Miracle-dz/UniFAR-FTUs huggingface dataset:
Specific Calpain Inhibition by Calpastatin Prevents Tauopathy and Neurodegeneration and Restores Normal Lifespan in Tau P301L Mice

Tau pathogenicity in Alzheimer's disease and other tauopathies is thought to involve the generation of hyperphosphorylated, truncated, and oligomeric tau species with enhanced neurotoxicity, although the generative mechanisms and the implications for disease therapy are not well understood. Here, we report a striking rescue from mutant tau toxicity in the JNPL3 mouse model of tauopathy. We show that pathological activation of calpains gives rise to a range of potentially toxic forms of tau, directly, and by activating cdk5. Calpain overactivation in brains of these mice is accelerated as a result of the marked depletion of the endogenous calpain inhibitor, calpastatin. When levels of this inhibitor are restored in neurons of JNPL3 mice by overexpressing calpastatin, tauopathy is prevented, including calpain-mediated breakdown of cytoskeletal proteins, cdk5 activation, tau hyperphosphorylation, formation of potentially neurotoxic tau fragments by either calpain or caspase-3, and tau oligomerization. Calpastatin overexpression also prevents loss of motor axons, delays disease onset, and extends survival of JNPL3 mice by 3 months to within the range of normal lifespan. Our findings support the therapeutic promise of highly specific calpain inhibition in the treatment of tauopathies and other neurodegenerative states.
Predictable Dynamics in the Small Stock Premium

We start this paper by providing a detailed study of how the mean monthly return on the Small-Minus-Big (SMB) Fama-French factor is affected by the January effect and the stock market return during the preceding month and preceding calendar year. We then proceed to building a predictive model for the monthly SMB factor return that incorporates the January effect and the dependence on both the market return during the preceding month and preceding calendar year. Our findings suggest that a positive small stock premium appears mainly during the years following the years with a negative return on the market as the result of a delayed and stronger reaction of small stocks to good news and a stronger January effect. We also argue that the January effect constitutes a much lesser part of the size effect than it was previously supposed.
WHAT CAN WE LEARN FROM COMMUNITY GENETICS

Throughout the 20th century, investigators argued that genetics should be incorporated into ecological explanations (Collins 1986). C. C. Adams (1915) suggested very early in the century that emerging concepts in Mendelian genetics could help ecologists to explain the distribution of land snails in the genus Io. Genecology developed from 1920 to 1950, with research focused on intraspecific variation that anticipated ecological genetics, which developed in the 1950s and 1960s. Evolutionary ecology emerged in the 1960s, driven by empirical results in three areas (Collins 1986): ecologically significant traits like competitive ability had a genetic basis; some kinds of evolutionary change progressed within the time required for many ecological process to reach completion; and, natural selection operated over spatial scales sufficiently small such that microevolution partially explained the distribution and abundance of populations over relatively short distances. By the late 1960s, ecologists were also becoming increasingly sensitive to the level of analysis at which natural selection was expected to operate. Futuyma (1986:307) integrated these ideas in defining evolutionary ecology as ‘‘the analysis of the evolutionary origin of ecological phenomena with an explicit recognition of the distinction among, and the consequences of, selection at various levels (gene, organism, kin group, population, or higher). ’’ While on sabbatical at Duke University in 1982, I discussed population genetics and ecology with Janis Antonovics as I worked on a study of the history of the integration of ecology and evolutionary theory leading to the emergence of evolutionary ecology (Collins 1986). My efforts to understand the intellectual issues that drove the integration led to the question: To what extent is the genetic composition of populations in a community a function of the other species comprising the community? Antonovics (1992) outlined a research program in community genetics that began to address this question. The papers for this Special Feature are the most recent use of genetics in ecology, but community genetics prompts a certain optimism for two reasons. First, as Neuhauser et al. (2003) show, our ability to model these interactions is improving. Advances in computational
A framed field experiment about policy measures: Testing the effectiveness of rewards or punishments with different probabilities as incentives in palm oil production

