bluuebunny/crossref_metadata_2025 huggingface dataset:
North and South Indian Populations Share a Common Ancestral Origin of Friedreich's Ataxia but Vary in Age of GAA Repeat Expansion
Authors: Singh Inder , Faruq Mohammed , Mukherjee Odity , Jain Sanjeev , Pal Pramod Kumar , Srivastav M. V. Padma , Behari Madhuri , Srivastava Achal K. , Mukerji Mitali
Published: March 2010

Friedreich's ataxia (FRDA) is caused by expansion of GAA repeats in the frataxin (FXN) gene on chromosome 9q13‐q21.1. We analysed the origin of FRDA in 21 North Indian (NI) and eight South Indian (SI) families using five single nucleotide polymorphisms (SNPs) and a microsatellite marker spanning the GAA repeats. The NI and SI families were derived from Indo‐European and Dravidian linguistic backgrounds respectively. The frequency of large normal (LNs) alleles of the GAA repeat correlate with the overall lower prevalence of FRDA in India compared to the European population. All of the expanded alleles in the Indian population share a common core haplotype suggesting a founder effect. The expanded alleles in the NI population demonstrate more similarity to those of Europeans in terms of age of GAA repeat expansion (15975 ± 2850 years) and association of LNs with expanded alleles. FRDA seems to have been introduced recently in the South Indian population since the average estimated age of the mutation in SI is 5425 ± 1750 years and unlike NI some of the haplotypes of LNs are not associated with the expanded alleles.
Analysis of Single Nucleotide Polymorphisms in the NOS2A Gene and Interaction with Smoking in Age‐Related Macular Degeneration
Authors: Ayala‐Haedo Juan A. , Gallins Paul J. , Whitehead Patrice L. , Schwartz Stephen G. , Kovach Jaclyn L. , Postel Eric A. , Agarwal Anita , Wang Gaofeng , Haines Jonathan L. , Pericak‐Vance Margaret A. , Scott William K.
Published: March 2010

Age‐related macular degeneration (AMD) is a complex degenerative retinal disease influenced by both genetic and environmental risk factors. We assessed whether single nucleotide polymorphisms (SNPs) in the NOS2A gene increase risk and modulate the effect of smoking in AMD. 998 Caucasian subjects (712 AMD cases and 286 controls) were genotyped for 17 SNPs in NOS2A. Multivariable logistic regression models containing SNP genotypes, age, sex, smoking status and genotype/smoking interaction were constructed. SNP rs8072199 was significantly associated with AMD (OR = 1.3; 95% CI : 1.02, 1.65; P= 0.035). A significant interaction with smoking was detected at rs2248814 (P= 0.037). Stratified data by genotypes demonstrated that the association between AMD and smoking was stronger in carriers of AA genotypes (OR = 35.98; 95% CI: 3.19, 405.98) than in carriers of the AG genotype (OR = 3.05; 95% CI: 1.36, 6.74) or GG genotype (OR = 2.1; 95% CI: 0.91, 4.84). The results suggest a possible synergistic interaction of AA genotype with smoking, although the result bears replication in larger samples. Our data suggests that SNPs in the NOS2A gene are associated with increased risk for AMD and might modulate the effect of smoking on AMD.
Regional differences in nerve terminal Na+ channel subtype expression and Na+ channel‐dependent glutamate and GABA release in rat CNS
Authors: Westphalen Robert I. , Yu Jieying , Krivitski Margarita , Jih Ting‐Yu , Hemmings Jr Hugh C.
Published: March 2010

J. Neurochem. (2010) 113, 1611–1620.

We tested the hypothesis that expression of pre‐synaptic voltage‐gated sodium channel (Nav) subtypes coupled to neurotransmitter release differs between transmitter types and CNS regions in a nerve terminal‐specific manner. Nav coupling to transmitter release was determined by measuring the sensitivity of 4‐aminopyridine (4AP)‐evoked [3H]glutamate and [14C]GABA release to the specific Nav blocker tetrodotoxin (TTX) for nerve terminals isolated from rat cerebral cortex, hippocampus, striatum and spinal cord. Expression of various Nav subtypes was measured by immunoblotting using subtype‐specific antibodies. Potencies of TTX for inhibition of glutamate and GABA release varied between CNS regions. However, the efficacies of TTX for inhibition of 4AP‐evoked glutamate release were greater than for inhibition of GABA release in all regions except spinal cord. The relative nerve terminal expression of total Nav subtypes as well as of specific subtypes varied considerably between CNS regions. The region‐specific potencies of TTX for inhibition of 4AP‐evoked glutamate release correlated with greater relative expression of total nerve terminal Nav and Nav1.2. Nerve terminal‐specific differences in the expression of specific Nav subtypes contribute to transmitter‐specific and regional differences in pharmacological sensitivities of transmitter release.
Distribution of catechol‐O‐methyltransferase (COMT) proteins and enzymatic activities in wild‐type and soluble COMT deficient mice
Authors: Myöhänen Timo T. , Schendzielorz Nadia , Männistö Pekka T.
Published: March 2010

