bluuebunny/crossref_metadata_2025 huggingface dataset:
RAX, the PKR activator, sensitizes cells to inflammatory cytokines, serum withdrawal, chemotherapy, and viral infection
Authors: Bennett Richard L. , Blalock William L. , Abtahi Dean M. , Pan Yu , Moyer Sue A. , May W. Stratford
Published: April 2006

While the interferon (IFN)–inducible double-stranded RNA (dsRNA)–dependent protein kinase PKR is reported to initiate apoptosis in some instances, the mechanism by which diverse stress stimuli activate PKR remains unknown. Now we report that RAX, the only known cellular activator for PKR, initiates PKR activation in response to a broad range of stresses including serum deprivation, cytotoxic cytokine or chemotherapy treatment, or viral infection. Thus, knock-down of RAX expression by 80% using small interfering RNA (siRNA) prevents IFNγ/tumor necrosis factor α (TNFα)–induced PKR activation and eIF2α phosphorylation, IκB degradation, IRF-1 expression, and STAT1 phosphorylation, resulting in enhanced murine embryonic fibroblast (MEF) cell survival. In contrast, expression of exogenous RAX, but not of the nonphosphorylatable, dominant-negative RAX(S18A) mutant, sensitizes cells to IFNγ/TNFα, mitomycin C (MMC), or serum deprivation in association with increased PKR activity and apoptosis. Furthermore, RAX(S18A) expression in Fanconi anemia complementation group C–null MEF cells not only prevents PKR activation but also blocks hypersensitivity to IFNγ/TNFα or mitomycin C that results in enhanced apoptosis. In addition, reduced RAX expression facilitates productive viral infection with vesicular stomatitis virus (VSV) and promotes anchorage-independent colony growth of MEF cells. Collectively, these data indicate that RAX may function as a negative regulator of growth that is required to activate PKR in response to a broad range of apoptosis-inducing stress.
Cell-surface association between matrix metalloproteinases and integrins: role of the complexes in leukocyte migration and cancer progression
Authors: Stefanidakis Michael , Koivunen Erkki
Published: April 2006

Leukocyte motility is known to be dependent on both β2-integrins and matrix metalloproteinases MMP-2/-9 or gelatinases, which mediate leukocyte adhesion and the proteolysis needed for invasion, respectively. Gelatinases not only play an important role in cell migration, tissue remodeling, and angiogenesis during development, but are also involved in the progression and invasiveness of many cancers, including leukemias. The concept that MMPs associate with integrins, as well as their importance in some physiologic and pathologic conditions, has been advanced previously but has not been examined on leukocytes. This review will examine mainly the function of the MMP-integrin complexes in normal leukocyte migration and the effect of integrin and broad-spectrum MMP inhibitors in tumor progression.
Direct costs of three models for the screening of latent tuberculosis infection
Authors: Wrighton-Smith P. , Zellweger J-P.
Published: April 2006

The aim of the present study was to compare the direct costs of three models for detection of latent tuberculosis infection (LTBI) in routine clinical practice in Switzerland.

Comparison of the overall costs of screening for LTBI, including medical and radiological examination, and preventive treatment associated with three screening models was carried out. Model 1 relies only on the tuberculin skin test (TST) according to the current national guidelines, model 2 relies on T-SPOT®.TB(Oxford Immunotec, Oxford, UK) only and model 3 relies on TST followed by confirmation of positive results by T-SPOT.TB. Costs were taken directly from the clinic's figures. Clinical assumptions were based on the 267 patients who were referred to the clinic over the study period.

Model 3 was found to be the most cost-effective. Using only the skin test (model 1) was the least cost-effective. If only one test for LTBI is to be used, then model 2 (using T-SPOT.TBonly) is cheaper than using the TST (model 1).

Screening for latent tuberculosis infection by tuberculin skin test followed by confirmation with T-SPOT.TBis less costly than screening with tuberculin skin test alone, as it allows a reduction in the number of people who receive preventive treatment. In groups with a high proportion of negative tuberculin skin tests, screening with T-SPOT.TBtest only may be the most cost-effective.
Assault‐injured Adolescents Presenting to the Emergency Department: Causes and Circumstances
Authors: Cheng Tina L. , Johnson Sara , Wright Joseph L. , Pearson‐Fields Amari Sokoya , Brenner Ruth , Schwarz Donald , O'Donnell Regina , Scheidt Peter C.
Published: April 2006

Objectives:
To describe the causes and circumstances of conflict leading to assault injury among urban youth seeking care in the emergency department.

Methods:
The authors conducted in‐person and telephone interviews with a convenience sample of 143 youth aged 12–19 years presenting to two urban emergency departments with an interpersonal assault injury. Patients were interviewed about the nature and circumstances of their injury. Descriptive analysis was performed, including stratified analysis by gender, age (12–15 vs. 16–19 years), and weapon use.

Results:
Seventy percent of patients knew or knew of the person(s) who injured them; most were friends, classmates, or acquaintances. More than half of the injuries (56%) were related to a past disagreement. Among assaults related to a past disagreement, 33% of patients had previous arguments with their assailant, 16% had previous fights, and 14% had previous weapons threats. Twenty‐nine percent had been previously threatened, and 11% had previously threatened their assailant. Twenty‐eight percent of patients believed they helped to cause the injury by provoking a fight or letting down their guard. Nearly two thirds (64%) believed there were things they could change to prevent future injury, including staying away from dangerous situations and bad influences or controlling their tempers.

