bluuebunny/crossref_metadata_2025 huggingface dataset:
Economic statistical design of a T2 control chart with double warning lines
Authors: Faraz Alireza , Saniga Erwin
Published: February 2010

Recent studies have shown that enhancing the common T2 control chart by using variable sample sizes (VSS) and variable sample intervals (VSI) sampling policies with a double warning line scheme (DWL) yields improvements in shift detection times over either pure VSI or VSS schemes in detecting almost all shifts in the process mean. In this paper, we look at this problem from an economical perspective, certainly at least as an important criterion as shift detection time if one considers what occurs in the industry today. Our method is to first construct a cost model to find the economic statistical design (ESD) of the DWL T2 control chart using the general model of Lorenzen and Vance (Technometrics 1986; 28:3–11). Subsequently, we find the values of the chart parameters which minimize the cost model using a genetic algorithm optimization method. Cost comparisons of Fixed ratio sampling, VSI, VSS, VSIVSS with DWL, and multivariate exponentially weighted moving average (MEWMA) charts are made, which indicate the economic efficacy of using either VSIVSS with DWL or MEWMA charts in practice if cost minimization is of interest to the control chart user. Copyright © 2010 John Wiley & Sons, Ltd.
Value of liver herniation in prediction of outcome in fetal congenital diaphragmatic hernia: a systematic review and meta‐analysis
Authors: Mullassery D. , Ba'ath M. E. , Jesudason E. C. , Losty P. D.
Published: February 2010

Objectives

Intrathoracic liver herniation (ILH) is being used to estimate prognosis and hence guide antenatal interventions in fetal congenital diaphragmatic hernia (CDH). However, the literature regarding its utility in this role is conflicting. This review systematically examines the currently available evidence of ILH use in fetal CDH.

Methods

MEDLINE and EMBASE databases were searched for the terms ((congenital diaphragmatic hernia) OR CDH) AND liver. Inclusion criteria were human case series of fetuses diagnosed with CDH using either ultrasound or magnetic resonance imaging. Included studies were required to have reported the antenatal liver position and the outcome (survival or not). Case reports, reviews and eventration series were excluded. Studies reporting similar cases from the same center over an overlapping time period were considered duplicates; only the larger of the studies were therefore included. Absolute totals were extracted and sums calculated. Fisher's exact test (FET) was used to compare survival rates in different groups.

Results

The original search retrieved 338 studies. Applying inclusion/exclusion criteria and removing duplicates left 21 case series in 20 studies. Retrieved studies differed in the definitions of liver herniation, survival and treatment modality. In total, there were 407 fetuses in the liver‐up (herniated) and 303 in the liver‐down (not herniated) groups. Survival rates were 45.4% and 73.9%, respectively. The difference was statistically significant (FET = 56.4, P < 0.005). Sensitivity analysis for cases that had only conventional postnatal treatment was still significant (FET = 52.8, P < 0.005).

Conclusions

Liver herniation is associated with poorer prognosis in fetal CDH. Grading liver herniation or using it as part of a panel of markers may enhance the value of liver herniation as a prognostic test in fetal CDH. Copyright © 2010 ISUOG. Published by John Wiley & Sons, Ltd.
Maternal renal interlobar vein impedance index is higher in early‐ than in late‐onset pre‐eclampsia
Authors: Gyselaers W. , Mesens T. , Tomsin K. , Molenberghs G. , Peeters L.
Published: February 2010

Objectives

To test the hypothesis that Doppler characteristics of maternal renal interlobar veins (RIV) are different between pregnancies affected by early‐onset pre‐eclampsia (EP) and those affected by late‐onset pre‐eclampsia (LP).

Methods

A gestational age of 34 weeks was considered to differentiate EP from LP. All women had a renal duplex scan according to a standard protocol, with known intraobserver correlation coefficient (0.88). Maximum (Vmax) and minimum (Vmin) RIV velocities were measured on two occasions (between 28 and 32 and between 34 and 37 weeks) in 18 women with uncomplicated pregnancy (UP). In women with EP (n = 32) or LP (n = 41), these variables were measured once, within 3 days following hospital admission. Delta velocity (DeltaV) was calculated as Vmax − Vmin and the RIV impedance index (RIVI) was calculated as DeltaV/Vmax. Data on neonatal outcome and maternal renal function were obtained for UP and those with EP and LP, and group‐specific means ± SD were calculated and compared.

Results

Compared with UP, the RIVI of both left and right kidneys was higher in those with EP (0.49 ± 0.13 vs. 0.36 ± 0.04, P = 0.0001, and 0.46 ± 0.15 vs. 0.33 ± 0.04, P = 0.0008) and in those with LP (0.41 ± 0.07 vs. 0.37 ± 0.06, P = 0.04, and 0.38 ± 0.12 vs. 0.30 ± 0.05, P = 0.009). RIVI was higher in pregnancies with EP than in those with LP (P ≤ 0.01), and this difference was associated with lower median birth‐weight percentiles (22.5 (interquartile range (IQR), 15–35) vs. 40.0 (IQR, 12–55), P = 0.01), higher maternal serum uric acid concentrations (419 ± 84 vs. 374 ± 85 µmol/L, P = 0.03) and higher proteinuria (4131 ± 3885 vs. 1190 ± 1133 mg/24 h, P < 0.0001).

