Systemic inflammation is established as part of late-stage severe lung disease, but molecular, functional, and phenotypic changes in peripheral immune cells in early disease stages remain ill ...defined. Chronic obstructive pulmonary disease (COPD) is a major respiratory disease characterized by small-airway inflammation, emphysema, and severe breathing difficulties. Using single-cell analyses we demonstrate that blood neutrophils are already increased in early-stage COPD, and changes in molecular and functional neutrophil states correlate with lung function decline. Assessing neutrophils and their bone marrow precursors in a murine cigarette smoke exposure model identified similar molecular changes in blood neutrophils and precursor populations that also occur in the blood and lung. Our study shows that systemic molecular alterations in neutrophils and their precursors are part of early-stage COPD, a finding to be further explored for potential therapeutic targets and biomarkers for early diagnosis and patient stratification.
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•Increase in blood neutrophil molecular states in early-stage COPD•Progenitor reprogramming is linked to altered blood neutrophil states•Neutrophil state abundance correlates with lung function decline
Kapellos et al. show that systemic molecular changes in neutrophils in early-stage COPD are associated with increased granulopoiesis and demonstrate that neutrophil transcriptomic states correlate with lung function decline.
For the first time near‐global retrievals of mesopause OH rotational temperatures from satellite‐borne Meinel band emission measurements are presented. The measurements of the OH (3‐1) Meinel band ...near 1.5 micron were performed with the SCIAMACHY instrument on the European Space Agency's environmental satellite Envisat. The derived OH (3‐1) rotational temperatures are shown to be in reasonable agreement with the CIRA (1986) atmosphere temperatures for the seasons and latitudes considered. The derived temperatures are in good agreement with ground‐based measurements of the OH rotational temperature performed with a CEDAR Mesospheric Temperature Mapper (MTM) at Maui, Hawaii (21°N/204°E), with the GRound based Infrared P‐branch Spectrometer I (GRIPS‐I) at Hohenpeißenberg (47°N/11°E) and with GRIPS‐II at Wuppertal (51°N/7°E). The SCIAMACHY limb nighttime observations provide a unique data set of near‐global OH rotational temperature to study seasonal and geographical variations, dynamical processes and possibly long‐term temperature trends, if an extended data set becomes available in the future.
We present the largest longitudinal study to date that examines the association between Kaposi's Sarcoma (KS) disease progression and the presence and viral load of human herpesvirus 8 (HHV-8).
...Ninety-six men were enrolled at HIV clinics in Atlanta, Georgia, who had KS (n = 47) or were without KS but seropositive for HHV-8. Visits occurred at 6-month intervals for 2 years at which the patient's KS status was evaluated and oral fluid and blood were collected for quantification of HHV-8 DNA and antibodies.
The presence of HHV-8 DNA in blood was more common (P < 0.001) and the viral load higher (P < 0.001) in men with KS in comparison with men without KS. Mean HHV-8 viral loads in blood and oral fluids were associated with disease status, being highest among patients with progressing KS, intermediate among patients with stable KS, and lowest among patients with regressing KS. Consistent with our previous report high antibody titers to HHV-8 orf 65 were inversely associated with HHV-8 shedding in oral fluid.
We observed a significant association between changes in KS disease severity and the presence and viral load of HHV-8. HHV-8 viral load in blood may provide useful information to clinicians for assessment of the risk of further disease progression in patients with KS.
To identify risk factors for Kaposi's sarcoma (KS) among men seropositive for both human herpesvirus 8 (HHV-8) and HIV.
Cross-sectional study of 91 HHV-8 seropositive, HIV seropositive men who have ...sex with men (57 with KS), and 70 controls at lower risk for KS.
Patients received clinical evaluations. Blood, oral fluids, semen, rectal brush, rectal swab, and urine were collected, and tests for HHV-8 were performed.
