bluuebunny/crossref_metadata_2025 huggingface dataset:
Sustained thromboprophylaxis mediated by an RBC-targeted pro-urokinase zymogen activated at the site of clot formation
Authors: Zaitsev Sergei , Spitzer Dirk , Murciano Juan-Carlos , Ding Bi-Sen , Tliba Samira , Kowalska M. Anna , Marcos-Contreras Oscar A. , Kuo Alice , Stepanova Victoria , Atkinson John P. , Poncz Mortimer , Cines Douglas B. , Muzykantov Vladimir R.
Published: April 2010

Plasminogen activators (PAs) are used to treat life-threatening thrombosis, but not for thromboprophylaxis because of rapid clearance, risk of bleeding, and central nervous system (CNS) toxicity. We describe a novel strategy that may help to overcome these limitations by targeting a thrombin-activated PA pro-drug to circulating red blood cells (RBCs). We fused a single chain antibody (scFv Ter-119) that binds to mouse glycophorin A (GPA) with a variant human single-chain low molecular weight urokinase construct that can be activated selectively by thrombin (scFv/uPA-T). scFv/uPA-T bound specifically to mouse RBCs without altering their biocompatibility and retained its zymogenic properties until converted by thrombin into an active 2-chain molecule. As a result, RBC-bound scFv/uPA-T caused thrombin-induced fibrinolysis. One hour and 48 hours after intravenous (IV) injection in mice, approximately 70% and approximately 35% of scFv/uPA-T was retained in the blood, respectively, and approximately 95% of the circulating scFv/uPA-T remained bound to RBCs. A single IV injection of scFv/uPA-T provided effective prophylaxis against arterial and venous thrombosis for up to 24 hours. Thus, prophylactic delivery of RBC-targeted PA pro-drugs activated selectively at the site of clot formation represents a new approach to prevent thrombosis in clinical settings where the risk of clotting is high.
Gene enrichment profiles reveal T-cell development, differentiation, and lineage-specific transcription factors including ZBTB25 as a novel NF-AT repressor
Authors: Benita Yair , Cao Zhifang , Giallourakis Cosmas , Li Chun , Gardet Agnès , Xavier Ramnik J.
Published: April 2010

The identification of transcriptional regulatory networks, which control tissue-specific development and function, is of central importance to the understanding of lymphocyte biology. To decipher transcriptional networks in T-cell development and differentiation we developed a browsable expression atlas and applied a novel quantitative method to define gene sets most specific to each of the represented cell subsets and tissues. Using this system, body atlas size datasets can be used to examine gene enrichment profiles from a cell/tissue perspective rather than gene perspective, thereby identifying highly enriched genes within a cell type, which are often key to cellular differentiation and function. A systems analysis of transcriptional regulators within T cells during different phases of development and differentiation resulted in the identification of known key regulators and uncharacterized coexpressed regulators. ZBTB25, a BTB-POZ family transcription factor, was identified as a highly T cell–enriched transcription factor. We provide evidence that ZBTB25 functions as a negative regulator of nuclear factor of activated T cells (NF-AT) activation, such that RNA interference mediated knockdown resulted in enhanced activation of target genes. Together, these findings suggest a novel mechanism for NF-AT mediated gene expression and the compendium of expression data provides a quantitative platform to drive exploration of gene expression across a wide range of cell/tissue types.
Modulation of SOCS protein expression influences the interferon responsiveness of human melanoma cells
Authors: Lesinski Gregory B , Zimmerer Jason M , Kreiner Melanie , Trefry John , Bill Matthew A , Young Gregory S , Becknell Brian , Carson William E
Published: April 2010

Background

Endogenously produced interferons can regulate the growth of melanoma cells and are administered exogenously as therapeutic agents to patients with advanced cancer. We investigated the role of negative regulators of interferon signaling known as suppressors of cytokine signaling (SOCS) in mediating interferon-resistance in human melanoma cells.