Conclusion

Maternal vascular maladaption in pre‐eclampsia is associated with abnormal Doppler findings in the venous compartment. RIVI is higher in EP than in LP pregnancies and this is associated with lower birth‐weight percentiles and higher proteinuria. Copyright © 2010 ISUOG. Published by John Wiley & Sons, Ltd.
Dietary specialization and Eucalyptus species preferences in Queensland koalas (Phascolarctos cinereus)
Authors: Higgins Alexis L. , Bercovitch Fred B. , Tobey Jennifer R. , Andrus Chris Hamlin
Published: February 2010

Koalas specialize on Eucalyptus leaves, but also feed selectively. Food choice is not random, but depends on various factors that are not well understood, although most research has focused on the role of secondary plant compounds. We studied the feeding choices of four adult male koalas housed at the San Diego Zoo. All subjects had a choice of nine types of Eucalyptus leaves over the eight‐week study. The most preferred species was E. camuldulensis, but individual males exhibited different feeding preferences. We conclude that food selectivity among koalas is probably due to multiple factors, rather than only a consequence of secondary plant chemicals. A combination of intrinsic factors, such as developmental trajectory and reproductive state, as well as extrinsic factors, such as leaf chemical fingerprint and moisture, probably interact to shape koala foraging preferences. Koalas forage almost exclusively on Eucalyptus species, but have evolved an adaptive flexibility, enabling them to exploit various Eucalyptus species. Zoo Biol 30:52–58, 2011. © 2010 Wiley‐Liss, Inc.
Flexible Thoracoscopy may Facilitate Video‐Assisted Thoracoscopic Lobectomy
Authors: Licht Peter B. , Ladegaard Lars
Published: February 2010

Background

Video‐assisted thoracoscopic lobectomy was introduced in the early 1990s but has not yet gained widespread acceptance. The VATS approach is still controversial although several studies suggest less postoperative morbidity compared with open thoracotomy. Nevertheless, some patients report long‐lasting chest wall pain following VATS procedures, and, in theory, such pain may be related to intercostal nerve injury. The present study presents our experience with a commercially available flexible thoracoscope.

Methods

The study was designed as a case‐control series of prospectively collected data to determine if performing VATS with a flexible thorascope could have benefits for both the patient and the surgeon.

Results

During the last 24 months 128 of 274 consecutive lobectomies (47%) were scheduled as VATS procedures with a new flexible high‐definition thoracoscope. Six operations (4.6%) were converted to open surgery but only one case was converted during the last 12 months. There was no hospital mortality. The median duration of the operation was 105 min (range: 50–289 min), and the median postoperative hospital stay was 4 days (range: 2–27 days). At routine follow‐up 2 weeks postoperatively all but three patients (2%) were considered pain free, which was significantly less than in 15 consecutive VATS lobectomies with rigid thoracoscopy performed prior to the introduction of flexible VATS (p= 0.02).

Conclusions

Video‐assisted thoracoscopic lobectomy by flexible thoracoscopy is feasible and in our opinion easier and safer compared with rigid thoracoscopy. In our experience all parts of the operation are better visualized and many surgical pitfalls may be avoided. Even during early phases of setting up the VATS lobectomy program, the duration of the operation is comparable with open surgery, and postoperative pain is low, possibly because porthole angulation is minimized.
Deep Venous Thrombosis After Surgery for Inflammatory Bowel Disease: Is Standard Dose Low Molecular Weight Heparin Prophylaxis Enough?
Authors: Scarpa Marco , Pilon Fabio , Pengo Vittorio , Romanato Giovanna , Ruffolo Cesare , Erroi Francesca , Elisa Bison , Frego Mauro , Ossi Elena , Manzato Enzo , Angriman Imerio
Published: February 2010

Background

Inflammatory bowel disease (IBD) and colorectal surgery are risk factors for deep venous thrombosis (DVT). The aim of this prospective study was to evaluate the effectiveness of standardized prophylactic low molecular weight heparin (LMWH) therapy in patients who underwent surgery for ulcerative colitis (UC) and Crohn’s disease (CD).

Patients and methods

Since 1999 all patients operated on for colorectal diseases in our institute have received 4,000 IU/day LMWH from the day of operation to discharge. The complete series of patients who had major colorectal surgery from 1999 until 2006 were reviewed for overt DVT episodes. Furthermore, 60 consecutive patients who were admitted for surgery for IBD were prospectively enrolled in the 2004–2006 period. Each patient underwent venous color Doppler ultrasound scan at admission and at discharge. Demographic data, disease activity, and clotting parameters were collected. Data were analyzed with Spearman’s correlation test, multiple regression, and receiver operating characteristics (ROC) curves analysis.

Results

The rate of DVT in UC patients was significantly higher than in colorectal cancer patients (p = 0.009), and the odds ratio (OR) for postoperative DVT in UC patients was 7.4 (95% CI 1.4–44.4; p = 0.017). Female gender, UC diagnosis, active rectal bleeding, aPTT value, aCL IgM, aβ2 IgM, and pANCA levels significantly correlated with postoperative DVT. At multivariate analysis only aCL IgM levels were found to be independently associated with postoperative DVT (p = 0.05).

