Ruptured aneurysm of the ulnar artery in a woman with neurofibromatosis

A 61-year-old woman with neurofibromatosis type 1 (Recklinghausen's disease) was referred for massive swelling of the right forearm, pain, increasing numbness, and impaired movement of the fingers. Angiography demonstrated a 13- × 11-mm aneurysm and a capped rupture of the ulnar artery. Because of the complicated soft-tissue condition, interventional treatment was indicated. Two 360° coils were placed for embolization of the ruptured aneurysm. Arterial involvement in neurofibromatosis is a well known but infrequent occurrence. Stenotic lesions predominate. Aneurysmal defects are less common, and rupture of peripheral arteries is exceptional

Quantum origin of quantum jumps: Breaking of unitary symmetry induced by information transfer and the transition from quantum to classical

Measurements transfer information about a system to the apparatus, and then further on -- to observers and (often inadvertently) to the environment. I show that even imperfect copying essential in such situations restricts possible unperturbed outcomes to an orthogonal subset of all possible states of the system, thus breaking the unitary symmetry of its Hilbert space implied by the quantum superposition principle. Preferred outcome states emerge as a result. They provide framework for the ``wavepacket collapse'', designating terminal points of quantum jumps, and defining the measured observable by specifying its eigenstates. In quantum Darwinism, they are the progenitors of multiple copies spread throughout the environment -- the fittest quantum states that not only survive decoherence, but subvert it into carrying information about them -- into becoming a witness.Comment: For comments see Seth Lloyd, NATURE 450, 1167 (2007

How Accurately do English for Academic Purposes Students use Academic Word List Words?

Previous corpus research on English for academic purposes (EAP) writing has analyzed how often additional language (L2) writers use words from the Academic Word List (AWL) (Coxhead, 2000), but few studies to date have explored how accurately those words are used. Therefore, the current study investigated how accurately and appropriately EAP writers (N = 409) use AWL words in their argumentative essays. The 230,694-word corpus was analyzed to identify AWL word families that occurred with at least 20 tokens. All tokens were then coded as being accurately used, or as containing a morphosyntactic or collocational error (or both). The findings showed that the EAP students’ overall accuracy rate was high (67%) and that collocational errors occurred more frequently than grammatical errors. Pedagogical implications for EAP programs are discussed

Interaction of vortices in superconductors with kappa close to 2^(-1/2)

Using a perturbative approach to the infinitely degenerate Bogomolnyi vortex state for a superconductor with kappa = 2^(-1/2), T -> T_c, we calculate the interaction of vortices in a superconductor with kappa close to 2^(-1/2). We find, numerically and analytically, that depending on the material the interaction potential between the vortices varies with decreasing kappa from purely repulsive (as in a type-II superconductor) to purely attractive (as in a type-I superconductor) in two different ways: either vortices form a bound state and the distance between them changes gradually from infinity to zero, or this transition occurs in a discontinuous way as a result of a competition between minima at infinity and zero. We study the discontinuous transition between the vortex and Meissner states caused by the non-monotonous vortex interaction and calculate the corresponding magnetization jump.Comment: v1:original submit v2:changed formate of images (gave problems to some) v3:corrected fig v4v6 (was -v4v6) orthographic corrections (and U_lat/int) mismatch v4:more small orthographic corrections v5:converted to revtex4 and bibTex v6:Renamed images to submit to pr

Tetramer enrichment reveals the presence of phenotypically diverse hepatitis C virus-specific CD8+T cells in chronic infection

Virus-specific CD8+ T cells are rarely detectable ex vivo by conventional methods during chronic hepatitis C virus (HCV) infection. In this study, however, we were able to detect and characterize HCV-specific CD8+ T cells in all chronically HCV genotype 1a-infected, HLA-A*02:01-positive patients analyzed by performing major histocompatibility complex (MHC) class I tetramer enrichment. Two-thirds of these enriched HCV-specific CD8+ T-cell populations displayed an effector memory phenotype, whereas, surprisingly, one-third displayed a naive-like phenotype despite ongoing viral replication. CD8+ T cells with an effector memory phenotype could not expand in vitro, suggesting exhaustion of these cells. Interestingly, some of the naive-like CD8+ T cells proliferated vigorously upon in vitro priming, whereas others did not. These differences were linked to the corresponding viral sequences in the respective patients. Indeed, naive-like CD8+ T cells from patients with the consensus sequence in the corresponding T-cell epitope did not expand in vitro. In contrast, in patients displaying sequence variations, we were able to induce HCV-specific CD8+ T-cell proliferation, which may indicate infection with a variant virus. Collectively, these data reveal the presence of phenotypically and functionally diverse HCV-specific CD8+ T cells at very low frequencies that are detectable in all chronically infected patients despite viral persistence. IMPORTANCE In this study, we analyzed CD8+ T-cell responses specific for HLA-A*02:01-restricted epitopes in chronically HCV-infected patients, using MHC class I tetramer enrichment. Importantly, we could detect HCV-specific CD8+ T-cell populations in all patients. To further characterize these HCV-specific CD8+ T-cell populations that are not detectable using conventional techniques, we performed phenotypic, functional, and viral sequence analyses. These data revealed different mechanisms for CD8+ T-cell failure in HCV infection, including T-cell exhaustion, viral escape, and functional impairment of naive-like HCV-specific CD8+ T cells

