bluuebunny/crossref_metadata_2025 huggingface dataset:
Herba Epimedii water extract elevates estrogen level and improves lipid metabolism in postmenopausal women
Authors: Yan Fang‐Fang , Liu Yan , Liu Yun‐Fang , Zhao Yu‐Xia
Published: August 2008

Hormone replacement therapy (HRT) can ameliorate lipid metabolism after menopause, but it is not suitable for long‐term use because of serious side effects. Herba Epimedii is a widely used herbal medicine in many Asian countries, it potentially treats menopausal syndrome and its complications with few side effects and good curative effects. The study aimed to evaluate the effects of Herba Epimedii water extract on blood lipid and sex hormone levels. Ninety subjects were randomly divided into two groups: a trial group which received Herba Epimedii water extract and a control group which was administered an equal amount of water placebo. At the baseline and after 6 months of medication, serum estradiol (E2), progesterone (P), testosterone (T), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL‐C) and low density lipoprotein cholesterol (LDL‐C) concentrations were measured. The results indicated that Herba Epimedii water extract decreased the TC and TG levels (p < 0.01). Furthermore, Herba Epimedii water extract significantly increased the serum level of E2 (p < 0.01) compared with the pre‐treatment level. In conclusion, Herba Epimedii water extract produces its beneficial actions in postmenopausal women. Copyright © 2008 John Wiley & Sons, Ltd.
Effect of honey on intestinal morphology, intraabdominal adhesions and anastomotic healing
Authors: Gollu Avni , Kismet Kemal , Kilicoglu Bulent , Erel Serap , Gonultas Mehmet Alpaslan , Sunay Asli Elif , Akkus Mehmet Ali
Published: August 2008

In the present study, attempts have been made to determine the effects of honey on intestinal morphology, postoperative adhesions, and the healing of colonic anastomoses in the rats after colonic resection and anastomosis. Thirty‐six rats were randomly divided into three groups each including 12 animals. Colonic resection and anastomosis were performed on all animals. Rats were fed with standard rat chow in group I, standard rat chow plus 10 g/kg/day honey in group II and artificial honey including the same caloric amount with honey in group III. Adhesion scores, bursting pressures and histopathological examinations were evaluated. Colonic bursting pressures of honey group were significantly better than control and artificial honey groups. Histological analysis of anastomotic site showed that submucosa and muscularis propria were nearly filled with granulation tissue and regular fibrin matrix in honey group. There was statistically significant difference between the adhesion scores of honey vs artificial honey and control groups. The scores of histological changes of ileum in honey group were significantly different from other groups. These results indicate a protective role of honey against intraabdominal adhesions and anastomotic dehiscence. Copyright © 2008 John Wiley & Sons, Ltd.
Triterpenoids and a sterol from the stem‐bark of Styrax japonica and their protein tyrosine phosphatase 1B inhibitory activities
Authors: Kwon Joo‐Hee , Chang Min‐Jung , Seo Hyo‐Won , Lee Jeong‐Hun , Min Byung‐Sun , Na MinKyun , Kim Jin Cheol , Woo Mi Hee , Choi Jae Sue , Lee Hyeong Kyu , Bae KiHwan
Published: August 2008

Five pentacyclic triterpenoids (1–5) and a sterol (6) were isolated from the stem‐bark of Styrax japonica. The six compounds, 1–6, were determined to be 3β‐acetoxy‐28‐hydroxyolean‐12‐ene (1), 3β‐acetoxyolean‐12‐en‐28‐acid (2), 3β‐acetoxyolean‐12‐en‐28‐aldehyde (3), 3β‐acetoxy‐17β‐hydroxy‐28‐norolean‐12‐ene (4), taraxerol (5) and stigmasterol (6), respectively, by spectroscopic means, including the 2D‐NMR technique. Compound 4 is a newly discovered natural compound. The protein tyrosine phosphatase 1B (PTP1B) inhibitory activities of the isolated compounds (1–6) were determined in vitro. Among the isolated compounds, 3β‐acetoxyolean‐12‐en‐28‐acid (2) and 3β‐acetoxyolean‐12‐en‐28‐aldehyde (3) had the most potent inhibitory PTP1B activity, with IC50 values of 7.8 and 9.3 µm, respectively. Copyright © 2008 John Wiley & Sons, Ltd.
Effects ofPolygala tenuifoliaroot extract on proliferation of neural stem cells in the hippocampal CA1 region
Authors: Park Hyun‐Ju , Lee Kiwon , Heo Hwon , Lee Myoungsun , Kim Jong Woo , Whang Wei Wan , Kwon Yunhee Kim , Kwon Hyockman
Published: August 2008

Neurogenesis persists in the adult mammalian brain and can be a target for modulation for therapeutic purposes. This study investigated the effect of aPolygala tenuifoliaroot extract on the proliferation of a stem cell population in the rat hippocampus. The root extract ofP. tenuifolia(2 mg/kg/day, 14 times intraperitoneal injections) increased the incorporation of bromodeoxyuridine (BrdU) into cells in the hippocampal CA1 region. This activity was enriched in the saponin‐containing fraction. The majority of cells labelled with BrdU were immunoreactive to nestin or Tuj1 and the percentages of nestin/BrdU‐ and Tuj1/BrdU‐double positive cells were increased by theP. tenuifoliaroot extract, suggesting that theP. tenuifoliaroot extract promotes the proliferation of neural stem cells. In addition, this extract promoted the neurite outgrowth of rat neuronal precursor cells, HiB5. These activities ofP. tenuifoliaroot extract may contribute to the therapeutic benefits of herbal medicines containingP. tenuifoliaroot for the treatment of patients with insomnia, neurosis and dementia. Copyright © 2008 John Wiley & Sons, Ltd.
Antimalarial activity of natural product extracts from Papua New Guinean and Australian plants against Plasmodium falciparum
Authors: Fernandez Liza S. , Jobling Michael F. , Andrews Katherine T. , Avery Vicky M.
Published: August 2008

