bluuebunny/crossref_metadata_2025 huggingface dataset:
Luciferase activity under direct ligand-dependent control of a muscarinic acetylcholine receptor
Authors: Thor Doreen , Le Duc Diana , Strotmann Rainer , Schöneberg Torsten
Published: May 2009

Background

Controlling enzyme activity by ligand binding to a regulatory domain of choice may have many applications e.g. as biosensors and as tools in regulating cellular functions. However, until now only a small number of ligand-binding domains have been successfully linked to enzyme activity. G protein-coupled receptors (GPCR) are capable of recognizing an extraordinary structural variety of extracellular signals including inorganic and organic molecules. Ligand binding to GPCR results in conformational changes involving the transmembrane helices. Here, we assessed whether ligand-induced conformational changes within the GPCR helix bundle can be utilized to control the activity of an integrated enzyme.

Results

As a proof of principle, we inserted the luciferase amino acid sequence into the third intracellular loop of the M3 muscarinic acetylcholine receptor. This fusion protein retained both receptor and enzyme function. Receptor blockers slightly but significantly reduced enzyme activity. By successive deletion mutagenesis the enzyme activity was optimally coupled to ligand-induced conformational helix movements.

Conclusion

Our results demonstrate that in engineered GPCR-enzyme chimeras, intracellular enzyme activity can be directly controlled by a GPCR serving as the extracellular ligand-binding domain.
Replication of porcine circoviruses
Authors: Faurez Florence , Dory Daniel , Grasland Béatrice , Jestin André
Published: May 2009

Porcine circoviruses are circular single-stranded DNA viruses that infect swine and wild boars. Two species of porcine circoviruses exist. Porcine circovirus type 1 is non pathogenic contrary to porcine circovirus type 2 which is associated with the disease known as Post-weaning Multisystemic Wasting Syndrome. Porcine circovirus DNA has been shown to replicate by a rolling circle mechanism. Other studies have revealed similar mechanisms of rolling-circle replication in plasmids and single-stranded viruses such as Geminivirus. Three elements are important in rolling-circle replication: i) a gene encoding initiator protein, ii) a double strand origin, and iii) a single strand origin. However, differences exist between viruses and plasmids and between viruses. Porcine circovirus replication probably involves a "melting pot" rather than "cruciform" rolling-circle mechanism.

This review provides a summary of current knowledge of replication in porcine circoviruses as models of the Circovirus genus. Based on various studies, the factors affecting replication are defined and the mechanisms involved in the different phases of replication are described or proposed.
Transduction of rat pancreatic islets with pseudotyped adeno-associated virus vectors
Authors: Craig Anthony T , Gavrilova Oksana , Dwyer Nancy K , Jou William , Pack Stephanie , Liu Eric , Pechhold Klaus , Schmidt Michael , McAlister Victor J , Chiorini John A , Blanchette-Mackie E Joan , Harlan David M , Owens Roland A
Published: May 2009

Background

Pancreatic islet transplantation is a promising treatment for type I diabetes mellitus, but current immunosuppressive strategies do not consistently provide long-term survival of transplanted islets. We are therefore investigating the use of adeno-associated viruses (AAVs) as gene therapy vectors to transduce rat islets with immunosuppressive genes prior to transplantation into diabetic mice.

Results

We compared the transduction efficiency of AAV2 vectors with an AAV2 capsid (AAV2/2) to AAV2 vectors pseudotyped with AAV5 (AAV2/5), AAV8 (AAV2/8) or bovine adeno-associated virus (BAAV) capsids, or an AAV2 capsid with an insertion of the low density lipoprotein receptor ligand from apolipoprotein E (AAV2apoE), on cultured islets, in the presence of helper adenovirus infection to speed expression of a GFP transgene. Confocal microscopy and flow cytometry were used. The AAV2/5 vector was superior to AAV2/2 and AAV2/8 in rat islets. Flow cytometry indicated AAV2/5-mediated gene expression in approximately 9% of rat islet cells and almost 12% of insulin-positive cells. The AAV2/8 vector had a higher dependence on the helper virus multiplicity of infection than the AAV 2/5 vector. In addition, the BAAV and AAV2apoE vectors were superior to AAV2/2 for transducing rat islets. Rat islets (300 per mouse) transduced with an AAV2/5 vector harboring the immunosuppressive transgene, tgfβ1, retain the ability to correct hyperglycemia when transplanted into immune-deficient diabetic mice.

Conclusion

AAV2/5 vectors may therefore be useful for pre-treating donor islets prior to transplantation.
Neuroligin1: a cell adhesion molecule that recruits PSD-95 and NMDA receptors by distinct mechanisms during synaptogenesis
Authors: Barrow Stephanie L , Constable John RL , Clark Eliana , El-Sabeawy Faten , McAllister A Kimberley , Washbourne Philip
Published: May 2009

Background

The cell adhesion molecule pair neuroligin1 (Nlg1) and β-neurexin (β-NRX) is a powerful inducer of postsynaptic differentiation of glutamatergic synapses in vitro. Because Nlg1 induces accumulation of two essential components of the postsynaptic density (PSD) – PSD-95 and NMDA receptors (NMDARs) – and can physically bind PSD-95 and NMDARs at mature synapses, it has been proposed that Nlg1 recruits NMDARs to synapses through its interaction with PSD-95. However, PSD-95 and NMDARs are recruited to nascent synapses independently and it is not known if Nlg1 accumulates at synapses before these PSD proteins. Here, we investigate how a single type of cell adhesion molecule can recruit multiple types of synaptic proteins to new synapses with distinct mechanisms and time courses.

