bluuebunny/crossref_metadata_2025 huggingface dataset:
Diacylglycerol kinases are essential for hepatocyte growth factor‐dependent proliferation and motility of Kaposi’s sarcoma cells
Authors: Baldanzi Gianluca , Pietronave Stefano , Locarno Deborah , Merlin Simone , Porporato Paolo , Chianale Federica , Filigheddu Nicoletta , Cantelmo Anna Rita , Albini Adriana , Graziani Andrea , Prat Maria
Published: April 2011

Hepatocyte growth factor (HGF) is involved in the pathogenesis of Kaposi’s sarcoma (KS), the most frequent neoplasia in patients with AIDS, characterized by proliferating spindle cells, infiltrating inflammatory cells, angiogenesis, edema, and invasiveness. In vitro, this factor sustains the biological behavior of KS derived cells, after activation of its receptor and the downstream MAPK and AKT signals. In other cell types, namely endothelial and epithelial cells, movement, proliferation, and survival stimulated by HGF and other growth factors and cytokines depend on diacylglycerol kinases (DGK). In an effort to identify new intracellular transducers operative in KS cells, which could represent therapeutic targets, we investigated the role of DGK in KS cell movement and proliferation by treating cells with the DGK pharmacological inhibitor R59949. We report that R59949 strongly inhibits HGF‐induced KS motility, proliferation, and anchorage‐independent growth with only a partial effect on cell adhesion and spreading. R59949 does not affect cell survival, HGF receptor activation, or the classical MAPK and AKT signalling pathways. Furthermore, we carried out an siRNA screen to characterize the DGK isoforms involved in KS motility and anchorage independent growth. Our data indicate a strong involvement of DGK‐δ in KS motility and of DGK‐ι in anchorage‐independent growth. These results indicate that DGK inhibition is sufficient to impair in vitro KS cell proliferation and movement and suggest that selected DGK represent new pharmacological targets to interfere with the malignant properties of KS, independently from the well‐known RAS/MAPK and PI3K/AKT pathways. (Cancer Sci 2011; 102: 1329–1336)
Serum fetuin‐A concentrations are elevated in subjects with impaired glucose tolerance and newly diagnosed type 2 diabetes
Authors: Ou Horng‐Yih , Yang Yi‐Ching , Wu Hung‐Tsung , Wu Jin‐Shang , Lu Feng‐Hwa , Chang Chih‐Jen
Published: April 2011

Objective  Hepatic steatosis is associated with an increased risk of diabetes. Although the levels of serum fetuin‐A, a liver‐derived glycoprotein that impairs insulin signalling, are positively correlated with hepatic steatosis, the levels of fetuin‐A in subjects with impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and newly diagnosed type 2 diabetes (NDD) have not been established. The aim of this study is to investigate the relationship among serum fetuin‐A concentrations, IFG, IGT and NDD in Chinese subjects without nonalcoholic fatty liver disease (NAFLD).

Design  A total of 360 age‐ and sex‐matched subjects with normal glucose tolerance (NGT), IFG, IGT and NDD were recruited in this case–control study.

Measurements  Each subject was assessed by abdominal ultrasound to exclude the presence of NAFLD. Serum fetuin‐A concentrations were measured by enzyme‐linked immunosorbent assay and compared between NGT, IFG, IGT and NDD groups. The association with clinical and metabolic parameters was also examined.

Results  Serum fetuin‐A concentrations were higher in NDD and IGT groups than NGT groups (341 ± 88, 335 ± 90, and 300 ± 75 μg/ml). In multiple linear regression analysis, IGT (P < 0·01) and NDD (P < 0·05) were the positively associated factors of serum fetuin‐A concentrations, but age (P < 0·05) was a negatively associated factor after adjusting for age, anthropometric indices, lipid profile, estimated glomerular filtration rate (eGFR), adiponectin, C‐reactive protein (CRP) and homeostasis model assessment (HOMA‐IR).

Conclusions  IGT and NDD are positively associated with serum fetuin‐A concentrations in subjects without NAFLD independent of cardiometabolic risk factors.
Aircraft‐derived regional scale CO2 fluxes from vegetated drained thaw‐lake basins and interstitial tundra on the Arctic Coastal Plain of Alaska
Authors: ZULUETA ROMMEL C. , OECHEL WALTER C. , LOESCHER HENRY W. , LAWRENCE WILLIAM T. , PAW U KYAW THA
Published: April 2011

The landscape surface of the Barrow Peninsula of Alaska is a mosaic of small ponds, thaw lakes, different aged vegetated drained thaw‐lake basins (VDTLBs), and interstitial tundra which have been dynamically formed by both short‐ and long‐term processes. We used a combination of tower‐ and aircraft‐based eddy covariance measurements to characterize the spatial and temporal patterns of CO2, latent, and sensible heat fluxes along with MODIS NDVI, and were able to scale the aircraft‐based CO2 fluxes to the 1802 km2 Barrow Peninsula region. During typical 2006 summer conditions, the midday hourly CO2 flux over the region was −2.04 × 105 kg CO2 h−1. The CO2 fluxes among the interstitial tundra, Ancient, and Old VDTLBs, as well as between the Medium and Young VDTLBs were not significantly different. Combined, the interstitial tundra and Old and Ancient VDTLBs represent∼67% of the Barrow Peninsula surface area, accounting for ∼59% of the regional flux signal. Although the Medium and Young VDTLBs represent ∼11% of the surface area, they account for a large portion, ∼35%, of the total regional flux. The remaining ∼22% of the surface area are lakes and contributed the remaining ∼6% of the total regional flux. Previous studies treated vegetated areas of the region as a single surface type with measurements from a few study sites; doing so could underestimate the regional flux by ∼22%. Here, we demonstrate that aircraft‐based systems have the ability to cover large spatial scales while measuring the turbulent fluxes across a number of surfaces and combined with ground‐ and satellite‐based measurements provide a valuable tool for both scaling and validation of regional‐scale fluxes.
An exploratory study of religious involvement as a moderator between anxiety, depressive symptoms and quality of life outcomes of older adults
Authors: Huang Chiung‐Yu , Hsu Mei‐Chi , Chen Tai‐Jui
Published: April 2011