J. Neurochem.(2010)113, 1632–1643.

Catechol‐O‐methyltranferase (COMT) has both soluble (S‐COMT) and membrane‐bound (MB‐COMT) isoforms. A specific COMT antibody was used in immunohistochemical and confocal co‐localization studies to explore the distribution of COMT in general in normal mice and MB‐COMT in particular, in an S‐COMT deficient mouse line. In the peripheral tissues, high COMT protein and activity levels were observed in liver and kidney, whereas in the brain, COMT expression and activity were much lower. MB‐COMT was widely distributed throughout all tissues, and overall, the MB‐COMT distribution mimicked the distribution of S‐COMT. MB‐COMT displayed some preference for brain tissue, notably in the hippocampus. MB‐COMT related enzymatic activity was also pronounced in the cerebral cortical areas and hypothalamus. MB‐COMT, like S‐COMT, was found to be an intracellular enzyme but it was not associated with plasma membranes in the brain. Both COMT forms were abundantly found in microglial cells and intestinal macrophages, but also in astroglial cells. COMT was also present in some neuronal cells, like pyramidal neurons, cerebellar Purkinje and granular cells and striatal spiny neurons, but not in major long projection neurons. Finally, it seemed that nuclear COMT is not visible in S‐COMT deficient mice.
PETROGRAPHIC AND GEOCHEMICAL EVIDENCE FOR LONG‐STANDING SUPPLY OF RAW MATERIALS IN NEOLITHIC POTTERY (MENDANDIA SITE, SPAIN)
Authors: ORTEGA L. A. , ZULUAGA M. C. , ALONSO‐OLAZABAL A. , MURELAGA X. , ALDAY A.
Published: March 2010

Pottery from the Neolithic Mendandia site has been studied. The radiocarbon dating of the site corresponds to a range of dates from 7488–7546 cal bc to 5283–5437 cal bc: the first occurrence of pottery is dated at 5968–6040 cal bc for the lower level III, and up to 5386–5560 cal bc for level II. The antiquity of the potsherds places them within the oldest pottery production sequences in the Iberian Peninsula, which adds to the interest of this study. Ten potsherds from level II and five from level III are analysed for their petrographic and chemical characterization. The petrographic data show two different methods of raw materials manufacture—intentionally tempered pottery (ITP), using calcite and/or limestone and grog, and naturally or non‐intentionally tempered pottery (NTP). According to the matrix paste features, on the basis of the amount, shape, and average or size range of the mineral inclusions, clayed (type A) and sandy (type B) paste types were established and related to two different source areas. The chemical features also indicate two raw material sources and are in agreement with the petrographic paste types. The absence of significant chemical and mineralogical differences between the pottery from levels II and III suggests two contrasting areas for raw materials supply that lasted for at least 600 years.
Predicting Stock Market Returns with Aggregate Discretionary Accruals
Authors: KANG QIANG , LIU QIAO , QI RONG
Published: March 2010

We find that the positive relation between aggregate accruals and one‐year‐ahead market returns documented in Hirshleifer, Hou, and Teoh [2009] is driven by discretionary accruals but not normal accruals. The return forecasting power of aggregate discretionary accruals is robust to choices of sample periods, return measurements, estimation methods, business condition and risk premium proxies, and accrual models used to isolate discretionary accruals. Our extensive analysis shows that aggregate discretionary accruals, in sharp contrast to aggregate normal accruals, contain little information about overall business conditions or aggregate cash flows and display little co‐movement with ICAPM‐motivated risk premium proxies. Our findings imply that aggregate discretionary accruals likely reflect aggregate fluctuations in earnings management, thereby favoring the behavioral explanation that managers time aggregate equity markets to report earnings.
The transient receptor potential channel antagonist SKF96365 is a potent blocker of low‐voltage‐activated T‐type calcium channels
Authors: Singh A , Hildebrand ME , Garcia E , Snutch TP
Published: March 2010

Background and purpose:  SKF96365 (SKF), originally identified as a blocker of receptor‐mediated calcium entry, is widely used diagnostically, as a blocker of transient receptor potential canonical type (TRPC) channels. While SKF has been used as a tool to define the functional roles of TRPC channels in various cell and tissue types, there are notable overlapping physiological and pathophysiological associations between TRPC channels and low‐voltage‐activated (LVA) T‐type calcium channels. The activity of SKF against T‐type Ca channels has not been previously explored, and here we systematically investigated the effects of SKF on recombinant and native voltage‐gated Ca channel‐mediated currents.

Experimental approach:  Effects of SKF on recombinant Ca channels were studied under whole‐cell patch clamp conditions after expression in HEK293 cells. The effect of SKF on cerebellar Purkinje cells (PCs) expressing native T‐type Ca channels was also assessed.

Key results:  SKF blocked recombinant Ca channels, representative of each of the three main molecular genetic classes (CaV1, CaV2 and CaV3) at concentrations typically utilized to assay TRPC function (10 µM). Particularly, human CaV3.1 T‐type Ca channels were more potently inhibited by SKF (IC50∼560 nM) in our experiments than previously reported for similarly expressed TRPC channels. SKF also inhibited native CaV3.1 T‐type currents in a rat cerebellar PC slice preparation.

