bluuebunny/crossref_metadata_2025 huggingface dataset:
PKC412 inhibits the zinc finger 198-fibroblast growth factor receptor 1 fusion tyrosine kinase and is active in treatment of stem cell myeloproliferative disorder
Authors: Chen Jing , DeAngelo Daniel J. , Kutok Jeffery L. , Williams Ifor R. , Lee Benjamin H. , Wadleigh Martha , Duclos Nicole , Cohen Sarah , Adelsperger Jennifer , Okabe Rachel , Coburn Allison , Galinsky Ilene , Huntly Brian , Cohen Pamela S. , Meyer Thomas , Fabbro Doriano , Roesel Johannes , Banerji Lolita , Griffin James D. , Xiao Sheng , Fletcher Jonathan A. , Stone Richard M. , Gilliland D. Gary
Published: September 2004

Human stem cell leukemia-lymphoma syndrome usually presents itself as a myeloproliferative disorder (MPD) that evolves to acute myeloid leukemia and/or lymphoma. The syndrome associated with t(8;13)(p11;q12) results in expression of the ZNF198-fibroblast growth factor receptor (FGFR) 1 fusion tyrosine kinase. Current empirically derived cytotoxic chemotherapy is inadequate for treatment of this disease. We hypothesized that small-molecule inhibitors of the ZNF198-FGFR1 fusion would have therapeutic efficacy. We characterized the transforming activity of ZNF198-FGFR1 in hematopoietic cells
in vitro
and
in vivo
. Expression of ZNF198-FGFR1 in primary murine hematopoietic cells caused a myeloproliferative syndrome in mice that recapitulated the human MPD phenotype. Transformation in these assays, and activation of the downstream effector molecules PLC-γ, STAT5, and phosphatidylinositol 3-kinase/AKT, required the proline-rich domains, but not the ZNF domains, of ZNF198. A small-molecule tyrosine kinase inhibitor, PKC412 (
N
-benzoyl-staurosporine) effectively inhibited ZNF198-FGFR1 tyrosine kinase activity and activation of downstream effector pathways, and inhibited proliferation of ZNF198-FGFR1 transformed Ba/F3 cells. Furthermore, treatment with PKC412 resulted in statistically significant prolongation of survival in the murine model of ZNF198-FGFR1-induced MPD. Based in part on these data, PKC412 was administered to a patient with t(8;13)(p11;q12) and was efficacious in treatment of progressive myeloproliferative disorder with organomegaly. Therefore, PKC412 may be a useful therapy for treatment of human stem cell leukemia-lymphoma syndrome.
Evidence for landscape-level, pollen-mediated gene flow from genetically modified creeping bentgrass with
CP4 EPSPS
as a marker
Authors: Watrud Lidia S. , Lee E. Henry , Fairbrother Anne , Burdick Connie , Reichman Jay R. , Bollman Mike , Storm Marjorie , King George , Van de Water Peter K.
Published: September 2004

Sampling methods and results of a gene flow study are described that will be of interest to plant scientists, evolutionary biologists, ecologists, and stakeholders assessing the environmental safety of transgenic crops. This study documents gene flow on a landscape level from creeping bentgrass (
Agrostis stolonifera
L.), one of the first wind-pollinated, perennial, and highly outcrossing transgenic crops being developed for commercial use. Most of the gene flow occurred within 2 km in the direction of prevailing winds. The maximal gene flow distances observed were 21 km and 14 km in sentinel and resident plants, respectively, that were located in primarily nonagronomic habitats. The selectable marker used in these studies was the
CP4 EPSPS
gene derived from
Agrobacterium
spp. strain CP4 that encodes 5-enol-pyruvylshikimate-3-phosphate synthase and confers resistance to glyphosate herbicide. Evidence for gene flow to 75 of 138 sentinel plants of
A. stolonifera
and to 29 of 69 resident
Agrostis
plants was based on seedling progeny survival after spraying with glyphosate in greenhouse assays and positive TraitChek, PCR, and sequencing results. Additional studies are needed to determine whether introgression will occur and whether it will affect the ecological fitness of progeny or the structure of plant communities in which transgenic progeny may become established.
Bulk-solvent and hydration-shell fluctuations, similar to α- and β-fluctuations in glasses, control protein motions and functions
Authors: Fenimore P. W. , Frauenfelder Hans , McMahon B. H. , Young R. D.
Published: September 2004

The concept that proteins exist in numerous different conformations or conformational substates, described by an energy landscape, is now accepted, but the dynamics is incompletely explored. We have previously shown that large-scale protein motions, such as the exit of a ligand from the protein interior, follow the dielectric fluctuations in the bulk solvent. Here, we demonstrate, by using mean-square displacements (msd) from Mössbauer and neutron-scattering experiments, that fluctuations in the hydration shell control fast fluctuations in the protein. We call the first type solvent-slaved or α-fluctuations and the second type hydration-shell-coupled or β-fluctuations. Solvent-slaved motions are similar to the α-fluctuations in glasses. Their temperature dependence can be approximated by a Vogel-Tammann-Fulcher relation and they are absent in a solid environment. Hydration-shell-coupled fluctuations are similar to the β-relaxation in glasses. They can be approximated by a Ferry or an Arrhenius relation, are much reduced or absent in dehydrated proteins, and occur in hydrated proteins even if embedded in a solid. They can be responsible for internal processes such as the migration of ligands within myoglobin. The existence of two functionally important fluctuations in proteins, one slaved to bulk motions and the other coupled to hydration-shell fluctuations, implies that the environment can control protein functions through different avenues and that no real protein transition occurs at ≈200 K. The large number of conformational substates is essential; proteins cannot function without this reservoir of entropy, which resides mainly in the hydration shell.
A poxvirus protein forms a complex with left-handed Z-DNA: Crystal structure of a Yatapoxvirus Zα bound to DNA
Authors: Ha Sung Chul , Lokanath Neratur K. , Van Quyen Dong , Wu Chun Ai , Lowenhaupt Ky , Rich Alexander , Kim Yang-Gyun , Kim Kyeong Kyu
Published: September 2004