Aims.  The aims of this study were to examine the relationships among religion, religious involvement, anxiety, depressive symptoms and quality of life in older adults with psychological problems and whether religious involvement moderated anxiety and depressive symptoms on the outcome of quality of life. Evidence for the mechanism through which religious involvement exerts its moderated effect on anxiety and depressive symptoms was provided.

Background.  Older adults suffering from stress may consequently have anxiety or depressive symptoms and their quality of life is also influenced. The meanings of religious involvement are well documented but less is known about moderating characteristics that determine which older adults with psychological problems are most likely to benefit.

Design.  A correlational, cross‐sectional study.

Methods.  The study was conducted in 2007–2008 with a purposive sample of 115 older adults who were 60 years of age or older at a psychiatric centre in Taiwan. Three reliable and valid questionnaires and a demographic sheet were administered.

Results.  Approximately 75% of older adults had mild to severe anxiety; 76·5% had depressive symptoms; and 67·8% of participants who had depressive symptoms also had comorbid anxiety. Findings indicated that there was a significant moderating effect for religious involvement on the quality of life outcome. Religious involvement significantly moderated anxiety and depressive symptoms on quality of life. Moreover, religious participants had a better quality of life and had lower anxiety and depressive symptoms than non‐religious participants.

Conclusion.  Testing for moderating effects provides important information regarding the benefits of religious involvement. The current study reveals that religious participants have lower levels of depressive symptoms and anxiety and better quality of life than non‐religious ones. Religious involvement plays a role in buffering the relationship between psychological problems and quality of life.

Relevance to clinical practice.  Nurses can encourage individuals with health problems to participate in religious involvement, which may help individuals to experience a feeling of support and enhance their quality of life.
Pharmacokinetic study of Rhizoma Curcumae Oil and Rhizoma Curcumae Oil‐β‐cyclodextrin inclusion complex in pigs after oral administration
Authors: YONG‐XUE S. , YONGJIN L. , DONGPING Z. , GANG W. , ZHICHANG L. , HAIYAN Z.
Published: April 2011

Yong‐Xue, S., Yongjin, L., Dongping, Z., Gang, W., Zhichang, L., Haiyan, Z. Pharmacokinetic study of Rhizoma Curcumae Oil and Rhizoma Curcumae Oil‐β‐cyclodextrin inclusion complex in pigs after oral administration. J. vet. Pharmacol. Therap. 35, 47–51.

Pharmacokinetics of Rhizoma Curcumae oil‐pure drug (RCO‐PD) and its β‐cyclodextrin inclusion complex (RCO‐βCD) were studied in a randomized two‐way crossover design following a single oral administration of the two formulations. Germacrone concentrations in plasma were determined by high‐performance liquid chromatography with UV detector. The concentrations vs. time data were analyzed by a noncompartmental pharmacokinetic method. The result showed that germacrone in both groups was rapidly absorbed followed by a slow elimination. The main parameters in RCO‐PD group were as follows: t1/2λz 6.63 ± 1.08 h, Cmax 2.50 ± 0.34 μg/mL, MRT 7.19 ± 0.93 h, and AUC0–∞ 13.92 ± 2.75 mg/L·h, while in RCO‐βCD group, t1/2λz 6.77 ± 0.67 h, Cmax 2.98 ± 0.24 μg/mL, MRT 8.87 ± 0.76 h, and AUC0–∞ 21.60 ± 1.95 mg/L·h, respectively. The above results indicated that Cmax, Tmax, AUC0–t, AUC0−∞, and MRT in RCO‐βCD group were significantly different from RCO‐PD group, and the relative bioavailability of RCO‐βCD group is significantly higher while compared to RCO‐PD group (F = 156%, with its 90% confidence interval of 145–169%).
A nationwide investigation on gestational age specific birthweight and mortality among Japanese twins
Authors: Tobe Ruoyan Gai , Mori Rintaro , Shinozuka Norio , Kubo Takahiko , Itabashi Kazuo
Published: April 2011

Tobe RG, Mori R, Shinozuka N, Kubo T, Itabashi K. A nationwide investigation on gestational age specific birthweight and mortality among Japanese twins. Paediatric and Perinatal Epidemiology 2011; 25: 228–235.

Gestational age specific birthweight has been used as an important indicator to identify the health status of neonates and to provide appropriate neonatal care services to those at high risk. To identify the gestational age specific birthweight of twins born in secondary and tertiary hospitals in Japan and to explore factors affecting mortality, we used a nationwide obstetric database in Japan. Liveborn twins from 2001 to 2005 in the database, which was established with the national Perinatal Health Care Project, were enrolled (n = 22 240). Obstetric data from the medical records were collected and analysed. Approximately 60% of liveborn twins were delivered between weeks 33 and 38, most frequently at 36 and 37 weeks. The mean birthweight of liveborn twins was 2084 g and the mean gestational age was 34.9 weeks. Intrauterine growth differed by parity, mode of delivery, birth order, chorionicity and sex. Using logistic regression, lower gestational age, small for gestational age, monochorionic twins and vaginal delivery tended to have higher risks of mortality.
Chrysomyinae (Diptera: Calliphoridae) is monophyletic: a molecular systematic analysis
Authors: SINGH BANESHWAR , WELLS JEFFREY D.
Published: April 2011

