bluuebunny/crossref_metadata_2025 huggingface dataset:
Dissociation between changes in muscle Na+-K+-ATPase isoform abundance and activity with consecutive days of exercise and recovery
Authors: Green H. J. , Duhamel T. A. , Stewart R. D. , Tupling A. R. , Ouyang J.
Published: January 2008

The early plasticity of vastus lateralis Na+-K+-ATPase to the abrupt onset of prolonged submaximal cycling was studied in 12 untrained participants (V̇o2 peak 44.8 ± 2.0 ml·kg−1·min−1, mean ± SE) using a 6-day protocol (3 days of exercise plus 3 days of recovery). Tissue samples were extracted prior to (Pre) and following exercise (Post) on day 1 (E1) and day 3 (E3) and on each day of recovery (R1, R2, R3) and analyzed for changes in maximal protein (βmax) (vanadate-facilitated [3H]ouabain binding), α- and β-isoform concentration (quantitative immunoblotting) and maximal Na+-K+-ATPase activity ( Vmax) (3- O-methylfluorescein K+-stimulated phosphatase assay). For βmax (pmol/g wet wt), an increase ( P < 0.05) of 11.8% was observed at R1 compared with E1-Pre (340 ± 14 vs 304 ± 17). For the α-isoforms α1, α2, and α3, increases ( P < 0.05) of 46, 42, and 31% were observed at R1, respectively. For the β-isoform, β1 and β2 increased ( P < 0.05) by 19 and 28% at R1, whereas β3 increased ( P < 0.05) by 18% at R2. With the exception of α2 and α3, the increases in the isoforms persisted at R3. Exercise resulted in an average decrease ( P < 0.05) in Vmax by 14.3%. No differences were observed in Vmax at E1 - Pre and E3 - Pre or between R1, R2, and R3. It is concluded that 3 days of prolonged exercise is a powerful stimulus for the rapid upregulation of the Na+-K+-ATPase subunit isoforms. Contrary to our hypothesis, the increase in subunit expression is not accompanied by increases in the maximal catalytic activity.
Neural Selectivity in Anterior Inferotemporal Cortex for Morphed Photographic Images During Behavioral Classification or Fixation
Authors: Liu Yan , Jagadeesh Bharathi
Published: January 2008

Anterior inferotemporal cortex (aIT) contributes to the ability to discriminate and classify complex images. To determine whether and what proportion of single neurons in aIT cortex can yield enough information to classify complex images, we recorded from aIT neurons during the presentation of morphed photographic images in sessions in which monkeys classified images in a two alternative forced-choice—delayed-match-to-sample (2AFC-DMS) task or in sessions in which they performed a fixation task. The sample stimuli were chosen from a sequence in which one image was gradually morphed into another in a pair, while the original pair of images served as choices. Responses of many individual neurons in aIT cortex during the behavioral classification of the images, decoded using an ideal observer analysis, were sufficiently selective to account for the observed behavioral classification of the images. The responses of a separate population of neurons in aIT cortex recorded in subsequent sessions while the monkeys viewed the same images, were less selective than neural responses measured during sessions in which the 2AFC-DMS task was performed. Our findings show that many neurons in aIT could provide sensory information sufficient for the classification of images when a 2AFC-DMS task was performed.
Enhanced Susceptibility to Chemical Induction of Ovarian Tumors in Mice with a Germ Line p53 Mutation
Authors: Wang Yian , Zhang Zhongqiu , Lu Yan , Yao Ruisheng , Jia Dongmei , Wen Weidong , LaRegina Marie , Crist Keith , Lubet Ronald , You Ming
Published: January 2008

Mice with a germ line p53 mutation (p53Ala135Val/wt) display increased susceptibility to lung, skin, and colon carcinogenesis. Here, we show that p53Ala135Val/wt mice developed ovarian tumors significantly more rapidly than their wild-type littermates after 7,12-dimethylbenz(a)anthracene (DMBA) treatment. Approximately 50% of the ovarian tumors in p53wt/wt mice and 23% in p53Ala135Val/wt mice are adenocarcinomas and the remaining tumors were adenocarcinoma mixed with sarcoma or ovarian sarcomas. All of the p53Ala135Val/wt mice had died of ovarian tumors 25 weeks after the initial DMBA treatment, whereas >50% of p53wt/wt mice were still alive. These mice not only have a shortened tumor latency but also closely resemble a subset of human ovarian tumors containing the p53 mutation. Microarray and GenMAPP analyses revealed that the mutant p53 (Ala135Val) affected several cellular processes, including the cell cycle, apoptosis, and Wnt pathways. These findings indicate that a germ line p53 mutation significantly enhanced DMBA-induced ovarian tumor development and progression. (Mol Cancer Res 2008;6(1):99–109)
Efficacy of Etanercept in Psoriatic Patients Previously Treated with Infliximab
Authors: Pitarch Gerard , Sánchez-Carazo José Luís , Mahiques Laura , Oliver Vicente
Published: January 2008

Background: There are few data to enable us to ascertain whether switching to another systemic agent is useful in patients with psoriasis who have not responded favorably to a first systemic treatment. Objective: To evaluate the efficacy and safety of etanercept in patients with moderate-to-severe plaque psoriasis previously treated with infliximab. Methods: We analyzed data from patients with moderate-to-severe psoriasis and a poor primary or secondary response to infliximab, and who were later treated with etanercept. Results: Data were collected from 8 patients who were first treated with infliximab. At 54 weeks of therapy, 25% had a psoriasis area and severity index (PASI) of 75. At 24 weeks of therapy with etanercept, 75% had a PASI of 75. Consecutive administration of both therapies did not increase the number of adverse events. Limitations:The data should be regarded with caution due to the scant number of patients. Conclusions: Switching from infliximab to etanercept can be useful and safe in nonresponders.
External Cephalic Version in Singleton Pregnancies at Term: A Retrospective Analysis
Authors: Zeck Willibald , Walcher Wolfgang , Lang Uwe
Published: January 2008

