‘Our Responsibility and Privilege to Fight Freedom’s Fight’: Neoconservatism, the Project for the New American Century, and the Making of the Invasion of Iraq in 2003

The Project for the New American Century (PNAC) was a neoconservative Washington, D.C. foreign policy think tank, comprised of seasoned foreign policy stalwarts who had served multiple presidential administrations as well as outside-the-beltway defense contractors, that was founded in 1997 by William Kristol, editor of the conservative political magazine The Weekly Standard, and Robert Kagan, a foreign policy analyst and political commentator currently at the Brookings Institution. The PNAC would shut down its operations in 2006. Using The Weekly Standard as its mouthpiece, the PNAC helped foment support for the removal of Iraqi president Saddam Hussein beginning in 1998, citing Iraq’s noncooperation with UN weapons inspections. The PNAC became further emboldened in its urgency and rhetoric to quell the geopolitical risk posed by Hussein after the 9/11 terror attacks. The only justifiable response the George W. Bush Administration could play in thwarting Hussein, the PNAC argued, involved a military action. Keywords: The Project for the New American Century; Iraq War; Saddam Hussein; The Weekly Standard; The Vulcans; weapons of mass destructio

Pharmacological Blockade of TRPM8 Ion Channels Alters Cold and Cold Pain Responses in Mice

TRPM8 (Transient Receptor Potential Melastatin-8) is a cold- and menthol-gated ion channel necessary for the detection of cold temperatures in the mammalian peripheral nervous system. Functioning TRPM8 channels are required for behavioral responses to innocuous cool, noxious cold, injury-evoked cold hypersensitivity, cooling-mediated analgesia, and thermoregulation. Because of these various roles, the ability to pharmacologically manipulate TRPM8 function to alter the excitability of cold-sensing neurons may have broad impact clinically. Here we examined a novel compound, PBMC (1-phenylethyl-4-(benzyloxy)-3-methoxybenzyl(2-aminoethyl)carbamate) which robustly and selectively inhibited TRPM8 channels in vitro with sub-nanomolar affinity, as determined by calcium microfluorimetry and electrophysiology. The actions of PBMC were selective for TRPM8, with no functional effects observed for the sensory ion channels TRPV1 and TRPA1. PBMC altered TRPM8 gating by shifting the voltage-dependence of menthol-evoked currents towards positive membrane potentials. When administered systemically to mice, PBMC treatment produced a dose-dependent hypothermia in wildtype animals while TRPM8-knockout mice remained unaffected. This hypothermic response was reduced at lower doses, whereas responses to evaporative cooling were still significantly attenuated. Lastly, systemic PBMC also diminished cold hypersensitivity in inflammatory and nerve-injury pain models, but was ineffective against oxaliplatin-induced neuropathic cold hypersensitivity, despite our findings that TRPM8 is required for the cold-related symptoms of this pathology. Thus PBMC is an attractive compound that serves as a template for the formulation of highly specific and potent TRPM8 antagonists that will have utility both in vitro and in vivo

Iterative Design and Usability Testing of the iMHere System for Managing Chronic Conditions and Disability

A novel mobile health platform, Interactive Mobile Health and Rehabilitation (iMHere), is being developed to support wellness and self-management among people with chronic disabilities. The iMHere system currently includes a smartphone app with six modules for use by persons with disabilities and a web portal for use by medical and rehabilitation professionals or other support personnel. Our initial clinical research applying use of this system provides insight into the feasibility of employing iMHere in the development of self-management skills in young adults (ages 18-40 years) with spina bifida (Dicianno, Fairman, McCue, Parmanto, Yih, et al., 2015). This article is focused on describing the iterative design of the iMHere system including usability testing of both the app modules and clinician portal. Our pilot population of persons with spina bifida fostered the creation of a system appropriate for people with a wide variety of functional abilities and needs. As a result, the system is appropriate for use by persons with various disabilities and chronic conditions, not only spina bifida. In addition, the diversity of professionals and support personnel involved in the care of persons with spina bifida (SB) also enabled the design and implementation of the iMHere system to meet the needs of an interdisciplinary team of providers who treat various conditions. The iMHere system has the potential to foster communication and collaboration among members of an interdisciplinary healthcare team, including individuals with chronic conditions and disabilities, for client-centered approach to support self-management skills.

