bluuebunny/crossref_metadata_2025 huggingface dataset:
Traumatic injuries to the primary dentition and effects on the permanent successors – a clinical follow‐up study
Authors: Sennhenn‐Kirchner Sabine , Jacobs Hans‐Georg
Published: April 2006

Abstract –  This study investigated problems in the permanent dentition that, according to history and records, were attributable to dental alveolar injuries of the primary dentition. 106 children have been involved in the study, who had experienced primary anterior tooth trauma affecting a total of 200 teeth. Thirty‐nine patients (81 teeth) were available for follow‐up examinations. In 25% of the cases followed up, damage was found on the successors in the secondary dentition (16 children/20 teeth). In half of the cases, a comparatively mild form of lesion like enamel discoloration was observed. This was the result of an injury during the tooth maturation process causing enamel hypoplasia. Clinically more relevant were the dental deformities: cessation of root formation or retention caused by ankylosis, which made up the remaining 50% of cases. This was confirmed by clinical long‐term observation. The different effects on the permanent teeth can only be detected by radiography after an interval of several months or may even be clinically assessed only after the eruption of the clinical crown.
Understanding Runaway Teens
Authors: Martinez Ruby J.
Published: April 2006

PROBLEM:  Large numbers of teenagers become “runaways” and put themselves at risk for physical and emotional harm. During the year 2002, an estimated 1.6 million U.S. youth aged 12 to 17 had run away from home and slept on the streets.

METHODS:  A qualitative exploratory method was used to study a sample of primarily ethnic minority youth found in a Midwestern inner city detention center. This study examined run behavior from the teenager’s own perspective to identify why they ran, how they kept themselves safe, and what factors contributed to ending a run.

FINDINGS:  Teens ran to gain control of their lives by changing their situation. They developed new affiliations to meet safety and sustenance needs and learned from experience that one cannot run from your problems. With experience, running became habitual.

CONCULSIONS:  Safer alternatives are needed for youth who cannot live at home.
OBTAINING FRACTURE INFORMATION FOR LOW‐PERMEABILITY (TIGHT) GAS SANDSTONES FROM SIDEWALL CORES
Authors: Laubach S. E. , Gale J. F. W.
Published: April 2006

We illustrate a fracture characterization technique applicable to all tight gas sandstones. The technique uses microfractures and cements in the rock mass identified using SEM‐based cathodoluminescence imaging to provide information on unsampled large fractures, including strike and cross‐cutting relationships, intensity, and likelihood of preserved open fractures. We applied the technique in two tight gas sandstone wells in the Pennsylvanian Pottsville Formation, Black Warrior Basin, Alabama, USA. In one well, data was obtained entirely from drilled 1–inch diameter sidewall cores that were oriented using image logs and features visible in cores. We predicted fracture porosity preservation in large fractures using late cements in the rock mass as a proxy for fracture observation. Results from the technique are consistent with what is known of large fractures in this area. Where we predicted open, high intensity fractures, substantial gas flares were observed during drilling. By combining microstructural and diagenetic observations, it is possible to overcome the inadequate fracture sampling that plagues evaluation of natural fractures and that relies solely on observations of macroscopically visible fractures.
SEISMIC FACIES ANALYSIS BASED ON 3D MULTI‐ATTRIBUTE VOLUME CLASSIFICATION, DARIYAN FORMATION, SE PERSIAN GULF
Authors: Farzadi P.
Published: April 2006

Interpretation of recently acquired 3D seismic data from the adjacent Sirri C and D oilfields in the SE Persian Gulf indicates that a 3D interpretation of seismic facies is crucial to resolve the internal stratal geometries of the Aptian Dariyan Formation. This carbonate formation passes southward into the Shu'aiba Formation, a prolific reservoir rock of similar facies in the UAE. Lack of exposures and limited cored intervals have forced reliance on the seismic data for evidence of the depositional environment and the internal architecture of potential reservoir rocks. The progradational nature of the Dariyan Formation and the occurrence of carbonate build‐ups within it make this stratal geometry complex. The complex internal heterogeneity of the build‐ups and presence of seismic noise make mapping of the build‐ups in 3D space using conventional seismic interpretation tools difficult, despite the availability of high‐quality 3D seismic data covering the area.

The high quality seismic and limited well data from this field is one of the few datasets of this kind presented in the literature. A procedure for the hierarchical multi‐attribute analysis of seismic facies using Paradigm's Seis Facies software is used in this study to provide a 3D interpretation of the stratal patterns. Principal component analysis reduces the noise and redundant data by representing the main data variances as a few vector components in a transformed coordinate system. Cluster analysis is performed using those components which have the greatest contribution to the maximum spread of the data variability. Six seismic attribute volumes are used in this study and the result is a single 3D classified volume.

Important new information obtained from within the Dariyan Formation gives new insights into its stratigraphic distribution and internal variability. This method of processing seismic data is a step towards exploring for subtle stratigraphic traps in the study area, and may help to identify exploration targets.
BIOMARKER GEOCHEMISTRY OF CRUDE OILS FROM THE QAIDAM BASIN, NW CHINA
Authors: Duan Yi , Zheng Chaoyang , Wang Zhiping , Wu Baoxiang , Wang Chuanyuan , Zhang Hui , Qian Yaorong , Zheng Guodong
Published: April 2006

A suite of 16 crude oil samples from 13 oilfields in the Qaidam Basin were analyzed using techniques including gas chromatography and gas chromatography ‐ mass spectrometry. Biomarker compositions and parameters were used to investigate the palaeoenvironmental and depositional conditions and to correlate the oils with eachother. Oils from the western Qaidam Basin have pristane/phytane (Pr/Ph) ratios of less than 0.7, and contain abundant gammacerane, C27 steranes, 4‐methyl steranes and long‐chain tricyclic terpanes. C29 sterane 20S/(20S+20R) and ββ/(ββ+αα) ratios show that the western Qaidam oils have variable maturities ranging from immature to mature. Oils from the northern Qaidam Basin, by contrast, have Pr/Ph ratios greater than 3, low gammacerane contents, and relatively abundant C29 steranes, bicyclic terpanes and alkylcyclohexanes. C29 sterane 20S/(20S+20R) and ββ/(ββ+αα) ratios indicate that the northern Qaidam oils are mature.