Background/Aims: The outcomes of external cephalic versions (ECV) performed at the University Hospital Graz in Austria were analyzed to determine to what extent the cesarean section rate can be reduced by an ECV program. Methods: All women who were admitted to the hospital with breech presentation at 37 weeks or later and underwent an attempt of ECV between 2002 and 2004 were recorded and retrospectively analyzed. Results: Of 136 cases51% were successful. Among these, the cesarean section rate was 13%. The cesarean section rate among all not successful cases was 82%. Of the successful cases which remained in cephalic presentation 92% were delivered vaginally and 5 were delivered by cesarean section. The cesarean section rate (8%) was slightly higher than in fetuses with cephalic presentation observed at the onset of contractions in 2004 (5.9%). No maternal or fetal complications or side effects occurred. Conclusion: Successful ECV beyond 37 weeks of gestation significantly decreases the cesarean section rate. ECV reduces the cesarean section rate among breech positions and decreases the risks related to breech delivery, when correctly performed and adequately monitored. ECV reduces higher costs connected with cesarean section.
Modulating Effects of Maternal Fish Consumption on the Occurrence of Respiratory Symptoms in Early Infancy Attributed to Prenatal Exposure to Fine Particles
Authors: Jedrychowski Wieslaw , Flak Elzbieta , Mroz Elzbieta , Pac Agnieszka , Jacek Ryszard , Sochacka-Tatara Elzbieta , Spengler John , Rauh Virginia , Perera Frederica
Published: January 2008

The purpose of the study was to test the hypothesis whether infants with higher prenatal exposure to fine particles (PM2.5) are at greater risk of developing respiratory symptoms and whether fish consumption in pregnancy may modulate the effect. The study was carried out in a cohort of 465 newborns in Krakow (Poland) who have been followed over the first 2 years of life and for whom data on the occurrence of respiratory symptoms and measurements of personal air monitoring in the second trimester of pregnancy were available. The incidence risk ratio (IRR) of respiratory symptoms due to prenatal PM2.5 exposure were adjusted for potential confounders (gender of child, breastfeeding, parity, maternal atopy, maternal education as a proxy for the socio-economic status, exposure to postnatal environmental tobacco smoke (ETS), and moulds in households) in the generalized estimating equations (GEE) statistical models. The adjusted risk of coughing was associated significantly with PM2.5 level (IRR = 2.51; 95% CI: 1.77–3.58), moulds in the household, parity, maternal atopy and postnatal ETS, but was lower in girls, and in infants whose mothers consumed more fish in pregnancy (IRR = 0.85; 95% CI: 0.79–0.91). The risk of wheezing was also correlated significantly with the prenatal exposure to PM2.5 (IRR = 1.36; 95% CI: 1.29–1.43) but also with the presence of moulds in homes, parity, maternal atopy and postnatal ETS. The occurrence of wheezing was associated inversely with the gender of child, gestational age, and fish consumption in pregnancy (IRR = 0.97; 95% CI: 0.95–0.99). Similarly, the risk of difficult (puffy) breathing increased with prenatal exposure to PM2.5 (IRR = 1.18; 95% CI: 1.12–1.25) moulds, maternal atopy, and parity. The symptom occurrence was lower in girls and associated inversely with the gestational age, and fish consumption in pregnancy (IRR = 0.94; 95% CI: 0.92–0.97). The results of the study support the hypothesis that fish consumption in pregnancy may mitigate the harmful effect of prenatal or perinatal exposure to components of PM2.5 resulting in an increased burden of respiratory infections among infants.
The Effect of Sibutramine Intake on Resting and Exercise Physiological Responses
Authors: Rotstein Arie , Inbar Omri , Vaisman Nachum
Published: January 2008

Aim: To evaluate the effect of a short-term sibutramine intake on energy expenditure and on physiological responses during rest, submaximal exercise and maximal exercise in obese women. Methods: Fifteen healthy obese female volunteers were randomly assigned to either a placebo (n = 6 – control) or sibutramine group (n = 9 – experimental) under double-blind conditions. Each subject was tested under resting conditions and then performed submaximal and maximal exercise tests. Subjects were retested under identical conditions following a 5-day administration of either sibutramine 10 mg·day–1 or a placebo. All measurements (i.e. weight, body composition, resting energy expenditure, heart rate, respiratory exchange ratio, ventilation, oxygen consumption, carbon dioxide production, systolic blood pressure, diastolic blood pressure and blood lactate concentration) were analyzed using a 2-way ANOVA with repeated measures. Results: Only heart rate during submaximal exercise was significantly different (higher) following short-term sibutramine administration when compared to placebo (p < 0.05). Conclusions: These data suggest that a recommended daily dose of 10 mg sibutramine does not affect energy expenditure or other selected cardiopulmonary responses during rest, submaximal exercise or maximal exercise. It is, therefore, suggested that weight loss during sibutramine treatment in humans is achieved mostly via a decrease in energy intake rather than through an increase in energy expenditure and thermogenesis.
Encephalization of Australian and New Guinean Marsupials
Authors: Ashwell K.W.S.
Published: January 2008