In the search for new antimalarial compounds, a subset of a natural product extract library prepared from plant samples collected from Papua New Guinea and Australia was screened for in vitro activity against the chloroquine‐sensitive 3D7 and chloroquine‐resistant Dd2 strains of Plasmodium falciparum. Using the incorporation of (3H)‐hypoxanthine into parasite nucleic acid as a marker of growth, 93 of the 794 extracts screened displayed >40% inhibition against 3D7 infected erythrocytes at 312 µge/mL. Antimalarial activity was confirmed in 48 of these extracts against both 3D7 and Dd2 infected erythrocytes at concentrations between 78 and 390 µge/mL, 14 of which caused >90% growth inhibition of 3D7 at the lowest concentration screened. Extracts were also tested for mammalian cell cytotoxicity to evaluate selectivity of action. Copyright © 2008 John Wiley & Sons, Ltd.
Efficacy of Brazilian propolis gel for the management of denture stomatitis: a pilot study
Authors: Santos Vagner R. , Gomes Rafael T. , Mesquita Ricardo A. de , Moura Mariela D. G. de , França Esdras C. , Aguiar Evandro G. de , Naves Marcelo D. , Abreu José A. S. , Abreu Sheila R. L.
Published: August 2008

Denture stomatitis presents as a chronic disease in denture‐bearing patients, especially under maxillary prosthesis. Despite the existence of a great number of antifungal agents, treatment failure is observed frequently. Propolis, a natural bee product, possesses well‐documented antifungal and anti‐inflammatory activities. The purpose of this study was to evaluate the clinical efficacy of a new Brazilian propolis gel formulation in patients diagnosed with denture stomatitis. Thirty complete‐denture wearers with denture stomatitis were enrolled in this pilot study. At baseline, clinical evaluation was performed by a single clinician and instructions for denture hygiene were provided. Fifteen patients received Daktarin®(Miconazole gel) and 15 received Brazilian propolis gel. All patients were recommended to apply the product four times a day during one week. Clinical evaluation was repeated by the same clinician after treatment. All patients treated with Brazilian propolis gel and Daktarin®had complete clinical remission of palatal edema and erythema. This new Brazilian propolis gel formulation had efficacy comparable to Daktarin®and could be an alternative topical choice for the treatment of denture stomatitis. Copyright © 2008 John Wiley & Sons, Ltd.
Differential effects of curcumin on cryopreserved versus fresh primary human hepatocytes
Authors: Illouz Severine , Alexandre Eliane , Pattenden Clare , Mark Louise , Bachellier Philippe , Webb M'Balu , Berry David , Dennison Ashley , Richert Lysiane
Published: August 2008

Curcumin (CUR) is a major component of a dietary spice derived from the roots of Curcuma longa. It has strong antioxidant activities and hepatoprotective properties. Primary human hepatocytes are clinically used in transplantation or in bioartificial liver devices for the treatment of patients with liver failure. Fresh and cryopreserved hepatocytes are also used in vitro for the study of drugs in pharmacotoxicology. We aimed to assess whether CUR could improve human liver cell viability and prevent oxidative damage responsible for large cell loss during cell preparation. Our study showed beneficial effects of CUR (25 µM) on freshly isolated human hepatocytes, increasing significantly metabolic activity of viable attached cells when seeded with CUR for 24 h. However CUR added during the cell isolation process did not have any significant impact on cell isolation outcomes or on cryopreservation outcomes. Conversely, CUR added during the thawing of frozen cells had a negative effect on the cell attachment capacity of hepatocytes that were cryopreserved in the presence or absence of CUR. In conclusion, although having positive effects on viability and challenge of oxidative stress on cultured human hepatocytes, CUR had no beneficial effect on cell isolation or cryopreservation outcomes. Copyright © 2008 John Wiley & Sons, Ltd.
Gallotannin ameliorates the development of streptozotocin‐induced diabetic nephropathy by preventing the activation of PARP
Authors: Chandak Prakash Gopaldas , Gaikwad Anil Bhanudas , Tikoo Kulbhushan
Published: August 2008

Poly(ADP‐ribose) polymerase (PARP) is known to be activated under conditions of oxidative stress and/or radiation exposure. The role of this enzyme has been well demonstrated in the streptozotocin (STZ) induced model of diabetes. Inhibition of PARP by specific inhibitors is known to prevent the development of STZ induced diabetic nephropathy by reduction in oxidative stress induced apoptosis. This study shows for the first time the role of poly(ADP‐ribose) glycohydrolase (PARG) inhibitors as an alternative approach for inhibition of PARP. Gallotannin (20 mg/kg/day, i.p.) treatment for 4 weeks led to a significant reduction in the levels of plasma creatinine which is a well known marker for diabetic nephropathy. Treatment with gallotannin resulted in protection up to a certain level of glomerular damage, suggesting compensatory glomerular hypertrophy. As a PARG inhibitor gallotannin treatment also showed protection in PARP cleavage which is a hallmark for apoptotic cell death signifying the protective role of gallotannin in cell death signaling. Copyright © 2008 John Wiley & Sons, Ltd.
Neuroprotective effect of genistein in 6‐hydroxydopamine Hemi‐parkinsonian rat model
Authors: Baluchnejadmojarad Tourandokht , Roghani Mehrdad , Nadoushan Mohammad Reza Jalali , Bagheri Maryam
Published: August 2008

