Miracle-dz/UniFAR-FTUs huggingface dataset:
Tsc 2 gene inactivation causes a more severe epilepsy phenotype than Tsc 1 inactivation in a mouse model of Tuberous Sclerosis Complex

Tuberous Sclerosis Complex (TSC) is an autosomal dominant, multi-system disorder, typically involving severe neurological symptoms, such as epilepsy, cognitive deficits and autism. Two genes, TSC1 and TSC2, encoding the proteins hamartin and tuberin, respectively, have been identified as causing TSC. Although there is a substantial overlap in the clinical phenotype produced by TSC1 and TSC2 mutations, accumulating evidence indicates that TSC2 mutations cause more severe neurological manifestations than TSC1 mutations. In this study, the neurological phenotype of a novel mouse model involving conditional inactivation of the Tsc2 gene in glial-fibrillary acidic protein (GFAP)-positive cells (Tsc2CKO mice) was characterized and compared with previously generated Tsc1CKO mice. Similar to Tsc1CKO mice, Tsc2CKO mice exhibited epilepsy, premature death, progressive megencephaly, diffuse glial proliferation, dispersion of hippocampal pyramidal cells and decreased astrocyte glutamate transporter expression. However, Tsc2CKO mice had an earlier onset and higher frequency of seizures, as well as significantly more severe histological abnormalities, compared with Tsc1CKO mice. The differences between Tsc1CKO and Tsc2CKO mice were correlated with higher levels of mammalian target of rapamycin (mTOR) activation in Tsc2CKO mice and were reversed by the mTOR inhibitor, rapamycin. These findings provide novel evidence in mouse models that Tsc2 mutations intrinsically cause a more severe neurological phenotype than Tsc1 mutations and suggest that the difference in phenotype may be related to the degree to which Tsc1 and Tsc2 inactivation causes abnormal mTOR activation.
Zebrafish early macrophages colonize cephalic mesenchyme and developing brain, retina, and epidermis through a M-CSF receptor-dependent invasive process.

The origin of resident (noninflammatory) macrophages in vertebrate tissues is still poorly understood. In the zebrafish embryo, we recently described a specific lineage of early macrophages that differentiate in the yolk sac before the onset of blood circulation. We now show that these early macrophages spread in the whole cephalic mesenchyme, and from there invade epithelial tissues: epidermis, retina, and brain--especially the optic tectum. In the panther mutant, which lacks a functional fms (M-CSF receptor) gene, early macrophages differentiate and behave apparently normally in the yolk sac, but then fail to invade embryonic tissues. Our video recordings then document for the first time the behavior of macrophages in the invaded tissues, revealing the striking propensity of early macrophages in epidermis and brain to wander restlessly among epithelial cells. This unexpected behavior suggests that tissue macrophages may be constantly "patrolling" for immune and possibly also developmental and trophic surveillance. At 60 h post-fertilization, all macrophages in the brain and retina undergo a specific phenotypic transformation, into "early (amoeboid) microglia": they become more highly endocytic, they down-regulate the L-plastin gene, and abruptly start expressing high levels of apolipoprotein E, a well-known neurotrophic lipid carrier.
EFFICIENT METHOD FOR IDENTIFYING MUTATED DRIVER PATHWAYS IN CANCER USING HARMONY SEARCH By Noura

Cancer research revolves around the study of diseases that involve unregulated cell growth so, if we think about therapeutic decision that can be made after surgical resection of tumors (adjuvant treatment) is based on an assessment of the risk of tumor relapse; such assessment enables scientists to focus on others strategies for classifying tumors. These strategies not only improve the classification of each tumor type, but also guide the development of therapeutic approaches to limiting tumor growth and contributing to the delivery of personalized medical care. This type of classification depends on identifying of mutated driver pathways in a particular kind of cancer. The maximum weight submatrix problem is used to identify the mutated driver pathways, where we need to test all the submatrices in the mutation matrix and each submatrix may performs a candidate solution for our problem. This procedure needs a lot of time and a special kind of processor. The standard methods that are used to solve this problem suffered from the limitation; thus we proposed the improved harmony search algorithm, which offered a higher number of suggested gene set solutions for mutated genes than did the standard genetic algorithm and the harmony search.
Reconciling different observational data sets from Surface Heat Budget of the Arctic Ocean (SHEBA) for model validation purposes