The subfamily Chrysomyinae includes blowflies of considerable ecological and applied importance. Previous extensive morphological investigations have affirmed chrysomyine monophyly, but did not support the monophyly of traditional chrysomyine tribes. Conversely, molecular systematic analyses suggested a para‐ or polyphyletic Chrysomyinae. Conflicting hypotheses have been proposed about the tribe‐level classification, and about the relationships of the obligate bird parasites Protocalliphora Hough and Trypocalliphora Peus. To understand chrysomyine evolution better, we reconstructed phylogenies of the Chrysomyinae based on 2285 bp of combined data from mitochondrial cytochrome oxidase c subunit 1 (COI) and nuclear carbamoylphosphate synthetase (CPS) genes. Maximum parsimony (MP), maximum likelihood (ML) and Bayesian analysis (BA) strongly supported the monophyly of Chrysomyinae and the paraphyly of the tribe Chrysomyini. BA and ML yielded a monophyletic tribe Phormiini, but this was unresolved by MP. A sister‐group relationship between Trypocalliphora and Protocalliphora indicates that obligate bird parasitism evolved once within the Calliphoridae. For the first time all Neotropical genera (Cochliomyia Townsend, Compsomyiops Townsend, Paralucilia Brauer and Bergenstamm, Hemilucilia Brauer and Chloroprocta Wulp) were found to comprise a single lineage, and Chrysomya Robineau‐Desvoidy, traditionally a member of Chrysomyini, was found to be closer to the Phormiini. Similarly, Hemilucilia + Chloroprocta was a monophyletic group. Every genus for which we examined more than one species was monophyletic.
Relative and absolute addressability of global disease burden in maternal and perinatal health by investment in R&D
Authors: Fisk Nicholas M. , McKee Martin , Atun Rifat
Published: April 2011

Maternal and perinatal disease accounts for nearly 10% of the global burden of disease, with only modest progress towards achievement of the Millennium Development Goals. Despite a favourable new global health landscape in research and development (R&D) to produce new drugs for neglected diseases, R&D investment in maternal/perinatal health remains small and non‐strategic. Investment in obstetric R&D by industry or the not‐for‐profit sector has lagged behind other specialties, with the number of registered pipeline drugs only 1–5% that for other major disease areas. Using a Delphi exercise with maternal/perinatal experts in global and translational research, we estimate that equitable pharmaceutical R&D and public sector research funding over the next 10–20 years could avert 1.1% and 1.9% of the global disease burden, respectively. In contrast, optimal uptake of existing research would prevent 3.0%, justifying the current focus on health service provision. Although R&D predominantly occurs in high‐income countries, more than 98% of the estimated reduction in disease burden in this field would be in developing countries. We conclude that better pharmaceutical and public sector R&D would prevent around 1/3 and 2/3, respectively, of the disease burden addressable by optimal uptake of existing research. Strengthening R&D may be an important complementary strategy to health service provision to address global maternal and perinatal disease burden.
The relationship between adenosine triphosphate within CD4+ T lymphocytes and acute rejection after liver transplantation
Authors: Dong Jia‐Yong , Yin Hao , Li Rui‐Dong , Ding Guo‐Shan , Fu Zhi‐Ren , Wu You‐Min , Wang Zheng‐Xin
Published: April 2011

Dong J‐Y, Yin H, Li R‐D, Ding G‐S, Fu Z‐R, Wu Y‐M, Wang Z‐X. The relationship between adenosine triphosphate within CD4+ T lymphocytes and acute rejection after liver transplantation. Clin Transplant 2011: 25: E292–E296. © 2011 John Wiley & Sons A/S.

Abstract:  Background:  There have been increasing interests in the relationship between CD4+ T lymphocytes and acute rejection (AR) in transplantation. In this study, we explore the role of CD4+ T lymphocytes after liver transplantation.

Methods:  From February to October 2009, 87 patients underwent liver transplantation. They were divided into the AR group and non‐acute rejection (NAR) group, with 56 healthy individuals in the control group. Blood specimens were collected preoperatively and at one, two, and four wk postoperatively for all groups and also on the day when AR occurred and one wk after intravenous glucocorticoid therapy for the AR group. Adenosine triphosphate (ATP) levels were measured using the ImmuKnow™ test kits for immune cell functions.

Results:  After transplantation, the ATP levels within CD4+ T lymphocytes were significantly elevated in the two groups when compared with the preoperative levels. It peaked in the AR group and was significantly higher than that of the NAR group (p < 0.05). By ROC curve analysis, the obvious elevation of the ATP value one wk after transplantation had better sensitivity and specificity in diagnosing the AR. The ATP sensitivity rate for early AR was 85.7% and specificity rate 80.9% when the cutoff value was 407 μg/L. The ATP value collected on the day of AR occurrence has apparently positive correlation with the rejection acting index (RAI) (p < 0.01). After the intravenous glucocorticoid therapy, all the ARs were reversed and the ATP value declined significantly compared with the control group and that on the day when AR occurred (p < 0.01).

