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Mycophenolic acid is an immunosuppressant administered as a bioavailable ester, mycophenolate mofetil. The pharmacokinetics of mycophenolic acid have been reported to be variable. Accurate measurement of concentrations of this drug could be important to adjust doses. The aim of this study was to compare the enzyme-multiplied immunoassay technique (EMIT [Dade Behring; San Jose, CA, U.S.A.]) for mycophenolic acid with a high-performance liquid chromatographic (HPLC) assay using samples collected from renal transplant recipients. The HPLC assay used solid phase extraction and a C18 stationary phase with ultraviolet (UV) detection (254 nm). The immunoassay required no manual sample preparation. Plasma samples (n=102) from seven patients, collected at various times after a dose, were analyzed using both methods. Both assays fulfilled quality-control criteria. Higher concentrations were consistently measured in patient samples when using EMIT. The mean (+/-standard deviation [SD]) bias (EMIT-HPLC) was 1.88+/-0.86 mg/L. The differences in concentrations were higher in the middle of a dosage interval, suggesting that a metabolite might have been responsible for overestimation. Measurement of glucuronide concentrations by HPLC demonstrated only a weak correlation between assay differences and glucuronide concentrations. If the crossreacting substance is active, EMIT could provide a superior measure of immunosuppression; if inactive, further work is needed to improve antibody specificity. In conclusion, it was found that EMIT overestimates the concentration of mycophenolic acid in plasma samples from renal transplant recipients compared with HPLC analysis.

Deux etudes paralleles furent conduites pour etudier la validite de l'auto-evaluation d'un apprentissage, l'une utilisant un programme d'aide a l'entretien structure de selection pour etudiants diplomes, l'autre un programme d'entrainement a la securite dans une grande entreprise industrielle. Les deux etudes inclurent un pre-test retrospectif et un post-test standard (ce qui veut dire que les sujets evaluaient leurs competences avant et apres l'apprentissage). A une recherche anterieure sur la validite des auto-evaluations d'apprentissage, furent ajoutees: (1) une interrogation vis-a-vis de l'effet du decalage dans le temps sur la validite de l'auto-evaluation ; (2) une inclusion de la comparaison des estimations de l'importance de l'effet d'apprentissage derivees des auto-evaluations et de mesures objectives; (3) une analyse des correlations intra et inter sujets. L'effet temps de l'auto-administration fut manipule experimentalement pour determiner si faire remplir les auto-rapports apres l'apprentissage generait moins de validite que d'attendre que les sujets aient l'opportunite d'appliquer leurs nouveaux acquis. Les resultats indiquent un effet limite de l'utilisation des intruments d'auto-evaluation, sans regard pour la date d'administration du questionnaire. Tandis que les estimations de l'effet dimension fondees sur l'auto-evaluation etaient semblables a celles derivees de mesures objectives, intra et inter correlations etaient faibles et sans consistance.

We evaluated the MEIA II with blood samples with added tacrolimus (3.0, 5.0, 11.0, and 22.0 μg/L). The assay had acceptable recoveries (99–103%) and intraday imprecision (

Two HPLC-UV assays are reported here: one is a rapid assay for mycophenolic acid (MPA) and the other is a simultaneous assay for MPA and its metabolite mycophenolic acid glucuronide (MPAG). For both methods, plasma samples (500 microl) with added internal standard were acidified and extracted using C18 solid-phase extraction cartridges. Chromatographic separation was achieved on a C18 Novapak column using a mobile phase consisting of methanol-0.05% orthophosphoric acid (40:60, v/v) for the rapid MPA assay and 30:70 for the simultaneous MPA and MPAG assay. The assays were linear over the ranges 0.1 to 50.0 mg/l for MPA and 2.8 to 225.8 mg/l for MPAG. Mean absolute recovery for all analytes was >99%. These methods are suitable for therapeutic drug monitoring and pharmacokinetic studies.

The accuracy and imprecision of three assays used for therapeutic monitoring of tacrolimus were tested using blood-containing weighed-in amounts of the drug, an enzyme-linked immunosorbent assay (ELISA), a microparticle enzyme immunoassay (MEIA I), and a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS2) assay. Accuracy was acceptable for the HPLC-MS2 assay at all concentrations tested (10% deviation) and for the ELISA at 1.0 and 4.0 microg/l. Accuracy was not acceptable for the ELISA at 15.0 and 50.0 microg/l or for the MEIA I at all concentrations tested. Imprecision was acceptable for the HPLC-MS2 assay at all concentrations tested (coefficient of variation10%), for the ELISA at 15.0 and 50.0 microg/l, and for the MEIA I at 15.0 and 50.0 microg/l. Imprecision was not acceptable for the ELISA at 1.0 and 4.0 microg/l or for the MEIA I at 1.0 and 4.0 microg/l. This assessment with weighed-in amounts of tacrolimus verified the HPLC-MS2 assay as a reference method. The performance of the two immunoassays with HPLC-MS2 was then compared in the clinical setting using blood from patients with liver (n = 30) and renal (n = 37) transplants. In the liver transplant group (127 samples), the range of tacrolimus concentrations measured by HPLC-MS2, ELISA, and MEIA I was 1.9 to 31.8, 2.1 to 35.0, and less than 0.1 to 36.5 mg/l, respectively. In the renal transplant group (129 samples), the ranges were 1.7 to 26.1, 1.9 to 24.4, and 0.9 to 28.5 microg/l, respectively. Compared with the HPLC-MS2, the ELISA had minimal bias (0.1 to 0.2 microg/l) but unacceptable variability in values (SD13%). The MEIA I had unacceptable bias (1.7-1.8 microg/l) and variability (SD23%). These data indicated that neither the ELISA nor MEIA I is interchangeable with HPLC-MS2. Moreover, in view of the current trend to reduce the therapeutic dose of tacrolimus, quantitative results using the MEIA I would not be obtainable during therapeutic drug monitoring in some patients in whom effective therapeutic concentrations can be less than 5.0 microg/l.