Conclusions:
Most assault injuries among adolescents involved past disagreements with people they knew. Many injured youth were mutually involved in conflict before their injury. Over time, many victims and perpetrators may be interchangeable. These data may help inform emergency department–based interventions to prevent assault injury.
Retinoic acid guides eye morphogenetic movements via paracrine signaling but is unnecessary for retinal dorsoventral patterning
Authors: Molotkov Andrei , Molotkova Natalia , Duester Gregg
Published: April 2006

Retinoic acid (RA) is required for patterning of the posterior nervous system, but its role in the retina remains unclear. RA is synthesized in discrete regions of the embryonic eye by three retinaldehyde dehydrogenases(RALDHs) displaying distinct expression patterns. Overlapping functions of these enzymes have hampered genetic efforts to elucidate RA function in the eye. Here, we report Raldh1, Raldh2 and Raldh3 single,double and triple null mice exhibiting progressively less or no RA synthesis in the eye. Our genetic studies indicate that RA signaling is not required for the establishment or maintenance of dorsoventral patterning in the retina, as we observe normal expression of Tbx5 and ephrin B2 (Efnb2)dorsally, plus Vax2 and Ephb2 ventrally. Instead, RA is required for the morphogenetic movements needed to shape the developing retina and surrounding mesenchyme. At early stages, Raldh2 expressed in mesenchyme and Raldh3 expressed in the retinal pigmented epithelium generate RA that delivers an essential signal to the neural retina required for morphogenetic movements that lead to ventral invagination of the optic cup. At later stages, Raldh1 expressed in dorsal neural retina and Raldh3 expressed in ventral neural retina (plus weaker expression of each in lens/corneal ectoderm) generates RA that travels to surrounding mesenchyme, where it is needed to limit the anterior invasion of perioptic mesenchyme during the formation of corneal mesenchyme and eyelids. At all stages, RA target tissues are distinct from locations of RA synthesis,indicating that RALDHs function cell-nonautonomously to generate paracrine RA signals that guide morphogenetic movements in neighboring cells.
Tracing the first waves of lymphopoiesis in mice
Authors: Yokota Takafumi , Huang Jiaxue , Tavian Manuela , Nagai Yoshinori , Hirose Jun , Zúñiga-Pflücker Juan-Carlos , Péault Bruno , Kincade Paul W.
Published: April 2006

RAG1/GFP knock-in mice were used to precisely chart the emergence and expansion of cells that give rise to the immune system. Lymphopoietic cells detectable in stromal co-cultures arose as early as E8.5, i.e. prior to establishment of the circulation within the paraaortic splanchnopleura (P-Sp). These cells were Tie2+ RAG1- CD34Lo/-Kit+ CD41-. While yolk sac (YS) also contained lymphopoietic cells after E9.5, CD41+ YS cells from ⩽25-somite embryos produced myelo-erythroid cells but no lymphocytes. Notch receptor signaling directed P-Sp cells to T lymphocytes but did not confer lymphopoietic potential on YS cells. Thus, definitive hematopoiesis arises in at least two independent sites that differ in lymphopoietic potential. Expression of RAG1, the earliest known lymphoid event, first occurred around E10.5 within the embryos. RAG1/GFP+ cells appeared in the liver at E11.0 and progenitors with B and/or T lineage potential were enumerated at subsequent developmental stages.
Differentiation of cerebellar cell identities in absence of Fgf signalling in zebrafish Otx morphants
Authors: Foucher Isabelle , Mione Marina , Simeone Antonio , Acampora Dario , Bally-Cuif Laure , Houart Corinne
Published: April 2006

Although the secreted molecule Fgf8 is a key player of the isthmic organiser function, the mechanisms by which it acts remain unclear. Here, we present evidence indicating that Fgf8 is not instructive in establishing zebrafish cerebellar cell identities, although it is required for proliferation and morphogenesis of this territory. We first show that, as in mouse, lack of Otx function in zebrafish leads to transformation of the presumptive mesencephalon into an extended rhombomere 1 (r1). Expanded Fgf8 expression was proposed to be the cause of this fate transformation. However, this report demonstrates that zebrafish embryos lacking both Otx and fgf8 functions retain an extended r1 and display differentiation of at least two cerebellar cell fates. We show that this is not caused by presence of other Fgfs, which implies that in absence of Otx,Fgf function is not necessary for the differentiation of cerebellar cell types. Otx proteins are therefore potent repressors of cerebellar fates, kept out of r1 progeny by Fgf8. Because Otx transcripts are not present in presumptive r1 territory prior to fgf8 expression, Fgf8 is required to maintain, rather than induce, the posterior boundary of Otx expression. This maintenance is enough to allow cerebellar differentiation.
DrosophilaEph receptor guides specific axon branches of mushroom body neurons
Authors: Boyle Monica , Nighorn Alan , Thomas John B.
Published: April 2006