Methods

Basal and interferon-alpha (IFN-α) or interferon-gamma (IFN-γ)-induced expression of SOCS1 and SOCS3 proteins was evaluated by immunoblot analysis in a panel of n = 10 metastatic human melanoma cell lines, in human embryonic melanocytes (HEM), and radial or vertical growth phase melanoma cells. Over-expression of SOCS1 and SOCS3 proteins in melanoma cells was achieved using the PINCO retroviral vector, while siRNA were used to inhibit SOCS1 and SOCS3 expression. Tyr701-phosphorylated STAT1 (P-STAT1) was measured by intracellular flow cytometry and IFN-stimulated gene expression was measured by Real Time PCR.

Results

SOCS1 and SOCS3 proteins were expressed at basal levels in melanocytes and in all melanoma cell lines examined. Expression of the SOCS1 and SOCS3 proteins was also enhanced following stimulation of a subset of cell lines with IFN-α or IFN-γ. Over-expression of SOCS proteins in melanoma cell lines led to significant inhibition of Tyr701-phosphorylated STAT1 (P-STAT1) and gene expression following stimulation with IFN-α (IFIT2, OAS-1, ISG-15) or IFN-γ (IRF1). Conversely, siRNA inhibition of SOCS1 and SOCS3 expression in melanoma cells enhanced their responsiveness to interferon stimulation.

Conclusions

These data demonstrate that SOCS proteins are expressed in human melanoma cell lines and their modulation can influence the responsiveness of melanoma cells to IFN-α and IFN-γ.
Comparison of endothelial progenitor cell function in type 2 diabetes with good and poor glycemic control
Authors: Churdchomjan Worachat , Kheolamai Pakpoom , Manochantr Sirikul , Tapanadechopone Pirath , Tantrawatpan Chairat , U-pratya Yaowalak , Issaragrisil Surapol
Published: April 2010

Background

Endothelial progenitor cells (EPCs) play an important role in vascular repair and a decrease in the number of EPCs is observed in type 2 diabetes. However, there is no report on the change of EPCs after glycemic control. This study therefore aimed to investigate the EPC number and function in patients with good and poor glycemic control.

Methods

The number of EPCs was studied using flow cytometry by co-expression of CD34 and VEGFR2. The EPCs were cultured and characterized by the expression of UEA-I, CD34, VEGFR2, vWF and Dil-Ac-LDL engulfment, as well as the ability to form capillary-like structures. An in vitro study on the effect of hyperglycemia on the proliferation and viability of the cultured EPCs was also performed.

Results

The number of EPCs in type 2 diabetes was significantly decreased compared with healthy controls and there was an inverse correlation between the EPC numbers and plasma glucose, as well as HbA1C. The number and function of EPCs in patients with good glycemic control were recovered compared with those with poor glycemic control. When glucose was supplemented in the culture in vitro, there was a negative effect on the proliferation and viability of EPCs, in a dose-dependent manner, whereas the enhancement of apoptosis was observed.

Conclusion

There was EPC dysfunction in type 2 diabetes which might be improved by strict glycemic control. However, the circulating EPC number and proliferative function in patients with good glycemic control did not reach the level in healthy controls.
A systematic review of clinical trials of pharmacological interventions for acute ischaemic stroke (1955-2008) that were completed, but not published in full
Authors: Gibson Lorna M , Brazzelli Miriam , Thomas Brenda M , Sandercock Peter AG
Published: April 2010

Background

We assessed the prevalence, and potential impact of, trials of pharmacological agents for acute stroke that were completed but not published in full. Failure to publish trial data is to be deprecated as it sets aside the altruism of participants' consent to be exposed to the risks of experimental interventions, potentially biases the assessment of the effects of therapies, and may lead to premature discontinuation of research into promising treatments.

