The detection of climate change due to the enhanced greenhouse effect

The greenhouse effect is accepted as an undisputed fact from both theoretical and observational considerations. In Earth's atmosphere, the primary greenhouse gas is water vapor. The specific concern today is that increasing concentrations of anthropogenically introduced greenhouse gases will, sooner or later, irreversibly alter the climate of Earth. Detecting climate change has been complicated by uncertainties in historical observations and measurements. Thus, the primary concern for the GEDEX project is how can climate change and enhanced greenhouse effects be unambiguously detected and quantified. Specifically examined are the areas of: Earth surface temperature; the free atmosphere (850 millibars and above); space-based measurements; measurement uncertainties; and modeling the observed temperature record

Limited effect of highly active antiretroviral therapy among HIV-positive injecting drug users on the population level

There is evidence that HIV-positive injecting drug users benefit less than other risk groups from highly active antiretroviral therapy that has been available since 1996. In this multicentre European study the impact of the availability of highly active antiretroviral therapy on the progression rates to AIDS and death among injecting drug users with a documented date of HIV seroconversion is studied. After highly active antiretroviral therapy became available the risk of AIDS and death for injecting drug users decreased by 28% and 36%, which is less than has been reported for other risk group

Structural Determination of the Broadly Reactive Anti-IGHV1-69 Anti-idiotypic Antibody G6 and Its Idiotope

The heavy chain IGHV1-69 germline gene exhibits a high level of polymorphism and shows biased use in protective antibody (Ab) responses to infections and vaccines. It is also highly expressed in several B cell malignancies and autoimmune diseases. G6 is an anti-idiotypic monoclonal Ab that selectively binds to IGHV1-69 heavy chain germline gene 51p1 alleles that have been implicated in these Ab responses and disease processes. Here, we determine the co-crystal structure of humanized G6 (hG6.3) in complex with anti-influenza hemagglutinin stem-directed broadly neutralizing Ab D80. The core of the hG6.3 idiotope is a continuous string of CDR-H2 residues starting with M53 and ending with N58. G6 binding studies demonstrate the remarkable breadth of binding to 51p1 IGHV1-69 Abs with diverse CDR-H3, light chain, and antigen binding specificities. These studies detail the broad expression of the G6 cross-reactive idiotype (CRI) that further define its potential role in precision medicine

Unique structural solution from a VH3-30 antibody targeting the hemagglutinin stem of influenza A viruses

Broadly neutralizing antibodies (bnAbs) targeting conserved influenza A virus (IAV) hemagglutinin (HA) epitopes can provide valuable information for accelerating universal vaccine designs. Here, we report structural details for heterosubtypic recognition of HA from circulating and emerging IAVs by the human antibody 3I14. Somatic hypermutations play a critical role in shaping the HCDR3, which alone and uniquely among VH3-30 derived antibodies, forms contacts with five sub-pockets within the HA-stem hydrophobic groove. 3I14 light-chain interactions are also key for binding HA and contribute a large buried surface area spanning two HA protomers. Comparison of 3I14 to bnAbs from several defined classes provide insights to the bias selection of VH3-30 antibodies and reveals that 3I14 represents a novel structural solution within the VH3-30 repertoire. The structures reported here improve our understanding of cross-group heterosubtypic binding activity, providing the basis for advancing immunogen designs aimed at eliciting a broadly protective response to IAV

Investigation of the 2006 Drought and 2007 Flood Extremes at the Southern Great Plains Through an Integrative Analysis of Observations

