bluuebunny/crossref_metadata_2025 huggingface dataset:
A survey on the preference for continuing professional dental education amongst general dental practitioners who attended the 26th Asia Pacific Dental Congress
Authors: Chan W. C. , Ng C. H. , Yiu B. K. , Liu C. Y. , Ip C. M. , Siu H. H. , Chiu G. K. C. , Hägg U. , Jin L. J.
Published: October 2006

Aims:  To identify the subjects of interest and to examine the modes as well as means of study for continuing professional dental education amongst general dental practitioners who attended the 26th Asia Pacific Dental Congress, 28 May—1 June 2004, Hong Kong.

Methods:  A total of 381 general dental practitioners as the registered conference delegates from Hong Kong, Mainland China and other Asia‐Pacific regions were randomly selected for the present survey. The survey was conducted through face‐to‐face interviews by a group of practising dentists in Hong Kong.

Results:  Overall, orthodontics and prosthodontics were the most popular subjects for clinical degree programmes, whilst oral implantology and cosmetic dentistry were the highly preferred subjects for continuing education courses. Concerning the preferred mode of study for degree programmes, the part‐time study mode was chosen by 68.3% of the participating dentists. A didactic teaching approach was preferred by most of the participants (81.7%) for postgraduate study. The majority of the interviewees (76.5%) were interested in a proposed clinical degree programme to be offered jointly by The University of Hong Kong and a leading university in the Mainland. Overall, there was no marked difference in the preference for continuing dental education amongst the respondents from Hong Kong, Mainland China and other Asia‐Pacific regions.

Conclusions:  The present survey shows the currently preferred specialty areas and subjects for continuing professional dental education amongst the general dental practitioners who attended the 26th Asia Pacific Dental Congress, with didactic teaching as the most preferred mode of study on a part‐time basis.
Implementing an Objective Structured Clinical Examination (OSCE) in dental education: effects on students’ learning strategies
Authors: Schoonheim‐Klein M. E. , Habets L. L. M. H. , Aartman I. H. A. , Van Der Vleuten C. P. , Hoogstraten J. , Van Der Velden U.
Published: October 2006

Objectives:  To investigate the effect of an Objective Structured Clinical Examination (OSCE) on dental students’ learning strategies and competence to manage periodontal diseases in patients. The implemented OSCE was expected to be superior to the existing Written Exam in fostering the acquisition of clinical competencies in terms of study strategies that are more oriented towards clinical practice, longer study time, greater clinical proficiency, and more realistic self‐assessment.

Material and methods:  After a clinical course in periodontology, 72 third year dental students were assessed summatively, either using a Written Exam or an OSCE (P‐OSCE). The students were informed beforehand about the assessment formats. The self‐assessed clinical competence, study time and strategies (i.e. practice with a manikin, peers and patient case) were evaluated by means of a questionnaire. After a comprehensive dental care course, all 72 students were assessed by an overall end‐of‐year OSCE, in which three periodontal stations were included ‘measuring pockets’, ‘educating patients’ and ‘tracing an X‐ray with bone‐loss’. The competence of the previous Written Exam group and the P‐OSCE group was investigated by determining the mean scores and pass‐fail scores of three periodontal test‐stations as well as the total score of the end‐of‐year OSCE. The degree of realistic self‐assessment was studied by correlating the self‐assessed competencies as evaluated by means of the questionnaire with the total score of the end‐of‐year OSCE.

Results:  Self‐assessed clinical competence, study time and study strategies showed no differences between the P‐OSCE and the Written Exam‐group. The clinical competence determined in the test‐station ‘measuring pockets’ in the end of year overall OSCE was higher for the P‐OSCE group (P = 0.05) when compared with the Written Exam group; the two groups performed equally well in the test station ‘educating patients’, whereas the performance in ‘tracing an X‐ray with bone‐loss’ was better in the Written Exam group. This group also had a higher total score in the end‐of‐year OSCE (P = 0.05). The degree of realistic self‐assessment was higher in the P‐OSCE group than in the Written Exam group: in the P‐OSCE group the self‐assessed clinical competencies correlated significantly with the total score of the overall end‐of‐year OSCE (P ≤ 0.05).

Conclusions:  No effects of the implementation of an OSCE in undergraduate periodontal education were observed in study strategies, but the implementation of an OSCE in undergraduate periodontal education appears to stimulate learning, resulting in greater achievement of specific clinical competence and a greater level of realistic self‐assessment.
Correlation of echocardiography parameters with cardiac magnetic resonance imaging in transfusion‐dependent thalassaemia major
Authors: Aessopos Athanassios , Giakoumis Anastasios , Fragodimitri Christina , Karabatsos Fotis , Hatziliami Antonia , Yousef Jacqueline , Gotsis Efstathios , Berdoukas Vasilis , Karagiorga Markissia
Published: October 2006

