Analysis of a fragmentary diatom record from Lake Van (Turkey) reveals substantial lake-level variability during previous interglacials MIS7 and MIS5e

Ancient lake sediments provide opportunities to reconstruct aquatic ecosystems during previous interglacials. In the summer of 2010, the ICDP project PALEOVAN drilled a complete succession of the lacustrine sedimentary sequence deposited during the last ~600,000 years in Lake Van, eastern Anatolia (Turkey). Previous palaeolimnological analysis of the Lake Van sediment record has shown diatoms to be absent over most of the sequence apart from a short interval during the Holocene. Here, we demonstrate the preservation of additional fragmentary diatom records during Marine Isotope Stage (MIS) 7 (243,000–191,000 years ago; Lisiecki and Raymo in Paleoceanography 20:PA1003, 2005; Jouzel et al. in Science 317:793–796, 2007) and MIS5e (130,000–116,000 years ago; Lisiecki and Raymo 2005; Jouzel et al. 2007), each spanning no more than a few thousand years. Although brief, the presence of contrasting diatom assemblages between these two interglacials provide a snapshot of varying water depth and, by inference, climate. Analysis of MIS7e samples suggests that lake water levels were low after a period when the lake was open (i.e., high lake levels with the presence of an outflow present), resulting in higher salinities and possibly less stable bottom waters, which switched between anoxic and oxic states more frequently. By contrast, the diatom assemblages during MIS5e are characteristic of fresh, relatively nutrient rich waters. This suggests that lake levels were high, that the lake was hydrologically open with an outlet, and that the bottom waters were anoxic for long periods of time. Furthermore, our palaeoconductivity estimates and modelling of the past lake volumes with respect to its salt content support the presence of an outflow

An economics perspective of patenting behavior in small entrepreneurial firms

This dissertation explores the use of patents as an Intellectual Property Protection Mechanism (IPPM) among small entrepreneurial firms both from a theoretical and an empirical perspective. I borrow from the patenting and firm signaling literature to frame my theoretical models and to ask empirical questions with an eye on broadening the scope of the existing literature. I start with a review of the patenting literature which motivated the need to document cross-country differences in patent laws. Theoretically, I model the use of patents among small firms as a signal of technological ability. I propose two patent signaling games where in both, a higher and a lower ability firm try to use the number of patents that they hold to signal their ability. However, in one model, patents are productive and generate higher profits whereas in the other they are not (in appendix B, I develop an augmented signaling model where start-ups are given the choice to either accept or decline an offer). Conditions for the existence of both pooling and separating equilibria are identified. In the pooling equilibria, types cannot be distinguished making patents an ambiguous signal. However, in the separating equilibria, patents are informative. Empirically, I first study relevant covariates that are associated with the use of patents as an IPPM among small firms using a probit model. Next, I make causal inferences about the theoretical models using a two-stage least squares estimator, a control function approach and a “full switching regression approach” to account for heterogenous treatment effects. I use Lewbel’s method of generated instruments combined with other external instruments as a robustness check. The results show that R&D intensity, firm size, market structure, the sector in which the firm operates, human capital and demographic characteristics of founders, firm location (in some instances) are all relevant covariates that are associated with the use of patents as an IPPM among small entrepreneurial firms. The empirical analyses also provided evidence in support of the model in which patents are a signal that do not impact a firm’s productivity measured as sales growth. The data used in the empirical sections come from the Advancing Knowledge-Intensive Innovation for Growth and Social Well-being in Europe (AEGIS) dataset which relate to small entrepreneurial firms in 10 European-Union countries

Enhanced self-renewal of hematopoietic stem/progenitor cells mediated by the stem cell gene Sall4

<p>Abstract</p> <p>Background</p> <p>Sall4 is a key factor for the maintenance of pluripotency and self-renewal of embryonic stem cells (ESCs). Our previous studies have shown that Sall4 is a robust stimulator for human hematopoietic stem and progenitor cell (HSC/HPC) expansion. The purpose of the current study is to further evaluate how Sall4 may affect HSC/HPC activities in a murine system.</p> <p>Methods</p> <p>Lentiviral vectors expressing Sall4A or Sall4B isoform were used to transduce mouse bone marrow Lin-/Sca1+/c-Kit+ (LSK) cells and HSC/HPC self-renewal and differentiation were evaluated.</p> <p>Results</p> <p>Forced expression of Sall4 isoforms led to sustained <it>ex vivo </it>proliferation of LSK cells. In addition, Sall4 expanded HSC/HPCs exhibited increased <it>in vivo </it>repopulating abilities after bone marrow transplantation. These activities were associated with dramatic upregulation of multiple HSC/HPC regulatory genes including HoxB4, Notch1, Bmi1, Runx1, Meis1 and Nf-ya. Consistently, downregulation of endogenous Sall4 expression led to reduced LSK cell proliferation and accelerated cell differentiation. Moreover, in myeloid progenitor cells (32D), overexpression of Sall4 isoforms inhibited granulocytic differentiation and permitted expansion of undifferentiated cells with defined cytokines, consistent with the known functions of Sall4 in the ES cell system.</p> <p>Conclusion</p> <p>Sall4 is a potent regulator for HSC/HPC self-renewal, likely by increasing self-renewal activity and inhibiting differentiation. Our work provides further support that Sall4 manipulation may be a new model for expanding clinically transplantable stem cells.</p