A conserved feature of poxviruses is a protein, well characterized as E3L in vaccinia virus, that confers IFN resistance on the virus. This protein comprises two domains, an N-terminal Z-DNA-binding protein domain (Zα) and a C-terminal double-stranded RNA-binding domain. Both are required for pathogenicity of vaccinia virus in mice infected by intracranial injection. Here, we describe the crystal structure of the Zα domain from the E3L-like protein of Yaba-like disease virus, a Yatapoxvirus, in a complex with Z-DNA, solved at a 2.0-Å resolution. The DNA contacting surface of Yaba-like disease virus Zα
E3L
closely resembles that of other structurally defined members of the Zα family, although some variability exists in the β-hairpin region. In contrast to the Z-DNA-contacting surface, the nonbinding surface of members of the Zα family are unrelated; this surface may effect protein-specific interactions. The presence of the conserved and tailored Z-DNA-binding surface, which interacts specifically with the zigzag backbone and
syn
base diagnostic of the Z-form, reinforces the importance to poxvirus infection of the ability of this protein to recognize the Z-conformation.
Entropy of dialogues creates coherent structures in e-mail traffic
Authors: Eckmann Jean-Pierre , Moses Elisha , Sergi Danilo
Published: September 2004

We study the dynamic network of e-mail traffic and find that it develops self-organized coherent structures similar to those appearing in many nonlinear dynamic systems. Such structures are uncovered by a general information theoretic approach to dynamic networks based on the analysis of synchronization among trios of users. In the e-mail network, coherent structures arise from temporal correlations when users act in a synchronized manner. These temporally linked structures turn out to be functional, goal-oriented aggregates that must react in real time to changing objectives and challenges (e.g., committees at a university). In contrast, static structures turn out to be related to organizational units (e.g., departments).
Key premises, a guide to Aedes aegypti (Diptera: Culicidae) surveillance and control
Authors: Chadee D.D.
Published: September 2004

The population densities of Aedes aegypti Linneaus in four towns in Trinidad were studied using standard house-to-house inspections of all water-holding containers to determine whether persistently positive containers and premises existed over a three-month period in the wet season, from May to July 2002. From a total of 1503 houses inspected, 223 were positive with 41 persistently positive over the three month period and classified as ‘key premises’. The definition of the term key premises is described and the rationale for its utilization discussed. A total of 24,439 containers was inspected from Santa Margarita (6407), Mt Lambert (5709), St Augustine (5384) and Curepe (6939) of which 1.3% or 334 containers were positive for A. aegypti larvae and pupae. A total of 16,507 immatures of A. aegypti were retrieved from these containers which comprised 17 container types but when these were ranked according to productivity levels, only water drums (average 53.5%), buckets (22.2%), tubs and basins (8.0%), water tanks (5.4%), brick holes (4.2%) and tyres (2.0%) were significant (P < 0.001) producers. The role that key premises play in the introduction and re-infestation of A. aegypti-free communities is described and illustrated. These results suggest that A. aegypti control programmes could be more cost effective and sustainable by concentrating efforts on key premises and key containers to control mosquito densities and Dengue transmission while reducing manpower needs and insecticide use.
FGF-18 is upregulated in the postnatal rat lung and enhances elastogenesis in myofibroblasts
Authors: Chailley-Heu Bernadette , Boucherat Olivier , Barlier-Mur Anne-Marie , Bourbon Jacques R.
Published: September 2004

The fibroblast growth factors (FGFs) are key players in fetal lung development, but little is known about their status in postnatal lung. Here, we investigated the expression pattern of FGF-18 transcripts through the perinatal period and evidenced a sevenfold increase after birth that paralleled changes in elastin expression. In vitro, recombinant human (rh)FGF-18 had a mitogenic activity on day 21 fetal rat lung fibroblasts and stimulated its own expression in the latter, whereas FGF-2 inhibited it. At 50 or 100 ng/ml, rhFGF-18 increased the expression of α-smooth muscle actin (α-SMA; 2.5-fold), a characteristic marker of myofibroblasts, of tropoelastin (6.5-fold), of lysyl oxidase (2-fold), and of fibulins 1 and 5 (8- and 2.2-fold) in confluent fibroblasts isolated from fetal day 21 lung; similar results were obtained with fibroblasts from day 3 postnatal lungs. Elastin protein expression was also slightly increased in fetal fibroblasts. Lung analysis on day 4 in rat pups that had received rhFGF-18 (3 μg) on days 0 and 1 showed a 1.7-fold increase of tropoelastin transcripts, whereas α-SMA transcripts were unchanged. In contrast, rhFGF-2 markedly decreased expression of elastin in vitro and in vivo and of fibulin 5 in vitro. In addition, vitamin A, which is known to enhance alveolar development, elevated FGF-18 and elastin expressions in day 2 lungs, thus advancing the biological increase. We postulate that FGF-18 is involved in postnatal lung development through stimulating myofibroblast proliferation and differentiation.
Soluble guanylyl cyclase during postnatal porcine pulmonary maturation
Authors: Moreno Laura , Gonzalez-Luis Gema , Cogolludo Angel , Lodi Federica , Lopez-Farre Antonio , Tamargo Juan , Villamor Eduardo , Perez-Vizcaino Francisco
Published: September 2004

