bluuebunny/crossref_metadata_2025 huggingface dataset:
Scalable Generation of High-Titer Recombinant Adeno-Associated Virus Type 5 in Insect Cells
Authors: Urabe Masashi , Nakakura Takayo , Xin Ke-Qin , Obara Yoko , Mizukami Hiroaki , Kume Akihiro , Kotin Robert M. , Ozawa Keiya
Published: January 2006

We established a method for production of recombinant adeno-associated virus type 5 (rAAV5) in insect cells by use of baculovirus expression vectors. One baculovirus harbors a transgene between the inverted terminal repeat sequences of type 5, and the second expresses Rep78 and Rep52. Interestingly, the replacement of type 5 Rep52 with type 1 Rep52 generated four times more rAAV5 particles. We replaced the N-terminal portion of type 5 VP1 with the equivalent portion of type 2 to generate infectious AAV5 particles. The rAAV5 with the modified VP1 required α2-3 sialic acid for transduction, as revealed by a competition experiment with an analog of α2-3 sialic acid. rAAV5-GFP/Neo with a 4.4-kb vector genome produced in HEK293 cells or Sf9 cells transduced COS cells with similar efficiencies. Surprisingly, Sf9-produced humanized
Renilla
green fluorescent protein (hGFP) vector with a 2.4-kb vector genome induced stronger GFP expression than the 293-produced one. Transduction of murine skeletal muscles with Sf9-generated rAAV5 with a 3.4-kb vector genome carrying a human secreted alkaline phosphatase (SEAP) expression cassette induced levels of SEAP more than 30 times higher than those for 293-produced vector 1 week after injection. Analysis of virion DNA revealed that in addition to a 2.4- or 3.4-kb single-stranded vector genome, Sf9-rAAV5 had more-abundant forms of approximately 4.7 kb, which appeared to correspond to the monomer duplex form of hGFP vector or truncated monomer duplex SEAP vector DNA. These results indicated that rAAV5 can be generated in insect cells, although the difference in incorporated virion DNA may induce different expression patterns of the transgene.
The Arg279Glu Substitution in the Adenovirus Type 11p (Ad11p) Fiber Knob Abolishes EDTA-Resistant Binding to A549 and CHO-CD46 Cells, Converting the Phenotype to That of Ad7p
Authors: Gustafsson Dan J. , Segerman Anna , Lindman Kristina , Mei Ya-Fang , Wadell Göran
Published: January 2006

The major determinant of adenovirus (Ad) attachment to host cells is the C-terminal knob domain of the trimeric fiber protein. Ad type 11p (Ad11p; species B2) in contrast to Ad7p (species B1) utilizes at least two different cellular attachment receptors, designated sBAR (species B adenovirus receptor) and sB2AR (species B2 adenovirus receptor). CD46 has recently been identified as one of the Ad11p attachment receptors. However, CD46 did not seem to constitute a functional receptor for Ad7p. Although Ad7p shares high knob amino acid identity with Ad11p, Ad7p is deficient in binding to both sB2AR and CD46. To determine what regions of the Ad11p fiber knob are necessary for sB2AR-CD46 interaction, we constructed recombinant fiber knobs (rFK) with Ad11p/Ad7p chimeras and Ad11p sequences having a single amino acid substitution from Ad7p. Binding of the constructs to A549 and CHO-CD46 BC1 isoform-expressing cells was analyzed by flow cytometry. Our results indicate that an Arg279Glu substitution is sufficient to convert the Ad11p receptor-interaction phenotype to that of Ad7p and abolish sB2AR and CD46 interaction. Also a Glu279Arg substitution in Ad7p rFKs increases CD46 binding. Thus, the lateral HI loop of the Ad11p fiber knob seems to be the key determinant for Ad11p sB2AR-CD46 interaction. This result is comparable to another non-coxsackie-adenovirus receptor binding Ad (Ad37p), where substitution of one amino acid abolishes virus-cell interaction. In conjunction with previous results, our findings also strongly suggest that sB2AR is equivalent to CD46.
Involvement of Multiple Epitope-Specific Cytotoxic T-Lymphocyte Responses in Vaccine-Based Control of Simian Immunodeficiency Virus Replication in Rhesus Macaques
Authors: Kawada Miki , Igarashi Hiroko , Takeda Akiko , Tsukamoto Tetsuo , Yamamoto Hiroyuki , Dohki Sachi , Takiguchi Masafumi , Matano Tetsuro
Published: January 2006

Cytotoxic T-lymphocyte (CTL) responses are crucial for the control of immunodeficiency virus replication. Possible involvement of a dominant single epitope-specific CTL in control of viral replication has recently been indicated in preclinical AIDS vaccine trials, but it has remained unclear if multiple epitope-specific CTLs can be involved in the vaccine-based control. Here, by following up five rhesus macaques that showed vaccine-based control of primary replication of a simian immunodeficiency virus, SIVmac239, we present evidence indicating involvement of multiple epitope-specific CTL responses in this control. Three macaques maintained control for more than 2 years without additional mutations in the provirus. However, in the other two that shared a major histocompatibility complex haplotype, viral mutations were accumulated in a similar order, leading to viral evasion from three epitope-specific CTL responses with viral fitness costs. Accumulation of these multiple escape mutations resulted in the reappearance of plasma viremia around week 60 after challenge. Our results implicate multiple epitope-specific CTL responses in control of immunodeficiency virus replication and furthermore suggest that sequential accumulation of multiple CTL escape mutations, if allowed, can result in viral evasion from this control.
Antibody Prophylaxis and Therapy against Nipah Virus Infection in Hamsters
Authors: Guillaume V. , Contamin H. , Loth P. , Grosjean I. , Courbot M. C. Georges , Deubel V. , Buckland R. , Wild T. F.
Published: January 2006