A large body of experimental evidence supports a role for oxidative stress as a mediator of nerve cell death in Parkinson's disease (PD). Phytoestrogens such as genistein have been reported to prevent neuronal degeneration caused by increased oxidative burden, therefore, this study examined whether genistein administration at a high dose would attenuate behavioral and structural abnormalities in an experimental model of PD in rat. For this purpose, unilateral intrastriatal 6‐hydroxydopamine (6‐OHDA, 12.5 µg/5 µL of saline‐ascorbate)‐lesioned rats were intraperitoneally pretreated with a single and high dose of genistein (10 mg/kg) 1 h before surgery. Apomorphine‐induced rotations and the number of Nissl‐stained neurons in the substantia nigra pars compacta (SNC) were counted after 2 weeks. Genistein administration could attenuate the rotational behavior in lesioned rats and protect the neurons of SNC against 6‐OHDA toxicity. Genistein administration has a protective effect against 6‐OHDA toxicity. Copyright © 2008 John Wiley & Sons, Ltd.
Antibacterial iridoid glucosides from Eremostachys laciniata
Authors: Modaressi Masoud , Delazar Abbas , Nazemiyeh Hossein , Fathi‐Azad Fatemeh , Smith Eileen , Rahman M. Mukhlesur , Gibbons Simon , Nahar Lutfun , Sarker Satyajit D.
Published: August 2008

Eremostachys laciniata (L) Bunge (family: Lamiaceae alt. Labiatae; subfamily: Lamioideae) is one of the 15 endemic Iranian herbs of the genus Eremostachys. A decoction of the roots and flowers of E. laciniata has traditionally been taken orally for the treatment of allergies, headache and liver diseases. Three antibacterial iridoid glucosides, phloyoside I (1), phlomiol (2) and pulchelloside I (3) have been isolated from the rhizomes of this plant. The structures of these compounds were elucidated unequivocally by a series of 1D and 2D NMR analyses. The antibacterial activity and brine shrimp toxicity of these compounds were assessed using the resazurin microtitre assay and the brine shrimp lethality assay, respectively. All three iridoid glycosides 1–3 exhibited from low to moderate levels (MIC = 0.05–0.50 mg/mL) of antibacterial activity. Of these compounds, compound 3 was the most active, and displayed antibacterial activity against 9 of 12 different strains tested. The most noteworthy activity of 3 was against Bacillus cereus, penicillin‐resistant Escherichia coli, Proteus mirabilis and Staphylococcus aureus with an MIC value of 0.05 mg/mL. Copyright © 2008 John Wiley & Sons, Ltd.
Pharmacological in vivo test to evaluate the bioavailability of some St John's Wort innovative oral preparations
Authors: Isacchi B. , Galeotti N. , Bergonzi M. C. , Ghelardini C. , Bilia A.R. , Vincieri F. F.
Published: August 2008

In this study, the optimisation of biopharmaceutical properties of a dried commercial extract of St John's Wort were evaluated employing the in vivo forced swimming test (FST). Three new dosage forms containing β‐cyclodextrin and surfactants (SDS, ASC8) were compared in the FST with the commercial extract. The commercial extract showed antidepressant activity in mice after 60 min at a dosage of 100 mg/kg. The same antidepressant activity appeared in 30 min with a micellar solution of SDS containing the same quantity of extract (100 mg/kg), while with micelles of ASC8 the effect appeared at 15 min and with a dosage of 30 mg/kg. In the case of β‐cyclodextrin the best results were obtained at 30 min, administering 60 mg/kg of the extract. Finally, the influence of the formulations on the water solubility of the constituents of the extract is reported. The tensides dramatically enhanced solubility, in particular that of the more lipophilic compounds, in the case of β‐cyclodextrin this effect was very pronounced for flavonoids and biapigenin, lower for hypericins and practically insignificant for hyperforins. Copyright © 2008 John Wiley & Sons, Ltd.
Increased renal expression of nitric oxide synthase and atrial natriuretic peptide in rats with glycyrrhizic‐acid‐induced hypertension
Authors: Ma Seong Kwon , Bae Eun Hui , Kim In Jin , Choi Ki Chul , Kim Suhn Hee , Lee JongUn , Kim Soo Wan
Published: August 2008

The present study aimed to examine whether there is an altered regulation of local hormonal systems in the kidney following the treatment of glycyrrhizic acid (GA), the active ingredient in licorice. Male Sprague‐Dawley rats were treated with GA for 3 weeks. The expression of mineralocorticoid receptor (MR) was determined in the kidney by immunoblotting and real‐time polymerase chain reaction (PCR). The protein expression of endothelial nitric oxide synthase (eNOS) and inducible NOS (iNOS) was determined. The expression of atrial natriuretic peptide (ANP), natriuretic peptide receptor (NPR)‐A and NPR‐C was determined by real‐time PCR. The activity of guanylyl cyclase was determined by the amount of cGMP generated in responses to sodium nitroprusside (SNP) or ANP. Following the GA treatment, systolic blood pressure was increased. The mRNA and protein expressions of MR were increased in the kidney. The protein expression of eNOS and iNOS was also increased. The expression of ANP mRNA was increased although that of NPR‐A and NPR‐C mRNA was not changed. The cGMP production provoked by either SNP or ANP was not changed. The increased expression of MR may contribute to GA‐induced hypertension. The enhanced expression of NOS and ANP may play a compensatory role in GA‐induced hypertension. Copyright © 2008 John Wiley & Sons, Ltd.
‘African potato’ (Hypoxis hemerocallidea corm): a plant‐medicine for modern and 21st century diseases of mankind? – a review
Authors: Owira Peter M. O. , Ojewole John A. O.
Published: August 2008