The nitric oxide (NO)/cGMP pathway plays a key role in the regulation of pulmonary vascular tone during the transition from the fetal to the neonatal circulation, and it is impaired in pathophysiological conditions such as pulmonary hypertension. In the present study, we have analyzed the changes in the function and expression of soluble guanylyl cyclase (sGC) in pulmonary arteries during early postnatal maturation in isolated third-branch pulmonary arteries from newborn (3–18 h of age) and 2-wk-old piglets. The expression of sGC β1-subunit in pulmonary arteries increased with postnatal age both at the level of mRNA and protein. The catalytic region of porcine sGC β1 was sequenced, showing a 92% homology with the human sequence. This age-dependent increase in sGC expression correlated with increased vasorelaxant responses to the physiological sGC activator NO and to the exogenous sGC activator YC-1, but not to the membrane-permeable cGMP analog 8-bromoguanosine 3′,5′-cyclic monophosphate. In conclusion, an increased expression of sGC in pulmonary conduit arteries from 2-wk-old compared with newborn piglets explains, at least partly, the age-dependent increase in the vasorelaxant response of NO and other activators of sGC.
Region-specific mechanical properties of the human patella tendon
Authors: Haraldsson B. T. , Aagaard P. , Krogsgaard M. , Alkjaer T. , Kjaer M. , Magnusson S. P.
Published: September 2004

The present study investigated the mechanical properties of tendon fascicles from the anterior and posterior human patellar tendon. Collagen fascicles from the anterior and posterior human patellar tendon in healthy young men (mean ± SD, 29.0 ± 4.6 yr, n = 6) were tested in a mechanical rig. A stereoscopic microscope equipped with a digital camera recorded elongation. The fascicles were preconditioned five cycles before the failure test based on pilot data on rat tendon fascicle. Human fascicle length increased with repeated cycles ( P < 0.05); cycle 5 differed from cycle 1 ( P < 0.05), but not cycles 2–4. Peak stress and yield stress were greater for anterior (76.0 ± 9.5 and 56.6 ± 10.4 MPa, respectively) than posterior fascicles (38.5 ± 3.9 and 31.6 ± 2.9 MPa, respectively), P < 0.05, while yield strain was similar (anterior 6.8 ± 1.0%, posterior 8.7 ± 1.4%). Tangent modulus was greater for the anterior (1,231 ± 188 MPa) than the posterior (583 ± 122 MPa) fascicles, P < 0.05. In conclusion, tendon fascicles from the anterior portion of the human patellar tendon in young men displayed considerably greater peak and yield stress and tangent modulus compared with the posterior portion of the tendon, indicating region-specific material properties.
Arterial pressure and muscle sympathetic nerve activity are increased after two hours of sustained but not cyclic hypoxia in healthy humans
Authors: Tamisier Renaud , Anand Amit , Nieto Luz M. , Cunnington David , Weiss J. Woodrow
Published: September 2004

Sustained and episodic hypoxic exposures lead, by two different mechanisms, to an increase in ventilation after the exposure is terminated. Our aim was to investigate whether the pattern of hypoxia, cyclic or sustained, influences sympathetic activity and hemodynamics in the postexposure period. We measured sympathetic activity (peroneal microneurography), hemodynamics [plethysmographic forearm blood flow (FBF), arterial pressure, heart rate], and peripheral chemosensitivity in normal volunteers on two occasions during and after 2 h of either exposure. By design, mean arterial oxygen saturation was lower during sustained relative to cyclic hypoxia. Baseline to recovery muscle sympathetic nerve activity and blood pressure went from 15.7 ± 1.2 to 22.6 ± 1.9 bursts/min ( P < 0.01) and from 85.6 ± 3.2 to 96.1 ± 3.3 mmHg ( P < 0.05) after sustained hypoxia, respectively, but did not exhibit significant change from 13.6 ± 1.5 to 17.3 ± 2.5 bursts/min and 84.9 ± 2.8 to 89.8 ± 2.5 mmHg after cyclic hypoxia. A significant increase in FBF occurred after sustained, but not cyclic, hypoxia, from 2.3 ± 0.2 to 3.29 ± 0.4 and from 2.2 ± 0.1 to 3.1 ± 0.5 ml·min−1·100 g of tissue−1, respectively. Neither exposure altered the ventilatory response to progressive isocapnic hypoxia. Two hours of sustained hypoxia increased not only muscle sympathetic nerve activity but also arterial blood pressure. In contrast, cyclic hypoxia produced slight but not significant changes in hemodynamics and sympathetic activity. These findings suggest the cardiovascular response to acute hypoxia may depend on the intensity, rather than the pattern, of the hypoxic exposure.
Inflammatory markers, D-dimer, pro-thrombotic factors, and physical activity levels in patients with peripheral arterial disease
Authors: McDermott Mary McGrae , Greenland Philip , Guralnik Jack M , Ferrucci Luigi , Green David , Liu Kiang , Criqui Michael H , Schneider Joseph R , Chan Cheeling , Ridker Paul , Pearce William H , Martin Gary , Clark Elizabeth , Taylor Lloyd
Published: September 2004