A high-performance liquid chromatography–atmospheric pressure chemical ionization–tandem mass spectrometry (HPLC–APCI–MS/MS) reference method for the quantitation of aldosterone in serum and plasma has been developed. Samples were extracted with dichloromethane/diethyl ether, containing flumethasone as internal standard (IS). Chromatography was performed on a phenyl column using 50 m m ammonium formate (pH 7.1)/methanol (50/50, v/v) as mobile phase. Analysis was in negative-ionization mode by selected reaction monitoring (aldosterone m / z 359.2 → 331.2; IS m / z 455.0 → 379.0). The assay was linear over the range 15–500 pg/mL, with limits of detection and quantitation of 10 and 15 pg/mL, respectively. Imprecisions of the assay at 15, 20, 150, and 450 pg/mL were 18.5, 8.8, 10.6, and 9.5%, respectively. The accuracy of the method ranged from 93.1 to 98.9% with absolute recoveries between 84.0 and 91.3% (aldosterone) and 88.0 and 92.3% (IS). We present a case study of a patient admitted, with suspected primary hyperaldosteronism, on the basis of a high radioimmunoassay (RIA) aldosterone concentration. The results suggest that RIA was unreliable, causing unnecessary patient discomfort and a costly 6-day hospital stay. The specific HPLC–API–MS/MS assay described offers the sensitivity and accuracy required to assess abnormal aldosterone production in hypertensive patients.

We have previously reported the placental metabolism of prednisolone to prednisone, 20alpha- and beta-dihydroprednisone and 20beta-dihydroprednisolone. In this study, the disposition of cortisol was investigated in vitro in the dual perfused, isolated human placental lobule after the addition of cortisol (1.2 micromol, n = 3 and 12 micromol, n = 4) to the maternal compartment. Analysis of 5 h maternal and fetal perfusate samples by high performance liquid chromatography-electrospray-tandem mass spectrometry (HPLC-ESI-MS/MS) revealed that cortisol was mainly metabolized to cortisone, but a significant production of 20alpha-dihydrocortisone, 20beta-dihydrocortisone, 20alpha-dihydrocortisol and 20beta-dihydrocortisol was also detected. Saturability of metabolism but not transfer was demonstrated. Metabolism was eliminated by co-perfusion with the potent 11beta-hydroxysteroid dehydrogenase (11beta-HSD) enzyme inhibitor 18beta-glycyrrhetinic acid (GA). The disposition of GA was analysed using HPLC-atmospheric pressure chemical ionisation-MS/MS (HPLC-APCI-MS/MS). GA was found to transfer from the maternal to the fetal circulations without detectable metabolism during 6 h of perfusion.

Summary A great deal of the literature on U.S. crude-oil supply claims that supplies are rapidly depleting. Newer prediction models have become fairly sophisticated but still lack adequate treatment of the physics of oil production and effects of technology. This paper addresses these issues and develops a model that is much less pessimistic and broader in range. Introduction Hubbert,1 who first began publishing his ideas in the 1950's, probably initiated the trend of claiming that supplies are rapidly depleting with the notion that U.S. crude-oil production would behave like a bell-shaped curve (Fig. 1). In spite of his lack of defensible theory, Hubbert used this reasoning to conclude the conterminous U.S. (e.g., not including Alaska) would produce no more than 170 billion bbl. Other, more contemporary, analysts perpetuate this notion with forecasts founded on similar principles.2,3 Four basic factors affect oil production:physics,economics,technology, andthe oil still in the ground. The model developed here incorporates these factors by use of basic production theory and multivariate regression analysis. The laws of physics require oil production to decline over time. Eq. 1, which can be derived from these laws, is commonly used to model this decline.4Equation (1) Proved reserves, Q, are calculated by determining the area beneath this curve over the anticipated life of the production, T. This relationship is shown byEquation (2a) for large T, andEquation (2b) for the general case. Note that proved reserves can be approximated by dividing the initial production, qi, by the decline rate, di, if a sufficiently long time interval, T, is assumed. Eq. 2b, for the general case, has been rearranged by solving for the decline rate. This relationship between production, decline rates, and proved reserves is powerful for several reasons.