Nipah virus
(NiV), a member of the
Paramyxoviridae
family, causes a zoonotic infection in which the reservoir, the fruit bat, may pass the infection to pigs and eventually to humans. In humans, the infection leads to encephalitis with >40 to 70% mortality. We have previously shown that polyclonal antibody directed to either one of two glycoproteins, G (attachment protein) or F (fusion protein), can protect hamsters from a lethal infection. In the present study, we have developed monoclonal antibodies (MAbs) to both glycoproteins and assessed their ability to protect animals against lethal NiV infection. We show that as little as 1.2 μg of an anti-G MAb protected animals, whereas more than 1.8 μg of anti-F MAb was required to completely protect the hamsters. High levels of either anti-G or anti-F MAbs gave a sterilizing immunity, whereas lower levels could protect against a fatal infection but resulted in an increase in anti-NiV antibodies starting 18 days after the viral challenge. Using reverse transcriptase PCR, the presence of NiV in the different organs could not be observed in MAb-protected animals. When the MAbs were given after infection, partial protection (50%) was observed with the anti-G MAbs when the animals were inoculated up to 24 h after infection, but administration of the anti-F MAbs protected some animals (25 to 50%) inoculated later during the infection. Our studies suggest that immunotherapy could be used for people who are exposed to NiV infections.
Dual Wavelength Imaging Allows Analysis of Membrane Fusion of Influenza Virus inside Cells
Authors: Sakai Tatsuya , Ohuchi Masanobu , Imai Masaki , Mizuno Takafumi , Kawasaki Kazunori , Kuroda Kazumichi , Yamashina Shohei
Published: January 2006

Influenza virus hemagglutinin (HA) is a determinant of virus infectivity. Therefore, it is important to determine whether HA of a new influenza virus, which can potentially cause pandemics, is functional against human cells. The novel imaging technique reported here allows rapid analysis of HA function by visualizing viral fusion inside cells. This imaging was designed to detect fusion changing the spectrum of the fluorescence-labeled virus. Using this imaging, we detected the fusion between a virus and a very small endosome that could not be detected previously, indicating that the imaging allows highly sensitive detection of viral fusion.
Arsenic Counteracts Human Immunodeficiency Virus Type 1 Restriction by Various TRIM5 Orthologues in a Cell Type-Dependent Manner
Authors: Sebastian Sarah , Sokolskaja Elena , Luban Jeremy
Published: January 2006

Arsenic trioxide (As
2
O
3
) increased human immunodeficiency virus type 1 (HIV-1) infectivity when particular
Homo sapiens
and
Cercopithecus aethiops
cell lines were used as targets. Knockdown of human TRIM5α by RNA interference eliminated the As
2
O
3
effect, demonstrating that the drug acts by modulating the activity of this retroviral restriction factor. In contrast, HIV-1 infectivity in target cell lines from other primate species (
Cercopithecus tantalus
,
Macaca mulatta
, and
Aotus trivirgatus
) was not increased by As
2
O
3
, despite the potent TRIM5-dependent HIV-1 restriction activity that these cells exhibit. To determine if As
2
O
3
responsiveness is characteristic of particular TRIM5 orthologues and not others, TRIM5 cDNAs from these five primate species were transduced into cat fibroblasts, which lack endogenous HIV-1 restriction activity and, therefore, responsiveness to As
2
O
3
. In this context, the HIV-1 restriction activity conferred by all TRIM5 orthologues was largely eliminated by As
2
O
3
. The effect of As
2
O
3
on HIV-1 restriction is thus shared by different TRIM5 orthologues but dependent on factors specific to the cell line in which TRIM5 is expressed.
THE EXTENSION TO THE TRANSVERSE MOMENTUM OF THE STATISTICAL PARTON DISTRIBUTIONS
Authors: BOURRELY CLAUDE , SOFFER JACQUES , BUCCELLA FRANCO
Published: January 2006

By extending the statistical distributions to the transverse degree of freedom, we account for a multiplicative factor in the Fermi–Dirac functions of the light quarks, we were led to introduce in a previous work to comply with experiment. We can also get light antiquark distributions, similar to those we proposed earlier.
HIGGS PRODUCTION IN ASSOCIATION WITH BOTTOM QUARKS AT HADRON COLLIDERS
Authors: DAWSON S. , JACKSON C. B. , REINA L. , WACKEROTH D.
Published: January 2006

We review the present status of the QCD corrected cross-sections and kinematic distributions for the production of a Higgs boson in association with bottom quarks at the Fermilab Tevatron and CERN Large Hadron Collider. Results are presented for the Minimal Supersymmetric Standard Model where, for large tan β, these production modes can be greatly enhanced compared to the Standard Model case. The next-to-leading order QCD results are much less sensitive to the renormalization and factorization scales than the lowest order results, but have a significant dependence on the choice of the renormalization scheme for the bottom quark Yukawa coupling. We also investigate the uncertainties coming from the Parton Distribution Functions and find that these uncertainties can be comparable to the uncertainties from the remaining scale dependence of the next-to-leading order results. We present results separately for the different final states depending on the number of bottom quarks identified.
PHOTOCURRENT ABSORPTION SPECTROSCOPIC STUDY OF Si0.6Ge0.4/Si QUANTUM WELLS
Authors: HUANG SHIHUA , WU FENGMIN , LIN JI , LU FANG
Published: January 2006

