Glucose metabolism and oscillatory behavior of pancreatic islets

A variety of oscillations are observed in pancreatic islets.We establish a model, incorporating two oscillatory systems of different time scales: One is the well-known bursting model in pancreatic beta-cells and the other is the glucose-insulin feedback model which considers direct and indirect feedback of secreted insulin. These two are coupled to interact with each other in the combined model, and two basic assumptions are made on the basis of biological observations: The conductance g_{K(ATP)} for the ATP-dependent potassium current is a decreasing function of the glucose concentration whereas the insulin secretion rate is given by a function of the intracellular calcium concentration. Obtained via extensive numerical simulations are complex oscillations including clusters of bursts, slow and fast calcium oscillations, and so on. We also consider how the intracellular glucose concentration depends upon the extracellular glucose concentration, and examine the inhibitory effects of insulin.Comment: 11 pages, 16 figure

Space-charge-limited flows in the quantum regime

This paper reviews the recent developments of space-charge-limited (SCL) flow or Child-Langmuir (CL) law in the quantum regime. According to the classical CL law for planar diodes, the current density scales as 3/23∕2’s power of gap voltage and to the inverse squared power of gap spacing. When the electron de Broglie wavelength is comparable or larger than the gap spacing, the classical SCL current density is enhanced by a large factor due to electron tunneling and exchange-correlation effects, and there is a new quantum scaling for the current density, which is proportional to the 1/21∕2’s power of gap voltage, and to the inverse fourth-power of gap spacing. It is also found that the classical concepts of the SCL flow such as bipolar flow, transit time, beam-loaded capacitance, emitted charge density, and magnetic insulation are no longer valid in quantum regime. In the quantum regime, there exists a minimum transit time of the SCL flows, in contrast to the classical solution. By including the surface properties of the emitting surface, there is a threshold voltage that is required to obtain the quantum CL law. The implications of the Fowler-Nordheim-like field emission in the presence of intense space charge over the nanometer scale is discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87757/2/056701_1.pd

Novel point mutations attenuate autotaxin activity

BACKGROUND: The secreted enzyme autotaxin (ATX) stimulates tumor cell migration, tumorigenesis, angiogenesis, and metastasis. ATX hydrolyzes nucleotides, but its hydrolysis of lysophospholipids to produce lysophosphatidic acid (LPA) accounts for its biological activities. ATX has been identified only as a constitutively active enzyme, and regulation of its activity is largely unexplored. In spite of its presence in plasma along with abundant putative substrate LPC, the product LPA is found in plasma at unexpectedly low concentrations. It is plausible that the LPA-producing activity of ATX is regulated by its expression and by access to substrate(s). For this reason studying the interaction of enzyme with substrate is paramount to understanding the regulation of LPA production. RESULTS: In this study we determine ATX hydrolytic activities toward several artificial and natural substrates. Two novel point mutations near the enzyme active site (H226Q and H434Q) confer attenuated activity toward all substrates tested. The Vmax for LPC compounds depends upon chain length and saturation; but this order does not differ among wild type and mutants. However the mutant forms show disproportionately low activity toward two artificial substrates, pNpTMP and FS-3. The mutant forms did not significantly stimulate migration responses at concentrations that produced a maximum response for WT-ATX, but this defect could be rescued by inclusion of exogenous LPC. CONCLUSION: H226Q-ATX and H434Q-ATX are the first point mutations of ATX/NPP2 demonstrated to differentially impair substrate hydrolysis, with hydrolysis of artificial substrates being disproportionately lower than that of LPC. This implies that H226 and H434 are important for substrate interaction. Assays that rely on hydrolyses of artificial substrates (FS-3 and pNpTMP), or that rely on hydrolysis of cell-derived substrate, might fail to detect certain mutated forms of ATX that are nonetheless capable of producing LPA in the presence of sufficient exogenous substrate. H420Q-ATX could not be differentiated from WT-ATX, indicating that histidine at position 420 is not required for any of the activities of ATX tested in this studyope

How many qubits are needed for quantum computational supremacy?

