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

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

The Forces of Ecosystem Evolution

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

Secular evolution versus hierarchical merging: galaxy evolution along the Hubble sequence, in the field and rich environments

In the current galaxy formation scenarios, two physical phenomena are invoked to build disk galaxies: hierarchical mergers and more quiescent external gas accretion, coming from intergalactic filaments. Although both are thought to play a role, their relative importance is not known precisely. Here we consider the constraints on these scenarios brought by the observation-deduced star formation history on the one hand, and observed dynamics of galaxies on the other hand: the high frequency of bars and spirals, the high frequency of perturbations such as lopsidedness, warps, or polar rings. All these observations are not easily reproduced in simulations without important gas accretion. N-body simulations taking into account the mass exchange between stars and gas through star formation and feedback, can reproduce the data, only if galaxies double their mass in about 10 Gyr through gas accretion. Warped and polar ring systems are good tracers of this accretion, which occurs from cold gas which has not been virialised in the system's potential. The relative importance of these phenomena are compared between the field and rich clusters. The respective role of mergers and gas accretion vary considerably with environment.Comment: 18 pages, 8 figures, review paper to "Penetrating Bars through Masks of Cosmic Dust: the Hubble Tuning Fork Strikes a New Note", Pilanesberg, ed. D. Block et al., Kluwe

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

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.

Academic Performance and Behavioral Patterns

Identifying the factors that influence academic performance is an essential part of educational research. Previous studies have documented the importance of personality traits, class attendance, and social network structure. Because most of these analyses were based on a single behavioral aspect and/or small sample sizes, there is currently no quantification of the interplay of these factors. Here, we study the academic performance among a cohort of 538 undergraduate students forming a single, densely connected social network. Our work is based on data collected using smartphones, which the students used as their primary phones for two years. The availability of multi-channel data from a single population allows us to directly compare the explanatory power of individual and social characteristics. We find that the most informative indicators of performance are based on social ties and that network indicators result in better model performance than individual characteristics (including both personality and class attendance). We confirm earlier findings that class attendance is the most important predictor among individual characteristics. Finally, our results suggest the presence of strong homophily and/or peer effects among university students

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

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

Patterns of sick-leave and health outcomes in injured workers with back pain

Little is known about the sick-leave experiences of workers who make a workers’ compensation claim for back pain. Our objective is to describe the 1-year patterns of sick-leave and the health outcomes of a cohort of workers who make a workers’ compensation claim for back pain. We studied a cohort of 1,831 workers from five large US firms who made incident workers’ compensation claims for back pain between January 1, 1999 and June 30, 2002. Injured workers were interviewed 1 month (n = 1,321), 6 months (n = 810) and 1 year (n = 462) following the onset of their pain. We described the course of back pain using four patterns of sick-leave: (1) no sick-leave, (2) returned to worked and stayed, (3) multiple episodes of sick-leave and (4) not yet returned to work. We described the health outcomes as back and/or leg pain intensity, functional limitations and health-related quality of life. We analyzed data from participants who completed all follow-up interviews (n = 457) to compute the probabilities of transition between patterns of sick-leave. A significant proportion of workers experienced multiple episodes of sick-leave (30.2%; 95% CI 25.0–35.1) during the 1-year follow-up. The proportion of workers who did not report sick-leave declined from 42.4% (95% CI 39.0–46.1) at 1 month to 33.6% (28.0–38.7) at 1 year. One year after the injury, 2.9% (1.6–4.9) of workers had not yet returned to work. Workers who did not report sick-leave and those who returned and stayed at work reported better health outcomes than workers who experienced multiple episodes of sick-leave or workers who had not returned to work. Almost a third of workers with an incident episode of back pain experience recurrent spells of work absenteeism during the following year. Our data suggest that stable patterns of sick-leave are associated with better health