The conserved Eph receptors and their Ephrin ligands regulate a number of developmental processes, including axon guidance. In contrast to the large vertebrate Eph/Ephrin family, Drosophila has a single Eph receptor and a single Ephrin ligand, both of which are expressed within the developing nervous system. Here, we show that Eph and Ephrin can act as a functional receptor-ligand pair in vivo. Surprisingly, and in contrast to previous results using RNA-interference techniques, embryos completely lacking Eph function show no obvious axon guidance defects. However, Eph/Ephrin signaling is required for proper development of the mushroom body. In wild type,mushroom body neurons bifurcate and extend distinct branches to different target areas. In Eph mutants, these neurons bifurcate normally, but in many cases the dorsal branch fails to project to its appropriate target area. Thus, Eph/Ephrin signaling acts to guide a subset of mushroom body branches to their correct synaptic targets.
vps25mosaics display non-autonomous cell survival and overgrowth, and autonomous apoptosis
Authors: Herz Hans-Martin , Chen Zhihong , Scherr Heather , Lackey Melinda , Bolduc Clare , Bergmann Andreas
Published: April 2006

Appropriate cell-cell signaling is crucial for proper tissue homeostasis. Protein sorting of cell surface receptors at the early endosome is important for both the delivery of the signal and the inactivation of the receptor, and its alteration can cause malignancies including cancer. In a genetic screen for suppressors of the pro-apoptotic gene hid in Drosophila,we identified two alleles of vps25, a component of the ESCRT machinery required for protein sorting at the early endosome. Paradoxically,although vps25 mosaics were identified as suppressors of hid-induced apoptosis, vps25 mutant cells die. However, we provide evidence that a non-autonomous increase of Diap1 protein levels, an inhibitor of apoptosis, accounts for the suppression of hid. Furthermore, before they die, vps25 mutant clones trigger non-autonomous proliferation through a failure to downregulate Notch signaling, which activates the mitogenic JAK/STAT pathway. Hid and JNK contribute to apoptosis of vps25 mutant cells. Inhibition of cell death in vps25 clones causes dramatic overgrowth phenotypes. In addition, Hippo signaling is increased in vps25 clones, and hippo mutants block apoptosis in vps25 clones. In summary,the phenotypic analysis of vps25 mutants highlights the importance of receptor downregulation by endosomal protein sorting for appropriate tissue homeostasis, and may serve as a model for human cancer.
C. elegansdystroglycan DGN-1 functions in epithelia and neurons, but not muscle, and independently of dystrophin
Authors: Johnson Robert P. , Kang Seong Hoon , Kramer James M.
Published: April 2006

The C. elegans dystroglycan (DG) homolog DGN-1 is expressed in epithelia and neurons, and localizes to basement membrane (BM) surfaces. Unlike vertebrate DG, DGN-1 is not expressed in muscle or required for muscle function. dgn-1 null mutants are viable but sterile owing to severe disorganization of the somatic gonad epithelium, and show defects in vulval and excretory cell epithelia and in motoneuron axon guidance. The defects resemble those of epi-1 laminin αB mutants, suggesting that DGN-1 serves as a receptor for laminin. dgn-1(0)/+ animals are fertile but show gonad migration defects in addition to the defects seen in homozygotes, indicating that DGN-1 function is dosage sensitive. Phenotypic analyses show that DGN-1 and dystrophin-associated protein complex (DAPC)components have distinct and independent functions, in contrast to the situation in vertebrate muscle. The DAPC-independent functions of DGN-1 in epithelia and neurons suggest that vertebrate DG may also act independently of dystrophin/utrophin in non-muscle tissues.
Stabilization of β-catenin impacts pancreas growth
Authors: Heiser Patrick W. , Lau Janet , Taketo Makoto M. , Herrera Pedro L. , Hebrok Matthias
Published: April 2006

A recent study has shown that deletion of β-catenin within the pancreatic epithelium results in a loss of pancreas mass. Here, we show that ectopic stabilization of β-catenin within mouse pancreatic epithelium can have divergent effects on both organ formation and growth. Robust stabilization of β-catenin during early organogenesis drives changes in hedgehog and Fgf10 signaling and induces a loss of Pdx1 expression in early pancreatic progenitor cells. Together, these perturbations in early pancreatic specification culminate in a severe reduction of pancreas mass and postnatal lethality. By contrast, inducing the stabilized form of β-catenin at a later time point in pancreas development causes enhanced proliferation that results in a dramatic increase in pancreas organ size. Taken together, these data suggest a previously unappreciated temporal/spatial role forβ-catenin signaling in the regulation of pancreas organ growth.
Agonist- and depolarization-induced signals for myosin light chain phosphorylation and force generation of cultured vascular smooth muscle cells
Authors: Woodsome Terence P. , Polzin Atsuko , Kitazawa Kazuyo , Eto Masumi , Kitazawa Toshio
Published: April 2006

Phosphorylation of myosin light chain (MLC) and contraction of differentiated smooth muscle cells in vascular walls are regulated by Ca2+-dependent activation of MLC kinase, and by Rho-kinase- or protein-kinases-C-dependent inhibition of MLC phosphatase (MLCP). We examined regulatory pathways for MLC kinase and MLCP in cultured vascular smooth muscle cells (VSMCs), and for isometric force generation of VSMCs reconstituted in collagen fibers. Protein levels of RhoA, Rho-kinase and MYPT1 (a regulatory subunit of MLCP) were upregulated in cultured VSMCs, whereas a MLCP inhibitor protein, CPI-17, was downregulated. Endothelin-1 evoked a steady rise in levels of Ca2+, MLC phosphorylation and the contractile force of VSMCs, whereas angiotensin-II induced transient signals. Also, Thr853 phosphorylation of MYPT1 occurred in response to stimuli, but neither agonist induced phosphorylation of MYPT1 at Thr696. Unlike fresh aortic tissues, removal of Ca2+ or addition of voltage-dependent Ca2+-channel blocker did not inhibit contractions of reconstituted VSMC fibers induced by agonists or even high concentrations of extracellular K+ ions. Inhibitors of Ins(1,4,5)P3-receptor and Rho-kinase antagonized agonist-induced or high-K+-induced contraction in both reconstituted fibers and fresh tissues. These results indicate that both Ins(1,4,5)P3-induced Ca2+ release and Rho-kinase-induced MYPT1 phosphorylation at Thr853 play pivotal roles in MLC phosphorylation of cultured VSMCs where either Ca2+-influx or CPI-17-MLCP signaling is downregulated.
A simplified method in the static plastic analysis of corrugated steel panels
Authors: Liang Y. H , Louca L. A , Hobbs R. E
Published: April 2006