Men and women with lower extremity peripheral arterial disease (PAD) have reduced physical activity levels compared with persons without PAD. We describe associations between physical activity levels with D-dimer, pro-coagulant factors, and inflammatory markers in patients with PAD. Participants were188 patients with PAD identified from non-invasive vascular laboratories. Physical activity was measured over 7 days with a vertical accelerometer. We measured the ankle brachial index (ABI) and levels of D-dimer, C-reactive protein (CRP), fibrinogen, serum amyloid A (SAA), prothrombin 1.2, t-PA antigen, PAI-1, and the t-PA antigen=PAI-1 ratio. Adjusting for age, sex, race, body mass index, ABI, comorbidities, smoking, total cholesterol=HDL ratio and statin use (for CRP only), we found significant inverse linear associations between physical activity levels and log D-dimer (p 1/4 0.002), log CRP (p < 0.001), fibrinogen (p 1/4 0.014), and log SAA (p 1/4 0.012). There were no significant associations between physical activity levels and other blood factors. In an analysis adjusting for all blood factors simultaneously along with known and potential confounders, log D-dimer was the only blood factor associated significantly with physical activity levels (p 1/4 0.036). Based on these findings, future studies should assess whether interventions to increase physical activity in patients with PAD reduce levels of D-dimer and inflammatory markers.
Endothelial dysfunction in patients with peripheral arterial disease and chronic hyperhomocysteinemia: potential role of ADMA
Authors: Sydow Karsten , Hornig Burkhard , Arakawa Naoshi , Bode-Böger Stefanie M , Tsikas Dimitrios , Münuzel Thomas , Böger Rainer H
Published: September 2004

Hyperhomocysteinemia is associated with an enhanced risk for cardiovascular disease. Patients with peripheral arterial disease (PAD) show an increased prevalence of hyper-homocysteinemia. A decreased biological activity of nitric oxide (NO) may contribute to homocysteine-associated endothelial dysfunction. This study was designed to investigate whether elevated levels of the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA) are involved in endothelial dysfunction in patients with chronic hyperhomocysteinemia and PAD. A total of 76 patients (58 males and 18 females; mean age 65.2 2.0 years) with PAD were included in the analysis and characterized according to demographic variables and cardiovascular risk factors. Flow-dependent vasodilation (FDD) was determined by high-resolution ultrasound in the radial artery. Total plasma homocysteine (plasma tHcy) and ADMA levels were measured by HPLC. Urinary nitrate was quantified using gas chromatography-mass spectrometry. Patients with plasma tHcy in the highest tertile (n 1/4 27; i.e. >10.6 mmol=l) had a mean plasma level of 14.4 1.2 mmol=l compared with 9.9 0.1 mmol=l in those patients in the middle tertile (n 1/4 22; p < 0.05) and 9.4 0.1 mmol=l in those in the lowest tertile (n 1/4 27; i.e. <9.6 mmol=l; p < 0.05). The hyperhomocysteinemic individuals (highest tertile) had a significantly decreased FDD compared with healthy age-matched controls (n 1/4 15) (7.6 1.0 vs 13.0 0.4%; p < 0.05), higher plasma ADMA concentrations (4.0 0.3 vs 2.6 0.3 mmol=l; p < 0.05), and a lower urinary nitrate excretion rate (89.5 13.4 vs 131.3 17.9 mmol=mmol creatinine; p < 0.05) compared with patients with plasma tHcy in the lowest tertile. Multivariate regression analysis including plasma tHcy, ADMA, total cholesterol, diabetes mellitus, smoking, and systolic blood pressure revealed ADMA as the only significant factor determining FDD (p < 0.05). In conclusion, we demonstrated a stronger relationship between impaired endothelial function and elevated ADMA levels in comparison with plasma tHcy concentrations in patients with PAD and chronic hyperhomocysteinemia. This may raise the question of whether different therapeutical options that interact indirectly with plasma tHcy, i.e. treatment with ACE inhibitors and AT1-receptor blockers to reduce ADMA plasma concentrations or L-arginine, could be a beneficial tool for treating patients with hyperhomocysteinemia.
Transcutaneous partial pressure of oxygen after surgical wounds
Authors: McPhail Ian R , Cooper Leslie T , Hodge David O , Cabanela Miguel E , Rooke Thom W
Published: September 2004

Transcutaneous partial pressure of oxygen (TcPO2) predicts wound healing in critical ischemia. However, no studies have controlled for the effect of wounds on TcPO2. In this study, in 24 hip or knee arthroplasty cases without vascular disease, TcPO2 was measured preoperatively at the incision site, contralaterally, and at a reference site on the chest wall. The measurements were repeated at 2 days and 2 months postoperatively and compared. TcPO2, normal preoperatively, decreased at all sites on the second postoperative day (p < 0.001), with a trend toward a greater decrease at the wound (p 1/4 0.09). All wounds healed, and TcPO2 returned to baseline at all sites 2 months postoperatively. In conclusion, acute surgical wounds are associated with a significant and widespread decrease in cutaneous TcPO2 in the setting of normal arterial perfusion. This decrease is likely multifactorial and deserves further investigation.
Synthesis and Secretion of Angiotensin II by the Prostate Gland in Vitro
Authors: O’Mahony Orla A. , Barker Stewart , Puddefoot John R. , Vinson Gavin P.
Published: September 2004