Conclusions

In conclusion, our study showed that prophylactic therapy with 4,000 IU/day LMWH was not completely effective for the prevention of postoperative DVT in patients with CD, and even less so in those with UC. In these patients, a more tailored prophylactic therapy should be considered, and further randomized controlled trials testing the effectiveness of different prophylactic protocols would be advisable. Furthermore, aCL IgM serum levels might be helpful in identifying IBD patients who are at higher risk of postoperative DVT.
Adenylosuccinate lyase deficiency in a Malaysian patient, with novel adenylosuccinate lyase gene mutations
Authors: Chen Bee Chin , McGown Ivan N. , Thong Meow Keong , Pitt James , Yunus Zabedah M. , Khoo Teck Beng , Ngu Lock Hock , Duley John A.
Published: February 2010

Most cases of adenylosuccinate lyase (ADSL OMIM 103050) deficiency reported to date are confined to the various European ethnic groups. We report on the first Malaysian case of ADSL deficiency, which appears also to be the first reported Asian case. The case was diagnosed among a cohort of 450 patients with clinical features of psychomotor retardation, global developmental delay, seizures, microcephaly and/or autistic behaviour. The patient presented with frequent convulsions and severe myoclonic jerk within the first few days of life and severe psychomotor retardation. The high performance liquid chromatography (HPLC) profile of the urine revealed the characteristic biochemical markers of succinyladenosine (S‐Ado) and succinyl‐aminoimidazole carboximide riboside (SAICAr). The urinary S‐Ado/SAICAr ratio was found to be 1.02 (type I ADSL deficiency). The patient was compound heterozygous for two novel mutations, c.445C > G (p.R149G) and c.774_778insG (p.A260GfsX24).
Comparison of leaf decomposition and macroinvertebrate colonization between exotic and native trees in a freshwater ecosystem
Authors: Alonso A. , González‐Muñoz N. , Castro‐Díez P.
Published: February 2010

One of the most important sources of energy in aquatic ecosystems is the allochthonous input of detritus. Replacement of native tree species by exotic ones affects the quality of detritus entering freshwater ecosystems. This replacement can alter nutrient cycles and community structure in aquatic ecosystems. The aims of our study were (1) to compare leaf litter decomposition of two widely distributed exotic species (Ailanthus altissima and Robinia pseudoacacia) with the native species they coexist with (Ulmus minor and Fraxinus angustifolia), and (2) to compare macroinvertebrate colonization among litters of the invasive and native species. Litter bags of the four tree species were placed in the water and collected every 2, 25, 39, 71, and 95 days in a lentic ecosystem. Additionally, the macroinvertebrate community on litter bags was monitored after 25, 39, and 95 days. Several leaf chemistry traits were measured at the beginning (% lignin; lignin:N, C:N, LMA) and during the study (leaf total nitrogen). We detected variable rates of decomposition among species (k values of 0.009, 0.008, 0.008, and 0.005 for F. angustifolia, U. minor, A. altissima and R. pseudoacacia, respectively), but we did not detect an effect of litter source (from native/exotic). In spite of its low decay, the highest leaf nitrogen was found in R. pseudoacacia litter. Macroinvertebrate communities colonizing litter bags were similar across species. Most of them were collectors (i.e., they feed on fine particulate organic matter), suggesting that leaf material of either invasive or native trees was used as substrate both for the animals and for the organic matter they feed on. Our results suggest that the replacement of the native Fraxinus by Robinia would imply a reduction in the rate of leaf processing and also a slower release of leaf nitrogen to water.
Protein Tyrosine Phosphatase‐1B (PTP‐1B) Knockdown Improves Palmitate‐Induced Insulin Resistance in C2C12 Skeletal Muscle Cells
Authors: Bakhtiyari Salar , Meshkani Reza , Taghikhani Mohammad , Larijani Bagher , Adeli Khosrow
Published: February 2010

Insulin resistance is the central defect in type 2 diabetes and obesity. During the development of insulin resistance a lipid accumulation is accompanied by increased PTP‐1B expression in the muscle. The aim of this study was to examine the effects of PTP‐1B knockdown on insulin signaling and insulin resistance in the presence or absence of palmitate in C2C12 skeletal muscle cells. A stable C2C12 cell line was established using short hairpin RNA (shRNA) to knockdown protein expression of PTP1B. Analysis of PTP‐1B protein expression and phosphorylation and protein levels of IRS‐1 and Akt were detected by western blot. The effects of PTP‐1B knockdown on the glucose uptake was also measured in C2C12 cells. The stable C2C12 cell line harboring the PTP‐1B shRNA showed 62% decrease in the PTP‐1B protein levels. 0.5 mM palmitate significantly induced insulin resistance in both control (26%) and PTP‐1B knockdown cells (16.5%) compared to the untreated cells. Under treatment with palmitate, insulin stimulated phosphorylation of IRS‐1 (Tyr632) and Akt (Ser473) in knockdown cells was significantly 1.55‐ and 1.86‐fold, respectively, greater than the controls. In the presence of palmitate, insulin dependent glucose uptake was significantly about 3‐fold higher in PTP‐1B knockdown stable C2C12 cells compared to the control cells. Our data showed that decreasing the PTP‐1B protein level by shRNA can enhance the activity of important elements of insulin signaling. The improvement in insulin action persisted even in palmitate treated insulin resistant myotubes.
Tuberculous Liver Abscess in a Case Without Lung Involvement
Authors: Lee Shou‐Wu , Lien Han‐Chung , Chang Chi‐Sen
Published: February 2010

Hepatic tuberculosis is an uncommon form of extrapulmonary tuberculosis, particularly when it presents in the form of liver abscess. Here, we report a 64‐year‐old man who was admitted to our hospital having experienced intermittent chills for 3 months. Aspiration of the liver abscess revealed neither bacteria nor acid‐fast bacilli, but pus and granulation tissue were found. Antituberculous therapy was started empirically and cultures of the abscess confirmed the presence of Mycobacterium tuberculosis 3 weeks later. We suggest that tuberculous liver abscess should be considered in patients not showing typical features or who fail to respond to antibiotics.
‘Off With Their Heads’: British Prime Ministers and the Power to Dismiss
Authors: King Anthony , Allen Nicholas
Published: February 2010