A reversed-phase high-performance liquid chromatography-electrospray-tandem mass spectrometry assay (HPLC-ESI-MS/MS) was developed to quantitate cortisol, cortisone, 20 alpha- and beta-dihydrocortisol, 20 alpha- and beta-dihydrocortisone, tetrahydrocortisol, and tetrahydrocortisone. The technique was used to analyze perfusate from the isolated human placental lobule for cortisol and its metabolites. Analytes were prepared from the perfusion medium using C18 solid-phase extraction cartridges. The internal standard for the analyses was 6 alpha-methylprednisolone. Chromatography was performed on a Novapak C18 column at ambient temperature using 53% methanol and 47% 10 mM ammonium formate buffer (pH 4.0) as mobile phase, at a flow rate of 80 microL/min. A PE-SCIEX API III triple quadrupole instrument was used for mass spectrometric detection. An ionspray (pneumatically assisted electrospray) interface was used in negative and positive ionization mode. The assay was linear over the range 100-2000 micrograms/L for each analyte. The instrumental limit of detection was 50 pg. Assay imprecision at 400 and 800 micrograms/L wasor = 10% (total coefficient of variation). Accuracy ranged between 83.2% for 20 beta-dihydrocortisone to 102.6% for cortisone. Recovery of 1000 micrograms/L analyte ranged from 91.3% for cortisone to 109.7% for tetrahydrocortisol.

Using random amplified polymorphic DNA (RAPD) analysis we assessed the genetic relationships between 16 accessions and cultivars of lentil (Lens culinaris ssp. culinaris) in the Australian lentil breeding program. All lines exhibited polymorphism with a maximum dissimilarity value of 0.36. This indicated a limited degree of genetic variation. Polymerase chain reaction (PCR) with primers based on the flanking regions of the 5S rRNA gene from Pisum sativum amplified the non-translated spacer (NTS) region from within the 5S rRNA gene of Lens. Three distinct amplification banding patterns differentiated between restricted genomic DNA of Lens spp. L. culinaris ssp. culinaris and L. culinaris ssp. orientalis shared similar markers of two distinctly different NTS sizes. L. nigricans and L. odemensis shared the same amplification pattern of a single sized NTS region. However, L. ervoides contained two separate sizes of NTS, distinct from other Lens species. In an effort to widen the genetic base of cultivated lentil, these species-specific molecular markers may be used to follow potential introgression between species.

Inheritance of resistance to anthracnose caused by Colletotrichum capsici (Syd.) Butler & Bisby was studied in interspecific Capsicum populations derived from a cross between a Thai elite cultivar Capsicum annuum L.‘Bangchang’ and a resistant line C. chinense Jacq.‘PBC932′. The resistance was assessed by measuring lesion area per fruit area (LFA) on detached chili fruits, using a laboratory-based injection inoculation. Nil symptoms resembling the resistant parent ‘PBC932’ were also identified in the progeny F2 and BC1 populations. Segregation of resistance (nil LFA) and susceptibility in the F2 fitted a 1: 3 Mendelian ratio, indicating that resistance was responsible by a single recessive gene. The segregation of the trait in the testcrosses in both BC1s also confirmed the 1: 3 gene segregating model as found in the F2.

Technologies that measure human nonverbal behavior have existed for some time, and their use in the analysis of social behavior has become more popular following the development of sensor technologies that record full-body movement. However, a standardized methodology to efficiently represent and analyze full-body motion is absent. In this article, we present automated measurement and analysis of body motion (AMAB), a methodology for examining individual and interpersonal nonverbal behavior from the output of full-body motion tracking systems. We address the recording, screening, and normalization of the data, providing methods for standardizing the data across recording condition and across subject body sizes. We then propose a series of dependent measures to operationalize common research questions in psychological research. We present practical examples from several application areas to demonstrate the efficacy of our proposed method for full-body measurements and comparisons across time, space, body parts, and subjects.

Nonsmall cell lung cancer (NSCLC) accounts for 85% of lung cancers, and is subdivided into two major histological subtypes: adenocarcinoma (ADC) and squamous cell carcinoma (SCC). There is an unmet need to further subdivide NSCLC according to distinctive molecular features that may be associated with responsiveness to therapies. Four primary tumor-derived xenograft proteomes (two-each ADC and SCC) were quantitatively compared by using a super-SILAC labeling approach together with ultrahigh-resolution MS. Proteins highly differentially expressed in the two subtypes were identified, including 30 that were validated in an independent cohort of 12 NSCLC primary tumor-derived xenograft tumors whose proteomes were quantified by an alternative, label-free shotgun MS methodology. The 30-protein signature contains metabolism enzymes including phosphoglycerate dehydrogenase, which is more highly expressed in SCC, as well as a comprehensive set of cytokeratins and other components of the epithelial barrier, which is therefore distinctly different between ADC and SCC. These results demonstrate the utility of the super-SILAC method for the characterization of primary tissues, and compatibility with datasets derived from different MS-based platforms. The validation of proteome signatures of NSCLC subtypes supports the further development and application of MS-based quantitative proteomics as a basis for precision classifications and treatments of tumors. All MS data have been deposited in the ProteomeXchange with identifier PXD000438 (http://proteomecentral.proteomexchange.org/dataset/PXD000438).