δ13C values, which range from ‐25.4‰ to ‐28.3‰ with the exception of one oil from the north (‐3l.6‰), are similar for oils from both the northern and western parts of the Qaidam Basin. The oils'carbon isotope compositions are similar to those of the organic matter in potential source rocks.

The western Qaidam oils are inferred to have originated from Tertiary source rocks deposited under anoxic and saline‐hypersaline lacustrine conditions with dominant algal organic matter. The northern Qaidam oils are interpreted to be derived from Jurassic source rocks which were deposited in a freshwater lacustrine environment and which are dominated by terrigenous organic matter.
Evidence for local specialization in a generalist mammalian herbivore, Neotoma fuscipes
Authors: Brooke McEachern Mary , A. Eagles‐Smith Collin , M. Efferson Charles , H. Van Vuren Dirk
Published: April 2006

Herbivores with very plastic dietary requirements, or so‐called generalist species, can include individuals that develop specialized feeding habits through their experience with local chemically‐defended plants. Local specialization has important implications for understanding a variety of ecological and evolutionary dynamics. However, the extent to which individuals within a generalist species specialize on local plants and the consequences of such specialization remain poorly understood, especially in non‐insect herbivores. To better understand this phenomenon, we determined the diet and food preferences of a generalist mammalian herbivore, the dusky‐footed woodrat (Neotoma fuscipes), in two adjacent but distinct plant communities. Based on a combination of cafeteria trials and stable isotope analyses (δ13C and δ15N), our results indicate that woodrats display preferences for local plants and tend to avoid novel chemically‐defended plants. Moreover, both methodologies support the conclusion that individual woodrats are dietary specialists restricting their diets to only a few (2‐3) of the available plant species. In juniper woodland, woodrats prefer western juniper (Juniperus occidentalis), while less than one km away in mixed‐coniferous forest, woodrats prefer incense cedar (Calocedrus decurrens). Both plants contain high levels of plant secondary compounds that require detoxification mechanisms within consumers. Therefore, preferences are likely indicative of underlying physiological adaptations that could promote further behavioral, physiological and ultimately genetic differences between woodrats in different habitats. This study provides additional evidence for local specialization and urges caution when using the term generalist to characterize feeding behaviors at the individual level.
Spatial distribution and environmental correlates of Australian snubfin and Indo‐Pacific humpback dolphins
Authors: J. Parra Guido , Schick Robert , J. Corkeron Peter
Published: April 2006

We present data on the spatial distribution of Australian snubfin and humpback dolphins using boat‐based line transect surveys in three adjacent bays located in the Far Northern Section of the Great Barrier Reef Marine Park, northeast Queensland. We used Geographic Information Systems (GIS), and both randomization and Mantel tests to examine the relationship between the spatial distribution of the dolphins and three simple, readily quantified, environmental variables: distance to land, distance to river mouth, and water depth. Mantel tests allowed us to make clear inferences about the correlation of the species’ distributions with environmental variables, while taking into account spatial autocorrelation and intercorrelation among variables. Randomization tests indicated snubfin and humpback dolphins occur closer to land than would be expected at random. Two‐sample randomization tests indicated snubfin dolphins were found closer to river mouths than were humpback dolphins. Taking spatial autocorrelation into account, Mantel tests indicated all environmental variables were correlated with the spatial distribution of snubfin and humpback dolphins. Interspecific differences in spatial distribution appeared to be related to proximity to river mouths. Preference by snubfin and humpback dolphins for nearshore, estuarine waters is likely related to the productivity of these tropical coastal areas. This spatial analysis suggests that existing protected areas in this region may not include the most critical habitats for snubfin and humpback dolphins. The techniques used here shown relationships between the spatial distribution of the dolphins and environmental features that should facilitate their management and conservation.
Effect of transdermal nicotine administration on exercise endurance in men
Authors: Mündel Toby , Jones David A.
Published: April 2006

Nicotine is widely reported to increase alertness, improve co‐ordination and enhance cognitive performance; however, to our knowledge there have been no attempts to replicate these findings in relation to exercise endurance. The purpose of this study was to determine the effects nicotine might have on cycling endurance, perception of exertion and a range of physiological variables. With local ethics committee approval and having obtained informed consent, 12 healthy, non‐smoking men (22 ± 3 years; maximal O2 uptake, 56 ± 6 ml kg−1 min−1, mean ±s.d.) cycled to exhaustion at 18°C and 65% of their peak aerobic power, wearing either a 7 mg transdermal nicotine patch (NIC) or a colour‐matched placebo (PLA) in a randomized cross‐over design; water was available ad libitum. Subjects were exercising at approximately 75% of their maximal O2 uptake with no differences in cadence between trials. Ten out of 12 subjects cycled for longer with NIC administration, and this resulted in a significant 17 ± 7% improvement in performance (P < 0.05). No differences were observed for perceived exertion, heart rate or ventilation. There were no differences in concentrations of plasma glucose, lactate or circulating fatty acids. In the absence of any effect on peripheral markers, we conclude that nicotine prolongs endurance by a central mechanism. Possible modes of action are suggested.
17β‐Oestradiol enhances the acute hypotensive effect of captopril in female ovariectomized spontaneously hypertensive rats
Authors: Giménez José , García M. Paz , Serna Mar , Bonacasa Bárbara , Carbonell Luis F. , Quesada Tomás , Hernández Isabel
Published: April 2006

