bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bim regulates BCR‐induced entry of B cells into the cell cycle
Authors: Craxton Andrew , Draves Kevin E. , Clark Edward A. 
Published: August 2007

AbstractBH3‐only Bcl‐2 homologs are key regulators of the intrinsic apoptotic pathway. In particular, Bim, is critical for mediating apoptosis of hematopoietic cells including B cells. While studies using Bcl‐2 Tg mice have defined an important role for Bcl‐2 in cell cycle control, the role of BH3‐only proteins is less clear. Using Bim KO mice, we show that Bim is required for B cells to enter the cell cycle normally. Bim KO B cells had reduced cell division compared to WT B cells in response to BCR, TLR3 or TLR4 signaling, whereas Bim deficiency did not affect TLR9‐induced B cell division. Cell cycle progression in BCR‐ and LPS‐stimulated Bim KO B cells was blocked at the G0–G1 stage. BCR‐induced p130 degradation and pRb hyperphosphorylation on Ser807/811, which are critical for G1 entry, were reduced in Bim KO compared to WT B cells. Likewise, BCR‐induced p27Kip1 degradation was decreased in Bim KO compared to WT B cells. These defects in BCR‐induced cell cycle entry correlated with a proximal defect in BCR‐mediated intracellular calcium release in Bim KO B cells. Our results suggest that the balance of pro‐ and anti‐apoptotic Bcl‐2 family proteins is critical for controlling both cell cycle progression and apoptosis in B cells.
Synthetic Studies Towards Bridgehead Diprenyl‐Substituted Bicyclo[3.3.1]nonane‐2,9‐diones as Models for Polyprenylated Acylphloroglucinol Construction
Authors: Pouplin Thomas , Tolon Blanca , Nuhant Philippe , Delpech Bernard , Marazano Christian 
Published: August 2007

AbstractThe synthesis of bridgehead diprenylated bicyclo[3.3.1]nonane‐2,9‐dione, based on a reductive rearrangement of an enol lactone, is presented. The same target could be reached by a one‐step sequence involving Michael addition of 2,6‐diprenylcyclohexanone onto acrolein and intramolecular aldol reaction. The first method could be extended to the formation of a compound with gem‐dimethyl substituents adjacent to the bridgehead position, but the construction of a suitably substituted enol lactone, with a view to polyprenylated acylphloroglucinol elaboration, could not be achieved. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Synthesis, X‐ray Crystal Structures and Solid‐State Fluorescence Properties of 3‐Dibutylamino‐6‐alkoxy‐6‐phenylnaphtho[2,3‐b]benzofuran‐11(6H)‐one Derivatives
Authors: Ooyama Yousuke , Mamura Toshiki , Yoshida Katsuhira 
Published: August 2007

AbstractNovel heterocyclic fluorophores – 6‐alkoxy‐3‐dibutylamino‐6‐phenylnaphtho[2,3‐b]benzofuran‐11(6H)‐ones 2a–2g with different chain lengths in alkoxy substituents non‐conjugatedly linked to the chromophore skeleton – have been derived from the quinol‐type compound 1, and their photophysical properties have been investigated in solution and in the solid state. In solution, the fluorophores 1 and 2a–2g exhibit similar fluorescence properties. In the solid state, however, the fluorophores 2a–2g exhibit stronger fluorescence properties than the quinol 1. Furthermore, the fluorescence quantum yields (Φ) of 2 in the solid state are higher than those of 2 in solution, and considerable differences in the solid‐state fluorescence were observed among the alkoxy derivatives 2a–2g. To elucidate the dramatic effect of the alkoxy substituents we performed semiempirical molecular orbital calculations (AM1 and INDO/S) and X‐ray crystallographic analysis. On the basis of the results of the calculations and the X‐ray crystal structures, the relationships between the solid‐state photophysical properties and the chemical and crystal structures of 1 and 2a–2g are discussed. It was confirmed that the introduction of long alkoxy chains such as butoxy and pentoxy groups in non‐conjugated linkage to the chromophore can efficiently prevent short π–π contacts between the fluorophores in molecular aggregation states and thus cause dramatic solid‐state fluorescence enhancements.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
The First Example of an Azaphenalene Profluorescent Nitroxide
Authors: Blinco James P. , McMurtrie John C. , Bottle Steven E. 
Published: August 2007