Methods

We searched the Cochrane Stroke Group's Specialised Register of Trials in June 2008 for completed trials of pharmacological interventions for acute ischaemic stroke, and searched MEDLINE and EMBASE (January 2007 - March 2009) for references to recent full publications. We assessed trial completion status from trial reports, online trials registers and correspondence with experts.

Results

We identified 940 trials. Of these, 125 (19.6%, 95% confidence interval 16.5-22.6) were completed but not published in full by the point prevalence date. They included 16,058 participants (16 trials had over 300 participants each) and tested 89 different interventions. Twenty-two trials with a total of 4,251 participants reported the number of deaths. In these trials, 636/4251 (15.0%) died.

Conclusions

Our data suggest that, at the point prevalence date, a substantial body of evidence that was of relevance both to clinical practice in acute stroke and future research in the field was not published in full. Over 16,000 patients had given informed consent and were exposed to the risks of therapy. Responsibility for non-publication lies with investigators, but pharmaceutical companies, research ethics committees, journals and governments can all encourage the timely publication of trial data.
Analysis of a zebrafish dync1h1mutant reveals multiple functions for cytoplasmic dynein 1 during retinal photoreceptor development
Authors: Insinna Christine , Baye Lisa M , Amsterdam Adam , Besharse Joseph C , Link Brian A
Published: April 2010

Background

Photoreceptors of the retina are highly compartmentalized cells that function as the primary sensory neurons for receiving and initiating transmission of visual information. Proper morphogenesis of photoreceptor neurons is essential for their normal function and survival. We have characterized a zebrafish mutation, cannonball, that completely disrupts photoreceptor morphogenesis.

Results

Analysis revealed a non-sense mutation in cytoplasmic dynein heavy chain 1 (dync1h1), a critical subunit in Dynein1, to underlie the cannonball phenotypes. Dynein1 is a large minus-end directed, microtubule motor protein complex that has been implicated in multiple, essential cellular processes. In photoreceptors, Dynein1 is thought to mediate post-Golgi vesicle trafficking, while Dynein2 is thought to be responsible for outer segment maintenance. Surprisingly, cannonball embryos survive until larval stages, owing to wild-type maternal protein stores. Retinal photoreceptor neurons, however, are significantly affected by loss of Dync1h1, as transmission electron microscopy and marker analyses demonstrated defects in organelle positioning and outer segment morphogenesis and suggested defects in post-Golgi vesicle trafficking. Furthermore, dosage-dependent antisense oligonucleotide knock-down of dync1h1 revealed outer segment abnormalities in the absence of overt inner segment polarity and trafficking defects. Consistent with a specific function of Dync1h1 within the outer segment, immunolocalization showed that this protein and other subunits of Dynein1 and Dynactin localized to the ciliary axoneme of the outer segment, in addition to their predicted inner segment localization. However, knock-down of Dynactin subunits suggested that this protein complex, which is known to augment many Dynein1 activities, is only essential for inner segment processes as outer segment morphogenesis was normal.

Conclusions

Our results indicate that Dynein1 is required for multiple cellular processes in photoreceptor neurons, including organelle positioning, proper outer segment morphogenesis, and potentially post-Golgi vesicle trafficking. Titrated knock-down of dync1h1 indicated that outer segment morphogenesis was affected in photoreceptors that showed normal inner segments. These observations, combined with protein localization studies, suggest that Dynein1 may have direct and essential functions in photoreceptor outer segments, in addition to inner segment functions.
Robust dynamical pattern formation from a multifunctional minimal genetic circuit
Authors: Rodrigo Guillermo , Carrera Javier , Elena Santiago F , Jaramillo Alfonso
Published: April 2010

Background

A practical problem during the analysis of natural networks is their complexity, thus the use of synthetic circuits would allow to unveil the natural mechanisms of operation. Autocatalytic gene regulatory networks play an important role in shaping the development of multicellular organisms, whereas oscillatory circuits are used to control gene expression under variable environments such as the light-dark cycle.

