hydrogen peroxide and also to the natural inflammatory lipid prostaglandin J2. Mutagenesis of the potential target cysteines showed that oxidation occurred preferentially on residues near the surface of the p38 molecule. Cysteine oxidation thus controls a functional redox switch regulating the intensity or duration of p38 activity that would not be revealed by immunodetection of phosphoprotein commonly interpreted as reflective of p38 activity

The dental calculus metabolome in modern and historic samples.

INTRODUCTION: Dental calculus is a mineralized microbial dental plaque biofilm that forms throughout life by precipitation of salivary calcium salts. Successive cycles of dental plaque growth and calcification make it an unusually well-preserved, long-term record of host-microbial interaction in the archaeological record. Recent studies have confirmed the survival of authentic ancient DNA and proteins within historic and prehistoric dental calculus, making it a promising substrate for investigating oral microbiome evolution via direct measurement and comparison of modern and ancient specimens. OBJECTIVE: We present the first comprehensive characterization of the human dental calculus metabolome using a multi-platform approach. METHODS: Ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) quantified 285 metabolites in modern and historic (200 years old) dental calculus, including metabolites of drug and dietary origin. A subset of historic samples was additionally analyzed by high-resolution gas chromatography-MS (GC-MS) and UPLC-MS/MS for further characterization of metabolites and lipids. Metabolite profiles of modern and historic calculus were compared to identify patterns of persistence and loss. RESULTS: Dipeptides, free amino acids, free nucleotides, and carbohydrates substantially decrease in abundance and ubiquity in archaeological samples, with some exceptions. Lipids generally persist, and saturated and mono-unsaturated medium and long chain fatty acids appear to be well-preserved, while metabolic derivatives related to oxidation and chemical degradation are found at higher levels in archaeological dental calculus than fresh samples. CONCLUSIONS: The results of this study indicate that certain metabolite classes have higher potential for recovery over long time scales and may serve as appropriate targets for oral microbiome evolutionary studies