AbstractThe synthesis of the first example of an azaphenalene‐based fused aromatic nitroxide TMAO, [1,1,3,3‐tetramethyl‐2,3‐dihydro‐2‐azaphenalen‐2‐yloxyl, (5)], is described. This novel nitroxide possesses some of the structural rigidity of the isoindoline class of nitroxides, as well as some properties akin to TEMPO nitroxides. Additionally, the integral aromatic ring imparts fluorescence that is switched on by radical scavenging reactions of the nitroxide, which makes it a sensitive probe for polymer degradation.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Multiple frequency dielectrophoresis
Authors: Urdaneta Mario , Smela Elisabeth 
Published: August 2007

AbstractA novel method of modeling multiple frequency dielectrophoresis (MFDEP) is introduced based on the concept of an effective Clausius–Mossotti factor, CMeff, for a particle that is exposed to electrical fields of different frequencies, coming either from one or multiple pairs of electrodes. This analysis clearly illustrates how adding frequencies adds control parameters, up to two additional parameters per frequency. As a result, MFDEP can be used for a wide variety of applications, including separating particles with very similar Clausius–Mossotti spectra, trapping multiple groups of cells simultaneously, and cancelling unwanted dielectrophoretic traps. Illustrating the modeling approach, we determine the CMeffs for live and dead yeast cells, and then predict their equilibrium distribution on a three‐electrode configuration, with two electrodes at different frequencies and the third electrode at ground. This prediction is validated experimentally, using MFDEP to selectively attract live cells to one location and dead cells to another, trapping both. These results demonstrate that the use of multiple frequencies for the manipulation of particles can enhance the performance of dielectrophoretic devices, not only for sorting, but also for such applications as patterning cells in close proximity for the formation of cell consortia.
EOF using the Ritz method: Application to superelliptic microchannels
Authors: Wang Chang Yi , Chang Chien C. 
Published: August 2007

AbstractAn efficient Ritz method is developed from the variational principle to solve the Poisson–Boltzmann equation under the Debye–Hückel approximation for studying the EOF in microchannels. The method is applied to the family of superelliptic cross sections which includes the elliptic channel and the rectangular channel as limiting cases. Several accurate tables presented are useful for design of electroosmotic channels, especially rectangular channels with rounded corners. It is shown how the flow rate Q is a sophisticated consequence of the nondimensional electrokinetic width K, the aspect ratio b as well as the superelliptic exponent n.
SNPlexing the human Y‐chromosome: A single‐assay system for major haplogroup screening
Authors: Berniell‐Lee Gemma , Sandoval Karla , Mendizabal Isabel , Bosch Elena , Comas David 
Published: August 2007

AbstractSNPs are one of the main sources of DNA variation among humans. Their unique properties make them useful polymorphic markers for a wide range of fields, such as medicine, forensics, and population genetics. Although several high‐throughput techniques have been (and are being) developed for the vast typing of SNPs in the medical context, population genetic studies involve the typing of few and select SNPs for targeted research. This results in SNPs having to be typed in multiple reactions, consuming large amounts of time and of DNA. In order to improve the current situation in the area of human Y‐chromosome diversity studies, we decided to employ a system based on a multiplex oligo ligation assay/PCR (OLA/PCR) followed by CE to create a Y multiplex capable of distinguishing, in a single reaction, all the major haplogroups and as many subhaplogroups on the Y‐chromosome phylogeny as possible. Our efforts resulted in the creation of a robust and accurate 35plex (35 SNPs in a single reaction) that when tested on 165 human DNA samples from different geographic areas, proved capable of assigning samples to their corresponding haplogroup.
Modelling dynamic water redistribution patterns in arid catchments in the Negev Desert of Israel
Authors: Buis E. , Veldkamp A. 
Published: August 2007