[1] Observations from the Surface Heat Budget of the Arctic Ocean (SHEBA) are analyzed to develop a consistent data set suitable for the validation of snow and sea ice components used in climate models. Since the snow depth is a crucial variable to properly determine the ice thickness evolution, several methods are tested to estimate the actual snow depth at the exact location of the measured internal temperatures. Snow and ice thickness gauge measurements show high spatial variability at small spatial scales. Consequently, individual measurements of snow/ice thickness are not representative of the thickness at the locations where temperature profiles were measured. Observed skin temperatures and snow internal temperature profiles suggest that the mean winter snow cover at the reference mass balance site was thicker by 11 cm when compared with gauge observations at a small distance from that reference site. The mean winter snow cover thickness measured at the SHEBA mass balance site, Pittsburgh, is larger by a factor of 2.3 when compared to the snow depth derived from precipitation measurements. Assuming continuity of heat fluxes at the snow-ice interface, an effective snow thermal conductivity of 0.50 Wm−1 K−1 is calculated. This is significantly higher than values generally used in climate models (0.31 Wm−1 K−1) or derived from in situ measurements (0.14 Wm−1 K−1) at SHEBA. Ocean heat fluxes, inferred from ice thickness and internal temperature measurements at various sites, are very consistent and match reasonably well those derived from turbulence measurements and a bulk formulation. A heat budget of surface fluxes shows a mean annual net imbalance of 1.5 Wm−2, with a mean energy deficit of 3.5 Wm−2 during winter and a mean surplus of 6.4 Wm−2 during summer.
Earnings Effects of Permanent Employment Promoting Reforms : Analysis of the 1997 Labour Market Reform in Spain

Temporary employment accounts in Spain for about one third of total salaried employment since the mid-Eighties, which triples European figures. In the Nineties, two labour market reforms were implemented in an attempt to reduce the very high incidence of temporary employment, achieving some positive effects on employment. However, we still have a very limited knowledge of the likely effects on earnings. Since the reform applied only to certain age groups, in this paper we use a natural experiment research design to assess the impact of the 1997 reform on earnings levels. Using data on the Spanish component of the ECHP, we find positive effects on earnings of young men signing new contracts from unemployment.
The Relationship between Storm Motion, Vertical Wind Shear, and Convective Asymmetries in Tropical Cyclones

Abstract The influence of the direction of storm motion on the azimuthal distribution of electrified convection in 35 Atlantic basin tropical cyclones from 1985 to 1999 was examined using data from the National Lightning Detection Network. In the inner 100 km, flashes most often occurred in the front half of storms, with a preference for the right-front quadrant. In the outer rainbands (r = 100–300 km), flashes occurred predominantly to the right of motion, although the maximum remained in the right-front quadrant. The results are shown to be consistent with previous studies of asymmetries in rainfall, radar reflectivity, and vertical motion with respect to tropical cyclone motion. The motion effect has been attributed to the influence of asymmetric friction in the tropical cyclone boundary layer. The authors previously found a strong signature in the azimuthal distribution of lightning with respect to vertical wind shear. Because both effects show clearly, vertical wind shear and storm motion must themse.
Nanomechanical properties and the hierarchical structure of elytra cuticle of dung beetle (Copris ochus Motschulsky)