Conclusions and implications:  SKF was a potent blocker of LVA T‐type Ca channels. We suggest caution in the interpretation of results using SKF alone as a diagnostic agent for TRPC activity in native tissues.
Angiogenesis: a new physiological role for N‐arachidonoyl serine and GPR55?
Authors: Ho W‐SV
Published: March 2010

N‐arachidonoyl serine (ARA‐S) is one of a number of acyl amino acids recently identified in mammalian tissues. It has been referred to as an endocannabinoid‐like lipid largely based on its structural similarities with the endocannabinoid, N‐arachidonoyl ethanolamide (anandamide). However, little is known about its potential physiological functions and receptor targets. In this issue of the British Journal of Pharmacology, Zhang and colleagues show that ARA‐S is a potent inducer of endothelial cell proliferation and migration, and angiogenesis in vitro. Furthermore, this pro‐angiogenic action is mediated, at least partly, by activation of the poorly characterized, G‐protein‐coupled GPR55 receptor. ARA‐S, via GPR55, increases phosphorylation of extracellular signal‐regulated kinases and Akt, and vascular endothelial growth factor signalling. These exciting findings highlight the endothelium as an endogenous target for ARA‐S and GPR55.
Spoilt for choice – evaluation of two different scoring systems for early hand eczema in teledermatological examinations
Authors: Baumeister Thomas , Weistenhöfer Wobbeke , Drexler Hans , Kütting Birgitta
Published: March 2010

Background: Besides improving working conditions and using personal protective equipment, early detection is most important in managing work‐related hand eczema. Implementing regular teledermatological skin screenings could be helpful, but none of the published hand eczema‐scores has hitherto been used in teledermatology.

Objective: Testing and comparing two validated scores [Osnabrück hand eczema severity index (OHSI); hand eczema severity index (HECSI)] for their suitability in an occupational telemedical screening.

Patients/Materials/Methods: One hundred and twenty photographic records of the hands of 30 male wet workers were examined twice with each score. Results were tested for reproducibility, intra‐observer reliability and inter‐score‐correlation.

Results: Examination time, mean score values, and score ranges reached did not differ significantly. The inter‐score‐correlation was moderate (correlation coefficients: 0.651 for first examination; 0.642 for second examination). In the qualitative assessment, the HECSI showed a better overall agreement between results of first and second examinations.

Conclusions: Both scores are suitable for assessing the skin condition in a teledermatological setting. The comparability is limited to qualitative assessment, as the strictly objective OHSI measures the extent of hand eczema and the finer graduated HECSI measures the intensity of hand eczema, adding a subjective component. For assessing minimal skin changes, a scoring system that reduces subjective elements while at the same time it offers a differentiated grading is advisable.
Patterns of liver iron accumulation in patients with sickle cell disease and thalassemia with iron overload
Authors: Hankins Jane S. , Smeltzer Matthew P. , McCarville M. Beth , Aygun Banu , Hillenbrand Claudia M. , Ware Russell E. , Onciu Mihaela
Published: March 2010

The rate and pattern of iron deposition and accumulation are important determinants of liver damage in chronically transfused patients. To investigate iron distribution patterns at various tissue iron concentrations, effects of chelation on hepatic iron compartmentalization, and differences between patients with sickle cell disease (SCD) and thalassemia major (TM), we prospectively investigated hepatic histologic and biochemical findings in 44 patients with iron overload (35 SCD and 9 TM). The median hepatic iron content (HIC) in patients with TM and SCD was similar at 12.9 and 10.3 mg Fe/g dry weight, respectively (P = 0.73), but patients with SCD had significantly less hepatic fibrosis and inflammation (P < 0.05), less hepatic injury, and significantly less blood exposure. Patients with SCD had predominantly sinusoidal iron deposition, but hepatocyte iron deposition was observed even at low HIC. Chelated patients had more hepatocyte and portal tract iron than non‐chelated ones, but similar sinusoidal iron deposition. These data suggest that iron deposition in patients with SCD generally follows the traditional pattern of transfusional iron overload; however, parenchymal hepatocyte deposition also occurs early and chelation removes iron preferentially from the reticuloendothelium. Pathophysiological and genetic differences affecting iron deposition and accumulation in SCD and TM warrants further investigation (http://www.clinicaltrials.gov # NCT00675038).
BSc2118 is a novel proteasome inhibitor with activity against multiple myeloma
Authors: Sterz Jan , Jakob Christian , Kuckelkorn Ulrike , Heider Ulrike , Mieth Maren , Kleeberg Lorenz , Kaiser Martin , Kloetzel Peter‐M. , Sezer Orhan , Von Metzler Ivana
Published: March 2010

Objectives:  The ubiquitin–proteasome system emerged as a new therapeutic target in cancer treatment. The purpose of this study was to elucidate the effects of the novel proteasome inhibitor BSc2118 on t(4;14) positive and negative multiple myeloma (MM) cells and normal peripheral blood mononuclear cells (PBMNC).

Methods:  Human MM cell lines OPM‐2, RPMI‐8226, and U266 and primary MM cells from bone marrow aspirates were exposed to BSc2118. Cytotoxicity levels were evaluated using the MTT‐test. BSc2118‐induced apoptosis was analyzed by annexin‐V assay. Further methods used included proteasomal activity determination, cell cycle analysis, western blot, and transcription factor assays.

Results:  In OPM‐2, RPMI‐8226, U266 cell lines and primary MM cells, BSc2118 caused dose‐dependent growth inhibitory effects. After 48 h, dose‐dependent apoptosis occurred both in cell lines and primary myeloma cells irrespective of t(4;14). A significant G2‐M cell cycle arrest occurred after 24 h. Furthermore, we observed a marked inhibition of intracellular proteasome activity, an increase in intracellular p21 levels, and an inhibition of NF‐κB activation. The toxicity against PBMNC remained low, suggesting a broad therapeutic range of this agent.

