Toward a unified description of hadro- and photoproduction: S-wave pi- and eta-photoproduction amplitudes

The Chew-Mandelstam parameterization, which has been used extensively in the two-body hadronic sector, is generalized in this exploratory study to the electromagnetic sector by simultaneous fits to the pion- and eta-photoproduction S-wave multipole amplitudes for center-of-mass energies from the pion threshold through 1.61 GeV. We review the Chew-Mandelstam parameterization in detail to clarify the theoretical content of the SAID hadronic amplitude analysis and to place the proposed, generalized SAID electromagnetic amplitudes in the context of earlier employed parameterized forms. The parameterization is unitary at the two-body level, employing four hadronic channels and the gamma-N electromagnetic channel. We compare the resulting fit to the MAID parameterization and find qualitative agreement though, numerically, the solution is somewhat different. Applications of the extended parameterization to global fits of the photoproduction data and to global fits of the combined hadronic and photoproduction data are discussed.Comment: 9 pages, 9 figures; added figures and tex

Differentiating Anti-Lamina Lucida and Anti-Sublamina Densa Anti-BMZ Antibodies by Indirect Immunofluorescence on 1.0 M Sodium Chloride-Separated Skin

L'immunofluorescence indirecte sur la peau séparée est une méthode fiable pour différencier les anticorps contre la lame transparente et les anticorps contre la sous-lame dense des maladies bulleuses et la différenciation entre les anticorps est essentielle pour un diagnostic exact chez certains malades. Les anticorps contre la lame transparente dans la pemphigoïde bulleuse peuvent présenter plusieurs spécificités

The Chagos Islands cases: the empire strikes back

Good governance requires the accommodation of multiple interests in the cause of decision making. However, undue regard for particular sectional interests can take their toll upon public faith in government administration. Historically, broad conceptions of the good of the commonwealth were employed to outweigh the interests of groups that resisted colonisation. In the decision making of the British Empire, the standard approach for justifying the marginalisation of the interests of colonised groups was that they were uncivilised and that particular hardships were the price to be paid for bringing to them the imperial dividend of industrial society. It is widely assumed that with the dismantling of the British Empire, such impulses and their accompanying jurisprudence became a thing of the past. Even as decolonisation proceeded apace after the Second World War, however, the United Kingdom maintained control of strategically important islands with a view towards sustaining its global role. In an infamous example from this twilight period of empire, in the 1960s imperial interests were used to justify the expulsion of the Chagos islanders from the British Indian Ocean Territory (BIOT). Into the twenty-first century, this forced elision of the UK’s interests with the imperial “common good” continues to take centre stage in courtroom battles over the islanders’ rights, being cited before domestic and international tribunals in order to maintain the Chagossians’ exclusion from their homeland. This article considers the new jurisprudence of imperialism which has emerged in a string of decisions which have continued to marginalise the Chagossians’ interests

Balancing Selection Maintains a Form of ERAP2 that Undergoes Nonsense-Mediated Decay and Affects Antigen Presentation

A remarkable characteristic of the human major histocompatibility complex (MHC) is its extreme genetic diversity, which is maintained by balancing selection. In fact, the MHC complex remains one of the best-known examples of natural selection in humans, with well-established genetic signatures and biological mechanisms for the action of selection. Here, we present genetic and functional evidence that another gene with a fundamental role in MHC class I presentation, endoplasmic reticulum aminopeptidase 2 (ERAP2), has also evolved under balancing selection and contains a variant that affects antigen presentation. Specifically, genetic analyses of six human populations revealed strong and consistent signatures of balancing selection affecting ERAP2. This selection maintains two highly differentiated haplotypes (Haplotype A and Haplotype B), with frequencies 0.44 and 0.56, respectively. We found that ERAP2 expressed from Haplotype B undergoes differential splicing and encodes a truncated protein, leading to nonsense-mediated decay of the mRNA. To investigate the consequences of ERAP2 deficiency on MHC presentation, we correlated surface MHC class I expression with ERAP2 genotypes in primary lymphocytes. Haplotype B homozygotes had lower levels of MHC class I expressed on the surface of B cells, suggesting that naturally occurring ERAP2 deficiency affects MHC presentation and immune response. Interestingly, an ERAP2 paralog, endoplasmic reticulum aminopeptidase 1 (ERAP1), also shows genetic signatures of balancing selection. Together, our findings link the genetic signatures of selection with an effect on splicing and a cellular phenotype. Although the precise selective pressure that maintains polymorphism is unknown, the demonstrated differences between the ERAP2 splice forms provide important insights into the potential mechanism for the action of selection

KN Scattering and the Nucleon Strangeness Radius

The leading non-zero electric moment of the nucleon strange-quark vector current is the mean square strangeness radius, $$. We evaluate the lightest OZI-allowed contribution to$$, arising from the kaon cloud, using dispersion relations. Drawing upon unitarity constraints as well as $K^{+}N$ scattering and $e^+e^-\to K\bar{K}$ cross section data, we find the structure of this contribution differs significantly from that suggested by a variety of QCD-inspired model calculations. In particular, we find evidence for a strong $\phi$-meson resonance which may enhance the scale of kaon cloud contribution to an observable level.Comment: 4 pages, RevTex, 1 PS figure, uses epsf.sty, revised to improve clarity, results unchange