AbstractIn arid climate regions, redistribution of runoff water is highly relevant for vegetation development. The process of water redistribution at catchment scale is studied with the landscape process model LAPSUS, mainly used for erosion and sedimentation modelling. LAPSUS, formerly applied in Mediterranean climates, is modified to deal with the arid climate of the Negev Desert of Israel. Daily event based model runs were used instead of yearly model runs, and the infiltration module was modified to better represent the spatial diversity in water availability in an arid catchment. The model is calibrated for two small catchments in the Negev Desert of Israel, Halluqim and Avdat. First, a sensitivity analysis of the modified LAPSUS is performed. Pore volume appears to have an especially strong influence on the modelling results. Second, the capability of LAPSUS to deal with varying surface characteristics is assessed by comparing the water redistribution patterns in the two catchments with field data. Simulation results demonstrate that the catchments respond very differently to precipitation. Water redistribution is larger in the dominantly bedrock covered Halluqim compared to the dominantly loess covered catchment of Avdat. Consequently, Halluqim has more positions with water accumulation than Avdat, and can sustain a larger vegetation cover, including Mediterranean species. Finally, the modelled infiltration patterns are compared with vegetation cover in the catchments. The results indicate that there is a broad agreement between infiltration and vegetation patterns, but locally there is a strong mismatch, indicating that some of the involved processes are still missing from the model. Copyright © 2007 John Wiley & Sons, Ltd.
How do streamflow generation mechanisms affect watershed hypsometry?
Authors: Huang Xiangjiang , Niemann Jeffrey D. 
Published: August 2007

AbstractSeveral studies have shown that the dominant streamflow generation mechanism in a river basin can leave distinct geomorphological signatures in basin topography. In particular, it has been suggested previously that basins generated by groundwater discharge tend to have a larger hypsometric integral than surface runoff basins because fluvial erosion is more focused in the valleys where groundwater discharge tends to occur. In this analysis, we aim to clarify this relationship by developing an alternative method to quantify the effects of streamflow generation mechanisms on basin hypsometry and by using a numerical model that can generate streamflow by different processes to evaluate the sensitivity of the results to the hydrological and geomorphological properties of the basin. The model results suggest that the hypsometric characteristics that are usually associated with groundwater discharge basins, such as a larger hypsometric integral, occur primarily when drainage networks are still advancing in the watershed. During later stages of development, an additional factor such as lithological controls or a distinct geomorphological process would be needed to preserve these features. The model results also show that the hypsometric effects are stronger when the parameters of the fluvial erosion process promote the influence of small discharge rates. Copyright © 2007 John Wiley & Sons, Ltd.
Determination of axial displacement extent based on transformer winding transfer function estimation using vector‐fitting method
Authors: Karimifard P. , Gharehpetian G. B. , Tenbohlen S. 
Published: August 2007

AbstractThis paper suggests a new method to determine the extent of the axial winding displacement which is based on the transfer function (TF) estimation using the vector‐fitting (VF) method. The identification of the TF in normal and displaced conditions can be achieved properly using VF methods. To study the different degrees of mechanical displacements, a verified detailed model of transformer in the frequency range of kHz < f <MHz has been used. A new index for the determination of the displacement extent has been presented, too. Copyright © 2007 John Wiley & Sons, Ltd.
Notch signaling modulates the activation of microglial cells
Authors: Grandbarbe Luc , Michelucci Alessandro , Heurtaux Tony , Hemmer Karin , Morga Eleonora , Heuschling Paul 
Published: August 2007