Absorption spectra of Si 0.6 Ge 0.4/ Si quantum wells are characterized by photocurrent measurements. The absorption coefficients of two different transitions, namely the transition between the Si band states and the discrete energy level in quantum wells, and the interlevel transition in quantum wells are deduced. They are directly proportional to (ℏω-ΔE)3/2 and δ(ℏω-Eeh), respectively. The valence band offsets of Si 0.6 Ge 0.4/ Si interface are 297 meV. The ground state energy levels in valence band and conduction band Si 0.6 Ge 0.4/ Si quantum wells are 37 meV and 23 meV, respectively.
QUANTUM FLUCTUATIONS OF A COULOMB POTENTIAL AS A SOURCE OF FLICKER NOISE
Authors: KAZAKOV KIRILL A.
Published: January 2006

The power spectrum of quantum fluctuations of the electromagnetic field produced by an elementary particle is determined. It is found that in a wide range of practically important frequencies the power spectrum of fluctuations exhibits an inverse frequency dependence. The magnitude of fluctuations produced by a conducting sample is shown to have a Gaussian distribution around its mean value, and its dependence on the sample geometry is determined. In particular, it is demonstrated that for geometrically similar samples the power spectrum is inversely proportional to the sample volume. It is also argued that the magnitude of fluctuations induced by an external electric field is proportional to the field strength squared. A comparison with experimental data on flicker noise measurements in continuous metal films is made.
ATOMIC FORCE MICROSCOPY AND XRD ANALYSIS OF SILVER FILMS DEPOSITED BY THERMAL EVAPORATION
Authors: MAQBOOL MUHAMMAD , KHAN TAHIRZEB
Published: January 2006

Thin films of pure silver were deposited on glass substrate by thermal evaporation process at room temperature. Surface characterization of the films was performed using X-ray diffraction (XRD) and atomic force microscopy (AFM). Thickness of the films varied between 20 nm and 72.8 nm. XRD analysis provided a sharp peak at 38.75° from silver. These results indicated that the films deposited on glass substrates at room temperature are crystalline. Three-dimension and top view pictures of the films were obtained by AFM to study the grain size and its dependency on various factors. Average grain size increased with the thickness of the deposited films. A minimum grain size of 8 nm was obtained for 20 nm thick films, reaching 41.9 nm when the film size reaches 60 nm. Grain size was calculated from the information provided by the XRD spectrum and averaging method. We could not find any sequential variation in the grain size with the growth rate.
Adenosine stimulates depolarization and rise in cytoplasmic [Ca2+] in type I cells of rat carotid bodies
Authors: Xu Fenglian , Xu Jianhua , Tse Frederick W. , Tse Amy
Published: January 2006

During hypoxia, the level of adenosine in the carotid bodies increases as a result of ATP catabolism and adenosine efflux via adenosine transporters. Using Ca2+imaging, we found that adenosine, acting via A2Areceptors, triggered a rise in cytoplasmic [Ca2+] ([Ca2+]i) in type I (glomus) cells of rat carotid bodies. The adenosine response could be mimicked by forskolin (but not its inactive analog), and could be abolished by the PKA inhibitor H89. Simultaneous measurements of membrane potential (perforated patch recording) and [Ca2+]ishowed that the adenosine-mediated [Ca2+]irise was accompanied by depolarization. Ni2+, a voltage-gated Ca2+channel (VGCC) blocker, abolished the adenosine-mediated [Ca2+]irise. Although adenosine was reported to inhibit a 4-aminopyridine (4-AP)-sensitive K+current, 4-AP failed to trigger any [Ca2+]irise, or to attenuate the adenosine response. In contrast, anandamide, an inhibitor of the TWIK-related acid-sensitive K+-1 (TASK-1) channels, triggered depolarization and [Ca2+]irise. The adenosine response was attenuated by anandamide but not by tetraethylammonium. Our results suggest that adenosine, acting via the adenylate cyclase and PKA pathways, inhibits the TASK-1 K+channels. This leads to depolarization and activation of Ca2+entry via VGCC. This excitatory action of adenosine on type I cells may contribute to the chemosensitivity of the carotid body during hypoxia.
G protein-coupled receptors serve as mechanosensors for fluid shear stress in neutrophils
Authors: Makino Ayako , Prossnitz Eric R. , Bünemann Moritz , Wang Ji Ming , Yao Weijuan , Schmid-Schönbein Geert W.
Published: January 2006