The British prime minister’s power to appoint and dismiss ministers is probably his most important single power. This article explores how prime ministers from Macmillan to Blair have used that power. The article considers the criteria that prime ministers use when choosing to appoint or dismiss individuals from office before examining the calculations and miscalculations that prime ministers have made in practice. Finally, the article analyses the way that prime ministers have exercised, in particular, their power to dismiss and finds that Thatcher was far more likely than others to sack cabinet colleagues on ideological or policy grounds. The article emphasizes that prime ministers’ relationships with especially powerful ministers – ‘big beasts of the jungle’ – are crucial to an understanding of British government at the top.
Electro-hydrodynamic particle levitation on electrodes
Authors: YARIV EHUD
Published: February 2010

The thin-Debye-layer model is utilized to analyse the electro-hydrodynamic flow about a colloidal particle which is exposed to a direct ionic current, emitted by a proximate reactive electrode. This flow is driven by electro-osmotic slip on the particle, as well as a comparable slip on the electrode itself. The small particle–electrode separation allows for the use of singular perturbation. Thus, the electro-neutral bulk-fluid domain is decomposed into an ‘inner’ gap region, where the electric field and shear rate are large, and an ‘outer’ region, consisting of the remaining bulk domain, where they are moderate. Matched asymptotic expansions in both regions provide the requisite flow field. The intensive shear rate in the narrow gap region is associated with a lubrication-type pressure build-up, which is responsible for the leading-order hydrodynamic force on the particle. This force acts to repel the particle away from the electrode, thereby supporting it against gravity. Its magnitude is inversely proportional to the gap width. At large distances from the particle the fluid velocity decays with the third power of distance, while near the electrode it decays with the fourth power. The inward pointing flow near the electrode tend to entrain neighbouring particles, thereby resulting in two-dimensional particle clusters. For equal values of particle and anode zeta potentials, this process is dominated by the particle-slip contribution.
Feedback control of unstable steady states of flow past a flat plate using reduced-order estimators
Authors: AHUJA S. , ROWLEY C. W.
Published: February 2010

We present an estimator-based control design procedure for flow control, using reduced-order models of the governing equations linearized about a possibly unstable steady state. The reduced-order models are obtained using an approximate balanced truncation method that retains the most controllable and observable modes of the system. The original method is valid only for stable linear systems, and in this paper, we present an extension to unstable linear systems. The dynamics on the unstable subspace are represented by projecting the original equations onto the global unstable eigenmodes, assumed to be small in number. A snapshot-based algorithm is developed, using approximate balanced truncation, for obtaining a reduced-order model of the dynamics on the stable subspace.

The proposed algorithm is used to study feedback control of two-dimensional flow over a flat plate at a low Reynolds number and at large angles of attack, where the natural flow is vortex shedding, though there also exists an unstable steady state. For control design, we derive reduced-order models valid in the neighbourhood of this unstable steady state. The actuation is modelled as a localized body force near the trailing edge of the flat plate, and the sensors are two velocity measurements in the near wake of the plate. A reduced-order Kalman filter is developed based on these models and is shown to accurately reconstruct the flow field from the sensor measurements, and the resulting estimator-based control is shown to stabilize the unstable steady state. For small perturbations of the steady state, the model accurately predicts the response of the full simulation. Furthermore, the resulting controller is even able to suppress the stable periodic vortex shedding, where the nonlinear effects are strong, thus implying a large domain of attraction of the stabilized steady state.
Vestibular evoked myogenic potentials in patients with fibromyalgia syndrome
Authors: Bayazit Y A , Celenk F , Gunduz A G , Gunduz B , Ondag N , Meray J
Published: February 2010

Objective:

To assess vestibular evoked myogenic potentials in patients with fibromyalgia syndrome.

Methods:

Twenty-four patients with fibromyalgia syndrome (two men and 22 women) and 21 female controls were included in the study. All patients underwent vestibular evoked myogenic potential testing.

Results:

Statistical comparison of fibromyalgia patients with control subjects showed a significant difference with respect to n23 latencies and interpeak latencies (p < 0.05). There was no significant difference in p13 latencies, nor in p13 amplitudes, n23 amplitudes or interpeak amplitudes (p > 0.05).

Conclusions:

Although patients with fibromyalgia syndrome generally have subjective neurotological symptoms, clinical and laboratory assessments usually fail to detect any objective abnormality. However, it is possible to detect abnormalities on vestibular evoked myogenic potential testing in such patients, indicating dysfunction in the vestibulospinal pathway, possibly in the saccule. Elongation of the n23 latency and of the interpeak latency of waves p13–n23, during vestibular evoked myogenic potential testing, may be a useful, objective indicator demonstrating neurotological involvement in fibromyalgia syndrome patients. Future research investigating the mechanisms of this latency elongation may help increase understanding of the pathogenesis of fibromyalgia syndrome.
NONRENEWABLE ENERGY RESOURCES AS INPUT FOR PHYSICAL CAPITAL ACCUMULATION: A NEW APPROACH
Authors: Pérez-Barahona Agustín
Published: February 2010

In contrast to the standard approach in energy economics, this paper assumes that physical capital accumulation is relatively more energy-intensive than consumption. By means of Gaussian hypergeometric functions, we provide a closed-form representation of the optimal solution paths of our variables in levels, whatever the initial conditions (i.e., global dynamics). We find that, in general, the optimal trajectories are nonmonotonic. P.S. Dasgupta and G.M. Heal [Review of Economic Studies(special number), 3–28 (1974)] pointed out this result (local dynamics) for the optimal consumption in a model with identical technology for both physical capital accumulation and consumption. However, our paper introduces five novelties with respect to their study, namely, global dynamics, the importance of the proportion of nonrenewable energy resources to endowment of physical capital [S(0)/K(0)], the role of technical progress, U-shaped behavior of consumption, and nonmonotonicity of resource extraction.
REPRESENTATIONS AND SUNSPOT STABILITY
Authors: Evans George W. , McGough Bruce
Published: February 2010