The renin angiotensin system has been shown to have tissue-related functions that are distinct from its systemic roles. We showed that angiotensin II type 1 (AT1) receptors are present in mammalian sperm, and angiotensin II stimulates sperm motility and capacitation. In addition, angiotensin II is present in human seminal plasma at concentrations higher than found in blood. In testing the possibility that the prostate may be the source of seminal plasma angiotensin II, mRNA coding for angiotensinogen, (pro)renin, and angiotensin-converting enzyme were identified by RT-PCR in rat and human prostate and in prostate LNCaP cells, as well as the angiotensin receptors types 1 and 2 (AT1 and AT2) in human tissues and AT1 in rat. In human tissue, immunocytochemistry showed cellular colocalization of renin with the AT1 receptor in secretory epithelial cells. Confirmation of the capacity of the prostate to secrete angiotensin II was shown by the detection of immunoreactive angiotensin in media removed from rat prostate organ cultures and LNCaP cells. Rat prostate angiotensin secretion was enhanced by dihydrotestosterone, but LNCaP angiotensin was stimulated by estradiol. This stimulation was blocked by tamoxifen. Rat prostate AT1 receptor expression was much greater in prepuberal than in postpuberal rats but was not affected by a low-sodium diet. It was, however, significantly enhanced by captopril pretreatment. These findings all suggest the independence of prostate and systemic renin angiotensin system regulation. The data presented here suggest that the prostate may be a source of the secreted angiotensin II found in seminal plasma.
Mathematical modelling and manufacturing of the internal toroidal tooth profile
Authors: Yao L , Dai J S , Li H
Published: September 2004

This paper investigates the toroidal tooth profile of an epicyclic gear train based on the analysis of the integrated motion from both sun-worm and planet worm-gears and develops a mathematical model based on the coordinate transformation between the coordinate system of the stationary internal gear and that of the planet worm-gear. The model is derived from the geometrical analysis of the meshing system and is used to model the meshing surface which is produced as a result from the enveloping surface. This is further extended to model the internal toroidal tooth profile in the stationary gear, the normal tooth profile and the helix trajectory. Based on these models, the shape of normal tooth section of the stationary toroidal tooth profile is obtained and the three-dimensional modelling of this tooth profile is completed. The paper further examines the case of manufacturing by developing a fly-blade for the machining process and develops a manufacturing procedure which successfully produced a stationary internal toroidal tooth profile manufactured by a fly-blade on a hob machine.
On the penetration of tubular drill pipes in horizontal oil wells
Authors: McCourt I , Truslove T , Kubie J
Published: September 2004

To carry out remedial work in oil wells through the production tubing string, a method using a continuous length of steel tubing or coiled tubing is used. Furthermore, coiled tubing can also be used for drilling and extending existing wells.

In horizontal wells, substantial frictional forces are generated which resist the motion of the tubular drill pipe as it is pushed into the well. As the penetration increases, the frictional forces arising from the contact of the tubing with the inner casing wall increase too, and the tubular pipe buckles. The buckling is initially sinusoidal but eventually transforms into helical. At this point the force required to push the tubular drill pipe rises dramatically, and the maximum penetration is then rapidly reached.

To date, scale model experimental studies on horizontal wells have not reproduced the actual conditions occurring in the wells. A new experimental rig has been designed that allows for the simulation and observation of all significant parameters. An analytical model has also been developed which is in excellent agreement with the experimental data. Governing modelling parameters have been identified which suggest ways to increase the penetration of tubular drill pipes in production oil wells.
A finite element analysis of idealized damage in beam structures
Authors: Alnefaie K A
Published: September 2004

The strain energy damage index (SEDI) and a nominally similar parameter called SEDI2 are reported to be insensitive to the magnitude of the underlying damage in beams, although they do help to locate the damage itself. A new damage-sensitive parameter, the modal moment index (MMI), is introduced. It is shown that the MMI also ‘jumps’ at the location of damage in the beam. In addition, it is established that the magnitude of the MMI is closely related to the decrease in relative modulus. It is concluded hence that the MMI seems to be a damage-sensitive parameter with potential for application in experimental modal analysis.
A unified viscoplastic description of 63Sn-37Pb solder alloy under cyclic straining and stressing
Authors: Yang X J , Chow C L , Lau K J
Published: September 2004

A unified viscoplastic constitutive model for the fatigue life prediction of solder alloy 63Sn-37Pb is presented. The model incorporates the strain rate effect, the creep-plastic interaction and the dwell time effect under cyclic strain and stress loading. The applicability of this constitutive model is examined with cyclic strain tests with different strain rates, and cyclic stress tests under different stress waveforms in order to verify the progressive viscoplastic deformation of 63Sn-37Pb solder alloy. The investigation reveals that the material constants in the constitutive model can be determined by performing simple tests such as creep and cyclic tension-compression loading. The predictions using the constitutive model are found to agree well with the experimental results of the solder alloy under different loading. The agreement demonstrates that the model can satisfactorily describe the viscoplastic deformation behaviour under cyclic strain loading or stress loading.
Optimization of open-die forging process design to ensure homogeneous grain size refinement of cast structures by three-dimensional rigid-plastic finite element analysis
Authors: Tamura K , Tajima J
Published: September 2004

Focusing on the rough-forging stage of the hot open-die forging process, the influence of pass schedule on the equivalent plastic strain distribution at the surface of a forged billet has been numerically analysed using a three-dimensional rigid-plastic finite element method. By analysing the circumferential distribution of the strain obtained by one forging pass, it has been clarified that the distribution is strongly influenced by the cross-sectional shape of a workpiece. By utilizing the analytical results, a new method has been developed to predict the cross-sectional shape and the strain distribution without numerically analysing all passes. As a result, a new pass schedule has been proposed to ensure homogeneous grain size refinement of cast structures and the effect of the pass schedule was verified by a real hot open-die forging experiment.
Chromosome 2q terminal deletion: Report of 6 new patients and review of phenotype‐breakpoint correlations in 66 individuals
Authors: Casas Kari A. , Mononen Tarja K. , Mikail Claudia N. , Hassed Susan J. , Li Shibo , Mulvihill John J. , Lin Henry J. , Falk Rena E.
Published: September 2004