Many cells respond to fluid shear stress but in a cell type-specific fashion. Fluid shear stress applied to leukocytes serves to control pseudopod formation, migration, and other functions. Specifically, fresh neutrophils or neutrophilic leukocytes derived from differentiated HL60 cells respond to fluid shear stress by cytoplasmic pseudopod retraction. The membrane elements that sense fluid shear and induce such a specific response are still unknown, however. We hypothesized that membrane receptors may serve as fluid shear sensors. We found that fluid shear decreased the constitutive activity of G protein-coupled receptors (GPCRs). Inhibition of GPCR constitutive activity by inverse agonists abolished fluid shear stress-induced cell area reduction. Among the GPCRs in neutrophils, the formyl peptide receptor (FPR) exhibits relatively high constitutive activity. Undifferentiated HL60 cells that lacked FPR formed few pseudopods and showed no detectable response to fluid shear stress, whereas expression of FPR in undifferentiated HL60 cells caused pseudopod projection and robust pseudopod retraction during fluid shear. FPR small interfering RNA-transfected differentiated HL60 cells exhibited no response to fluid shear stress. These results suggest that GPCRs serve as mechanosensors for fluid shear stress in neutrophils by decreasing its constitutive activity and reducing pseudopod projection.
Temporal differences in bladder dysfunction caused by diabetes, diuresis, and treated diabetes in mice
Authors: Daneshgari Firouz , Huang Xiao , Liu Guiming , Bena James , Saffore Lateef , Powell C. Thomas
Published: January 2006

Diabetic bladder dysfunction is a common complication of diabetes mellitus (DM) with poorly understood natural history. This study examined the temporal changes in bladder function 3, 9, 12, and 20 wk after induction of DM by streptozotocin (STZ) in male C57BL/6 mice compared with that in age-matched diabetic mice treated with insulin, 5% sucrose-induced diuretic mice, and sham-treated control mice. Conscious cystometrograms of mice were examined in addition to the measurements of micturition cycle. Diabetes resulted in decreased body weight. Bladder weight, urine output, bladder capacity, and compliance increased in the DM and diuretic groups. Peak voiding pressure (PVP) increased initially in both DM and diuretic mice. However, in DM mice, PVP dropped dramatically at and after 12 wk. Similar changes in the capacity, compliance, and emptying ability of the bladder were seen during the first 9 wk of the diabetes or diuresis, whereas significant decline in the emptying ability of the bladder was only seen in diabetes after 12 wk of disease in mice. Long-term insulin replacement effectively reversed most changes in bladder function. These results suggest that the transition from a compensated to a decompensated bladder dysfunction occurs 9–12 wk after induction of DM in mice by STZ.
Representation of Auditory Signals in the M-Cell: Role of Electrical Synapses
Authors: Szabo T. M. , Weiss S. A. , Faber D. S. , Preuss T.
Published: January 2006

The teleost Mauthner (M-) cell mediates a sound-evoked escape behavior. A major component of the auditory input is transmitted by large myelinated club endings of the posterior VIIIth nerve. Paradoxically, although nerve stimulations revealed these afferents have mixed electrical and glutamatergic synapses on the M-cell's distal lateral dendrite, paired pre- and postsynaptic recordings indicated most individual connections are chemically silent. To determine the sensory information encoded and the relative contributions of these two transmission modes, M-cell responses to acoustic stimuli in air were recorded intracellularly. Excitatory postsynaptic potentials (EPSPs) evoked by both short 100- to 900-Hz “pips” and longer-lasting amplitude- and frequency-modulated sounds were dominated by fast, repetitive EPSPs superimposed on an underlying slow depolarization. Fast EPSPs 1) have kinetics comparable to presynaptic action potentials, 2) are maximal on the distal lateral dendrite, and 3) are insensitive to GluR antagonists. They presumably are coupling potentials, and power spectral analysis indicated they constitute a high-pass signal that accurately tracks sound frequency and amplitude. The spatial profile of the slow EPSP suggests both proximal and distal dendritic sources, a result supported by predictions of a multicompartmental model and the effects of AMPAR antagonists, which preferentially reduced the proximal component. Thus a second class of afferents generates a portion of the slow EPSP that, with sound stimuli, demonstrate that the dominant mode of transmission at LMCE synapses is electrical. The slow EPSP is a dynamic, low-pass representation of stimulus strength. Accordingly, amplitude and phase information, which are segregated in other systems, are faithfully represented in the M-cell.
β2 and β4 Subunits of BK Channels Confer Differential Sensitivity to Acute Modulation by Steroid Hormones
Authors: King J. T. , Lovell P. V. , Rishniw M. , Kotlikoff M. I. , Zeeman M. L. , McCobb D. P.
Published: January 2006

Membrane-associated receptors for rapid, steroidal neuromodulation remain elusive. Estradiol has been reported to facilitate activation of voltage- and Ca2+-dependent BK potassium channels encoded by Slo, if associated with β1 subunits. We show here that 1) multiple members of the β family confer sensitivity to multiple steroids on BK channels, 2) that β subunits differentiate between steroids, and 3) that different βs have distinct relative preferences for particular steroids. Expressed in HEK 293 cells, inside-out patches with channels composed of Slo-α alone showed no steroid sensitivity. Cells expressing αβ4 exhibited potent, rapid, reversible, and dose-dependent potentiation by corticosterone (CORT; a glucocorticoid), and were potentiated to a lesser degree by other sex and stress steroids. In contrast, αβ2 channels were potentiated more strongly by dehydroepiandrosterone (DHEA; an enigmatic, stress-related adrenal androgen), and to a lesser extent by CORT, estradiol, testosterone, and DHEA-S. Cholesterol had no effect on any BK channel compositions tested. Conductance–voltage plots of channels composed of α plus β2 or β4 subunits were shifted in the negative direction by steroids, indicating greater activation at negative voltages. Thus our results argue that the variety of Slo-β subunit coexpression patterns occurring in vivo expands the repertoire of Slo channel gating in yet another dimension not fully appreciated, rendering BK gating responsive to dynamic fluctuations in a multiple of steroid hormones.
p53 and p66 Proteins Compete for Hypoxia-Inducible Factor 1 Alpha Stabilization in Young and Old Rat Hearts Exposed to Intermittent Hypoxia
Authors: Bianchi Giuseppina , Di Giulio Camillo , Rapino Cinzia , Rapino Monica , Antonucci Adriano , Cataldi Amelia
Published: January 2006