Conclusion:  Taken together, BSc2118 shows significant antimyeloma activity and may be considered as a promising agent in cancer drug development.
Triose phosphate isomerase deficiency associated with two novel mutations in TPI gene
Authors: Fermo Elisa , Bianchi Paola , Vercellati Cristina , Rees David C. , Marcello Anna P. , Barcellini Wilma , Zanella Alberto
Published: March 2010

We report the clinical, haematological and molecular characteristics of two triose phosphate isomerase deficient patients affected by haemolytic anaemia and neuromuscular impairment. The sequence of complete TPI gene showed the presence of two previously undescribed mutations: c.722 T>C (Phe240Ser) and c.28 insG; each of the two unrelated patients showed the new mutation in compound heterozygosity with the most common variant Glu104Asp. The association of Glu104Asp with c.28 insG resulted in a very severe clinical pattern.
Understanding and Application of Different Breast Imaging Studies
Authors: Park J. M.
Published: March 2010

There are many different imaging studies that can be used to evaluate breast lesions. This article will provide a brief introduction to each of the different examination modalities, including mammography, ultrasound and magnetic resonance imaging as well as image‐guided invasive procedures. General guidelines for recommended use of each modality are suggested.
Effects of transportation during the hot season, breed and electrical stimulation on histochemical and meat quality characteristics of goat longissimus muscle
Authors: KADIM Isam T. , MAHGOUB Osman , AL‐MARZOOQI Waleed , KHALAF Samera , AL‐SINAWI Shadia S. H. , AL‐AMRI Issa
Published: March 2010

The effects of transportation and electrical stimulation (90 V) on physiological, histochemical and meat quality characteristics of two breeds of Omani goats were assessed. Twenty 1‐year‐old male goats from each breed (Batina and Dhofari) were divided into two groups: 3 h transported during the hot season (42°C day time temperature) and non‐transported. Animals were blood‐sampled before loading and prior to slaughter. Electrical stimulation was applied 20 min postmortem to 50% randomly selected carcasses of both breeds. Temperature and pH decline of the Longissimus was monitored. Ultimate pH, shear force, sarcomere length, myofibrillar fragmentation index, expressed juice, cooking loss and colour were measured from samples of Longissimus dorsi muscles. Electrical stimulation and transportation had a significant effect on most biochemical and meat quality characteristics of Longissimus dorsi. The transported goats had higher plasma cortisol (P < 0.01), adrenaline, nor‐adrenaline and dopamine concentrations (P < 0.05) than non‐transported goats. Electrical stimulation resulted in a significantly (P < 0.05) more rapid muscle pH fall during the first 12 h after slaughter. Muscles from electrically‐stimulated carcasses had significantly (P < 0.05) longer sarcomeres, lower shear force value, a lighter colour (higher L* value), higher expressed juice and myofibrillar fragmentation index than those from non‐stimulated ones. Meat from transported goats had significantly higher pH, expressed juice and shear force, but contained significantly lower sarcomere length and L* values than non‐transported goats. The proportion of the myosin ATPase staining did not change as a function of stimulation, transportation or breed. These results indicated that subjecting goats to transportation for 3 h under high ambient temperatures can generate major physiological and muscle metabolism responses. Electrical stimulation improved quality characteristics of meat from both groups. This indicates that electrical stimulation may reduce detrimental effects of transportation on meat quality of Omani goats.
Phenological stages of willow (Salix)
Authors: Saska Margaret M. , Kuzovkina Yulia A.
Published: March 2010

The practice of uniform recording of biological plant growth stages or events has long been practiced in agricultural production. In this study the BBCH (Biologishe Bundesanstalt, Bundessortenamt and CHemical Industry) code has been applied to four precocious species of willows to define growth stages important to this group. The studied taxa represent varieties of potential importance in the Floral Industry. A new BBCH code is proposed where the annual cycle of willows is divided into clearly recognisable and easily distinguishable developmental phases which include eight principal stages, 30 secondary stages and six mesostages. Photographs illustrate the physical appearance of select stages. This proposed BBCH code shows a unified approach which may be applied to a large number of Salix species.
Reviewing the Technical Designs for Experiments with Ultraviolet‐B Radiation and Impact on Photosynthesis, DNA and Secondary Metabolism
Authors: Xu Chenping , Sullivan Joe H.
Published: March 2010

The ultraviolet‐B (UV‐B) portion of sunlight has received much attention in the last three decades, because radiation from this spectral region increases due to the stratospheric ozone depletion, which results from increases of chlorofluorocarbons in the atmosphere. Plant responses to UV‐B exposure vary greatly and the interpretation of and comparison between studies is hindered, mainly by the contrasting experimental conditions used and interactive factors such as low light levels and possible artifacts due to the artificial experimental conditions. It seems likely that increases in solar UV‐B radiation of the magnitude anticipated under current stratospheric ozone projections will not significantly inhibit photosynthesis and cause DNA damage in plants. This is in part due to the well‐evolved protection mechanisms present in most plant species. One of the significant plant responses to UV‐B is changes in foliar secondary chemistry, which could be translated into significant effects at higher trophic levels through plant‐herbivore interactions and decomposition. Enhanced UV‐B radiation due to stratospheric ozone depletion could also cause morphological changes that would affect competitive interactions, especially if contrasting UV‐B sensitivity exists among the competitors.
Novel Insights from Live‐imaging in Shoot Meristem Development
Authors: Sijacic Paja , Liu Zhongchi
Published: March 2010