The act of conducting an insider attack carries with it cognitive and social challenges that may affect an offender's day-to-day work behavior. We test this hypothesis by examining the language used in e-mails that were sent as part of a 6-hr workplace simulation. The simulation involved participants (N = 54) examining databases and exchanging information as part of a four-stage organized crime investigation. After the first stage, 25% of the participants were covertly incentivized to act as an “insider” by providing information to a provocateur. Analysis of the language used in participants' e-mails found that insiders became more self-focused, showed greater negative affect, and showed more cognitive processing compared to their coworkers. At the interpersonal level, insiders showed significantly more deterioration in the degree to which their language mimicked other team members over time. Our findings demonstrate how language may provide an indirect way of identifying employees who are undertaking an insider attack. (PsycINFO Database Record (c) 2013 APA, all rights reserved)

Ascochyta rabiei is the most significant foliar disease of chickpea (Cicer arietinum) worldwide, and can cause both yield loss and reduced seed quality. Significant mean disease score differences were observed from the reactions among a collection of Ascochyta rabiei isolates and chickpea hosts at both seedling and maturity growth stages (P

The ANKS1A gene product, also known as Odin, was first identified as a tyrosine-phosphorylated component of the epidermal growth factor receptor network. Here we show that Odin functions as an effector of EGFR recycling. In EGF-stimulated HEK293 cells tyrosine phosphorylation of Odin was induced prior to EGFR internalization and independent of EGFR-to-ERK signaling. Over-expression of Odin increased EGF-induced EGFR trafficking to recycling endosomes and recycling back to the cell surface, and decreased trafficking to lysosomes and degradation. Conversely, Odin knockdown in both HEK293 and the non-small cell lung carcinoma line RVH6849, which expresses roughly 10-fold more EGF receptors than HEK293, caused decreased EGFR recycling and accelerated trafficking to the lysosome and degradation. By governing the endocytic fate of internalized receptors, Odin may provide a layer of regulation that enables cells to contend with receptor cell densities and ligand concentration gradients that are physiologically and pathologically highly variable.

We test the common assumption that information ‘rich’ contexts lead to more accurate personality judgments than information ‘lean’ contexts. Pairs of unacquainted students rendered judgments of one another's personalities after interacting in one of three, increasingly rich, contexts: Internet ‘chat’, telephone, or face-to-face. Accuracy was assessed by correlating participants' judgments with a measure of targets' personalities that averaged self and informant ratings. As predicted, the visible traits of extraversion and conscientiousness were judged more accurately than the less visible traits of neuroticism and openness. However, judgment accuracy also depended on context. Judgments of extraversion and neuroticism improved as context richness increased (i.e., from Internet ‘chat’ to face-to-face), whereas judgments of conscientiousness and openness improved as context richness decreased (i.e., from face-to-face to Internet ‘chat’). Our findings suggest that context richness shapes not only the availability of personality cues but also the relevance of cues in any given context.

The capacity of liquid chromatography-tandem mass spectrometry (LC-MS2) to detect and define individual components in a complex mixture has been utilized to develop a quantitative assay of the potent immunosuppressant drug, tacrolimus. Trough blood concentrations were measured in 175 samples obtained over several weeks after liver transplantation from seven patients. The assay was linear over the range of 0.2 to 100 micrograms/L. Imprecision was

The current approach for therapeutic drug monitoring in renal transplant recipients receiving mycophenolate mofetil (MMF) is measurement of total mycophenolic acid (MPA) concentration. Because MPA is highly bound, during hypoalbuminemia the total concentration no longer reflects the free (pharmacologically active) concentration. The authors investigated what degree of hypoalbuminemia causes a significant change in protein binding and thus percentage free MPA. Forty-two renal transplant recipients were recruited for the study. Free and total concentrations of MPA (predose, and 1, 3, and 6 hours post-MMF dose samples) and plasma albumin concentrations were determined on day 5 posttransplantation. Six-hour area under the concentration-time curve (AUC(0-6)) values were calculated for free and total MPA, and percentage free MPA was determined for each patient. The authors found a significant relationship between low albumin concentrations and increased percentage free MPA (Spearman correlation = -0.54, P0.0001). Receiver operating characteristic (ROC) curve analysis was performed on the albumin versus percentage free MPA data. The cutoff value of albumin determined from the ROC analysis that differentiated normal from elevated percentage free MPA (defined asor = 3%) in this patient population was 31 g/L. At this cutoff value albumin was found to be a good predictor of altered free MPA percentage, with a sensitivity and specificity of 0.75 and 0.80, respectively, and an area under the ROC curve of 0.79. To rationalize MMF dosing regimens in hypoalbuminemic patients (plasma albuminor = 31 g/L), clinicians should consider monitoring the free MPA concentration.

Mass spectrometry-based technologies are increasingly utilized in drug discovery. Phosphoproteomics in particular has allowed for the efficient surveying of phosphotyrosine signaling pathways involved in various diseases states, most prominently in cancer. We describe a phosphotyrosine-based proteomics screening approach to identify signaling pathways and tyrosine kinase inhibitor targets in highly tumorigenic human lymphoma-like primary cells. We identified several receptor tyrosine kinase pathways and validated SRC family kinases (SFKs) as potential drug targets for targeted selection of small molecule inhibitors. BMS-354825 (dasatinib) and SKI-606 (bosutinib), second and third generation clinical SFK/ABL inhibitors, were found to be potent cytotoxic agents against tumorigenic cells with low toxicity to normal pediatric stem cells. Both SFK inhibitors reduced ERK1/2 and AKT phosphorylation and induced apoptosis. This study supports the adaptation of high-end mass spectrometry techniques for the efficient identification of candidate tyrosine kinases as novel therapeutic targets in primary cancer cell lines.