Results

We propose a new mechanism to generate developmental patterns and oscillations using a minimal number of genes. For this, we design a synthetic gene circuit with an antagonistic self-regulation to study the spatio-temporal control of protein expression. Here, we show that our minimal system can behave as a biological clock or memory, and it exhibites an inherent robustness due to a quorum sensing mechanism. We analyze this property by accounting for molecular noise in an heterogeneous population. We also show how the period of the oscillations is tunable by environmental signals, and we study the bifurcations of the system by constructing different phase diagrams.

Conclusions

As this minimal circuit is based on a single transcriptional unit, it provides a new mechanism based on post-translational interactions to generate targeted spatio-temporal behavior.
Activation of Mineralocorticoid Receptors by Exogenous Glucocorticoids and the Development of Cardiovascular Inflammatory Responses in Adrenalectomized Rats
Authors: Young Morag J. , Morgan James , Brolin Kim , Fuller Peter J. , Funder John W.
Published: April 2010

Activation of the mineralocorticoid receptor (MR) in the context of a high salt intake produces cardiovascular inflammation plus cardiac fibrosis and failure. Inactivation of vascular 11β-hydroxysteroid dehydrogenase type 2 activity in intact animals by carbenoxolone (CBX) produces a similar pathology, presumably reflecting coronary vascular MR activation by endogenous glucocorticoids. To test this hypothesis, we have used adrenalectomized rats, without endogenous corticosteroids, and examined the consequences of corticosterone (CORT) replacement on a series of cardiovascular disease parameters. Uninephrectomized adrenalectomized Sprague Dawley rats given 1% NaCl/0.3% KCl to drink were treated for 8 d as follows: control; 20 mg deoxycorticosterone (DOC); 2 mg/d CORT; 2.5 mg/d CBX; CORT plus CBX (CORT/CBX); and CORT/CBX plus 100 mg/kg·d eplerenone. Markers of cardiac oxidative stress (p22phox and NOX4 mRNA) were up-regulated in the DOC and CORT/CBX groups; in contrast, inflammatory cell infiltration was increased and endothelial nitric oxide synthase down-regulated by CORT as well as by DOC and CORT/CBX. In the kidney, connective tissue growth factor mRNA levels were increased by DOC and CORT/CBX; in contrast, DOC had no effect on mRNA levels for channel inducing factor or endothelin 3, which were elevated only by CORT/CBX. All changes noted were reversed by eplerenone. Rats given 10-fold lower CORT (0.2 mg/d) with or without CBX showed no change in any parameter. These results suggest that there exist distinct but overlapping ligand-specific MR-mediated tissue responses to a classic mineralocorticoid (DOC) and to the glucocorticoid CORT, in the presence and absence of CBX to block vascular 11β-hydroxysteroid dehydrogenase type 2.
Continuous and Cyclic Progesterone Differentially Interact with Estradiol in the Regulation of Alzheimer-Like Pathology in Female 3×Transgenic-Alzheimer’s Disease Mice
Authors: Carroll Jenna C. , Rosario Emily R. , Villamagna Angela , Pike Christian J.
Published: April 2010

Depletion of estrogens and progesterone at menopause has been linked to an increased risk for the development of Alzheimer’s disease (AD) in women. A currently controversial literature indicates that although treatment of postmenopausal women with hormone therapy (HT) may reduce the risk of AD, several parameters of HT may limit its potential efficacy and perhaps, even exacerbate AD risk. One such parameter is continuous vs. cyclic delivery of the progestogen component of HT. Recent experimental evidence suggests that continuous progesterone can attenuate neural actions of estradiol (E2). In the present study, we compared the effects of continuous and cyclic progesterone treatment in the presence and absence of E2 in ovariectomized 3×Tg-AD mice, a transgenic mouse model of AD. We found that ovariectomy-induced hormone depletion increases AD-like pathology in female 3×Tg-AD mice, including accumulation of β-amyloid, tau hyperphosphorylation, and impaired hippocampal-dependent behavior. E2 treatment alone prevents the increases in pathology. Continuous progesterone did not affect β-amyloid levels when delivered alone but blocked the Aβ-lowering action of E2. In contrast, cyclic progesterone significantly reduced β-amyloid levels by itself and enhanced rather than inhibited the E2 effects. These results provide new insight into the neural interactions between E2 and progesterone that may prove valuable in optimizing HT regimens in postmenopausal women.
Dual-targeting siRNAs
Authors: Tiemann Katrin , Höhn Britta , Ehsani Ali , Forman Stephen J. , Rossi John J. , Sætrom Pål
Published: April 2010