Coordinated Regulation of SIV Replication and Immune Responses in the CNS

Central nervous system (CNS) invasion during acute-stage HIV-infection has been demonstrated in a small number of individuals, but there is no evidence of neurological impairment at this stage and virus infection in brain appears to be controlled until late-stage disease. Using our reproducible SIV macaque model to examine the earliest stages of infection in the CNS, we identified immune responses that differentially regulate inflammation and virus replication in the brain compared to the peripheral blood and lymphoid tissues. SIV replication in brain macrophages and in brain of SIV-infected macaques was detected at 4 days post-inoculation (p.i.). This was accompanied by upregulation of innate immune responses, including IFNβ, IFNβ-induced gene MxA mRNA, and TNFα. Additionally, IL-10, the chemokine CCL2, and activation markers in macrophages, endothelial cells, and astrocytes were all increased in the brain at four days p.i. We observed synchronous control of virus replication, cytokine mRNA levels and inflammatory markers (MHC Class II, CD68 and GFAP) by 14 days p.i.; however, control failure was followed by development of CNS lesions in the brain. SIV infection was accompanied by induction of the dominant-negative isoform of C/EBPβ, which regulates SIV, CCL2, and IL6 transcription, as well as inflammatory responses in macrophages and astrocytes. This synchronous response in the CNS is in part due to the effect of the C/EBPβ on virus replication and cytokine expression in macrophage-lineage cells in contrast to CD4+ lymphocytes in peripheral blood and lymphoid tissues. Thus, we have identified a crucial period in the brain when virus replication and inflammation are controlled. As in HIV-infected individuals, though, this control is not sustained in the brain. Our results suggest that intervention with antiretroviral drugs or anti-inflammatory therapeutics with CNS penetration would sustain early control. These studies further suggest that interventions should target HIV-infected individuals with increased CCL2 levels or HIV RNA in the CNS

Researching the use of force: The background to the international project

This article provides the background to an international project on use of force by the police that was carried out in eight countries. Force is often considered to be the defining characteristic of policing and much research has been conducted on the determinants, prevalence and control of the use of force, particularly in the United States. However, little work has looked at police officers’ own views on the use of force, in particular the way in which they justify it. Using a hypothetical encounter developed for this project, researchers in each country conducted focus groups with police officers in which they were encouraged to talk about the use of force. The results show interesting similarities and differences across countries and demonstrate the value of using this kind of research focus and methodology

Triad pattern algorithm for predicting strong promoter candidates in bacterial genomes

Abstract Background Bacterial promoters, which increase the efficiency of gene expression, differ from other promoters by several characteristics. This difference, not yet widely exploited in bioinformatics, looks promising for the development of relevant computational tools to search for strong promoters in bacterial genomes. Results We describe a new triad pattern algorithm that predicts strong promoter candidates in annotated bacterial genomes by matching specific patterns for the group I σ70 factors of Escherichia coli RNA polymerase. It detects promoter-specific motifs by consecutively matching three patterns, consisting of an UP-element, required for interaction with the α subunit, and then optimally-separated patterns of -35 and -10 boxes, required for interaction with the σ70 subunit of RNA polymerase. Analysis of 43 bacterial genomes revealed that the frequency of candidate sequences depends on the A+T content of the DNA under examination. The accuracy of in silico prediction was experimentally validated for the genome of a hyperthermophilic bacterium, Thermotoga maritima, by applying a cell-free expression assay using the predicted strong promoters. In this organism, the strong promoters govern genes for translation, energy metabolism, transport, cell movement, and other as-yet unidentified functions. Conclusion The triad pattern algorithm developed for predicting strong bacterial promoters is well suited for analyzing bacterial genomes with an A+T content of less than 62%. This computational tool opens new prospects for investigating global gene expression, and individual strong promoters in bacteria of medical and/or economic significance.</p

Integrated analyses of single-cell atlases reveal age, gender, and smoking status associations with cell type-specific expression of mediators of SARS-CoV-2 viral entry and highlights inflammatory programs in putative target cells

The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, creates an urgent need for identifying molecular mechanisms that mediate viral entry, propagation, and tissue pathology. Cell membrane bound angiotensin-converting enzyme 2 (ACE2) and associated proteases, transmembrane protease serine 2 (TMPRSS2) and Cathepsin L (CTSL), were previously identified as mediators of SARS-CoV2 cellular entry. Here, we assess the cell type-specific RNA expression of ACE2, TMPRSS2, and CTSL through an integrated analysis of 107 single-cell and single-nucleus RNA-Seq studies, including 22 lung and airways datasets (16 unpublished), and 85 datasets from other diverse organs. Joint expression of ACE2 and the accessory proteases identifies specific subsets of respiratory epithelial cells as putative targets of viral infection in the nasal passages, airways, and alveoli. Cells that co-express ACE2 and proteases are also identified in cells from other organs, some of which have been associated with COVID-19 transmission or pathology, including gut enterocytes, corneal epithelial cells, cardiomyocytes, heart pericytes, olfactory sustentacular cells, and renal epithelial cells. Performing the first meta-analyses of scRNA-seq studies, we analyzed 1,176,683 cells from 282 nasal, airway, and lung parenchyma samples from 164 donors spanning fetal, childhood, adult, and elderly age groups, associate increased levels of ACE2, TMPRSS2, and CTSL in specific cell types with increasing age, male gender, and smoking, all of which are epidemiologically linked to COVID-19 susceptibility and outcomes. Notably, there was a particularly low expression of ACE2 in the few young pediatric samples in the analysis. Further analysis reveals a gene expression program shared by ACE2(+)TMPRSS2(+) cells in nasal, lung and gut tissues, including genes that may mediate viral entry, subtend key immune functions, and mediate epithelial-macrophage cross-talk. Amongst these are IL6, its receptor and co-receptor, IL1R, TNF response pathways, and complement genes. Cell type specificity in the lung and airways and smoking effects were conserved in mice. Our analyses suggest that differences in the cell type-specific expression of mediators of SARS-CoV-2 viral entry may be responsible for aspects of COVID-19 epidemiology and clinical course, and point to putative molecular pathways involved in disease susceptibility and pathogenesis