Institutional barriers and industry dynamics

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108084/1/smj2152.pd

The pathogen recognition sensor, NOD2, is variably expressed in patients with pulmonary tuberculosis

Background: NOD2, an intracellular pathogen recognition sensor, modulates innate defences to muropeptides derived from various bacterial species, including Mycobacterium tuberculosis (MTB). Experimentally, NOD2 attenuates two key putative mycobactericidal mechanisms. TNF-alpha synthesis is markedly reduced in MTB-antigen stimulated-mononuclear cells expressing mutant NOD2 proteins. NOD2 agonists also induce resistance to apoptosis, and may thus facilitate the survival of MTB in infected macrophages. To further define a role for NOD2 in disease pathogenesis, we analysed NOD2 transcriptional responses in pulmonary leucocytes and mononuclear cells harvested from patients with pulmonary tuberculosis (PTB).Methods: We analysed NOD2 mRNA expression by real-time polymerase chain-reaction in alveolar lavage cells obtained from 15 patients with pulmonary tuberculosis and their matched controls. We compared NOD2 transcriptional responses, in peripheral leucocytes, before and after anti-tuberculous treatment in 10 patients. In vitro, we measured NOD2 mRNA levels in MTB-antigen stimulated-mononuclear cells.Results: No significant differences in NOD2 transcriptional responses were detected in patients and controls. In some patients, however, NOD2 expression was markedly increased and correlated with toll-like-receptor 2 and 4 expression. In whole blood, NOD2 mRNA levels increased significantly after completion of anti-tuberculosis treatment. NOD2 expression levels did not change significantly in mononuclear cells stimulated with mycobacterial antigens in vitro.Conclusion: There are no characteristic NOD2 transcriptional responses in PTB. Nonetheless, the increased levels of NOD2 expression in some patients with severe tuberculosis, and the increases in expression levels within peripheral leucocytes following treatment merit further studies in selected patient and control populations

Prediction of pre-eclampsia: a protocol for systematic reviews of test accuracy

BACKGROUND: Pre-eclampsia, a syndrome of hypertension and proteinuria, is a major cause of maternal and perinatal morbidity and mortality. Accurate prediction of pre-eclampsia is important, since high risk women could benefit from intensive monitoring and preventive treatment. However, decision making is currently hampered due to lack of precise and up to date comprehensive evidence summaries on estimates of risk of developing pre-eclampsia. METHODS/DESIGN: A series of systematic reviews and meta-analyses will be undertaken to determine, among women in early pregnancy, the accuracy of various tests (history, examinations and investigations) for predicting pre-eclampsia. We will search Medline, Embase, Cochrane Library, MEDION, citation lists of review articles and eligible primary articles and will contact experts in the field. Reviewers working independently will select studies, extract data, and assess study validity according to established criteria. Language restrictions will not be applied. Bivariate meta-analysis of sensitivity and specificity will be considered for tests whose studies allow generation of 2 × 2 tables. DISCUSSION: The results of the test accuracy reviews will be integrated with results of effectiveness reviews of preventive interventions to assess the impact of test-intervention combinations for prevention of pre-eclampsia

Exploring synergies and trade-offs among the sustainable development goals: collective action and adaptive capacity in marginal mountainous areas of India