Background: During development and aging, as well as under hypoxia, many cells can adapt to a stressful environment, while others are damaged and die by apoptosis. In particular, intermittent hypoxia, i.e., hypoxia followed by reoxygenation, determines different responses in young and adult myocardia. Objective: In the rat myocardium exposed to hypoxia, the roles played by p53 and p66 Shc proteins in matching, in an age-dependent mode, in stabilizing hypoxia-inducible factor-1α (HIF-1α), and in preventing its biological activity, which usually induces synthesis of rescue proteins against this stress, were investigated. Methods: Five animals from three groups, each consisting of 10 male Wistar rats, 8 days and 3 and 24 months old, were kept under physiological conditions; 5 young and 5 old rats were exposed to intermittent hypoxic challenges (12 h at 10% O2 followed by 12 h at 21% O2) for 8 days. Pregnant rats were kept for 3 days under hypoxic conditions before delivery, and 5 neonate rats were kept in intermittent hypoxia for 8 days. Left ventricles were excised and processed for TUNEL and Western blotting analyses. Results: HIF-1α stabilization by p53 along with decline in Bcl2, substantial caspase-3 expression, and a large number of apoptotic events make the hypoxic young myocardium the most damaged when compared to the neonatal one, in which HIF-1α is not stabilized. Moreover, high expression and activation of p66 in hypoxic young and in normoxic old myocardia suggests a pathological increase of the response to oxidative stress in the former and a physiological progressive increase in the latter. Conclusions: The different responses to hypoxic challenge during life show that the young seem the most reactive and damaged, as is well documented by p53-mediated HIF-1α stabilization. The neonate, not showing any modification in terms of HIF-1α expression and activation, seems ‘adapted’ to such an environment, since it was maintained in hypoxia 3 days before and 8 days after birth. In the old, increasing p66 expression and tyrosine phosphorylation, probably exerting a slight HIF-1α stabilization in the two experimental conditions, provide evidence of longevity and oxidative stress resistance, as suggested by the low number of apoptotic events seen upon hypoxic challenge, and this fact could be due to impairment of oxygen-sensing mechanisms or to adaptation of the cells to apoptosis.
Pharmacokinetics of Fluoxetine in Elderly Men and Women
Authors: Ferguson James M. , Hill Heather
Published: January 2006

Fluoxetine is widely prescribed as an antidepressant for geriatric patients. Despite a large scientific literature describing its efficacy and safety, there are few published data describing the pharmacokinetics of fluoxetine in the elderly. Given the common practice of polypharmacy in this population, additional pharmacokinetic information in elderly men and women is needed so that physicians can better assess potential drug-drug interactions. Twenty-five subjects, men and women between ages 65 and 83, received 20 mg of fluoxetine for 1 week followed by 40 mg for 5 weeks. Serum fluoxetine levels were measured during the period of drug administration and for 8 weeks after. The plasma concentration of fluoxetine and norfluoxetine in our subjects was higher than previously reported in the literature. Elderly women had a significantly higher serum level of norfluoxetine than men. The terminal half-life of norfluoxetine was longer in patients over age 75; elderly women had a significantly slower rate of norfluoxetine elimination than similarly aged men.
Effect of Age on the Relationship of Occupational Social Class with Prevalence of Modifiable Cardiovascular Risk Factors and Cardiovascular Diseases
Authors: Myint Phyo K. , Luben Robert N. , Welch Ailsa A. , Bingham Sheila A. , Wareham Nicholas J. , Khaw Kay-Tee
Published: January 2006

Background: Previous studies on cardiovascular risk profile in different socioeconomic status were focused on younger populations and many of them have not been able to take into account age and sex differences. Objectives: To investigate the relationship of occupational social class with the prevalence of cardiovascular disease risk factors and cardiovascular diseases in younger (<65 years) and older (≧65 years) men and women. Methods: A population-based-cross sectional study was conducted in a general community in Norfolk, United Kingdom. Participants were 23,085 men and women aged 40–79 years, recruited from general practice age-sex registers as part of European Prospective Investigation into Cancer-Norfolk (EPIC-Norfolk). The prevalence of cardiovascular risk factors and cardiovascular diseases were examined. Results: The prevalence of smoking was significantly higher in those in manual social classes particularly in the younger (<65) age group. Younger women in manual social classes were more likely to be smokers compared to older women in the same social class. Being in manual social classes was associated with higher cholesterol levels in women but lower cholesterol levels in men. Manual social class was associated with higher physical activity in those younger than 65 years but this association was reversed in those 65 years or older. Conclusion: Occupational social class is differently related to cardiovascular risk factors in individuals depending on their age and sex. This may reflect differences in behavior at work and leisure, which vary by sex and pre- and postretirement. Interventions to promote health and reduce social inequalities need to take age and gender into account.
Demonstration of a Threshold Response in a Proteolytic Feedback System: Control of the Autoactivation of Factor XII
Authors: Jesty Jolyon , Rodriguez José , Beltrami Edward
Published: January 2006