We report a new patient with terminal deletion of chromosome 2 with breakpoint at 2q36 and five additional new patients with 2q terminal deletion with breakpoint at 2q37. Hemidiaphragmatic hernia is a novel finding in one patient with a breakpoint at 2q37.1. In comparing these patients to 60 previously reported individuals with 2q terminal deletions, certain physical abnormalities are loosely associated with positions of breakpoint. For example, facial features (e.g., prominent forehead, depressed nasal bridge, and dysmorphic ears and nose), short stature, and short hands and feet were frequent in patients with breakpoints at or proximal to 2q37.3. Reports of horseshoe kidney and Wilms tumor were limited to patients with a breakpoint at 2q37.1, and structural brain anomalies and tracheal anomalies were reported only in patients with breakpoints at or proximal to 2q37.1. Cleft palate was reported only in patients with the most proximal breakpoints (2q36 or 2q35). Neurological effects including developmental delay, mental retardation, autistic‐like behavior, and hypotonia were typical in this patient population but did not stratify in severity according to breakpoint. Terminal deletion of the long arm of chromosome 2 should be considered in the infant with marked hypotonia, poor feeding, gastroesophageal reflux, and growth delay, and the older child with developmental delay, autistic behavior, and the characteristic facial and integumentary features described herein. Assignment of clinical features to specific breakpoints and refinement of predictive value may be useful in counseling. © 2004 Wiley‐Liss, Inc.
Increased risk of symptomatic gallbladder disease in adults with Down syndrome
Authors: Tyler Carl V. , Zyzanski Stephen J. , Runser Lloyd
Published: September 2004

Previous reports have documented an increased prevalence of asymptomatic cholelithiasis among children with Down syndrome. Whether this predisposes adults with Down syndrome to symptomatic gallbladder disease has not been studied. A case control study compared the rate of symptomatic gallbladder disease in 28 index cases of adults with Down syndrome and that of sex‐matched controls. The rate of gallbladder disease was 25% among the Down syndrome group, compared to 4.5% among the control group (P = 0.002). Patients with Down syndrome were also more likely to have a family medical history of gallbladder disease. Utilizing logistic regression analysis, the adjusted relative risk for gallbladder disease among individuals with Down syndrome was 3.52. © 2004 Wiley‐Liss, Inc.
Structured model of influenza virus replication in MDCK cells
Authors: Sidorenko Y. , Reichl U.
Published: September 2004

Intracellular events that take place during influenza virus replication in animal cells are well understood qualitatively. However, to better understand the complex interaction of the virus with its host cell and to quantitatively analyze the use of cellular resources for virion formation or the overall dynamic for the entire infection cycle, a mathematical model for influenza virus replication has to be formulated. Here, we present a structured model for the single‐cell reproductive cycle of influenza A virus in animal cells that accounts for the individual steps of the process such as attachment, internalization, genome replication and translation, and progeny virion assembly. The model describes an average cell surrounded by a small quantity of medium and infected by a low number of virus particles. The model allows estimation of the cellular resources consumed by virus replication. Simulation results show that the number of cellular surface receptors and endosomes, as well as other resources, such as the number of free nucleotides or amino acids, is not significantly influenced by influenza virus propagation. A factor that limits the growth rate of progeny viruses and their release is the total amount of matrix proteins (M1) in the nucleus while other newly synthesized viral proteins (e.g., nucleoprotein NP) and viral RNAs accumulate. During budding, synthesis of vRNPs (viral ribonucleoprotein complexes) represents another limiting factor. Based on this model it is also possible to analyze effects of parameter changes on the dynamics of virus replication, to identify possible targets for molecular engineering, or to develop strategies for improving yields in vaccine production processes. Furthermore, a better insight into the interactions of viruses and host cells might help to improve our understanding of virus‐related diseases and to develop therapies. © 2004 Wiley Periodicals, Inc.
pH, redox, and oxygen microprofiles in rhizosphere of bulrush (Scirpus validus) in a constructed wetland treating municipal wastewater
Authors: Bezbaruah Achintya N. , Zhang Tian C.
Published: September 2004

Microenvironmental studies regarding plant oxygen release in a wastewater environment are important to understand the principles of constructed wetlands for wastewater treatment. pH, oxidation reduction potential (ORP), and dissolved oxygen (DO) microprofiles for the lateral and main roots of the bulrush (Scirpus validus) in a vertical flow constructed wetland fed with municipal wastewater were measured using microelectrode techniques. pH was found to be low (6.91–6.98) near the lateral root surface, indicating possible nitrification or H+ extrusion. The ORP at the lateral root surface was between +250 and +317 mV and gradually reached the bulk solution ORP (+14 to –54 mV) at a radial distance of ∼4,750 μm. DO values at the lateral root surface varied from 0.64–2.04 mg L−1 as bulk biochemical oxygen demand (BOD) changed from 24 to 1,267 mg L−1. DO at the lateral root surface and the thickness of the oxygen layer around the root marginally increased with an increase in bulk BOD, while ORP at the lateral and main root surface decreased. pH and DO values did not change near the main root and had the bulk solution values. The results of this study provide insights into root‐induced microenvironments and would be helpful for the quantification of the total amount of oxygen contributed by plants in constructed wetlands. © 2004 Wiley Periodicals, Inc.
Investigation of optimal transduction conditions for baculovirus‐mediated gene delivery into mammalian cells
Authors: Hsu Ching‐Suei , Ho Yi‐Chen , Wang Kuei‐Chun , Hu Yu‐Chen
Published: September 2004