Conclusions:  During the early postoperative period (especially at first week after liver transplantation), the elevation of ATP levels within CD4+ T lymphocytes has good sensitivity and specificity in diagnosing the AR at early stage. And the degree of AR has positive relationship with ATP value. After the intravenous glucocorticoid therapy, the obvious declination of AR might be used in evaluating the effectiveness of anti‐rejection treatment.
The relationship between body mass index and outcomes in leukemic patients undergoing allogeneic hematopoietic stem cell transplantation
Authors: Hadjibabaie Molouk , Tabeefar Hamed , Alimoghaddam Kamran , Iravani Masood , Eslami Kaveh , Honarmand Hooshyar , Javadi Mohammad reza , Khatami Farnaz , Ashouri Asieh , Ghavamzadeh Ardeshir
Published: April 2011

Hadjibabaie M, Tabeefar H, Alimoghaddam K, Iravani M, Eslami K, Honarmand H, Javadi M, Khatami F, Ashouri A, Ghavamzadeh A. The relationship between body mass index and outcomes in leukemic patients undergoing allogeneic hematopoietic stem cell transplantation.  Clin Transplant 2012: 26: 149–155.  © 2011 John Wiley & Sons A/S.

Abstract:  Hematopoietic stem cell transplantation (HSCT) is being used increasingly in an attempt to cure many hematological disorders. Obesity has become a world wide phenomenon and is a known risk factor for numerous medical conditions, but its role in transplant outcomes remained controversial. Total of 192 patients with acute leukemia who underwent sibling HLA matched HSCT were analyzed to find the effect of pre‐transplant body mass index (BMI) on transplant outcomes such as time to engraftment, infections, graft vs. host disease (GvHD), and overall survival (OS) for the period of three yr (April 2006–March 2009). There was a significant correlation between higher pre‐transplant BMI and shorter engraftment time (p = 0.010); but no relation between BMI and GvHD, infection, and OS was found. The results of this study showed that patients with higher BMI may have a shorter engraftment time; but lower, although not significant, survival rate compared to non‐obese patients.
Use of antipsychotic medications in patients with Parkinson's disease at Auckland City Hospital
Authors: Bloomfield K. , MacDonald L. , Finucane G. , Snow B. , Roxburgh R.
Published: April 2011

Background:  The American Academy of Neurology considers clozapine first line treatment for psychosis in Parkinson's disease (PD). In practice, patients are typically treated with quetiapine initially despite only level C evidence for use due to concern about side‐effects, and changed to clozapine if they fail this.

Aim:  To review the use of antipsychotics in patients with PD and the demographics of PD patients who develop psychosis.

Methods:  Patients with PD on antipsychotic medications were identified by the Movement Disorder Nurse Specialist database and by reviewing patients admitted to Auckland City Hospital from January 2006 until March 2008. The demographic data, details of PD and antipsychotic use and comorbidities were recorded.

Results:  Sixty‐six patients with PD on antipsychotics were identified. The mean age was 75 years and 48 (73%) were in residential care. Patients admitted on antipsychotics had longer disease duration (P < 0.001) and were more likely to have cognitive impairment (P= 0.02) than those admitted not on antipsychotics. The most common indication for use was hallucinations. Patients on clozapine were younger (P < 0.005) and had less comorbidity (P= 0.04) than those on quetiapine. Fifty per cent (6/12) of patients on clozapine had previously failed quetiapine.

Conclusion:  Quetiapine has a good efficacy rate with minimal side‐effects. This study lends support to the assumption that quetiapine is a useful medication. However, clozapine also was well tolerated and could be considered for use more frequently than it is.
Association between serum cystatin C, monocytes and other inflammatory markers
Authors: Evangelopoulos A. A. , Vallianou N. G. , Bountziouka V. , Katsagoni C. , Bathrellou E. , Vogiatzakis E. D. , Bonou M. S. , Barbetseas J. , Avgerinos P. C. , Panagiotakos D. B.
Published: April 2011

Background:  Cystatin C is a marker of renal function that appears to be associated with inflammation. The aim of the present study was to investigate whether there is any relationship between cystatin C, total and differential leukocyte count and other inflammatory markers.

Methods:  Cystatin C, creatinine, high sensitivity C‐reactive protein (hs‐CRP), haptoglobin, ferritin, serum albumin, glucose, total cholesterol, HDL and triglycerides together with total and differential leukocyte count were determined in 490 adults (46 ± 16 years, 40% men) who underwent a typical health examination. Glomerular filtration rate was estimated by the simplified Modification of Diet in Renal Disease formula. Anthropometric and lifestyle characteristics were also recorded.

Results:  After adjustment for demographic risk factors, comorbid health conditions and renal function, a positive and independent relationship of serum cystatin C levels with peripheral monocyte blood count (regression coefficient ± SE: 12 ± 3.38, P < 0.001) and white blood count (0.616 ± 0.278, P= 0.027) was evident. In this multiple linear regression analysis, other inflammatory markers (i.e. hs‐CRP, haptoglobin, ferritin, albumin) did not seem to affect cystatin C blood levels.

Conclusion:  The results of this study demonstrated that monocytes, which play an important role in chronic inflammation and atherosclerosis, were independently related with cystatin C concentrations. This finding may provide a plausible link for the usefulness of cystatin C in predicting increased cardiovascular risk.
Looking at debit and credit card fraud
Authors: Porkess Roger , Mason Stephen
Published: April 2011

This article, written jointly by a mathematician and a barrister, looks at some of the statistical issues raised by court cases based on fraud involving chip and PIN cards. It provides examples and insights that statistics teachers should find helpful.
What is a p‐value?
Authors: Humphrey Patricia
Published: April 2011

An in‐class activity is described that can be used not only to motivate hypothesis testing, but also to understand and compute the p‐value and power in a statistical test.
Classroom projects – full steam ahead
Authors: du Feu Chris
Published: April 2011