Results

Nlg1 was present in young cortical neurons in two distinct pools before synaptogenesis, diffuse and clustered. Time-lapse imaging revealed that the diffuse Nlg1 aggregated at, and the clustered Nlg1 moved to, sites of axodendritic contact with a rapid time course. Using a patching assay that artificially induced clusters of Nlg, the time course and mechanisms of recruitment of PSD-95 and NMDARs to those Nlg clusters were characterized. Patching Nlg induced clustering of PSD-95 via a slow palmitoylation-dependent step. In contrast, NMDARs directly associated with clusters of Nlg1 during trafficking. Nlg1 and NMDARs were highly colocalized in dendrites before synaptogenesis and they became enriched with a similar time course at synapses with age. Patching of Nlg1 dramatically decreased the mobility of NMDAR transport packets. Finally, Nlg1 was biochemically associated with NMDAR transport packets, presumably through binding of NMDARs to MAGUK proteins that, in turn, bind Nlg1. This interaction was essential for colocalization and co-transport of Nlg1 with NMDARs.

Conclusion

Our results suggest that axodendritic contact leads to rapid accumulation of Nlg1, recruitment of NMDARs co-transported with Nlg1 soon thereafter, followed by a slower, independent recruitment of PSD-95 to those nascent synapses.
IL-18 and IL-33 elicit Th2 cytokines from basophils via a MyD88- and p38α-dependent pathway
Authors: Kroeger Kelly M , Sullivan Brandon M , Locksley Richard M
Published: May 2009

Signal identified by which basophils express cytokines involved in allergy independent of the more classically studied basophil activation pathway induced by cross-linking of surface IgE receptors.

IL-4 and IL-13 are instrumental in the development and progression of allergy and atopic disease. Basophils represent a key source of these cytokines and produce IL-4 and IL-13 when stimulated with IL-18, a member of the IL-1 family of cytokines. Comparative analyses of the effects of caspase-1-dependent IL-1 family cytokines on basophil IL-4 and IL-13 production have not been performed, and the signaling pathway proteins required for FcεRI-independent Th2 cytokine production from basophils remain incompletely defined. Using mouse bone marrow-derived cultured basophils, we found that IL-4 and IL-13 are produced in response to IL-18 or IL-33 stimulation. IL-18- or IL-33-mediated Th2 cytokine production is dependent on MyD88 and p38α signaling proteins. In addition, basophil survival increased in the presence of IL-18 or IL-33 as a result of increased Akt activation. Studies in vivo confirmed the potency of IL-18 and IL-33 in activating cytokine release from mouse basophils.
Pancreatic lipase-related protein 2 (PLRP2) induction by IL-4 in cytotoxic T lymphocytes (CTLs) and reevaluation of the negative effects of its gene ablation on cytotoxicity
Authors: Alves Bryce N , Leong Jeff , Tamang David L , Elliott Viki , Edelnant Jillian , Redelman Doug , Singer Cherie A , Kuhn Andrew R , Miller Rita , Lowe Mark E , Hudig Dorothy
Published: May 2009

Ablation of the gene for the lipase PLRP2 reduces perforin-dependent CTL cytotoxicity, even under conditions when PLRP2 is unexpressed, raising serious doubts about PLRP2s function in cytotoxicity.

Pancreatic lipase-related protein 2 (PLRP2) is induced by IL-4 in vitro in cytotoxic T lymphocyte (CTL) clones and CTLs from immunized wild-type (WT) PLRP2+/+ are more cytotoxic than PLRP2−/− CTLs, suggesting to previous investigators that the lipase PLRP2 might support CTL functions. Here, we further evaluate PLRP2 in CTLs. We found that PLRP2 was optimally induced in splenocytes by 3.5 × 10−8 M IL-4 by day 6 after activation and was restricted to CD8+ T cells. PLRP2 mRNA was detected inconsistently (and at low levels) after activation in the presence of IL-2. Cytotoxicity in 4 h 51Cr assays of WT CTLs was ∼3-fold the activity of PLRP2−/− CTLs cultured with IL-4 and, with IL-2, was unexpectedly ∼2 fold the activity of PLRP2−/− CTLs. Thus, PLRP2 gene ablation affected short-term (perforin-dependent) cytotoxicity, even under the IL-2 conditions. Other variables failed to account for the reduced cytotoxicity. Granzyme B levels, activation markers, and CD8+ T cell frequencies were similar for WT vs. PLRP2−/− CTLs (with either cytokine). Addition of rPLRP2 to IL-4 induced PLRP2−/− CTLs (or to cytotoxic granule extracts) failed to increase lysis, suggesting that the missing mediator is more than released PLRP2. Cytotoxicity of WT and PLRP2−/− CTLs was similar in 2-day tumor survival assays with IL-4, which can be mediated by perforin-independent mechanisms. We conclude that extracellular PLRP2 lipase is unable to directly augment the cytotoxicity that was lost by PLRP2 ablation and that after reevaluation, the question of what is PLRP2’s role in CD8 T cells is still unanswered.
Improving adaptive subtraction in seismic multiple attenuation
Authors: Huo Shoudong , Wang Yanghua
Published: May 2009