Microscopic imaging of fluorescent reporters for key meristem regulators in live tissues is emerging as a powerful technique, enabling researchers to observe dynamic spatial and temporal distribution of hormonal and developmental regulators in living cells. Aided by time‐lapse microphotography, new types of imaging acquisition and analysis software, and computational modeling, we are gaining significant insights into shoot apical meristem (SAM) behavior and function. This review is focused on summarizing recent advances in the understanding of SAM organization, development, and behavior derived from live‐imaging techniques. This includes the revelation of mechanical forces in microtubule‐controlled anisotropic growth, the role of the CLV‐WUS network in the specification of peripheral zone and central zone cells, the multiple feedback loops involving cytokinin in controlling WUS expression, auxin dynamics in determining the position of new primordia, and, finally, sequence of regulatory events leading to de novo assembly of shoots from callus in culture. Future studies toward formulating “digital SAM” that incorporates multi‐dimensional data ranging from images of SAM morphogenesis to a genome‐scale expression map of SAM will greatly enhance our ability to understand, predict, and manipulate SAM, containing the stem cells that give rise to all above ground parts of a plant.
Muscle metaboreflex control of the circulation during exercise
Authors: Boushel R.
Published: March 2010

This review covers the control of blood pressure, cardiac output and muscle blood flow by the muscle metaboreflex which involves chemically sensitive nerves located in muscle parenchyma activated by metabolites accumulating in the muscle during contraction. The efferent response to metaboreflex activation is an increase in sympathetic nerve activity that constricts the systemic vasculature and also evokes parallel inotropic and chronotropic effects on the heart to increase cardiac output. The metaboreflex elicits a significant blood pressure elevating response during exercise and functions to redistribute blood flow and blood volume. Regional specificity in the efferent response to the metaboreflex activated from either the leg or the arm is seen in the balance between signals for vasoconstriction to curtail blood flow and signals to increase cardiac output. The metaboreflex has dual functions. It can both elevate and decrease muscle blood flow depending on (1) the intensity and mode of contraction, (2) the limb in which the reflex is evoked, (3) the strength of the signal defined by the muscle mass, (4) the extent to which blood flow is redistributed from inactive vascular beds to increase central blood volume and (5) the extent to which cardiac output can be increased.
Prevalence and incidence rates of Crohn's disease in mainland China: A meta‐analysis of 55 years of research
Authors: ZHENG Jia Ju , ZHU Xia Shuang , HUANGFU Zhao , SHI Xiao Hua , GUO Zhi Rong
Published: March 2010

OBJECTIVES:  To better understand the occurrence of Crohn's disease in mainland China and to give an updated overview of the current status of the disease.

METHODS:  We previously performed a computer‐based literature search using 50 years of records from the Chinese Database of Biology and Medicine (1979 to 2002), combined with a manual year‐by‐year search of the literature from 1950 to 1978. Using a similar method, descriptive epidemiological data of the last 5 years (2003 to September 2007) were collected, pooled with our previous data and re‐analyzed.

RESULTS:  In total, 3618 cases of Crohn's disease since 1950 have been reported from 29 provinces and cities in mainland China, comprising 2112 male and 1506 female patients, with a male predominance of 1.40:1. More than 75 percent of the patients were aged from 20 to 50 years old, with a mean age of 36.9 ± 4.4 (1– 84) years. The extrapolated disease incidence and prevalence rates are 0.848/105 and 2.29/105 person/year, respectively.

CONCLUSION:  The incidence and prevalence rates of Crohn's disease have been increasing rapidly, and the disease is no longer uncommon in China, but these rates are still lower than those in developed countries and other Asian countries. An underestimation may occur because patients who were misdiagnosed or did not seek medical advice could not be included in the study. A future population‐based survey is warranted.
Correlation of pulmonary function variables with hemodynamic measurements in patients with pulmonary arterial hypertension
Authors: Arunthari Vichaya , Burger Charles Dwayne , Lee Augustine Sung‐hi
Published: March 2010

Introduction:  A reduced diffusing capacity of the lung for carbon monoxide (DLCO) measured during a pulmonary function test can suggest pulmonary arterial hypertension (PAH). The DLCO has been reported to weakly correlate with pulmonary hemodynamics.

Objective:  To determine whether the relationship between the DLCO and pulmonary arterial pressures can be strengthened by normalizing the DLCO to spirometric variables.

Patient and Methods:  Patients were seen at a tertiary care referral center. Consecutive subjects who underwent right heart catheterization (RHC) for the evaluation of suspected PAH from 01 January 1991 through 01 October 2006 were identified. Pulmonary function testing (PFT) data performed within 60 days of the RHC was collected. Spearman rank correlation between PFT and RHC variables was calculated.

Results:  One hundred thirty‐eight patients who had an RHC performed had complete PFTs available. No significant correlation was identified between the mean pulmonary artery pressure and the pulmonary vascular resistance against the DLCO, nor the DLCO when normalized to: forced expiratory volume in 1 s, forced vital capacity, total lung capacity or alveolar volume. Spirometric subgroups were identified by standard definitions of restrictive and/or obstructive ventilatory defects. Clinical subgroups were classified based on the clinically diagnosed cause of the patient's PAH. Again, no significant correlation was identified between the PFT variables and RHC measurements in these stratified subgroups.