Practical project work based on eBay selling prices is described. It is suitable for secondary school students of a wide range of statistical expertise and it may be used to introduce a statistical package.
Regulation of Akt and Wnt signaling by the group II metabotropic glutamate receptor antagonist LY341495 and agonist LY379268
Authors: Sutton Laurie P. , Rushlow Walter J.
Published: April 2011

J. Neurochem. (2011) 117, 973–983.

Metabotropic glutamate receptors 2/3 (mGlu2/3) have been implicated in schizophrenia and as a novel treatment target for schizophrenia. The current study examined whether mGlu2/3 regulates Akt (protein kinase B) and Wnt (Wingless/Int‐1) signaling, two cascades associated with schizophrenia and modified by antipsychotics. Western blotting revealed increases in phosphorylated Akt (pAkt) and phosphorylated glycogen synthase kinase‐3 (pGSK‐3) following acute and repeated treatment of LY379268 (mGlu2/3 agonist), whereas increases in dishevelled‐2 (Dvl‐2), dishevelled‐3 (Dvl‐3), GSK‐3 and β‐catenin were only observed following repeated treatment. LY341495 (mGlu2/3 antagonist) induced the opposite response compared with LY379268. Co‐immunoprecipitation experiments showed an association between the mGlu2/3 complex and Dvl‐2 providing a possible mechanism to explain how the mGlu2/3 can mediate changes in Wnt signaling. However, there was no association between the mGlu2/3 complex and Akt suggesting that changes in Akt signaling following LY341495 and LY379268 treatments may not be directly mediated by the mGlu2/3. Finally, an increase in locomotor activity induced by LY341495 treatment correlated with increased pAkt and pGSK‐3 levels and was attenuated by the administration of the GSK‐3 inhibitor, SB216763. Overall, the results suggest that mGlu2/3 regulates Akt and Wnt signaling and LY379268 treatment has overlapping effects with D2 dopamine receptor antagonists (antipsychotic drugs).
New species and records of the genera Milichia Meigen and Milichiella Giglio‐Tos (Diptera, Milichiidae) from the Oriental region and Seram Island
Authors: IWASA Mitsuhiro
Published: April 2011

The species of the genera Milichia and Milichiella in the Oriental region and Seram Is. are taxonomically investigated. Three new species, Milichia linealis sp. nov. from the Philippines, Milichiella sulawesiensis sp. nov. and Milichiella nigella sp. nov. from Indonesia, are described. New distributional data of Milichiella bakeri Aldrich from Indonesia and M. spinthera Hendel from Indonesia, Nepal and Thailand are given. Keys to the species of Milichia and Milichiella in the Oriental region and Seram Is. are provided.
On Different Types of Uncertainties in the Context of the Precautionary Principle
Authors: Aven Terje
Published: April 2011

Few policies for risk management have created more controversy than the precautionary principle. A main problem is the extreme number of different definitions and interpretations. Almost all definitions of the precautionary principle identify “scientific uncertainties” as the trigger or criterion for its invocation; however, the meaning of this concept is not clear. For applying the precautionary principle it is not sufficient that the threats or hazards are uncertain. A stronger requirement is needed. This article provides an in‐depth analysis of this issue. We question how the scientific uncertainties are linked to the interpretation of the probability concept, expected values, the results from probabilistic risk assessments, the common distinction between aleatory uncertainties and epistemic uncertainties, and the problem of establishing an accurate prediction model (cause‐effect relationship). A new classification structure is suggested to define what scientific uncertainties mean.
Ferroelectric Domain Structures and Electrical Properties of Fine‐Grained Lead‐Free Sodium Potassium Niobate Ceramics
Authors: Eriksson Mirva , Yan Haixue , Viola Giuseppe , Ning Huanpo , Gruner Daniel , Nygren Mats , Reece Mike J. , Shen Zhijian
Published: April 2011

Piezoelectric ceramics of the composition Na0.5K0.5NbO3 (NKN) with grain sizes in the range of 0.2–1 μm were fabricated by spark plasma sintering. Ferroelectric domain size decreases with decreasing grain size and non‐180° ferroelectric domains walls were still visible in 200 nm sized grains. The Curie point of the ceramics was grain size independent. This suggests that the critical grain size for a single domain single grain structure for NKN is <200 nm. Optimized processing conditions enabled ceramics of high densities (>99.5% theoretical density) to be made at T≥850°C. For the dense ceramics (grain size ≥350 nm), the room temperature dielectric constant and coercive field increased with decreasing grain size. The remnant polarization was grain size independent. The material sintered at 850°C is a very good candidate for lead‐free piezoelectric applications because of its high piezoelectric constant (d33=160 ± 2 pC/N).
Conformation of the Dileucine‐Based Sorting Motif in HIV‐1 Nef Revealed by Intermolecular Domain Assembly
Authors: Horenkamp Florian A. , Breuer Sebastian , Schulte Antje , Lülf Sebastian , Weyand Michael , Saksela Kalle , Geyer Matthias
Published: April 2011

The human immunodeficiency virus 1 (HIV‐1) Nef protein is a pathogenicity factor required for effective progression to AIDS, which modulates host cell signaling pathways and T‐cell receptor internalization. We have determined the crystal structure of Nef, allele SF2, in complex with an engineered SH3 domain of human Hck showing unnaturally tight binding and inhibitory potential toward Nef. This complex provides the most complete Nef structure described today, and explains the structural basis of the high affinity of this interaction. Intriguingly, the 33‐residue C‐terminal flexible loop is resolved in the structure by its interactions with a highly conserved hydrophobic groove on the core domain of an adjacent Nef molecule. The loop mediates the interaction of Nef with the cellular adaptor protein machinery for the stimulated internalization of surface receptors. The endocytic dileucine‐based sorting motif is exposed at the tip of the acidic loop, giving the myristoylated Nef protein a distinctly dipolar character. The intermolecular domain assembly of Nef provides insights into a possible regulation mechanism for cargo trafficking.
Comparative QSAR Analyses of Competitive CYP2C9 Inhibitors using Three‐Dimensional Molecular Descriptors
Authors: Lather Viney , Fernandes Miguel X.
Published: April 2011