Palm oil production creates negative externalities, e.g., through intensive fertiliser applica-tion. If policy wants to limit externalities, an effective, sustainable and efficient measure seems desira-ble. Embedded in a framed field experiment in Indonesia, we apply a business simulation game to test ex ante several incentives for reducing the use of fertiliser in palm oil production. These incentives are arranged in the form of different designs, i.e., either a reward or punishment, varying in their magni-tude and probability of occurrence but constant in the effect on expected income. Results show that participants react significantly different depending on the incentive design. A high reward with a low probability to occur has been found to be the most effective and sustainable incentive design. For effi-ciency, a low and certain reward is indicated to be the best design.
Ecological modernisation, environmental knowledge and national character: A preliminary analysis of the Netherlands

Comparative research regarding the varying capabilities of the advanced countries to pursue strategies consistent with ecological modernisation has typically focused on institutional and economic capacity. Though these features certainly shape preparedness for this policy programme in important ways, they do not provide sufficient insight into the ability of individual nations to meet the rigorous requirements of ecological modernisation. More specifically, this policy programme is dependent upon a firm commitment to science and a preference to address environmental problems in technological terms. However, environmental decision‐making, particularly among members of the lay public, is predicated upon numerous epistemologies and countries exhibit considerable variation in their propensity to align their policies with strict rational reasoning. This study introduces a typology that identifies four archetypal environmental knowledge orientations: rational ecologism, Prometheanism, Arcadianism, and ecocidal mysticism. The concept of national character offers one approach for operationalising this typology for empirical application and a case study of the Netherlands suggests that the Dutch style of interpreting indeterminate environmental data is broadly consistent with the principles of ecological modernisation.
Bone Marrow Evaluation in Initial Staging of Lymphoma: 18F-FDG PET/CT Versus Bone Marrow Biopsy

Purpose The evaluation of bone marrow infiltration (BMI) is of crucial importance in the staging of lymphoma. Although bone marrow biopsy (BMB) is the reference standard for the evaluation of BMI, it has limitations. PET/CT has become an excellent tool in staging of lymphoma, and bone marrow uptake is correlated with the involvement of lymphoma. The aim of this study was to assess the utility of PET/CT and its concordance with BMB in the detection of BMI in patients with diffuse large B-cell lymphoma (DLBCL) and Hodgkin lymphoma (HL). Patients and Methods One hundred forty-seven patients with DLBCL (84) and HL (63) were referred for a PET/CT and a BMB (unilateral) at the initial staging. The reference standard was BMB. Results Bone marrow infiltration was detected by PET/CT in 39 (26%) and by BMB in 21 (14%) cases. There was concordance between PET/CT and BMB in 128 patients (87%) (74 DLBCL, 54 HL), 21 with positive PET/CT and BMB results and 107 with negative PET/CT and BMB results. Discordant results were observed in 19 patients (14%); 18 of them with positive PET/CT and negative standard BMB results (not performed in active sites). The sensitivity, specificity, accuracy, as well as positive and negative predictive values of FDG-PET/CT for the detection of BMI were 95%, 86%, 87%, 54%, and 99%, respectively. Conclusions PET/CT detects more bone marrow involvement in DLBCL and HL compared with BMB. Its good concordance with BMB makes it a complementary technique, as it helps select the biopsy site in cases with negative results.
Transplantation of the uterus in sheep: Methodology and early reperfusion events

Aim: Uterine transplantation is developing into a clinical treatment for uterine factor infertility. An animal model with a similar uterus size and vessels to humans and with pregnancy extending over several months would be beneficial for research on uterine transplantation. The aim of this study was to develop and evaluate autotransplantation of the sheep uterus to an orthotopic position in the pelvis.
Picking Winners? A Survey of the Mean Reversion and Overreaction of Stock Prices Literature

This paper surveys, and suggests a possible synthesis of, two growing literatures concerning stock market anomalies. The first concentrates on identifying contrarian trading rules, capable of generating profits, when securities are segregated on the basis of past earnings, or share price performance. The other simply examines the time-series properties of security prices to find evidence of low-frequency negative autocorrelation, or 'mean-reversion. ' We seek to articulate the points of interdependence between the two strands of research and the problems of joint hypothesis testing implied by the close relation between 'overreaction' and 'mean-reversion' tests. Copyright 1996 by Blackwell Publishers Ltd
Determinants of the Size and Composition of US Corporate Boards: 1935-2000

