Executive Secrets: Covert Action and the Presidency

A frank and refreshing evaluation of several Chief Executives, their Directors of Central Intelligence, and even some lower in the hierarchy, Executive Secrets shines light on the development and execution of foreign policy through the understanding of the tools available, of which covert action may be least known and understood. This book is a great tool for the press, the public, and many political appointees in the National Security System. A History Book Club Selection with a foreword by Mark Bowden, author of Black Hawk Down. [Daugherty] gives a frank and refreshing evaluation of several Chief Executives, their Directors of Central Intelligence, and even some lover in the hierarchy. Anyone interested or involved in the development and execution of foreign policy must know the tools available, of which covert action may be least known and understood. This understanding is also pertinent to a wider audience: the press, the public, and many political appointees in the National Security system. This book should help. -- Air Power History A most informative study of covert action.... This well-researched, thoughtful book is a valuable work that will be treasured by scholars and professionals in the field. Highly recommended. -- Choice A hard-hitting, balanced and highly successful effort to deal with the issue of presidential responsibility for covert action. -- John Stempel, Patterson School of Diplomacy, University of Kentucky Daugherty has done us all a tremendous service by attempting to rescue the Agency from the myths, both well-meaning and malevolent, that shape our understanding of it. . . . This book ought to dispel some of the fog that obscures our understanding of the C.I.A. and that prompts the gigantic mood swings in our attitude toward intelligence gathering and covert actions. -- Mark Bowden, from the foreword There are some interesting and carefully drawn vignettes of covert operations here that demonstrate a skillful blending of declassified documents, investigative reports, and secondary sources. It is these case studies that make this one of those essential works for specialists in intelligence policy. -- Register of the Kentucky Historical Society If you are a keen observer of the agency, this one will interest and instruct you. -- Rockland (ME) Courier-Gazette Offers a richly textured book that clears up some common misconceptions of the CIA, as well as an insider\u27s perspective on how covert action really works, or fails. -- Savannah (GA) Morning News Readers of this timely and occasionally revelatory account may be surprised to learn that President Carter approved a covert action program to attack the internal legitimacy of the Soviet system, and that he repeatedly relied on covert action to achieve his foreign policy aims. -- Zbigniew Brzezinski Named a 2005 Choice Outstanding Academic Title. [Daugherty] has done a great service for those wanting to seriously understand the realistic capabilities of the organization. This is not an easy task, for the CIA has been the subject of many books, movies, and certain mindsets in the population. --Foreign Area Officer Journalhttps://uknowledge.uky.edu/upk_political_science_american_politics/1038/thumbnail.jp

Life in Hot Carbon Monoxide: The Complete Genome Sequence of Carboxydothermus hydrogenoformans Z-2901

We report here the sequencing and analysis of the genome of the thermophilic bacterium Carboxydothermus hydrogenoformans Z-2901. This species is a model for studies of hydrogenogens, which are diverse bacteria and archaea that grow anaerobically utilizing carbon monoxide (CO) as their sole carbon source and water as an electron acceptor, producing carbon dioxide and hydrogen as waste products. Organisms that make use of CO do so through carbon monoxide dehydrogenase complexes. Remarkably, analysis of the genome of C. hydrogenoformans reveals the presence of at least five highly differentiated anaerobic carbon monoxide dehydrogenase complexes, which may in part explain how this species is able to grow so much more rapidly on CO than many other species. Analysis of the genome also has provided many general insights into the metabolism of this organism which should make it easier to use it as a source of biologically produced hydrogen gas. One surprising finding is the presence of many genes previously found only in sporulating species in the Firmicutes Phylum. Although this species is also a Firmicutes, it was not known to sporulate previously. Here we show that it does sporulate and because it is missing many of the genes involved in sporulation in other species, this organism may serve as a “minimal” model for sporulation studies. In addition, using phylogenetic profile analysis, we have identified many uncharacterized gene families found in all known sporulating Firmicutes, but not in any non-sporulating bacteria, including a sigma factor not known to be involved in sporulation previously

Comparative Genomics of Emerging Human Ehrlichiosis Agents

Anaplasma (formerly Ehrlichia) phagocytophilum, Ehrlichia chaffeensis, and Neorickettsia (formerly Ehrlichia) sennetsu are intracellular vector-borne pathogens that cause human ehrlichiosis, an emerging infectious disease. We present the complete genome sequences of these organisms along with comparisons to other organisms in the Rickettsiales order. Ehrlichia spp. and Anaplasma spp. display a unique large expansion of immunodominant outer membrane proteins facilitating antigenic variation. All Rickettsiales have a diminished ability to synthesize amino acids compared to their closest free-living relatives. Unlike members of the Rickettsiaceae family, these pathogenic Anaplasmataceae are capable of making all major vitamins, cofactors, and nucleotides, which could confer a beneficial role in the invertebrate vector or the vertebrate host. Further analysis identified proteins potentially involved in vacuole confinement of the Anaplasmataceae, a life cycle involving a hematophagous vector, vertebrate pathogenesis, human pathogenesis, and lack of transovarial transmission. These discoveries provide significant insights into the biology of these obligate intracellular pathogens

