Miracle-dz/UniFAR-FTUs huggingface dataset:
Primary Megakaryocytes Reveal a Role for Transcription Factor NF-E2 in Integrin (cid:97) IIb (cid:98) 3 Signaling

Platelet integrin (cid:97) IIb (cid:98) 3 responds to intracellular signals by binding ﬁbrinogen and triggering cytoskeletal reorganization, but the mechanisms of (cid:97) IIb (cid:98) 3 signaling remain poorly understood. To better understand this process, we established conditions to study (cid:97) IIb (cid:98) 3 signaling in primary murine megakaryocytes. Unlike platelets, these platelet precursors are amenable to genetic manipulation. Cytokine-stimu-lated bone marrow cultures produced three arbitrary populations of (cid:97) IIb (cid:98) 3-expressing cells with increasing size and DNA ploidy: small progenitors, intermediate-size young megakaryocytes, and large mature megakaryocytes. A majority of the large megakaryocytes bound ﬁbrinogen in response to agonists, while almost none of the smaller cells did. Fibrinogen binding to large megakaryocytes was inhibited by Sindbis virus-mediated expression of isolated (cid:98) 3 integrin cytoplasmic tails. Strikingly, large megakaryocytes from mice deﬁ-cient in the transcription factor NF-E2 failed to bind ﬁbrinogen in response to agonists, despite normal surface expression of (cid:97) IIb (cid:98) 3. Furthermore, while megakaryocytes from wild-type mice spread on immobilized ﬁbrinogen and exhibited ﬁlopodia, lamellipodia and Rho-dependent focal adhesions and stress ﬁbers, NF-E2–deﬁcient megakaryocytes adhered poorly. These studies establish that agonist-induced activation of (cid:97) IIb (cid:98) 3 is controlled by NF-E2–regulated signaling pathways that mature late in megakaryocyte development and converge at the (cid:98) 3 cytoplasmic tail. Megakaryocytes provide a physiologically relevant and tractable system for analysis of bidirectional (cid:97) IIb (cid:98) 3 signaling. blots were probed with a rabbit polyclonal antibody specific for Sindbis E1 protein (a gift from J.H. Strauss, California Institute of Technology, Pasadena, CA) or with a murine monoclonal antibody to Rho (Santa Cruz Biotechnology, Santa Cruz, CA). Blots were developed for 0.5–2 min by chemiluminescence (ECL; Amersham Corp.).
Simulation of Collapse of Granular Columns Using the Discrete Element Method

AbstractIn this study, a three-dimensional (3D) numerical investigation of axisymmetric collapse of granular columns has been conducted using the discrete element method (DEM). The simulated granular columns have a constant initial radius of 5.68 mm and three aspect ratios: 0.55, 1.0, and 2.0. The columns consist of uniform spherical quartz particles with a diameter of 0.32 mm. In the DEM model, rotational velocities of particles are reduced by a factor at every time step to partially account for the additional rolling resistance due to the effect of particle shape and hysteretic contact behavior. The simple linear contact model is used; however, its performance is improved by using different stiffness values calculated by nonlinear Hertz–Mindlin contact model for each aspect ratio. The simulated final deposit heights, runout distances, and energy dissipation values are in good agreement with experimental observations reported in the literature. The effects of initial porosity and rotational resistance on.
Comparison of excitatory currents activated by different transmitters on crustacean muscle. II. Glutamate-activated currents and comparison with acetylcholine currents present on the same muscle

The properties of glutamate-activated excitatory currents on the gm6 muscle from the foregut of the spiny lobsters Panulirus argus and interruptus and the crab Cancer borealis were examined using either noise analysis, analysis of synaptic current decays, or slow iontophoretic currents. The properties of acetylcholine currents activated in nonjunctional regions of the gm6 muscle were also examined. At 12 degrees C and -80 mV, the predominant time constant of power spectra from glutamate-activated current noise was approximately 7 ms and the elementary conductance was approximately 34 pS. At 12 degrees C and -80 mV, the predominant time constant of acetylcholine- activated channels was approximately 11 ms with a conductance of approximately 12 pS. Focally recorded glutamatergic extracellular synaptic currents on the gm6 muscle decayed with time constants of approximately 7-8 ms at 12 degrees C and -80 mV. The decay time constant was prolonged e-fold about every 225-mV hyperpolarization in membrane potential. The Q10 of the time constant of the synaptic current decay was approximately 2.6. The voltage dependence of the steady-state conductance increase activated by iontophoretic application of glutamate has the opposite direction of the steady-state conductance activated by cholinergic agonists when compared on the gm6 muscles. The glutamate-activated conductance increase is diminished with hyperpolarization. The properties of the marine crustacean glutamate channels are discussed in relation to glutamate channels in other organisms and to the acetylcholine channels found on the gm6 muscle and the gm1 muscle of the decapod foregut (Lingle and Auerbach, 1983).
inhibition of dipeptidyl peptidase-4: The mechanisms of action and clinical use of vildagliptin for the management of type 2 diabetes