In seismic multiple attenuation, once the multiple models have been built, the effectiveness of the processing depends on the subtraction step. Usually the primary energy is partially attenuated during the adaptive subtraction if an [Formula: see text]-norm matching filter is used to solve a least-squares problem. The expanded multichannel matching (EMCM) filter generally is effective, but conservative parameters adopted to preserve the primary could lead to some remaining multiples. We have managed to improve the multiple attenuation result through an iterative application of the EMCM filter to accumulate the effect of subtraction. A Butterworth-type masking filter based on the multiple model can be used to preserve most of the primary energy prior to subtraction, and then subtraction can be performed on the remaining part to better suppress the multiples without affecting the primaries. Meanwhile, subtraction can be performed according to the orders of the multiples, as a single subtraction window usually covers different-order multiples with different amplitudes. Theoretical analyses, and synthetic and real seismic data set demonstrations, proved that a combination of these three strategies is effective in improving the adaptive subtraction during seismic multiple attenuation.
Relationship Between Age and Axillary Lymph Node Involvement in Women With Breast Cancer
Authors: Wildiers Hans , Van Calster Ben , van de Poll-Franse Lonneke V. , Hendrickx Wouter , Røislien Jo , Smeets Ann , Paridaens Robert , Deraedt Karen , Leunen Karin , Weltens Caroline , Van Huffel Sabine , Christiaens Marie-Rose , Neven Patrick
Published: May 2009

Purpose

To study the relation between the presence of axillary lymph node (LN) involvement and age in breast cancer.

Patients and Methods

The breast cancer database of the University Hospitals Leuven contains complete data on 2,227 patients with early breast cancer consecutively treated between 2000 and 2005. A multivariate piecewise logistic regression model was used to analyze LN involvement in relation to age at diagnosis. A similar analysis was then performed on a large, independent, population-based database from the Eindhoven Cancer Registry to investigate whether the effects of the Leuven model could be replicated.

Results

We observed a piecewise effect of age. That is, women up to 70 years of age were less likely to have positive LNs with increasing age (odds ratio per 10-year increase, 0.87). In contrast, older women were more likely to have positive LNs with increasing age. However, for older women, the effect of age interacted with tumor size (P = .0044), suggesting that increasing age is associated with increased risk of LN involvement, mainly in small tumors. These findings were replicated in the Eindhoven Cancer Registry database.

Conclusion

Axillary LN involvement varies with age at diagnosis; its probability decreases with increasing age up to the age of approximately 70 years, but increases again thereafter. However, this increase is mainly seen in smaller tumors and suggests a different behavior of small breast cancers in older adult patients. We hypothesize that decreased immune defense mechanisms, related with aging, may play a role in earlier invasion into LNs.
Adjuvant Hormonal Therapy Use Among Insured, Low-Income Women With Breast Cancer
Authors: Kimmick Gretchen , Anderson Roger , Camacho Fabian , Bhosle Monali , Hwang Wenke , Balkrishnan Rajesh
Published: May 2009

Purpose

Use of adjuvant hormonal therapy, which significantly decreases breast cancer mortality, has not been well described among poor women, who are at higher risk of cancer-related death. Here we explore use of adjuvant hormonal therapy in an insured, low-income population.

Methods

A North Carolina Cancer Registry–Medicaid linked data set was used. Women with hormone receptor–positive or unknown, nonmetastatic breast cancer, diagnosed between 1998 and 2002, were included. Main outcomes were (1) prescription fill within 1 year of diagnosis, (2) adherence (medication possession ratio), and (3) persistence (absence of a 90-day gap in prescription fills over 12 months).

Results

The population consisted of 1,491 women (mean age, 67 years). Sixty-four percent filled prescriptions. Predictors of prescription fill included the following: older age (odds ratio [OR], 1.01; P = .017), greater number of prescription medications (OR, 1.06; P < .001), nonmarried status (OR, 1.82; P = .001), higher stage (OR, 1.83; P < .001), positive hormone receptor status (positive v unknown, OR, 1.98; P < .001), not receiving adjuvant chemotherapy (OR, 1.74; P = .001), receipt of adjuvant radiation (OR, 1.55; P = .004), and treatment in a small hospital (OR, 1.49; P = .024). Adherence and persistence rates were 60% and 80%, respectively. Nonmarried status predicted greater adherence (OR, 1.90; P = .006) and persistence (OR, 1.75; P = .031).

Conclusion

Prescription fill, adherence, and persistence to adjuvant hormonal therapy among socioeconomically disadvantaged women are low. Improving use of adjuvant hormonal therapy may lead to lower breast cancer–specific mortality in this population.
Health-Related Quality of Life As a Survival Predictor for Patients With Localized Head and Neck Cancer Treated With Radiation Therapy
Authors: Meyer François , Fortin André , Gélinas Michel , Nabid Abdenour , Brochet François , Têtu Bernard , Bairati Isabelle
Published: May 2009

Purpose

To assess the added prognostic value for overall survival (OS) of baseline health-related quality of life (HRQOL) and of early changes in HRQOL among patients with localized head and neck cancer (HNC) treated with radiation therapy.

Patients and Methods

All 540 patients with HNC who participated in a randomized trial completed two HRQOL instruments before radiation therapy: the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) and the Head and Neck Radiotherapy Questionnaire. Six months after the end of radiation therapy, 497 trial participants again completed the two HRQOL instruments. During the follow-up, 179 deaths were observed. Multivariate Cox proportional hazards models were used to test whether HRQOL variables, baseline and change, provided additional prognostic value beyond recognized prognostic factors.