AbstractThe Notch signaling pathway plays a crucial role in specifying cellular fate in metazoan development by regulating communication between adjacent cells. Correlative studies suggested an involvement of Notch in hematopoietic cell development. Here, we report that the Notch pathway is expressed and active in microglial cells. During inflammatory activation, the transcription of the Notch down‐stream effector Hes1 is downregulated. When Notch1 transcription in microglia is inhibited, an upregulation of the expression of pro‐inflammatory cytokines is observed. Notch stimulation in activated microglia, using a soluble form of its ligand Jagged1, induces a decrease in pro‐inflammatory cytokines secretion and nitric oxide production as well as an increase in phagocytic activity. Notch‐stimulation is accompanied by an increase in the rate of STAT3 phosphorylation and nuclear translocation. Our results show that the Notch pathway plays an important role in the control of inflammatory reactions in the CNS. © 2007 Wiley‐Liss, Inc.
Decreased estradiol release from astrocytes contributes to the neurodegeneration in a mouse model of Niemann‐Pick disease type C
Authors: Chen Gang , Li Hai‐Min , Chen Yi‐Ren , Gu Xiao‐Song , Duan Shumin 
Published: August 2007

AbstractNiemann‐Pick disease type C (NPC) is a deadly neurodegenerative disease often caused by mutation in a gene called NPC1, which results in the accumulation of unesterified cholesterol and glycosphingolipids in the endosomal–lysosomal system. Most studies on the mechanisms of neurodegeneration in NPC have focused on neurons. However, the possibility also exists that NPC1 affects neuronal functions indirectly by acting on other cells that are intimately interacting with neurons. In this study, using a heterotypic neuron‐glia coculture system, we found that wild‐type neurons cultured on a layer of NPC1−/− astrocytes showed decreased neurite growth compared with those cultured on wild‐type astrocytes. RT‐PCR and immunohistochemical assessments showed significantly lower expression of neurosteroid enzymes and StAR (steroidogenic acute regulatory protein) in NPC1−/− astrocyte cultures than in wild‐type cultures. Furthermore, a reduced level of estradiol was measured from both astrocyte culture medium and whole brains from NPC1−/− mice. Administration of 17β‐estradiol to neonatal NPC1−/− mice significantly delayed the onset of neurological symptoms, increased Purkinje cell survival, and extended the animals' life span. Our findings suggest that astrocyte dysfunction contributes to the neurodegeneration of NPC and estradiol treatment may be useful in ameliorating progression of the disease. © 2007 Wiley‐Liss, Inc.
Myelin‐associated glycoprotein reduces axonal branching and enhances functional recovery after sciatic nerve transection in rats
Authors: Tomita Koichi , Kubo Tateki , Matsuda Ken , Yano Kenji , Tohyama Masaya , Hosokawa Ko 
Published: August 2007

AbstractThe mature peripheral nervous system (PNS) generally shows better regeneration of injured axons as opposed to the central nervous system (CNS). However, complete functional recovery is rarely achieved even in the PNS although morphologically good axonal regeneration often occurs. This mainly results from aberrant reinnervation due to extensive branching of cut axons with consequent failure of synchronized movements of the muscles. Myelin‐associated glycoprotein (MAG), a well‐characterized molecule existing both in the CNS and PNS myelin, is considered to be a potent inhibitor of axonal regeneration especially in the CNS. In the present study, we investigated whether MAG has any effects not only on axonal elongation, but also on axonal branching. We show herein that MAG minimized branching of the peripheral axons both in vitro and in vivo via activation of RhoA. Furthermore, after sciatic nerve transection in rats, focal and temporary application of MAG to the lesion dramatically enhanced the functional recovery. Using double retrograde labeling and preoperative/postoperative labeling of spinal neurons, reduced hyperinnervation and improved accuracy of target reinnervation was confirmed, respectively. In conclusion, as MAG significantly improves the quality of axonal regeneration, it can be used as a new therapeutic approach for peripheral nerve repair with possible focal and temporary application. © 2007 Wiley‐Liss, Inc.
Region‐of‐interest‐based analysis with application of cortical thickness variation of left planum temporale in schizophrenia and psychotic bipolar disorder
Authors: Qiu Anqi , Vaillant Marc , Barta Patrick , Ratnanather J.Tilak , Miller Michael I. 
Published: August 2007