One of the biggest challenges in QSAR studies using three‐dimensional descriptors is to generate the bioactive conformation of the molecules. Comparative QSAR analyses have been performed on a dataset of 34 structurally diverse and competitive CYP2C9 inhibitors by generating their lowest energy conformers as well as additional multiple conformers for the calculation of molecular descriptors. Three‐dimensional descriptors accounting for the spatial characteristics of the molecules calculated using E‐Dragon were used as the independent variables. The robustness and the predictive performance of the developed models were verified using both the internal [leave‐one‐out (LOO)] and external statistical validation (test set of 12 inhibitors). The best models (MLR using GETAWAY descriptors and partial least squares using 3D‐MoRSE) were obtained by using the multiple conformers for the calculation of descriptors and were selected based upon the higher external prediction ( values of 0.65 and 0.63, respectively) and lower root mean square error of prediction (0.48 and 0.48, respectively). The predictive ability of the best model, i.e., MLR using GETAWAY descriptors was additionally verified on an external test set of quinoline‐4‐carboxamide analogs and resulted in an value of 0.6. These simple and alignment‐independent QSAR models offer the possibility to predict CYP2C9 inhibitory activity of chemically diverse ligands in the absence of X‐ray crystallographic information of target protein structure and can provide useful insights about the ADMET properties of candidate molecules in the early phases of drug discovery.
Quantum Yields and Quantitative Spectra of Firefly Bioluminescence with Various Bivalent Metal Ions
Authors: Wang Yu , Kubota Hidehiro , Yamada Nobuyuki , Irie Tsutomu , Akiyama Hidefumi
Published: April 2011

We measured quantitative spectra of firefly (Photinus pyralis) bioluminescence in the presence of Zn2+ and other bivalent metal ions to investigate the effects of these metal ions on luciferin‐luciferase reaction. We studied the dependence of the quantum yield and spectrum on quantity and kind of bivalent metal ions. Adding various amounts of Mg2+, Mn2+ and Ca2+ produced virtually no change in the quantum yields or the spectra of bioluminescence. In contrast, increasing amounts of ions such as Zn2+ and Cd2+ decreased quantum yields and changed the bioluminescence color from yellow‐green to red. Quantitative analysis showed that the sensitivities of the quantum yield and color to various metal ions were in the order of Hg2+>Zn2+, Cd2+>Ni2+, Co2+, Fe2+≫Mg2+, Mn2+, Ca2+. We propose that the changes in quantum yield and spectrum caused by the metal ions are due to their effect on luciferase that surrounds oxyluciferin during its radioactive decay. We also found that having more metal ions accelerated bioluminescence reactions. The sensitivity of the reaction rate had no correlation with those of the quantum yield and spectrum.
Decreased prothrombin time after intravitreal bevacizumab in the early period in patients with proliferative diabetic retinopathy
Authors: Qian Jing , Jiang Yan‐Rong
Published: April 2011

Purpose:  To evaluate the effect of intravitreal bevacizumab (Avastin; Genentech, Inc., San Francisco, CA, USA) (IVB) injection on prothrombin time (PT) in patients with proliferative diabetic retinopathy (PDR) and nondiabetic patients.

Methods:  Eighty‐nine patients received primary IVB (1.25 mg) in one eye were investigated. The patients were divided into three groups: 34 PDR (diabetic group), 26 nondiabetic (nondiabetic group) patients received IVB and 29 PDR patients without IVB (control group). The levels of PT were detected before and after IVB in study groups and at corresponding time‐points in the control group. Paired samples t‐test was conducted to compare the statistical differences of PT in each group.

Results:  Significant difference (p < 0.001) of the levels of PT before and after IVB was observed in diabetic group in the early period, and the PT changes (11.0 ± 0.56 before and 10.6 ± 0.45 after IVB) were in fact within the normal range. There were no significant differences in other groups and other time‐points (all p > 0.05).

Conclusions:  Intravitreal bevacizumab may lead to a decrease in the levels of PT in the early period after IVB in PDR patients, suggesting a temporarily potential effect of IVB on the extrinsic clotting pathway of blood coagulation cascade in diabetic patients.
Pharmacological Properties of the Central Antihypertensive Agent, Moxonidine
Authors: Edwards Lincoln P. , Brown‐Bryan Terry A. , McLean Lancelot , Ernsberger Paul
Published: April 2011

The sympathetic nervous system plays a central role in the pathophysiology not only of hypertension and other cardiovascular diseases but also metabolic disorders including disturbances of glucose and lipid homeostasis. A centrally acting sympathetic agent is therefore attractive not only for lowering blood pressure, but also intervening with multiple disease processes. Older agents such as clonidine and guanabenz have numerous side effects, including sedation and dry mouth that limit their acceptability to patients. Moxonidine and the related agent rilmenidine have greatly reduced side effects, because they have reduced activity at the α2‐adrenergic receptors that mediate these undesirable actions. Instead, moxonidine and rilmenidine act primarily through a novel cellular site, termed the I1‐imidazoline receptor. The molecular biology of the I1‐imidazoline receptor protein has recently been described, and the cell signaling pathways linked to this protein have been characterized. Moxonidine has unique effects on a number of cell types through this unusual cellular site of action. There are multiple therapeutic implications of these cellular actions, especially for metabolic syndrome and its associated derangements in glucose and lipid metabolism. Finally, the clinical trials that seemed to identify an unfavorable outcome in severe heart failure are dissected and critiqued. We conclude that moxonidine and future successors to this agent could be of great value in treating multiple chronic diseases.
The production‐ecological sustainability of cassava, sugarcane and sweet sorghum cultivation for bioethanol in Mozambique
Authors: DE VRIES SANDER C. , VAN DE VEN GERRIE W. J. , VAN ITTERSUM MARTIN K. , GILLER KEN E.
Published: April 2011