: Postprandial hyperglycemia in type 2 diabetes is characterized by impaired insulin secretion and action, decreased glucose effectiveness and defective suppression of glucagon secretion. Newly available therapies for type 2 diabetes target the pathway of the incretin hormone glucagon-like peptide-1 (GLP-1). Oral inhibitors of dipeptidyl peptidase-4 (DPP-4) raise the level of endogenous GLP-1 by inhibiting its clearance thereby lowering fasting and postprandial glucose concentrations. Unlike compounds which act as agonists of the GLP-1 receptor, DPP-4 inhibitors are not associated with significant effects on gastrointestinal motility, which led to a controversy around the mechanisms responsible for their glucose-lowering effects. Here we review the evidence in regards to the mechanisms whereby DPP-4 inhibitors lower glucose concentrations. Their effects are most likely mediated by an increase in endogenous GLP-1, although additional mechanisms may be involved. The pharmacology, efficacy and safety of vildagliptin, a novel DPP-4 inhibitor, are also discussed.
Receiver function migration image of the deep structure in the Bohai Bay Basin, eastern China

We apply a receiver function poststack migration method to image the crustal and upper mantle structures beneath the Bohai Bay Basin, eastern China. The thick sediments of the basin appear to have a substantial influence on the migrated image of the deep structure. By using the surface reflected PpPs multiples instead of the commonly used Ps converted phases, a curved Moho is coherently imaged, showing a thinned crust of ∼30 km in the basin area compared with the >40‐km thick crust in the west mountain range. By incorporating the sedimentary velocity model into migration, both the 410‐km and the 660‐km discontinuities present a simple structural feature with relatively flat topography within the basin's interior, although possible local structural complexities may exist at the base of the upper mantle around the boundary areas of the basin. The mantle transition zone is on average 10–15 km thicker than the global average, reflecting a cold lower upper mantle environment that is distinct from the warm shallow upper mantle of the region.
Neotenic formation in laboratory colonies of the termite Coptotermes gestroi after orphaning

Abstract The termite Coptotermes gestroi (Wasmann 1896) (Rhinotermitidae: Coptotermitinae) is an exotic species in Brazil and information concerning its reproductive developmental biology is scarce. We induced the formation of neotenics in laboratory colonies through orphaning experiments. Orphaning experiments were conducted in three-year old colonies of C. gestroi kept under laboratory conditions. After three months, eight nymphoid neotenics were observed in one colony after queen removal. Histological analysis showed that these neotenics were non-functional. The results suggest that these individuals may have arisen from the first nymphal instar (N1) or from an early N1 instar after one or two larval moults. Neotenics also were recorded on two incipient colonies of C. gestroi that lost the queen naturally.
Modeling impact of FORMOSAT‐7/COSMIC‐2 mission on ionospheric space weather monitoring

For the past decade, the paucity of ionospheric observations has made it almost impossible to reconstruct the three‐dimensional structures of global ionospheric electron density. The Formosa Satellite‐3/Constellation Observing System for Meteorology, Ionosphere and Climate (FORMOSAT‐3/COSMIC, F3/C) constellation has provided ionospheric electron density profiles with high vertical resolution through radio occultation measurements. Slated for deployment starting in 2016, the FORMOSAT‐7/COSMIC‐2 (F7/C2) constellation will further provide more than 4 times the number of the F3/C occultation soundings. An observing system simulation experiment is conducted to determine the impact of F7/C2 on ionospheric weather monitoring. The results first show that the F7/C2 observations can reconstruct 3‐D ionospheric structure with a data accumulation period of 1 h, which can advance studies of small spatial/temporal scale variation/signatures in the ionosphere. Comparing to assimilation results of F3/C, the assimilation system significantly reduces the error arising in the models and observations after assimilating synthetic observations of F7/C2. During this observing system simulation experiment period, the averaged root‐mean‐square error percentage for the results of F7/C2 is about 4.4%, lower than that of F3/C 7.3%. Furthermore, even with an assimilation window of less than 60 min, the F7/C2 RMS errors still yield reliable values compared to the F3/C results. This paper represents a major advance in ionospheric weather monitoring for the future mission.
Cosmogenic effects in Mbale, L5/6 chondrite