The objective of this study was to investigate whether the acute haemodynamic effects of angiotensin‐converting enzyme inhibition with captopril could be enhanced by oestrogen administration, and then to evaluate the mechanisms involved in this enhancement. All experiments were performed in 18‐week‐old female spontaneously hypertensive rats arranged in three experimental groups: intact; ovariectomized (OVX); and ovariectomized plus treatment with 17β‐oestradiol (OVX + E2). These groups were used to evaluate the effects of captopril administration alone, or following bradykinin B2 receptor blockade or nitric oxide synthase inhibition, on a number of haemodynamic parameters (mean arterial pressure, cardiac index, vascular resistance and heart rate). The drop in mean arterial pressure and vascular resistance index in response to captopril was more pronounced in intact and ovariectomized rats treated with 17β‐oestradiol than in ovariectomized animals. Blockade of bradykinin B2 receptors or inhibition of nitric oxide synthesis attenuated the synergy between 17β‐oestradiol and captopril. It is concluded that ovariectomy blunted the blood pressure and vascular resistance index drop observed in intact rats in response to captopril. Treatment with 17β‐oestradiol prevented the blunted response to captopril in ovariectomized rats. Kinins and nitric oxide may be involved in the mechanisms of 17β‐oestradiol potentiation of the haemodynamic effects of captopril.
Crossbridge and non‐crossbridge contributions to tension in lengthening rat muscle: force‐induced reversal of the power stroke
Authors: Pinniger G. J. , Ranatunga K. W. , Offer G. W.
Published: April 2006

Lengthening of active muscle is an essential feature of animal locomotion, but the molecular processes occurring are incompletely understood. We therefore examined and modelled tension responses to ramp stretches (5% fibre length, L0) over a wide range of velocities (0.1–10 L0 s−1) of tetanized intact rat muscle fibre bundles (L0∼2 mm) with a resting sarcomere length of 2.5 μm at 20°C. Tension rose to a peak during stretch and decayed afterwards to a level which was higher than the prestretch tetanic tension. This residual force enhancement was insensitive to velocity. The tension rise during stretch showed an early transition (often appearing as an inflection) at ∼1 ms. Both the stretch (L1) and the tension rise at this transition increased in proportion to velocity. A second transition, marked by a reduction in slope, occurred at a stretch of ∼18 nm per half‐sarcomere; the rise in tension at this transition increased with velocity towards a plateau. Based on analyses of the velocity dependence of the tension and modelling, we propose that the initial steep increase in tension arises from increasing strain of all attached crossbridges and that the first transition reflects the tension loss due to the original post‐stroke heads executing a reverse power stroke. Modelling indicates that the reduction in slope at the second transition occurs when the last of the heads that were attached at the start of the ramp become detached. Thereafter, the crossbridge cycle is largely truncated, with prepower stroke crossbridges rapidly detaching at high strain and attaching at low strain, the tension being borne mainly by the prestroke heads. Analysis of the tension decay after the ramp and the velocity dependence of the peak tension suggest that a non‐crossbridge component increasingly develops tension throughout the stretch; this decays only slowly, reaching at 500 ms after the ramp ∼20% of its peak value. This is supported by the finding that, in the presence of 10 μmN‐benzyl‐p‐toluene sulphonamide (a myosin inhibitor), while isometric tension is reduced to ∼15%, and the crossbridge contribution to stretch‐induced tension rise is reduced to 30–40%, the peak non‐crossbridge contribution and the residual force enhancement remain high. We propose that the residual force enhancement is due to changes upon activation in parallel elastic elements, specifically that titin stiffens and C‐protein–actin interactions may be recruited.
Detached Eddy Simulation of Film Cooling Performance on the Trailing Edge Cutback of Gas Turbine Airfoils
Authors: Martini P. , Schulz A. , Bauer H. -J. , Whitney C. F.
Published: April 2006

The present study deals with the unsteady flow simulation of trailing edge film cooling on the pressure side cut back of gas turbine airfoils. Before being ejected tangentially on the inclined cut-back surface, the coolant air passes a partly converging passage that is equipped with turbulators such as pin fins and ribs. The film mixing process on the cut back is complicated. In the near slot region, due to the turbulators and the blunt pressure side lip, turbulence is expected to be anisotropic. Furthermore, unsteady flow phenomena like vortex shedding from the pressure side lip might influence the mixing process (i.e., the film cooling effectiveness on the cut-back surface). In the current study, three different internal cooling designs are numerically investigated starting from the steady RaNS solution, and ending with unsteady detached eddy simulations (DES). Blowing ratios M=0.5; 0.8; 1.1 are considered. To obtain both, film cooling effectiveness as well as heat transfer coefficients on the cut-back surface, the simulations are performed using adiabatic and diabatic wall boundary conditions. The DES simulations give a detailed insight into the unsteady film mixing process on the trailing edge cut back, which is indeed influenced by vortex shedding from the pressure side lip. Furthermore, the time averaged DES results show very good agreement with the experimental data in terms of film cooling effectiveness and heat transfer coefficients.
Thermal-Mechanical
Life Prediction System for Anisotropic Turbine
Components
Authors: Cunha F.
J. , Dahmer M.
T. , Chyu M.
K.
Published: April 2006