Mathematical analysis of positive feedback loops in proteolytic systems has previously suggested that when the active enzymes are subject to inhibitory control these systems will exhibit threshold behavior. This is demonstrated in the present study, for the autolytic activation of factor XII in the presence of a contact activator and an irreversible inhibitor of factor XIIa. The threshold between the two system states – complete factor XII activation, or complete stability – is dependent on the kinetic balance between the catalytic rate of autoactivation and rate of enzyme (factor XIIa) inhibition. Activation of the system can be brought about by either increasing the catalytic rate (in this study, by using more potent contact-activation conditions), or by lowering the enzyme inhibition rate. Previous mathematical work predicted complete stability in a positive-feedback system that is below threshold, and this has been experimentally confirmed.
A Model for the Formation and Lysis of Blood Clots
Authors: Anand M. , Rajagopal K. , Rajagopal K.R.
Published: January 2006

Both biochemical and mechanical factors have to be taken into account if a meaningful model for the formation, growth, and lysis of clots in flowing blood is to be developed. Most models that are currently in use neglect one or the other of these factors. We have previously reported a model [J Theoret Med 2003;5:183–218] that we believe is a step in this direction, incorporating many of the crucial biochemical and rheological factors that play a role in the formation, growth, and lysis of clots. While this model takes into account the extrinsic pathway of coagulation, it largely ignores the intrinsic pathway. Here, we discuss some of the general issues with respect to mathematical modeling of thrombus formation and lysis, as well as specific aspects of the model that we have developed.
Cochlear Electrode Arrays: Past, Present and Future
Authors: Spelman Francis A.
Published: January 2006

Cochlear implants are very successful devices: more than 60000 people use them throughout the world. Key to the success of these prostheses is the development of electrode arrays that place contacts close to the target neurons, survive for decades in the tissues of the inner ear, and that provide reliable and repeatable excitation to the cells of the auditory nerve. This article describes the early electrode arrays and their development into the arrays that are used presently in clinical cochlear prostheses. While integrated circuit techniques were proposed and tested in the laboratory two decades ago, the present clinical devices still are hand built and made of wire-based technologies. Current approaches that seek to automate the construction of cochlear electrode arrays are described and discussed.
The Development of a Biologically-Inspired Directional Microphone for Hearing Aids
Authors: Miles R.N. , Hoy R.R.
Published: January 2006

The development of novel microfabrication techniques for producing a directional microphone for hearing aids is here described. The mechanisms underlying both the structure and function of these unusual microphones were originally inspired by the ears of an inconspicuous insect, the parasitoid fly Ormia ochracea. The structure of Ormia’s ears inspired new approaches to design directional microphones that are more sensitive and have lower thermal noise than that typical of those using traditional approaches. The mechanisms for directional hearing in this animal are discussed along with the engineering design concepts that they have inspired, because they illustrate how basic research can inspire technology development–translational research. However, to realize the potential of bioexploitation this microphone diaphragm concept would have been very difficult to realize without the availability of new silicon microfabrication technologies. Thus, this report can be viewed as an example of what may be possible with the application of new fabrication methods to microphones. Challenges and opportunities provided by the use of silicon microfabrication technology for microphones are discussed.
The Effect of Phenotype on Mechanical Stretch-Induced Vascular Smooth Muscle Cell Apoptosis
Authors: Su Baogen Y. , Shontz Kimberly M. , Flavahan Nicholas A. , Nowicki Philip T.
Published: January 2006

The present study evaluated mechanical stretch-induced apoptosis in swine vascular smooth muscle cells (VSMC) of different phenotypes. We demonstrated that differentiated VSMC express a greater level of Bcl-2-associated death factor (BAD) and have a significant cell loss when exposed to mechanical stretch (10% elongation, 1 Hz) for 24 h. We further demonstrated that apoptosis was significantly increased only in differentiated VSMC exposed to mechanical stretch. To test the hypothesis that the intracellular level of BAD in VSMC determines its response to mechanical stretch-induced apoptosis, we examined whether BAD expression was upregulated by mechanical stretch-induced apoptosis and was associated with the increase in the apoptosis level of differentiated VSMC. When exposed to mechanical stretch, the expression of BAD in differentiated VSMC was elevated at 1 h and remained at higher levels during the application of stretch (24 h). In contrast, Bcl-2 expression was suppressed during the application of stretch. Moreover, the proapoptotic function of BAD was inhibited by overexpression of Bcl-2 through transient transfection of VSMC with pCEP4-Bcl-2 or incubation of VSMC with vascular epithelial growth factor. These results suggest that mechanical stretch-induced VSMC apoptosis is phenotype dependent. The higher levels of apoptosis of differentiated VSMC upon mechanical stretch were, at least in part, dependent on their intrinsic level of BAD.
Biomechanical Strength of Reconstruction Plates when Used for Medial Support of Med-El Cochlear Implants: Implications for Diagnostic MRI
Authors: Poetker David M. , Wackym P. Ashley , Yoganandan Narayan , Runge-Samuelson Christina L. , Firszt Jill B. , Pintar Frank A.
Published: January 2006