Signatures of arithmetic simplicity in metabolic network architecture

Metabolic networks perform some of the most fundamental functions in living cells, including energy transduction and building block biosynthesis. While these are the best characterized networks in living systems, understanding their evolutionary history and complex wiring constitutes one of the most fascinating open questions in biology, intimately related to the enigma of life's origin itself. Is the evolution of metabolism subject to general principles, beyond the unpredictable accumulation of multiple historical accidents? Here we search for such principles by applying to an artificial chemical universe some of the methodologies developed for the study of genome scale models of cellular metabolism. In particular, we use metabolic flux constraint-based models to exhaustively search for artificial chemistry pathways that can optimally perform an array of elementary metabolic functions. Despite the simplicity of the model employed, we find that the ensuing pathways display a surprisingly rich set of properties, including the existence of autocatalytic cycles and hierarchical modules, the appearance of universally preferable metabolites and reactions, and a logarithmic trend of pathway length as a function of input/output molecule size. Some of these properties can be derived analytically, borrowing methods previously used in cryptography. In addition, by mapping biochemical networks onto a simplified carbon atom reaction backbone, we find that several of the properties predicted by the artificial chemistry model hold for real metabolic networks. These findings suggest that optimality principles and arithmetic simplicity might lie beneath some aspects of biochemical complexity

Informing evaluation of a smartphone application for people with acquired brain injury: a stakeholder engagement study

Background Brain in Hand is a smartphone application (app) that allows users to create structured diaries with problems and solutions, attach reminders, record task completion and has a symptom monitoring system. Brain in Hand was designed to support people with psychological problems, and encourage behaviour monitoring and change. The aim of this paper is to describe the process of exploring the barriers and enablers for the uptake and use of Brain in Hand in clinical practice, identify potential adaptations of the app for use with people with acquired brain injury (ABI), and determine whether the behaviour change wheel can be used as a model for engagement. Methods We identified stakeholders: ABI survivors and carers, National Health Service and private healthcare professionals, and engaged with them via focus groups, conference presentations, small group discussions, and through questionnaires. The results were evaluated using the behaviour change wheel and descriptive statistics of questionnaire responses. Results We engaged with 20 ABI survivors, 5 carers, 25 professionals, 41 questionnaires were completed by stakeholders. Comments made during group discussions were supported by questionnaire results. Enablers included smartphone competency (capability), personalisation of app (opportunity), and identifying perceived need (motivation). Barriers included a physical and cognitive inability to use smartphone (capability), potential cost and reliability of technology (opportunity), and no desire to use technology or change from existing strategies (motivation). The stakeholders identified potential uses and changes to the app, which were not easily mapped onto the behaviour change wheel, e.g. monitoring fatigue levels, method of logging task completion, and editing the diary on their smartphone. Conclusions The study identified that both ABI survivors and therapists could see a use for Brain in Hand, but wanted users to be able to personalise it themselves to address individual user needs, e.g. monitoring activity levels. The behaviour change wheel is a useful tool when designing and evaluating engagement activities as it addresses most aspects of implementation, however additional categories may be needed to explore the specific features of assistive technology interventions, e.g. technical functions

The variable link between PNA and NAO in observations and in multi-century CGCM simulations

The link between the Pacific/North American pattern (PNA) and the North Atlantic Oscillation (NAO) is investigated in reanalysis data (NCEP, ERA40) and multi-century CGCM runs for present day climate using three versions of the ECHAM model. PNA and NAO patterns and indices are determined via rotated principal component analysis on monthly mean 500 hPa geopotential height fields using the varimax criteria. On average, the multi-century CGCM simulations show a significant anti-correlation between PNA and NAO. Further, multi-decadal periods with significantly enhanced (high anti-correlation, active phase) or weakened (low correlations, inactive phase) coupling are found in all CGCMs. In the simulated active phases, the storm track activity near Newfoundland has a stronger link with the PNA variability than during the inactive phases. On average, the reanalysis datasets show no significant anti-correlation between PNA and NAO indices, but during the sub-period 1973–1994 a significant anti-correlation is detected, suggesting that the present climate could correspond to an inactive period as detected in the CGCMs. An analysis of possible physical mechanisms suggests that the link between the patterns is established by the baroclinic waves forming the North Atlantic storm track. The geopotential height anomalies associated with negative PNA phases induce an increased advection of warm and moist air from the Gulf of Mexico and cold air from Canada. Both types of advection contribute to increase baroclinicity over eastern North America and also to increase the low level latent heat content of the warm air masses. Thus, growth conditions for eddies at the entrance of the North Atlantic storm track are enhanced. Considering the average temporal development during winter for the CGCM, results show an enhanced Newfoundland storm track maximum in the early winter for negative PNA, followed by a downstream enhancement of the Atlantic storm track in the subsequent months. In active (passive) phases, this seasonal development is enhanced (suppressed). As the storm track over the central and eastern Atlantic is closely related to the NAO variability, this development can be explained by the shift of the NAO index to more positive values