Modern gas turbine engines provide large amounts of thrust and withstand severe thermal-mechanical conditions during the load and mission operations characterized by cyclic transients and long dwell times. All these operational factors can be detrimental to the service life of turbine components and need careful consideration. Engine components subject to the harshest environments are turbine high-pressure vanes and rotating blades. Therefore, it is necessary to develop a turbine component three-dimensional life prediction system, which accounts for mission transients, anisotropic material properties, and multi-axial, thermal-mechanical, strain, and stress fields. This paper presents a complete life prediction approach for either commercial missions or more complex military missions, which includes evaluation of component transient metal temperatures, resolved maximum shear stresses and strains, and subsequent component life capability for fatigue and creep damage. The procedure is based on considering all of the time steps in the mission profile by developing a series of extreme points that envelop every point in the mission. Creep damage is factored into the component capability by debiting thermal-mechanical accumulated cycles using the traditional Miner’s rule for accumulated fatigue and creep damage. Application of this methodology is illustrated to the design of the NASA Energy Efficient Engine (E3) high pressure turbine blade with operational load shakedown leading to stress relaxation on the external hot surfaces and potential state of overstress in the inner cold rib regions of the airfoil.
Comparison of Turbine Tip Leakage Flow for Flat Tip and Squealer Tip Geometries at High-Speed Conditions
Authors: Key Nicole L. , Arts Tony
Published: April 2006

The tip leakage flow characteristics for flat and squealer turbine tip geometries are studied in the von Karman Institute Isentropic Light Piston Compression Tube facility, CT-2, at different Reynolds and Mach number conditions for a fixed value of the tip gap in a nonrotating, linear cascade arrangement. To the best knowledge of the authors, these are among the very few high-speed tip flow data for the flat tip and squealer tip geometries. Oil flow visualizations and static pressure measurements on the blade tip, blade surface, and corresponding endwall provide insight to the structure of the two different tip flows. Aerodynamic losses are measured for the different tip arrangements, also. The squealer tip provides a significant decrease in velocity through the tip gap with respect to the flat tip blade. For the flat tip, an increase in Reynolds number causes an increase in tip velocity levels, but the squealer tip is relatively insensitive to changes in Reynolds number.
Atomic Pillar-Based Nanoprecipitates Strengthen AlMgSi Alloys
Authors: Chen J. H. , Costan E. , van Huis M. A. , Xu Q. , Zandbergen H. W.
Published: April 2006

Atomic-resolution electron microscopy reveals that pillarlike silicon double columns exist in the hardening nanoprecipitates of AlMgSi alloys, which vary in structure and composition. Upon annealing, the Si
2
pillars provide the skeleton for the nanoparticles to evolve in composition, structure, and morphology. We show that they begin as tiny nuclei with a composition close to Mg
2
Si
2
Al
7
and a minimal mismatch with the aluminum matrix. They subsequently undergo a one-dimensional growth in association with compositional change, becoming elongated particles. During the evolution toward the final Mg
5
Si
6
particles, the compositional change is accompanied by a characteristic structural change. Our study explains the nanoscopic reasons that the alloys make excellent automotive materials.
Atomic-Scale Coupling of Photons to Single-Molecule Junctions
Authors: Wu S. W. , Ogawa N. , Ho W.
Published: April 2006

Spatial resolution at the atomic scale has been achieved in the coupling of light to single molecules adsorbed on a surface. Electron transfer to a single molecule induced by green to near-infrared light in the junction of a scanning tunneling microscope (STM) exhibited spatially varying probability that is confined within the molecule. The mechanism involves photo-induced resonant tunneling in which a photoexcited electron in the STM tip is transferred to the molecule. The coupling of photons to the tunneling process provides a pathway to explore molecular dynamics with the combined capabilities of lasers and the STM.
A Plant miRNA Contributes to Antibacterial Resistance by Repressing Auxin Signaling
Authors: Navarro Lionel , Dunoyer Patrice , Jay Florence , Arnold Benedict , Dharmasiri Nihal , Estelle Mark , Voinnet Olivier , Jones Jonathan D. G.
Published: April 2006

Plants and animals activate defenses after perceiving pathogen-associated molecular patterns (PAMPs) such as bacterial flagellin. In
Arabidopsis
, perception of flagellin increases resistance to the bacterium
Pseudomonas syringae
, although the molecular mechanisms involved remain elusive. Here, we show that a flagellin-derived peptide induces a plant microRNA (miRNA) that negatively regulates messenger RNAs for the F-box auxin receptors TIR1, AFB2, and AFB3. Repression of auxin signaling restricts
P. syringae
growth, implicating auxin in disease susceptibility and miRNA-mediated suppression of auxin signaling in resistance.
Biomechanics and tennis
Authors: Elliott B
Published: April 2006

Success in tennis requires a mix of player talent, good coaching, appropriate equipment, and an understanding of those aspects of sport science pertinent to the game. This paper outlines the role that biomechanics plays in player development from sport science and sport medicine perspectives. Biomechanics is a key area in player development because all strokes have a fundamental mechanical structure and sports injuries primarily have a mechanical cause.
Extensor carpi ulnaris injuries in tennis players: a study of 28 cases
Authors: Montalvan B , Parier J , Brasseur J L , Viet D L , Drape J L
Published: April 2006

Pain on the ulnar side of the wrist is common among elite tennis players. Ten years of experience has allowed identification of a pathology involving the extensor carpi ulnaris (ECU) tendon. On the basis of 28 clinical cases seen over the last five years, three clinical patterns are described: (a) acute instability of the ECU; (b) tendinopathy; (c) ECU rupture. Each of these clinical entities requires a different therapeutic approach. A review of the relevant anatomy is provided.
Voluntary fluid intake and core temperature responses in adolescent tennis players: sports beverage versus water
Authors: Bergeron M F , Waller J L , Marinik E L
Published: April 2006

Objective:To examine differences in ad libitum fluid intake, comparing a 6% carbohydrate/electrolyte drink (CHO-E) and water, and associated differences in core temperature and other selected physiological and perceptual responses in adolescent athletes during tennis training in the heat.