"We examine the determinants of the size and composition of corporate boards for a sample of 82 US companies that survived during the period 1935-2000. Our hypotheses lead to predictions that firm size, growth opportunities, merger activity, and geographical expansion are important determinants of these board characteristics. We find empirical evidence that the four variables are significant determinants of the size and/or composition of boards. After controlling for these determinants of board characteristics, we find no robust relation between firm performance and either board size or composition". Copyright (c) 2009 Financial Management Association International.
Is the 1918 Influenza Pandemic Over? Long‐Term Effects of In Utero Influenza Exposure in the Post‐1940 U.S. Population

This paper uses the 1918 influenza pandemic as a natural experiment for testing the fetal origins hypothesis. The pandemic arrived unexpectedly in the fall of 1918 and had largely subsided by January 1919, generating sharp predictions for long‐term effects. Data from the 1960–80 decennial U.S. Census indicate that cohorts in utero during the pandemic displayed reduced educational attainment, increased rates of physical disability, lower income, lower socioeconomic status, and higher transfer payments compared with other birth cohorts. These results indicate that investments in fetal health can increase human capital.
Synchrotron‐Based Micro‐CT Imaging of the Human Lung Acinus

Structural data about the human lung fine structure are mainly based on stereological methods applied to serial sections. As these methods utilize 2D images, which are often not contiguous, they suffer from inaccuracies which are overcome by analysis of 3D micro‐CT images of the never‐sectioned specimen. The purpose of our study was to generate a complete data set of the intact three‐dimensional architecture of the human acinus using high‐resolution synchrotron‐based micro‐CT (synMCT). A human lung was inflation‐fixed by formaldehyde ventilation and then scanned in a 64‐slice CT over its apex to base extent. Lung samples (8‐mm diameter, 10‐mm height, N = 12) were punched out, stained with osmium tetroxide, and scanned using synMCT at (4 μm)3 voxel size. The lung functional unit (acinus, N = 8) was segmented from the 3D tomographic image using an automated tree‐analysis software program. Morphometric data of the lung were analyzed by ANOVA. Intra‐acinar airways branching occurred over 11 generations. The mean acinar volume was 131.3 ± 29.2 mm3 (range, 92.5–171.3 mm3) and the mean acinar surface was calculated with 1012 ± 26 cm2. The airway internal diameter (starting from the bronchiolus terminalis) decreases distally from 0.66 ± 0.04 mm to 0.34 ± 0.06 mm (P < 0.001) and remains constant after the seventh generation (P < 0.5). The length of each generation ranges between 0.52 and 0.93 mm and did not show significant differences between the second and eleventh generation. The branching angle between daughter branches varies between 113‐degree and 134‐degree without significant differences between the generations (P < 0.3). This study demonstrates the feasibility of quantitating the 3D structure of the human acinus at the spatial resolution readily achievable using synMCT. Anat Rec 293:1607–1614, 2010. © 2010 Wiley‐Liss, Inc.
Prognostic Value of Total Atrial Conduction Time Measured with Tissue Doppler Imaging to Predict the Maintenance of Sinus Rhythm after External Electrical Cardioversion of Persistent Atrial Fibrillation

Atrial fibrillation (AF) is the most common sustained arrhythmia, with a high recurrence rate, especially during the first months after cardioversion (CV). Few parameters have been evaluated as predictors for the maintenance of sinus rhythm (SR), with limited results. Recently total atrial conduction time (TACT) has been proposed as independent predictor of AF recurrence. The aim of this study was to investigate the prognostic value of TACT, measured using PA‐TDI duration, to predict 1‐year maintenance of restored SR after electrical CV.
The Role of the Cytoskeleton and Myosin-Vc in the Targeting of KCa3.1 to the Basolateral Membrane of Polarized Epithelial Cells