The traditional uses, therapeutic attributes, phytochemical and pharmacological profiles of ‘African potato’ (Hypoxis hemerocallidea corm) extracts have been reviewed. Available biomedical evidence suggests that ‘African potato’ is a potential plant‐medicine for some modern and 21st century diseases of mankind. Thus far, biomedical evidence has revealed that ‘African potato’ extracts possess antiinflammatory, antineoplastic, antioxidant, antidiabetic and antiinfective properties in vivo and in vitro. However, more laboratory and clinical studies are required to clarify these observations, and to isolate, purify and characterize the active chemical constituents responsible for the herb's pharmaco‐therapeutic effects. Copyright © 2008 John Wiley & Sons, Ltd.
Boundary‐layer ventilation by baroclinic life cycles
Authors: Sinclair V. A. , Gray S. L. , Belcher S. E.
Published: August 2008

Ventilation of the boundary layer has an important effect on local and regional air quality and is a prerequisite for long‐range pollution transport. Once in the free troposphere, pollutants can alter the chemical composition of the troposphere and impact on the Earth's radiative forcing. Idealised baroclinic life cycles, LC1 and LC2, have been simulated in a three‐dimensional dry hemispheric model in the presence of boundary‐layer turbulent fluxes. A passive tracer is added to the simulations to represent pollution emitted at, or near, the surface. A simple conveyor‐belt diagnostic is developed to objectively identify regions of the boundary layer that can be ventilated by either warm or cold conveyor belts. Transport of pollutants within and above the boundary layer is examined on synoptic scales. Three different physical mechanisms are found to interact with each other to ventilate pollutants out of the boundary layer. These mechanisms are turbulent mixing within the boundary layer, horizontal advection due to Ekman convergence and divergence within the boundary layer, and advection by the warm conveyor belt. The mass of tracer ventilated by the two life cycles is remarkably similar given the differences in frontal structure, suggesting that the large‐scale baroclinicity is an effective constraint on ventilation. Copyright © 2008 Royal Meteorological Society
Use of Canadian Quick covariances in the Met Office data assimilation system
Authors: Jackson D. R. , Keil M. , Devenish B. J.
Published: August 2008

In this paper, we describe the use of Canadian Quick (CQ) covariances in the Met Office assimilation system. These covariances have two particular advantages over other methods (such as the National Meteorological Center (NMC) method). First, they are calculated from a single long forecast run, rather than a series of short forecasts, and thus are much quicker to produce. Second, in cases where the vertical range of the assimilation system increases, they can be used immediately.

Here, we compare the performance of CQ and NMC covariances in a troposphere/stratosphere configuration of the Met Office assimilation system. The forecast model used has 50 levels from the surface to 63 km. In general, the performance of the two covariances is similar. However, it is clear that a consequence of the bootstrapping approach that was used to develop the NMC covariances is noisy patterns in the error covariances which adversely affects mean errors, particularly in the winter middle and high latitudes above the 10 hPa level. In addition, the NMC covariances show evidence of gravity waves, which appear to have been generated spuriously by the 3D‐Var assimilation due to lack of dynamical balance in the 3D‐Var analyses. Such signals are absent in the trials where CQ covariances are used.

The CQ method was also used to generate covariances for expanded versions of the model which spans the surface to around 80–84 km. Trial results are generally in good agreement with Earth Observing System Microwave Limb Sounder (EOS MLS) correlative measurements. Through this work, the CQ approach is proving to be a very effective tool for developing and testing new models which will be used to provide operational weather forecasts at the Met Office. The results show that the CQ approach is a quick and effective alternative to the NMC method, and can produce similar or sometimes better results. It is a particularly useful tool in the development of new assimilation systems. © Crown Copyright 2008 Reproduced with the permission of Her Majesty's St ationery Office. Published by J ohn Wiley & Sons, Ltd
Numerical test of a simple approach for using TOMS total ozone data in hurricane environment
Authors: Wu Yonghui , Zou X.
Published: August 2008

Using a regime‐dependent linear regression model that maps TOMS observed total column ozone (O3) into model mean vertically‐integrated potential vorticity (MPV): O3 = α × MPV + β, where the regression constants α and β are evaluated separately for data in regions strongly and weakly influenced by deep convection/southerly advection, respectively, TOMS ozone data can readily be incorporated into a hurricane forecast model. Case‐studies of several hurricanes are conducted applying such a simple regime‐dependent linear regression model to TOMS ozone data assimilation. Improvements in the track prediction are shown. A detailed analysis of how TOMS total ozone affects the track prediction is conducted for Hurricane Erin (2001). A significant improvement in the track prediction for Hurricane Erin (2001) using TOMS ozone occurred at about 20 hours into the model forecast, when the control forecast experiences a sudden increase of track error. It is found that such an improvement in the track prediction of Hurricane Erin is mainly due to differences in the steering flows of the two forecast experiments, resulting from the presence of an upstream middle‐latitude ozone trough and a downstream low‐latitude ozone trough. An examination of the time evolution of these two troughs in both forecast experiments indicates that both troughs became stronger and moved closer to Hurricane Erin with time in the forecast experiment with the assimilation of TOMS ozone data than did those in the control forecast. Copyright © 2008 Royal Meteorological Society
Development of a solenoid RF coil for animal imaging in 3 T high‐magnetic‐field MRI
Authors: Lee Hong‐Seok , Woo Dong‐Cheol , Min Kwang‐Hong , Kim Yong‐Kwon , Lee Heung‐Kyu , Choe Bo‐Young
Published: August 2008