Natural biomaterials are complex composites in hierarchical structure and multifunction. They have some special structures and functions because of their evolution through the exchanges of energy, matter and information with their surroundings over millions of years. The cuticle represents 25% of the dry weight of the entire insect body. It is tenacity, waterproof and lightweight which is an excellent crude composite material. An increasing interest in bionic design of materials based on structures of natural biomaterials has led to the nanomechanical characterization of biomaterials. Quantitive measurement of mechanical properties of insect cuticle will help to develop biomimetic materials suitable for industrial products. Field emission scanning electron microscopy (FESEM) was used to investigate the detail structure of elytra cross section in transverse direction and longitudinal direction. Shown in transverse direction, the fibers of the deeper layers of the endocuticle are orientated in rotation angle and neighbor fibers are rotated in relation to the each other in the same direction. While the fibers in longitudinal direction show the epicuticle, exocuticle and endocuticle clearly hierarchically structure in parallel. In this work, the mechanical properties of the elytra cuticle of dung beetle Copris ochus Motschulsky, reduced modulus and hardness in nano-scale, were investigated by using a nanoindenter. The reduced modulus (Ev) and hardness (Hv) of surface cuticle in the vertical direction obtained by nanoindentation was 5.96 ± 0.32GPa and 0.32 ± 0.09GPa, respectively. The nanoindentation result was shown that the reduced modulus (Et, El) and hardness (Ht, Hl) of each layer was gradually reduced from the outer layer to the inner layer in the transverse direction and the longitudinal direction, respectively. Ev was less than the largest Et presented at outer layer (7.34 ± 0.27GPa) and was larger than that of El (6.05 ± 1.12GPa) which shows the anisotropy of chitin fibers. It was supposedly formed as a result of the composite effect of the hierarchically structure.
Thymocyte-Dendritic Cell Interactions near Sources of CCR7 Ligands in the Thymic Cortex1

Little is known about the dynamics of the interactions between thymocytes and other cell types, as well as the spatiotemporal distribution of thymocytes during positive selection in the microenvironment of the cortex. We used two-photon laser scanning microscopy of the mouse thymus to visualize thymocytes and dendritic cells (DCs) and to characterize their interactions in the cortex. We show that thymocytes make frequent contacts with DCs in the thymic cortex and that these associations increase when thymocytes express T cell receptors that mediate positive selection. We also show that cortical DCs and the chemokine CCL21 expression are closely associated with capillaries throughout the cortex. The overexpression of the chemokine receptor CCR7 in thymocytes results in an increase in DC-thymocyte interactions, while the loss of CCR7 in the background of a positive-selecting TCR reduces the extent of DC-thymocyte interactions. These observations identify a vasculature-associated microenvironment within the thymic cortex that promotes interactions between DCs and thymocytes that are receiving positive selection signals.
Gender Differences in Competition : The Role of Socialization

This study uses an experimental task to explore whether there are gender differences in selecting into competitive environments across two distinct societies: the Maasai in Tanzania and the Khasi in India. One unique aspect of these civilizations is that the Maasai represent a textbook example of a patriarchal society whereas the Khasi are matrilineal. Similar to the extant evidence drawn from experimental data in Western cultures, Maasai men opt to compete at roughly twice the rate as Maasai women. Interestingly, this result is reversed amongst the Khasi, where women choose the competitive environment considerably more often than Khasi men, and even choose to compete weakly more often than Maasai men. These results provide initial insights into the underpinnings of the factors hypothesized to be important determinants of the observed gender differences. In particular, the data provide a first piece of evidence that the existing societal structure is crucially linked to the observed gender differences in competitiveness.
Palaeocene–Eocene paratropical floral change in North America: responses to climate change and plant immigration

The Initial Eocene Thermal Maximum (IETM) at c. 55 Ma represents a period of rapid global warming that lasted less than 200 ka. The response of vegetation to such an event, and particularly warm-adapted highly diverse vegetation types, is poorly understood. Using pollen floral, clay mineral and stable carbon isotope analyses of sediments from the upper Tuscahoma Formation on the eastern US Gulf Coast (eastern Mississippi and western Alabama), we document paratropical floral changes across the Palaeocene–Eocene boundary from the Wahalak #2 and lower Harrell cores. Data indicate strong changes in the abundance of kaolinite that correlate with changes in relative abundance of native pollen taxa. There is no evidence for a transient, extra-tropical flora on the US Gulf Coast that may characterize the IETM. Immigration and extinction are not associated with this event. Instead, Early Eocene plant immigration occurs in pulses and therefore is not associated directly with climate change during the IETM. The two cores share the same regional species pool but compositional differences are stronger between cores than they are either through changes in environment, increased soil erosion or chemical weathering, or through the introduction of non-native plants. Our data suggest that vegetation change across the Palaeocene–Eocene boundary is not a single event but rather a sequence of cascading events.
The Empirical Determinants of Credit Default Swap Spreads: A Quantile Regression Approach