Methods:Fourteen healthy, fit, young tennis players (nine male; five female; mean (SD) age 15.1 (1.4) years; weight 60.6 (8.3) kg; height 172.8 (8.6) cm) completed two 120 minute tennis specific training sessions on separate days (randomised, crossover design) in a warm environment (wet bulb globe temperature: CHO-E, 79.3 (2.6) °F; water, 79.9 (2.2) °F; p>0.05).

Results:There were no significant differences (p>0.05) between the trials with respect to fluid intake, urine volume, fluid retention, sweat loss, perceived exertion, thirst, or gastrointestinal discomfort. However, there was a difference (p<0.05) in the percentage body weight change after training (CHO-E, −0.5 (0.7)%; water, −0.9 (0.6)%). Urine specific gravity before training (CHO-E, 1.024 (0.006); water, 1.025 (0.005)) did not correlate significantly (p>0.05) with any of these measurements or with core body temperature. In examining the main effect for trial, the CHO-E trial showed a significantly lower (p<0.001) mean body temperature (irrespective of measurement time) than the water trial. However, the mean body temperature in each trial was not associated (p>0.05) with fluid intake, fluid retention, sweat loss, or percentage body weight change.

Conclusion:Ad libitum consumption of a CHO-E drink may be more effective than water in minimising fluid deficits and mean core temperature responses during tennis and other similar training in adolescent athletes.
LEGENDRIAN VERTICAL CIRCLES IN SMALL SEIFERT SPACES
Authors: WU HAO
Published: April 2006

We discuss the relations between the e0 invariant of a tight contact small Seifert space and the twisting numbers of Legendrian vertical circles in it, and apply these relations to classify up to isotopy tight contact structures on small Seifert spaces with e0 ≠ 0, -1, -2.
Comparison of lung sound transducers using a bioacoustic transducer testing system
Authors: Kraman Steve S. , Wodicka George R. , Pressler Gary A. , Pasterkamp Hans
Published: April 2006

Sensors used for lung sound research are generally designed by the investigators or adapted from devices used in related fields. Their relative characteristics have never been defined. We employed an artificial chest wall with a viscoelastic surface and a white noise signal generator as a stable source of sound to compare the frequency response and pulse waveform reproduction of a selection of devices used for lung sound research. We used spectral estimation techniques to determine frequency response and cross-correlation of pulses to determine pulse shape fidelity. The sensors evaluated were the Siemens EMT 25 C accelerometer (Siemens); PPG 201 accelerometer (PPG); Sony ECM-T150 electret condenser microphone with air coupler (air coupler; with cylindrical air chambers of 5-, 10-, and 15-mm diameter and conical air chamber of 10-mm diameter); Littman classic stethoscope head (Littman) connected to an electret condenser microphone; and the Andries Tek (Andries) electronic stethoscope. We found that the size and shape of the air coupler chamber to have no important effect on the detected sound. The Siemens, air coupler, and Littman performed similarly with relatively flat frequency responses from 200 to 1,200 Hz. The PPG had the broadest frequency response, with useful sensitivity extending to 4,000 Hz. The Andries' frequency response was the poorest above 1,000 Hz. Accuracy in reproducing pulses roughly corresponded with the high-frequency sensitivity of the sensors. We conclude that there are important differences among commonly used lung sound sensors that have to be defined to allow the comparison of data from different laboratories.
IL-1β decreases the elastic modulus of human tenocytes
Authors: Qi Jie , Fox Ann Marie , Alexopoulos Leonidas G. , Chi Liqun , Bynum Donald , Guilak Farshid , Banes Albert J.
Published: April 2006

Cellular responses to mechanical stimuli are regulated by interactions with the extracellular matrix, which, in turn, are strongly influenced by the degree of cell stiffness (Young's modulus). It was hypothesized that a more elastic cell could better withstand the rigors of remodeling and mechanical loading. It was further hypothesized that interleukin-1β (IL-1β) would modulate intracellular cytoskeleton polymerization and regulate cell stiffness. The purpose of this study was to investigate the utility of IL-1β to alter the Young's modulus of human tenocytes. Young's modulus is the ratio of the stress to the strain, E = stress/strain = (F/ A)/(Δ L/ L0), where L0is the equilibrium length, Δ L is the length change under the applied stress, F is the force applied, and A is the area over which the force is applied. Human tenocytes were incubated with 100 pM recombinant human IL-1β for 5 days. The Young's modulus was reduced by 27–63%. Actin filaments were disrupted in >75% of IL-1β-treated cells, resulting in a stellate shape. In contrast, immunostaining of α-tubulin showed increased intensity in IL-1β-treated tenocytes. Human tenocytes in IL-1β-treated bioartificial tendons were more tolerant to mechanical loading than were untreated counterparts. These results indicate that IL-1β reduced the Young's modulus of human tenocytes by disrupting the cytoskeleton and/or downregulating the expression of actin and upregulating the expression of tubulins. The reduction in cell modulus may help cells to survive excessive mechanical loading that may occur in damaged or healing tendons.
Darbepoetin alfa Administered Every Other Week Maintains Hemoglobin Levels over 52 Weeks in Patients with Chronic Kidney Disease Converting from Once-Weekly Recombinant Human Erythropoietin: Results from Simplify the Treatment of Anemia with Aranesp (STAAR)
Authors: Hertel Joachim , Locay Harold , Scarlata Debra , Jackson Lynnae , Prathikanti Radha , Audhya Paul
Published: April 2006