Hydrological years 2006 (HY06, 10/2005-09/2006) and 2007 (HY07, 10/2006-09/2007) provide a unique opportunity to examine hydrological extremes in the central US because there are no other examples of two such highly contrasting precipitation extremes occurring in consecutive years at the Southern Great Plains (SGP) in recorded history. The HY06 annual precipitation in the state of Oklahoma, as observed by the Oklahoma Mesonet, is around 61% of the normal (92.84 cm, based on the 1921-2008 climatology), which results in HY06 the second-driest year in the record. In particular, the total precipitation during the winter of 2005-06 is only 27% of the normal, and this winter ranks as the driest season. On the other hand, the HY07 annual precipitation amount is 121% of the normal and HY07 ranks as the seventh-wettest year for the entire state and the wettest year for the central region of the state. Summer 2007 is the second-wettest season for the state. Large-scale dynamics play a key role in these extreme events. During the extreme dry period (10/2005-02/2006), a dipole pattern in the 500-hPa GH anomaly existed where an anomalous high was over the southwestern U.S. region and an anomalous low was over the Great Lakes. This pattern is associated with inhibited moisture transport from the Gulf of Mexico and strong sinking motion over the SGP, both contributing to the extreme dryness. The precipitation deficit over the SGP during the extreme dry period is clearly linked to significantly suppressed cyclonic activity over the southwestern U.S., which shows robust relationship with the Western Pacific (WP) teleconnection pattern. The precipitation events during the extreme wet period (May-July 2007) were initially generated by active synoptic weather patterns, linked with moisture transport from the Gulf of Mexico by the northward low level jet, and enhanced by the mesoscale convective systems. Although the drought and pluvial conditions are dominated by large-scale dynamic patterns, we have demonstrated that the two positive feedback processes during the extreme dry and wet periods found in this study play a key role to maintain and reinforce the length and severity of existing drought and flood events. For example, during the extreme dry period, with less clouds, LWP, PWV, precipitation, and thinner Cu cloud thickness, more net radiation was absorbed and used to evaporate water from the ground. The evaporated moisture, however, was removed by low-level divergence. Thus, with less precipitation and removed atmospheric moisture, more absorbed incoming solar radiation was used to increase surface temperature and to make the ground drier

Substitution in a sense

The Reference Principle (RP) states that co-referring expressions are everywhere intersubstitutable salva congruitate. On first glance, (RP) looks like a truism, but a truism with some bite: (RP) transforms difficult philosophical questions about co-reference into easy grammatical questions about substitutability. This has led a number of philosophers to think that we can use (RP) to make short work of certain longstanding metaphysical debates. For example, it has been suggested that all we need to do to show that the predicate ‘( ) is a horse’ does not refer to a property is point out that ‘( ) is a horse’ and ‘the property of being a horse’ are not everywhere intersubstitutable salva congruitate. However, when we understand ‘substitution’ in the simplest and most straightforward way, (RP) is no truism; in fact, natural languages are full of counterexamples to the principle. In this paper, I introduce a new notion of substitution, and then develop and argue for a version of (RP) that is immune to these counterexamples. Along the way I touch on the following topics: the relation between argument forms and their natural language instances; the reification of sense; the difference between terms and predicates; and the relation between reference and disquotation. I end by arguing that my new version of (RP) cannot be used to settle metaphysical debates quite as easily as some philosophers would like

Positive Selection Drives Preferred Segment Combinations during Influenza Virus Reassortment

Influenza A virus (IAV) has a segmented genome that allows for the exchange of genome segments between different strains. This reassortment accelerates evolution by breaking linkage, helping IAV cross species barriers to potentially create highly virulent strains. Challenges associated with monitoring the process of reassortment in molecular detail have limited our understanding of its evolutionary implications. We applied a novel deep sequencing approach with quantitative analysis to assess the in vitro temporal evolution of genomic reassortment in IAV. The combination of H1N1 and H3N2 strains reproducibly generated a new H1N2 strain with the hemagglutinin and nucleoprotein segments originating from H1N1 and the remaining six segments from H3N2. By deep sequencing the entire viral genome, we monitored the evolution of reassortment, quantifying the relative abundance of all IAV genome segments from the two parent strains over time and measuring the selection coefficients of the reassorting segments. Additionally, we observed several mutations coemerging with reassortment that were not found during passaging of pure parental IAV strains. Our results demonstrate how reassortment of the segmented genome can accelerate viral evolution in IAV, potentially enabled by the emergence of a small number of individual mutation

Positive Selection Drives Preferred Segment Combinations during Influenza Virus Reassortment

Influenza A virus (IAV) has a segmented genome that allows for the exchange of genome segments between different strains. This reassortment accelerates evolution by breaking linkage, helping IAV cross species barriers to potentially create highly virulent strains. Challenges associated with monitoring the process of reassortment in molecular detail have limited our understanding of its evolutionary implications. We applied a novel deep sequencing approach with quantitative analysis to assess the in vitro temporal evolution of genomic reassortment in IAV. The combination of H1N1 and H3N2 strains reproducibly generated a new H1N2 strain with the hemagglutinin and nucleoprotein segments originating from H1N1 and the remaining six segments from H3N2. By deep sequencing the entire viral genome, we monitored the evolution of reassortment, quantifying the relative abundance of all IAV genome segments from the two parent strains over time and measuring the selection coefficients of the reassorting segments. Additionally, we observed several mutations coemerging with reassortment that were not found during passaging of pure parental IAV strains. Our results demonstrate how reassortment of the segmented genome can accelerate viral evolution in IAV, potentially enabled by the emergence of a small number of individual mutation