We study the empirical determinants of Credit Default Swap (CDS) spreads through quantile regressions. In addition to traditional variables, such as implied volatility, put skew, historical stock return, leverage, profitability, and ratings, the results indicate that CDS premiums are strongly determined by CDS illiquidity costs, measured by absolute bid‐ask spreads. The quantile regression approach reveals that high‐risk firms are more sensitive to changes in the explanatory variables that low‐risk firms. Furthermore, the goodness‐of‐fit of the model increases with CDS premiums, which is consistent with the credit spread puzzle.
Eligibility for Social Security Disability Insurance

In order to understand whom among the non-disabled older population experiences a health problem later in life and applies for Social Security Disability Insurance, it is necessary to investigate patterns of coverage and reasons for non-coverage. This paper shows that while the safety net program covers most American workers, a substantial group of older women is not covered. In this sense, the program is not helpful to workers reaching their late 50’s and early 60’s with health-related problems.
When Science Offers Salvation: Patient Advocacy and Research Ethics

1. Patient Advocacy and the Changing Research Environment 2. Advocates on the Research Team - Shaping and Assessing Science 3. Hope Versus Hypothesis Testing: Expanding Access to Experimental Interventions 4. Fairness in Allocating Government Research Funds 5. Public Participation in Allocating Government Research Funds 6. Advocates in Research Ethics Oversight: A Voice for the Public? 7. Advocacy for Accuracy in Research Reporting 8. Research Advocacy Today and Tomorrow
Direct Demonstration of Structural Similarity between Native and Denatured Eglin C †

To characterize the long-range structure that persists in the unfolded form of the 70-residue protein eglin C, residual dipolar couplings (RDCs) for HN-N and HA-CA bond vectors were measured by NMR spectroscopy for both its low pH, urea denatured state and its native state. When the data sets for the two different structural states were compared, a statistically significant correlation was found, with both sets of dipolar couplings yielding a correlation coefficient of r) 0.47 to 0.51. This finding directly demonstrates that the denatured state of eglin C has a nativelike global structure, a conclusion reached indirectly for staphylococcal nuclease by combining two different types of NMR data. A simple computer simulation showed that the degree of variation in phi and psi angles that yields the RDC correlation of r) 0.5 was inversely dependent on the statistical segment length, ranging from (6 to (30 degrees at the upper limit. Stable nativelike topologies that persist on unfolding would explain the rapid refolding kinetics displayed by many proteins and might provide a natural barrier against amyloid fibril formation. The denatured states of proteins play important roles in folding and in numerous biological and pathological phenomena. In addition to being the starting point for experimental analysis of the kinetics of folding, the denatured state can interact with intracellular chaperones, proteases, and the cell's transport machinery; in some cases, it readily aggregates to form insoluble amyloid fibrils. While protein chemists have long presumed that denatured proteins are more or less random, experimental data over the past 10-20 years has shown that significant residual structure often persists (1-7). Obviously, the details of this persistent structure could provide important clues to a more complete understanding of how proteins are able to fold so rapidly and how they avoid the formation of insoluble aggregates. Multiple technical problems limit the utility of experimental methods in probing the residual structure in denatured proteins, many being a direct consequence of the fact that denatured proteins do not have a single conformation. Instead, they populate many diverse, rapidly interconverting conformations in a complex and dynamic ensemble. Consequently , experimental data always represent ensemble-averaged parameters. NMR 1 methods can provide useful information about local structure, permitting identification of persistent turns and segments of alpha helices (3-7). By detecting segments undergoing slower or smaller structural fluctuations, spin relaxation methods can identify regions with residual structure in denatured proteins (8-11), although the interpretation of …
N-terminal horseshoe conformation of DCC is functionally required for axon guidance and might be shared by other neural receptors