Conclusion:  In patients with suspected PAH, invasive hemodynamic measurements of PAH do not correlate with PFT variables, even when corrected for spirometric volumes, and regardless of the subgroup of ventilatory physiology or clinical diagnosis.

Please cite this paper as: Arunthari V, Burger CD and Lee AS. Correlation of pulmonary function variables with hemodynamic measurements in patients with pulmonary arterial hypertension. Clin Respir J 2011; 5: 35–43.
Predictors of long‐term survival of lung cancer patients in a Norwegian community
Authors: Skaug Knut , Eide Geir Egil , Gulsvik Amund
Published: March 2010

Introduction: Few population‐based studies are available on more than 5 years survival of lung cancer patients.

Objectives: The aims of this report were to study the survival and the predictors of survival in all lung cancer patients in a defined population and to determine whether and how the length of time from symptom onset to confirmed diagnosis (delay time) influenced survival.

Methods: In a retrospective study, all incident cases from the Norwegian Cancer Registry and the hospital records in the Haugalandet area from 1990 to 1996 were followed until 31 December 2008. The dates of symptom onset, diagnosis, and death and information about demographics, initial stage, performance status, histology and initial symptoms were recorded.

Results: Of a total of 271 patients, 57 (21%) were women, and the mean age at diagnosis was 67.4 years. One‐year survival was 29.2%, and five‐ and 10‐year survival was 8.5% and 5.5%, respectively. The median (inter quartile range, IQR) survival time was 5.7 (1.9, 14.1) months and the median (IQR) delay time was 2.2 (1.1, 3.7) months. Twenty‐five patients (10% of those who died) had a non‐lung cancer cause of death. No weight loss at the time of diagnosis was a significant predictor for long survival in addition to younger age, limited stage, good functional performance and surgical treatment, but delay time for diagnosis had no effect on survival time for lung cancer.

Conclusion: In the whole population of lung cancer patients, long‐term survival remains poor and is not influenced by the diagnostic delay time.

Please cite this paper as: Skaug K, Eide GE and Gulsvik A. Predictors of long‐term survival of lung cancer patients in a Norwegian community.Clin Respir J2011; 5: 50–58.
Shareholder Value: Principles, Declarations, and Actions
Authors: Loderer Claudio , Roth Lukas , Waelchli Urs , Joerg Petra
Published: March 2010

This paper is about shareholder value. We examine whether welfare considerations justify that target and whether competitive markets force firms to pursue it. We also argue that shareholder value is strictly an ill‐defined goal. We report evidence from a large sample of listed firms across the world that many managers do not even mention shareholders in their mission statements. However, firms that do disclose a commitment to shareholders seem to perform better in terms of stock price and operating performance.
Takeover Immunity, Takeovers, and the Market for Nonexecutive Directors
Authors: Ashraf Rasha , Chakrabarti Rajesh , Fu Richard , Jayaraman Narayanan
Published: March 2010

We develop and test two competing hypotheses that relate the market for nonexecutive directors to the level of external monitoring mechanism of the firms they serve. The Reward for Discretion Hypothesis posits that directors are valued more when they display discretion concerning their choice of antitakeover provision (ATP) levels rather than follow a rule. Alternatively, the CEO Risk Aversion Hypothesis implies that CEOs seek directors with inclination for uniform and high ATP levels. We examine how changes in ATP levels and approval of value creating/destroying acquisitions affect the careers of nonexecutive directors. Our results, based on data from about 3,000 listed US companies during 1994‐2003, support the Reward for Discretion Hypothesis.
The Long‐Run Performance of Sponsored and Conventional Spin‐Offs
Authors: Klein April , Rosenfeld James
Published: March 2010

A sponsored spin‐off takes place when an equity stake in a subsidiary is sold to an outside investor before going public. The stock return performance of a sample of 57 sponsored spin‐offs from 1994 to 2005 is significantly negative over a three‐year period following the spin‐off date. The parent firms' stock performance for the year preceding (following) the spin‐off date are below average (average) suggesting that their earlier performances were adversely affected by their subsidiaries and motivated the parents to spin them off. We also find that parent firms underinvest in the subsidiary prior to the spin‐off, which could have motivated the subsidiary to seek outside funding sources before going public.
Dendritic cells fused with allogeneic hepatocellular carcinoma cell line compared with fused autologous tumor cells as hepatocellular carcinoma vaccines
Authors: Yang Jing‐Yue , Cao Da‐Yong , Ma Long‐Yang , Liu Wen‐Chao
Published: March 2010

Purpose:  To investigate the specific antitumor responses against autologous hepatocellular carcinoma (HCC) cells of dendritic cells (DCs) fused with allogeneic HCC cell line, and evaluated the feasibility of BEL7402 as an alternative strategy to deliver shared HCC antigens to DCs.

Methods:  Previous studies demonstrated fusions of patient‐derived DCs and autologous tumor cells could induce T‐cell responses against autologous tumors. These fusion cells require patient‐derived tumor cells, which are not, however, always available. Here, we report the fusing of autologous DCs with allogeneic HCC cell line to induced cytotoxic T‐lymphocyte (CTL) response against autologous HCC cells compare with autologous tumor cells.