The purpose of this study was to develop a solenoid coil for use with small animals in a 3 Tesla horizontal magnetic resonance imaging (MRI) system, and to investigate image quality by examination of parameters such as signal‐to‐noise ratio (SNR) and Q‐factor. A receiver solenoid coil was formed by winding three separate coils of copper tape around an acryl cylinder. The cylinder was supported at each end. A euthanized rat weighing 240 g was used as a subject animal for imaging. A cylindrical plastic tube containing a solution of 0.7 g/L CuSO4 was used as a phantom. Measured SNRs were 985 in the phantom image 995 in the rat. The Q‐factor was 89 in the phantom and 84 in the rat, in the loaded condition. The homogeneity of the radiofrequency (RF) field was good and the resolution of the image was sufficient to distinguish internal organs from one another in the abdomen of a rat. This study has demonstrated that a solenoid coil may be used to produce good quality images of small animals. SCANNING 30: 419–425, 2008. © 2008 Wiley Periodicals, Inc.
Combating against internet worms in large‐scale networks: an autonomic signature‐based solution
Authors: Simkhada Kumar , Taleb Tarik , Waizumi Yuji , Jamalipour Abbas , Nemoto Yoshiaki
Published: August 2008

In this paper, we propose a signature‐based hierarchical email worm detection (SHEWD) system to detect e‐mail worms in large‐scale networks. The proposed system detects novel worms and instantly generates their signatures. This feature helps to check the spread of any kind of worm—knownorunknown.

We envision a two‐layer hierarchical architecture comprising local security managers (LSMs), metropolitan security managers (MSM), and a global security manager (GSM). Local managers collectsuspiciousflows and hand them to metropolitan managers. Metropolitan managers then use cluster analysis to sort worms from the suspicious flows. The sorted worms are used to generate the worm signature which is relayed to the global manager and then to all the collaborating networks. A separate scheme is proposed to automatically select suitable values of the system parameters. This parameter selection procedure takes into account the current network state and thethreat levelof the ongoing attack. The performance of the whole system is investigated using real network traffic with traces of worms. Experimental results demonstrate that the proposed scheme is capable to accurately detect email worms during the early phase of their propagations. Copyright © 2008 John Wiley & Sons, Ltd.
Brain mapping with transcranial magnetic stimulation using a refined correlation ratio and Kendall's τ
Authors: Matthäus L. , Trillenberg P. , Fadini T. , Finke M. , Schweikard A.
Published: August 2008

Transcranial magnetic stimulation provides a mean to stimulate the brain non‐invasively and painlessly. The effect of the stimulation hereby depends on the stimulation coil used and on its placement. This paper presents a mapping algorithm based on the assumption of a monotonous functional relationship between the applied electric field strength at the representation point of a muscle and the evoked motor potential. We combine data from coil characteristics, coil placement, and stimulation outcome to calculate a likelihood map for the representation of stimulated muscles in the brain. Hereby, correlation ratio (CR) and Kendall's rank coefficient τ are used to find areas in the brain where there is most likely a functional or monotonous relationship between electric field strength applied to this area and the muscle response. First results show a good accordance of our method with mapping from functional magnetic resonance imaging.

In our case, classical evaluation of CR with binning is impossible, because sample data sets are too small and data are continuous. We therefore introduce a refined CR formula based on a Parzen windowing of the X‐data to solve the problem. In contrast to usual windowing approaches, which require numeric integration, it can be evaluated directly in O(n2) time. Hence, its advantage lies in fast evaluation while maintaining robust applicability to small sample sets. We suggest that the presented formula can generally be used in CR‐related problems where sample size is small and data range is continuous. Copyright © 2008 John Wiley & Sons, Ltd.
Combining data from primary and ancillary surveys to assess the association between neighborhood‐level characteristics and health outcomes: the Multi‐Ethnic Study of Artherosclerosis
Authors: Sánchez B. N. , Raghunathan T. E. , Diez Roux A. V. , Zhu Y. , Lee O.
Published: August 2008

There is increasing interest in understanding the role of neighborhood‐level factors on the health of individuals. Many large‐scale epidemiological studies that accurately measure health status of individuals and individual risk factors exist. Sometimes these studies are linked to area‐level databases (e.g. census) to assess the association between crude area‐level characteristics and health. However, information from such databases may not measure the neighborhood‐level constructs of interest. More recently, large‐scale epidemiological studies have begun collecting data to measure specific features of neighborhoods using ancillary surveys. The ancillary surveys are composed of a separate, typically larger, set of individuals. The challenge is then to combine information from these two surveys to assess the role of neighborhood‐level factors. We propose a method for combining information from the two data sources using a likelihood‐based framework. We compare it with currently used ad hoc approaches via a simulation study. The simulation study shows that the proposed approach yields estimates with better sampling properties (less bias and better coverage probabilities) compared with the other approaches. However, there are cases where some ad hoc approaches may provide adequate estimates. We also compare the methods by applying them to the Multi‐Ethnic Study of Atherosclerosis and its Neighborhood Ancillary Survey. Copyright © 2008 John Wiley & Sons, Ltd.
Graphical diagnostics to check model misspecification for the proportional odds regression model
Authors: Liu Ivy , Mukherjee Bhramar , Suesse Thomas , Sparrow David , Park Sung Kyun
Published: August 2008