Molecular markers were used to characterise sugarcane intergeneric hybrids between S. officinarum and E. arundinaceus. Very simple diagnostic tools for hybrid identification among the progeny were derived from isozyme electrophoresis and a sequence-tagged PCR. Two enzyme systems (GOT and MDH B) and PCR amplification revealing spacer-size variation in the 5s-rDNA cluster were found most convenient. Specific characterisation of the two genomic components was possible using RFLP and in situ hybridisation. The strong molecular differentiation between S. officinarum and E. arundinaceus allows the identification of numerous Erianthus-specific RFLP bands in the hybrids. Genomic DNA in situ hybridisation allows for the differentiation of the chromosomes contributed by S. officinarum and E. arundinaceus in chromosome preparations of the hybrids. In situ hybridisation with the 18s-5.8s-25s rDNA probe highlights the basic chromosome numbers in the two parental species. The potential of these techniques to monitor the Erianthus genome during the introgression process is discussed.

Organ transplant recipients have an increased risk of non-melanoma skin cancer (NMSC) development. Immunosuppressive agents, given to these patients to prevent organ rejection, are widely recognized to play a key role in the increased incidence of malignancy. However, different immunosuppressive agents, such as rapamycin and tacrolimus, which both prevent organ rejection, convey different risks of tumor formation. Using a UV-induced murine model of squamous cell carcinoma (SCC); HPV38 E6E7, we aim to determine whether these discrepancies are due to differences in the mechanism of immune suppression, in contrast to the much discussed direct effects of these drugs on tumor cells (i.e. immune-independent). Using customized rapamycin- and tacrolimus-incorporated feed to allow long-term administration, clinically relevant whole blood drug concentrations were obtained and validated using LC-MS/MS. Both systemic and local immunosuppression was functionally determined via adoptively transferred transgenic T-cell assay and skin allograft rejection profile, respectively. Notably however, preliminary data suggests phenotypic and functional differences of skin-residing T-cell subpopulations may exist when mice are treated with either rapamycin or tacrolimus, alluding to their potential role in the pathogenesis of NMSC. Short-term contact hypersensitivity responses (CHS) to OVA were abrogated in both rapamycin and tacrolimus-treated mice. However, prolonging the challenge phase enhanced the long-term CHS response in rapamycin-treated but not in tacrolimus-treated mice compared to normal feed controls. This enhanced response was correlated with an increased number of effector memory CD8+ T-cell population in the challenged ear skin. Using established chronic UV dosing schedules for SCC development in HPV38 E6E7 mice, tumor samples along with surrounding UV-exposed skin and fur-covered UV-protected skin samples were analyzed with FACs under the influence of these drugs. Preliminary data suggests that the formation of resident-memory CD8+ T-cells may be favored when treated with rapamycin, as higher percentages of CD8+ T-cells were present in the lesions of rapamycin-treated mice compared to tacrolimus and controls. In addition, LC-MS/MS analysis indicated that the concentration of rapamycin in the skin was significantly lower when compared to tacrolimus, whilst clinically relevant immunosuppressive concentrations of both drugs were maintained in the blood and kidneys. Through this project, we will expand our knowledge base regarding mechanisms of SCC formation in immunosuppressed patients. Citation Format: Ji-Won Jung, Paul J. Taylor, Fiona Simpson, Ian H. Frazer, James W. Wells. The impact of rapamycin and tacrolimus treatment on resident CD8+ T-cell populations in cutaneous squamous cell carcinoma. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B055.

The freshwater planarian Schmidtea mediterranea has been used in research for over 100 years, and is an emerging stem cell model because of its capability of regenerating large portions of missing body parts. Exteriorly, planarians are covered in mucous secretions of unknown composition, implicated in locomotion, predation, innate immunity, and substrate adhesion. Although the planarian genome has been sequenced, it remains mostly unannotated, challenging both genomic and proteomic analyses. The goal of the current study was to annotate the proteome of the whole planarian and its mucous fraction. The S. mediterranea proteome was analyzed via mass spectrometry by using multidimensional protein identification technology with whole-worm tryptic digests. By using a proteogenomics approach, MS data were searched against an in silico translated planarian transcript database, and by using the Swiss-Prot BLAST algorithm to identify proteins similar to planarian queries. A total of 1604 proteins were identified. The mucous subproteome was defined through analysis of a mucous trail fraction and an extract obtained by treating whole worms with the mucolytic agent N-acetylcysteine. Gene Ontology analysis confirmed that the mucous fractions were enriched with secreted proteins. The S. mediterranea proteome is highly similar to that predicted for the trematode Schistosoma mansoni associated with intestinal schistosomiasis, with the mucous subproteome particularly highly conserved. Remarkably, orthologs of 119 planarian mucous proteins are present in human mucosal secretions and tear fluid. We suggest planarians have potential to be a model system for the characterization of mucous protein function and relevant to parasitic flatworm infections and diseases underlined by mucous aberrancies, such as cystic fibrosis, asthma, and other lung diseases.