Using normality theory and a simplified beam model, a theoretical method is built up to evaluate the relationship between the central deflection of a corrugated panel and external uniformly distributed pressure load. The interaction between the bending moment and the membrane force in the panel is included, as well as the influence of connections. This theoretical model is calibrated against finite element analyses. The results show encouraging agreement.
Full-field pulsed magnetophotoelasticity – experimental implementation
Authors: Gibson S , Jewell G. W , Tomlinson R. A
Published: April 2006

This paper contains a description of the experimental procedure employed when using a pulsed magnetopolariscope (PMP) and some initial full-field through-thickness measurements of the stress distribution present in samples containing three-dimensional stresses. The instrument uses the theory of magnetophotoelasticity (MPE), which is an experimental stress analysis technique that involves the application of a magnetic field to a birefringent model within a polariscope. MPE was developed for through-thickness stress measurement where the integrated through-thickness birefringent measurement disguises the actual stress distribution. The technique is used mainly in toughened glass, where the through-thickness distribution can reduce its overall strength and so its determination is important.

To date, MPE has provided a single-point two-dimensional through-thickness measurement and the analysis time is prohibitive for the investigation of an area that may contain high localized stresses. The pulsed magnetopolariscope (PMP) has been designed to enable the application of full-field three-dimensional MPE, described in a companion paper. Using a proof-of-concept PMP, several experimental measurements were made; these were promising and demonstrate the potential of the new instrument. Further development of this technique presents several exciting possibilities, including a tool for the measurement of the distribution of the principal stress difference seen in a general three-dimensional model.
An experimental assessment of lawnmower blade loading
Authors: Andrews S , Wild P , Strong D
Published: April 2006

An experimental study of the loading to which a lawnmower blade is subjected during normal operation has been performed. The blade of a consumer-grade walk-behind electric lawnmower was instrumented with strain gauge bridges and strain data were collected using a slip ring assembly and personal-computer-based data acquisition system with integral amplifier. Blade strains were monitored over a range of grass-cutting conditions. It was found that blade strain was dependent principally upon the rotational speed, with no perceptible effect due to cutting conditions, other than the indirect effect due to blade speed changes. The measured strains also compared well with calculated strains, particularly at low speeds. At higher speeds, there were small differences between measured and calculated strains and these differences are attributed to the effects of blade deflection. The results of this study suggest that blade stresses can be accurately calculated using models which include only the effects of rotation. Relative to other possible types of loading (i.e. aerodynamic and grass impacts), rotational effects are easily modelled. At higher speeds, models should include the effects of large-displacement non-linearities to account for the effects of blade deflection. These findings will enable engineers and designers to perform analyses that will minimize the repetitive and often extended empirical testing in arriving at a final mower blade design. Where empirical testing is required, these results indicate that such testing should be based on blade rotation rather than on static fixtures in which cyclic deflection of the blade is applied.
Aerodynamic research using the Moulton small-wheeled bicycle
Authors: Moulton A. E. , Hadland A , Milliken D. L.
Published: April 2006

This short article describes aerodynamic research carried out using the Moulton small-wheeled bicycle. Alex Moulton's initial research, applying streamlined cowlings to his early small-wheeled bicycles, is briefly described. His later collaboration with Douglas Milliken is covered in greater detail. Milliken's many experiments with fairings included wind tunnel tests in crosswinds, an aspect of bicycle science rarely investigated hitherto. An important finding was the ability for a streamlined bicycle under certain conditions to sail. The Moulton—Milliken collaboration led to the development of fully streamlined bicycles, using the conventional riding position, which twice broke a speed record.
Hub shape effects on the inducers performance under cavitation
Authors: Mejri I , Bakir F , Kouidri S , Noguera R , Rey R
Published: April 2006

In this work, experimental and three-dimensional numerical simulations are pursued with the intent of elucidating the differences that the hub shape has on three inducer performances and on other important engineering properties in cavitating and non-cavitating regimes. Two inducers have a cylindrical hub and the third one has a conical hub. They are noted as BH inducer (big hub), SH inducer (small hub), and CH inducer (conical hub). These machines were designed with the goal to reduce the amount of cavitation and vibration, on the one hand, and to improve the overall performance, on the other hand. Both sets of experimental and numerical data suggest that the cavitating and non-cavitating performances are affected by changes in the hub shape. The hub configuration and cavitation numbers considered give rise to various cavitation structures on the suction side of the blades, characterized — at some flow rates — by recirculating flow regions and backflow vortices. The results show the relative superiority of the CH inducer through the critical cavitation coefficient of 5 per cent, even if this inducer is very unstable for all flow rates. It was also found that the BH inducer is the most stable and that for a 15 per cent head drop, the three inducers have quite the same performances.