In-Flight Water Quality Monitoring on the International Space Station (ISS): Measuring Biocide Concentrations with Colorimetric Solid Phase Extraction (CSPE)

The colorimetric water quality monitoring kit (CWQMK) was delivered to the International Space Station (ISS) on STS-128/17A and was initially deployed in September 2009. The kit was flown as a station development test objective (SDTO) experiment to evaluate the acceptability of colorimetric solid phase extraction (CSPE) technology for routine water quality monitoring on the ISS. During the SDTO experiment, water samples from the U.S. water processor assembly (WPA), the U.S. potable water dispenser (PWD), and the Russian system for dispensing ground-supplied water (SVO-ZV) were collected and analyzed with the CWQMK. Samples from the U.S. segment of the ISS were analyzed for molecular iodine, which is the biocide added to water in the WPA. Samples from the SVOZV system were analyzed for ionic silver, the biocide used on the Russian segment of the ISS. In all, thirteen in-flight analysis sessions were completed as part of the SDTO experiment. This paper provides an overview of the experiment and reports the results obtained with the CWQMK. The forward plan for certifying the CWQMK as operational hardware and expanding the capabilities of the kit are also discussed

Social sciences research in neglected tropical diseases 3: Investment in social science research in neglected diseases of poverty: a case study of Bill and Melinda Gates Foundation

This article has been made available through the Brunel Open Access Publishing Fund.BACKGROUND: The level of funding provides a good proxy for the level of commitment or prioritisation given to a particular issue. While the need for research relevant to social, economic, cultural and behavioural aspects of neglected tropical diseases (NTD) control has been acknowledged, there is limited data on the level of funding that supports NTD social science research. METHOD: A case study was carried out in which the spending of a major independent funder, the Bill and Melinda Gates Foundation (BMGF) - was analysed. A total of 67 projects funded between October 1998 and November 2008 were identified from the BMGF database. With the help of keywords within the titles of 67 grantees, they were categorised as social science or non-social science research based on available definition of social science. A descriptive analysis was conducted. RESULTS: Of 67 projects analysed, 26 projects (39%) were social science related while 41 projects (61%) were basic science or other translational research including drug development. A total of US$697 million was spent to fund the projects, of which 35$ 241 million) went to social science research. Although the level of funding for social science research has generally been lower than that for non-social science research over 10 year period, social science research attracted more funding in 2004 and 2008. CONCLUSION: The evidence presented in this case study indicates that funding on NTD social science research compared to basic and translational research is not as low as it is perceived to be. However, as there is the acute need for improved delivery and utilisation of current NTD drugs/technologies, informed by research from social science approaches, funding priorities need to reflect the need to invest significantly more in NTD social science research

Generation and analysis of a mouse intestinal metatranscriptome through Illumina based RNA-sequencing

With the advent of high through-put sequencing (HTS), the emerging science of metagenomics is transforming our understanding of the relationships of microbial communities with their environments. While metagenomics aims to catalogue the genes present in a sample through assessing which genes are actively expressed, metatranscriptomics can provide a mechanistic understanding of community inter-relationships. To achieve these goals, several challenges need to be addressed from sample preparation to sequence processing, statistical analysis and functional annotation. Here we use an inbred non-obese diabetic (NOD) mouse model in which germ-free animals were colonized with a defined mixture of eight commensal bacteria, to explore methods of RNA extraction and to develop a pipeline for the generation and analysis of metatranscriptomic data. Applying the Illumina HTS platform, we sequenced 12 NOD cecal samples prepared using multiple RNA-extraction protocols. The absence of a complete set of reference genomes necessitated a peptide-based search strategy. Up to 16% of sequence reads could be matched to a known bacterial gene. Phylogenetic analysis of the mapped ORFs revealed a distribution consistent with ribosomal RNA, the majority from Bacteroides or Clostridium species. To place these HTS data within a systems context, we mapped the relative abundance of corresponding Escherichia coli homologs onto metabolic and protein-protein interaction networks. These maps identified bacterial processes with components that were well-represented in the datasets. In summary this study highlights the potential of exploiting the economy of HTS platforms for metatranscriptomics

Cloud feedbacks in extratopical cyclones: insight from long-term satellite data and high-resolution global simulations