Results

The baseline EORTC QLQ-C30 physical functioning (PF) score was an independent predictor of OS. The hazard ratio (HR) associated with a 10-point increment in baseline PF was 0.87 (95% CI, 0.81 to 0.94). In multivariate models, the change in HRQOL was significantly associated with OS for most HRQOL dimensions. Among these, PF change was the strongest predictor. The magnitude of the association between PF change and survival decreased over time. At 1 year, the HR associated with a positive PF change of 10 points was 0.75 (95% CI, 0.68 to 0.83). After PF is taken into account, no other HRQOL variable was associated with survival.

Conclusion

Our findings indicate that both baseline PF and PF change provide added prognostic value for OS beyond established predictors in patients with HNC. Assessing HRQOL could help better predict survival of cancer patients.
Palliative Cancer Care a Decade Later: Accomplishments, the Need, Next Steps—From the American Society of Clinical Oncology
Authors: Ferris Frank D. , Bruera Eduardo , Cherny Nathan , Cummings Charmaine , Currow David , Dudgeon Deborah , JanJan Nora , Strasser Florian , von Gunten Charles F. , Von Roenn Jamie H.
Published: May 2009

Purpose

In 1998, the American Society of Clinical Oncology (ASCO) published a special article regarding palliative care and companion recommendations. Herein we summarize the major accomplishments of ASCO regarding palliative cancer and highlight current needs and make recommendations to realize the Society's vision of comprehensive cancer care by 2020.

Methods

ASCO convened a task force of palliative care experts to assess the state of palliative cancer care in the Society's programs. We reviewed accomplishments, assessed current needs, and developed a definition of palliative cancer. Senior ASCO members and the Board of Directors reviewed and endorsed this article for submission to Journal of Clinical Oncology.

Results

Palliative cancer care is the integration into cancer care of therapies that address the multiple issues that cause suffering for patients and their families and impact their life quality. Effective provision of palliative cancer care requires an interdisciplinary team that can provide care in all patient settings, including outpatient clinics, acute and long-term care facilities, and private homes. Changes in current policy, drug availability, and education are necessary for the integration of palliative care throughout the experience of cancer, for the achievement of quality improvement initiatives, and for effective palliative cancer care research.

Conclusion

The need for palliative cancer care is greater than ever notwithstanding the strides made over the last decade. Further efforts are needed to realize the integration of palliative care in the model and vision of comprehensive cancer care by 2020.
Phase II Multicenter Trial of Imatinib in 10 Histologic Subtypes of Sarcoma Using a Bayesian Hierarchical Statistical Model
Authors: Chugh Rashmi , Wathen J. Kyle , Maki Robert G. , Benjamin Robert S. , Patel Shreyaskumar R. , Myers Paul A. , Priebat Dennis A. , Reinke Denise K. , Thomas Dafydd G. , Keohan Mary L. , Samuels Brian L. , Baker Laurence H.
Published: May 2009

Purpose

The purpose of this trial was to assess the efficacy of imatinib in patients with one of 10 different subtypes of advanced sarcoma.

Patients and Methods

Eligible patients were treated daily with imatinib dosed at 300 mg twice a day (for body-surface area ≥ 1.5 m2). The primary end point was response (clinical benefit response [CBR]), defined as complete (CR) or partial response (PR) at 2 months, or stable disease, CR, or PR at 4 months. Rules for early termination within each disease type were based on a Bayesian hierarchical probability model (BHM) accounting for correlation of the responses of the 10 subtypes. Available tissue samples were analyzed for molecules within the KIT/platelet-derived growth factor receptor (PDGFR) signal transduction pathway.

Results

One hundred eighty-five assessable patients with one of 10 subtypes of sarcoma were treated. One CR and three PRs were achieved. A CBR was achieved in 28 patients treated overall and by subtype: two angiosarcomas (n = 16), 0 Ewing (n = 13), one fibrosarcoma (n = 12), six leiomyosarcomas (n = 29), seven liposarcomas (n = 31), three malignant fibrous histiocytomas (n = 30), five osteosarcomas (n = 27), one malignant peripheral-nerve sheath tumor (n = 7), 0 rhabdomyosarcoma (n = 2), and three synovial sarcomas (n = 22). Variable expression and mutations within the KIT/PDGFR pathway were observed.

Conclusion

This is the first phase II study of a new agent in sarcoma to include sufficient patients with each of the common histologic subtypes to permit generalizable conclusions. The BHM is an effective method for studying rare diseases and their subtypes, when it is reasonable to assume that their response rates are exchangeable. Although rare dramatic responses were seen, imatinib is not an active agent in advanced sarcoma in these subtypes.
Prognostic Importance of MN1 Transcript Levels, and Biologic Insights From MN1-Associated Gene and MicroRNA Expression Signatures in Cytogenetically Normal Acute Myeloid Leukemia: A Cancer and Leukemia Group B Study
Authors: Langer Christian , Marcucci Guido , Holland Kelsi B. , Radmacher Michael D. , Maharry Kati , Paschka Peter , Whitman Susan P. , Mrózek Krzysztof , Baldus Claudia D. , Vij Ravi , Powell Bayard L. , Carroll Andrew J. , Kolitz Jonathan E. , Caligiuri Michael A. , Larson Richard A. , Bloomfield Clara D.
Published: May 2009

Purpose

To determine the prognostic importance of the meningioma 1 (MN1) gene expression levels in the context of other predictive molecular markers, and to derive MN1 associated gene– and microRNA–expression profiles in cytogenetically normal acute myeloid leukemia (CN-AML).