Background and objective: Heart iron load (cardiac Fe) can be indirectly quantified by cardiac magnetic resonance (CMR) T2*. CMR accessibility is limited, whereas echocardiography (Echo) is relatively inexpensive and readily available. The objective was to find Echo parameters that may be useful for predicting cardiac Fe. Design and methods: We compared a number of parameters derived from Echo to cardiac Fe in 142 thalassaemia major patients who had undergone a CMR study. Results: All patients with decreased left ventricular (LV) function had cardiac Fe. After removing those patients from the analysis, the total diameter index (Tdi) >5.57 cms/m2, left atrial diameter index >2.41 cm/m2, and the diastolic parameter E/A > 1.96 were highly specific (91.4%, 97.1% and 96.9% respectively) but had low sensitivity (31.8%, 20.45% and 21.8%) in predicting iron load. A right ventricular index >1.47 cm/m2, LV systolic index >2.26 cm/m2 or Tdi >6.26 cm/m2 discriminated between patients with no, or mild to moderate cardiac Fe from those with heavy load, with specificity of 91%, 98.5%, and 98.5%, respectively, but with low sensitivity. Interpretation and conclusions: Echo parameters for cardiac Fe prediction have restricted value, whereas CMR is essential to assess cardiac Fe. However, patients with decreased LV systolic function should be considered a priori as having cardiac Fe, and chelation therapy should be intensified. This also applies to patients who have the above‐described Echo criterion values, even if CMR is not available. Once a patient is found by CMR to have cardiac Fe, then the above Echo criterion values may be useful for ongoing monitoring.
Nevus lipomatosus cutaneus superficialis (Hoffmann–Zurhelle) in a Chimpanzee (Pan troglodytes)
Authors: Klopfleisch Robert , Langner Christoph , Von Felbert Inga , Rudnick Jens‐Christian , Teifke Jens Peter
Published: October 2006

Background  A 32‐year‐old, male chimpanzee (Pan troglodytes) kept in a zoo developed a focally extensive, proliferative, cerebriform, dermal mass at the left inner thigh extending to the inguinal region. After surgical removal, the mass recurred and extended progressively over a period of 5 years.

Methods and Results  At necropsy, a 20 × 20 cm large, well defined, papular and partly verrucous, rubbery mass composed of multiple large, soft nodules measuring up to 4 cm in diameter was observed in the left thigh and inguinal region. Histological examination revealed a multifocal expansion of the dermis by mature adipocytes that were arranged in small islands to large lobular aggregates. Dermal proliferations of adipocytes were almost completely separated from the subcutaneous adipose tissue.

Conclusions  This is the first report of a unique lesion that resembles human Nevus lipomatosus cutaneus superficialis in a chimpanzee and is different from lipoma or liposarcoma.
FREQUENCY OF SALMONELLA, CAMPYLOBACTER, LISTERIA AND ENTEROBACTERIACEAE DETECTION IN COMMERCIALLY COOL WATER‐WASHED SHELL EGGS
Authors: JONES DEANA R. , MUSGROVE MICHAEL T. , CAUDILL A. BROOKE , CURTIS PATRICIA A.
Published: October 2006

The effect of cool water washing on shell egg temperature and pathogen detection was examined. Three temperature schemes were utilized in commercial dual washer systems: (1) HH = 48.9C, 48.9C; (2) HC = 48.9C, 23.9C; and (3) CC = 23.9C, 23.9C. HH eggsmaintainedthe highest surface temperature (26.25C in‐line, 20.25C off‐line and 23.25C combined, P < 0.05). The lowest temperatures were found in the CC eggs (21.25C in‐line, 17.25C off‐line and 19.25C combined). The frequency of Enterobacteriaceae detection in shell and membrane emulsions was greatest for the CC eggs (P < 0.05 for in‐line and combined). There was no difference in Enterobacteriaceae detection for the off‐line facility. Salmonella was detected in three of 384 samples from the in‐line facility. They were found in HC (2) and CC (1) shell emulsions. Two of 384 samples were positive for Campylobacter from the in‐line facility (CC). Three wash water samples were positive for Listeria in the off‐line facility (1 HC, 2 CC). No pathogens were detected in the egg contents during this study. The results of this study indicate that warm followed by cool water washing has the potential of decreasing egg temperature while maintaining surface microbiology at an acceptable level.
EFFECT OF GAMMA IRRADIATION ON SOME CHARACTERISTICS OF SHELL EGGS AND MAYONNAISE PREPARED FROM IRRADIATED EGGS
Authors: AL‐BACHIR MAHFOUZ , ZEINOU RUBA
Published: October 2006

Shell eggs were irradiated at doses of 0.0, 0.5, 1.0 and 1.5 kGy of gamma irradiation. Immediately after irradiation, bacterial, physical and chemical analyses of eggs and sensory evaluation of the mayonnaise prepared from irradiated egg yolk were performed. Results indicated that all doses of gamma irradiation reduced the total counts of mesophilic bacteria and total coliforms of eggs. The radiation dose required to reduce theSalmonellaload one log cycle (D10) in eggs was 448 Gy. Eggs irradiated with 1.5 kGy may be suitable microbiologically to prepare safe mayonnaise. There were no significant differences in saturated fatty acids (C14:0; C16:0; C18:0) and thiobarbituric acidvalues between the yolk lipid extracted from irradiated eggs and that of nonirradiated ones. Gamma irradiation reduced the viscosity of egg whites. Sensory evaluation showed no significant differences between mayonnaises prepared from irradiated and nonirradiated egg yolks.
Predicting the invasion success of Mediterranean alien plants from their introduction characteristics
Authors: W. Lambdon Philip , E. Hulme Philip
Published: October 2006