AbstractIn neuroimaging studies, spatial normalization and multivariate testing are central problems in characterizing group variation of functions (e.g., cortical thickness, curvature, functional response) in an atlas coordinate system across clinical populations. We present a region‐of‐interest (ROI)‐based analysis framework for detecting such a group variation. This framework includes two main techniques: ROI‐based registration via large deformation diffeomorphic metric surface mapping and a multivariate testing using a Gaussian random field (GRF) model on the cortical surface constructed by the eigenfunctions of the Laplace–Beltramioperator. We compared our GRF statistical model with a pointwise hypothesis testing approach, whose P‐value is corrected using false discovery rate or random field theory at several smoothness scales. As an illustration, we applied this framework to a clinical study of the cortical thickness of the left planum temporale (PT) in subjects with psychotic bipolar disorder, schizophrenia, and healthy comparison controls. Our results show that the anterior portion of the left PT is thinner in the psychotic bipolar and schizophrenic groups than in the healthy control group, and the posterior portion of the left PT shows the reversal finding. Moreover, there may be a greater thickness variation in the left PT in psychotic bipolar patients when compared with that in schizophrenic patients. Hum Brain Mapp, 2008. © 2007 Wiley‐Liss, Inc.
Institutional factors and HIV/AIDS, TB and Malaria
Authors: Simmonds Stephanie 
Published: August 2007

AbstractThis paper outlines the principal institutional factors affecting the slow progress in reaching agreed targets in Africa regarding the prevention and control of HIV/AIDS, TB and Malaria. It focuses on three key factors: political analysis, strategic business approach and international inputs.Most of the analyses tend to look at the technical aspects of disease prevention and control, of political analysis there is a marked absence. Yet, we know that wider contextual or macro factors such as power and political decision making can make or break a programme.Many senior managers in public sector institutions are preoccupied with day‐to‐day work. Successful businesses in the private sector have some things in common with each other. Outstanding leadership, a strategic and action orientated culture, highly focused on comparative strengths on priorities and quality being some of the key ones. Adopting such successful business characteristics might make the difference to public institutions.The move to results based institutions by focussing on outputs and outcomes is for the better. However, we still need to rigorously examine the quality of inputs that the increasing availability of funds is being used on. This is especially so in relation to needing a better balance between aid for health services and that for institutional and health systems development. In addition, technical advisers from development partners need to work more across a ministry of health on institutional and management change to have a greater impact on achieving targets. Copyright © 2007 John Wiley & Sons, Ltd.
Parameterization of azole‐bridged dinuclear platinum anticancer drugs via a QM/MM force matching procedure
Authors: Spiegel Katrin , Magistrato Alessandra , Maurer Patrick , Ruggerone Paolo , Rothlisberger Ursula , Carloni Paolo , Reedijk Jan , Klein Michael L. 
Published: August 2007

AbstractAzole‐bridged diplatinum compounds are promising new anticancer drugs designed to induce small distortions upon DNA alkylation, able to circumvent resistance problems of existing platinum drugs. Hybrid quantum classical (QM/MM) molecular dynamics (MD) simulations of different azole‐bridged platinum drugs have recently revealed the nature of the local deformations at the DNA binding site. However, the description of global slow converging rearrangements cannot be addressed by QM/MM MD due to the short time scale accessible. Extensive classical MD simulations are therefore mandatory to describe accurately the structural distortions in the DNA double helix. This issue is now addressed by developing a new set of accurate force field parameters of the platinated moiety via a recently proposed force matching procedure of the classical forces to ab initio forces obtained from QM/MM trajectories. The accuracy of our force field parameters is validated by comparison of structural properties from classical MD and hybrid QM/MM simulations. The structural characteristics of the Pt‐lesion are well reproduced during classical MD compared with QM/MM simulations and available experimental data. The global distortions in the DNA duplex upon binding of dinuclear Pt‐compounds are very small and rather opposite to those induced by cisplatin. Thus, the force match approach significantly extends the potentialities of molecular simulations in the study of anticancer drugs and of the interactions with their biological targets. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008