Patients and Methods

MN1 expression was measured in 119 untreated primary CN-AML adults younger than 60 years by real-time reverse-transcriptase polymerase chain reaction. Patients were also tested for FLT3, NPM1, CEBPA, and WT1 mutations, MLL partial tandem duplications, and BAALC and ERG expression. Gene- and microRNA-expression profiles were attained by performing genome-wide microarray assays. Patients were intensively treated on two first-line Cancer and Leukemia Group B clinical trials.

Results

Higher MN1 expression associated with NPM1 wild-type (P < .001), increased BAALC expression (P = .004), and less extramedullary involvement (P = .01). In multivariable analyses, higher MN1 expression associated with a lower complete remission rate (P = .005) after adjustment for WBC; shorter disease-free survival (P = .01) after adjustment for WT1 mutations, FLT3 internal tandem duplications (FLT3-ITD), and high ERG expression; and shorter survival (P = .04) after adjustment for WT1 and NPM1 mutations, FLT3-ITD, and WBC. Gene- and microRNA-expression profiles suggested that high MN1 expressers share features with high BAALC expressers and patients with wild-type NPM1. Higher MN1 expression also appears to be associated with genes and microRNAs that are active in aberrant macrophage/monocytoid function and differentiation.

Conclusion

MN1 expression independently predicts outcome in CN-AML patients. The MN1 gene- and microRNA-expression signatures suggest biologic features that could be exploited as therapeutic targets.
CUT!... Flannery O'Connor's Apotemnophiliac Allegories
Authors: Evans David H.
Published: May 2009

Grotesque or damaged bodies play a central role in a number of Flannery O'Connor's most powerful stories. One route for interpreting their significance is to approach them by way of a rare psychological condition that has been named apotemnophilia. Apotemnophiliacs experience an overwhelming desire to amputate one of more of their perfectly healthy limbs. Among the things that make the condition particularly mysterious is the challenge it offers to our standard conception of what constitutes a “whole” body. Two of O'Connor's most celebrated stories, “The Life You Save May Be Your Own” and “Good Country People,” have at their center amputated bodies, those of Tom T. Shiftlet and Hulga Hopewell respectively. Evans argues that those incomplete bodies are intended to contest the notion of “wholeness” as a spiritual or existential ideal. On the contrary, O'Connor's stories drive her characters towards a necessary recognition of their incompleteness. Finally, the allegorical form of O'Connor's fiction itself constitutes a parallel to the amputated and imperfect condition of the bodies that inhabit them. Just as the bodies point insistently to their own incompleteness, so the stories advertise their own inadequacy, forcing upon the reader a kind of hermeneutic phantom pain, an importunate demand for interpretation that can, however, never be fully satisfied.
Beyond the Appomattox: Comments on Israel on the Appomattox: A Southern Experiment in Black Freedom from the 1790s Through the Civil War, by Melvin Patrick Ely
Authors: Saville Julie
Published: May 2009

Inspired by Israel on the Appomattox's imaginative reconstruction of the contingencies of manumission and conditional emancipation prior to the Civil War, Julie Saville considers gradual emancipation's resemblances to aspects of twentieth-century notions of “minimalist democracy.” A premise that economic activities can be meaningfully separated from political participation and human rights undergirds many of the institutional and customary interactions that the book has uncovered. Melvin Ely also sheds new light on the symbolic work that racial stereotypes accomplished for their producers. Such features would seem to make the Virginians' projects of gradual emancipation less “visionary” but no less significant than this important study has revealed.
Investigation of a LOCAL Calibration Procedure for near Infrared Instruments
Authors: Shenk John S. , Westerhaus Mark O. , Berzaghi Paolo
Published: May 2009

A new procedure (LOCAL) for local calibrations is presented. LOCAL selects spectra from a library of samples and computes a PLS calibration equation for each constituent of the sample. This study evaluated the performances of LOCAL on the prediction of ground corn grain and haylage using several different combinations of data transformations, wavelength segment reduction, number of PLS factors and samples used in calibration. LOCAL resulted in lower SEP values for all the constituents of corn and dry matter of haylage with improvements ranging between 6 to 13%. Global calibrations had only a small advantage over LOCAL (1–2%) in the prediction of acid detergent fibre and crude protein in haylage. The two most important variables controlling the accuracy of predictions were number of samples in the calibration and number of PLS factors in the solution. Best results were obtained using 150 to 225 samples and more than 20 PLS factors per calibration equation. The speed of the LOCAL procedure is 0.5–2 s per sample on a 90 MHz computer. With this speed and accuracy, LOCAL is now available for real-time routine operation on a Windows platform.
Commercial Wheatflour Authentication by Discriminant Analysis of near Infrared Reflectance Spectra
Authors: Sirieix A. , Downey G.
Published: May 2009

This paper reports an application of qualitative analysis in the flour milling industry based on near infrared spectroscopy and a factorial discriminant procedure. Samples of different commercial flour types were collected from a number of mills and a discriminant model developed; evaluation of this model on a different set of 99 samples produced a correct classification rate of 97%.
Two-Dimensional Vibration Spectroscopy. V: Correlation of Mid- and near Infrared of Hard Red Winter and Spring Wheats
Authors: Barton F.E. , Himmelsbach D.S. , Archibald D.D.
Published: May 2009