Encephalization of Australian marsupials was analyzed using the endocranial volume (ECV) of 52 species of Dasyuromorphia and Notoryctemorphia, 14 species of Peramelemorphia and 116 species of Diprotodontia from Australia and New Guinea and compared with 16 species of Ameridelphian marsupials and 3 species of native and recently introduced Australian eutherian carnivores (dingo, feral cat and feral fox). Linear regression analysis of the relationship between ECV and body weight for marsupials revealed that allometric parameters for these groups are different from those previously derived for samples of (mainly eutherian) mammals, with higher slopes for Dasyuromorphia and Diprotodontia and lower slopes for Ameridelphians and Peramelemorphia. Absolute ECV for small Australian and New Guinea marsupial carnivores (Antechinus and Sminthopsis) were found to be comparable to eutherians of similar body weight, but large marsupial carnivores such as the Tasmanian devil and thylacine had substantially smaller ECVs than eutherian carnivores of similar body weight. Similarly, members of some superfamilies within Diprotodontia (Burramyoidea, Petauroidea, Tarsipedoidea) had ECVs comparable to prosimians, whereas bandicoots, bilbies and many macropods were found to be poorly encephalized. When both encephalization quotient (EQ) and residuals from regression analysis were used to compare relative ECV of extinct/threatened species with common species there were no significant differences for any of the orders of Australian marsupials, suggesting that encephalization is not a major factor in the current extinction crisis for Australian marsupials. Similarly there were no consistent differences in relative ECV between marsupials from New Guinea and associated islands compared to Australia or between arid and non-arid Australian regions for any of the marsupial orders. The results indicate that marsupials are not uniformly poorly encephalized and that small marsupial carnivores and some members of Diprotodontia are of comparable encephalization to eutherians of similar body weight. In particular, honey possums and some gliders show an encephalization level comparable to prosimians, perhaps reflecting convergence in adaptation to similar arboreal niches.
Hydroxyethyl Starch Inhibits Endothelium-Derived Relaxation in Porcine Coronary Arteries
Authors: Dagtekin Oguzhan , Krep Henning , Fischer Jürgen Hartmut
Published: January 2008

Objective: Hydroxyethyl starch (HES) solutions are widely used for fluid resuscitation. We studied the effects of HES on endothelium-dependent relaxation (EDR), especially on the endothelium-derived hyperpolarizing factor (EDHF). Methods: Four-millimeter-long rings of fresh porcine coronary arteries from the local slaughterhouse were consecutively tested with or without HES (6 mg/ml). Indomethacin (10 µmol/l) was added in all measurements to eliminate prostacyclin effects. Prostaglandin F2α (10 µmol/l) was used for contraction and bradykinin (10–10 to 10–5 mol/l) for inducing EDR, which was calculated in percentage of the precontraction. After blocking all nitric oxide formation by N-nitro-L-arginine (300 µmol/l), the experiments were repeated to assess the EDHF-mediated relaxation response to bradykinin. Results: HES 6 mg/ml induced a significant (p < 0.01) reduction in EDR (n = 8). After incubation with HES and nitric oxide blockage with N-nitro-L-arginine, the relaxation response was reduced especially for the bradykinin concentrations of 10–6 mol/l (p < 0.05) and 10–5 mol/l (p < 0.01). Conclusion: For the clinically relevant concentration of 6 mg/ml HES, a significant reduction in EDR and the EDHF can be found in epicardial coronary arteries of the pig.
Extracellular ATP Increases L-Carnitine Transport and Content in C2C12 Cells
Authors: Rigault Caroline , Bernard Arnaud , Georges Béatrice , Kandel Adeline , Pfützner Elisabeth , Le Borgne Françoise , Demarquoy Jean
Published: January 2008

Extracellular ATP regulates cell proliferation, muscle contraction and myoblast differentiation. ATP present in the muscle interstitium can be released from contracting skeletal muscle cells. L-Carnitine is a key element in muscle cell metabolism, as it serves as a carrier for fatty acid through mitochondrial membranes, controlling oxidation and energy production. Treatment of C2C12 cells with 1 mmol/l of ATP induced a marked increase in L-carnitine uptake that was associated with an increase in L-carnitine content in these cells. These effects were found to be dependent on the density of the cultured cells and on the dose of ATP. The use of specific inhibitors of P2X and P2Y receptors abolished the effect of ATP on L-carnitine metabolism. As ATP can be released from stressed or exercising cells, it can be hypothesized that ATP acts as a messenger in the muscle. ATP will be released to recruit the next cells and increase their metabolism.
Prevalence and Consultation Behavior of Self-Reported Rectal Bleeding by Face-to-Face Interview in an Asian Community
Authors: Basaranoglu Metin , Celebi Selman , Ataseven Huseyin , Rahman Suheyla , Deveci S. Erhan , Acık Yasemin
Published: January 2008