Although baculovirus‐mediated gene delivery into mammalian cells has been documented in a wealth of the literature, systematic investigation of the optimal transduction conditions remains unavailable. In this work, a transduction protocol using unconcentrated baculovirus is proposed for simple and efficient gene delivery into HeLa cells. We found that ∼75–85% of the cells could be readily transduced and express the reporter protein when virus transduction occurred for 4 h at 25°C using Dulbecco's phosphate‐buffered saline (D‐PBS) as the surrounding solution. This method contrasts with previous protocols in which transduction occurs for 1 h at 37°C using growth medium (e.g., DMEM) as the surrounding solution. Investigation of the physical parameters led to the findings that: 1) baculovirus uptake by HeLa cells continued for at least 4 h in the event of high virus dosage, which led to higher gene expression; 2) the half‐life of baculovirus dramatically decreased at 37°C; 3) EGTA pretreatment did not apparently facilitate the gene delivery when the cells grew to multilayers; and 4) lower transduction efficiency and gene expression were obtained when DMEM was used (in comparison with D‐PBS and TNM‐FH), suggesting that DMEM contains certain inhibitory factors for baculovirus transduction. Our data uncovered several aspects that were not investigated before and the optimized transduction conditions allowed for gene delivery as efficient as that by the protocols commonly employed by others, but eliminated the need for virus ultracentrifugation. The protocol not only represented a simpler approach, but also considerably reduced possible virus inactivation during ultracentrifugation, thus making it easier to convert the baculovirus/mammalian cell system to a tool for eukaryotic protein production on a larger scale. © 2004 Wiley Periodicals, Inc.
Detection of biomolecular interaction between biotin and streptavidin on a self‐assembled monolayer using magnetic nanoparticles
Authors: Arakaki Atsushi , Hideshima Sho , Nakagawa Takahito , Niwa Daisuke , Tanaka Tsuyoshi , Matsunaga Tadashi , Osaka Tetsuya
Published: September 2004

For developing a magnetic bioassay system, an investigation to determine the presence of a specific biomolecular interaction between biotin and streptavidin was done using magnetic nanoparticles and a silicon substrate with a self‐assembled monolayer. Streptavidin was immobilized on the magnetic particles, and biotin was attached to the monolayer‐modified substrate. The reaction of streptavidin‐modified magnetic particles on the biotin‐modified substrate was clearly observed under an optical microscope. The magnetic signals from the particles were detected using a magnetic force microscope. The results of this study demonstrate that the combination of a monolayer‐modified substrate with biomolecule‐modified magnetic particles is useful for detecting biomolecular interactions in medical and diagnostic analyses. © 2004 Wiley Periodicals, Inc.
Densonucleosis virus purification by ion exchange membranes
Authors: Specht Rachel , Han Binbing , Wickramasinghe S. Ranil , Carlson Jonathan O. , Czermak Peter , Wolf Anne , Reif Oscar‐Werner
Published: September 2004

Preparative chromatography is widely used in the downstream purification of biopharmaceutical products. Replacement of resins by membranes as chromatographic supports, overcomes many of the limitations associated with resin‐based chromatography such as high‐pressure drops, slow processing rates due to pore diffusion and channeling of the feed through the bed. In particular, adsorptive membranes may be ideally suited for virus capture. Virus capture is critical in a number of applications. In gene therapy and vaccine production, large‐scale purification of virus vectors is often essential. In the manufacture of biopharmaceuticals, validation of virus clearance is critical.

Here results for purification of Aedes aegypti densonucleosis virus (AeDNV) using anion and cation exchange membranes are presented. AeDNV is a non‐enveloped, single‐stranded mosquito‐specific parvovirus. Virus particles are around 20 nm in size. AeDNV could find potential applications in integrated vector‐borne disease control programs. In addition, capture of parvovirus for validation of virus clearance in the manufacture of biopharmaceuticals is of commercial importance.

By adjusting the pH of the feed stream, AeDNV particles may be adsorbed by both anion and cation exchange membranes. However, strongly basic anion exchange membranes were the most effective in adsorbing AeDNV particles. Adsorption and subsequent elution of AeDNV by anion exchange membranes leads to significant virus concentration. Dynamic and static capacities for anion exchange membranes were similar. Further, a sharp elution curve was obtained suggesting that pore diffusional resistances are insignificant. The adsorption of AeDNV particles by anion exchange membranes may be described by a linear isotherm. © 2004 Wiley Periodicals, Inc.
Simple and extractionless high‐performance liquid chromatographic determination of rosiglitazone in human plasma and application to pharmacokinetics in humans
Authors: Kim Kyoung‐Ah , Park Ji‐Young
Published: September 2004

A simple and extractionless HPLC method using ﬂuorescence detection was developed for the determination of rosiglitazone in human plasma. After deproteinization using perchloric acid the plasma samples were directly injected onto the HPLC system. The mobile phase was composed of acetonitrile (52%) and 20 mm ammonium acetate (48%, pH 7.5), and analysis was run at a ﬂow rate of 0.2 mL/min with the detector operating at 247 nm for excitation wavelength and at 367 nm for emission wavelength, respectively. The method has a mean recovery of 97%, while the intra‐day and inter‐day precisions were all less than 7%. This method is simple, speciﬁc, sensitive and requires only a small plasma volume with short analytical time, and is suitable for the determination of plasma rosiglitazone in routine measurements for pharmacokinetic studies. Copyright © 2004 John Wiley & Sons, Ltd.
QoS guarantee in telecommunication networks: technologies and solutions
Authors: Fortunato Enzo , Marchese Mario , Mongelli Maurizio , Raviola Annamaria
Published: September 2004

The aim of this paper is to show the effect of the presence of specific management functions within a network that offers quality of service (QoS). The objective is not privileging a particular technology but to highlight the importance to know which control functions a solution may use, which performance limits the functions have and what can be a realistic user expectation.