Through a Glass, Darkly:The CIA and Oral History

This article broaches the thorny issue of how we may study the history of the CIA by utilizing oral history interviews. This article argues that while oral history interviews impose particular demands upon the researcher, they are particularly pronounced in relation to studying the history of intelligence services. This article, nevertheless, also argues that while intelligence history and oral history each harbour their own epistemological perils and biases, pitfalls which may in fact be pronounced when they are conjoined, the relationship between them may nevertheless be a productive one. Indeed, each field may enrich the other provided we have thought carefully about the linkages between them: this article's point of departure. The first part of this article outlines some of the problems encountered in studying the CIA by relating them to the author's own work. This involved researching the CIA's role in US foreign policy towards Afghanistan since a landmark year in the history of the late Cold War, 1979 (i.e. the year the Soviet Union invaded that country). The second part of this article then considers some of the issues historians must confront when applying oral history to the study of the CIA. To bring this within the sphere of cognition of the reader the author recounts some of his own experiences interviewing CIA officers in and around Washington DC. The third part then looks at some of the contributions oral history in particular can make towards a better understanding of the history of intelligence services and the CIA

Phylogenomics of the Reproductive Parasite Wolbachia pipientis wMel: A Streamlined Genome Overrun by Mobile Genetic Elements

The complete sequence of the 1,267,782 bp genome of Wolbachia pipientis wMel, an obligate intracellular bacteria of Drosophila melanogaster, has been determined. Wolbachia, which are found in a variety of invertebrate species, are of great interest due to their diverse interactions with different hosts, which range from many forms of reproductive parasitism to mutualistic symbioses. Analysis of the wMel genome, in particular phylogenomic comparisons with other intracellular bacteria, has revealed many insights into the biology and evolution of wMel and Wolbachia in general. For example, the wMel genome is unique among sequenced obligate intracellular species in both being highly streamlined and containing very high levels of repetitive DNA and mobile DNA elements. This observation, coupled with multiple evolutionary reconstructions, suggests that natural selection is somewhat inefficient in wMel, most likely owing to the occurrence of repeated population bottlenecks. Genome analysis predicts many metabolic differences with the closely related Rickettsia species, including the presence of intact glycolysis and purine synthesis, which may compensate for an inability to obtain ATP directly from its host, as Rickettsia can. Other discoveries include the apparent inability of wMel to synthesize lipopolysaccharide and the presence of the most genes encoding proteins with ankyrin repeat domains of any prokaryotic genome yet sequenced. Despite the ability of wMel to infect the germline of its host, we find no evidence for either recent lateral gene transfer between wMel and D. melanogaster or older transfers between Wolbachia and any host. Evolutionary analysis further supports the hypothesis that mitochondria share a common ancestor with the α-Proteobacteria, but shows little support for the grouping of mitochondria with species in the order Rickettsiales. With the availability of the complete genomes of both species and excellent genetic tools for the host, the wMel–D. melanogaster symbiosis is now an ideal system for studying the biology and evolution of Wolbachia infections