By endowing his agents with simple forecasting models, or representations, M. Woodford (“Learning to Believe in Sunspots,” Econometrica 58, 277–307, 1990) found that finite state Markov sunspot equilibria may be stable under learning. We show that common factor representations generalize to all sunspot equilibria the representations used by Woodford. We find that if finite state Markov sunspots are stable under learning then all sunspots are stable under learning, provided common factor representations are used.
Oscillatory motion of drainage divides
Authors: Stark Colin P.
Published: February 2010

A simple model of topographic ridge evolution is developed in which mass‐wasting is treated as a vectorial erosion process. Channel incision drives backcutting as well as downcutting of the connected hillslope and the result is a mobile drainage divide that exhibits sustained horizontal and vertical motions mediated by asynchronous, asymmetric channel incision rates. The model resolves a ridge cross‐section into coupled hillslope and channel links and the model equations are found to form a low‐dimensional, non‐linear dynamical system. For weak forcing of hillslope erosion the system converges to a stable, symmetric geometry, but for strong forcing a limit cycle arises and the divide oscillates back and forth over time. The lessons to draw from this model are that such low‐dimensional dynamical behavior: (i) may explain the sinuous planform of interfluves; (ii) may form a key constituent of the high‐dimensional dynamics of landscape evolution as a whole.
Parkinson's Disease Spatial Covariance Pattern: Noninvasive Quantification with Perfusion MRI
Authors: Ma Yilong , Huang Chaorui , Dyke Jonathan P , Pan Hong , Alsop David , Feigin Andrew , Eidelberg David
Published: February 2010

Parkinson's disease (PD) is associated with elevated expression of a specific disease-related spatial covariance pattern (PDRP) in radiotracer scans of cerebral blood flow and metabolism. In this study, we scanned nine early-stage patients with PD and nine healthy controls using continuous arterial spin labeling (CASL) perfusion magnetic resonance imaging (pMRI). Parkinson's disease-related metabolic pattern expression in CASL pMRI scans was compared with the corresponding 18F-fluorodeoxyglucose positron emission tomography values. The PDRP expression was abnormally elevated ( P<0.01) in patients scanned with either modality, and the two values were highly intercorrelated ( P<0.0001). Perfusion MRI methods can be used for accurate quantification of disease-related covariance patterns.
Neuronal Estrogen Receptor-α Mediates Neuroprotection by 17β-Estradiol
Authors: Elzer Joachim G , Muhammad Sajjad , Wintermantel Tim M , Regnier-Vigouroux Anne , Ludwig Jochen , Schütz Günther , Schwaninger Markus
Published: February 2010

17β-Estradiol (E2) was shown to exert neuroprotective effects both in in vitro and in vivo models of stroke. Although these effects of E2 are known to require estrogen receptor-α (ERα), the cellular target of estrogen-mediated neuroprotection remains unknown. Using cell type-specific ER mutant mice in an in vivo model of stroke, we specifically investigated the role of ERα in neuronal cells versus its role in the microglia in the mediation of neuroprotection by estrogens. We generated and analyzed two different tissue-specific knockout mouse lines lacking ERα either in cells of myeloid lineage, including microglia, or in the neurons of the forebrain. Both E2-treated and E2-untreated mutant and control mice were subjected to a permanent middle cerebral artery occlusion for 48 h, and the infarct volume was quantified. Although the infarct volume of E2-treated female myeloid-specific ERα knockout mice was similar to that of E2-treated control mice, both male and female neuron-specific ERα mutant mice had larger infarcts than did control mice after E2 treatment. We conclude that neuronal ERα in female and male mice mediates neuroprotective estrogen effects in an in vivo mouse model of stroke, whereas microglial ERα is dispensable.
Role of CCL2 (MCP-1) in Traumatic Brain Injury (TBI): Evidence from Severe TBI Patients and CCL2−/− Mice
Authors: Semple Bridgette D , Bye Nicole , Rancan Mario , Ziebell Jenna M , Morganti-Kossmann M Cristina
Published: February 2010

Cerebral inflammation involves molecular cascades contributing to progressive damage after traumatic brain injury (TBI). The chemokine CC ligand-2 (CCL2) (formerly monocyte chemoattractant protein-1, MCP-1) is implicated in macrophage recruitment into damaged parenchyma after TBI. This study analyzed the presence of CCL2 in human TBI, and further investigated the role of CCL2 in physiological and cellular mechanisms of secondary brain damage after TBI. Sustained elevation of CCL2 was detected in the cerebrospinal fluid (CSF) of severe TBI patients for 10 days after trauma, and in cortical homogenates of C57Bl/6 mice, peaking at 4 to 12 h after closed head injury (CHI). Neurological outcome, lesion volume, macrophage/microglia infiltration, astrogliosis, and the cerebral cytokine network were thus examined in CCL2-deficient (−/−) mice subjected to CHI. We found that CCL2−/− mice showed altered production of multiple cytokines acutely (2 to 24 h); however, this did not affect lesion size or cell death within the first week after CHI. In contrast, by 2 and 4 weeks, a delayed reduction in lesion volume, macrophage accumulation, and astrogliosis were observed in the injured cortex and ipsilateral thalamus of CCL2−/− mice, corresponding to improved functional recovery as compared with wild-type mice after CHI. Our findings confirm the significant role of CCL2 in mediating post-traumatic secondary brain damage.
Imaging Cortical Dopamine D1 Receptors Using [11C]NNC112 and Ketanserin Blockade of the 5-HT2A Receptors
Authors: Catafau Ana M , Searle Graham E , Bullich Santiago , Gunn Roger N , Rabiner Eugenii A , Herance Raul , Radua Joaquim , Farre Magi , Laruelle Marc
Published: February 2010