Background and Aim: Although rectal bleeding is a common gastrointestinal symptom, there are very few community-based studies, and all of these studies were conducted in the West. So far the epidemiologic characteristics of rectal bleeding have not been defined in an Asian country. We aimed to characterize self-reported rectal bleeding and its association with functional bowel disorders in Turkey. Factors affecting healthcare-seeking behavior were reviewed as well. Subjects and Methods: In this study, 760 subjects were chosen randomly. Questionnaires were completed by nurses during face-to-face interviews with each participant. Results: Of the 707 (93%) subjects included in this study, 9.5% had functional dyspepsia, 8.6% had irritable bowel syndrome (IBS), 24.5% had functional constipation, and 13.8% had functional abdominal bloating. The prevalence of rectal bleeding in the previous year was 14.7%. The recent onset of rectal bleeding was 2.7%. Rectal bleeding was more common among subjects younger than 45 years. Subjects who had functional constipation or constipation-dominant IBS reported rectal bleeding more frequently than others. The rate of consultation was only 41.3% among the subjects with rectal bleeding. Subjects aged ≧45 years and who had marked bleeding or bleeding more than twice a day or fear of cancer sought healthcare more frequently than others. Conclusion: Rectal bleeding is as common a symptom in Turkey as in Western countries. Advanced age and fear of cancer were independent predictors of consultation behavior in this group.
Mesoscale Simulations of the Land Surface Effects of Historical Logging in a Moist Continental Climate Regime
Authors: Klingaman Nicholas P. , Butke Jason , Leathers Daniel J. , Brinson Kevin R. , Nickl Elsa
Published: January 2008

An enhanced knowledge of the feedbacks from land surface changes on regional climates is of great importance in the attribution of climate change. To explore the effects of deforestation on a midlatitude climate regime, two sets of two five-member ensembles of 28-day simulations were conducted using the fifth-generation Pennsylvania State University–National Center for Atmospheric Research Mesoscale Model (MM5) coupled to the “Noah” land surface model. The four ensembles represented conditions in summer (August) and winter (February) across the northern mid-Atlantic United States before and after extensive late-nineteenth-century logging of hardwood forests in central and northern Pennsylvania. Prelogging ensembles prescribed a vegetative cover of an evergreen needleleaf forest; postlogging ensembles prescribed sparse vegetation and bare soil to simulate clear-cut deforestation. The results of the MM5 experiments showed a decided seasonality in the response of the land surface–atmosphere system to deforestation, with much stronger effects arising in summer. In August, deforestation caused a repartitioning of the surface energy budget, beginning with a decrease in the latent heat flux of more than 60 W m−2 across the land cover–forcing area, representing almost one-half of the latent heat flux under prelogging land cover. Concomitant with this decrease in evapotranspiration, mean 2-m air temperatures warmed by at least 1.5°C. Increases in sensible heat flux led to a 150-m mean increase in the height of the atmospheric boundary layer over the deforested area. Low-level atmospheric mixing ratios and total precipitation decreased under clear-cut conditions. Mean soil moisture increased in all model levels to 150 cm because of a decrease in vegetative uptake of water, except at the 5-cm level at which such decreases were effectively balanced by greater soil evaporation and less precipitation. A strong diurnal variation in the response to deforestation of ground and lower-atmosphere temperatures and heat fluxes was also identified for the summer season. The February simulations showed the effects of deforestation during low-insolation months to be small and variable. The strong response of the summer land surface–atmosphere system to deforestation shown here suggests that land cover changes can appreciably affect regional climates. Thus, the role of human-induced and naturally occurring land cover variability should not be ignored in the attribution of climate change.
Subgrid-Scale Parameterization with Conditional Markov Chains
Authors: Crommelin Daan , Vanden-Eijnden Eric
Published: January 2008

A new approach is proposed for stochastic parameterization of subgrid-scale processes in models of atmospheric or oceanic circulation. The new approach relies on two key ingredients: first, the unresolved processes are represented by a Markov chain whose properties depend on the state of the resolved model variables; second, the properties of this conditional Markov chain are inferred from data. The parameterization approach is tested by implementing it in the framework of the Lorenz ’96 model. Performance of the parameterization scheme is assessed by inspecting probability distributions, correlation functions, and wave properties, and by carrying out ensemble forecasts. For the Lorenz ’96 model, the parameterization algorithm is shown to give good results with a Markov chain with a few states only and to outperform several other parameterization schemes.
Acceleration of the Brewer–Dobson Circulation due to Increases in Greenhouse Gases
Authors: Garcia Rolando R. , Randel William J.
Published: January 2008

The acceleration of the Brewer–Dobson circulation under rising concentrations of greenhouse gases is investigated using the Whole Atmosphere Community Climate Model. The circulation strengthens as a result of increased wave driving in the subtropical lower stratosphere, which in turn occurs because of enhanced propagation and dissipation of waves in this region. Enhanced wave propagation is due to changes in tropospheric and lower-stratospheric zonal-mean winds, which become more westerly. Ultimately, these trends follow from changes in the zonal-mean temperature distribution caused by the greenhouse effect. The circulation in the middle and upper stratosphere also accelerates as a result of filtering of parameterized gravity waves by stronger subtropical westerly winds.
Interdecadal Sea Surface Temperature Variability in the Equatorial Pacific Ocean. Part II: The Role of Equatorial/Off-Equatorial Wind Stresses in a Hybrid Coupled Model
Authors: McGregor Shayne , Holbrook Neil J. , Power Scott B.
Published: January 2008

