1,168 research outputs found

    The Forces of Ecosystem Evolution

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    Ecosystems are the result of a delicate balance between centripetal forces that push economic activities toward integration, and centrifugal forces that pull economic activities out onto the market. Ecosystems evolve when these forces change. For example, technological complementarities—the main source of centripetal force—are dynamic and may be commoditized, generalized, or standardized over time. Management and coordination also change: for example, open innovation practices enable firms to move innovation activities from the in-house R&D lab out into the ecosystem. This article discusses how such dynamics in technologies and management lead to ecosystem evolution

    Response of stratospheric water vapor and ozone to the unusual timing of El Niño and the QBO disruption in 2015–2016

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    This is the final version. Available from European Geosciences Union via the DOI in this record.The stratospheric circulation determines the transport and lifetime of key trace gases in a changing climate, including water vapor and ozone, which radiatively impact surface climate. The unusually warm El Niño–Southern Oscillation (ENSO) event aligned with a disrupted Quasi-Biennial Oscillation (QBO) caused an unprecedented perturbation to this circulation in 2015–2016. Here, we quantify the impact of the alignment of these two phenomena in 2015–2016 on lower stratospheric water vapor and ozone from satellite observations. We show that the warm ENSO event substantially increased water vapor and decreased ozone in the tropical lower stratosphere. The QBO disruption significantly decreased global lower stratospheric water vapor and tropical ozone from early spring to late autumn. Thus, this QBO disruption reversed the lower stratosphere moistening triggered by the alignment of the warm ENSO event with westerly QBO in early boreal winter. Our results suggest that the interplay of ENSO events and QBO phases will be crucial for the distributions of radiatively active trace gases in a changing future climate, when increasing El Niño-like conditions and a decreasing lower stratospheric QBO amplitude are expected.European CommissionEuropean CommissionNatural Environment Research Council (NERC)Helmholtz Associatio

    Origin of symbol-using systems: speech, but not sign, without the semantic urge

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    Natural language—spoken and signed—is a multichannel phenomenon, involving facial and body expression, and voice and visual intonation that is often used in the service of a social urge to communicate meaning. Given that iconicity seems easier and less abstract than making arbitrary connections between sound and meaning, iconicity and gesture have often been invoked in the origin of language alongside the urge to convey meaning. To get a fresh perspective, we critically distinguish the origin of a system capable of evolution from the subsequent evolution that system becomes capable of. Human language arose on a substrate of a system already capable of Darwinian evolution; the genetically supported uniquely human ability to learn a language reflects a key contact point between Darwinian evolution and language. Though implemented in brains generated by DNA symbols coding for protein meaning, the second higher-level symbol-using system of language now operates in a world mostly decoupled from Darwinian evolutionary constraints. Examination of Darwinian evolution of vocal learning in other animals suggests that the initial fixation of a key prerequisite to language into the human genome may actually have required initially side-stepping not only iconicity, but the urge to mean itself. If sign languages came later, they would not have faced this constraint

    Discrepancies between survey and administrative data on the use of mental health services in the general population: findings from a study conducted in Québec

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    <p>Abstract</p> <p>Background</p> <p>Population surveys and health services registers are the main source of data for the management of public health. Yet, the validity of survey data on the use of mental health services has been questioned repeatedly due to the sensitive nature of mental illness and to the risk of recall bias. The main objectives of this study were to compare data on the use of mental health services from a large scale population survey and a national health services register and to identify the factors associated with the discrepancies observed between these two sources of data.</p> <p>Methods</p> <p>This study was based on the individual linkage of data from the cycle 1.2 of the Canadian Community Health Survey (CCHS-1.2) and from the health services register of the Régie de l'assurance maladie du Québec (RAMQ). The RAMQ is the governmental agency managing the Quebec national health insurance program. The analyses mostly focused on the 637 Quebecer respondents who were recorded as users of mental health services in the RAMQ and who were self-reported users or non users of these services in the CCHS-1.2.</p> <p>Results</p> <p>Roughly 75%, of those recorded as users of mental health services users in the RAMQ's register did not report using mental health services in the CCHS-1.2. The odds of disagreement between survey and administrative data were higher in seniors, individuals with a lower level of education, legal or de facto spouses and mothers of young children. They were lower in individuals with a psychiatric disorder and in frequent and more recent users of mental health services according to the RAMQ's register.</p> <p>Conclusions</p> <p>These findings support the hypotheses that social desirability and recall bias are likely to affect the self-reported use of mental health services in a population survey. They stress the need to refine the investigation of mental health services in population surveys and to combine survey and administrative data, whenever possible, to obtain an optimal estimation of the population need for mental health care.</p

    Constitutive cytoplasmic localization of p21Waf1/Cip1 affects the apoptotic process in monocytic leukaemia