[11C]NNC112 (8-chloro-7-hydroxy-3-methyl-5-(7-benzofuranyl)-2,3,4,5-tetrahydro-IH-3-benzazepine), a selective positron-emission tomography (PET) ligand for the D1 receptor (R) over the 5-HT2A R in vitro, has shown lower selectivity in vivo, hampering measurement of D1 R in the cortex. [11C]NNC112 PET and intravenous (i.v) ketanserin challenge were used to (1) confirm the previous findings of [11C]NNC112 in vivo D1 R selectivity, and (2) develop a feasible methodology for imaging cortical D1 R without contamination by 5-HT2A R. Seven healthy volunteers underwent [11C]NNC112 PET scans at baseline and after a 5-HT2A R-blocking dose of ketanserin (0.15 mg/kg, i.v.). Percent BPND change between the post-ketanserin and baseline scans was calculated. Irrespective of the quantification method used, ketanserin pretreatment led to significant decrease of BPND in the cortical (∼30%) and limbic regions (∼20%) but not in the striatum, which contains a much lower amount of 5-HT2A R. Therefore, ketanserin allows D1 R signal to be detected by [11C]NNC112 PET without significant 5-HT2A R contamination. These data confirm the presence of a significant 5-HT2A R contribution to cortical [11C]NNC112 signal, and call for caution in the interpretation of published [11C]NNC112 PET findings on cortical D1 R in humans. In the absence of more selective ligands, [11C]NNC112 PET with ketanserin can be used for cortical D1 R imaging in vivo.
The Interaction between Tumor Necrosis Factor-Like Weak Inducer of Apoptosis and its Receptor Fibroblast Growth Factor-Inducible 14 Promotes the Recruitment of Neutrophils into the Ischemic Brain
Authors: Haile Woldeab B , Echeverry Ramiro , Wu Jialing , Yepes Manuel
Published: February 2010

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor-inducible 14 (Fn14) are expressed in endothelial cells and perivascular astrocytes. Here, we show that TWEAK induces a dose-dependent increase in the expression of the chemokine monocyte chemoattractant protein-1 (MCP-1) in astrocytes, and that this effect is mediated by its interaction with Fn14 via nuclear factor-κB pathway activation. Exposure to oxygen-glucose deprivation (OGD) conditions increases TWEAK and Fn14 mRNA expression in wild-type (Wt) astrocytic cultures. Likewise, incubation under OGD conditions induces the expression of MCP-1 in Wt astrocytes but not in astrocytes deficient on either TWEAK (TWEAK−/−) or Fn14 (Fn14−/−). We also found that TWEAK induces the passage of neutrophils to the abluminal side of an in vitro model of the blood–brain barrier. Our earlier studies indicate that cerebral ischemia increases the expression of TWEAK and Fn14 in the endothelial cell-basement membrane-astrocyte interface. Here, we report that middle cerebral artery occlusion increases the expression of MCP-1 and the recruitment of neutrophils into the ischemic tissue in Wt but not in TWEAK−/− or Fn14−/− mice. These novel results indicate that during cerebral ischemia, the interaction between TWEAK and Fn14 leads to the recruitment of leukocytes into the ischemic tissue.
Quantitative Functional Magnetic Resonance Imaging of Brain Activity Using Bolus-Tracking Arterial Spin Labeling
Authors: Kelly Michael E , Blau Christoph W , Griffin Karen M , Gobbo Oliviero L , Jones James FX , Kerskens Christian M
Published: February 2010

Blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) is the most widely used method for mapping neural activity in the brain. The interpretation of altered BOLD signals is problematic when cerebral blood flow (CBF) or cerebral blood volume change because of aging and/or neurodegenerative diseases. In this study, a recently developed quantitative arterial spin labeling (ASL) approach, bolus-tracking ASL (btASL), was applied to an fMRI experiment in the rat brain. The mean transit time (MTT), capillary transit time (CTT), relative cerebral blood volume of labeled water (rCBVlw), relative cerebral blood flow (rCBF), and perfusion coefficient in the forelimb region of the somatosensory cortex were quantified during neuronal activation and in the resting state. The average MTT and CTT were 1.939±0.175 and 1.606±0.106 secs, respectively, in the resting state. Both times decreased significantly to 1.616±0.207 and 1.305±0.201 secs, respectively, during activation. The rCBVlw, rCBF, and perfusion coefficient increased on average by a factor of 1.123±0.006, 1.353±0.078, and 1.479±0.148, respectively, during activation. In contrast to BOLD techniques, btASL yields physiologically relevant indices of the functional hyperemia that accompanies neuronal activation.
G-CSF Administration is Neuroprotective following Transient Cerebral Ischemia Even in the Absence of a Functional NOS-2 Gene
Authors: Gibson Claire L , Bath Philip MW , Murphy Sean P
Published: February 2010

