Symmetric signaling by an asymmetric 1 erythropoietin : 2 erythropoietin receptor complex

Thesis (M. Eng.)--Massachusetts Institute of Technology, Biological Engineering Division, 2008.Includes bibliographical references (p. 43-46).One erythropoietin molecule binds asymmetrically to two identical receptor monomers via erythropoietin site 1 and site 2, although it is unclear how asymmetry affects receptor activation and signaling. Here we report the computational design and experimental validation of two mutant erythropoietin receptors: one that binds only to erythropoietin site 1 but not site 2, and one that binds only to site 2 but not site 1. Expression of either mutant receptor alone in Ba/F3 cells cannot elicit a signal in response to erythropoietin, but when co-expressed, there is a proliferative response and activation of the JAK2 Stat5 signaling pathway. A truncated erythropoietin receptor with only one cytosolic tyrosine (Y343), on only one receptor monomer is sufficient for signaling in response to erythropoietin, regardless of the monomer on which it is located. The same results apply to having only one conserved juxtamembrane hydrophobic L253 or W258 residue, essential for JAK2 activation, in the full-length receptor dimer. We conclude that despite asymmetry in the ligand-receptor dimer interaction, both sides are competent for signaling, and we suggest that the receptors signal equally.by Yingxin Zhang.M.Eng

Identification of Core Technology of Digital SPC Exchange and Intelligentialize Prospect of Electronic Communication Equipment Industry

digital SPC switch belongs to the communication system equipment manufacturing class and belongs to the high-tech industry. Mastering the core technology of digital SPC switch is related to communication security and national information security. HuaWei has already mastered the core technology of digital SPC switch, and on this basis has accumulated the core technology capability to develop intelligently. In this paper, patent data is used to analyze the patent family of digital SPC switches at home and abroad, and based on this analysis and identification of core technologies, and finally, the intelligent development direction of the industry is predicted

Net Ecosystem Production (NEP) of the Great Plains, United States

Gross primary production (GPP) and ecosystem respiration (Re) are the fundamental environmental characteristics that promote carbon exchanges with the atmosphere (Chapin and others, 2009), although other exchanges of carbon, such as direct oxidation (Lovett and others, 2006), can modify net ecosystem production (NEP). The accumulation of carbon in terrestrial ecosystems results in systems in which soil organic matter (SOM) carbon often exceeds biomass carbon (Post and Kwon, 2000). This SOM pool exists at a steady state between GPP and Re in ecosystems unless drivers change or the ecosystem endures environmental perturbations (for example, climatic). As indicated by Wilhelm and others (2011), conversion of grasslands to agriculture and cultivation can result in reduced soil carbon, with the release of carbon dioxide (CO2 ) to the atmosphere by stimulated oxidation and higher Re; therefore, land-use and land management practices have clear effects on NEP, with potential repercussions on ecosystems. The recent demand for biofuels has changed land-use and cropping patterns, especially in Midwestern United States (Wilhelm and others, 2011). It is important to ensure the sustainability of these and other land uses and to assess the effects on NE

Evaluation of Carbon Fluxes and Trends (2000e2008) in the Greater Platte River Basin: A Sustainability Study for Potential Biofuel Feedstock Development

This study evaluates the carbon fluxes and trends and examines the environmental sustainability (e.g., carbon budget, source or sink) of the potential biofuel feedstock sites identified in the Greater Platte River Basin (GPRB). A 9-year (2000e2008) time series of net ecosystem production (NEP), a measure of net carbon absorption or emission by ecosystems, was used to assess the historical trends and budgets of carbon flux for grasslands in the GPRB. The spatially averaged annual NEP (ANEP) for grassland areas that are possibly suitable for biofuel expansion (productive grasslands) was 71e169 g C m2 year1 during 2000e2008, indicating a carbon sink (more carbon is absorbed than released) in these areas. The spatially averaged ANEP for areas not suitable for biofuel feedstock development (less productive or degraded grasslands) was 47 to 69 g C m2 year1 during 2000e2008, showing a weak carbon source or a weak carbon sink (carbon emitted is nearly equal to carbon absorbed). The 9-year pre-harvest cumulative ANEP was 1166 g C m2 for the suitable areas (a strong carbon sink) and 200 g C m2 for the non-suitable areas (a weak carbon sink). Results demonstrate and confirm that our method of dynamic modeling of ecosystem performance can successfully identify areas desirable and sustainable for future biofuel feedstock development. This study provides useful information for land managers and decision makers to make optimal land use decisions regarding biofuel feedstock development and sustainability