We present an approach for providing quantitative insight into the production‐ecological sustainability of biofuel feedstock production systems. The approach is based on a simple crop‐soil model and was used for assessing feedstock from current and improved production systems of cassava for bioethanol. Assessments were performed for a study area in Mozambique, a country considered promising for biomass production. Our focus is on the potential role of smallholders in the production of feedstock for biofuels. We take cassava as the crop for this purpose and compare it with feedstock production on plantations using sugarcane, sweet sorghum and cassava as benchmarks. Production‐ecological sustainability was defined by seven indicators related to resource‐use efficiency, soil quality, net energy production and greenhouse gas (GHG) emissions. Results indicate that of the assessed systems, sugarcane performed better than cassava, although it requires substantial water for irrigation. Targeted use of nutrient inputs improved sustainability of smallholder cassava. Cassava production systems on more fertile soils were more sustainable than those on less fertile soils; the latter required more external inputs for achieving the same output, affecting most indicators negatively and reducing the feasibility for smallholders. Cassava and sweet sorghum performed similarly. Cassava production requires much more labour per hectare than production of sugarcane or sweet sorghum. Production of bioethanol feedstock on cultivated lands was more sustainable and had potential for carbon sequestration, avoiding GHG emissions from clearing natural vegetation if new land is opened.
A five‐year clinical and radiographic follow‐up of bipolar hip arthroplasty with insertion of a porous‐coated anatomic femoral component without cement
Authors: Cao Cheng‐fu , Zhou Jun‐jie , Pang Jin‐hui , Chen Xian‐qi
Published: April 2011

Objective:  To evaluate the clinical and radiographic outcomes of bipolar hip arthroplasty with a cementless porous‐coated anatomic femoral component.

Methods:  Fifty‐nine patients (86 hips) with a minimum 3.5‐year follow‐up were followed up for a mean of 5.2 years (from January 2005 to January 2007). Standard clinical evaluation utilizing the Harris hip score and radiographic evaluation based on the criteria of the Hip Society were used in this prospective study. Radiographic assessment included evaluation of calcar remodeling and pedestal formation.

Results:  The average age of the patients (24 men and 35 women) at the time of surgery was 71.4 years (range, 69–84 years). The average preoperative Harris hip score was 48.5 ± 4.0 (range, 25–65) points, pain score 15.2 ± 3.9 (range, 0–20) points and functional score 26.7 ± 4.6 (range, 9–40) points. At the time of the latest follow‐up, the average Harris hip score was 96.1 ± 2.1 (range, 67–100) points, pain score 42.6 ± 6.3 (range, 32–54) points and functional score 45.5 ± 4.7 (range, 29–56) points. Five hips (5.81%) had pain in the anterior part of the thigh. Two hips (2.33%) required revision of the femoral component because of aseptic loosening and periprosthetic fracture. Radiographic assessment revealed consistent evidence of proximal bone ingrowth. No completely radiolucent lines were identified, except around stems that had loosened. Twenty‐seven femoral components (31.4%) had associated slight pedestal formation. No osteolytic lesions of the femur were identified. Nonprogressive pelvic osteolysis was identified in four hips, none of the lesions being ≥2 mm in diameter.

Conclusion:  An anatomically designed prosthesis can provide good clinical results, with low incidence of thigh pain and loosening of the component.
Surgical management of cervical cord injury with ossification of the cervical posterior longitudinal ligament
Authors: Yang Da‐long , Zhang Ying‐ze , Shen Yong , Cao Jun‐ming
Published: April 2011

Objective:  To identify an appropriate surgical approach for the management of cervical cord injury with ossification of the posterior longitudinal ligament.

Methods:  A retrospective study of 25 cases of cervical cord injury with ossification of the posterior longitudinal ligament was performed. Two cases were classified as Frankel grade A, three as grade B, fourteen as grade C, and six as grade D. Treatment procedures consisted of anterior decompression with instrumentation (twelve patients), posterior decompression (eight patients), and combined anterior and posterior decompression (five patients).

Results:  There were no iatrogenic injuries of great vessels, trachea, esophagus or spinal cord. All patients were followed up for 15–86 months (average, 38.3 months). All segment with anterior fixation attained solid fusion, without implants loosening or breakage. No reclosed open‐door was found after posterior laminoplasty. Twenty‐one patients improved by one to two Frankel grades. The patients with complete spinal cord injury achieved no neurologic recovery, but did experience relief of upper limb pain or numbness.

Conclusion:  The surgical outcomes of cervical cord injury with ossification of the posterior longitudinal ligament were satisfactory. It is important to select a suitable surgical approach according to the findings on radiological imaging and the clinical characteristics and general condition of the patients.
Biomechanical stability of lower cervical spine immediately after discectomy with grafting
Authors: Yin De‐zhen , Xin Xiao‐tang , Yang Rui , Shi Yu‐peng , Shen Hui‐yong
Published: April 2011

Objective:  Anterior cervical discectomy is commonly used to treat radiculopathy and myelopathy. Although the size of the implanted graft may influence the clinical outcome of anterior reconstruction of the cervical spine, the ideal graft height remains arguable. The objective of the current study was to study the interrelations of graft height and immediate biomechanical stability in an anterior cervical discectomy model.