The cumulative logit or the proportional odds regression model is commonly used to study covariate effects on ordinal responses. This paper provides some graphical and numerical methods for checking the adequacy of the proportional odds regression model. The methods focus on evaluating functional misspecification for specific covariate effects, but misspecification of the link function can also be dealt with under the same framework. For the logistic regression model with binary responses, Arbogast and Lin (Statist. Med.2005;24:229–247) developed similar graphical and numerical methods for assessing the adequacy of the model using the cumulative sums of residuals. The paper generalizes their methods to ordinal responses and illustrates them using an example from the VA Normative Aging Study. Simulation studies comparing the performance of the different diagnostic methods indicate that some of the graphical methods are more powerful in detecting model misspecification than the Hosmer–Lemeshow‐type goodness‐of‐fit statistics for the class of models studied. Copyright © 2008 John Wiley & Sons, Ltd.
Bias in frequently reported analyses of subfertility trials
Authors: Dias Sofia , McNamee Roseanne , Vail Andy
Published: August 2008

Randomized controlled trials in subfertility are often designed so that participants in each trial arm are offered the randomized treatment for up to k cycles, until success occurs. In clinical journals, success probabilities are often reported ‘per cycle’ and inferential procedures carried out as if all cycles were independent. However, this assumption does not hold. In this paper we consider the implications of such an assumption when we have a heterogeneous (Beta) patient population. We conducted a simulation study to assess the bias of estimates of the risk difference, risk ratio and odds ratio calculated using the total number of randomized women or the total number of treatment cycles as the unit of analysis, as well as the coverage of their confidence intervals (CIs). We found that the commonly reported ‘per cycle’ analyses are more biased and have poorer coverage of the CIs than the analyses based on the total number of women, in heterogeneous populations. Such information will help researchers who wish to interpret publications when the number of randomized participants is not extractable. Copyright © 2008 John Wiley & Sons, Ltd.
Joint analysis of multi‐level repeated measures data and survival: an application to the end stage renal disease (ESRD) data
Authors: Liu Lei , Ma Jennie Z. , O'Quigley John
Published: August 2008

Shared random effects models have been increasingly common in the joint analyses of repeated measures (e.g. CD4 counts, hemoglobin levels) and a correlated failure time such as death. In this paper we study several shared random effects models in the multi‐level repeated measures data setting with dependent failure times. Distinct random effects are used to characterize heterogeneity in repeated measures at different levels. The hazard of death may be dependent on random effects from various levels. To simplify the estimation procedure, we adopt the Gaussian quadrature technique with a piecewise log‐linear baseline hazard for the death process, which can be conveniently implemented in the freely available software aML. As an example, we analyze repeated measures of hematocrit level and survival for end stage renal disease patients clustered within a randomly selected 126 dialysis centers in the U.S. renal data system data set. Our model is very comprehensive yet easy to implement, making it appealing to general statistical practitioners. Copyright © 2008 John Wiley & Sons, Ltd.
Statistical performance of cladistic strategies for haplotype grouping in pharmacogenetics
Authors: Lunceford Jared K. , Liu Nancy
Published: August 2008

Haplotypes comprising multiple single nucleotide polymorphisms (SNPs) are popular covariates for capturing the key genetic variation present over a region of interest in the DNA sequence. Although haplotypes can provide a clearer assessment of genetic variation in a region than their component SNPs considered individually, the multi‐allelic nature of haplotypes increases the complexity of the statistical models intended to discover association with outcomes of interest. Cladistic methods cluster haplotypes according to the estimates of their genealogical closeness and have been proposed recently as strategies for reducing model complexity and increasing power. Two examples are methods based on a haplotype nesting algorithm described by Templeton et al. (Genetics 1987; 117:343–351) and hierarchical clustering of haplotypes as described by Durrant et al. (Am. J. Hum. Genet. 2004; 75:35–43). In the context of assessing the pharmacogenetic effects of candidate genes, for which high‐density SNP data have been gathered, we have conducted a simulation‐based case study of the testing and estimation properties of two strategies based on Templeton's algorithm (TA), one being that described by Seltman et al. (Am. J. Hum. Genet. 2001; 68:1250–1263; Genet. Epidemiol. 2003; 25:48–58), as well as the method of Durrant et al. using data from a diabetes clinical trial. Even after adjusting for multiplicity, improvements in power can be realized using cladistic approaches with treatment group sizes in the range expected for standard trials, although these gains may be sensitive to the cladistic structure used. Differences in the relative performance of the cladistic approaches examined were observed with the clustering approach of Durrant et al. showing statistical properties superior to the methods based on TA. Copyright © 2008 John Wiley & Sons, Ltd.
Regression splines in the time‐dependent coefficient rates model for recurrent event data
Authors: Amorim Leila D. , Cai Jianwen , Zeng Donglin , Barreto Maurício L.
Published: August 2008