Two-dimensional correlation spectroscopy across the near infrared (NIR) and mid-infrared (MIR) regions have been used to explain the NIR spectra of hard red winter and spring wheat and provide additional confidence in analytical models developed with empirical data. Recent studies have shown that the major C–H stretching vibrations and some of the aromatic C–H and ring stretching vibrations and the minor vibrations in the “fingerprint” region are correlated also. The technique has been expanded to include Raman spectra. The Raman spectra were enhanced with Maximum Likelihood methods to improve signal-to-noise (S/N) while maintaining resolution. This was necessary to eliminate the effects of fluorescence which degrades S/N. The use of NIR lasers at 1.1 μm generally eliminates fluorescence as a problem, but it is still quite prevalent in agricultural materials. The original study did not show any significant correlations to aromatic functionality. However, the band at 1552 nm correlates to the Raman and not to the MIR. This band has shown up in NIR spectroscopy models for the determination of lignin, but is not readily observed in the MIR. Thus it correlates to a Raman active rather than a MIR active band. The same phenomena are observed for the amide I, II and III bands for wheat. The interesting features from NIR and MIR are that there are correlations that distinguish winter from spring wheat. These, and the Raman spectra of wheat, will be shown. These studies show that multiple regions of the electromagnetic spectrum can be, and in deed need to be, used to interpret adequately the spectral and statistical results we have traditionally obtained in the NIR.
Faculty without Students: Resource Allocation in Higher Education
Authors: Johnson William R , Turner Sarah
Published: May 2009

Colleges and universities display substantial differences in the ratio of students to faculty across fields or disciplines. At Harvard University, for example, economics has about 16 students majoring in the subject per full-time-teaching equivalent, while in other departments such as astronomy, Slavic, German, and Celtic, the number of teaching faculty exceeds the number of student majors. We begin by presenting some evidence on the extent of the variation in faculty resource allocation by field and the broad changes over the last several decades. We then consider potential economic explanations for these striking patterns. For example, a basic education production function, which seeks to maximize aggregate student learning subject to a faculty salary budget constraint, will require that faculty be allocated across fields so that relative marginal gains in student learning equal relative faculty salaries. Differences across fields in student–faculty ratios could then arise either from differences in the pedagogical technology across fields or variation in relative faculty salaries. Additional university goals, such as research and graduate program productivity, or adjustment costs, as imposed by the tenure system, could also generate variation across fields in student–faculty ratios. However, we have only limited evidence that these arguments can explain the ongoing disparities in student–faculty ratios across fields and disciplines, which suggests that a substantial part of the explanation may reside in the politics rather than the economics of decision making in institutions of higher education.
The Economic Effects of Climate Change
Authors: Tol Richard S. J
Published: May 2009

I review the literature on the economic impacts of climate change, an externality that is unprecedentedly large, complex, and uncertain. Only 14 estimates of the total damage cost of climate change have been published, a research effort that is in sharp contrast to the urgency of the public debate and the proposed expenditure on greenhouse gas emission reduction. These estimates show that climate change initially improves economic welfare. However, these benefits are sunk. Impacts would be predominantly negative later in the century. Global average impacts would be comparable to the welfare loss of a few percent of income, but substantially higher in poor countries. Still, the impact of climate change over a century is comparable to economic growth over a few years. There are over 200 estimates of the marginal damage cost of carbon dioxide emissions. The uncertainty about the social cost of carbon is large and right-skewed. For a standard discount rate, the expected value is $50/tC, which is much lower than the price of carbon in the European Union but much higher than the price of carbon elsewhere. Current estimates of the damage costs of climate change are incomplete, with positive and negative biases. Most important among the missing impacts are the indirect effects of climate change on economic development; large-scale biodiversity loss; low-probability, high-impact scenarios; the impact of climate change on violent conflict; and the impacts of climate change beyond 2100. From a welfare perspective, the impact of climate change is problematic because population is endogenous, and because policy analyses should separate impatience, risk aversion, and inequity aversion between and within countries.
The Role of Prices in Measuring the Poor's Living Standards
Authors: Broda Christian , Leibtag Ephraim , Weinstein David E
Published: May 2009

In this paper, we revisit two pieces of conventional wisdom in the current debate about poverty, paying close attention to the price data underlying these findings: that the poor pay more than households of higher income for the goods and services they purchase; and that poverty rates, at least as measured by the U.S. Census, have remained essentially flat since the late 1960s, raising questions about the success of the policies implemented to reduce poverty. By examining scanner data on thousands of household purchases, we find that the poor pay less—not more—for the goods they purchase. And by extending the advances on price measurement in the recent decade back to the 1970s, we find that current poverty rates are less than half of the official numbers.
DExD/H-box Prp5 protein is in the spliceosome during most of the splicing cycle
Authors: Kosowski Tomasz R. , Keys Heather R. , Quan Tiffani K. , Ruby Stephanie W.
Published: May 2009