Understanding the targeting of KCa3.1 to the basolateral membrane (BLM) of polarized epithelial cells is still emerging. Here, we examined the role of the cytoskeleton (microtubules and microfilaments) and Myosin-Vc (Myo-Vc) in the targeting of KCa3.1 in Fischer rat thyroid epithelial cells. We used a pharmacological approach with immunoblot (for the BLM expression of KCa3.1), Ussing chamber (functional BLM expression of KCa3.1) and siRNA experiments. The actin cytoskeleton inhibitors cytochalasin D (10 μM, 5 h) and latrunculin A (10 μM, 5 h) reduced the targeting of KCa3.1 to the BLM by 88 ± 4 and 70 ± 5%, respectively. Colchicine (10 μM, 5 h) a microtubule inhibitor reduced targeting of KCa3.1 to the BLM by 63 ± 7% and decreased 1-EBIO-stimulated KCa3.1 K+ current by 46 ± 18%, compared with control cells. ML9 (10 μM, 5 h), an inhibitor of myosin light chain kinase, decreased targeting of the channel by 83 ± 2% and reduced K+ current by 54 ± 8% compared to control cells. Inhibiting Myo-V with 2,3-butanedione monoxime (10 mM, 5 h) reduced targeting of the channel to the BLM by 58 ± 5% and decreased the stimulated current of KCa3.1 by 48 ± 12% compared with control cells. Finally, using siRNA for Myo-Vc, we demonstrated that knockdown of Myo-Vc reduced the BLM expression of KCa3.1 by 44 ± 7% and KCa3.1 K+ current by 1.04 ± 0.14 μA compared with control cells. These data suggest that the microtubule and microfilament cytoskeleton and Myo-Vc are critical for the targeting of KCa3.1.
Global physical activity questionnaire (GPAQ): nine country reliability and validity study.

PURPOSE Instruments to assess physical activity are needed for (inter)national surveillance systems and comparison. METHODS Male and female adults were recruited from diverse sociocultural, educational and economic backgrounds in 9 countries (total n = 2657). GPAQ and the International Physical Activity Questionnaire (IPAQ) were administered on at least 2 occasions. Eight countries assessed criterion validity using an objective measure (pedometer or accelerometer) over 7 days. RESULTS Reliability coefficients were of moderate to substantial strength (Kappa 0.67 to 0.73; Spearman's rho 0.67 to 0.81). Results on concurrent validity between IPAQ and GPAQ also showed a moderate to strong positive relationship (range 0.45 to 0.65). Results on criterion validity were in the poor-fair (range 0.06 to 0.35). There were some observed differences between sex, education, BMI and urban/rural and between countries. CONCLUSIONS Overall GPAQ provides reproducible data and showed a moderate-strong positive correlation with IPAQ, a previously validated and accepted measure of physical activity. Validation of GPAQ produced poor results although the magnitude was similar to the range reported in other studies. Overall, these results indicate that GPAQ is a suitable and acceptable instrument for monitoring physical activity in population health surveillance systems, although further replication of this work in other countries is warranted.
Requiem for Kyoto: An Economic Analysis of the Kyoto Protocol

This paper uses the newly developed RICE-98 model to analyze the economics of the Kyoto Protocol. It analyzes versions of the Kyoto Protocol that have different approaches to trading emissions rights and compares these with efficient approaches. The major conclusions are: (a) the net global cost of the Kyoto Protocol is $716 billion in present value, (b) the United States bears almost two thirds of the global cost; and (c) the benefit-cost ratio of the Kyoto Protocol is 1/7. Additionally, the emissions strategy is highly cost-ineffective, with the global temperature reduction achieved at a cost almost 8 times the cost of a strategy which is cost-effective in terms of "where" and "when" efficiency. These conclusions assume that trading in carbon permits is allowed among the Annex I countries.
Econometricians Have Their Moments: GMM at 32

The 2013 Nobel Prize for Economics was awarded to Eugene Fama, Lars Hansen and Robert Shiller for their work on empirical asset pricing. Hansen's primary contribution to the cited work was the development of the generalised method of moments (GMM), a statistical method that has proved such a valuable tool for testing the validity of empirical asset pricing models. The public announcement of the award also acknowledges the wider impact of GMM on empirical analysis in economics and beyond, referring to the 1982 Econometrica paper in which Hansen introduced the method as ‘one of the most influential in econometrics’. In this paper, we reflect on how the GMM-based inference framework has evolved since 1982, reviewing developments on four main issues: model diagnostic testing, moment selection, identification and inference in misspecified models. We also illustrate the broader influence of GMM on econometrics by briefly exploring the connections between GMM and three other estimation methods: indirect inference, moment inequality based techniques, and a group of techniques that can be presented equivalently within either the generalised empirical likelihood or info-metric frameworks.
Equally Weighted vs. Long‐Run Optimal Portfolios