Granulocyte colony-stimulating factor (G-CSF) is a candidate neuroprotective factor following cerebral ischemia. To determine whether G-CSF acts partly through the inhibition of nitric oxide synthase (NOS)-2 expression, we administered G-CSF to male NOS-2−/− mice after cerebral ischemia. Although male NOS-2−/− mice exhibit resistance to the gross effects of cerebral ischemia, they display neuronal loss and skilled motor deficits following cerebral ischemia. Administration of G-CSF during reperfusion reduced motor deficit and neuronal loss. Thus, G-CSF is still effective in NOS-2 gene-deficient mice, suggesting that part of the mechanism of action is independent of NOS-2.
Dynamic Metabolic Response to Multiple Spreading Depolarizations in Patients with Acute Brain Injury: An Online Microdialysis Study
Authors: Feuerstein Delphine , Manning Andrew , Hashemi Parastoo , Bhatia Robin , Fabricius Martin , Tolias Christos , Pahl Clemens , Ervine Max , Strong Anthony J , Boutelle Martyn G
Published: February 2010

Spreading depolarizations (SDs) occur spontaneously with high incidence in patients with acute brain injury. They can be detected by subdural electrocorticographic recordings. We here characterize the dynamic metabolic response to these events. A microdialysis catheter was inserted into perilesional cortical tissue adjacent to a strip for electrocorticography following craniotomy in 10 patients. The microdialysis catheter was connected to an online microdialysis assay measuring glucose and lactate concentrations every 30 to 60 secs. Spontaneously occurring SDs systematically caused a reduction in dialysate glucose by −32.0 μmol/L (range: −92.3 to −18.4 μmol/L, n=90) and increase in lactate by +23.1 μmol/L (range: +5.5 to +93.6 μmol/L, n=49). The changes were sustained at 20 mins after the SD events and highly significant using an area under the curve analysis ( P<0.0001). Multiple and frequent SDs led to a progressive stepwise depletion of brain glucose. Hence, SD events cause a massive energy imbalance and their frequent occurrence leads to a local insufficiency of glucose supply. Such a failure would compromise cellular repolarization and hence tissue viability. The findings offer a new mechanism to account for otherwise unexplained instances of depletion of brain microdialysate glucose.
Oxidative Stress Increases Phosphorylation of IκB Kinase-α by Enhancing NF-κB-Inducing Kinase after Transient Focal Cerebral Ischemia
Authors: Song Yun Seon , Kim Min-Soo , Kim Hyun-Ae , Jung Bo-In , Yang Jiwon , Narasimhan Purnima , Kim Gab Seok , Jung Joo Eun , Park Eun-Hee , Chan Pak H
Published: February 2010

The IκB kinase (IKK) complex is a central component in the classic activation of the nuclear factor-κB (NF-κB) pathway. It has been reported to function in physiologic responses, including cell death and inflammation. We have shown that IKK is regulated by oxidative status after transient focal cerebral ischemia (tFCI) in mice. However, the mechanism by which oxidative stress influences IKKs after tFCI is largely unknown. Nuclear accumulation and phosphorylation of IKKα (pIKKα) were observed 1 h after 30 mins of tFCI in mice. In copper/zinc-superoxide dismutase knockout mice, levels of NF-κB-inducing kinase (NIK) (an upstream kinase of IKKα), pIKKα, and phosphorylation of histone H3 (pH3) on Ser10 were increased after tFCI and were higher than in wild-type mice. Immunohistochemistry showed nuclear accumulation and pIKKα in mouse brain endothelial cells after tFCI. Nuclear factor-κB-inducing kinase was increased, and it enhanced pH3 by inducing pIKKα after oxygen–glucose deprivation (OGD) in mouse brain endothelial cells. Both NIK and pH3 interactions with IKKα were confirmed by coimmunoprecipitation. Treatment with IKKα small interfering RNA significantly reduced cell death after OGD. These results suggest that augmentation of NIK, IKKα, and pH3 in response to oxidative stress is involved in cell death after cerebral ischemia (or stroke).
Long pulse H− beam extraction with a rf driven ion source on a high power level
Authors: Kraus W. , Fantz U. , Franzen P.
Published: February 2010

IPP Garching is investigating the applicability of rf driven negative ion sources for the neutral beam injection of International Thermonuclear Experimental Reactor. The setup of the tested source was improved to enable long pulses up to 100 kW rf power. The efficiency of negative ion production decreases at high power. The extracted H− currents as well as the symmetry of the plasma density close to the plasma grid and of the beam divergence depend on the magnetic filter field. The pulse duration is limited by the increase in coextracted electrons, which depends on the rf power and the caesium conditions on the plasma grid.
A calorimetric probe for plasma diagnostics
Authors: Stahl Marc , Trottenberg Thomas , Kersten Holger
Published: February 2010

A calorimetric probe for plasma diagnostics is presented, which allows measurements of the power taken by a test substrate. The substrate can be biased and used as an electric probe in order to obtain information about the composition of the total heating power. A new calibration technique for calorimetric probes, which uses monoenergetic electrons at low pressure, has been developed for an improved accuracy. The use of the probe is exemplified with an experiment where both energetic neutral atoms and ions heat the test substrate.
Accurate ab initio potential energy curve of O2. II. Core-valence correlations, relativistic contributions, and vibration-rotation spectrum
Authors: Bytautas Laimutis , Matsunaga Nikita , Ruedenberg Klaus
Published: February 2010