Methods:  Six fresh‐frozen human cadaver cervical spines (C1–T1) were tested in five sequential states. The first state tested was the “normal” state (specimens with intact discs). The other four states were tested after C5–C6 discectomy by the Smith‐Robinson graft technique, using graft thicknesses of 100%, 120%, 140%, and 160% of the baseline height. The baseline height was defined as the intervertebral disc height of C5–C6 at the intact stage. Intervertebral segment flexion, extension, bending and rotation of C5–C6 were recorded using a 3D laser scanner and analyzed using Geomagic Studio 5.0 software.

Results:  Bone grafting at 100% baseline height after discectomy provided the least stability and the greatest movement range. With increasing height of grafts, the movement range of the cervical spine declined. Immediate stability of the operated segments was significantly increased by grafting with 140% and 160% baseline heights compared to the baseline height condition.

Conclusions:  Strut‐graft with appropriate distraction after Smith‐Robinson anterior cervical discectomy plays an important role in the whole immediate biomechanical stability of the lower cervical spine. A graft height of 40% greater than baseline may be ideal after single discectomy in clinical practice.
Novel sulfobutyl ether cyclodextrin gradient leads to highly active liposomal irinotecan formulation
Authors: Li ChunLei , Cui JingXia , Wang CaiXia , Li YanHui , Zhang Lan , Xiu Xian , Li YongFeng , Wei Na , Zhang Li , Wang Ping
Published: April 2011

Objectives

Liposomal delivery of irinotecan could provide protection against drug hydrolysis, deliver more active lactone form to tumours and prolong irinotecan exposure time. Nevertheless, conventional drug-loading technologies have typically resulted in undesired drug retention properties. To resolve the problem, a modified gradient loading method was developed and the resulting formulations were evaluated in a systemic manner.

Methods

Irinotecan was loaded into liposomes using a novel sulfobutyl ether beta-cyclodextrin (sbe-CD) gradient. The effect of drug-to-lipid ratio (D/L) and polyethylene glycol (PEG) grafting density were investigated. Drug release experiments were performed in ammonium-containing medium based on the fluorescence dequenching phenomenon of irinotecan. Pharmacokinetic studies were performed in normal balb/c mice treated with different formulations. To compare the anti-tumour effect of different formulations, an RM-1 prostate cancer model was used. Acute toxicity studies were performed in healthy female c57 mice.

Key findings

Irinotecan could be encapsulated into liposomes with > 90% loading efficiency at a high drug-to-lipid mass ratio (> 0.5). In-vitro release experiments revealed that sbe-CD anion was more able to retain irinotecan than sulfate. Moreover, the elevated D/L ratio elicited decreased drug release kinetics. Both trends had also been observed when the effects of anions and D/L ratio on half-life of irinotecan were assessed. Pegylated liposomal irinotecan loaded with sbe-CD/triethylammonium gradient had irinotecan half-life values ranging from 9.4 to 13.1 h, surpassing vesicles prepared by the triethylammonium sulfate method (∼4.5 h). In the RM-1 tumour model, all the liposomal irinotecan formulations were more therapeutically active than free irinotecan and the formulation with a high D/L ratio was the most efficacious. Moreover, the high D/L formulation might be less toxic than free irinotecan based on acute toxicity studies.

Conclusions

The novel sbe-CD gradient could mediate effective irinotecan loading and improve irinotecan retention, thus resulting in highly active liposomal irinotecan formulations. The improvement in drug retention might be associated with the formation of complicated aggregates inside vesicles.
Laser Beam Jitter Control Using Recursive-Least-Squares Adaptive Filters
Authors: Yoon Hyungjoo , Bateman Brett E. , Agrawal Brij N.
Published: April 2011

The primary focus of this research is to develop and implement control schemes for combined broadband and narrowband disturbances to optical beams. The laser beam jitter control testbed developed at the Naval Postgraduate School is used for development of advanced jitter control techniques. First, we propose a least quadratic Gaussian feedback controller with integrator for cases when only the error signal (the difference between the desired and the actual beam positions) is available. An anti-notch filter is also utilized to attenuate a vibrational disturbance with a known frequency. Next, we develop feedforward adaptive filter methods for cases when a reference signal, which is highly correlated with the jitter disturbance, is available. A filtered-X recursive least-squares algorithm with an integrated bias estimator is proposed to deal with a constant bias disturbance. Finally, experimental results are provided to validate and compare the performance of the developed control techniques. The designed adaptive filter has a simple structure but shows good jitter rejection performance, thanks to the use of a reference signal.
A Frequency Domain Finite Element Approach for Three-Dimensional Gear Dynamics
Authors: Cooley Christopher G. , Parker Robert G. , Vijayakar Sandeep M.
Published: April 2011

A finite element formulation for the dynamic response of gear pairs is proposed. Following an established approach in lumped parameter gear dynamic models, the static solution is used as the excitation in a frequency domain solution of the finite element vibration model. The nonlinear finite element/contact mechanics formulation provides an accurate calculation of the static solution and average mesh stiffness that are used in the dynamic simulation. The frequency domain finite element calculation of dynamic response compares well with numerically integrated (time domain) finite element dynamic results and previously published experimental results. Simulation time with the proposed formulation is two orders of magnitude lower than numerically integrated dynamic results. This formulation admits system level dynamic gearbox response, which may include multiple gear meshes, flexible shafts, rolling element bearings, housing structures, and other deformable components.