Abstract— Measurements of particle tracks, cosmogenic radionuclides, and rare gas isotopes in Mbale indicate that the meteoroid had a simple, one‐stage exposure for 30.2 Ma in interplanetary space. On the basis of the measured track production rates and 60Co and 26Al activities, the meteoroid is estimated to be a sphere with a radius of ∼36 cm. The activities of several cosmogenic radionuclides (i.e., 57Co, 54Mn, 22Na, 44Ti, and 26Al) in two fragments having different shielding, as estimated by their track density and 60Co activity, provide the depth variation in their production rates. Cobalt‐57, 54Mn and 22Na activities agree with the production that is expected around the maximum of the solar cycle 22 as calculated from the Sunspot numbers. The U, Th‐4He and K‐40Ar ages are measured to be 0.54 Ga indicating a late thermal event which is in agreement with the thermal history of some other L group chondrites. The trapped N has δ15N of −57 ± 4%o, which is much lighter than the average L‐group chondrite value; this indicates the presence of an isotopically anomalous light N component.
Hepatic manifestations of celiac disease

: Different hepatic and biliary tract disorders may occur with celiac disease. Some have been hypothesized to share genetic or immunopathogenetic factors, such as primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis. Other hepatic changes in celiac disease may occur with malnutrition resulting from impaired nutrient absorption, including hepatic steatosis. In addition, celiac disease may be associated with rare hepatic complications, such as hepatic T-cell lymphoma.
Role of combination bortezomib and pegylated liposomal doxorubicin in the management of relapsed and/or refractory multiple myeloma

: The ﬁ rst in class proteasome inhibitor bortezomib (B) received its initial regulatory approval for therapy of patients with multiple myeloma (MM) in the relapsed/refractory setting. Modulation of proteasome function, however, is also a rational strategy for chemosensitiza-tion, and a variety of agents have shown synergistic activity with bortezomib pre-clinically, including anthracyclines. This formed the basis for evaluation of a regimen of bortezomib with pegylated liposomal doxorubicin (PLD). PLD + B, in a phase I study, induced a predictable and manageable toxicity proﬁ le, and showed encouraging anti-MM activity. In a recent international, randomized phase III trial, PLD + B demonstrated a superior overall response rate and response quality compared to bortezomib alone, as well as a longer time to progression, duration of response, progression-free survival, and overall survival. Sub-analyses revealed beneﬁ ts in almost all clinically relevant subgroups, including several which would be considered to have high-risk disease. These ﬁ ndings have led to the establishment of the PLD + B regimen as one of the standards of care for patients with relapsed and/or refractory myeloma. Efforts are now underway to build on this combination further by adding other active anti-myeloma agents. In this review, we will discuss the role of PLD + B as an important addition to our therapeutic armamentarium for patients with MM.
Acceptability and effectiveness of chickpea sesame-based ready-to-use therapeutic food in malnourished HIV-positive adults

Objective : A prospective descriptive study to assess acceptability and effectiveness of a locally made ready-to-use therapeutic food (RUTF) in HIV-infected chronically sick adults (CSA) with mid-upper-arm circumference (MUAC) (cid:2) 210 mm or pitting edema. Methods: Sixty-three wasted AIDS adults were prescribed 500 g representing ~2600 kcal/day of locally made RUTF for three months and routine cotrimoxazole. Weight, height, MUAC, Karnofsky score and morbidity were measured at admission and at monthly intervals. The amount of RUTF intake and acceptability were assessed monthly. Results: Ninety-ﬁ ve percent (60/63) of the CSA that were invited to join the study agreed to participate. Mean daily intake in these 60 patients was 300 g/person/day (~1590 Kcal and 40 g of protein). Overall, 73.3% (44/60) gained weight, BMI, and MUAC. The median weight, MUAC and BMI gains after three months were 3.0 kg, 25.4 mm, and 1.1 kg/m 2 , respectively. The intervention improved the physical activity performance of participants and 78.3% (47/60) regained sufﬁ cient strength to walk to the nearest health facility. Mortality at three months was 18.3% (11/60). Conclusion: Locally made RUTF was acceptable to patients and was associated with a rapid weight gain and physical activity performance. The intervention is likely to be more cost effective than nutritional support using usual food-aid commodities.
Physiological Ecology of the Alpine Timberline: Tree Existence at High Altitudes with Special Reference to the European Alps