Background/Aim: Darbepoetin alfa, an effective treatment for anemia of chronic kidney disease (CKD), can be administered at extended intervals. Simplify the Treatment of Anemia with Aranesp® (STAAR), a multicenter, 52-week study, was conducted to assess the efficacy of darbepoetin alfa administered subcutaneously every other week (Q2W) in maintaining hemoglobin (Hb) in CKD patients not receiving dialysis. Methods: This is a subgroup analysis of subjects converted from once-weekly (QW) recombinant human erythropoietin (rHuEPO; US Aranesp package insert) and who received up to 52 weeks of darbepoetin alfa therapy (evaluation period 20–32 weeks). Enrolled subjects had a creatinine clearance ≤70 ml/min or an estimated glomerular filtration rate ≤60 ml/min and transferrin saturation ≧20%. Darbepoetin alfa doses were titrated to maintain Hb levels ≤12 g/dl. The primary endpoint was mean Hb during evaluation. Results: There were 524 subjects enrolled in the study who were previously receiving rHuEPO QW. Mean Hb ± standard deviation was 11.2 ± 1.27 g/dl at baseline, and the least squares mean ± SE was 11.4 ± 0.04 during evaluation. The mean ± SD Q2W darbepoetin alfa dose was 49.7 ± 21.9 µg at baseline and 48.9 ± 35.5 µg at evaluation. Darbepoetin alfa was well tolerated. Conclusions: Study subjects with CKD receiving QW rHuEPO were effectively converted to Q2W darbepoetin alfa, which was well tolerated. Hb levels were maintained over 52 weeks without a significant change in darbepoetin alfa dose.
Soluble CD40L Levels Are Regulated by the −3459 A>G Polymorphism and Predict Myocardial Infarction and the Efficacy of Antithrombotic Treatment in Non-ST Elevation Acute Coronary Syndrome
Authors: Mälarstig Anders , Lindahl Bertil , Wallentin Lars , Siegbahn Agneta
Published: April 2006

Objectives—

Current evidence suggests the CD40–CD40L pathway as a key process in the development, progression, and outcome of acute coronary syndrome (ACS). The aim was to investigate the prognostic importance of soluble (s) CD40L levels, single nucleotide polymorphisms (SNP) in the CD40LG gene, and the relation between sCD40L and SNPs in patients with acute coronary syndromes (ACS).

Methods and Results—

Samples were obtained on admission from 2359 patients with non-ST elevation ACS randomized to an early invasive versus a conservative and to placebo controlled long-term dalteparin treatment in the FRISC-II study. The −3459 A>G SNP was identified as a novel regulator of sCD40L levels (
P
=0.001). In the placebo-treated group, sCD40L levels above median were associated with a 2.5-fold increased risk of myocardial infarction (MI) (
P
≤0.001) but not with raised mortality. In the dalteparin treated group, sCD40L showed no association with MI (
P
=0.75). Consequently, dalteparin treatment was effective in reducing the risk of MI only in patients with sCD40L levels above median. A combined assessment of troponin-T and sCD40L complemented the prognostic information on risk of MI.

Conclusions—

We identified a SNP in the CD40LG gene as a novel regulator of sCD40L plasma concentrations. Soluble CD40L levels above median reflect a prothrombotic state, which can be managed with the use of intense anti-thrombotic treatments.
Human Paraoxonase-1 Overexpression Inhibits Atherosclerosis in a Mouse Model of Metabolic Syndrome
Authors: Mackness Bharti , Quarck Rozenn , Verreth Wim , Mackness Mike , Holvoet Paul
Published: April 2006

Background—

The metabolic syndrome is typified by obesity, dyslipidemia, diabetes, hypertension, increased oxidative stress, and accelerated atherosclerosis. Paraoxonase1 (PON1), a high-density lipoprotein (HDL)-associated antioxidant enzyme that prevents the oxidation of low-density lipoprotein (LDL), is low in the metabolic syndrome.

Methods and Results—

We used adenovirus-mediated PON1 gene transfer (AdPON1) to overexpress human PON1 in mice with combined leptin and LDL receptor deficiency, a model of metabolic syndrome. PON1 activity, plasma lipids, the titer of autoantibodies against malondialdehyde (MDA)-modified LDL, and atherosclerosis in AdPON1 mice were compared with these in mice that received a control recombinant adenovirus (AdRR5). PON1 activity was increased 4.4-fold (
P
<0.001) in AdPON1 mice (N=12), whereas in AdRR5 mice (N=11) activity did not change. Expressing human PON1 significantly reduced the total plaque volume, the volume of plaque macrophages, and of plaque-associated oxidized LDL. It increased the percentage of smooth muscle cells in the plaques. Expressing human PON1 lowered the titer of autoantibodies against MDA-modified LDL, a proxy for oxidized LDL in mice. It had no overall effect on plasma total cholesterol and triglycerides, as evidenced by the similar area under the curves, and on the HDL distribution profile.