The main experimental and numerical results presented here concern the overall performances, especially the hydrodynamic mechanism of head drop and the visualization of three-dimensional flow structures. We also present the vibratory behaviour versus the flow rate and the suction pressure. The computational three-dimensional flow in non-cavitating regimes enabled us to explain the unstable and cavitating operation for off-design conditions. The numerical computation in cavitating flows is carried out using the computational fluid dynamics (CFD) software CFX-TASCFlow2.12, which cavitation model was validated on our BH inducer.
Three-dimensional quasi-unsteady flow simulation in a centrifugal pump: Comparison with experimental results
Authors: Asuaje M , Bakir F , Kergourlay G , Noguera R , Rey R
Published: April 2006

This work aims at assessing the velocity field, pressure, and radial thrust distribution inside a centrifugal pump (ENSIVAL-MORET MP 250.200.400 pump, diameter = 408 mm, five blades, specific speed = 32) at various flowrates. A three-dimensional flow simulation is first presented for the isolated impeller. A three-dimensional quasi-unsteady flow simulation of the impeller—volute assembly is then performed for several impeller blades and volute tongue relative positions. The computed pressure fields enable to evaluate the radial thrust on the pump shaft and to study its variations with the flowrates. The computed pressure fluctuations match the measures obtained from 10 unsteady pressure sensors placed on the impeller shroud and volute, so that the validity of the computed radial thrust is acknowledged.
Micro-elastohydrodynamic lubrication of coated cylinders using coupled differential deflection method
Authors: Elsharkawy A. A. , Holmes M. J. A. , Evans H. P. , Snidle R. W.
Published: April 2006

A numerical solution for the micro-elastohydrodynamic lubrication (EHL) problem of two coated elastic bodies in line contact is presented. This incorporates non-Newtonian behaviour of the lubricant, using an Eyring-type non-linear viscous model. The surface elastic deformations are computed from full elasticity analysis of layered elastic half-spaces. The coupled differential deflection method is used in the numerical solution of the micro-EHL mathematical model. Results are presented for smooth surface, steady-state problems that compare the influence of coating elastic modulus and coating thickness on calculated lubricant pressure and film thickness distributions. Some transient results are also included, where the effect of coatings on a single ridge feature and on a rough surface in rolling/sliding contact is examined.
Boussinesq-Cerruti functions and a simple technique for substantial acceleration of subsurface stress computations in elastic half-spaces
Authors: Nikas George K
Published: April 2006

The Boussinesq-Cerruti potential functions for the calculation of subsurface stresses and displacements in elastic half-spaces are presented in full and in clear formulation. They were expanded and optimized for fast computational analysis of subsurface stress and displacement fields, including fatigue life computations. A simple technique was developed to accelerate the computations by omitting the stress contribution of parts of the loaded boundary if the said contribution is lower than a predetermined limit. The error of this approximation was defined and formulated for the comparison of various solutions. The technique was applied in a computationally intensive problem involving a rolling-sliding-spinning elastohydrody-namic, elliptical, heavily loaded contact, and three-dimensional subsurface stress and displacement fields were calculated with hundreds of thousands of surface gridpoints and tens of thousands of subsurface gridpoints, followed by the computation of fatigue lives of the contacting solids. Results are presented for a smooth contact, but the method has been applied and is particularly useful for rough contacts as well. The results show a two to ten-fold acceleration of computations, which reduces the computational times by 50-95 per cent for a negligible-to-small loss of accuracy. In real terms, this means reduction of computer time from days to hours or from hours to minutes.
10,10′-Dimethyl-9,9′-biacridine Acting as a Novel Organic Outer-Sphere Electron-Transfer Reagent
Authors: Fukuzumi Shunichi , Tokuda Yoshihiro
Published: April 2006

Rates of Electron-transfer (ET) reactions from 10,10′-dimethyl-9,9′-biacridine [(AcrH)2] to various inorganic and organic one-electron oxidants depend solely on the one-electron reduction potentials of the oxidants irrespective of the size of the oxidants, indicating that (AcrH)2 acts as a novel outer-sphere organic ET reagent.
Reaction of Hex-1-enopyranose-3-uroses with Organometallic Reagents. Regio- and Stereoselective Introduction of Allylic Substituents on Pyranose Ring
Authors: Takiya Masashi , Ishii Mari , Shibata Koichi , Mikami Yuji , Mitsunobu Oyo
Published: April 2006

4,6-O-Benzylidene-1,2-dideoxy-d-threo-hex-1-enopyranose-3-urose reacted with allylic organometallic reagents, CH2=CR–CH2–Metal [R = H or CH3; Metal = MgCl, AlEt2, or Ti(OPri)3], to selectively give 4,6-O-benzylidene-1,2-dideoxy-3-C-(2-propenyl- or 2-methyl-2-propenyl)-d-lyxo-hex-1-enopyranose. On the other hand, the erythro isomer gave 3-C-(2-propenyl- or 2-methyl-2-propenyl)-d-arabino-hex-1-enopyranose and the corresponding ribo isomer in a ratio ranging from 1 : 1 to 10 : 1
Synthesis of Chiral Bitetralin-strapped “Twin Coronet” Porphyrins. Catalytic and Asymmetric Epoxidation of Styrene Derivatives
Authors: Naruta Yoshinori , Ishihara Nobuo , Tani Fumito , Maruyama Kazuhiro
Published: April 2006