Many modeling studies have been carried out to investigate the role of oceanic Rossby waves linking the off-equatorial and equatorial Pacific Ocean. Although the equatorial ocean response to off-equatorial wind stress forcing alone tends to be relatively small, it is clear that off-equatorial oceanic Rossby waves affect equatorial Pacific Ocean variability on interannual through to interdecadal time scales. In the present study, a hybrid coupled model (HCM) of the equatorial Pacific (between 12.5°S and 12.5°N) was developed and is used to estimate the magnitude of equatorial region variability arising from off-equatorial (poleward of 12.5° latitude) wind stress forcing. The HCM utilizes a reduced-gravity ocean shallow-water model and a statistical atmosphere derived from monthly output from a 100-yr Australian Bureau of Meteorology Research Centre (now the Centre for Australian Weather and Climate Research) coupled general circulation model integration. The equatorial region wind stress forcing is found to dominate both the interannual and interdecadal SST variability. The equatorial response to off-equatorial wind stress forcing alone is insufficient to initiate an atmospheric feedback that significantly amplifies the original equatorial region variability. Consequently, the predictability of equatorial region SST anomalies (SSTAs) could be limited to ∼1 yr (the maximum time it takes an oceanic Rossby wave to cross the Pacific Ocean basin in the equatorial region). However, the results also suggest that the addition of off-equatorial wind stress forcing to the HCM leads to variations in equatorial Pacific background SSTA of up to almost one standard deviation. This off-equatorially forced portion of the equatorial SSTA could prove critical for thresholds of El Niño–Southern Oscillation (ENSO) because they can constructively interfere with equatorially forced SSTA of the same sign to produce significant equatorial region ENSO anomalies.
Asymmetry of the Indian Ocean Dipole. Part II: Model Diagnosis*
Authors: Hong Chi-Cherng , Li Tim , Luo Jing-Jia
Published: January 2008

In this second part of a two-part paper, the mechanism for the amplitude asymmetry of SST anomalies (SSTA) between positive and negative Indian Ocean dipole (IOD) events is investigated through the diagnosis of coupled model simulations. Same as the observed in Part I, a significant negative skewness appears in the IOD east pole (IODE) in September–November (SON), whereas there is no significant skewness in the IOD west pole (IODW). A sensitivity experiment shows that the negative skewness in IODE appears even in the case when the ENSO is absent.

The diagnosis of the model mixed layer heat budget reveals that the negative skewness is primarily induced by the nonlinear ocean temperature advection and the asymmetry of the cloud–radiation–SST feedback, consistent with the observation (Part I). However, the simulated latent heat flux anomaly is greatly underestimated in IODE during the IOD developing stage [June–September (JJAS)]. As a result, the net surface heat flux acts as strong thermal damping. The underestimation of the latent heat flux anomaly in the IODE is probably caused by the westward shift of along-coast wind anomalies off Sumatra.
Observations and Numerical Simulation of Upper Boundary Layer Rapid Drying and Moistening Events during the International H2O Project (IHOP_2002)
Authors: Tanamachi Robin L. , Feltz Wayne F. , Xue Ming
Published: January 2008

On the morning of 12 June 2002, a series of upper boundary layer (UBL) rapid drying and moistening events (RDEs and RMEs, respectively) occurred at the “Homestead” site of the International H2O Project (IHOP_2002). Over a period of 10 h, atmospheric water vapor in the UBL decreased or increased within a matter of minutes four separate times. High-temporal-resolution data of the RDEs and RMEs collected by numerous instruments deployed for this intensive observation period are presented. The results of an Advanced Regional Prediction System (ARPS) simulation of the weather conditions around the time period reproduced one of the two RDE–RME pairs with reasonably accurate amplitude and timing. Both the observational data and ARPS numerical model output indicate that the second RDE–RME pair resulted from the interaction between a dry air mass descending from the Rocky Mountains and a cold pool–internal undular bore couplet propagating over the Homestead site from a mesoscale convective complex to the north. The RDEs and RMEs, which were rarely observed during IHOP_2002, are believed to be an indirect indicator of such bores.
Sasaki’s Pivotal Contribution: Calculus of Variations Applied to Weather Map Analysis
Authors: Lewis John , Lakshmivarahan S.
Published: January 2008

Yoshikazu Sasaki developed a variational method of data assimilation, a cornerstone of modern-day analysis and prediction in meteorology. Fundamentally, he formulated data assimilation as a constrained minimization problem with equality constraints. The generation of this idea is tracked by analyzing his education and research at the University of Tokyo in the immediate post–World War II (WWII) period. Despite austere circumstances—including limited financial support for education, poor living conditions, and a lack of educational resources—Sasaki was highly motivated and overcame these obstacles on his path to developing this innovative method of weather map analysis. The stages of his intellectual development are followed where information comes from access to his early publications, oral histories, and letters of reminiscence.

It has been argued that Sasaki’s unique contribution to meteorological data assimilation stems from his deterministic view of the problem—a view founded on the principles of variational mechanics. Sasaki’s approach to the problem is compared and contrasted with the stochastic view that was pioneered by Arnt Eliassen. Both of these optimal approaches are viewed in the context of the pragmatic–operational objective analysis schemes that were developed in the 1950s–1960s. Finally, current-day methods [e.g., three- and four-dimensional variational data assimilation (3DVAR and 4DVAR)] are linked to the optimal methods of Eliassen and Sasaki.
Autonomy and Control in Public Hospital Reforms in Singapore
Authors: Ramesh M.
Published: January 2008

The Singapore government began to reform public hospitals in the mid-1980s because of mounting public expenditures on health care. It granted public hospitals managerial autonomy and required them to compete for patients' fees. Correspondingly, patients were required to pay a larger proportion of the costs. When subsequent evidence showed that costs were increasing rather than decreasing, in the mid-1990s the government began to reassert its control while retaining the essence of the earlier reforms. In recent years, the reforms have emphasized management autonomy coupled with strong government guidance. This article assesses the autonomy and control mechanisms in place to promote effective service delivery in public hospitals in Singapore and concludes that reliance on market competition requires more state intervention than often realized. For market competition to deliver outcomes that are not only economically efficient and consumer-friendly but also politically acceptable, constant governmental oversight and coordination is essential.
Thermal dependency of RAG1 self-association properties
Authors: De Pallabi , Zhao Shuying , Gwyn Lori M , Godderz LeAnn J , Peak Mandy M , Rodgers Karla K
Published: January 2008

Background

Functional immunoglobulin and T cell receptor genes are produced in developing lymphocytes by V(D)J recombination. The initial site-specific DNA cleavage steps in this process are catalyzed by the V(D)J recombinase, consisting of RAG1 and RAG2, which is directed to appropriate DNA cleavage sites by recognition of the conserved recombination signal sequence (RSS). RAG1 contains both the active site and the RSS binding domains, although RAG2 is also required for DNA cleavage activity. An understanding of the physicochemical properties of the RAG proteins, their association, and their interaction with the RSS is not yet well developed.

