Large-scale air mass characteristics observed over the remote tropical Pacific Ocean during March-April 1999: Results from PEM-Tropics B field experiment

Eighteen long-range flights over the Pacific Ocean between 38° S to 20° N and 166° E to 90° W were made by the NASA DC-8 aircraft during the NASA Pacific Exploratory Mission (PEM) Tropics B conducted from March 6 to April 18, 1999. Two lidar systems were flown on the DC-8 to remotely measure vertical profiles of ozone (O3), water vapor (H2O), aerosols, and clouds from near the surface to the upper troposphere along their flight track. In situ measurements of a wide range of gases and aerosols were made on the DC-8 for comprehensive characterization of the air and for correlation with the lidar remote measurements. The transition from northeasterly flow of Northern Hemispheric (NH) air on the northern side of the Intertropical Convergence Zone (ITCZ) to generally easterly flow of Southern Hemispheric (SH) air south of the ITCZ was accompanied by a significant decrease in O3, carbon monoxide, hydrocarbons, and aerosols and an increase in H2O. Trajectory analyses indicate that air north of the ITCZ came from Asia and/or the United States, while the air south of the ITCZ had a long residence time over the Pacific, perhaps originating over South America several weeks earlier. Air south of the South Pacific Convergence Zone (SPCZ) came rapidly from the west originating over Australia or Africa. This air had enhanced O3 and aerosols and an associated decrease in H2O. Average latitudinal and longitudinal distributions of O3 and H2O were constructed from the remote and in situ O3 and H2O data, and these distributions are compared with results from PEM-Tropics A conducted in August-October 1996. During PEM-Tropics B, low O3 air was found in the SH across the entire Pacific Basin at low latitudes. This was in strong contrast to the photochemically enhanced O3 levels found across the central and eastern Pacific low latitudes during PEM-Tropics A. Nine air mass types were identified for PEM-Tropics B based on their O3, aerosols, clouds, and potential vorticity characteristics. The data from each flight were binned by altitude according to air mass type, and these results showed the relative observational frequency of the different air masses as a function of altitude in seven regions over the Pacific. The average chemical composition of the major air mass types was determined from in situ measurements in the NH and SH, and these results provided insight into the origin, lifetime, and chemistry of the air in these regions. Copyright 2001 by the American Geophysical Union

Statistical Epistemic Logic

We introduce a modal logic for describing statistical knowledge, which we call statistical epistemic logic. We propose a Kripke model dealing with probability distributions and stochastic assignments, and show a stochastic semantics for the logic. To our knowledge, this is the first semantics for modal logic that can express the statistical knowledge dependent on non-deterministic inputs and the statistical significance of observed results. By using statistical epistemic logic, we express a notion of statistical secrecy with a confidence level. We also show that this logic is useful to formalize statistical hypothesis testing and differential privacy in a simple and abstract manner

Low incidence of limb-girdle muscular dystrophy type 2C revealed by a mutation study in Japanese patients clinically diagnosed with DMD

<p>Abstract</p> <p>Background</p> <p>Limb-girdle muscular dystrophy type 2C (LGMD2C) is an autosomal recessive muscle dystrophy that resembles Duchenne muscular dystrophy (DMD). Although DMD is known to affect one in every 3500 males regardless of race, a widespread founder mutation causing LGMD2C has been described in North Africa. However, the incidence of LGMD2C in Japanese has been unknown because the genetic background remains uncharacterized in many patients clinically diagnosed with DMD.</p> <p>Methods</p> <p>We enrolled 324 patients referred to the Kobe University Hospital with suspected DMD. Mutations in the dystrophin or the SGCG genes were analyzed using not only genomic DNA but also cDNA.</p> <p>Results</p> <p>In 322 of the 324 patients, responsible mutations in the dystrophin were successfully revealed, confirming DMD diagnosis. The remaining two patients had normal dystrophin expression but absence of γ-sarcoglycan in skeletal muscle. Mutation analysis of the SGCG gene revealed homozygous deletion of exon 6 in one patient, while the other had a novel single nucleotide insertion in exon 7 in one allele and deletion of exon 6 in the other allele. These mutations created a stop codon that led to a γ-sarcoglycan deficiency, and we therefore diagnosed these two patients as having LGMD2C. Thus, the relative incidence of LGMD2C among Japanese DMD-like patients can be calculated as 1 in 161 patients suspected to have DMD (2 of 324 patients = 0.6%). Taking into consideration the DMD incidence for the overall population (1/3,500 males), the incidence of LGMD2C can be estimated as 1 per 560,000 or 1.8 per million.</p> <p>Conclusions</p> <p>To the best of our knowledge, this is the first study to demonstrate a low incidence of LGMD2C in the Japanese population.</p