This study focused on the implementation of microsatellite markers to determine the diversity among elite inbred lines representing the Vietnamese maize breeding program. Genetic relationships were assessed using twenty loci to gain an understanding of the width of the program compared to other Asia programs, as well as develop a DNA fingerprint database. The PIC value of the 20 loci ranged from 0.10 to 0.83 with those containing a tetra-repeat the most informative (mean PIC = 0.60). The amount of genetic diversity among the lines assessed was similar to the levels identified in other Asian breeding programs. Future monitoring will be important to maintain genetic breadth of the Vietnamese program and minimize risks from narrowing in future targeted selective breeding strategies. This will be facilitated through implementation of the developed robust SSR-based DNA fingerprint database, which will also be used for true-to-type identification, hybrid confirmation and potential trait selection.

The authors examined the backgrounds and social experiences of female terrorists to test conflicting accounts of the etiology of this offending group. Data on 222 female terrorists and 269 male terrorists were examined across 8 variables: age at first involvement, educational achievement, employment status, immigration status, marital status, religious conversion, criminal activity, and activist connections. The majority of female terrorists were found to be single, young (

Background Serum hepcidin concentration is potentially affected by inflammation and iron stores in chronic liver disease (CLD), but little is known about the relationship between hepcidin and the degree of hepatic fibrosis. We investigated the potential role of serum hepcidin as a biomarker of advanced liver disease. Methods Serum hepcidin was measured in 332 adults with CLD of varying aetiologies, 45 healthy and 50 non-liver disease patient controls. Liver biopsy data were available for 228 CLD subjects. Results Hepcidin was decreased in CLD patients compared with non-liver disease patient controls (P similar to

Time and time again, the Department of Defense, the Executive Branch, and other government officials have claimed publicly that Guantanamo Bay detainees who have been released have “returned to the battlefield” where they have then been re-captured or killed. On January 13, 2009, during a press conference the Department of Defense provided its 43rd attempt to report on the number of detainees released from Guantanamo who returned to the battlefield. This latest report alleges that 61 detainees have returned to the battlefield. This report seeks to examine the last numbers.

The defining characteristic of an “urban legend” is its ability to perpetuate itself not only without factual support but also in the face of overwhelming factual evidence to the contrary. While it is unsurprising to find urban legends kept alive in the unmoderated precincts of the internet, it is shocking to discover one depicted as truth in an opinion written by a United States Supreme Court Justice.Just this month, however, Justice Antonin Scalia, in his dissent in Boumediene v. Bush, repeated the persistent yet false accusation that “[a]t least 30 of those prisoners hitherto released from Guantanamo Bay have returned to the battlefield.” His source for this misinformation was a year-old Senate Minority Report, which in turn was based on misinformation provided by the Department of Defense.Justice Scalia’s reliance upon the these sources would be more justifiable had this urban legend not (one would have thought) been permanently interred by later developments, including a Department of Defense press release issued in 2007, as well as hearings held before the House Foreign Relations Committee less than two weeks before Justice Scalia’s dissent was released.On December 10, 2007, the Seton Hall Center for Policy and Research issued a report entitled The Meaning of “Battlefield”: An Analysis of the Government’s Representations of “Battlefield Capture” and “Recidivism” of the Guantanamo Detainees, demonstrating that statements asserting that thirty former detainees had returned to the battlefield were inaccurate. Further developments, including recent hearings before Congress at which more information was provided by the Department of Defense, confirm that the claim there have been thirty recidivists is simply wrong and has no place in a reasoned public debate about Guantanamo.

Computerized crime linkage systems are meant to assist the police in determining whether crimes have been committed by the same offender. In this article, the authors assess these systems critically and identify four assumptions that affect the effectiveness of these systems. These assumptions are that (a) data in the systems can be coded reliably, (b) data in the systems are accurate, (c) violent serial offenders exhibit consistent but distinctive patterns of behavior, and (d) analysts have the ability to use the data in the systems to link crimes accurately. The authors argue that there is no compelling empirical support for any of the four assumptions, and they outline a research agenda for testing each assumption. Until evidence supporting these assumptions becomes available, the value of linkage systems will remain open to debate.

Ray blight disease of pyrethrum (Tanacetum cinerariifolium) is shown to be caused by more than one species of Stagonosporopsis. The Australian pathogen, previously identified as Phoma ligulicola var. inoxydabilis, represents a new species described as Stagonosporopsis tanaceti based on morphological characters and a five-gene phylogeny employing partial sequences of the actin, translation elongation factor 1-alpha, internal transcribed spacers and 5.8S of the nrDNA, 28S large subunit and beta-tubulin 2 gene sequences. Furthermore, the two varieties of Stagonosporopsis ligulicola are elevated to species level as S. chrysanthemi and S. inoxydabilis based on their DNA phylogeny and morphology.

This article examines the triple-interact, a cue-response-cue-response sequence that plays an important role in organizing negotiators’ behavior. Drawing on theories of interpersonal orientation and framing, we propose four types of triple-interact and make predictions about the relative occurrence and behavioral content of each type. We test these predictions by analyzing the conditional probabilities among behaviors in 29 conflict negotiations. Results show consistent use of the four types of triple-interact irrespective of time period and negotiation outcome. In order of decreasing frequency, negotiators used triple-interacts that reciprocated the current position, reoriented between cooperative and competitive positions, reframed perceptions of the current position, and restructured the interaction onto a new issue. However, the content of triple-interacts differed over time and outcome. In comparison to unsuccessful negotiations, successful negotiations involved triple-interacts that were more likely to end with integrative behavior and, during the second half of interaction, more likely to focus on substantive rather than relational issues.