Results

Here, we further our investigations into the self-association properties of RAG1 by demonstrating that despite the presence of multiple RAG1 oligomers, only the dimeric form maintains the ability to interact with RAG2 and the RSS. However, facile aggregation of the dimeric form at physiological temperature may render this protein inactive in the absence of RAG2. Upon addition of RAG2 at 37°C, the preferentially stabilized V(D)J recombinase:RSS complex contains a single dimer of RAG1.

Conclusion

Together these results confirm that the functional form of RAG1 in V(D)J recombination is in the dimeric state, and that its stability under physiological conditions likely requires complex formation with RAG2. Additionally, in future structural and functional studies of RAG1, it will be important to take into account the temperature-dependent self-association properties of RAG1 described in this study.
Aortic valve replacement in a young patient with essential thrombocytosis
Authors: Ahmed Kashif , Vohra Hunaid A , Milne Alison , Langley Stephen M
Published: January 2008

Essential Thrombocythcythaemia (ET) is an uncommon type of myeloproliferative disorder, characterised by both thrombotic and haemorrhagic diathesis. No clear guidelines exist for the pre- and post-operative management of patients undergoing cardiac surgery in the haematological and surgical literature. This condition has profound implications in patients undergoing cardiac surgery with the use of cardiopulmonary bypass, where heparin is used for anti-coagulation. This dilemma is further compounded in the setting of a young patient undergoing aortic valve replacement (AVR), where insertion of a mechanical prosthesis would be the procedure of choice. This would require life-long anticoagulation with warfarin which can predispose these patients to catastrophic bleeding. Using a tissue valve will subject the patient to multiple redo operations in the patient's lifetime. We report a young patient with ET requiring AVR and discuss the dilemmas surrounding the choice of prosthesis in this patient.
Meta-Analysis of Phase II Cooperative Group Trials in Metastatic Stage IV Melanoma to Determine Progression-Free and Overall Survival Benchmarks for Future Phase II Trials
Authors: Korn Edward L. , Liu Ping-Yu , Lee Sandra J. , Chapman Judith-Anne W. , Niedzwiecki Donna , Suman Vera J. , Moon James , Sondak Vernon K. , Atkins Michael B. , Eisenhauer Elizabeth A. , Parulekar Wendy , Markovic Svetomir N. , Saxman Scott , Kirkwood John M.
Published: January 2008

Purpose

Objective tumor response rates observed in phase II trials for metastatic melanoma have historically not provided a reliable indicator of meaningful survival benefits. To facilitate using overall survival (OS) or progression-free survival (PFS) as an endpoint for future phase II trials, we evaluated historical data from cooperative group phase II trials to attempt to develop benchmarks for OS and PFS as reference points for future phase II trials.

Patients and Methods

Individual-level and trial-level data were obtained for patients enrolled onto 42 phase II trials (70 trial arms) that completed accrual in the years 1975 through 2005 and conducted by Southwest Oncology Group, Eastern Cooperative Oncology Group, Cancer and Leukemia Group B, North Central Cancer Treatment Group, and the Clinical Trials Group of the National Cancer Institute of Canada. Univariate and multivariate analyses were performed to identify prognostic variables, and between-trial(-arm) variability in 1-year OS rates and 6-month PFS rates were examined.

Results

Statistically significant individual-level and trial-level prognostic factors found in a multivariate survival analysis for OS were performance status, presence of visceral disease, sex, and whether the trial excluded patients with brain metastases. Performance status, sex, and age were statistically significant prognostic factors for PFS. Controlling for these prognostic variables essentially eliminated between-trial variability in 1-year OS rates but not in 6-month PFS rates.

Conclusion

Benchmarks are provided for 1-year OS or OS curves that make use of the distribution of prognostic factors of the patients in the phase II trial. A similar benchmark for 6-month PFS is provided, but its use is more problematic because of residual between-trial variation in this endpoint.
Outcomes and Cost of Outpatient or Inpatient Management of 712 Patients With Febrile Neutropenia
Authors: Elting Linda S. , Lu Charles , Escalante Carmelita P. , Giordano Sharon H. , Trent Jonathan C. , Cooksley Catherine , Avritscher Elenir B.C. , Shih Ya-Chen Tina , Ensor Joe , Bekele B. Nebiyou , Gralla Richard J. , Talcott James A. , Rolston Kenneth
Published: January 2008

Purpose

We retrospectively compared the outcomes and costs of outpatient and inpatient management of low-risk outpatients who presented to an emergency department with febrile neutropenia (FN).

Patients and Methods

A single episode of FN was randomly chosen from each of 712 consecutive, low-risk solid tumor outpatients who had been treated prospectively on a clinical pathway (1997-2003). Their medical records were reviewed retrospectively for overall success (resolution of all signs and symptoms of infection without modification of antibiotics, major medical complications, or intensive care unit admission) and nine secondary outcomes. Outcomes were assessed by physician investigators who were blinded to management strategy. Outcomes and costs (payer's perspective) in 529 low-risk outpatients were compared with 123 low-risk patients who were psychosocially ineligible for outpatient management (no access to caregiver, telephone, or transportation; residence > 30 minutes from treating center; poor compliance with previous outpatient therapy) using univariate statistical tests.