The paper focuses on the meaning of QoS and on the applications requiring quality, then describes QoS solutions including transport technologies, QoS‐oriented technologies, parameters and management functions. In more detail, the effect on QoS provision of the following issues is investigated and discussed concerning the possibility (or not) to aggregate and differentiate traffic, the implementation of call admission control and of traffic filtering to limit flows to their committed rates. Again, the conclusions should not be considered a merit mark about technology, but only an investigation about: what users and customers should expect by the technologies using specific control functions evidencing that the real limitations are not imposed by a specific technology, whose features may be changed and extended, but by the application of control functions that can guarantee requirements' matching. Copyright © 2004 John Wiley & Sons, Ltd.
Inhibitory effects of novel tetrahydropyridine derivatives on nitric oxide and reactive oxygen species production in glioma cells
Authors: Yoon Kyoung Jin P. , Redda Kinfe K. , Mazzio Elizabeth , Soliman Karam F.A.
Published: September 2004

The immune response in the central nervous system involves the degeneration of neurological tissue. The therapeutic use of nonsteroidal anti‐inflammatory agents (NSAIDs) can be effective in reducing inflammation and associated neurodegeneration. The current study was designed to examine the effects of previously synthesized N‐(substituted benzoylamino)‐4‐ethyl‐1,2,3,6‐tetrahydropyridines (THPs) on free radical and nitric oxide (NO) generation in C6 glioma cells activated with bacterial endotoxin [lipopolysaccharide (LPS): Escherichia coli 0111:B4] and interferon‐γ. Stimulated C6 cells exhibited elevated iNOS protein expression, an increase of reactive oxygen species and NO2−. All parameters were attenuated significantly by indomethacin and various THPs (4‐Ome, 3‐CF3, 4‐Me, 4‐Et, 4‐t‐butyl, and 4‐n‐butyl). The results indicate a possible role for THP derivatives as anti‐inflammatory agents. Drug Dev. Res. 61:189–196, 2004. © 2004 Wiley‐Liss, Inc.
Augmentation of all‐trans‐retinoic acid concentration in plasma by preventing inflammation responses induced by atRA‐loaded microspheres with concurrent treatment of dexamethasone
Authors: Park Kyeongsoon , Choi Yongdoo , Kim Sang Yoon , Byun Youngro
Published: September 2004

All‐trans retinoic acid (atRA)‐loaded microspheres severely induce inflammatory responses after microsphere implantation. Fibroblasts and a thick band of fibrous capsule resulting from the inflammatory responses could hamper drug permeation to the bloodstream because fibroblasts actively metabolize atRA into polar metabolites and the thick fibrous capsule acts as a diffusion barrier. In the present study, we investigated whether the fibroblast proliferation and collagen deposition induced by atRA released from microspheres might affect the atRA concentration in plasma and atRA metabolism with or without treatment of dexamethasone as an anti‐inflammatory drug. After subcutaneous injection of atRA‐loaded microspheres in rats, it was observed that atRA‐loaded microspheres induced severe inflammatory responses and stimulated fibroblast proliferation and collagen deposition in fibrous capsules. On the other hand, the orally treated dexamethasone effectively prevented inflammatory responses in a dose‐dependent manner and suppressed about 49% of the number of fibroblasts and collagen deposition in fibrous capsules at 14 days. In addition, after the treatment of dexamethasone, the atRA concentration in plasma was increased, and its metabolism was decreased approximately by 40% at 7 days, compared to the group treated alone with atRA‐loaded microspheres. In conclusion, the concurrent treatment of dexmethasone with atRA‐loaded microspheres could prevent inflammatory responses and metabolism of atRA, thereby maintaining the atRA concentration in plasma for longer periods in the therapeutic range. Drug Dev. Res. 61:197–206, 2004. © 2004 Wiley‐Liss, Inc.
Effects of a new 1,3,4‐thiadiazolium mesoionic compound, MI‐D, on the acute inflammatory response
Authors: Cardoso Júlio C. , Cadena Sílvia M. S. C. , Zampronio Aleksander , Arruda Ana Maria S. , Carnieri Eva G. S. , Echevarria Aurea , Constantin Jorgete , Bracht Adelar , Oliveira Maria Benigna M.
Published: September 2004

A new mesoionic compound, 4‐phenyl‐5‐(4‐nitro‐cinnamoyl)‐1,3,4‐thiadiazolium‐2‐phenylamine (MI‐D), is described along with some of its biological properties. Its effects on hepatic metabolism, on O and nitric oxide (NO) production, and in in vivo models for potential antinociceptive, antipyretic, and antiinflammatory activities were determined. In perfused rat liver, MI‐D (25 µM) stimulated glycogenolysis (95%), and inhibited oxygen uptake (37%) with affecting glycolysis. In phorbol 12‐myristate 13‐acetate‐stimulated macrophages, O generation was reduced (95%) by MI‐D (15 µM), whereas the production of NO was unaffected. MI‐D (2 mg/kg) inhibited (55%) the number of abdominal writhings induced by acetic acid. At 1 mg/kg, MI‐D inhibited the febrile response (5 h) induced by lipopolysaccharide (LPS) and was also effective against a preexisting febrile response. Treatment with MI‐D (1 mg/kg) reduced by 67% prostaglandin (PGE2) levels in the cerebrospinal fluid of LPS‐exposed mice, and at a higher dose (8 mg/kg) MI‐D inhibited paw edema formation (2 h) induced by carrageenan. MI‐D has a spectrum of activities similar to other nonsteroidal antiinflammatory drugs, qualifying it as a potential anti‐inflammatory drug. Drug Dev. Res. 61:207–217, 2004. © 2004 Wiley‐Liss, Inc.