We describe a model to predict the invasion success of alien plants on Mediterranean islands, according to their mode, frequency and time since introduction and simple species traits. The model was developed using canonical discriminant analysis to identify categories of low‐ and high‐risk species. Whilst classifying ca 80% of the data set correctly, the type II error rate remained moderately high, which limits its value in practical terms. This level of accuracy is typical of similar models, and critical analysis of the weaknesses is necessary to develop long‐term improvements in methodology. Sensitivity analysis indicates that, overall, mode of introduction had an important influence on invasiveness, with species introduced for public amenity being more likely to attain high‐risk status than species introduced privately to gardens. Frequency and time since introduction had a relatively minor influence on the model outcome, but remained highly confounded with other variables. Although invasion success, as measured by the number of islands colonized, is expected to increase over time, it was not possible to estimate the rates of expansion from historical trends, which are complicated by changes in import fashions over the centuries. Many older introductions were crops, whereas there has been a recent tendency towards exotic ornamentals and weedy species. Despite a fundamental influence on the results, similar historical influences are seldom taken into account adequately during trait analyses. Unravelling such inter‐correlations between predictors is therefore an important challenge for the future of screening protocols.
The electrogenicity of the rat sodium–bicarbonate cotransporter NBCe1 requires interactions among transmembrane segments of the transporter
Authors: Choi Inyeong , Soo Yang Han , Boron Walter F.
Published: October 2006

The electrogenic Na+–HCO3− cotransporter (NBCe1) plays a central role in intracellular pH (pHi) regulation as well as HCO3− secretion by pancreatic ducts and HCO3− reabsorption by renal proximal tubules. To understand the structural requirements for the electrogenicity of NBCe1, we constructed chimeras of NBCe1‐A and the electroneutral NBCn1‐B, and used two‐electrode voltage clamp to measure electrogenic transporter current in Xenopus oocytes exposed to 5% CO2–26 mm HCO3−(pH 7.40). The chimera consisting of NBCe1‐A (i.e. NBCe1‐A ‘background’) with the cytoplasmic N‐terminal domain (Nt) of NBCn1‐B had a reversal potential of −156.3 mV (compared with a membrane potential Vm of −43.1 mV in a HCO3−‐free solution) and a slope conductance of 3.0 μS (compared with 12.5 μS for NBCe1‐A). Also electrogenic were chimeras with an NBCe1‐A background but with NBCn1‐B contributing the extracellular loop (L) between transmembrane segment (TM) 5 and 6 (−140.9 mV/11.1 μS), the cytoplasmic C‐terminal domain (Ct; −123.8 mV/9.7 μS) or Nt + L + Ct (−120.9 mV/3.7 μS). Reciprocal chimeras (with an NBCn1 background but with NBCe1 contributing Nt, L, Ct or Nt + L + Ct) produced no measurable electrogenic transporter currents in the presence of CO2–HCO3−. pHi recovered from an acid load, but without the negative shift of Vm that is characteristic of electrogenic Na+–HCO3− cotransporters. Thus, these chimeras were electroneutral, as were two others consisting of NBCe1(Nt–L)/NBCn1(TM6–Ct) and NBCn1(Nt–L)/NBCe1(TM6–Ct). We propose that the electrogenicity of NBCe1 requires interactions between TM1–5 and TM6–13.
Macrophages promote muscle membrane repair and muscle fibre growth and regeneration during modified muscle loading in mice in vivo
Authors: Tidball James G. , Wehling‐Henricks Michelle
Published: October 2006

Muscle injury or modified muscle use can stimulate muscle invasion by leucocytes that have the potential to increase tissue damage or promote tissue growth and repair. In the present investigation, we examined the role of macrophages in muscle injury, repair and regeneration during modified muscle loading. Weight‐bearing was removed from the hindlimbs of mice for 10 days followed by reloading through normal ambulation. During the unloading period, soleus muscle fibre cross‐section decreased by 38%. Prior to the onset of reloading, mice received a series of intraperitoneal injections of anti‐F4/80, which binds a mouse macrophage surface antigen. Although anti‐F4/80 injections did not affect macrophage numbers in soleus muscles at 2 days of reloading, macrophages were reduced by 86% at 4 days of reloading. Muscle membrane lysis during the reloading period did not differ at 2 days of reloading between anti‐F4/80‐treated mice and mice that received isotype control antibody. However, control animals showed large decreases in the number of fibres with membrane lesions at 4 days of reloading, but this membrane repair did not occur in macrophage‐depleted mice. Macrophage‐depletion also reduced muscle regeneration (indicated by central nucleation) and satellite cell differentiation (indicated by reductions in MyoD‐expressing satellite cells) and prevented growth of muscle fibres that normally occurred in control animals between days 2 and 4 of reloading. These findings collectively show that macrophages play a significant role in muscle fibre membrane repair, regeneration and growth during increased muscle use after a period of atrophy.
Response characteristics of the pigeon's pretectal neurons to illusory contours and motion
Authors: Niu Yu‐Qiong , Xiao Qian , Liu Rui‐Feng , Wu Le‐Qing , Wang Shu‐Rong
Published: October 2006

Misinterpretations of visual information received by the retina are called visual illusions, which are known to occur in higher brain areas. However, whether they would be also processed in lower brain structures remains unknown, and how to explain the neuronal mechanisms underlying the motion after‐effect is intensely debated. We show by extracellular recording that all motion‐sensitive neurons in the pigeon's pretectum respond similarly to real and illusory contours, and their preferred directions are identical for both contours in unidirectional cells, whereas these directions are changed by 90 deg for real versus illusory contours in bidirectional cells. On the other hand, some pretectal neurons produce inhibitory (excitatory) after‐responses to cessation of prolonged motion in the preferred (null) directions, whose time course is similar to that of the motion after‐effect reported by humans. Because excitatory and inhibitory receptive fields of a pretectal cell overlap in visual space and possess opposite directionalities, after‐responses to cessation of prolonged motion in one direction may create illusory motion in the opposite direction. It appears that illusory contours and motion could be detected at the earliest stage of central information processing and processed in bottom‐up streams, and that the motion after‐effect may result from functional interactions of excitatory and inhibitory receptive fields with opposite directionalities.
Genetically encoded Ca2+ indicators: using genetics and molecular design to understand complex physiology
Authors: Kotlikoff Michael I.
Published: October 2006