Results

Overall success was 80% among low-risk outpatients and 79% among low-risk inpatients. Response to initial antibiotics was 81% among outpatients and 80% among inpatients (P = .94); 21% of those initially treated as outpatients subsequently required hospitalization. All patients ultimately responded to antibiotics; there were no deaths. Serious complications were rare (1%) and equally frequent between the groups. The mean cost of therapy among inpatients was double that of outpatients ($15,231 v $7,772; P < .001).

Conclusion

Outpatient management of low-risk patients with FN is as safe and effective as inpatient management of low-risk patients and is significantly less costly.
Multicenter, Phase II Trial of Sunitinib in Previously Treated, Advanced Non–Small-Cell Lung Cancer
Authors: Socinski Mark A. , Novello Silvia , Brahmer Julie R. , Rosell Rafael , Sanchez Jose M. , Belani Chandra P. , Govindan Ramaswamy , Atkins James N. , Gillenwater Heidi H. , Pallares Cinta , Tye Lesley , Selaru Paulina , Chao Richard C. , Scagliotti Giorgio V.
Published: January 2008

Purpose

Aberrant vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) signaling have been shown to play a role in non–small-cell lung cancer (NSCLC) pathogenesis and are associated with decreased survival. We evaluated the clinical activity and tolerability of sunitinib malate (SU11248), an oral, multitargeted tyrosine kinase inhibitor that blocks the activity of receptors for VEGF and PDGF, as well as related tyrosine kinases in patients with previously treated, advanced NSCLC.

Patients and Methods

Patients with stage IIIB or IV NSCLC for whom platinum-based chemotherapy had failed received 50 mg/d of sunitinib for 4 weeks followed by 2 weeks of no treatment in 6-week treatment cycles. The primary end point was objective response rate (ORR); secondary end points included progression-free survival, overall survival, and safety.

Results

Of the 63 patients treated with sunitinib, seven patients had confirmed partial responses, yielding an ORR of 11.1% (95% CI, 4.6% to 21.6%). An additional 18 patients (28.6%) experienced stable disease of at least 8 weeks in duration. Median progression-free survival was 12.0 weeks (95% CI, 10.0 to 16.1 weeks), and median overall survival was 23.4 weeks (95% CI, 17.0 to 28.3 weeks). Therapy was generally well tolerated.

Conclusion

Sunitinib has promising single-agent activity in patients with recurrent NSCLC, with an ORR similar to that of currently approved agents and an acceptable safety profile. Further evaluation in combination with other targeted agents and chemotherapy in patients with NSCLC is warranted.
Electrochemical Dissolution and Redeposition of Electropolymerized Polyindole Film
Authors: Kim Sang-kook , Kumamoto Takuya , Ishikawa Tsutomu , Seki Hiroko , Ozawa Tomoyuki , Hoshino Katsuyoshi
Published: January 2008

An electropolymerized polyindole film was solubilized into a dichloromethane solution by its electrochemical reduction, and the electrochemical reoxidation of the soluble species produced the film again on the electrode surface. These dissolution and redeposition behavior were investigated by using cyclic voltammetry, UV–vis, NMR, FT-IR, and MALDI-TOFMS measurements.
MicroRNA expression in the adult mouse central nervous system
Authors: Bak Mads , Silahtaroglu Asli , Møller Morten , Christensen Mette , Rath Martin F. , Skryabin Boris , Tommerup Niels , Kauppinen Sakari
Published: January 2008

microRNAs are ∼22 nucleotide endogenous noncoding RNAs that post-transcriptionally repress expression of protein-coding genes by base-pairing with the 3′-untranslated regions of the target mRNAs. We present here an inventory of miRNA expression profiles from 13 neuroanatomically distinct areas of the adult mouse central nervous system (CNS). Microarray profiling in combination with real-time RT-PCR and LNA (locked nucleic acid)-based in situ hybridization uncovered 44 miRNAs displaying more than threefold enrichment in the spinal cord, cerebellum, medulla oblongata, pons, hypothalamus, hippocampus, neocortex, olfactory bulb, eye, and pituitary gland. These findings suggest that a large number of mouse CNS-expressed miRNAs may be associated with specific functions within these regions. Notably, more than 50% of the identified mouse CNS-enriched miRNAs showed different expression patterns compared to those reported in zebrafish, although the mature miRNA sequences are nearly 100% conserved between the two vertebrate species. The inventory of miRNA profiles in the adult mouse CNS presented here provides an important step toward further elucidation of miRNA function and miRNA-related gene regulatory networks in the mammalian central nervous system.
Cognitive behaviour therapy in patients with schizophrenia who are not prescribed antipsychotic medication: A case series
Authors: Christodoulides T. , Dudley R. , Brown S. , Turkington D. , Beck Aaron T.
Published: January 2008

Objectives. Cognitive behaviour therapy (CBT) as an adjunct to medication has been shown to improve symptom management in patients with schizophrenia. However, little is understood about the value of CBT for people who are not prescribed antipsychotic medication.

Design. A post hoc case series design was used to examine the outcome data of three participants selected from a randomized controlled trial for CBT for schizophrenia. The participants were included if they had received CBT and were not prescribed antipsychotic medication during active treatment.

Results. The three patients improved on outcome measures of psychopathology, depression, or negative symptoms, some to a clinically significant degree.