Purpose:It is hypothesized that a mesh reconstruction plate designed to fit a cochlear implant (CI) internal device will provide immediate structural support to the site of the implant and that this strength far exceeds the forces induced by a 1.5-tesla MRI. Procedures: Human calvarial specimens were drilled and plated with reconstruction mesh. Force was applied until failure was reached. Results: Mean maximum force, mean force to first failure and mean displacement measures for group 1 (resorbable mesh, n = 10) were 302.9 N, 283.0 N and 3.05 mm, respectively. The mean maximum force for group 2 (0.4-mm titanium mesh, n = 10) and group 3 (0.6-mm titanium mesh, n = 8), were 121.3 and 234.0 N, respectively. Mean force of first failure was 92.0 N for group 2 and 164.8 N for group 3. Conclusions: The force required for failure of the mesh is significantly greater than the 0.17 N exerted on a CI magnet by a 1.5-tesla MRI scan.
The Role of Matrix Metalloproteinase 9 in Early Neurological Worsening of Acute Lacunar Infarction
Authors: Kim Young Seo , Lee Kyu-Yong , Koh Seong-Ho , Park Chang Yun , Kim Hyun Young , Lee Young Joo , Kim Hee Tae , Kim Juhan , Kim Myung-Ho , Kim Kyung Suk , Chang Dae-il , Kim Seung Hyun
Published: January 2006

The involvement of matrix metalloproteinases (MMPs) in ischemic-stroke-induced inflammatory response has recently been suggested; however, the relationship between MMPs and stroke progression has not been evaluated. We investigated the role of MMPs in neurological worsening of acute lacunar infarction. Forty-nine consecutive patients with an acute lacunar infarction (as defined by clinical and MRI criteria within 48 h after stroke onset) were evaluated. Clinical, biochemical, rheological, inflammatory and other parameters were compared between progressive and nonprogressive groups. Among the variables, only inflammatory parameters, including MMP-9 and erythrocyte sedimentation rate, were associated with neurological worsening of acute lacunar infarction (p < 0.05). These results suggest that the inflammatory process could play an important role in early neurological worsening of acute lacunar infarction.
Examination by Near-Infrared Spectroscopy for Evaluation of Piano Performance as a Frontal Lobe Activation Task
Authors: Hashimoto Keiji , Tategami Shoko , Okamoto Takatsugu , Seta Hiroshi , Abo Masahiro , Ohashi Masahiro
Published: January 2006

The purpose of this study was to reveal the activation of the frontal lobe in piano performance by the use of near-infrared spectroscopy. Participants wereseven healthy volunteer music college students. The results of the examination showed a tendency towards an increase in total hemoglobin volume over a wider area in the frontal part of the brain during an appropriate piano task compared with an easy piano task or the Keio version of the Wisconsin Card Sorting Test. The results suggest that piano performance is recognized as a frontal lobe-activating task and that performance of an appropriate piano task can be expected to elicit wider activation of the frontal lobe than an easy one.
Patterns of Perfection in Damascius' Life of Isidore
Authors: O'Meara Dominic
Published: January 2006

In this article, it is shown that, following the precedent set in particular by Marinus' Life of Proclus, Damascius, in his Life of Isidore, uses biography so as to illustrate philosophical progress through the Neoplatonic scale of virtues. Damascius applies this scale, however, to a wide range of figures belonging to pagan philosophical circles of the fifth century AD: they show different degrees and forms of progress in this scale and thus provide an edificatory panorama of patterns of philosophical perfection. Each level of the scale of virtues is shown to be exemplified in Damascius' biographies. It is suggested that few, in Damascius' opinion, reached the highest levels of virtue and that philosophical decline is intimated in his descriptions of his contemporaries.
Electrical and Mechanical Characterization of Hybrid CFRP Sheets
Authors: Wu Z. S. , Yang C. Q. , Tobe Y. H. , Ye L. P. , Harada T.
Published: January 2006

This study brings forth the electrical and mechanical models of a new kind of hybrid carbon fiber-reinforced polymer (HCFRP) composites consisting of several types of carbon fibers with different strengths and Young’s moduli. Then, an experimental program with some main variables including the carbon fiber types and their volume fractions has been carried out. Six types of specimens have been fabricated to investigate the mechanical properties and self-health monitoring function of the HCFRP sheets with different types of carbon fiber and volume fractions. The experimental results indicate that the hybridization of several types of carbon fibers is an effective method for upgrading the mechanical properties of the HCFRP sheets. The electrical resistance of the HCFRP sheets changes with the strain in a stepwise manner due to the gradual macro-fracture of different types of carbon fibers. The number of steps is related to the number of carbon fiber types. It has also been shown that the ruptured carbon fibers can still contribute to the current conduction through transverse electrical conduction. The good correlations between the mechanical and electrical behaviors reveal the self-health monitoring function of the HCFRP sheets.
Identification of Fiber-reinforced Plastic Failure Mechanisms from Acoustic Emission Data using Neural Networks
Authors: Ativitavas Nat , Pothisiri Thanyawat , Fowler Timothy J.
Published: January 2006

