A Covolume Method Based on Rotated Bilinears for the Generalized Stokes Problem

We introduce a covolume or marker and cell (MAC) method for approximating the generalized Stokes problem on an axiparallel domain. Two grids are needed, the primal grid made up of rectangles and the dual grid of quadrilaterals. The velocity is approximated by nonconforming rotated bilinear elements with degrees of freedom at midpoints of rectangular elements and the pressure by piecewise constants. The error in the velocity in the Hh norm and the pressure in the L2 norm are of first order, provided that the exact velocity is in H2 and the exact pressure in H1

Cdk5 Phosphorylates Dopamine D2 Receptor and Attenuates Downstream Signaling

The dopamine D2 receptor (DRD2) is a key receptor that mediates dopamine-associated brain functions such as mood, reward, and emotion. Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase whose function has been implicated in the brain reward circuit. In this study, we revealed that the serine 321 residue (S321) in the third intracellular loop of DRD2 (D2i3) is a novel regulatory site of Cdk5. Cdk5-dependent phosphorylation of S321 in the D2i3 was observed in in vitro and cell culture systems. We further observed that the phosphorylation of S321 impaired the agonist-stimulated surface expression of DRD2 and decreased G protein coupling to DRD2. Moreover, the downstream cAMP pathway was affected in the heterologous system and in primary neuronal cultures from p35 knockout embryos likely due to the reduced inhibitory activity of DRD2. These results indicate that Cdk5-mediated phosphorylation of S321 inhibits DRD2 function, providing a novel regulatory mechanism for dopamine signaling.X111111sciescopu

Estimation of Effective Plant Area Index for South Korean Forests Using LiDAR System

Light Detection and Ranging (LiDAR) systems can be used to estimate both vertical and horizontal forest structure. Woody components, the leaves of trees and the understory can be described with high precision, using geo-registered 3D-points. Based on this concept, the Effective Plant Area Indices (PAIe) for areas of Korean Pine (Pinus koraiensis), Japanese Larch (Larix leptolepis) and Oak (Quercus spp.) were estimated by calculating the ratio of intercepted and incident LIDAR laser rays for the canopies of the three forest types. Initially, the canopy gap fraction (GLiDAR) was generated by extracting the LiDAR data reflected from the canopy surface, or inner canopy area, using k-means statistics. The LiDAR-derived PAIe was then estimated by using GLIDAR with the Beer-Lambert law. A comparison of the LiDAR-derived and field-derived PAIe revealed the coefficients of determination for Korean Pine, Japanese Larch and Oak to be 0.82, 0.64 and 0.59, respectively. These differences between field-based and LIDAR-based PAIe for the different forest types were attributed to the amount of leaves and branches in the forest stands. The absence of leaves, in the case of both Larch and Oak, meant that the LiDAR pulses were only reflected from branches. The probability that the LiDAR pulses are reflected from bare branches is low as compared to the reflection from branches with a high leaf density. This is because the size of the branch is smaller than the resolution across and along the 1 meter LIDAR laser track. Therefore, a better predictive accuracy would be expected for the model if the study would be repeated in late spring when the shoots and leaves of the deciduous trees begin to appear

Differential regulation of BACE1 expression by oxidative and nitrosative signals

<p>Abstract</p> <p>Background</p> <p>It is well established that both cerebral hypoperfusion/stroke and type 2 diabetes are risk factors for Alzheimer's disease (AD). Recently, the molecular link between ischemia/hypoxia and amyloid precursor protein (APP) processing has begun to be established. However, the role of the key common denominator, namely nitric oxide (NO), in AD is largely unknown. In this study, we investigated redox regulation of BACE1, the rate-limiting enzyme responsible for the β-cleavage of APP to Aβ peptides.</p> <p>Results</p> <p>Herein, we studied events such as S-nitrosylation, a covalent modification of cysteine residues by NO, and H₂O₂-mediated oxidation. We found that NO and H₂O₂differentially modulate BACE1 expression and enzymatic activity: NO at low concentrations (<100 nM) suppresses BACE1 transcription as well as its enzymatic activity while at higher levels (0.1-100 μM) NO induces S-nitrosylation of BACE1 which inactivates the enzyme without altering its expression. Moreover, the suppressive effect on BACE1 transcription is mediated by the NO/cGMP-PKG signaling, likely through activated PGC-1α. H₂O₂(1-10 μM) induces BACE1 expression via transcriptional activation, resulting in increased enzymatic activity. The differential effects of NO and H₂O₂on BACE1 expression and activity are also reflected in their opposing effects on Aβ generation in cultured neurons in a dose-dependent manner. Furthermore, we found that BACE1 is highly S-nitrosylated in normal aging brains while S-nitrosylation is markedly reduced in AD brains.</p> <p>Conclusion</p> <p>This study demonstrates for the first time that BACE1 is highly modified by NO via multiple mechanisms: low and high levels of NO suppress BACE1 via transcriptional and post translational regulation, in contrast with the upregulation of BACE1 by H₂O₂-mediated oxidation. These novel NO-mediated regulatory mechanisms likely protect BACE1 from being further oxidized by excessive oxidative stress, as from H₂O₂and peroxynitrite which are known to upregulate BACE1 and activate the enzyme, resulting in excessive cleavage of APP and Aβ generation; they likely represent the crucial house-keeping mechanism for BACE1 expression/activation under physiological conditions.</p

Escape from adamantane: Scaffold optimization of novel P2X7 antagonists featuring complex polycycles

The adamantane scaffold, despite being widely used in medicinal chemistry, is not devoid of problems. In the recent years we have developed new polycyclic scaffolds as surrogates of the adamantane group with encouraging results in multiple targets. As an adamantane scaffold is a common structural feature in several P2X7 receptor antagonists, herein we report the synthesis and pharmacological evaluation of multiple replacement options of adamantane that maintain a good activity profile. Molecular modeling studies support the binding of the compounds to a site close to the central pore, rather than to the ATP-binding site and shed light on the structural requirements for novel P2X7 antagonists

Partisan Asymmetries in Online Political Activity

We examine partisan differences in the behavior, communication patterns and social interactions of more than 18,000 politically-active Twitter users to produce evidence that points to changing levels of partisan engagement with the American online political landscape. Analysis of a network defined by the communication activity of these users in proximity to the 2010 midterm congressional elections reveals a highly segregated, well clustered partisan community structure. Using cluster membership as a high-fidelity (87% accuracy) proxy for political affiliation, we characterize a wide range of differences in the behavior, communication and social connectivity of left- and right-leaning Twitter users. We find that in contrast to the online political dynamics of the 2008 campaign, right-leaning Twitter users exhibit greater levels of political activity, a more tightly interconnected social structure, and a communication network topology that facilitates the rapid and broad dissemination of political information.Comment: 17 pages, 10 figures, 6 table

Orbital quantization in the high magnetic field state of a charge-density-wave system

A superposition of the Pauli and orbital coupling of a high magnetic field to charge carriers in a charge-density-wave (CDW) system is proposed to give rise to transitions between subphases with quantized values of the CDW wavevector. By contrast to the purely orbital field-induced density-wave effects which require a strongly imperfect nesting of the Fermi surface, the new transitions can occur even if the Fermi surface is well nested at zero field. We suggest that such transitions are observed in the organic metal $\alpha$-(BEDT-TTF)$_2$KHg(SCN)$_4$ under a strongly tilted magnetic field.Comment: 14 pages including 4 figure