Conclusions. CBT is a feasible treatment for people with schizophrenia who are not prescribed antipsychotic medication. It may be a valuable alternative to medication in treating symptoms of schizophrenia.
Cannabinoids Desensitize Capsaicin and Mustard Oil Responses in Sensory Neurons via TRPA1 Activation
Authors: Akopian Armen N. , Ruparel Nikita B. , Patwardhan Amol , Hargreaves Kenneth M.
Published: January 2008

Although the cannabinoid agonistsR-(+)-(2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]pyrol[1,2,3-de]-1,4-benzoxazin-6-yl)-(1-naphthalenyl) methanone mesylate [WIN 55,212-2 (WIN)] and (R,S)-3-(2-iodo-5-nitrobenzoyl)-1-(1-methyl-2-piperidinylmethyl)-1H-indole (AM1241) exert peripheral antihyperalgesia in inflammatory pain models, the mechanism for cannabinoid-induced inhibition of nociceptive sensory neurons has not been fully studied. Because TRPV1 and TRPA1 channels play important roles in controlling hyperalgesia in inflammatory pain models, we investigated their modulation by WIN and AM1241. The applications of WIN (>5 μm) and AM1241 (>30 μm) inhibit responses of sensory neurons to capsaicin and mustard oil. To determine potential mechanisms for the inhibition, we evaluated cannabinoid effects on nociceptors. WIN and AM1241 excite sensory neurons in a concentration-dependent manner via a nonselective Ca2+-permeable channel. The expression of TRP channels in CHO cells demonstrates that both WIN and AM1241 activate TRPA1 and, by doing so, attenuate capsaicin and mustard oil responses. Using TRPA1-specific small interfering RNA or TRPA1-deficient mice, we show that the TRPA1 channel is a sole target through which WIN and mustard oil activate sensory neurons. In contrast, AM1241 activation of sensory neurons is mediated by TRPA1 and an unknown channel. The knockdown of TRPA1 activity in neurons completely eliminates the desensitizing effects of WIN and AM1241 on capsaicin-activated currents. Furthermore, the WIN- or AM1241-induced inhibition of capsaicin-evoked nocifensive behavior via peripheral actions is reversed in TRPA1 null-mutant mice. Together, this study demonstrates that certain cannabinoids exert their peripheral antinocifensive actions via activation of the TRPA1 channel on sensory neurons.
Netrin-1 Is a Novel Myelin-Associated Inhibitor to Axon Growth
Authors: Löw Karin , Culbertson Maya , Bradke Frank , Tessier-Lavigne Marc , Tuszynski Mark H.
Published: January 2008

We investigated the influence of the bifunctional guidance molecule netrin-1 on axonal growth in the injured adult spinal cord. In the adult, netrin-1 is expressed on mature oligodendrocytes, cells of the central canal, and the meninges. Netrin-1 protein in white matter is selectively enriched adjacent to paranodal loops of myelin in nodes of Ranvier. The repulsion-mediating netrin-1 uncoordinated-5 (UNC5) receptors are expressed by neurons of the corticospinal and rubrospinal projections, and by intrinsic neurons of the spinal cord, both before and after spinal cord injury. Neutralization of netrin-1 in myelin prepared from adult rat spinal cord using UNC5 receptor bodies increases neurite outgrowth from UNC5-expressing spinal motor neuronsin vitro. Furthermore, axon regeneration is inhibited in a netrin-1-enriched zone, devoid of other myelin-associated inhibitors, within spinal cord lesion sitesin vivo. We conclude that netrin-1 is a novel oligodendrocyte-associated inhibitor that can contribute to axonal growth failure after adult spinal cord injury.
Metabotropic Glutamate Receptor Type 5-Dependent Long-Term Potentiation of Excitatory Synapses on Fast-Spiking GABAergic Neurons in Mouse Visual Cortex
Authors: Sarihi Abdolrahman , Jiang Bin , Komaki Alireza , Sohya Kazuhiro , Yanagawa Yuchio , Tsumoto Tadaharu
Published: January 2008

Long-term potentiation (LTP) of excitatory synapses on GABAergic neurons in layer II/III of visual cortical slices was examined in GAD67-GFP knock-in mice by whole-cell recordings of EPSPs evoked by layer IV stimulation. Theta burst stimulation (TBS) paired with postsynaptic depolarization induced LTP in 14 of 19 fast-spiking GABAergic (FS-GABA) neurons, whereas only in 6 of 17 non-FS GABAergic neurons. The mean magnitude of LTP in the former cell group was larger than that in the latter. The paired-pulse stimulation protocol and coefficient of variation analysis indicated that LTP of excitatory synapses on FS-GABA neurons may be postsynaptic in origin. Filling postsynaptic cells with a Ca2+-chelator blocked the induction of LTP, suggesting an involvement of postsynaptic Ca2+rise. The developmental analysis of LTP indicated that almost the same magnitude of LTP was induced after postnatal day 17 to the young adulthood, suggesting no age dependence after eye opening. This form of LTP was dependent neither on NMDA receptors nor voltage-gated Ca2+channels (L and T types). An antagonist for type 5 metabotropic glutamate receptors (mGluR5) blocked this form of LTP, whereas an antagonist for mGluR1 was not effective. An agonist for mGluR1/5 induced potentiation of EPSPs of FS-GABA neurons in concentration- and use-dependent manners. This potentiation and TBS-induced LTP occluded each other. Further pharmacological analyses suggested that this form of LTP at FS-GABA neurons is induced through an activation of mGluR5, which triggers Ca2+release from internal stores via activations of phospholipase C and inositol triphosphate.