Integration across time determines path deviation discrimination for moving objects.

YesBackground: Human vision is vital in determining our interaction with the outside world. In this study we characterize our ability to judge changes in the direction of motion of objects-a common task which can allow us either to intercept moving objects, or else avoid them if they pose a threat. Methodology/Principal Findings: Observers were presented with objects which moved across a computer monitor on a linear path until the midline, at which point they changed their direction of motion, and observers were required to judge the direction of change. In keeping with the variety of objects we encounter in the real world, we varied characteristics of the moving stimuli such as velocity, extent of motion path and the object size. Furthermore, we compared performance for moving objects with the ability of observers to detect a deviation in a line which formed the static trace of the motion path, since it has been suggested that a form of static memory trace may form the basis for these types of judgment. The static line judgments were well described by a 'scale invariant' model in which any two stimuli which possess the same two-dimensional geometry (length/width) result in the same level of performance. Performance for the moving objects was entirely different. Irrespective of the path length, object size or velocity of motion, path deviation thresholds depended simply upon the duration of the motion path in seconds. Conclusions/Significance: Human vision has long been known to integrate information across space in order to solve spatial tasks such as judgment of orientation or position. Here we demonstrate an intriguing mechanism which integrates direction information across time in order to optimize the judgment of path deviation for moving objects.Wellcome Trust, Leverhulme Trust, NI

Transcriptional responses of Burkholderia cenocepacia to polymyxin B in isogenic strains with diverse polymyxin B resistance phenotypes

<p>Abstract</p> <p>Background</p> <p><it>Burkholderia cenocepacia </it>is a Gram-negative opportunistic pathogen displaying high resistance to antimicrobial peptides and polymyxins. We identified mechanisms of resistance by analyzing transcriptional changes to polymyxin B treatment in three isogenic <it>B. cenocepacia </it>strains with diverse polymyxin B resistance phenotypes: the polymyxin B-resistant parental strain K56-2, a polymyxin B-sensitive K56-2 mutant strain with heptoseless lipopolysaccharide (LPS) (RSF34), and a derivative of RSF34 (RSF34 4000B) isolated through multiple rounds of selection in polymyxin B that despite having a heptoseless LPS is highly polymyxin B-resistant.</p> <p>Results</p> <p>A heptoseless LPS mutant of <it>B. cenocepacia </it>was passaged through multiple rounds of selection to regain high levels of polymyxin B-resistance. This process resulted in various phenotypic changes in the isolate that could contribute to polymyxin B resistance and are consistent with LPS-independent changes in the outer membrane. The transcriptional response of three <it>B. cenocepacia </it>strains to subinhibitory concentrations of polymyxin B was analyzed using microarray analysis and validated by quantitative Real Time-PCR. There were numerous baseline changes in expression between the three strains in the absence of polymyxin B. In both K56-2 and RSF34, similar transcriptional changes upon treatment with polymyxin B were found and included upregulation of various genes that may be involved in polymyxin B resistance and downregulation of genes required for the synthesis and operation of flagella. This last result was validated phenotypically as both swimming and swarming motility were impaired in the presence of polymyxin B. RSF34 4000B had altered the expression in a larger number of genes upon treatment with polymyxin B than either K56-2 or RSF34, but the relative fold-changes in expression were lower.</p> <p>Conclusions</p> <p>It is possible to generate polymyxin B-resistant isolates from polymyxin B-sensitive mutant strains of <it>B. cenocepacia</it>, likely due to the multifactorial nature of polymyxin B resistance of this bacterium. Microarray analysis showed that <it>B. cenocepacia </it>mounts multiple transcriptional responses following exposure to polymyxin B. Polymyxin B-regulated genes identified in this study may be required for polymyxin B resistance, which must be tested experimentally. Exposure to polymyxin B also decreases expression of flagellar genes resulting in reduced swimming and swarming motility.</p