Men with KS were more likely to have HHV-8 DNA in peripheral blood mononuclear cells (PBMC) than men without KS 35.1 versus 5.9%, odds ratio (OR), 8.6, 95% confidence interval (CI), 1.9-39.9. The prevalence of HHV-8 DNA in oral fluids was similar for the two groups (37.0 versus 32.4%; OR, 1.2; 95% CI, 0.5-3.0). HHV-8 DNA was rarely detected in specimens of other types from these men, or in any specimens from the 70 controls. Among men with KS, HHV-8 DNA in PBMC was associated with new KS lesions (OR, 4.5; 95% CI, 1.4-14.5), and HHV-8 DNA in oral fluids was associated with oropharyngeal KS lesions (OR, 3.1; 95% CI, 1.0-10.1). Men with high HHV-8 antibody titers were more likely to have KS (OR, 9.6; 95% CI, 1.2-78.2), but were less likely to have new KS lesions (OR, 0.2; 95% CI, 0.0-1.1) or HHV-8 DNA in PBMC (OR, 0.2; 95% CI, 0.0-1.6) or oral fluids (OR, undefined; = 0.001).
In HHV-8- and HIV-seropositive men, HHV-8 DNA is associated with KS. Among men without KS, HHV-8 DNA is most commonly found in oral fluids. High HHV-8 antibody titers may protect against circulating HHV-8 and new KS lesions.
Microglia maintain homeostasis in the brain. However, with age, they become primed and respond more strongly to inflammatory stimuli. We show here that microglia from aged mice had upregulated mTOR ...complex 1 signaling controlling translation, as well as protein levels of inflammatory mediators. Genetic ablation of mTOR signaling showed a dual yet contrasting effect on microglia priming: it caused an NF-κB-dependent upregulation of priming genes at the mRNA level; however, mice displayed reduced cytokine protein levels, diminished microglia activation, and milder sickness behavior. The effect on translation was dependent on reduced phosphorylation of 4EBP1, resulting in decreased binding of eIF4E to eIF4G. Similar changes were present in aged human microglia and in damage-associated microglia, indicating that upregulation of mTOR-dependent translation is an essential aspect of microglia priming in aging and neurodegeneration.
ROOT is an object-oriented C++ framework conceived in the high-energy physics (HEP) community, designed for storing and analyzing petabytes of data in an efficient way. Any instance of a C++ class ...can be stored into a ROOT file in a machine-independent compressed binary format. In ROOT the TTree object container is optimized for statistical data analysis over very large data sets by using vertical data storage techniques. These containers can span a large number of files on local disks, the web, or a number of different shared file systems. In order to analyze this data, the user can chose out of a wide set of mathematical and statistical functions, including linear algebra classes, numerical algorithms such as integration and minimization, and various methods for performing regression analysis (fitting). In particular, the RooFit package allows the user to perform complex data modeling and fitting while the RooStats library provides abstractions and implementations for advanced statistical tools. Multivariate classification methods based on machine learning techniques are available via the TMVA package. A central piece in these analysis tools are the histogram classes which provide binning of one- and multi-dimensional data. Results can be saved in high-quality graphical formats like Postscript and PDF or in bitmap formats like JPG or GIF. The result can also be stored into ROOT macros that allow a full recreation and rework of the graphics. Users typically create their analysis macros step by step, making use of the interactive C++ interpreter CINT, while running over small data samples. Once the development is finished, they can run these macros at full compiled speed over large data sets, using on-the-fly compilation, or by creating a stand-alone batch program. Finally, if processing farms are available, the user can reduce the execution time of intrinsically parallel tasks — e.g. data mining in HEP — by using PROOF, which will take care of optimally distributing the work over the available resources in a transparent way.
Program title: ROOT
Catalogue identifier: AEFA_v1_0
Program summary URL:
http://cpc.cs.qub.ac.uk/summaries/AEFA_v1_0.html
Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland
Licensing provisions: LGPL
No. of lines in distributed program, including test data, etc.: 3 044 581
No. of bytes in distributed program, including test data, etc.: 36 325 133
Distribution format: tar.gz
Programming language: C++
Computer: Intel i386, Intel x86-64, Motorola PPC, Sun Sparc, HP PA-RISC
Operating system: GNU/Linux, Windows XP/Vista, Mac OS X, FreeBSD, OpenBSD, Solaris, HP-UX, AIX
Has the code been vectorized or parallelized?: Yes
RAM:
>
55
Mbytes
Classification: 4, 9, 11.9, 14
Nature of problem: Storage, analysis and visualization of scientific data
Solution method: Object store, wide range of analysis algorithms and visualization methods
Additional comments: For an up-to-date author list see:
http://root.cern.ch/drupal/content/root-development-team and
http://root.cern.ch/drupal/content/former-root-developers
Running time: Depending on the data size and complexity of analysis algorithms
References:
1
http://root.cern.ch.