This article reviews genetically encoded Ca2+ indicators (GECIs), with a focus on the use of these novel molecules in the context of understanding complex cell signalling in mammals, in vivo. The review focuses on the advantages and limitations of specific GECI design strategies and the results of experiments in which these molecules have been expressed in transgenic mice, concentrating particularly on recent experiments from our laboratory in which physiological signalling could be monitored in vivo. Finally, newer strategies for effective genetic specification of GECIs are briefly reviewed.
Predominant α2/β2/γ3 AMPK activation during exercise in human skeletal muscle
Authors: Birk J. B. , Wojtaszewski J. F. P.
Published: October 2006

5′AMP‐activated protein kinase (AMPK) is a key regulator of cellular metabolism and is regulated in muscle during exercise. We have previously established that only three of 12 possible AMPK α/β/γ‐heterotrimers are present in human skeletal muscle. Previous studies describe discrepancies between total AMPK activity and regulation of its target acetyl‐CoA‐carboxylase (ACC)β. Also, exercise training decreases expression of the regulatory γ3 AMPK subunit and attenuates α2 AMPK activity during exercise. We hypothesize that these observations reflect a differential regulation of the AMPK heterotrimers. We provide evidence here that only the α2/β2/γ3 subunit is phosphorylated and activated during high‐intensity exercise in vivo. The activity associated with the remaining two AMPK heterotrimers, α1/β2/γ1 and α2/β2/γ1, is either unchanged (20 min, 80% maximal oxygen uptake ) or decreased (30 or 120 s sprint‐exercise). The differential activity of the heterotrimers leads to a total α‐AMPK activity, that is decreased (30 s trial), unchanged (120 s trial) and increased (20 min trial). AMPK activity associated with the α2/β2/γ3 heterotrimer was strongly correlated to γ3‐associated α‐Thr‐172 AMPK phosphorylation (r2= 0.84, P < 0.001) and to ACCβ Ser‐221 phosphorylation (r2= 0.65, P < 0.001). These data single out the α2/β2/γ3 heterotrimer as an important actor in exercise‐regulated AMPK signalling in human skeletal muscle, probably mediating phosphorylation of ACCβ.
Postnatal changes in ventilation during normoxia and acute hypoxia in the rat: implication for a sensitive period
Authors: Liu Qiuli , Lowry Timothy F. , Wong‐Riley Margaret T. T.
Published: October 2006

Previously, we found heightened expression of inhibitory neurochemicals and depressed expression of excitatory neurochemicals with a sudden drop in metabolic activity around postnatal day (P) 12 in rat brainstem respiratory nuclei, suggesting that this period is a critical window during which respiratory control or regulation may be distinctly different. To test this hypothesis, the hypoxic ventilatory responses (HVR) to 10% oxygen were tested in rats every day from P0 to P21. Our data indicate that (1) during normoxia (N), breathing frequency (f) increased with age, peaking at P13, followed by a gradual decline, whereas both tidal volume (VT) and minute ventilation () significantly increased in the second postnatal week, followed by a progressive increase inVTand a relative plateau in; (2) during 5 min of hypoxia (H),exhibited a biphasic response from P3 onward. Significantly, the ratio oftowas generally > 1 during development, except for P13–16, when it was < 1 after the first 1–2 min, with the lowest value at P13; (3) the H : N ratio forf,VTandduring the first 30 s and the last minute of hypoxia all showed a distinct dip at P13, after which theVTandvalues rose again, while thefvalues declined through P21; and (4) the H : N ratios forf,VTandaveraged over 5 min of hypoxia all exhibited a sudden fall at P13. Thefratio remained low thereafter, while those forVTandincreased again with age until P21. Thus, hypoxic ventilatory response is influenced by bothfandVTbefore P13, but predominantly byVTafter P13. The striking changes in normoxic ventilation as well as HVR at or around P13, together with our previous neurochemical and metabolic data, strongly suggests that the end of the second postnatal week is a critical period of development for brainstem respiratory nuclei in the rat.
Radar Imaging of Binary Near-Earth Asteroid (66391) 1999 KW4
Authors: Ostro Steven. J. , Margot Jean-Luc , Benner Lance A. M. , Giorgini Jon D. , Scheeres Daniel J. , Fahnestock Eugene G. , Broschart Stephen B. , Bellerose Julie , Nolan Michael C. , Magri Christopher , Pravec Petr , Scheirich Petr , Rose Randy , Jurgens Raymond F. , De Jong Eric M. , Suzuki Shigeru
Published: October 2006

High-resolution radar images reveal near-Earth asteroid (66391) 1999 KW4 to be a binary system. The ∼1.5-kilometer-diameter primary (Alpha) is an unconsolidated gravitational aggregate with a spin period ∼2.8 hours, bulk density ∼2 grams per cubic centimeter, porosity ∼50%, and an oblate shape dominated by an equatorial ridge at the object's potential-energy minimum. The ∼0.5-kilometer secondary (Beta) is elongated and probably is denser than Alpha. Its average orbit about Alpha is circular with a radius ∼2.5 kilometers and period ∼17.4 hours, and its average rotation is synchronous with the long axis pointed toward Alpha, but librational departures from that orientation are evident. Exotic physical and dynamical properties may be common among near-Earth binaries.
The Phase-Dependent Infrared Brightness of the Extrasolar Planet ʊ Andromedae b
Authors: Harrington Joseph , Hansen Brad M. , Luszcz Statia H. , Seager Sara , Deming Drake , Menou Kristen , Cho James Y.-K. , Richardson L. Jeremy
Published: October 2006