We have developed an algorithm for the prediction of dual-targeting short interfering RNAs (siRNAs) in which both strands are deliberately designed to separately target different mRNA transcripts with complete complementarity. An advantage of this approach versus the use of two separate duplexes is that only two strands, as opposed to four, are competing for entry into the RNA-induced silencing complex. We chose to design our dual-targeting siRNAs as Dicer substrate 25/27mer siRNAs, since design features resembling pre-microRNAs (miRNAs) can be introduced for Dicer processing. Seven different dual-targeting siRNAs targeting genes that are potential targets in cancer therapy have been developed including Bcl2, Stat3, CCND1, BIRC5, and MYC. The dual-targeting siRNAs have been characterized for dual target knockdown in three different cell lines (HEK293, HCT116, and PC3), where they were as effective as their corresponding single-targeting siRNAs in target knockdown. The algorithm developed in this study should prove to be useful for predicting dual-targeting siRNAs in a variety of different targets and is available from http://demo1.interagon.com/DualTargeting/.
Use of Myeloperoxidase for Risk Stratification in Acute Heart Failure
Authors: Reichlin Tobias , Socrates Thenral , Egli Patrick , Potocki Mihael , Breidthardt Tobias , Arenja Nisha , Meissner Julia , Noveanu Markus , Reiter Mirjam , Twerenbold Raphael , Schaub Nora , Buser Andreas , Mueller Christian
Published: April 2010

Background: Myeloperoxidase (MPO) is a biomarker of inflammation and oxidative stress produced by neutrophils, monocytes, and endothelial cells. Concentrations of MPO predict mortality in patients with chronic heart failure. This study sought to investigate the diagnostic accuracy and prognostic value of MPO in patients with acute heart failure (AHF).

Methods: We prospectively enrolled 667 patients presenting to the emergency department with dyspnea and observed them for 1 year. MPO and B-type natriuretic peptide (BNP) were measured at presentation. Two independent cardiologists adjudicated final discharge diagnoses.

Results: MPO concentrations were similar in patients with AHF (n = 377, median 139 pmol/L) and patients with noncardiac causes of dyspnea (n = 290, median 150 pmol/L, P = 0.26). The diagnostic accuracy of MPO for AHF was limited [area under the ROC curve (AUC) 0.53] and inferior to that of BNP (AUC 0.95, P < 0.001). In patients with AHF, MPO concentrations above the lowest tertile (MPO >99 pmol/L) were associated with significantly increased 1-year mortality (hazard ratio 1.58, P = 0.02). The combination of MPO (≤99 vs >99 pmol/L) and BNP (median of ≤847 vs >847 ng/L) improved the prediction of 1-year mortality (hazard ratio 2.80 for both variables increased vs both low, P < 0.001). After adjustment for cardiovascular risk factors in multivariable Cox proportional hazard analysis, increases in MPO contributed significantly toward the prediction of 1-year mortality (hazard ratio 1.51, P = 0.045).