A negative extratropical shortwave cloud feedback driven by changes in cloud optical depth is a feature of global climate models (GCMs). A robust positive trend in observed liquid water path (LWP) over the last two decades across the warming Southern Ocean supports the negative shortwave cloud feedback predicted by GCMs. This feature has been proposed to be due to transitions from ice to liquid with warming. To gain insight into the shortwave cloud feedback we examine extratropical cyclone variability and the response of extratropical cyclones to transient warming in GCM simulations. Multi-Sensor Advanced Climatology Liquid Water Path (MAC-LWP) microwave observations of cyclone properties from the period 1992–2015 are contrasted with GCM simulations, with horizontal resolutions ranging from 7 km to hundreds of kilometers. We find that inter-cyclone variability in LWP in both observations and models is strongly driven by the moisture flux along the cyclone's warm conveyor belt (WCB). Stronger WCB moisture flux enhances the LWP within cyclones. This relationship is replicated in GCMs, although its strength varies substantially across models. It is found that more than 80 % of the enhancement in Southern Hemisphere (SH) extratropical cyclone LWP in GCMs in response to a transient 4 K warming can be predicted based on the relationship between the WCB moisture flux and cyclone LWP in the historical climate and their change in moisture flux between the historical and warmed climates. Further, it is found that that the robust trend in cyclone LWP over the Southern Ocean in observations and GCMs is consistent with changes in the moisture flux. We propose two cloud feedbacks acting within extratropical cyclones: a negative feedback driven by Clausius–Clapeyron increasing water vapor path (WVP), which enhances the amount of water vapor available to be fluxed into the cyclone, and a feedback moderated by changes in the life cycle and vorticity of cyclones under warming, which changes the rate at which existing moisture is imported into the cyclone. Both terms contribute to increasing LWP within the cyclone. While changes in moisture flux predict cyclone LWP trends in the current climate and the majority of changes in LWP in transient warming simulations, a portion of the LWP increase in response to climate change that is unexplained by increasing moisture fluxes may be due to phase transitions. The variability in LWP within cyclone composites is examined to understand what cyclonic regimes the mixed-phase cloud feedback is relevant to. At a fixed WCB moisture flux cyclone LWP increases with increasing sea surface temperature (SST) in the half of the composite poleward of the low and decreases in the half equatorward of the low in both GCMs and observations. Cloud-top phase partitioning observed by the Atmospheric Infrared Sounder (AIRS) indicates that phase transitions may be driving increases in LWP in the poleward half of cyclones

Quantum memories at finite temperature

To use quantum systems for technological applications one first needs to preserve their coherence for macroscopic time scales, even at finite temperature. Quantum error correction has made it possible to actively correct errors that affect a quantum memory. An attractive scenario is the construction of passive storage of quantum information with minimal active support. Indeed, passive protection is the basis of robust and scalable classical technology, physically realized in the form of the transistor and the ferromagnetic hard disk. The discovery of an analogous quantum system is a challenging open problem, plagued with a variety of no-go theorems. Several approaches have been devised to overcome these theorems by taking advantage of their loopholes. The state-of-the-art developments in this field are reviewed in an informative and pedagogical way. The main principles of self-correcting quantum memories are given and several milestone examples from the literature of two-, three- and higher-dimensional quantum memories are analyzed

Assessing the utility of CASP14 models for molecular replacement

Funder: CCP4Funder: Max‐Planck‐Gesellschaft; Id: http://dx.doi.org/10.13039/501100004189Abstract: The assessment of CASP models for utility in molecular replacement is a measure of their use in a valuable real‐world application. In CASP7, the metric for molecular replacement assessment involved full likelihood‐based molecular replacement searches; however, this restricted the assessable targets to crystal structures with only one copy of the target in the asymmetric unit, and to those where the search found the correct pose. In CASP10, full molecular replacement searches were replaced by likelihood‐based rigid‐body refinement of models superimposed on the target using the LGA algorithm, with the metric being the refined log‐likelihood‐gain (LLG) score. This enabled multi‐copy targets and very poor models to be evaluated, but a significant further issue remained: the requirement of diffraction data for assessment. We introduce here the relative‐expected‐LLG (reLLG), which is independent of diffraction data. This reLLG is also independent of any crystal form, and can be calculated regardless of the source of the target, be it X‐ray, NMR or cryo‐EM. We calibrate the reLLG against the LLG for targets in CASP14, showing that it is a robust measure of both model and group ranking. Like the LLG, the reLLG shows that accurate coordinate error estimates add substantial value to predicted models. We find that refinement by CASP groups can often convert an inadequate initial model into a successful MR search model. Consistent with findings from others, we show that the AlphaFold2 models are sufficiently good, and reliably so, to surpass other current model generation strategies for attempting molecular replacement phasing