Summary Deleted in colorectal cancer (DCC) is a receptor for the axon guidance cues netrin-1 and draxin. The interactions between these guidance cues and DCC play a key role in the development of the nervous system. In the present study, we reveal the crystal structure of the N-terminal four Ig-like domains of DCC. The molecule folds into a horseshoe-like configuration. We demonstrate that this horseshoe conformation of DCC is required for guidance-cue-mediated axonal attraction. Structure-based mutations that disrupt the DCC horseshoe indeed impair its function. A comparison of the DCC horseshoe with previously described horseshoe structures has revealed striking conserved structural features and important sequence signatures. Using these signatures, a genome-wide search allows us to predict the N-terminal horseshoe arrangement in a number of other cell surface receptors, nearly all of which function in the nervous system. The N-terminal horseshoe appears to be evolutionally selected as a platform for neural receptors.
Transient and Steady-State Analysis of the Affine Combination of Two Adaptive Filters

In this paper, we propose an approach to the transient and steady-state analysis of the affine combination of one fast and one slow adaptive filters. The theoretical models are based on expressions for the excess mean-square error (EMSE) and cross-EMSE of the component filters, which allows their application to different combinations of algorithms, such as least mean-squares (LMS), normalized LMS (NLMS), and constant modulus algorithm (CMA), considering white or colored inputs and stationary or nonstationary environments. Since the desired universal behavior of the combination depends on the correct estimation of the mixing parameter at every instant, its adaptation is also taken into account in the transient analysis. Furthermore, we propose normalized algorithms for the adaptation of the mixing parameter that exhibit good performance. Good agreement between analysis and simulation results is always observed.
Evidence of Rabies Virus Exposure among Humans in the Peruvian Amazon

In May of 2010, two communities (Truenococha and Santa Marta) reported to be at risk of vampire bat depredation were surveyed in the Province Datem del Marañón in the Loreto Department of Perú. Risk factors for bat exposure included age less than or equal to 25 years and owning animals that had been bitten by bats. Rabies virus neutralizing antibodies (rVNAs) were detected in 11% (7 of 63) of human sera tested. Rabies virus ribonucleoprotein (RNP) immunoglobulin G (IgG) antibodies were detected in the sera of three individuals, two of whom were also seropositive for rVNA. Rabies virus RNP IgM antibodies were detected in one respondent with no evidence of rVNA or RNP IgG antibodies. Because one respondent with positive rVNA results reported prior vaccination and 86% (six of seven) of rVNA-positive respondents reported being bitten by bats, these data suggest nonfatal exposure of persons to rabies virus, which is likely associated with vampire bat depredation.
Host defence during Klebsiella pneumonia relies on haematopoietic-expressed Toll-like receptors 4 and 2

In this study, the relative roles of Toll-like receptor (TLR)2 and TLR4 were investigated independently and together. Moreover, we studied the role of haematopoietic compartment in anti-Klebsiella host defence. We infected TLR2 and TLR4 single-, and TLR2×4 double knockout (KO) animals with different doses of Klebsiella pneumoniae. In addition, bone marrow chimeric mice were created and infected. TLR4 played a more prominent role in antibacterial defence than TLR2, considering that only TLR4 KO mice demonstrated enhanced bacterial growth in lungs and spleen 24 h after infection with 3×103 colony-forming units of Klebsiella compared with wild-type (WT) mice. In late-stage infection or after exposure to a higher infectious dose, bacterial counts in lungs of TLR2 KO animals were elevated compared with WT mice and TLR2×4 KO animals were more susceptible to infection than TLR4 KO mice. TLR signalling in cells of haematopoietic origin is of primary importance in host defence against K. pneumoniae. These data suggest that: 1) TLR4 drives the antibacterial host response after induction of pneumonia with relatively low Klebsiella doses; 2) TLR2 becomes involved at a later phase of the infection and/or upon exposure to higher bacterial burdens; and 3) haematopoietic TLR2 and TLR4 are important for an adequate host response during Klebsiella pneumonia.