The star υ Andromedae is orbited by three known planets, the innermost of which has an orbital period of 4.617 days and a mass at least 0.69 that of Jupiter. This planet is close enough to its host star that the radiation it absorbs overwhelms its internal heat losses. Here, we present the 24-micrometer light curve of this system, obtained with the Spitzer Space Telescope. It shows a variation in phase with the orbital motion of the innermost planet, demonstrating that such planets possess distinct hot substellar (day) and cold antistellar (night) faces.
BLACK HOLES REMNANTS IN EXTRA DIMENSIONS AND DARK MATTER
Authors: NOZARI KOUROSH , MEHDIPOUR S. HAMID
Published: October 2006

Bekenstein–Hawking formalism of black hole thermodynamics should be modified to incorporate quantum gravitational effects. Generalized Uncertainty Principle (GUP) provides a suitable framework to perform such modifications. In this paper, we consider a general form of GUP to find black hole thermodynamics in a model universe with large extra dimensions. We will show that black holes radiate mainly in the four-dimensional brane. Existence of black holes remnants as a possible candidate for dark matter is discussed.
NEW AdS3 BRANES AND BOUNDARY STATES
Authors: RAJARAMAN ARVIND
Published: October 2006

We examine D-branes on AdS3, and find a 3-brane wrapping the entire AdS3, in addition to 1-branes and instantonic 2-branes previously discussed in the literature. The 3-brane is found using a construction of Maldacena, Moore, and Seiberg. We show that all these branes satisfy Cardy's condition and extract the open string spectrum on them.
BOLTZMANN–SHANNON ENTROPY: GENERALIZATION AND APPLICATION
Authors: CHAKRABARTI C. G. , CHAKRABARTY I.
Published: October 2006

The paper deals with the generalization of both Boltzmann entropy and distribution in the light of most-probable interpretation of statistical equilibrium. The statistical analysis of the generalized entropy and distribution leads to some new interesting results of significant physical importance.
Beneficial effect of glatiramer acetate (Copaxone) on immune modulation of experimental hepatic fibrosis
Authors: Horani Amjad , Muhanna Nidal , Pappo Orit , Melhem Alaa , Alvarez Carlos E. , Doron Sarit , Wehbi Wehbi , Dimitrios Karussis , Friedman Scott L. , Safadi Rifaat
Published: October 2006

While CD8 subsets activate hepatic fibrosis, natural killer (NK) cells exhibit antifibrotic activity. Glatiramer acetate (GA) is an immune modulator for multiple sclerosis. We assessed the potential impact of GA on mouse hepatic fibrogenesis. Hepatic fibrosis was induced in C57BL/6 mice by intraperitoneal administration of carbon tetrachloride (CCl4) for 6 wk. During the last 2 wk, animals were also treated with either GA (200 μ/day ip) or medium and compared with naive and fibrotic mice (8 animals/group). GA markedly attenuated fibrosis without altering reactive oxygen species production. By morphometric measurement of Sirius red-stained tissue sections, the relative fibrosis area decreased from 5.28 ± 0.32% (mean ± SE) in the untreated CCl4group to 2.01 ± 0.28% in CCl4+GA-treated animals, compared with 0.38 ± 0.07% in naive mice. α-Smooth muscle actin immunoblotting and mRNA expression revealed a similar pattern. Serum aminotransferase and Ishak-Knodell necroinflammatory score were markedly elevated, to the same extent, in both CCl4-treated groups. Fibrosis induction was associated with significant increase in CD8 subsets and decrease in CD4 T cells. After GA treatment, however, NK content, CD4+CD25+FoxP3+cells, hepatic expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and apoptosis of hepatic stellate cells were all increased. Serum interleukin (IL)-10 levels markedly rose, whereas IL-4 fell. In vitro activation of human hepatic stellate cells cocultured with hepatitis C virus-derived peripheral blood lymphocytes decreased when lymphocytes were preincubated with GA before coculture. In an animal model of hepatic fibrosis, GA has an antifibrotic effect associated with decreased CD8 cells and reduced serum IL-4 levels and increased NK cells, CD4+CD25+FoxP3+cells, TRAIL, and elevated serum IL-10 levels.
TLRs in the Gut. III. Immune responses to flagellin in Crohn's disease: good, bad, or irrelevant?
Authors: Gewirtz Andrew T.
Published: October 2006

Recent observations suggest that bacterial flagellin may be a target of the seemingly aberrant innate and adaptive immune responses that are associated with Crohn's disease. This article discusses the evidence that supports a role for flagellin in Crohn's disease and considers the potential roles of these responses in the pathophysiology of this disorder.
Hypersensitivity of myofilament response to Ca2+ in association with maladaptation of estrogen-deficient heart under diabetes complication
Authors: Thawornkaiwong Ariyaporn , Pantharanontaga Jantarima , Wattanapermpool Jonggonnee
Published: October 2006