General Features of the Upper Timberline. - Reasons for Occurrence of Timberlines and Their Experimental Investigation. - Some Milestones in the History of Ecophysiological Research Concerning Alpine Timberline. - 1. Natural Regeneration of Tree Stands at Timberline. - 1.1 Seed Production. Frequency of Seed Years, Quantity, and Quality of Seed. - 1.2 Dispersal of Seed. - 1.3 Maturation of Seed. - 1.4 Germination. - 1.5 Vegetative Propagation. - 2. Growth of Trees at Timberline. - 2.1 Height Growth. - 2.2 Growth of Leaves. - 2.3 Diameter Growth. - 2.4 Root Growth and Mycorrhizae. - 3. Dry Matter Production of Trees at Timberline. - 3.1 Photosynthesis. - 3.1.1 Dependence of Photosynthesis on External Factors and Their Significance for CO2-uptake of Trees at Timberline. - 3.1.1.1 Light. - 3.1.1.2 Temperature. - 3.1.1.3 Wind. - 3.1.1.4 CO2-Content of the Atmosphere. - 3.1.1.5 Soil Temperature. - 3.1.1.6 Atmospheric and Soil Moisture. - 3.1.2 Annual Course of Net Photosynthesis of Trees at Timberline. - 3.1.2.1 Seedlings of Pinus cembra Covered by Winter Snow. - 3.1.2.2 Trees of Pinus cembra Exposed Above the Winter Snow-Pack. - 3.1.2.3 Larix decidua. - 3.1.2.4 Other Published Investigations. - 3.1.3 Photosynthesis with Respect to Altitude. - 3.2 Dark Respiration with Respect to Altitude and Timberline. - 3.3 Carbon Balance of Trees at Timberline. - 3.3.1 Dark Respiration. - 3.3.2 Winter Respiration. - 3.3.3 Root Respiration. - 3.3.4 Stem Respiration. - 3.4 Net Carbon Gain and Biomass Increment at Elevations up to Timberline. - 3.4.1 Reduction in Dry Matter Production from Valley Floor to Timberline. - 3.4.2 Primary Production of Trees in the Timberline Ecotone. - 3.5 Primary Production and Nitrogen Nutrition. - 4. Water Relations of Trees at Timberline. - 4.1 Water Relations in Summer. - 4.1.1 Precipitation and Soil Moisture. - 4.1.2 Evaporation. - 4.1.3 Transpiration of Trees. - 4.1.4 Water Balance in Trees. - 4.2 Water Relations in Winter. - 5. Climatic Resistance and Damage of Trees at Timberline. - 5.1 Frost Damage. - 5.2 Ultraviolet and High Intensity Radiation Damage. - 5.3 Heat Damage. - 5.4 Mechanical Damage. - 5.4.1 Wind. - 5.4.2 Snow. - 5.5 Winter Desiccation or "Frost-drought" Damage. - 5.5.1 Progression of Desiccation. - 5.5.2 Causes of Desiccation Damage. - 5.5.3 Experimental Evidence for the Michaelis Hypothesis. - 5.5.4 An Analysis of Dynamic Processes at Timberline. - 6. Synopsis. - 6.1 Carbon Budget. - 6.2 The Course of Developmental Phases. - 6.3 Climatic Resistance. - References. - Taxonomic Index.
Developing a European internet and kiosk-based health information system