Engineered artificial antigen presenting cells facilitate direct and efficient expansion of tumor infiltrating lymphocytes

<p>Abstract</p> <p>Background</p> <p>Development of a standardized platform for the rapid expansion of tumor-infiltrating lymphocytes (TILs) with anti-tumor function from patients with limited TIL numbers or tumor tissues challenges their clinical application.</p> <p>Methods</p> <p>To facilitate adoptive immunotherapy, we applied genetically-engineered K562 cell-based artificial antigen presenting cells (aAPCs) for the direct and rapid expansion of TILs isolated from primary cancer specimens.</p> <p>Results</p> <p>TILs outgrown in IL-2 undergo rapid, CD28-independent expansion in response to aAPC stimulation that requires provision of exogenous IL-2 cytokine support. aAPCs induce numerical expansion of TILs that is statistically similar to an established rapid expansion method at a 100-fold lower feeder cell to TIL ratio, and greater than those achievable using anti-CD3/CD28 activation beads or extended IL-2 culture. aAPC-expanded TILs undergo numerical expansion of tumor antigen-specific cells, remain amenable to secondary aAPC-based expansion, and have low CD4/CD8 ratios and FOXP3+ CD4+ cell frequencies. TILs can also be expanded directly from fresh enzyme-digested tumor specimens when pulsed with aAPCs. These "young" TILs are tumor-reactive, positively skewed in CD8+ lymphocyte composition, CD28 and CD27 expression, and contain fewer FOXP3+ T cells compared to parallel IL-2 cultures.</p> <p>Conclusion</p> <p>Genetically-enhanced aAPCs represent a standardized, "off-the-shelf" platform for the direct ex vivo expansion of TILs of suitable number, phenotype and function for use in adoptive immunotherapy.</p

Drosophila melanogaster as a Model Host for the Burkholderia cepacia Complex

Colonization with bacterial species from the Burkholderia cepacia complex (Bcc) is associated with fast health decline among individuals with cystic fibrosis. In order to investigate the virulence of the Bcc, several alternative infection models have been developed. To this end, the fruit fly is increasingly used as surrogate host, and its validity to enhance our understanding of host-pathogen relationships has been demonstrated with a variety of microorganisms. Moreover, its relevance as a suitable alternative to mammalian hosts has been confirmed with vertebrate organisms.The aim of this study was to establish Drosophila melanogaster as a surrogate host for species from the Bcc. While the feeding method proved unsuccessful at killing the flies, the pricking technique did generate mortality within the populations. Results obtained with the fruit fly model are comparable with results obtained using mammalian infection models. Furthermore, validity of the Drosophila infection model was confirmed with B. cenocepacia K56-2 mutants known to be less virulent in murine hosts or in other alternative models. Competitive index (CI) analyses were also performed using the fruit fly as host. Results of CI experiments agree with those obtained with mammalian models.We conclude that Drosophila is a useful alternative infection model for Bcc and that fly pricking assays and competition indices are two complementary methods for virulence testing. Moreover, CI results indicate that this method is more sensitive than mortality tests