Role of Host Genetic Factors in the Outcome of Hepatitis C Virus Infection

The natural history of hepatitis C virus (HCV) infection is determined by a complex interplay between host genetic, immunological and viral factors. This review highlights genes involved in innate and adaptive immune responses associated with different outcomes of HCV infection. For example, an association of HCV clearance with certain HLA alleles has been demonstrated. The mechanisms responsible for these associations have been linked to specific T cell responses for some particular alleles (e.g., HLA-B27). Genetic associations involved in T cell regulation and function further underline the role of the adaptive immune response in the natural history of HCV infection. In addition, some genes involved in innate NK cell responses demonstrate the complex interplay between components of the immune system necessary for a successful host response to HCV infection

Histamine can be Formed and Degraded in the Human and Mouse Heart

Histamine is metabolized by several enzymes in vitro and in vivo. The relevance of this metabolism in the mammalian heart in vivo is unclear. However, histamine can exert positive inotropic effects (PIE) and positive chronotropic effects (PCE) in humans via H2- histamine receptors. In transgenic mice (H2-TG) that overexpress the human H2 receptor in cardiomyocytes but not in wild-type littermate mice (WT), histamine induced PIE and PCE in isolated left or right atrial preparations. These H2-TG were used to investigate the putative relevance of histamine degrading enzymes in the mammalian heart. Histidine, the precursor of histamine, increased force of contraction (FOC) in human atrial preparations. Moreover, histamine increased the phosphorylation state of phospholamban in human atrium. Here, we could detect histidine decarboxylase (HDC) and histamine itself in cardiomyocytes of mouse hearts. Moreover, our data indicate that histamine is subject to degradation in the mammalian heart. Inhibition of the histamine metabolizing enzymes diamine oxidase (DAO) and monoamine oxidase (MAO) shifted the concentration response curves for the PIE in H2-TG atria to the left. Moreover, activity of histamine metabolizing enzymes was present in mouse cardiac samples as well as in human atrial samples. Thus, drugs used for other indication (e.g. antidepressants) can alter histamine levels in the heart. Our results deepen our understanding of the physiological role of histamine in the mouse and human heart. Our findings might be clinically relevant because we show enzyme targets for drugs to modify the beating rate and force of the human heart

An alternative CYB5A transcript is expressed in aneuploid ALL and enriched in relapse

Background: B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a genetically heterogenous malignancy with poor prognosis in relapsed adult patients. The genetic basis for relapse in aneuploid subtypes such as near haploid (NH) and high hyperdiploid (HeH) BCP-ALL is only poorly understood. Pathogenic genetic alterations remain to be identified. To this end, we investigated the dynamics of genetic alterations in a matched initial diagnosis-relapse (ID-REL) BCP-ALL cohort. Here, we firstly report the identification of the novel genetic alteration CYB5Aalt, an alternative transcript of CYB5A, in two independent cohorts. Methods: We identified CYB5alt in the RNAseq-analysis of a matched ID-REL BCP-ALL cohort with 50 patients and quantified its expression in various molecular BCP-ALL subtypes. Findings were validated in an independent cohort of 140 first diagnosis samples from adult BCP-ALL patients. Derived from patient material, the alternative open reading frame of CYB5Aalt was cloned (pCYB5Aalt) and pCYB5Aalt or the empty vector were stably overexpressed in NALM-6 cells. RNA sequencing was performed of pCYB5Aalt clones and empty vector controls followed by differential expression analysis, gene set enrichment analysis and complementing cell death and viability assays to determine functional implications of CYB5Aalt. Results: RNAseq data analysis revealed non-canonical exon usage of CYB5Aalt starting from a previously undescribed transcription start site. CYB5Aalt expression was increased in relapsed BCP-ALL and its occurrence was specific towards the shared gene expression cluster of NH and HeH BCP-ALL in independent cohorts. Overexpression of pCYB5Aalt in NALM-6 cells induced a distinct transcriptional program compared to empty vector controls with downregulation of pathways related to reported functions of CYB5A wildtype. Interestingly, CYB5A wildtype expression was decreased in CYB5Aalt samples in silico and in vitro. Additionally, pCYB5Aalt NALM-6 elicited a more resistant drug response. Conclusions: Across all age groups, CYB5Aalt was the most frequent secondary genetic event in relapsed NH and HeH BCP-ALL. In addition to its high subgroup specificity, CYB5Aalt is a novel candidate to be potentially implicated in therapy resistance in NH and HeH BCP-ALL. This is underlined by overexpressing CYB5Aalt providing first evidence for a functional role in BCL2-mediated apoptosis

Immunodominance of HLA-A2-restricted hepatitis C virus-specific CD8+ T cell responses is linked to naive-precursor frequency

The impact of naïve precursor frequency on human virus-specific CD8+ T cell immunodominance is not well understood. Using a recently developed MHC class I tetramer enrichment protocol, we found a conserved hierarchy and >10-fold difference in naïve precursor frequencies across three HLA-A2 restricted HCV-specific epitopes. Importantly, the NS31406 epitope with the highest naïve precursor frequency in healthy donors was also the most frequently targeted epitope in a large cohort of chronically HCV-infected patients, both ex vivo and after in vitro stimulation. These results indicate for the first time that immunodominance in a human viral infection is linked to naïve precursor frequency