The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease

Many common variants have been associated with hematological traits, but identification of causal genes and pathways has proven challenging. We performed a genome-wide association analysis in the UK Biobank and INTERVAL studies, testing 29.5 million genetic variants for association with 36 red cell, white cell, and platelet properties in 173,480 European-ancestry participants. This effort yielded hundreds of low frequency (<5%) and rare (<1%) variants with a strong impact on blood cell phenotypes. Our data highlight general properties of the allelic architecture of complex traits, including the proportion of the heritable component of each blood trait explained by the polygenic signal across different genome regulatory domains. Finally, through Mendelian randomization, we provide evidence of shared genetic pathways linking blood cell indices with complex pathologies, including autoimmune diseases, schizophrenia, and coronary heart disease and evidence suggesting previously reported population associations between blood cell indices and cardiovascular disease may be non-causal.We thank members of the Cambridge BioResource Scientific Advisory Board and Management Committee for their support of our study and the National Institute for Health Research Cambridge Biomedical Research Centre for funding. K.D. is funded as a HSST trainee by NHS Health Education England. M.F. is funded from the BLUEPRINT Grant Code HEALTH-F5-2011-282510 and the BHF Cambridge Centre of Excellence [RE/13/6/30180]. J.R.S. is funded by a MRC CASE Industrial studentship, co-funded by Pfizer. J.D. is a British Heart Foundation Professor, European Research Council Senior Investigator, and National Institute for Health Research (NIHR) Senior Investigator. S.M., S.T, M.H, K.M. and L.D. are supported by the NIHR BioResource-Rare Diseases, which is funded by NIHR. Research in the Ouwehand laboratory is supported by program grants from the NIHR to W.H.O., the European Commission (HEALTH-F2-2012-279233), the British Heart Foundation (BHF) to W.J.A. and D.R. under numbers RP-PG-0310-1002 and RG/09/12/28096 and Bristol Myers-Squibb; the laboratory also receives funding from NHSBT. W.H.O is a NIHR Senior Investigator. The INTERVAL academic coordinating centre receives core support from the UK Medical Research Council (G0800270), the BHF (SP/09/002), the NIHR and Cambridge Biomedical Research Centre, as well as grants from the European Research Council (268834), the European Commission Framework Programme 7 (HEALTH-F2-2012-279233), Merck and Pfizer. DJR and DA were supported by the NIHR Programme ‘Erythropoiesis in Health and Disease’ (Ref. NIHR-RP-PG-0310-1004). N.S. is supported by the Wellcome Trust (Grant Codes WT098051 and WT091310), the EU FP7 (EPIGENESYS Grant Code 257082 and BLUEPRINT Grant Code HEALTH-F5-2011-282510). The INTERVAL study is funded by NHSBT and has been supported by the NIHR-BTRU in Donor Health and Genomics at the University of Cambridge in partnership with NHSBT. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, the Department of Health of England or NHSBT. D.G. is supported by a “la Caixa”-Severo Ochoa pre-doctoral fellowship

Peptide immunotherapy in allergic asthma generates IL-10-dependent immunological tolerance associated with linked epitope suppression

Treatment of patients with allergic asthma using low doses of peptides containing T cell epitopes from Fel d 1, the major cat allergen, reduces allergic sensitization and improves surrogate markers of disease. Here, we demonstrate a key immunological mechanism, linked epitope suppression, associated with this therapeutic effect. Treatment with selected epitopes from a single allergen resulted in suppression of responses to other ("linked") epitopes within the same molecule. This phenomenon was induced after peptide immunotherapy in human asthmatic subjects and in a novel HLA-DR1 transgenic mouse model of asthma. Tracking of allergen-specific T cells using DR1 tetramers determined that suppression was associated with the induction of interleukin (IL)-10(+) T cells that were more abundant than T cells specific for the single-treatment peptide and was reversed by anti -IL-10 receptor administration. Resolution of airway pathophysiology in this model was associated with reduced recruitment, proliferation, and effector function of allergen-specific Th2 cells. Our results provide, for the first time, in vivo evidence of linked epitope suppression and IL-10 induction in both human allergic disease and a mouse model designed to closely mimic peptide therapy in humans

Phenotypic Characterization of EIF2AK4 Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease with an emerging genetic basis. Heterozygous mutations in the gene encoding the bone morphogenetic protein receptor type 2 (BMPR2) are the commonest genetic cause of PAH, whereas biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene (EIF2AK4) are described in pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Here, we determine the frequency of these mutations and define the genotype-phenotype characteristics in a large cohort of patients diagnosed clinically with PAH. METHODS: Whole-genome sequencing was performed on DNA from patients with idiopathic and heritable PAH and with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis recruited to the National Institute of Health Research BioResource-Rare Diseases study. Heterozygous variants in BMPR2 and biallelic EIF2AK4 variants with a minor allele frequency of <1:10 000 in control data sets and predicted to be deleterious (by combined annotation-dependent depletion, PolyPhen-2, and sorting intolerant from tolerant predictions) were identified as potentially causal. Phenotype data from the time of diagnosis were also captured. RESULTS: Eight hundred sixty-four patients with idiopathic or heritable PAH and 16 with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis were recruited. Mutations in BMPR2 were identified in 130 patients (14.8%). Biallelic mutations in EIF2AK4 were identified in 5 patients with a clinical diagnosis of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Furthermore, 9 patients with a clinical diagnosis of PAH carried biallelic EIF2AK4 mutations. These patients had a reduced transfer coefficient for carbon monoxide (Kco; 33% [interquartile range, 30%-35%] predicted) and younger age at diagnosis (29 years; interquartile range, 23-38 years) and more interlobular septal thickening and mediastinal lymphadenopathy on computed tomography of the chest compared with patients with PAH without EIF2AK4 mutations. However, radiological assessment alone could not accurately identify biallelic EIF2AK4 mutation carriers. Patients with PAH with biallelic EIF2AK4 mutations had a shorter survival. CONCLUSIONS: Biallelic EIF2AK4 mutations are found in patients classified clinically as having idiopathic and heritable PAH. These patients cannot be identified reliably by computed tomography, but a low Kco and a young age at diagnosis suggests the underlying molecular diagnosis. Genetic testing can identify these misclassified patients, allowing appropriate management and early referral for lung transplantation