In the first paper of this series, a very accurate ab initio potential energy curve of the Σ3g− ground state of O2 has been determined in the approximation that all valence shell electron correlations were calculated at the complete basis set limit. In the present study, the corrections arising from core electron correlations and relativity effects, viz., spin-orbit coupling and scalar relativity, are determined and added to the potential energy curve. From the 24 points calculated on this curve, an analytical expression in terms of even-tempered Gaussian functions is determined and, from it, the vibrational and rotational energy levels are calculated by means of the discrete variable representation. We find 42 vibrational levels. Experimental data (from the Schumann–Runge band system) only yield the lowest 36 levels due to significant reduction in the transition intensities of higher levels. For the 35 term values G(v), the mean absolute deviation between theoretical and experimental data is 12.8 cm−1. The dissociation energy with respect to the lowest vibrational energy is calculated within 25 cm−1 of the experimental value of 41 268.2±3 cm−1. The theoretical crossing between the Σ3g− state and the Σ1g+ state is found to occur at 2.22 Å and the spin-orbit coupling in this region is analyzed.
Size distributions of nanoscopic holes in Ti/h-BN and Ti/B nanocomposites
Authors: Čížek J. , Procházka I. , Morozova O. S. , Borchers C. , Pundt A.
Published: February 2010

Positron annihilation spectroscopy was employed for defect studies of “Ti”-based nanocomposites prepared by high-energy ball milling and consisting of Ti nanoparticles separated by hexagonal boron nitride (h-BN) or boron (B) additive. The size distribution of nanoscopic holes in nanocomposites was determined directly from measurement of ortho-positronium (Ps) lifetimes. Chemical environment of defects was characterized using coincidence Doppler broadening. It was found that size of nanoscopic holes is reduced with increasing milling time in H2/He atmosphere and also probability of Ps formation in holes decreases. At the same time the Ti content in the vicinity of holes increases. This can be explained by (i) increased intermixing of Ti particles with h-BN or B additive and by (ii) filling the nanoscopic holes with absorbed hydrogen. Analysis of obtained results showed that both these processes take place during milling of nanocomposites. In addition, it was found that the effect of filling the nanoscopic pores with hydrogen is enhanced in TiH2 milled with h-BN or B in He atmosphere. Comparison of nanocomposites with h-BN and B additive showed that sufficiently long milling time leads to a similar size distribution of nanoscopic holes in Ti/h-BN and Ti/B, despite the fact that it differs substantially in the initial powders. However, density of nanoscopic holes in Ti/B is significantly lower than in Ti/h-BN nanocomposites.
Production of a coherent pair of light beams with a microwave frequency difference from a single extended-cavity diode laser
Authors: Yim Sin Hyuk , Cho D.
Published: February 2010

We produced a pair of coherent laser beams with a 3-GHz frequency difference by optically phase locking two modes from a single, multimode extended-cavity diode laser. This method is complementary to either a direct modulation or an optical phase locking of two independent lasers. A large differential frequency shift between the two modes of the laser allows efficient phase locking. We developed a simple theory to account for the large differential frequency shift. Allan deviation of the beat frequency when the two modes are phase-locked drops as an inverse of the measurement time and it reaches 10−14 when the time is 1 h. Coherent population trapping spectroscopy of Rb atoms using the phase-locked beams resulted in a spectrum as narrow as that of the case using direct modulation by a stable frequency synthesizer.
Fluid phase coexistence and critical behavior from simulations in the restricted Gibbs ensemble
Authors: Ashton Douglas J. , Wilding Nigel B. , Sollich Peter
Published: February 2010

The symmetrical restricted Gibbs ensemble (RGE) is a version of the Gibbs ensemble in which particles are exchanged between two boxes of fixed equal volumes. It has recently come to prominence because—when combined with specialized algorithms—it provides for the study of near-coexistence density fluctuations in highly size-asymmetric binary mixtures. Hitherto, however, a detailed framework for extracting accurate estimates of critical point and coexistence curve parameters from RGE density fluctuations has been lacking. Here we address this problem by exploiting an exact link between the RGE density fluctuations and those of the grand canonical ensemble. In the subcritical region we propose and test a simple method for obtaining accurate estimates of coexistence densities. In the critical region we identify an observable that serves as a finite system size estimator for the critical point parameters, and present a finite-size scaling theory that allows extrapolation to the thermodynamic limit.
Does Brillouin light scattering probe the primary glass transition process at temperatures well above glass transition?
Authors: Voudouris P. , Gomopoulos N. , Le Grand A. , Hadjichristidis N. , Floudas G. , Ediger M. D. , Fytas G.
Published: February 2010

The primary α-relaxation time (τα) for molecular and polymeric glass formers probed by dielectric spectroscopy and two light scattering techniques (depolarized light scattering and photon correlation spectroscopy) relates to the decay of the torsional autocorrelation function computed by molecular dynamics simulation. It is well known that Brillouin light scattering spectroscopy (BLS) operating in gigahertz frequencies probes a fast (10–100 ps) relaxation of the longitudinal modulus M∗. The characteristic relaxation time, irrespective of the fitting procedure, is faster than the α-relaxation which obeys the non-Arrhenius Vogel–Fulcher–Tammann equation. Albeit, this has been noticed, it remains a puzzling finding in glass forming systems. The available knowledge is based only on temperature dependent BLS experiments performed, however, at a single wave vector (frequency). Using a new BLS spectrometer, we studied the phonon dispersion at gigahertz frequencies in molecular [o-terphenyl (OTP)] and polymeric [polyisoprene (PI) and polypropylene (PP)] glass formers. We found that the hypersonic dispersion does relate to the glass transition dynamics but the disparity between the BLS-relaxation times and τα is system dependent. In PI and PP, the former is more than one order of magnitude faster than τα, whereas the two relaxation times become comparable in the case of OTP. The difference between the two relaxation times appears to relate to the “breadth” of the relaxation time distribution function. In OTP the α-relaxation process assumes a virtually single exponential decay at high temperatures well above the glass transition temperature, in clear contrast with the case of the amorphous bulk polymers.