Results:  These DC/ BEL7402 fusion cells co‐expressed tumor‐associated antigens and DC‐derived costimulatory and major histocompatibility complex molecules. Both CD4+ and CD8 T+ cells were activated by the fusion cells as demonstrated by the proliferation of T‐cells, the production of cytokines and the simultaneous induction of specific CTL responses. Significantly, CTL induced by dendritic cell/allogeneic BEL7402 fusion cells were able to kill autologous HCC cells by human leukocyte antigen‐A2 restricted mechanisms. The results did not show significant difference between DC fusion with autologous hepatocellular carcinoma cells and DC fusion with allogeneic hepatocellular carcinoma cell line.

Conclusions:  The fusion of allogeneic HCC cell line and autologous DCs may have applications in antitumor immunotherapy through cross‐priming against shared tumor antigens and may provide a platform for adoptive immunotherapy.
Effect of genipin on cholestasis induced by estradiol‐17β‐glucuronide and lithocholate‐3‐O‐glucuornide in rats
Authors: Goto Hideaki , Takikawa Hajime
Published: March 2010

Aim:  Genipin is reported to stimulate the insertion of multidrug resistance protein 2 (Mrp2) in the bile canalicular membrane, thereby causing choleresis by the increased the biliary excretion of glutathione, which has been considered to be a substrate of Mrp2. In the present study, we examined the effect of genipin on cholestasis induced by estradiol‐17β‐glucuronide and lithocholate‐3‐O‐glucuronide, Mrp2 substrates, in rats. Further, the effect of genipin on the biliary excretion of substrates of P‐glycoprotein (P‐gp), vinblastine and erythromycin, was also studied.

Methods:  The effect of genipin infusion at the rate of 0.5 µmol/min/100 g on cholestasis induced by estradiol‐17β‐glucuronide (0.075 µmol/min/100 g for 20 min) and lithocholate‐3‐O‐glucuronide (0.15 µmol/min/100 g for 40 min) was studied. The effect of genipin infusion on the biliary excretion of a tracer dose of vinblastine and erythromycin infused at the rate of 0.1 µmol/min/100 g was also studied.

Results:  Genipin relieved estradiol‐17β‐glucuronide‐induced cholestasis, and cumulative biliary estradiol‐17β‐glucuronide excretion for 120 min was increased from 50 ± 20%–81 ± 20% dose. In contrast, genipin had no effect on lithocholate‐3‐O‐glucuronide‐induced cholestasis. Biliary excretion of a tracer dose of vinblastine and the maximum biliary excretion of erythromycin were significantly decreased by genipin.

Conclusions:  Genipin protected estradiol‐17β‐glucuronide‐induced cholestasis. The mechanism of the protection of cholestasis by genipin is unknown, but it is speculated to be due to a conformational change of P‐gp by genipin, in addition to the stimulation of Mrp2 insertion into the bile canaliculi.
Vibration Analysis of a Floating Roof Subjected to Radial Second Mode of Sloshing
Authors: Utsumi M. , Ishida K.
Published: March 2010

In a previous paper, a cost-efficient modal analysis method for the vibration of a floating roof coupled with nonlinear sloshing in a circular cylindrical oil storage tank is presented. This method is extended to the case in which the out-of-plane deformation of the roof-deck caused by the radial second mode of sloshing induces an elliptical deformation of the pontoon around the deck. First, the radial contraction of the deck is calculated from the slope of the out-of-plane deformation of the deck, and the following two points are confirmed: (i) the circumferential variation in this radial contraction results in the elliptical deformation of the pontoon, and (ii) the present theoretical prediction for the radial contraction is in good agreement with a numerical result obtained by LS-DYNA. Based on these points, the stresses arising in the pontoon are calculated by considering the contraction of the deck as an enforced displacement of the pontoon. Numerical results show that (a) the elliptical deformation of the pontoon causes a large circumferential in-plane stress, (b) reduction achieved by the increase in the thickness of the deck is larger for the radial contraction of the deck and the stresses in the pontoon than for the out-of-plane deformation of the deck, and (c) the radial contraction of the deck for a fixed value of the out-of-plane deformation of the deck increases with the decrease in the radius of the deck.
A Risk-Informed Approach to Leak-Before-Break Assessment of Pressure Tubes in CANDU Reactors
Authors: Pandey M. D. , Sahoo A. K.
Published: March 2010

The leak-before-break (LBB) assessment of pressure tubes is intended to demonstrate that in the event of through-wall cracking of the tube, there will be sufficient time followed by the leak detection, for a controlled shutdown of the reactor prior to the rupture of the pressure tube. CSA Standard N285.8 (2005, “Technical Requirements for In-Service Evaluation of Zirconium Alloy Pressure Tubes in CANDU Reactors,” Canadian Standards Association) has specified deterministic and probabilistic methods for LBB assessment. Although the deterministic method is simple, the associated degree of conservatism is not quantified and it does not provide a risk-informed basis for the fitness for service assessment. On the other hand, full probabilistic methods based on simulations require excessive amount of information and computation time, making them impractical for routine LBB assessment work. This paper presents an innovative, semiprobabilistic method that bridges the gap between a simple deterministic analysis and complex simulations. In the proposed method, a deterministic criterion of CSA Standard N285.8 is calibrated to specified target probabilities of pressure tube rupture based on the concept of partial factors. This paper also highlights the conservatism associated with the current CSA Standard. The main advantage of the proposed approach is that it retains the simplicity of the deterministic method, yet it provides a practical, risk-informed basis for LBB assessment.
Ratchet Boundary Determination Using a Noncyclic Method
Authors: Adibi-Asl R. , Reinhardt W.
Published: March 2010