A consortium of partner organisations (universities, health care organisations and information technology companies) from Northern Ireland, Germany, Portugal and Italy have collaborated to develop a multi-lingual, multi-media Internet and kiosk-based health information system in cardiology and skin cancer. The project, CATCH II (Citizens Advisory System based on Telematics for Communication and Health), has been funded by the European Commission under the Fourth Framework Research and Development TELEMATICS Applications Program (TAP), Health Care Sector. In this paper we provide an overview of the system and the methodological approach adopted. Key characteristics with respect to the technical architecture and flexible customisation of different web and kiosk-based versions will be presented. In particular, the development of dedicated software for the procurement, structuring and management of the information knowledge-base is illustrated. Some of the most interesting findings from a cross-national study of 'health information needs on the internet' are presented along with information on the validation of the system by the general public, content providers and health care authorities.
Identifying drivers that influence the spatial distribution of woody vegetation in Kruger National Park, South Africa

Understanding the dynamics of woody tree species distribution in savanna systems remains a challenge despite considerable attention the topic has received in recent years. Disturbances such as fire and elephant effects on woody vegetation are well documented, yet the influence of these factors on emerging landscape-scale patterns such as height and species distributions continue to be poorly understood. The aim of this study was to identify how a suite of environmental variables (rainfall, temperature, aspect, slope, geology, fire frequency and elephant density) and their relative contributions, may affect woody species distribution in relation to structural height classes. Using the Maximum Entropy model for three structural height classes of the fifteen most frequently occurring woody species in the Kruger National Park (South Africa), the environmental variables best explaining each species distribution were identified. The three structural classes were defined to capture canopy height categories of sp.
Archaeocyaths from South America: review and a new record

In South America, autochthonous archaeocyathan faunas preserved in Early Cambrian limestones have not been found yet. Nevertheless, a few well‐documented occurrences of these fossils in clasts contained in coarse‐grained rocks of a wide age range have been discovered in recent years. Erratic limestone blocks from the Late Carboniferous–Early Permian Fitzroy Tillite Formation in the Falkland/Malvinas Islands yielded three archaeocyath taxa. Also, seven taxa were reported from archaeocyathan limestone clasts in a metaconglomerate of the Cambro‐Ordovician El Jagüelito Formation in northern Patagonia. In addition, a new record from the Late Carboniferous–Early Permian Sauce Grande Formation diamictites in Sierras Australes, Buenos Aires Province, Argentina, is presented herein. Preservation of this scarce new material is poor, but at least three different taxa can be distinguished. The most likely source of all archaeocyathan limestone clasts found in southern South America is the Shackleton Limestone from the Transantarctic Mountains in East Antarctica. The new record from the Sauce Grande Formation and the inferred clast provenance reinforce the correlation between this unit, the Dwyka Tillite (South Africa) and the Fitzroy Tillite Formation (Falklands/Malvinas), suggesting a very wide distribution of these Antarctic occurrences during the Late Carboniferous–Early Permian Gondwana glaciation (Episode III). Thus, even though being allochthonous, archaeocyaths are emerging as a new key biological feature for Gondwana palaeogeographic reconstructions. Copyright © 2012 John Wiley & Sons, Ltd.
GalNAc- - O -benzyl Inhibits NeuAc (cid:97) 2-3 Glycosylation and Blocks the Intracellular Transport of Apical Glycoproteins and Mucus in Differentiated HT-29 Cells

Exposure for 24 h of mucus-secreting HT-29 cells to the sugar analogue GalNAc- (cid:97) - O -benzyl results in inhibition of Gal (cid:98) 1-3GalNAc: (cid:97) 2,3-sialyltransferase, reduced mucin sialylation, and inhibition of their secretion (Huet, G. , I. Kim, C.
Model Projections of the Changes in Atmospheric Circulation and Surface Climate over North America, the North Atlantic, and Europe in the Twenty-First Century

AbstractThe impacts of climate change on the North America–North Atlantic–Europe sector are studied using a coupled general circulation model: the Climate Model, version 3 (CM3) and a high-resolution atmosphere-only model, the High Resolution Atmospheric Model (HiRAM)—both developed at the Geophysical Fluid Dynamics Laboratory. The CM3 experiment is conducted under two climate change scenarios for the 1860–2100 period. The sea surface temperature (SST) forcing prescribed in the “time slice” integrations with HiRAM is derived from observations for the 1979–2008 period and projection by CM3 for the 2086–95 period.The wintertime response in the late twenty-first century is characterized by an enhancement of the positive phase of the North Atlantic Oscillation in sea level pressure (SLP) and poleward and eastward displacements of the Atlantic jet stream and storm track. The forcing pattern due to eddy vorticity fluxes in the perturbed storm track matches well with the response pattern of the SLP field in the .