The amelioration of cardioprotective effect of estrogen in diabetes suggests potential interactive action of estrogen and insulin on myofilament activation. We compared Ca2+-dependent Mg2+-ATPase activity of isolated myofibrillar preparations from hearts of sham and 10-wk ovariectomized rats with or without simultaneous 8 wk-induction of diabetes and from diabetic-ovariectomized rats with estrogen and/or insulin supplementation. Similar magnitude of suppressed maximum myofibrillar ATPase activity was demonstrated in ovariectomized, diabetic, and diabetic-ovariectomized rat hearts. Such suppressed activity and the relative suppression in α-myosin heavy chain level in ovariectomy combined with diabetes could be completely restored by estrogen and insulin supplementation. Conversely, the myofilament Ca2+ hypersensitivity detected only in the ovariectomized but not diabetic group was also observed in diabetic-ovariectomized rats, which was restored upon estrogen supplementation. Binding kinetics of β1-adrenergic receptors and immunoblots of β1-adrenoceptors as well as heat shock 72 (HSP72) were analyzed to determine the association of changes in receptors and HSP72 to that of the myofilament response to Ca2+. The amount of β1-adrenoceptors significantly increased concomitant with Ca2+ hypersensitivity of the myofilament, without differences in the receptor binding affinity among the groups. In contrast, changes in HSP72 paralleled that of maximum myofibrillar ATPase activity. These results indicate that hypersensitivity of cardiac myofilament to Ca2+ is specifically induced in ovariectomized rats even under diabetes complication and that alterations in the expression of β1-adrenoceptors may, in part, play a mechanistic role underlying the cardioprotective effects of estrogen that act together with Ca2+ hypersensitivity of the myofilament in determining the gender difference in cardiac activation.
Sex differences in energy metabolism and performance of teleost cardiac tissue
Authors: Battiprolu Pavan K. , Harmon Kelli J. , Rodnick Kenneth J.
Published: October 2006

This study examined the effects of different oxygenation levels and substrate availability on cardiac performance, metabolism, and biochemistry in sexually immature male and female rainbow trout ( Oncorhynchus mykiss). Ventricle strips were electrically paced (0.5 Hz, 14°C) in hyperoxic or hypoxic Ringer solution. Our results demonstrate that 1) males sustain isometric force production ( F) longer than females under hyperoxia (Po2= 640 mmHg) with exogenous glucose present; 2) contractility is not maintained under moderate (Po2= 130 mmHg) or severe hypoxia (Po2= 10–20 mmHg) with glucose in either sex; however, following reoxygenation, F is higher in females compared with males; and 3) female tissue has higher lactate levels, net lactate efflux, and lactate dehydrogenase activity than males, whereas males have higher glycogen, citrate synthase, and β-hydroxy acyl-CoA dehydrogenase activities, and greater inotropic responses to exogenous glucose and octanoate. No sex differences were detected in responsiveness to epinephrine and inhibitors of glucose transport or activities of hexokinase and pyruvate kinase. We conclude that sex differences exist in rainbow trout cardiac tissue: females appear to prefer glycolysis for ATP production, whereas males have a higher capacity for aerobic and lipid metabolism.
Hydrogen sulfide and its possible roles in myocardial ischemia in experimental rats
Authors: Zhu Yi Zhun , Wang Zhong Jing , Ho Peiying , Loke Yoke Yun , Zhu Yi Chun , Huang Shan Hong , Tan Chee Sin , Whiteman Matt , Lu Jia , Moore Philip K.
Published: October 2006

The role of hydrogen sulfide (H2S) in myocardial infarction (MI) has not been previously studied. We therefore investigated the effect of H2S in a rat model of MI in vivo. Animals were randomly divided into three groups ( n = 80) and received either vehicle, 14 μmol/kg of sodium hydrosulfide (NaHS), or 50 mg/kg propargylglycine (PAG) everyday for 1 wk before surgery, and the treatment was continued for a further 2 days after MI when the animals were killed. The mortality was 35% in vehicle-treated, 40% in PAG-treated, and 27.5% in NaHS-treated ( P < 0.05 vs. vehicle) groups. Infarct size was 52.9 ± 3.5% in vehicle-treated, 62.9 ± 7.6% in PAG-treated, and 43.4 ± 2.8% in NaHS-treated ( P < 0.05 vs. vehicle) groups. Plasma H2S concentration was significantly increased after MI (59.2 ± 7.16 μM) compared with the baseline concentration (i.e., 38.2 ± 2.07 μM before MI; P < 0.05). Elevated plasma H2S after MI was abolished by treatment of animals with PAG (39.2 ± 5.02 μM). We further showed for the first time cystathionine-gamma-lyase protein localization in the myocardium of the infarct area by using immunohistochemical staining. In the hypoxic vascular smooth muscle cells, we found that cell death was increased under the stimuli of hypoxia but that the increased cell death was attenuated by the pretreatment of NaHS (71 ± 1.2% cell viability in hypoxic vehicle vs. 95 ± 2.3% in nonhypoxic control; P < 0.05). In conclusion, endogenous H2S was cardioprotective in the rat model of MI. PAG reduced endogenous H2S production after MI by inhibiting cystathionine-gamma-lyase. The results suggest that H2S might provide a novel approach to the treatment of MI.
VEGF gradients, receptor activation, and sprout guidance in resting and exercising skeletal muscle
Authors: Mac Gabhann Feilim , Ji James W. , Popel Aleksander S.
Published: October 2006