Conflicting conclusions have been drawn from comparisons of high-performance liquid chromatography (HPLC) and the Abbott Diagnostics monoclonal fluorescence polarization immunoassay (mFPIA) for cyclosporin. The aim of this study was to compare whole blood cyclosporin A (CsA) concentrations measured by both mFPIA and HPLC in liver and heart transplant patients. One hundred and twenty-four liver and 62 heart transplant patient samples were assayed by both methods. Assay imprecision for both methods during the studies was < 7% over the range 150-800 micrograms/L. At an HPLC-determined concentration of 100 micrograms/L, mFPIA overestimated CsA by 60% (liver) and 77% (heart). At 300 micrograms/L, the overestimation was 40% (liver) and 45% (heart). On this basis, the mFPIA is not interchangeable with HPLC.

Relationships between specific supervisory support behaviours and training transfer among subordinates were investigated in the context of a team-building training programme. Ninety-nine employees who attended outdoor team-building training and their supervisors rated the extent to which trainees transferred each of twenty-one trained skills to the work-place. Additionally, trainees responded to an open-ended question regarding what, if anything, they applied from the training to the work-place. Ratings of transfer, provided by both trainees and their supervisors, and coded responses to the open-ended question indicated that: (1) most trainees transferred only a small to moderate amount of skills from the outdoor training; (2) the amount of training transfer varied across trainees; and (3) skills reportedly transferred the most concerned seeking and listening to the views and ideas of other team members. Trainees also rated whether their supervisors displayed each of twenty-seven specific supervisory supp...

Rhopalosiphum maidis (Fitch), Aphis gossypii Glover and Myzus persicae (Sultzer) transmitted the Australian sugarcane strain of sugarcane mosaic virus (SCMV‐SC) in a non‐persistent manner, whereas Melanaphis sacchari (Zehntner), Hysteroneura setariae (Thomas), Hyperomyzus lactucae (L.) and Aphis nerii Boyer de Fonscolombe did not transmit the virus. Calculated transmission rate per aphid was higher (12–16%) when sweetcorn was the source of SCMV‐SC than when sugarcane was the source (2–5%). M. sacchari (a non‐vector) and A. gossypii (a vector) were the most prevalent aphids caught on sticky yellow traps in the Isis and Bundaberg districts in 1989–91. Three vector species, A craccivora Koch, A. gossypii and R. maidis, were trapped mainly in spring, summer and autumn, and a fourth vector species, R. padi (L.) was trapped only in winter. Since vector species were active during all seasons, there is always potential for transmission of SCMV‐SC if host, virus and environmental factors are favourable. Copyright

Silver nitrate (AgNO), an inhibitor of the physiological action of ethylene, reduced cell growth, promoted ethylene production, increased the yield of protoplasts and reduced shoot regeneration from sugarcane heterogeneous cell suspension cultures. The increase in the rate of protoplast isolation from cultures treated with AgNO (0 to 59 μM) correlate with an increase in endogenous ethylene production by the cells. The addition to the culture medium of chemicals that either inhibited (aminoethoxyvinylglycine, AVG) or promoted (aminocyclopropane-1-carboxylic acid, ACC) ethylene biosynthesis did not alter the number of protoplasts isolated from these cultures. However, protoplasts were isolated with AVG in combination with AgNO even though ethylene production was inhibited. These results suggested that AgNO may be having another more direct effect on protoplast release. One such site may be the cell wall or on cell metabolism conditioning cells to release protoplasts after enzyme treatment.

Although the aldosterone/renin ratio (ARR) is the most reliable screening test for primary aldo-steronism, false positives and negatives occur. Dietary salt restriction, concomitant malignant or renovascular hypertension, pregnancy and treatment with diuretics (including spironolactone), dihydropyridine calcium blockers, angiotensin converting enzyme inhibitors, and angiotensin receptor antagonists can produce false negatives by stimulating renin. We recently reported selective serotonin reuptake inhibitors lower the ratio. Because potassium regulates aldosterone, uncorrected hypokalemia can lead to false negatives. Beta-blockers, alpha-methyldopa, clonidine, and nonsteroidal anti-inflammatory drugs suppress renin, raising the ARR with potential for false positives. False positives may occur in patients with renal dysfunction or advancing age. We recently showed that (1) females have higher ratios than males, and (2) false positive ratios can occur during the luteal menstrual phase and while taking an oral ethynylestradiol/drospirenone (but not implanted subdermal etonogestrel) contraceptive, but only if calculated using direct renin concentration and not plasma renin activity. Where feasible, diuretics should be ceased at least 6 weeks and other interfering medications at least 2 before ARR measurement, substituting noninterfering agents (e. g., verapamil slow-release±hydralazine and prazosin or doxazosin) were required. Hypokalemia should be corrected and a liberal salt diet encouraged. Collecting blood midmorning from seated patients following 2-4 h upright posture improves sensitivity. The ARR is a screening test only and should be repeated once or more before deciding whether to proceed to confirmatory suppression testing. Liquid chromatography-tandem mass spectrometry aldosterone assays represent a major advance towards addressing inaccuracies inherent in other available methods.