Many epidemiologic studies involve the occurrence of recurrent events and much attention has been given for the development of modeling techniques that take into account the dependence structure of multiple event data. This paper presents a time‐dependent coefficient rates model that incorporates regression splines in its estimation procedure. Such methods would be appropriate in situations where the effect of an exposure or covariates changes over time in recurrent event data settings. The finite sample properties of the estimators are studied via simulation. Using data from a randomized community trial that was designed to evaluate the effect of vitamin A supplementation on recurrent diarrheal episodes in small children, we model the functional form of the treatment effect on the time to the occurrence of diarrhea. The results describe how this effect varies over time. In summary, we observed a major impact of the vitamin A supplementation on diarrhea after 2 months of the dosage, with the effect diminishing after the third dosage. The proposed method can be viewed as a flexible alternative to the marginal rates model with constant effect in situations where the effect of interest may vary over time. Copyright © 2008 John Wiley & Sons, Ltd.
Empirical analysis for investigating the effect of object‐oriented metrics on fault proneness: a replicated case study
Authors: Aggarwal K. K. , Singh Yogesh , Kaur Arvinder , Malhotra Ruchika
Published: August 2008

The importance of software measurement is increasing, leading to the development of new measurement techniques. Many metrics have been proposed related to the various object‐oriented (OO) constructs like class, coupling, cohesion, inheritance, information hiding and polymorphism. The purpose of this article is to explore relationships between the existing design metrics and probability of fault detection in classes. The study described here is a replication of an analogous study conducted by Briandet al. The aim is to provide empirical evidence to draw the strong conclusions across studies. We used the data collected from Java applications for constructing a prediction model. Results of this study show that many metrics capture the same dimensions in the metric set, hence are based on comparable ideas and provides redundant information. It is shown that by using a subset of metrics prediction models can be built to identify faulty classes. The model predicts faulty classes with more than 90% accuracy. The predicted model shows that import coupling and size metrics are strongly related to fault proneness, confirming the results from previous studies. However, there are also differences reported in this study with respect to previous studies such as inheritance metric which counts methods inherited in a class is also included in the predicted model. Copyright © 2008 John Wiley & Sons, Ltd.
Energy evaluation of inelastic structures subjected to random earthquake excitations
Authors: Wang Zhe , Wong Kevin K. F.
Published: August 2008

The modified force analogy method combined with static condensation is applied to study the seismic behaviour of inelastic structures, while energy transfer and dissipation in the structure during an earthquake hazard are investigated through energy formulation based on the equation of motion. The earthquake ground motion is modelled as a non‐stationary Gaussian random process. Rigid‐end offsets of the plastic hinges forming on the members, as well as the ability for panel zones to deform, are included in the structural analysis model. Monte Carlo simulation method is performed on a six‐story real moment‐resisting frame to determine the mean and the standard deviation of seismic energy dissipation time histories. Based on this combination of the force analogy method and energy formulation in the equation of motion with the stochastic earthquake model, the feasibility of the analysis procedure for studying the dynamics of inelastic structures is demonstrated through varying the rigidity of panel zones. Copyright © 2008 John Wiley & Sons, Ltd.
Comparative study of structural material quantities of multi‐storey linear‐type residential buildings
Authors: Kim Sang Bum , Lee Young Hak , Scanlon Andrew
Published: August 2008

One of the main factors in the selection of the structural system for a multi‐storey linear‐type residential building is the initial construction cost of various structural systems. In many Asian countries, composite steel and concrete construction, and cast‐in‐place concrete framing construction are the most commonly used structural systems. However, there is insufficient data related to relative construction costs of these two structure types. In this paper, a representative floor plan was developed based on the examination of existing buildings of this type. A comparison of structural material quantities for representative building models up to 40 storeys in height using both types of structural systems was performed. Six models were developed based on a typical floor plan and were designed for gravity and lateral loadings. Quantities of materials for each model were calculated and compared in terms of each main structural material such as steel, concrete and reinforcement, and ratios of structural material quantities. The information presented can be utilized with appropriate cost data to compare estimates of initial construction costs of the two structural systems. Copyright © 2008 John Wiley & Sons, Ltd.
SSADH deficiency leads to elevated extracellular GABA levels and increased GABAergic neurotransmission in the mouse cerebral cortex
Authors: Drasbek K. R. , Vardya I. , Delenclos M. , Gibson K. M. , Jensen K.
Published: August 2008

Succinic semialdehyde dehydrogenase (SSADH) deficiency is an inherited disorder in which patients display neurodevelopmental retardation, ataxia, and epileptic seizures. The recently engineered SSADH knock‐out (KO) mouse models the severe form of the human disorder. The SSADH enzyme participates in the breakdown of the inhibitory neurotransmitter GABA, and studies have shown increases in brain GABA and downregulation of GABAA receptor β2 subunits in the cerebral cortex of these mice. Here, we used brain slice electrophysiology to investigate the alterations in GABA neurotransmission in SSADH KO mouse cortex. In layer 2/3 pyramidal cells, spontaneous inhibitory postsynaptic currents (IPSCs), reflecting activity of GABAergic synaptic contacts, were normal in SSADH KO mice. Also, IPSCs evoked by electrical single‐axon stimulation in KO mice were normal. In contrast, tonic inhibition mediated by presumed extrasynaptic GABAA receptors was strongly increased, indicating significantly raised extracellular GABA levels. The excessive cortical GABAergic neurotransmission may participate in the seizure activity in SSADH deficiency.
Germination responses of Erica andevalensis to different chemical and physical treatments
Authors: Rossini Oliva S. , Leidi E. O. , Valdés B.
Published: August 2008