Molecular MRI of Inflammation in Atherosclerosis

Inflammatory activity in atherosclerotic plaque is a risk factor for plaque rupture and atherothrombosis and may direct interventional therapy. Inflammatory activity can be evaluated at the (sub)cellular level using in vivo molecular MRI. This paper reviews recent progress in contrast-enhanced molecular MRI to visualize atherosclerotic plaque inflammation. Various MRI contrast agents, among others ultra-small particles of iron oxide, low-molecular-weight Gd-chelates, micelles, liposomes, and perfluorocarbon emulsions, have been used for in vivo visualization of various inflammation-related targets, such as macrophages, oxidized LDL, endothelial cell expression, plaque neovasculature, MMPs, apoptosis, and activated platelets/thrombus. An enzyme-activatable magnetic resonance contrast agent has been developed to study myeloperoxidase activity in inflamed plaques. Agents creating contrast based on the chemical exchange saturation transfer mechanism were used for thrombus imaging. Transfer of these molecular MRI techniques to the clinic will critically depend on the safety profiles of these newly developed magnetic resonance contrast agents

A Unique Regulator Contributes to Quorum Sensing and Virulence in Burkholderia cenocepacia

Burkholderia cenocepacia causes chronic and life-threatening respiratory infections in immunocompromized people. The B. cenocepacia N-acyl-homoserine lactone (AHL)-dependent quorum sensing system relies on the production of AHLs by the synthases CepI and CciI while CepR, CciR and CepR2 control expression of many genes important for pathogenesis. Downstream from, and co-transcribed with cepI, lies BCAM1871 encoding a hypothetical protein that was uncharacterized prior to this study. Orthologs of B. cenocepacia BCAM1871 are uniquely found in Burkholderia spp and are conserved in their genomic locations in pathogenic Burkholderia. We observed significant effects on AHL activity upon mutation or overexpression of BCAM1871, although these effects were more subtle than those observed for CepI indicating BCAM1871 acts as an enhancer of AHL activity. Transcription of cepI, cepR and cciIR was significantly reduced in the BCAM1871 mutant. Swimming and swarming motilities as well as transcription of fliC, encoding flagellin, were significantly reduced in the BCAM1871 mutant. Protease activity and transcription of zmpA and zmpB, encoding extracellular zinc metalloproteases, were undetectable in the BCAM1871 mutant indicating a more significant effect of mutating BCAM1871 than cepI. Exogenous addition of OHL restored cepI, cepR and fliC transcription but had no effect on motility, protease activity or zmpA or zmpB transcription suggesting AHL-independent effects. The BCAM1871 mutant exhibited significantly reduced virulence in rat chronic respiratory and nematode infection models. Gene expression and phenotypic assays as well as vertebrate and invertebrate infection models showed that BCAM1871 significantly contributes to pathogenesis in B. cenocepacia

A Step Forward in Molecular Diagnostics of Lyssaviruses – Results of a Ring Trial among European Laboratories

Rabies is a lethal and notifiable zoonotic disease for which diagnostics have to meet the highest standards. In recent years, an evolution was especially seen in molecular diagnostics with a wide variety of different detection methods published. Therefore, a first international ring trial specifically designed on the use of reverse transcription polymerase chain reaction (RT-PCR) for detection of lyssavirus genomic RNA was organized. The trial focussed on assessment and comparison of the performance of conventional and real-time assays. In total, 16 European laboratories participated. All participants were asked to investigate a panel of defined lyssavirus RNAs, consisting of Rabies virus (RABV) and European bat lyssavirus 1 and 2 (EBLV-1 and -2) RNA samples, with systems available in their laboratory. The ring trial allowed the important conclusion that conventional RT-PCR assays were really robust assays tested with a high concordance between different laboratories and assays. The real-time RT-PCR system by Wakeley et al. (2005) in combination with an intercalating dye, and the combined version by Hoffmann and co-workers (2010) showed good sensitivity for the detection of all RABV samples included in this test panel. Furthermore, all used EBLV-specific assays, real-time RT-PCRs as well as conventional RT-PCR systems, were shown to be suitable for a reliable detection of EBLVs. It has to be mentioned that differences were seen in the performance between both the individual RT-PCR systems and the laboratories. Laboratories which used more than one molecular assay for testing the sample panel always concluded a correct sample result. Due to the markedly high genetic diversity of lyssaviruses, the application of different assays in diagnostics is needed to achieve a maximum of diagnostic accuracy. To improve the knowledge about the diagnostic performance proficiency testing at an international level is recommended before using lyssavirus molecular diagnostics e.g. for confirmatory testing