The DExD/H-box Prp5 protein (Prp5p) is an essential, RNA-dependent ATPase required for pre-spliceosome formation during nuclear pre-mRNA splicing. In order to understand how this protein functions, we used in vitro, biochemical assays to examine its association with the spliceosome from Saccharomyces cerevisiae. GST-Prp5p in splicing assays pulls down radiolabeled pre-mRNA as well as splicing intermediates and lariat product, but reduced amounts of spliced mRNA. It cosediments with active spliceosomes isolated by glycerol gradient centrifugation. In ATP-depleted extracts, GST-Prp5p associates with pre-mRNA even in the absence of spliceosomal snRNAs. Maximal selection in either the presence or absence of ATP requires a pre-mRNA with a functional intron. Prp5p is present in the commitment complex and functions in subsequent pre-spliceosome formation. Reduced Prp5p levels decrease levels of commitment, pre-spliceosomal and spliceosomal complexes. Thus Prp5p is most likely an integral component of the spliceosome, being among the first splicing factors associating with pre-mRNA and remaining until spliceosome disassembly. The results suggest a model in which Prp5p recruits the U2 snRNP to pre-mRNA in the commitment complex and then hydrolyzes ATP to promote stable association of U2 in the pre-spliceosome. They also suggest that Prp5p could have multiple ATP-independent and ATP-dependent functions at several stages of the splicing cycle.
A single RNA-dependent RNA polymerase assembles with mutually exclusive nucleotidyl transferase subunits to direct different pathways of small RNA biogenesis
Authors: Lee Suzanne Rebecca , Talsky Kristin Benjamin , Collins Kathleen
Published: May 2009

Members of the conserved family of eukaryotic RNA-dependent RNA polymerases (Rdrs) synthesize double-stranded RNA (dsRNA) intermediates in diverse pathways of small RNA (sRNA) biogenesis and RNA-mediated silencing. Rdr-dependent pathways of sRNA production are poorly characterized relative to Rdr-independent pathways, and the Rdr enzymes themselves are poorly characterized relative to their viral RNA-dependent RNA polymerase counterparts. We previously described a physical and functional coupling of the Tetrahymena thermophila Rdr, Rdr1, and a Dicer enzyme, Dcr2, in the production of ∼24-nucleotide (nt) sRNA in vitro. Here we characterize the endogenous complexes that harbor Rdr1, termed RDRCs. Distinct RDRCs assemble to contain Rdr1 and subsets of the total of four tightly Rdr1-associated proteins. Of particular interest are two RDRC subunits, Rdn1 and Rdn2, which possess noncanonical ribonucleotidyl transferase motifs. We show that the two Rdn proteins are uridine-specific polymerases of separate RDRCs. Two additional RDRC subunits, Rdf1 and Rdf2, are present only in RDRCs containing Rdn1. Rdr1 catalytic activity is retained in RDRCs purified from cell extracts lacking any of the nonessential RDRC subunits (Rdn2, Rdf1, Rdf2) or if the RDRC harbors a catalytically inactive Rdn. However, specific disruption of each RDRC imposes distinct loss-of-function consequences at the cellular level and has a differential impact on the accumulation of specific 23–24-nt sRNA sequences in vivo. The biochemical and biological phenotypes of RDRC subunit disruption reveal a previously unanticipated complexity of Rdr-dependent sRNA biogenesis in vivo.
Sex Differences in the Association Between Adiponectin and BMD, Bone Loss, and Fractures: The Rancho Bernardo Study
Authors: Araneta Maria Rosario G , von Mühlen Denise , Barrett-Connor Elizabeth
Published: May 2009

We evaluated sex differences in the prospective association between adiponectin with BMD, bone loss, and fractures. Adiponectin, an adipose-derived protein with insulin-sensitizing properties, is also expressed in bone-forming cells. Conflicting results and sex differences in the adiponectin-BMD association have been reported in cross-sectional studies. Serum adiponectin was measured in fasting blood samples obtained in 1984–1987 in 447 postmenopausal women (mean age: 76 yr) and 484 men (mean age: 75 yr). Four years later, BMD was measured at the midshaft radius by single photon absorptiometry and at the femoral neck, total hip, and lumbar spine by DXA. In 1992–1996, axial BMD was remeasured in 261 women and 264 men. Multivariable analysis adjusted for age, weight, calcium intake, type 2 diabetes, alcohol intake, and exercise. Among women, adiponectin was inversely associated with BMD at the femoral neck (β = −0.002, p = 0.007), total hip (β = −0.002, p = 0.009), lumbar spine (β = −0.003, p = 0.008), and midshaft radius (β = −0.002, p = 0.01) after 4.4 yr and at the femoral neck and total hip 8.6 yr later. Among men, adiponectin was inversely associated with BMD at the femoral neck, (β = −0.002, p = 0.03), total hip (β = −0.004, p < 0.001), and midshaft radius (β = −0.003, p < 0.001) after 4.4 yr and at the hip 8.6 yr later. Adiponectin was not associated with 4-yr bone loss in either sex but was associated with vertebral fractures (adjusted OR: 1.13; 95% CI: 1.08–1.23; p = 0.009) among men only. Adiponectin was inversely associated with BMD; however, sex differences were observed by anatomical site and with regards to vertebral fractures.
Teriparatide Reduces Bone Microdamage Accumulation in Postmenopausal Women Previously Treated With Alendronate
Authors: Dobnig Harald , Stepan Jan J , Burr David B , Li Jiliang , Michalská Dana , Sipos Adrien , Petto Helmut , Fahrleitner-Pammer Astrid , Pavo Imre
Published: May 2009