Conclusion—

Our data suggest that in this mouse model of metabolic syndrome, expressing human PON1 inhibited the development of atherosclerosis, probably by reducing the amount of oxidized LDL in plasma and in the plaque, thereby preventing its proatherogenic effects. Adenovirus-mediated gene transfer of human PON1 may be a potential and useful tool to prevent/retard atherosclerosis in humans.
New Insights to Vascular Smooth Muscle Cell and Pericyte Differentiation of Mouse Embryonic Stem Cells In Vitro
Authors: Lindskog Henrik , Athley Elisabet , Larsson Erik , Lundin Samuel , Hellström Mats , Lindahl Per
Published: April 2006

Objective—

The molecular mechanisms that regulate pericyte differentiation are not well understood, partly because of the lack of well-characterized in vitro systems that model this process. In this article, we develop a mouse embryonic stem (ES) cell-based angiogenesis/vasculogenesis assay and characterize the system for vascular smooth muscle cell (VSMC) and pericyte differentiation.

Methods and Results—

ES cells that were cultured for 5 days on OP9 stroma cells upregulated their transcription of VSMC and pericyte selective genes. Other SMC marker genes were induced at a later time point, which suggests that vascular SMC/pericyte genes are regulated by a separate mechanism. Moreover, sequence analysis failed to identify any conserved CArG elements in the vascular SMC and pericyte gene promoters, which indicates that serum response factor is not involved in their regulation. Gleevec, a tyrosine kinase inhibitor that blocks platelet-derived growth factor (PDGF) spell-receptor signaling, and a neutralizing antibody against transforming growth factor (TGF) β1, β2, and β3 failed to inhibit the induction of vascular SMC/pericyte genes. Finally, ES-derived vascular sprouts recruited cocultured MEF cells to pericyte-typical locations. The recruited cells activated expression of a VSMC- and pericyte-specific reporter gene.

Conclusions—

We conclude that OP9 stroma cells induce pericyte differentiation of cocultured mouse ES cells. The induction of pericyte marker genes is temporally separated from the induction of SMC genes and does not require platelet-derived growth factor B or TGFβ1 signaling.
Lipoprotein-Associated Phospholipase A
2
Predicts Future Cardiovascular Events in Patients With Coronary Heart Disease Independently of Traditional Risk Factors, Markers of Inflammation, Renal Function, and Hemodynamic Stress
Authors: Koenig Wolfgang , Twardella Dorothee , Brenner Hermann , Rothenbacher Dietrich
Published: April 2006

Objectives—

We sought to evaluate whether lipoprotein-associated phospholipase A
2
(Lp-PLA
2
), an emerging marker of cardiovascular risk, is associated with prognosis in patients with coronary heart disease (CHD).

Methods and Results—

Plasma concentrations and activity of Lp-PLA
2
were determined in 1051 patients aged 30 to 70 years with CHD who were followed for &4 years. A Cox proportional hazards model was used to determine the prognostic value of Lp-PLA
2
after adjustment for various covariates, including markers of inflammation, renal function, and hemodynamic stress. In multivariable analyses, Lp-PLA
2
mass and activity were strongly associated with cardiovascular events after controlling for traditional risk factors, severity of CHD, statin treatment, cystatin C, and N-terminal proBNP. The hazard ratio (HR) for recurrent events was 2.65 (95% confidence interval [CI], 1.47 to 4.76) for the top tertile of Lp-PLA
2
mass compared with the bottom tertile and 2.40 (95% CI, 1.35 to 4.29) for Lp-PLA
2
activity. After additional adjustment for low-density lipoprotein (LDL), the HRs were only moderately attenuated (mass: 2.09; 95% CI, 1.10 to 3.96; activity: 1.81; 95% CI, 0.94 to 3.49, respectively), but the latter was no longer statistically significant.

Conclusions—

Increased concentrations of Lp-PLA
2
predict future cardiovascular events in patients with manifest CHD independent of a variety of potential risk factors including markers of inflammation, renal function, and hemodynamic stress.
A Calmodulin-Binding Site on Cyclin E Mediates Ca
2+
-Sensitive G
1
/S Transitions in Vascular Smooth Muscle Cells
Authors: Choi Jaehyun , Chiang Andrew , Taulier Nicolas , Gros Robert , Pirani Asif , Husain Mansoor
Published: April 2006

Calcium transients are known to control several transition points in the eukaryotic cell cycle. For example, we have previously shown that a coordinate elevation in the intracellular free calcium ion concentration is required for G
1
- to S-phase cell cycle progression in vascular smooth muscle cells (VSMC). However, the molecular basis for this Ca
2+
sensitivity was not known. Using buffers with differing [Ca
2+
], we found that the kinase activity of mouse and human cyclin E/CDK2, but not other G
1
/S-associated cell cycle complexes, was responsive to physiological changes in [Ca
2+
]. We next determined that this Ca
2+
-responsive kinase activity was dependent on a direct interaction between calmodulin (CaM), one of the major Ca
2+
-signal transducers of eukaryotic cells, and cyclin E. Pharmacological inhibition of CaM abrogated the Ca
2+
sensitivity of cyclin E/CDK2 and retarded mouse VSMC proliferation by causing G
1
arrest. We next defined the presence of a highly conserved 22 amino acid N-terminal CaM-binding motif in mammalian cyclin E genes (dissociation constant, 1.5±0.1 μmol/L) and showed its essential role in mediating Ca
2+
-sensitive kinase activity of cyclin E/CDK2. Mutant human cyclin E protein, lacking this CaM-binding motif, was incapable of binding CaM or responding to [Ca
2+
]. Taken together, these findings reveal CaM-dependent cyclin E/CDK2 activity as a mediator of the known Ca
2+
sensitivity of the G
1
/S transition of VSMC.
Insulin-Like Growth Factor-1 and PTEN Deletion Enhance Cardiac L-Type Ca
2+
Currents via Increased PI3Kα/PKB Signaling
Authors: Sun Hui , Kerfant Benoit-Gilles , Zhao Dongling , Trivieri Maria G. , Oudit Gavin Y. , Penninger Josef M. , Backx Peter H.
Published: April 2006