Conclusions: MPO is an independent predictor of 1-year mortality in AHF, is additive to BNP, and could be helpful in identifying patients with a favorable prognosis despite increased BNP concentrations.
Tell Us About It: Diverse student voices in creative practice
Authors: Finnigan Terry
Published: April 2010

This paper reflects on the development of a student voice project that researched into the positive learning experiences of high achieving art and design students from a wide variety of backgrounds. We wanted to build up a bank of positive case studies of student learning experiences
and explore the institutional and personal factors that contributed to their academic success. The students chose to respond in varying ways often using the visual medium through sketchbooks, DVDs, books and board games. These have been shared with staff and students through exhibitions and
workshops where, they can interact with the artefacts and discuss diversity and achievement. This project has captured the imagination and interest of the wider HE sector as it relates both to student voice and diversity. It has also been transformational in our own CETL developments around
co-creating solutions with students.
writing design: A collaboration between the Write Now CETL and The Sir John Cass Department of Art, Media and Design
Authors: Bhagat Dipti , O'Neill Peter
Published: April 2010

This brief report describes a writing-in-the-disciplines collaboration between the Write Now CETL and the Department of Art, Media and Design at London Metropolitan University. The project, writing design, aims to enable year one design practice-based students to write critically,
confidently and effectively about design and design practice in its historical and theoretical contexts. writing design involved curricular change, embedded writing workshops and staff development to achieve these goals.
Reviews
Authors: Boys Jos , Finnigan Terry
Published: April 2010

Unspoken Interactions: exploring the unspoken dimension of learning and teaching in creative subjects, Edited by Noam Austerlitz, (2008) The Centre for Learning and Teaching in Design (cltad), University of the Arts 2 -6 Catton Street, London WC1R 4A ISBN 978-0-9541439-9-2
269 pages Paperback. 20 pounds plus p+p. Buy online at http://www.arts.ac.uk/clipcetl-unspokeninteractionsanthology.htm

Inspiring
Writing in Art and Design: Taking a Line for a Write, Pat Francis (2009) Bristol: Intellect; (256 pp.), ISBN 978-1-84150-256-4 (pbk), 20.50
Geometrical Evaluation and Experimental Verification to Determine Representative Volume Elements of Heterogeneous Asphalt Mixtures
Authors: Kim Yongrak , Lee Junghun , Lutif Jamilla E. S.
Published: April 2010

This paper presents an experimental verification of geometrically defined representative volume elements (RVEs) of heterogeneous asphalt concrete mixtures before any significant damage is initiated. A typical dense-graded Superpave mixture (12.5 mm nominal maximum aggregate size) is selected as a representative roadway paving mixture and used in this study to accomplish two parallel approaches: Geometrical analysis of mixture heterogeneity using two-dimensional actual images of asphalt concrete inner structures and experimental evaluation through uniaxial tensile tests of asphalt concrete mixtures incorporated with digital image correlation (DIC) technique. To properly address the significant heterogeneity of asphalt concrete mixtures in defining the RVE, several geometrical factors such as area fraction, gradation, orientation, and the distribution of aggregate particles in asphalt concrete mixtures are considered altogether. For the uniaxial tensile test with the DIC, the mean strains and their standard deviations captured by DIC are analyzed to confirm statistical homogeneity of RVEs evaluated from the geometrical analyses. The two approaches present similar results, indicating that typical dense-graded asphalt mixtures can be characterized for their material properties with an approximate RVE size of 60 mm. Findings from this study further imply that the simple geometrical analysis can be an efficient tool to reasonably determine the RVE of asphalt mixtures and other granular composites where significant heterogeneity is involved.
The consequence of arterial stiffness parameters to predict the cardiovascular mortality in hemodialysis patients: a prospective cohort study
Authors: El Hadj Othmane Taha , Kiss István , Nemcsik János , Fekete Cs. Bertalan , Deák György , Egresits József , Fodor Erzsébet , Németh K. Zsófia , Szabó Tamás , Szathmári Miklós , Tislér András
Published: April 2010