Quantum computational supremacy arguments, which describe a way for a quantum computer to perform a task that cannot also be done by a classical computer, typically require some sort of computational assumption related to the limitations of classical computation. One common assumption is that the polynomial hierarchy (PH) does not collapse, a stronger version of the statement that P $\neq$ NP, which leads to the conclusion that any classical simulation of certain families of quantum circuits requires time scaling worse than any polynomial in the size of the circuits. However, the asymptotic nature of this conclusion prevents us from calculating exactly how many qubits these quantum circuits must have for their classical simulation to be intractable on modern classical supercomputers. We refine these quantum computational supremacy arguments and perform such a calculation by imposing fine-grained versions of the non-collapse assumption. Each version is parameterized by a constant $a$ and asserts that certain specific computational problems with input size $n$ require $2^{an}$ time steps to be solved by a non-deterministic algorithm. Then, we choose a specific value of $a$ for each version that we argue makes the assumption plausible, and based on these conjectures we conclude that Instantaneous Quantum Polynomial-Time (IQP) circuits with 208 qubits, Quantum Approximate Optimization Algorithm (QAOA) circuits with 420 qubits and boson sampling circuits (i.e. linear optical networks) with 98 photons are large enough for the task of producing samples from their output distributions up to constant multiplicative error to be intractable on current technology. In the first two cases, we extend this to constant additive error by introducing an average-case fine-grained conjecture.Comment: 24 pages + 3 appendices, 8 figures. v2: number of qubits calculation updated and conjectures clarified after becoming aware of Ref. [42]. v3: Section IV and Appendix C added to incorporate additive-error simulation

Influence of operating parameters on the biodegradation of steroid estrogens and nonylphenolic compounds during biological wastewater treatment processes

This document is the unedited author's version of a Submitted Work that was subsequently accepted for publication in Environmental Science & Technology, copyright © American Chemical Society after peer review. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/es901612v.This study investigated operational factors influencing the removal of steroid estrogens and nonylphenolic compounds in two sewage treatment works, one a nitrifying/denitrifying activated sludge plant and the other a nitrifying/denitrifying activated sludge plant with phosphorus removal. Removal efficiencies of >90% for steroid estrogens and for longer chain nonylphenol ethoxylates (NP4−12EO) were observed at both works, which had equal sludge ages of 13 days. However, the biological activity in terms of milligrams of estrogen removed per day per tonne of biomass was found to be 50−60% more efficient in the nitrifying/denitrifying activated sludge works compared to the works which additionally incorporated phosphorus removal. A temperature reduction of 6 °C had no impact on the removal of free estrogens, but removal of the conjugated estrone-3-sulfate was reduced by 20%. The apparent biomass sorption (LogKp) values were greater in the nitrifying/denitrifying works than those in the nitrifying/denitrifying works with phosphorus removal for both steroid estrogens and nonylphenolic compounds possibly indicating a different cell surface structure and therefore microbial population. The difference in biological activity (mg tonne−1 d−1) identified in this study, of up to seven times, suggests that there is the potential for enhancing the removal of estrogens and nonylphenols if more detailed knowledge of the factors responsible for these differences can be identified and maximized, thus potentially improving the quality of receiving waters.Public Utilities Board (Singapore), Anglian Water Ltd, Severn Trent Water Ltd, Thames Water Utilities Ltd, United Utilities 393 Plc and Yorkshire Water Services

Global economic trade-offs between wild nature and tropical agriculture

Global demands for agricultural and forestry products provide economic incentives for deforestation across the tropics. Much of this deforestation occurs with a lack of information on the spatial distribution of benefits and costs of deforestation. To inform global sustainable land-use policies, we combine geographic information systems (GIS) with a meta-analysis of ecosystem services (ES) studies to perform a spatially explicit analysis of the trade-offs between agricultural benefits, carbon emissions, and losses of multiple ecosystem services because of tropical deforestation from 2000 to 2012. Even though the value of ecosystem services presents large inherent uncertainties, we find a pattern supporting the argument that the externalities of destroying tropical forests are greater than the current direct economic benefits derived from agriculture in all cases bar one: when yield and rent potentials of high-value crops could be realized in the future. Our analysis identifies the Atlantic Forest, areas around the Gulf of Guinea, and Thailand as areas where agricultural conversion appears economically efficient, indicating a major impediment to the long-term financial sustainability of Reducing Emissions from Deforestation and forest Degradation (REDD+) schemes in those countries. By contrast, Latin America, insular Southeast Asia, and Madagascar present areas with low agricultural rents (ARs) and high values in carbon stocks and ES, suggesting that they are economically viable conservation targets. Our study helps identify optimal areas for conservation and agriculture together with their associated uncertainties, which could enhance the efficiency and sustainability of pantropical land-use policies and help direct future research efforts.Luis R. Carrasco, Edward L. Webb, William S. Symes, Lian P. Koh, Navjot S. Sodh

Cigarette smoking and risk of total knee replacement for severe osteoarthritis among Chinese in Singapore - the Singapore Chinese health study

10.1016/j.joca.2014.03.013Osteoarthritis and Cartilage226764-77