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    In the present study, we analysed the expression and localization of p21Waf1/Cip1 in normal and malignant haematopoietic cells. We demonstrate that in normal monocytic cells, protein kinase C (PKC)-induced p21 gene activation, which is nuclear factor-κB (NF-κB) independent, results in predominantly cytoplasmic localized p21 protein. In acute monocytic leukaemia (M4, M5), monocytic blasts (N=12) show constitutive cytoplasmic p21 expression in 75% of the cases, while in myeloid leukaemic blasts (N=10), low nuclear and cytoplasmic localization of p21 could be detected, which is also PKC dependent. Constitutive p21 expression in monocytic leukaemia might have important antiapoptotic functions. This is supported by the finding that in U937 cells overexpressing p21, VP16-induced apoptosis is significantly reduced (20.0±0.9 vs 55.8±3.8%, P<0.01, N=5), reflected by a reduced phosphorylation of p38 and JNK. Similarly, AML blasts with high cytoplasmic p21 were less sensitive to VP16-induced apoptosis as compared to AML cases with low or undetectable p21 expression (42.25 vs 12.3%, P<0.01). Moreover, complex formation between p21 and ASK1 could be demonstrated in AML cells, by means of coimmunoprecipitation. In summary, these results indicate that p21 has an antiapoptotic role in monocytic leukaemia, and that p21 expression is regulated in a PKC-dependent and NF-κB independent manner.

    Tapes, transcripts and trials:The routine contamination of police interview evidence

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    This article addresses a serious, but currently unacknowledged, problem of evidential consistency regarding police-suspect interview evidence. It sheds light on flaws in current criminal procedure through the lens of linguistics, focusing on key stages of currently accepted practice which fly in the face of what linguists have long known about language. It demonstrates that, in stark contrast to the strict principles of preservation applied to physical evidence, interview data go through significant transformation between their creation in the interview room and their presentation in the courtroom, especially through changes in format between written and spoken text. It argues that, despite the safeguards provided by PACE 1984, there is nonetheless a level of routine distortion and contamination unintentionally built in to the current system of presenting police interviews as evidence in England & Wales

    Antibody-free magnetic cell sorting of genetically modified primary human CD4+ T cells by one-step streptavidin affinity purification.

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    Existing methods for phenotypic selection of genetically modified mammalian cells suffer disadvantages of time, cost and scalability and, where antibodies are used to bind exogenous cell surface markers for magnetic selection, typically yield cells coated with antibody-antigen complexes and beads. To overcome these limitations we have developed a method termed Antibody-Free Magnetic Cell Sorting in which the 38 amino acid Streptavidin Binding Peptide (SBP) is displayed at the cell surface by the truncated Low Affinity Nerve Growth Receptor (LNGFRF) and used as an affinity tag for one-step selection with streptavidin-conjugated magnetic beads. Cells are released through competition with the naturally occurring vitamin biotin, free of either beads or antibody-antigen complexes and ready for culture or use in downstream applications. Antibody-Free Magnetic Cell Sorting is a rapid, cost-effective, scalable method of magnetic selection applicable to either viral transduction or transient transfection of cell lines or primary cells. We have optimised the system for enrichment of primary human CD4+ T cells expressing shRNAs and exogenous genes of interest to purities of >99%, and used it to isolate cells following Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 genome editing

    Genetic Deletion of a Single Immunodominant T-cell Response Confers Susceptibility to Virus-induced Demyelination

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    An important question in neuropathology involves determining the antigens that are targeted during demyelinating disease. Viral infection of the central nervous system (CNS) leads to T-cell responses that can be protective as well as pathogenic. In the Theiler’s murine encephalomyelitis virus (TMEV) model of demyelination it is known that the immune response to the viral capsid protein 2 (VP2) is critical for disease pathogenesis. This study shows that expressing the whole viral capsid VP2 or the minimal CD8-specific peptide VP2(121-130) as “self” leads to a loss of VP2-specific immune responses. Loss of responsiveness is caused by T cell-specific tolerance, as VP2-specific antibodies are generated in response to infection. More importantly, these mice lose the CD8 T-cell response to the immunodominant peptide VP2(121-130), which is critical for the development of demyelinating disease. The transgenic mice fail to clear the infection and develop chronic demyelinating disease in the spinal cord white matter. These findings demonstrate that T-cell responses can be removed by transgenic expression and that lack of responsiveness alters viral clearance and CNS pathology. This model will be important for understanding the mechanisms involved in antigen-specific T-cell deletion and the contribution of this response to CNS pathology

    Neck pain and anxiety do not always go together

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    Chronic pain and psychosocial distress are generally thought to be associated in chronic musculoskeletal disorders such as non-specific neck pain. However, it is unclear whether a raised level of anxiety is necessarily a feature of longstanding, intense pain amongst patient and general population sub-groups. In a cohort of 70 self-selected female, non-specific neck pain sufferers, we observed relatively high levels of self-reported pain of 4.46 (measured on the 11 point numerical pain rating scale (NRS-101)) and a longstanding duration of symptoms (156 days/year). However, the mean anxiety scores observed (5.49), fell well below the clinically relevant threshold of 21 required by the Beck Anxiety Inventory. The cohort was stratified to further distinguish individuals with higher pain intensity (NRS>6) and longer symptom duration (>90 days). Although a highly statistically significant difference (p = 0.000) was subsequently observed with respect to pain intensity, in the resulting sub-groups, none such a difference was noted with respect to anxiety levels. Our results indicate that chronic, intense pain and anxiety do not always appear to be related. Explanations for these findings may include that anxiety is not triggered in socially functional individuals, that individual coping strategies have come into play or in some instances that a psychological disorder like alexithymia could be a confounder. More studies are needed to clarify the specific role of anxiety in chronic non-specific musculoskeletal pain before general evidence-driven clinical extrapolations can be made
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