Suppression of bone turnover by bisphosphonates is associated with increased bone microdamage accumulation in animal models. Our objective was to study the effects of teriparatide treatment on changes in microdamage accumulation at the iliac crest in previously treatment-naïve patients or in those switched from alendronate to teriparatide. Sixty-six postmenopausal women with osteoporosis (mean age, 68.0 yr; and mean BMD T-score of −2.8 at lumbar spine and −1.7 at total hip; 62% with prevalent fractures) entered this prospective, nonrandomized study and started with 24-mo 20 μg/d subcutaneous teriparatide treatment in monotherapy: 38 patients stopped previous alendronate treatment (10 mg/d or 70 mg/wk for a mean duration of 63.6 mo) and switched to teriparatide, whereas 28 were previously treatment naïve. Thirty-one paired biopsies with two intact cortices were collected and analyzed for microstructure and microdamage accumulation at baseline and after 24 mo of teriparatide administration. After 24 mo of teriparatide treatment, crack density (Cr.Dn), crack surface density (Cr.S.Dn), and crack length (Cr.Le) were decreased in previously alendronate-treated patients, whereas only Cr.Le was reduced in former treatment-naïve patients. Patients with lower initial femoral neck BMD also showed a higher reduction of microdamage accumulation. Better bone microarchitecture correlated positively, whereas bone turnover markers and age did not correlate with reduced microdamage accumulation on teriparatide. In conclusion, teriparatide reduces microdamage accumulation in the iliac crest of patients previously treated with alendronate. There is insufficient evidence to suggest that age or bone turnover would be associated with this change.
Increased Bone Resorption Is Associated With Increased Risk of Cardiovascular Events in Men: The MINOS Study
Authors: Szulc Pawel , Samelson Elizabeth J , Kiel Douglas P , Delmas Pierre D
Published: May 2009

Better assessment of the association between cardiovascular disease and osteoporosis in older men may help identify shared etiologies for bone and heart health in this population. We assessed the association of BMD and bone turnover markers (BTMs) with risk of cardiovascular events (myocardial infarction or stroke) in 744 men ≥50 yr of age. During the 7.5-yr prospective follow-up, 43 strokes and 40 myocardial infarctions occurred in 79 men. After adjustment for confounders (age, weight, height, smoking, education, physical activity, self-reported history of diabetes, hypertension, and prevalent ischemic heart disease), men in the lowest quartile of BMD at the spine, whole body, and forearm had a 2-fold increased risk of cardiovascular events. Men in the highest quartile of bone resorption markers (deoxypyridinoline [DPD], C-telopeptide of type I collagen) had a 2-fold increased risk of cardiovascular events (e.g., multivariable-adjusted hazard ratio [including additional adjustment for BMD] was 2.11 [95% CI: 1.26–3.56], for the highest quartile of free DPD relative to the lowest three quartiles). The results were similar for men without prevalent ischemic heart disease and for myocardial infarction and stroke analyzed separately. Our data suggest that men with low BMD or high bone resorption may be at increased risk of myocardial infarction and stroke in addition to fracture. Thus, men with osteoporosis may benefit from screening for cardiovascular disease. Further study to elucidate the biological mechanism shared by bone and vascular disease may help efforts to identify men at risk or develop treatment.
Improving the Speed of AFM by Mechatronic Design and Modern Control MethodsGeschwindigkeitsverbesserung beim AFM mittels mechatronischem Design und modernen Regelmethoden
Authors: Schitter Georg
Published: May 2009

In Atomic Force Microscopy (AFM) high-performance and high-precision control of the AFM scanner and of the imaging forces is crucial. Particularly at high imaging speeds the dynamic behaviour of the scanner may cause imaging artifacts and limit the maximum imaging rate. This contribution discusses and presents recent improvements in AFM instrumentation for faster imaging by means of mechatronic design and utilizing modern control engineering methods. Combining these improvements enables AFM imaging at more than two orders of magnitudes faster than conventional AFMs.
Graves' orbitopathy in a patient with adrenoleukodystrophy after bone marrow transplantation
Authors: Vardizer Y , Lupetti A , Vandelanotte S , Lankester A C , Wiersinga W M , Baldeschi L
Published: May 2009

Objective

For many years, the treatment of X-linked childhood cerebral adrenoleukodystrophy (XALD) consisted of hydrocortisone replacement and a mixture of short chain-fatty acids, known as ‘Lorenzo's oil’. Recently, bone marrow transplantation (BMT) has also been used.

Case report

We report the case of a patient affected by XALD who developed Graves' hyperthyroidism (GH) and Graves' orbitopathy (GO) after BMT and who we could follow-up for 6.5 years afterwards.

Evidence synthesis

A boy affected by XALD was treated at the age of 6 years, with a whole BMT from his sister. One year after BMT, the transplanted patient presented TSH at the lower normal value and 3 years later he developed thyrotoxicosis. After a further 2 years, the patient developed GO, which showed clinical evidence of reactivation 5 years after its onset as a consequence of an attempt to treat thyrotoxicosis by means of I131 (300 MBq). Seven years after BMT, the donor showed alterations of thyroid autoimmunity and 1 year thereafter she developed GH. She never presented GO during a subsequent 5 year follow-up.

Conclusions

This case illustrates that autoimmunity originating from a pre-symptomatic donor can be transferred into the host during allogeneic stem cell transplantation. In cases where autoimmune phenomena are recognized in the donor prior to donation, alternative donors or T-cell manipulation of the graft might be considered.