A simple and systematic procedure is proposed for shakedown analysis using a combination of linear and nonlinear finite element analysis (FEA). The method can identify the boundary between the shakedown and ratcheting domains directly and does not require a cyclic analysis (noncyclic). The proposed method performs an elastic-plastic FEA to determine the reduction in load carrying capacity due to the cyclic secondary loads. An elastic modulus adjustment procedure is then used to generate statically admissible stress distributions and kinematically admissible strain distributions under the applied primary loads. By modifying the local elastic moduli it is possible to obtain inelastic-like stress redistribution. The method is demonstrated with a “two-bar structure” model based on analytical routine. The analysis is then applied to some typical shakedown problems including the “classical Bree problem,” the “bimaterial cylinder,” and the “plate with a hole subjected to radial temperature gradient.”
Erosion in Nuclear Piping Systems
Authors: Crockett Harold M. , Horowitz Jeffrey S.
Published: March 2010

Various mechanisms degrade components and power piping in nuclear power plants. The mechanism with the greatest consequence has been flow-accelerated corrosion (FAC). FAC has caused ruptures and leaks and has led to numerous piping replacements. United States utilities use a combination of EPRI guidance, software, and aggressive inspection programs to deal with FAC. However, current technology does not detail guidance for erosive forms of attack including, cavitation erosion, flashing erosion, droplet impingement, and solid particle erosion. These forms of degradation have caused shutdowns, and leaks have become a maintenance issue. This brief will present a description of erosive damage mechanisms found in nuclear power plants.
Axial Stiffness Analysis of Corrugated Tubes
Authors: Qian Caifu , Sun Cunzheng , Xiao Jinhua
Published: March 2010

In this study, axial stiffness analysis of corrugated tubes was carried out numerically and experimentally. By performing axial loading-displacement analysis, a so-called stiffness weakness factor Kf for the corrugated tube was proposed and formulated. Both corrugated and smooth double-tube heat exchangers were designed and tested under thermal loadings. Results show that the proposed formula for the stiffness weakness factor Kf is accurate enough for the engineering application of the corrugated tubes in constructing heat exchangers.
Welding Residual Stress Solutions for Dissimilar Metal Surge Line Nozzle Welds
Authors: Rudland D. , Csontos A. , Zhang T. , Wilkowski G.
Published: March 2010

At the end of 2006, defects were identified using ultrasonic testing in three of the pressurizer nozzle dissimilar metal (DM) welds at the Wolf Creek nuclear power plant. Understanding welding residual stress is important in the evaluation of why and how these defects occur, which in turn helps to determine the reliability of nuclear power plants. This paper presents analytical predictions of welding residual stress in the surge nozzle geometry identified at Wolf Creek. The analysis procedure in this paper includes not only the pass-by-pass welding steps, but also other essential fabrication steps of pressurizer surge nozzles. Detailed welding simulation analyses have been conducted to predict the magnitude of these stresses in the weld material. Case studies were carried out to investigate the change in the DM main weld stress fields resulting from different boundary conditions, material strength, weld sequencing, as well as simulation of the remaining piping system stiffness. A direct comparison of these analysis methodologies and results has been made in this paper. Weld residual stress results are compared directly to those calculated by the nuclear industry.
Load and Resistance Factor Design (LRFD) of Nuclear Straight Pipes for Loads That Cause Primary Stress
Authors: Avrithi Kleio , Ayyub Bilal M.
Published: March 2010

Class 2 and 3 nuclear piping is designed according to the allowable stress design (ASD) method used in the ASME Boiler and Pressure Vessel (B&PV) code, Sec. III, Division 1, NC and ND-3600 according to which safety factors applied to the strength of steel (resistance) provide acceptable safety margins for the piping design. This paper describes the development of design equations according to the load and resistance factor design (LRFD) method for loads that cause primary stress such as sustained weight, internal pressure, and earthquake for different levels of piping operation. The LRFD method differs from the ASD since multiple factors, applied separately to each load and the strength of steel, provide safety margins that correspond to a known and acceptable probability of failure for the piping. Load combinations are provided, statistical properties for the variables under consideration are presented and the partial safety factors are moreover illustrated for different values of the target reliability index.
Isolation and Characterization of Circulating Tumor Cells from Patients with Localized and Metastatic Prostate Cancer
Authors: Stott Shannon L. , Lee Richard J. , Nagrath Sunitha , Yu Min , Miyamoto David T. , Ulkus Lindsey , Inserra Elizabeth J. , Ulman Matthew , Springer Simeon , Nakamura Zev , Moore Alessandra L. , Tsukrov Dina I. , Kempner Maria E. , Dahl Douglas M. , Wu Chin-Lee , Iafrate A. John , Smith Matthew R. , Tompkins Ronald G. , Sequist Lecia V. , Toner Mehmet , Haber Daniel A. , Maheswaran Shyamala
Published: March 2010

Automated imaging of prostate-specific cancer cells from the blood provides a measure of circulating tumor cell half-life after tumor resection.
Keep Walking
Authors: Carlson Nichole
Published: March 2010

Proximity to parks and paths is associated with an increased probability of walking in older men.
Tumor Imaging: Surgeons Can Have It All
Authors: Cheng Elaine
Published: March 2010

Tumor visualization with activatable cell-penetrating peptides during surgery allows more complete tumor removal.