“Twin-coronet” porphyrins bearing optically active 1,1′-bitetrahydronaphthalene derivatives on the both faces of the porphyrin were prepared as enantioselective oxidation catalysts modeling on cytochrome P-450s. The eclipsed isomer of the corresponding iron(III) porphyrins catalyzed epoxidation of styrenes substituted with electron-withdrawing groups in high e.e. (61–89%) and high product selectivity.
Novel DNA Analog for Potential Gene Regulating Agent. A Convenient Synthesis of α-Oligodeoxyribonucleotide Phosphorothioate Bearing 3′-Monophosphate
Authors: Shinozuka Kazuo , Morita Tsutomu , Hirota Yoshiki , Sawai Hiroaki
Published: April 2006

α-2′-Deoxyoctathymydilic acid phosphorothioate analog bearing 3′-monophosphate was conveniently synthesized via phosphoramidite method using a riboadenosine attached Teflon-based solid support. The obtained oligomer exhibited enhanced stability toward the digestion by common nucleases.
Superconducting Transition of a Grease-Coated Crystal of κ-(BEDT-TTF)2Cu[N(CN)2]Cl
Authors: Kobayashi Hayao , Bun Kozo , Miyamoto Akihito , Naito Toshio , Kato Reizo , Kobayashi Akiko , Williams Jack M
Published: April 2006

Superconducting transition of the grease-coated crystal of κ-(BEDT-TTF)2Cu[N(CN)2]Cl has been confirmed. There are at least three types of these crystals with different resistivity behaviors, of which the crystal exhibiting a resistivity anomaly around 50 K, undergoes a superconducting transition at 12.5 K, when it is coated with Apiezon L grease.
Tetiakis(trimethylsilyl)silane-Mediated Photochemical Alkylation of Heteroaromatic Bases with Alkyl Halides
Authors: Togo Hideo , Hayashi Ken , Yokoyama Masataka
Published: April 2006

Alkyl halides reacted with protonated heteroaromatic bases in the presence of tetrakis(trimethylsilyl)silane (TTMS) under irradiation with high pressure mercury lamp to give the corresponding alkylated heteroaromatic bases. This is the first report on the photochemical use of TTMS for organic synthesis.
Compositionally and functionally distinct editosomes in Trypanosoma brucei
Authors: Panigrahi Aswini K. , Ernst Nancy Lewis , Domingo Gonzalo J. , Fleck Michele , Salavati Reza , Stuart Kenneth D.
Published: April 2006

Uridylate insertion/deletion RNA editing in Trypanosoma brucei mitochondria is catalyzed by a multiprotein complex, the ∼20S editosome. Editosomes purified via three related tagged RNase III proteins, KREN1 (KREPB1/TbMP90), KREPB2 (TbMP67), and KREN2 (KREPB3/TbMP61), had very similar but nonidentical protein compositions, and only the tagged member of these three RNase III proteins was identified in each respective complex. Three new editosome proteins were also identified in these complexes. Each tagged complex catalyzed both precleaved insertion and deletion editing in vitro. However, KREN1 complexes cleaved deletion but not insertion editing sites in vitro, and, conversely, KREN2 complexes cleaved insertion but not deletion editing sites. These specific nuclease activities were abolished by mutations in the putative RNase III catalytic domain of the respective proteins. Thus editosomes appear to be heterogeneous in composition with KREN1 complexes catalyzing cleavage of deletion sites and KREN2 complexes cleaving insertion sites while both can catalyze the U addition, U removal, and ligation steps of editing.
Feasibility of Standardization of Serum C-Peptide Immunoassays with Isotope-Dilution Liquid Chromatography–Tandem Mass Spectrometry
Authors: Rodríguez Cabaleiro Diego , Stöckl Dietmar , Kaufman Jean M , Fiers Tom , Thienpont Linda M
Published: April 2006

Background: Serum C-peptide concentrations reflect pancreatic function in different clinical and diagnostic settings; however, the utility of C-peptide testing is limited by the lack of standardized commercial immunoassays. Standardization can best be done by split-sample comparison with a hierarchically higher reference measurement procedure with a set of native sera. For serum peptides, isotope-dilution liquid chromatography–mass spectrometry (ID-LC/MS) is recommended as a reference measurement procedure.

Methods: We evaluated the analytical performance characteristics of an ID-LC/tandem MS procedure for measurement of serum C-peptide after a 2-step solid-phase extraction. To investigate the feasibility of this procedure for use in standardization, we also performed a method comparison with 3 representative commercial assays.

Results: The ID-LC/tandem MS procedure showed maximum within-run, between-run, and total CVs on dedicated sera (C-peptide concentrations, 1.6 and 4.0 μg/L) of 2.1%, 2.5%, and 2.9%, respectively; an accuracy of 94.6%–104.1%; a minimum trueness of 98.1% (95% confidence interval, 96.2%–100.0%), and limits of quantification and detection of 0.15 and 0.03 μg/L, respectively. Deming linear regression analysis of the method-comparison data showed that the immunoassays correlated well with ID-MS and were specific, but lacked intercomparability and trueness. We propose that the deficiencies can be resolved by recalibration on the basis of the method comparison.