Erica andevalensis Cabezudo & Rivera is a threatened edaphic endemic species of Andalusia (SW Spain). Under natural conditions, the plants produce a very large number of small seeds (0.3–0.4 mm) but very few seedlings survive. Different treatments (high temperature, cold pre‐treatment, nitrogen salts, and gibberellic acid applications) were tested to assess germination patterns in different populations and to determinate the most favorable conditions for germination. Gibberellic acid was provided in five different concentrations from 0 to 400 ppm GA3, while nitrogen was applied as 10 mM of either KNO3 or NH4NO3. The effect of pH on germination was also tested. The species always showed a low germination rate (6.50–22%) that was not stimulated either by 1 or 4 months in dry cold pre‐treatment, nitrogen application, acid pH medium, or by high temperature (80°C for 10 min); although gibberellic acid application (100–400 ppm) significantly enhanced germination. The highest percentage of germination (41.6%) was achieved with a mean germination time to start germination (t0) of 7.6 ± 0.54 days when the seeds were subjected to 400 ppm gibberellic acid treatment. The population origin did not have a significant effect on germination percentage.
Intragenic microdeletion of RUNX2 is a novel mechanism for cleidocranial dysplasia
Authors: Lee Ming Ta Michael , Tsai Anne Chun-Hui , Chou Ching-Heng , Sun Feng-Mei , Huang Li-Chen , Yen Pauline , Lin Chyi-Chyang , Liu Chih-Yang , Wu Jer-Yuarn , Chen Yuan-Tsong , Tsai Fuu-Jen
Published: August 2008

Cleidocranial dysplasia (CCD; MIM 119600) is a rare autosomal dominant disorder characterized by facial, dental, and skeletal malformations. To date, rearrangement and mutations involving RUNX2, which encodes a transcription factor required for osteoblast differentiation on 6p21, has been the only known molecular etiology for CCD. However, only 70% patients were found to have point mutations, 13% large/contiguous deletion but the rest of 17% remains unknown. We ascertained a family consisted of eight affected individuals with CCD phenotypes. Direct sequencing analysis revealed no mutations in the RUNX2. Real time quantitative PCR were performed which revealed an exon 2 to exon 6 intragenic deletion in RUNX2. Our patients not only demonstrated a unique gene change as a novel mechanism for CCD, but also highlight the importance of considering “deletion” and “duplication” in suspected familial cases before extensive effort of gene hunting be carried.
Fatty Acid, Tocopherol and Sterol Compositions of Canadian Prairie Fruit Seed Lipids
Authors: Anwar Farooq , Przybylski Roman , Rudzinska Magdalena , Gruczynska Eliza , Bain John
Published: August 2008

The seeds of four prairie fruits—chokecherry (Prunus virginiana), thorny buffaloberry (Shepherdia argentea), Woods’ rose (Rosa woodsii) and hawthorn (Crataegus × mordenensis)—from Southern Alberta were investigated. The lipid contents of the seeds were found to be 10.4, 11.5, 3.7 and 3.4%, respectively. The tested seed lipids contained mainly linoleic acid in the range from 27.9 to 65.6% and oleic acid from 19.7 to 61.9%. The thorny buffaloberry and Woods’ rose seed lipids contained 29.2 and 30.8% of linolenic acid, respectively. The contents of palmitic and stearic acids ranged from 3.2 to 5.4% and 1.6 to 2.2%, respectively. The contents of total tocopherols in the chokecherry, thorny buffaloberry, Woods’ rose and hawthorn seed lipids accounted for 595, 897, 2,358 and 2,837 mg/kg, respectively. The main sterols in the lipids were β‐sitosterol, Δ5‐avenasterol, cycloartenol, campesterol, stigmasterol and gramisterol. The results of the present study show that the lipids from the seeds of the investigated prairie fruits could be a good source of valuable essential fatty acids, tocopherols and sterols, thus suggesting their application as functional foods and nutraceuticals.
INEQUALITIES FOR SUPERADDITIVE FUNCTIONALS WITH APPLICATIONS
Authors: DRAGOMIR SEVER S.
Published: August 2008

Some inequalities for superadditive functionals defined on convex cones in linear spaces are given, with applications for various mappings associated with the Jensen, Hölder, Minkowski and Schwarz inequalities.
A NOTE ON THE UNCLOUDING THE SKY OF NEGATIVELY CURVED MANIFOLDS
Authors: BORBÉLY ALBERT
Published: August 2008

The problem of finding geodesics that avoid certain obstacles in negatively curved manifolds has been studied in different situations. In this note we give a generalization of the unclouding theorem of J. Parkkonen and F. Paulin: there is a constant s0=1.534 such that for any Hadamard manifold M with curvature ≤−1 and for any family of disjoint balls or horoballs {Ca}a∈A and for any point p∈M−⋃ a∈ACa if we shrink these balls uniformly by s0 one can always find a geodesic ray emanating from p that avoids the shrunk balls. It will be shown that in the theorem above one can replace the balls by arbitrary convex sets.
MEASURES ON EFFECT ALGEBRAS
Authors: LAIZHEN LUO , RONGLU LI
Published: August 2008

In this paper, by introducing the bounded variation measure defined on effect algebras, we present the equivalent conditions about uniformly strongly additive measures.
SEMIGROUPS OF LINEAR TRANSFORMATIONS WITH RESTRICTED RANGE
Authors: SULLIVAN R. P.
Published: August 2008

In 1975, Symons described the automorphisms of the semigroup T(X,Y ) consisting of all total transformations from a set X into a fixed subset Y of X. Recently Sanwong, Singha and Sullivan determined all maximal (and all minimal) congruences on T(X,Y ), and Sommanee studied Green’s relations in T(X,Y ). Here, we describe Green’s relations and ideals for the semigroup T(V,W) consisting of all linear transformations from a vector space V into a fixed subspace W of V.