Extensive experimental studies have identified vascular endothelial growth factor (VEGF) concentrations and concentration gradients as major factors in angiogenesis; however, localized in vivo measurements of these parameters have not been possible. We developed a three-dimensional computational model of skeletal muscle fibers, blood vessels, and interstitial space. Here it is applied to rat extensor digitorum longus. VEGF isoforms are secreted by myocytes, diffuse through extracellular matrix and basement membranes, and bind endothelial cell surface receptors on blood vessels. In addition, one isoform, VEGF164, binds to proteoglycans in the interstitial space. VEGF secretion rate is determined from the predicted tissue oxygen level through its effect on the hypoxia inducible factor-1α transcription factor. We estimate VEGF secretion and its concentrations and gradients in resting muscle and for different levels of exercise. The effects of low levels of inspired oxygen are also studied. We predict that the high spatial heterogeneity of muscle fiber VEGF secretion in hypoxic tissue leads to significant gradients of VEGF concentration and VEGF receptor activation. VEGF concentration gradients are predicted to be significant in both resting and exercising muscle (4% and 6–8% change in VEGF over 10 μm, respectively), sufficient for chemotactic guidance of 50-μm-long sprout tip cells. VEGF gradients also result in heterogeneity in VEGF receptor activation—a possible explanation for the stochasticity of sprout location. In the absence of interstitial flow, gradients are 10-fold steeper in the transverse direction (i.e., perpendicular to the muscle fibers) than in the longitudinal direction. This may explain observed perpendicular anastomoses in skeletal muscle.
MEK–ERK Inhibition Corrects the Defect in VLDL Assembly in HepG2 Cells
Authors: Tsai Julie , Qiu Wei , Kohen-Avramoglu Rita , Adeli Khosrow
Published: October 2006

Objective—

Hepatic VLDL assembly is defective in HepG2 cells, resulting in the secretion of immature triglyceride-poor LDL-sized apoB particles. We investigated the mechanisms underlying defective VLDL assembly in HepG2 and have obtained evidence implicating the MEK–ERK pathway.

Methods and Results—

HepG2 cells exhibited considerably higher levels of the ERK1/2 mass and activity compared with primary hepatocytes. Inhibition of ERK1/2 using the MEK1/MEK2 inhibitor, U0126 (but not the inactive analogue) led to a significant increase in apoB secretion. In the presence of oleic acid, ERK1/2 inhibition caused a major shift in the lipoprotein distribution with a majority of particles secreted as VLDL, an effect independent of insulin. In contrast, overexpression of constitutively active MEK1 decreased apoB and large VLDL secretion. MEK1/2 inhibition significantly increased both cellular and microsomal TG mass, and mRNA levels for DGAT-1 and DGAT-2. In contrast to ERK, modulation of the PI3-K pathway or inhibition of the p38 MAP kinase, had no effect on lipoprotein density profile. Modulation of the MEK–ERK pathway in primary hamster hepatocytes led to changes in apoB secretion and altered the density profile of apoB-containing lipoproteins.

Conclusion—

Inhibition of the overactive ras-MEK–ERK pathway in HepG2 cells can correct the defect in VLDL assembly leading to the secretion of large, VLDL-sized particles, similar to primary hepatocytes, implicating the MEK–ERK cascade in VLDL assembly in the HepG2 model. Modulation of this pathway in primary hepatocytes also regulates apoB secretion and appears to alter the formation of VLDL-1 sized particles.
Adenosine Restores Angiotensin II–Induced Contractions by Receptor-Independent Enhancement of Calcium Sensitivity in Renal Arterioles
Authors: Lai En Yin , Martinka Peter , Fähling Michael , Mrowka Ralf , Steege Andreas , Gericke Adrian , Sendeski Mauricio , Persson P.B. , Persson A. Erik G. , Patzak Andreas
Published: October 2006

Adenosine is coupled to energy metabolism and regulates tissue blood flow by modulating vascular resistance. In this study, we investigated isolated, perfused afferent arterioles of mice, which were subjected to desensitization during repeated applications of angiotensin II. Exogenously applied adenosine restores angiotensin II–induced contractions by increasing calcium sensitivity of the arterioles, along with augmented phosphorylation of the regulatory unit of the myosin light chain. Adenosine restores angiotensin II–induced contractions via intracellular action, because inhibition of adenosine receptors do not prevent restoration, but inhibition of NBTI sensitive adenosine transporters does. Restoration was prevented by inhibition of Rho-kinase, protein kinase C, and the p38 mitogen-activated protein kinase, which modulate myosin light chain phosphorylation and thus calcium sensitivity in the smooth muscle. Furthermore, adenosine application increased the intracellular ATP concentration in LuciHEK cells. The results of the study suggest that restoration of the angiotensin II–induced contraction by adenosine is attributable to the increase of the calcium sensitivity by phosphorylation of the myosin light chain. This can be an important component of vascular control during ischemic and hypoxic conditions. Additionally, this mechanism may contribute to the mediation of the tubuloglomerular feedback by adenosine in the juxtaglomerular apparatus of the kidney.
Cyclic AMP Imaging in Adult Cardiac Myocytes Reveals Far-Reaching β1-Adrenergic but Locally Confined β2-Adrenergic Receptor–Mediated Signaling
Authors: Nikolaev Viacheslav O. , Bünemann Moritz , Schmitteckert Eva , Lohse Martin J. , Engelhardt Stefan
Published: October 2006