Conclusions: The ID-LC/tandem MS procedure is suitable for specific and accurate measurement of basal and stimulated serum concentrations of proinsulin C-peptide fragment 33–63 and is suitable for use in standardization of C-peptide immunoassays.
Increased Pregnancy-Associated Plasma Protein-A as a Marker for Peripheral Atherosclerosis: Results from the Linz Peripheral Arterial Disease Study
Authors: Mueller Thomas , Dieplinger Benjamin , Poelz Werner , Haltmayer Meinhard
Published: April 2006

Background: The aim of the present investigation was to test the hypothesis that pregnancy-associated plasma protein-A (PAPP-A), a zinc-binding metalloproteinase implicated in acute coronary syndrome, is associated with atherosclerotic peripheral arterial disease (PAD).

Methods: The study comprised 433 patients with symptomatic atherosclerotic PAD (i.e., chronic limb ischemia) and 433 controls matched to the patients with PAD in a 1:1 design by sex, age (±2 years), and diabetes mellitus status. Serum PAPP-A concentrations were measured with an enzymatically amplified 2-step sandwich-type immunoassay.

Results: The entire study sample included 612 male and 254 female patients with a median age of 68 years. The median PAPP-A value was higher in the patients with PAD than in the referents (0.81 vs 0.64 mU/L; P <0.001). After we adjusted for several possible confounding variables with multivariable logistic regression, odds ratios for PAD were 1.59 (95% confidence interval, 1.00–2.52; P = 0.049), 2.28 (1.45–3.61; P <0.001), and 2.86 (1.78–4.59; P <0.001) in the 2nd, 3rd, and 4th quartiles of serum PAPP-A concentrations compared with the first quartile. In the present study, PAPP-A added to the predictive value of other markers commonly in use.

Conclusions: PAPP-A was associated with atherosclerotic PAD in the elderly sample studied. Because atherosclerotic PAD is considered an indicator of systemic atherosclerotic disease in elderly patients, the present results indicate that circulating PAPP-A may be a marker for systemic atherosclerotic disease.
Normal Misbehavior: Scientists Talk about the Ethics of Research
Authors: De Vries Raymond , Anderson Melissa S. , Martinson Brian C.
Published: April 2006

Those concerned with protecting the integrity of science generally focus on the serious but rare infractions of falsification, fabrication, and plagiarism (FFP). While the violations of FFP are clear threats to the quality of scientific work and public trust in science, are they the behaviors that researchers themselves find most troubling? Noticing that scientists seldom are asked to report their perceptions of the behaviors that pose problems for the enterprise of science, we conducted six focus groups with researchers from major research universities. A total of 51 scientists participated in our focus-group discussions, which lasted from 1.5 to 2 hours each. We found that while researchers were aware of the problems of FFP, in their eyes misconduct generally is associated with more mundane, everyday problems in the work environment. These more common problems fall into four categories: The meaning of data, the rules of science, life with colleagues, and the pressures of production in science. Focus on the “normal misbehaviors” that are part of the ordinary life of researchers allows us to see the way the organization of science generates both compliance and deviance from ethical norms.
Scientists' Perceptions of Organizational Justice and Self-Reported Misbehaviors
Authors: Martinson Brian C. , Anderson Melissa S. , Crain A. Lauren , De Vries Raymond
Published: April 2006

Policymakers concerned about maintaining the integrity of science have recently expanded their attention from a focus on misbehaving individuals to characteristics of the environments in which scientists work. Little empirical evidence exists about the role of organizational justice in promoting or hindering scientific integrity. Our findings indicate that when scientists believe they are being treated unfairly they are more likely to behave in ways that compromise the integrity of science. Perceived violations of distributive and procedural justice were positively associated with self-reports of misbehavior among scientists.
Visual Display Terminal Work and Sick Building Syndrome—The Role of Psychosocial Distress in the Relationship
Authors: Kubo Tatsuhiko , Mizoue Tetsuya , Ide Reiko , Tokui Noritaka , Fujino Yoshihisa , Minh Pham Truong , Shirane Kiyoyumi , Matsumoto Tetsuro , Yoshimura Takesumi
Published: April 2006

Visual Display Terminal Work and Sick Building Syndrome—The Role of Psychosocial Distress in the Relationship: Tatsuhiko Kubo, et al. Department of Clinical Epidemiology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health—The present study investigated the association between visual display terminal (VDT) work and sick building syndrome (SBS) and the role of psychosocial factors in the relationship. Subjects were 2,161 Japanese office workers who responded to a cross‐sectional anonymous self‐administered questionnaire survey. Questions included were derived from the Miljömedicin 040, a validated questionnaire on SBS symptoms. After exclusion of data with missing information, data for 1,881 subjects were used for analysis. Multivariate logistic regression was used to estimate the odds ratio for SBS with adjustment for potential confounding factors, including psychosocial work stress. In multivariate analysis, the odds ratio for SBS was significantly elevated for men engaged in VDT work for 4 or more hours a day (OR=2.5, 95%CI: 1.0, 5.9) compared with less than 1 hour a day, showing a significant trend association (P for trend=0.04). In women, although the odds ratio for SBS with VDT use of 4 or more hours a day was somewhat elevated with adjustment for non‐psychosocial factors (OR=1.5, 95%CI: 0.5, 4.3), the increase was greatly attenuated after adjustment for psychosocial work distress (OR=1.1). In conclusion, our study suggests that extended hours of VDT use might be related to increased SBS symptoms. Moreover, psychosocial distress related to VDT work might mediate the relationship between VDT use and SBS symptoms in women.
Expression of Heme Oxygenase‐1 in the Lungs of Rats Exposed to Crystalline Silica
Authors: Nagatomo Hiroko , Morimoto Yasuo , Oyabu Takako , Hirohashi Masami , Ogami Akira , Yamato Hiroshi , Kuroda Kaori , Higashi Toshiaki , Tanaka Isamu
Published: April 2006