Global environmental change (GEC) threatens to undermine the sustainable development goals (SDGs). Smallholders in marginal mountainous areas (MMA) are particularly vulnerable due to precarious livelihoods in challenging environments. Acting collectively can enable and constrain the ability of smallholders to adapt to GEC. The objectives of this paper are: (i) identify collective actions in four MMA of the central Indian Himalaya Region, each with differing institutional contexts; (ii) assess the adaptive capacity of each village by measuring livelihood capital assets, diversity, and sustainable land management practices. Engaging with adaptive capacity and collective action literatures, we identify three broad approaches to adaptive capacity relating to the SDGs: natural hazard mitigation (SDG 13), social vulnerability (SDG 1, 2 and 5), and social–ecological resilience (SDG 15). We then develop a conceptual framework to understand the institutional context and identify SDG synergies and trade-offs. Adopting a mixed method approach, we analyse the relationships between collective action and the adaptive capacity of each village, the sites where apparent trade-offs and synergies among SDGs occur. Results illustrate each village has unique socio-environmental characteristics, implying distinct development challenges, vulnerabilities and adaptive capacities exist. Subsequently, specific SDG synergies and trade-offs occur even within MMA, and it is therefore crucial that institutions facilitate locally appropriate collective actions in order to achieve the SDGs. We suggest that co-production in the identification, prioritisation and potential solutions to the distinct challenges facing MMA can increase understandings of the specific dynamics and feedbacks necessary to achieve the SDGs in the context of GEC

Family Influences on the Long Term Post-Disaster Recovery of Puerto Rican Youth

This study focused on characteristics of the family environment that may mediate the relationship between disaster exposure and the presence of symptoms that met DSM-IV diagnostic criteria for symptom count and duration for an internalizing disorder in children and youth. We also explored how parental history of mental health problems may moderate this meditational model. Approximately 18 months after Hurricane Georges hit Puerto Rico in 1998, participants were randomly selected based on a probability household sample using 1990 US Census block groups. Caregivers and children (N=1,886 dyads) were interviewed with the Diagnostic Interview Schedule for Children and other questionnaires in Spanish. Areas of the family environment assessed include parent-child relationship quality, parent-child involvement, parental monitoring, discipline, parents’ relationship quality and parental mental health. SEM models were estimated for parents and children, and by age group. For children (4–10 years old), parenting variables were related to internalizing psychopathology, but did not mediate the exposure-psychopathology relationship. Exposure had a direct relationship to internalizing psychopathology. For youth (11–17 years old), some parenting variables attenuated the relation between exposure and internalizing psychopathology. Family environment factors may play a mediational role in psychopathology post-disaster among youth, compared to an additive role for children. Hurricane exposure had a significant relation to family environment for families without parental history of mental health problems, but no influence for families with a parental history of mental health problems

Acute effects of fine particulate air pollution on ST segment height: A longitudinal study

Background The mechanisms for the relationship between particulate air pollution and cardiac disease are not fully understood. Air pollution-induced myocardial ischemia is one of the potentially important mechanisms. Methods We investigate the acute effects and the time course of fine particulate pollution (PM2.5) on myocardium ischemic injury as assessed by ST-segment height in a community-based sample of 106 healthy non-smokers. Twenty-four hour beat-to-beat electrocardiogram (ECG) data were obtained using a high resolution 12-lead Holter ECG system. After visually identifying and removing all the artifacts and arrhythmic beats, we calculated beat-to-beat ST-height from ten leads (inferior leads II, III, and aVF; anterior leads V3 and V4; septal leads V1 and V2; lateral leads I, V5, and V6,). Individual-level 24-hour real-time PM2.5 concentration was obtained by a continuous personal PM2.5 monitor. We then calculated, on a 30-minute basis, the corresponding time-of-the-day specific average exposure to PM2.5 for each participant. Distributed lag models under a linear mixed-effects models framework were used to assess the regression coefficients between 30-minute PM2.5 and ST-height measures from each lead; i.e., one lag indicates a 30-minute separation between the exposure and outcome. Results The mean (SD) age was 56 (7.6) years, with 41% male and 74% white. The mean (SD) PM2.5 exposure was 14 (22) μg/m3. All inferior leads (II, III, and aVF) and two out of three lateral leads (I and V6), showed a significant association between higher PM2.5 levels and higher ST-height. Most of the adverse effects occurred within two hours after PM2.5 exposure. The multivariable adjusted regression coefficients β (95% CI) of the cumulative effect due to a 10 μg/m3 increase in Lag 0-4 PM2.5 on ST-I, II, III, aVF and ST-V6 were 0.29 (0.01-0.56) μV, 0.79 (0.20-1.39) μV, 0.52 (0.01-1.05) μV, 0.65 (0.11-1.19) μV, and 0.58 (0.07-1.09) μV, respectively, with all p < 0.05. Conclusions Increased PM2.5 concentration is associated with immediate increase in ST-segment height in inferior and lateral leads, generally within two hours. Such an acute effect of PM2.5 may contribute to increased potential for regional myocardial ischemic injury among healthy individuals