β1- and β2-adrenergic receptors (βARs) are known to differentially regulate cardiomyocyte contraction and growth. We tested the hypothesis that these differences are attributable to spatial compartmentation of the second messenger cAMP. Using a fluorescent resonance energy transfer (FRET)-based approach, we directly monitored the spatial and temporal distribution of cAMP in adult cardiomyocytes. We developed a new cAMP-FRET sensor (termed HCN2-camps) based on a single cAMP binding domain of the hyperpolarization activated cyclic nucleotide-gated potassium channel 2 (HCN2). Its cytosolic distribution, high dynamic range, and sensitivity make HCN2-camps particularly well suited to monitor subcellular localization of cardiomyocyte cAMP. We generated HCN2-camps transgenic mice and performed single-cell FRET imaging on freshly isolated cardiomyocytes. Whole-cell superfusion with isoproterenol showed a moderate elevation of cAMP. Application of various phosphodiesterase (PDE) inhibitors revealed stringent control of cAMP through PDE4>PDE2>PDE3. The β1AR-mediated cAMP signals were entirely dependent on PDE4 activity, whereas β2AR-mediated cAMP was under control of multiple PDE isoforms. β1AR subtype–specific stimulation yielded ≈2-fold greater cAMP responses compared with selective β2-subtype stimulation, even on treatment with the nonselective PDE inhibitor 3-isobutyl-1-methylxanthine (IBMX) (ΔFRET, 17.3±1.3% [β1AR] versus 8.8±0.4% [β2AR]). Treatment with pertussis toxin to inactivate Gidid not affect cAMP production. Localized β1AR stimulation generated a cAMP gradient propagating throughout the cell, whereas local β2AR stimulation did not elicit marked cAMP diffusion. Our data reveal that in adult cardiac myocytes, β1ARs induce far-reaching cAMP signals, whereas β2AR-induced cAMP remains locally confined.
Model-Reduced Variational Data Assimilation
Authors: Vermeulen P. T. M. , Heemink A. W.
Published: October 2006

This paper describes a new approach to variational data assimilation that with a comparable computational efficiency does not require implementation of the adjoint of the tangent linear approximation of the original model. In classical variational data assimilation, the adjoint implementation is used to efficiently compute the gradient of the criterion to be minimized. Our approach is based on model reduction. Using an ensemble of forward model simulations, the leading EOFs are determined to define a subspace. The reduced model is created by projecting the original model onto this subspace. Once this reduced model is available, its adjoint can be implemented very easily and can be used to approximate the gradient of the criterion. The minimization process can now be solved completely in reduced space with negligible computational costs. If necessary, the procedure can be repeated a few times by generating new ensembles closer to the most recent estimate of the parameters. The reduced-model-based method has been tested on several nonlinear synthetic cases for which a diffusion coefficient was estimated.
The Impact of Moist Singular Vectors and Horizontal Resolution on Short-Range Limited-Area Ensemble Forecasts for Two European Winter Storms
Authors: Walser André , Arpagaus Marco , Appenzeller Christof , Leutbecher Martin
Published: October 2006

This paper studies the impact of different initial condition perturbation methods and horizontal resolutions on short-range limited-area ensemble predictions for two severe winter storms. The methodology consists of 51-member ensembles generated with the global ensemble prediction system (EPS) of the European Centre for Medium-Range Weather Forecasts, which are downscaled with the nonhydrostatic limited-area model Lokal Modell. The resolution dependency is studied by comparing three different limited-area ensembles: (a) 80-km grid spacing, (b) 10-km grid spacing, and (c) 10-km grid spacing with a topography coarse grained to 80-km resolution. The initial condition perturbations of the global ensembles are based on singular vectors (SVs), and the tendencies are not perturbed (i.e., no stochastic physics). Two configurations are considered for the initial condition perturbations: (i) the operational SV configuration: T42 truncation, 48-h optimization time, and dry tangent-linear model, and (ii) the “moist SV” configuration: TL95 truncation, 24-h optimization time, and moist tangent-linear model.

Lokal Modell ensembles are analyzed for the European winter storms Lothar and Martin, both occurring in December 1999, with particular attention paid to near-surface wind gusts. It is shown that forecasts using the moist SV configuration predict higher probabilities for strong wind gusts during the storm period compared to forecasts with the operational SV configuration. Similarly, the forecasts with increased horizontal resolution—even with coarse topography—lead to higher probabilities compared with the low-resolution forecasts. Overall, the two case studies suggest that currently developed operational high-resolution limited-area EPSs have a great potential to improve early warnings for severe winter storms, particularly when the driving global EPS employs moist SVs.
A Semi-Implicit Runge–Kutta Time-Difference Scheme for the Two-Dimensional Shallow-Water Equations
Authors: Kar Sajal K.
Published: October 2006

A semi-implicit, two time-level, three-step iterative time-difference scheme is proposed for the two-dimensional nonlinear shallow-water equations in a conservative flux form. After a semi-implicit linearization of the governing equations, the linear gravity wave terms are time discretized implicitly using a second-order trapezoidal scheme applied over each iterative step, whereas the nonlinear terms including horizontal advection and other terms left over from the semi-implicit linearization are time discretized explicitly using a third-order Runge–Kutta scheme. The effectiveness of the scheme in terms of numerical accuracy, stability, and efficiency is established through a forced initial-boundary value problem studied using a two-dimensional shallow-water model.
High Winds Generated by Bow Echoes. Part II: The Relationship between the Mesovortices and Damaging Straight-Line Winds
Authors: Wakimoto Roger M. , Murphey Hanne V. , Davis Christopher A. , Atkins Nolan T.
Published: October 2006

Airborne radar analysis of a mesovortex that developed near the apex of a bow echo is presented. The mesovortex was shown to play a critical role in determining the location of intense “straight-line” wind damage at the surface. The perturbation pressure gradient force (in natural coordinates) along the parcel path accelerated the horizontal winds; however, intense mesovortices modified the low-level outflow and largely determined the locations where the strongest winds occurred. Regions of maximum winds are accounted for as a superposition of the vortex and the flow in which it is embedded. The strongest winds occur on the side of the vortex where translation and rotation effects are in the same direction. This model explains the observed tongue of high wind speeds that were confined to the periphery of the mesovortex. The origin of the mesovortex is also examined. Similarities and differences of this bow echo event with recent modeling studies are presented.