Expression of Heme Oxygenase‐1 in the Lungs of Rats Exposed to Crystalline Silica: Hiroko Nagatomo, et al. Department of Occupational Pneumology, Institute of Industrial and Ecological Sciences, University of Occupational and Environmental Health—Oxidative stress is thought to be the pathogenesis of pulmonary fibrosis induced by particles, and heme oxygenase‐1 (HO‐1) protects lung tissue against oxidative stress. We hypothesized that HO‐1 is also associated with oxidative lung injury caused by exposure to particles. The present study was conducted to investigate the time course of HO‐1 expression of lungs exposed to crystalline silica in vivo. Male Wistar rats were administered 1 mg or 2 mg of crystalline silica suspended in saline by a single intratracheal instillation and were sacrificed at 3 d, 1 wk, 1 month, 3 months and 6 months of recovery time. The expression of HO‐1 was observed by western blot analysis and immunostaining. Protein levels of HO‐1 were increased compared to the controls at 3 d, and from 1 month to 6 months following intratracheal instillation of 2 mg of crystalline silica. The levels of HO‐1 were increased compared to the controls from 1 month to 6 months following intratracheal instillation of 1 mg of crystalline silica. Many HO‐1 positive cells were found particularly in the alveolar macrophages during immunostaining. These findings suggest that HO‐1 is related to lung injury arising from exposure to crystalline silica.
Two New Criteria of the Metabolic Syndrome: Prevalence and the Association with Brachial‐Ankle Pulse Wave Velocity in Japanese Male Workers
Authors: Miyaki Koichi , Hara Asako , Naito Mariko , Naito Toru , Nakayama Takeo
Published: April 2006

Two New Criteria of the Metabolic Syndrome: Prevalence and the Association with Brachial‐Ankle Pulse Wave Velocity in Japanese Male Workers: Koichi Miyaki, et al. Department of Preventive Medicine and Public Health, School of Medicine, Keio University—In 1998 and 2001, The World Health Organization and the National Cholesterol Education Program Adult Treatment Panel III proposed working criteria for the metabolic syndrome (MS), but they are not perfect for use in diverse ethnicities. In 2005, the International Diabetes Federation (IDF) and eight societies in Japan respectively proposed new criteria. However, there has been no report regarding the application of these new criteria in Japanese workplaces. We conducted a cross‐sectional study of 377 healthy Japanese men aged 20–64 yr who worked in a chemical factory in Kanagawa, Japan. Participants completed a self‐reported questionnaire, underwent a physical examination including waist measurements and brachial‐ankle pulse wave velocity (baPWV), and provided overnight fasting blood samples. The prevalence of MS in Japanese men was 17.0% and 13.5% according to the new IDF and Japanese criteria respectively. In both of the new criteria, baPWV was significantly higher in those with MS than those without MS (1,563 ± 264.2 vs 1,362 ± 204.6 cm/sec, p<0.001 in the new IDF criterion; 1,574 ± 265.2 vs 1,368 ± 209.1 cm/sec, p<0.001 in the Japanese criterion). In the analysis of the 5 or 6 subgroups stratified according to the number of MS components, baPWV increased significantly with increasing number of MS components (p for trend<0.01 in both criteria). The new IDF and Japanese criterion are both good for diagnosing MS among Japanese because a linear increase in baPWV occurred with increasing MS components after adjustment for potential confounding factors. Further studies are expected using these new criteria.
Hazards of X‐Ray Radiation on the Quantitative and Phagocytic Functions of Polymorphonuclear Neutrophils in X‐Ray Technicians
Authors: Meo Sultan A , Drees Abdul Majeed Al , Zadi Syed Za , Damgh Salah Al , Al‐Tuwaijri Ali S
Published: April 2006

Hazards of X‐Ray Radiation on the Quantitative and Phagocytic Functions of Polymorphonuclear Neutrophils in X‐Ray Technicians: Sultan A Meo, et al. Department of Physiology, College of Medicine, King Khalid University Hospital, Saudi Arabia—Over exposure to X‐ray radiation is detrimental to the living cells and may lead to development of life‐threatening diseases. It is intuitive to postulate that a low level exposure may lead to functional abnormalities in human immune cells. Therefore, the objective of the present study was to study the effects of X‐ray radiation on the total leukocyte count (TLC) and phagocytic activity of Polymorphonuclear neutrophils (PMN). A group of 42 apparently healthy X‐ray technicians were recruited with age ranging from 25–50 years. They were matched with another group of 42 control healthy volunteer subjects in terms of age, sex and ethnic variation. The mean exposure level of X‐ray radiation in X‐ray technicians was 72.4 mrem per calendar quarter and 289.6 mrem per year. TLC was performed by using a Beckman Coulter counter and phagocytic activity of whole blood and PMN was determined by measuring chemiluminescence (CL) response with a chemiluminescence luminometer. The mean value of CL response was significantly decreased (p<0.0005) in X‐ray technicians, even though they had low levels of exposure, compared to their controls. However, no significant difference was observed in TLC between the two groups at this low level of exposure. Exposure to X‐ray radiation decreases the physiological functions of PMN as measured by decreasing chemiluminescence response even at low levels of exposure.