Personalized local heating neutralizing individual, spatial and temporal thermo-physiological variances in extreme cold environments

In this paper, we investigate the feasibility, robustness and optimization of introducing personal comfort systems (PCS), apparatuses that promises in energy saving and comfort improvement, into a broader range of environments. We report a series of laboratory experiments systematically examining the effect of personalized heating in neutralizing individual, spatial and temporal variations of thermal demands. The experiments were conducted in an artificial climate chamber at -15 degC in order to simulate extreme cold environments. We developed a heating garment with 20 pieces of 20 * 20 cm2 heating cloth (grouped into 9 regions) comprehensively covering human body. Surface temperatures of the garment can be controlled independently, quickly (within 20 seconds), precisely (within 1 degC) and easily (through a tablet) up to 45 degC. Participants were instructed to adjust surface temperatures of each segment to their preferences, with their physiological, psychological and adjustment data collected. We found that active heating could significantly and stably improve thermal satisfaction. The overall TSV and TCV were improved 1.50 and 1.53 during the self-adjustment phase. Preferred heating surface temperatures for different segments varied widely. Further, even for the same segment, individual differences among participants were considerable. Such variances were observed through local heating powers, while unnoticeable among thermal perception votes. In other words, all these various differences could be neutralized given the flexibility in personalized adjustments. Our research reaffirms the paradigm of "adaptive thermal comfort" and will promote innovations on human-centric design for more efficient PCSs

Entertainment apps, limited attention and investment performance

With the advent of the “information age,” investors are now faced with the challenges of the “mobile age,” which has had a profound impact on the daily lives of people worldwide. Investors must process more information while experiencing increasing mobile phone-related distractions, particularly those generated by the fast-growing entertainment-type app industry. Attention is a limited cognitive resource that is vital for deliberate and thoughtful analysis. We analyzed data from an online peer-to-peer lending market to evaluate the impact of mobile distractions on investment performance. Our findings revealed that investors with a large number of mobile phone entertainment apps were more likely to exhibit higher default rates and lower investment returns. The results are robust, even when using exogenous internet service outage of the entertainment server and instrumental variables. We observed that the negative impact of distraction was more pronounced on Fridays and in regions with high-speed Internet access. A further examination of the mechanisms underlying this phenomenon revealed that investment decisions made while being distracted by mobile apps were influenced by information neglect and familiarity biases

Symmetric Signaling by an Asymmetric 1 Erythropoietin: 2 Erythropoietin Receptor Complex

Via sites 1 and 2, erythropoietin binds asymmetrically to two identical receptor monomers, although it is unclear how asymmetry affects receptor activation and signaling. Here we report the design and validation of two mutant erythropoietin receptors that probe the role of individual members of the receptor dimer by selectively binding either site 1 or site 2 on erythropoietin. Ba/F3 cells expressing either mutant receptor do not respond to erythropoietin, but cells co-expressing both receptors respond to erythropoietin by proliferation and activation of the JAK2-Stat5 pathway. A truncated receptor with only one cytosolic tyrosine (Y343) is sufficient for signaling in response to erythropoietin, regardless of the monomer on which it is located. Similarly, only one receptor in the dimer needs a juxtamembrane hydrophobic L253 or W258 residue, essential for JAK2 activation. We conclude that despite asymmetry in the ligand-receptor interaction, both sides are competent for signaling, and appear to signal equally.National Institutes of Health (U.S.) (Grant P01 HL32262)Amgen Inc. (Research Grant)National Institutes of Health (U.S.) (Grant GM 065418)United States. Dept. of Energy. Computational Science Graduate Fellowship (DE-FG02-97ER25308)National Institutes of Health (U.S.). Ruth L. Kirschstein National Research Service Award (Postdoctoral Fellowship 5F32HL077036