Ca
2+
influx through the L-type Ca
2+
channel (
I
Ca,L
) is a key determinant of cardiac contractility and is modulated by multiple signaling pathways. Because the regulation of
I
Ca,L
by phosphoinositide-3-kinases (PI3Ks) and phosphoinositide-3-phosphatase (PTEN) is unknown, despite their involvement in the regulation of myocardial growth and contractility,
I
Ca,L
was recorded in myocytes isolated from mice overexpressing a dominant-negative p110α mutant (
DN-p110α
) in the heart, lacking the PI3Kγ gene (
PI3Kγ
−/−
) or with muscle-specific ablation of PTEN (
PTEN
−/−
). Combinations of these genetically altered mice were also examined. Although there were no differences in the expression level of Ca
V
1.2 proteins, basal
I
Ca,L
densities were larger (
P
<0.01) in
PTEN
−/−
myocytes compared with littermate controls,
PI3Kγ
−/−
, or
DN-p110α
myocytes and showed negative shifts in voltage dependence of current activation. The
I
Ca,L
differences seen in
PTEN
−/−
mice were eliminated by pharmacological inhibition of either PI3Ks or protein kinase B (PKB) as well as in
PTEN
−/−
/
DN-p110α
double mutant mice but not in
PTEN
−/−
/
PI3Kγ
−/−
mice. On the other hand, application of insulin-like growth factor-1 (IGF-1), an activator of PKB, increased
I
Ca,L
in control and
PI3Kγ
−/−
, while having no effects on
I
Ca,L
in
DN-p110α
or
PTEN
−/−
mice. The
I
Ca,L
increases induced by IGF-1 were abolished by PKB inhibition. Our results demonstrate that IGF-1 treatment or inactivation of PTEN enhances
I
Ca,L
via PI3Kα-dependent increase in PKB activation.
Regular Transfusion Lowers Plasma Free Hemoglobin in Children With Sickle-Cell Disease at Risk for Stroke
Authors: Lezcano Nelson E. , Odo Nadine , Kutlar Abdullah , Brambilla Donald , Adams Robert J.
Published: April 2006

Background and Purpose—

Intravascular hemolysis releases large amounts of free hemoglobin (PFH) in plasma of sickle- cell disease (SCD) patients. PFH has been associated with harmful endothelial actions including scavenging nitric oxide (NO). Whether PFH plays a role in stroke in SCD has not been examined.

Methods—

Serum levels of PFH, lactate dehydrogenase, and total bilirubin were measured in stored sera from children at risk for stroke treated in a randomized controlled trial of regular red cell transfusion (STOP study). Baseline and post-treatment (≈1 year of transfusion) were compared to determine whether treatment (which reduces stroke risk by 90%) was associated with reduction in markers of hemolysis.

Results—

Baseline serum PFH values did not differ between treatment groups. PFH declined with repeated transfusion from 78.7±8.2 mg/dL to 34.4±3.4 mg/dL (
P
<0.001). With only episodic or no transfusion the drop was smaller: 80.9±7.5 to 62.8±5.0 (
P
=0.019). The decrease was larger in those with regular transfusion (56% versus 22%;
P
<0.001). Reduction of lactate dehydrogenase and total bilirubin was observed only in those on regular transfusion.

Conclusions—

Regular transfusion which lowers stroke risk is associated with a significant reduction in PFH. A role for PFH in promoting stroke in SCD should be investigated.
Potential Contribution of NF-κB in Neuronal Cell Death in the Glutathione Peroxidase-1 Knockout Mouse in Response to Ischemia-Reperfusion Injury
Authors: Crack Peter J. , Taylor Juliet M. , Ali Uğur , Mansell Ashley , Hertzog Paul J.
Published: April 2006

Background and Purpose—

We have previously identified an increased susceptibility of Gpx1
−/−
mice to increased infarct size after middle cerebral artery occlusion (MCAO). This study was designed to elucidate the mechanisms involved in elevated neuronal cell death arising from an altered endogenous oxidant state.

Methods—

Gpx1
−/−
mice were exposed to transient MCAO and reperfusion by intraluminal suture blockade. Protein expression of the p65 subunit of transcription factor nuclear factor-κB (NF-κB) was examined by immunohistochemistry and Western Analysis. NF-κB DNA-protein activity was assessed by electrophoretic mobility shift assays (EMSA). Wild-type and Gpx1
−/−
mice were exposed to MCAO with or without the NF-κB inhibitor, pyrrolidinedithiocarbamate (PDTC).

Results—

Upregulation of the p65 subunit of NF-κB and subsequent p65 phosphorylation at serine 536 was detected in the Gpx1
−/−
brains after stroke. EMSAs revealed that increased ischemia-enhanced DNA binding of NF-κB was observed in Gpx1
−/−
mice compared with wild-type. Supershift assays indicated that the p50 and p65 subunits participated in the bound NF-κB complex. The NF-κB inhibitor PDTC, a potential antioxidant, was able to afford partial neuroprotection in the Gpx1
−/−
mice.

Conclusions—

NF-κB is upregulated in the Gpx1
−/−
mouse, and this upregulation contributes to the increased cell death seen in the Gpx1
−/−
after MCAO. The activation of NF-κB may increase the expression of downstream target genes that are involved in the progression of neural injury after MCAO.