The identification of the type of discontinuities or failure mechanisms within fiber-reinforced plastic (FRP) structures normally requires the use of local nondestructive testing (NDT) methods, which is time and labor intensive. The global NDT methods, e.g., the use of acoustic emission (AE) data, are viewed as a more powerful alternative for the identification of FRP failure mechanisms. Despite numerous investigations on the subject, no specific conclusions have been reached. In this study, the identification of the various failure mechanisms of FRP using AE data is investigated. The neural network technique is used to perform pattern recognition of AE data for the identification of FRP failure mechanism. An extensive experimental program, using coupon and full-scale specimens, is conducted to construct the AE database for training and testing the neural networks. Two network systems are developed based on two different training approaches: backpropagation and probabilistic method. In addition, two levels of neural networks - primary and secondary - are used to enhance the accuracy of the prediction. Various AE correlation plots are used as trial input data to feed the networks. It is demonstrated that the identification results from using the proposed network systems are very promising, with the overall performance of up to 97% accuracy.
Joint Actions and Group Agents
Authors: Pettit Philip , Schweikard David
Published: January 2006

Joint action and group agency have emerged as focuses of attention in recent social theory and philosophy but they have rarely been connected with one another. The argument of this article is that whereas joint action involves people acting together to achieve any sort of result, group agency requires them to act together for the achievement of one result in particular: the construction of a centre of attitude and agency that satisfies the usual constraints of consistency and rationality in adequate measure. The main discovery in the recent theory of group agency is that this result is not easily achieved; no regular voting procedure will ensure, for example, that a group of individually consistent agents will display consistency in group judgments.
How Not to Think about Rules and Rule Following
Authors: Bernasconi-Kohn Lorenzo
Published: January 2006

This article offers a critique of Karsten Stueber’s account of rule following as presented in his article “How to Think about Rules and Rule Following.” The task Stueber sets himself is of defending the idea that human practices are bound and guided by rules (both causally and normatively) while avoiding the discredited “cognitive model of rule following.” This article argues that Stueber’s proposal is unconvincing because it falls foul of the very problems it sets out to avoid. Stueber’s defense of rules as normative guides is shown to be either circular or burdened with an infinite regress, while his account of rules as causal determinants of our actions is shown to lapse back into the “cognitive model” that he explicitly rejects.
How to Structure a Social Theory?
Authors: Stueber Karsten R.
Published: January 2006

This essay challenges King’s argument for the claim that social relations have to be conceived of as primary and main ontological category for an adequate analysis of the social realm. The author shows that King’s arguments do not succeed in fully replacing the categories of agency and structure that are pervasive in contemporary social theory. At most, King succeeds in delineating a neglected area of social theory, something that should be taken into account in addition to structure and agency.
Marx for the Present
Authors: Hudelson Richard
Published: January 2006

Marxism as a political movement appears to have exhausted itself, but Marx the thinker engages us still. In different ways Allan Megill and David Steele work to dispel the lingering shade of Marx, exposing what each sees as a deep flaw in Marxist thought. In contrast, the papers collected in Marxism and Social Sciences argue for the continued merit of many of Marx’s ideas. Each book makes a significant contribution to our ongoing dialogue with Marx.
Diabetes Nurse Educators and Preconception Counseling
Authors: Michel Brenda , Charron-Prochownik Denise
Published: January 2006

Purpose: The purpose of this study was to examine the diabetes nurse educator’s role, practice, and training in preconception counseling (PC) when caring for adolescents with diabetes.

Methods: A descriptive, correlational research design, using a cross-sectional survey technique, was used. Subjects were 2003 registered nurse members of the American Association of Diabetes Educators. A survey instrument was developed by the investigator and placed on the World Wide Web.

Results: Although most of the diabetes nurse educators were aware of PC, most reported not having received any training in PC and would benefit from this education. Thirty percent of the respondents did not routinely provide PC to their adult female clients, and 40% did not provide this to adolescents.

Conclusions: Results of this study suggest that the diabetes nurse educators in this sample would benefit from receiving instruction about PC. The diabetes nurse educators should be trained to provide PC to all female clients with diabetes of childbearing age starting at puberty.
Low-Glycemic Index Carbohydrates
Authors: Burani Johanna , Longo Palma J.
Published: January 2006

Purpose: This retrospective study evaluated the incorporation of low-glycemic index (GI) carbohydrates into daily meal planning as an effective behavioral lifestyle change to improve glycemic control and weight management in patients with type 1 and 2 diabetes.

Methods: Twenty-one subjects participated in this study. All office visits and interview sessions took place in a 2-physician private medical practice setting in Wayne, New Jersey. Patients’ pre- and postcounseling HbA1c and body mass index (BMI) values and their antidiabetic medication dosages were recorded. Audiotaped interviews were conducted using the 10-question Glycemic Index Foods Quiz (GIFQ) and the 29-question Interview Questionnaire (IQ). The GI values of pre- and postcounseling meals were calculated. Assessment was based on triangulating the subjects’ adherence to the low-GI carbohydrate behavioral change and the primary outcome measures: HbA1c and BMI.

Results: Low-GI medical nutrition therapy (LGI-MNT) counseling reduced HbA1c by 19% (mean drop of 1.5 U) and decreased BMI by 8% (mean loss of 17 pounds). This was accomplished by the participants independently lowering the GI values of their meals by 25% (mean reduction of 15 points). Results were achieved over a time frame of 3 to 36 months from the initial LGI-MNT counseling session.

Conclusions: Daily incorporation of low-GI carbohydrates in meal planning can be an effective diabetes self-management strategy for glycemic control and weight management. The documented responses to the subjects’ conceptual and practical knowledge of the GI confirm their acceptance of this approach as a permanent behavioral lifestyle change and not a “diet.” The positive results of this study attest to what worked for these subjects, inviting diabetes educators to consider offering low-GI dietary advice to their diabetes patients.