Out-of-sample experiments cast doubt on the ability of portfolio optimizing strategies to outperform equally weighted portfolios, when investors have a 1-month time horizon. This paper examines whether this finding holds for longer investment horizons over which the optimizing strategy exploits linear predictability in returns. Our experiments indicate that investors with longer horizons on average would have benefited, ex post, from an optimizing strategy over the period 1995–2009. We analyze performance sensitivity to investor risk aversion, to the number of predictors included in the forecasting model and to the deduction of transaction costs from portfolio performance.
Regulation of Cellular Dynamics and Chromosomal Binding Site Preference of Linker Histones H1.0 and H1.X

ABSTRACT Linker histones play important roles in the genomic organization of mammalian cells. Of the linker histone variants, H1.X shows the most dynamic behavior in the nucleus. Recent research has suggested that the linker histone variants H1.X and H1.0 have different chromosomal binding site preferences. However, it remains unclear how the dynamics and binding site preferences of linker histones are determined. Here, we biochemically demonstrated that the DNA/nucleosome and histone chaperone binding activities of H1.X are significantly lower than those of other linker histones. This explains why H1.X moves more rapidly than other linker histones in vivo. Domain swapping between H1.0 and H1.X suggests that the globular domain (GD) and C-terminal domain (CTD) of H1.X independently contribute to the dynamic behavior of H1.X. Our results also suggest that the N-terminal domain (NTD), GD, and CTD cooperatively determine the preferential binding sites, and the contribution of each domain for this determination is different depending on the target genes. We also found that linker histones accumulate in the nucleoli when the nucleosome binding activities of the GDs are weak. Our results contribute to understanding the molecular mechanisms of dynamic behaviors, binding site selection, and localization of linker histones.
The International Journal of Biostatistics A Refreshing Account of Principal Stratification

Pearl (2011) invites researchers to contribute to a discussion on the logic and utility of principal stratification in causal inference, raising some thought-provoking questions. In our commentary, we discuss the role of principal stratification in causal inference, describing why we view the principal stratification framework as useful for addressing causal inference problems where causal estimands are defined in terms of intermediate outcomes. We focus on mediation analysis and principal stratification analysis, showing that they generally involve different causal estimands and answer different questions. We argue that even when principal stratification may not answer the causal questions of primary interest, it can be a preliminary analysis of the data to assess the plausibility of identifying assumptions. We also discuss the use of principal stratification to address issues of surrogate outcomes. Our discussion stresses that a principal stratification analysis should account for all the principal strata and evaluate the distributions of potential outcomes in each of the principal strata. To this end, we view a Bayesian analysis particularly suited for drawing inference on principal strata membership and principal strata effects.
Elevated Cardiac Troponin (cTnI) Levels Correlate with the Clinical and Echocardiographic Evidences of Severe Myocarditis in Scorpion Sting Envenomation.

OBJECTIVE This study was to evaluate the predictive value of the cardiac troponins in scorpion sting myocarditis at a tertiary care hospital in Raichur, (Karnataka state) India. METHODS A total of 84 consecutive patients were prospectively studied. The data included the demographics, the time of presentation to the hospital, the clinical features, the cardiac troponin levels and the echocardiographic findings. RESULTS 12 patients with only local symptoms had troponin levels of less than 0.01μg/L. 12 patients with local and systemic symptoms without an echocardiac evidence of myocarditis had troponin values of 0.01 to 0.11 μg/L. 60 patients with an echocardiographic evidence of myocarditis had troponin levels of above 0.11 μg/L. 6 patients with severe myocarditis who required ventilator support or which led to death had troponin values which were higher than 10 μg/L. CONCLUSIONS High cardiac troponin levels predict myocarditis in scorpion sting envenomation and they can be a useful tool in guiding the therapy early.