Satellite observations have produced global measurements of hydroxyl (OH) in the atmosphere that reveals a sharp peak in OH density near an altitude of 65 to 70 km. These findings are are consistent ...with observations from the Halogen Occultation Experiment that show an unexplained H2O layer at the same level.
To study the natural history and pathogenesis of human herpesvirus 8 (HHV-8) infection in HHV-8-seropositive, immunosuppressed men.
Longitudinal study of 87 HHV-8- and HIV-seropositive men 42 with ...Kaposi's sarcoma (KS) during four visits over a 2 month period.
: Patients provided oral fluid and blood. HHV-8 antibody titers were measured with peptide-based enzyme-linked immunosorbent assays (ELISA) for ORF65 and K8.1; HHV-8 DNA was detected with polymerase chain reaction ELISA.
HHV-8 DNA was present in oral fluid or peripheral blood mononuclear cells (PBMC) at one or more of the four visits in 71% of men with KS and 56% of men without KS. The strongest correlate of HHV-8 DNA in PBMC was the presence of KS odds ratio (OR), 8.7; 95% confidence interval (CI), 3.4-22. Detection of HHV-8 DNA in oral fluid or PBMC was often intermittent, but individuals who shed virus at one time point were more likely to shed at other times. Some men had incomplete epitope recognition in their anti-HHV-8 antibody response. High antibody titers were associated with the absence of circulating HHV-8, particularly for the ORF65 seroassay (OR, 0.16; 95% CI, 0.05-0.51).
Among HHV-8 seropositive men, circulating virus is common even in the absence of disease. The link between KS and HHV-8 DNA in PBMC suggests that anti-herpes drugs may impede KS development or progression. Seroassays should target multiple epitopes to achieve maximal sensitivity. HHV-8 replication may be limited by high antibody titers or other immune function for which antibodies are a marker.
Recent experiments in the Trident laser facility (Los Alamos National Laboratory) have shown that hollow conical targets with a flat top at the tip can enhance the maximum energy of proton beams ...created during the interaction of an ultra-intense short laser pulse with the target (Gaillard S A et al 2011 Phys. Plasmas 18 056710). The proton energies that have been seen in these experiments are the highest energies observed so far in laser-driven proton acceleration. This is attributed to a new acceleration mechanism, direct light pressure acceleration of electrons (DLLPA), which increases the number and energy of hot electrons that drive the proton acceleration. This acceleration process of protons due to a two-temperature sheath formed at the flat-top rear side is very robust and produces a large number of protons per shot, similar to what is regularly observed in target normal sheath acceleration (Hatchett S P et al 2000 Phys. Plasmas 7 2076, Maksimchuk A et al 2000 Phys. Rev. Lett. 84 4108, Snavely R A et al 2000 Phys. Rev. Lett. 85 2945) with flat foils. In this paper, we investigate the electron kinetics during DLLPA, showing that they are governed by two mechanisms, both of which lead to continuous electron acceleration along the inner cone wall. Based on our model, we predict the scaling of the hot electron temperature and ion maximum energy with both laser and target geometrical parameters. The scaling of with the laser strength parameter a0 leads to an ion energy scaling that surpasses that of some recently proposed acceleration mechanisms such as radiation pressure acceleration (RPA), while in addition the maximum electron energy is found to scale linearly with the length of the cone neck. We find that when optimizing parameters, high proton energies suitable for applications can be reached using compact short-pulse laser systems with pulse durations of only a few tens to hundreds of laser periods.
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