[Correction Notice: An erratum for this article was reported in Vol 17(1) of Journal of Occupational Health Psychology (see record 2011-29717-003). The affiliation of author Paul J. Taylor was incorrectly listed as University of Liverpool. The correct affiliation is Lancaster University. All versions of this article have been corrected.] Although safety-specific transformational leadership is known to encourage employee safety voice behaviors, less is known about what makes this style of leadership effective. We tested a model that links safety-specific transformational leadership to safety voice through various dimensions of trust. Data from 150 supervisor-employee dyads from the United Kingdom oil industry supported our predictions that the effects of safety-specific transformational leadership are sequentially mediated by affect-based trust beliefs and disclosure trust intentions. Moreover, we found that reliance trust intentions moderated the effect of disclosure: employees' disclosure intentions mediated the effects of affect-based trust on safety voice behaviors only when employees' intention to rely on their leader was moderate to high. These findings suggest that leaders seeking to encourage safety voice behaviors should go beyond “good reason” arguments and develop affective bonds with their employees

Colorectal cancer (CRC) is the second leading cause of death from cancer. The MET receptor tyrosine kinase and/or its ligand HGF are frequently amplified or overexpressed in CRC. It is known that tyrosine phosphorylated proteins are involved in progression and metastasis of colorectal cancer; however, little is known about the MET phospho-proteome in CRC. High resolution mass spectrometry was used to characterize immunoaffinity-purified, phosphotyrosine (pY)-containing tryptic peptides of the MET-expressing CRC cell model, DLD1. A total of 266 unambiguously identified pY sites spanning 168 proteins were identified. Quantification of mass spectrometry ion currents identified 161 pY sites, including many not previously linked to MET signaling, that were modulated in abundance by HGF stimulation. Overlay of these data with protein-protein interaction data sets suggested that many of the identified HGF-modulated phospho-proteins may be directly or indirectly associated with MET. Analysis of pY sequence motifs indicated a prevalence of Src family kinase consensus sequences, and reciprocal signaling between Src and MET was confirmed by using selective small molecule inhibitors of these kinases. Therefore, using quantitative phospho-proteomics profiling, kinase modulation by ligand and inhibitors, and data integration, an outline of the MET signaling network was generated for the CRC model.

Genomic libraries enriched for microsatellites from Colletotrichum capsici, one of the major causal agents of anthracnose disease in chilli pepper (Capsicum spp.), were developed using a modified hybridization procedure. Twenty-seven robust primer pairs were designed from microsatellite flanking sequences and were characterized using 52 isolates from three countries India, Sri Lanka and Thailand. Highest gene diversity of 0.857 was observed at the CCSSR1 with up to 18 alleles among all the isolates whereas the differentiation ranged from 0.05 to 0.45. The sequence-tagged microsatellite site markers developed in this study will be useful for genetic analyses of C. capsici populations.

Although researchers know much about the causes of aggression, they know surprisingly little about how aggression leads to violence or how violence is controlled. To explore the microregulation of violence, we conducted a systematic behavioral analysis of footage from closed-circuit television surveillance of public spaces. Using 42 incidents involving 312 people, we compared aggressive incidents that ended in violence with those that did not. Behaviors of antagonists and third parties were coded as either escalating or conciliatory acts. Results showed that third parties were more likely to take conciliatory actions than to escalate violence and that this tendency increased as group size increased. This analysis revealed a pattern of third-party behaviors that prevent aggression from becoming violent and showed that conciliatory behaviors are more successful when carried out by multiple third parties than when carried out by one person. We conclude by emphasizing the importance of collective third-party dynamics in understanding conflict resolution.

We conducted a survey of 89 randomly selected New Zealand organizations with at least 300 employees to determine 1) what purposes performance appraisal systems serve, 2) characteristics of those systems, and 3) any difficulties organizations have had in implementing them. Human resource directors indicated that appraisal information was used most often to give individual performance feedback. Links between appraisals and pay were widespread, but generally indirect and informal. In contrast to the emphasis of past research on rating errors and cognitive processes in performance evaluations , primary difficulties identified by these human resource directors were 1) managers failing to discuss and improve performance problems with subordinates, and 2) the setting of vague performance objectives. The most frequently cited change which organizations made and were considering making was simplifying appraisal forms and procedures. Ways in which organizations can improve how appraisal systems meet their primary o...

Rust resistance was shown to be highly heritable, and most genetic variance was shown to be additive. Thus, selection of rust-resistant parents should be effective in producing resistant progeny. Crosses between susceptible parents are rejected by the Bureau of Sugar Experiment Stations computerised system for choosing crosses, and this strategy has resulted in the planting of very few crosses with high rust susceptibility.

The inheritance of Fiji disease resistance in sugarcane was studied, so that strategies for breeding for resistance could be developed. Resistance was highly heritable and most of the genetic variance was additive when infection pressure was low to moderate. Infection pressure was very heavy in one experiment and this reduced discrimination between parent clones and families. The data were skewed and this affected statistical and genetical analyses which showed that non-additive genetic variance was high. In general, however, it was concluded that selection of resistant parents would produce families with resistant progeny. Some moderately susceptible families produced a small number of resistant progeny and, if these families have agronomic merit, the breeding strategy should enable such families to be planted. The computerised strategy adopted rejects crosses if the average susceptibility of the two parents is too high, and emphasises the use of more resistant parent clones. As some susceptible clones will be selected, clones are subjected to a field screening trial as soon as practicable. These strategies have reduced the percentage of susceptible clones in the population from 70–80% to 20–30%.