Korábbi vizsgálatok eredményei alapján az érfali tágulékonyság paraméterei összefüggést mutatnak a cardiovascularis mortalitással hemodializált betegekben. A különböző paraméterek relatív prognosztikus értékét ugyanakkor egy közös kohorszban eddig nem vizsgálták.Módszer:Dialízis előtt és után 98 betegnél mértük a carotis-femoralis pulzushullám terjedési sebességét, a carotis augmentációs indexét, a carotis pulzusnyomását és a carotis-brachialis pulzusnyomás amplifikációját. A betegeket 29 hónapig (medián) (tartomány 1–35) követtük, majd a cardiovascularis mortalitás és a kiinduláskor mért tágulékonysági paraméterek közötti összefüggést vizsgáltuk log-rank tesztek, illetve a korhoz, diabeteshez és korábban meglévő cardiovascularis megbetegedéshez illesztett Cox-féle regressziós modellek alkalmazásával.Eredmények:A követés alatt 40 beteg halt meg (mortalitási ráta 20,7/100 betegév), köztük 25-en cardiovascularis ok következtében. A dialízis előtt és után mért pulzushullám-terjedési sebességet tercilisei, illetve a dialízis előtt mért pulzusnyomás-amplifikáció tercilise szignifikáns összefüggést mutattak a cardiovascularis mortalitással (log-rank p-értékek 0,012 és 0,011 a pre- és posztdialízis pulzushullám-terjedési sebesség, illetve <0,001 és 0,321 a pre- és posztdialízis pulzusnyomás-amplifikáció esetén). Az augmentációs indexek, illetve a carotispulzusnyomás-értékek nem álltak összefüggésben a cardiovascularis mortalitással. Cox-modellben az 1 m/s-mal gyorsabb pre- és posztdialízis pulzushullám-terjedési sebességéhez tartozó relatív rizikó 1,24 (1,07–1,44) és 1,17 (1,06–1,28) volt. 10%-kal kisebb predialízispulzusnyomás-amplifikációval járó rizikónövekedés 41% (3–92%) volt. Egy közös modellben vizsgálva mind a predialízispulzushullám-terjedési sebesség, mind a pulzusnyomás-amplifikáció szignifikáns összefüggést mutatott a cardiovascularis túléléssel [relatív rizikó: 1,23 (1,07–1,42) és 1,39 (1,02–1,89)].Következtetés:Hemodializált betegekben az érfali tágulékonyságot leíró különböző paraméterek közül a pulzushullám-terjedési sebesség a mérés idejétől független, konzekvens összefüggést mutat a cardiovascularis mortalitással. Ugyanakkor a predialízispulzusnyomás-amplifikációs érték további prognosztikus információt hordoz.
Radioprotectors and Mitigators of Radiation-Induced Normal Tissue Injury
Authors: Citrin Deborah , Cotrim Ana P. , Hyodo Fuminori , Baum Bruce J. , Krishna Murali C. , Mitchell James B.
Published: April 2010

Radiation is used in the treatment of a broad range of malignancies. Exposure of normal tissue to radiation may result in both acute and chronic toxicities that can result in an inability to deliver the intended therapy, a range of symptoms, and a decrease in quality of life. Radioprotectors are compounds that are designed to reduce the damage in normal tissues caused by radiation. These compounds are often antioxidants and must be present before or at the time of radiation for effectiveness. Other agents, termed mitigators, may be used to minimize toxicity even after radiation has been delivered. Herein, we review agents in clinical use or in development as radioprotectors and mitigators of radiation-induced normal tissue injury. Few agents are approved for clinical use, but many new compounds show promising results in preclinical testing.
Recent Advances in Combined Modality Therapy
Authors: Mierzwa Michelle L. , Nyati Mukesh K. , Morgan Meredith A. , Lawrence Theodore S.
Published: April 2010

Combined modality therapy emerged from preclinical data showing that carefully chosen drugs could enhance the sensitivity of tumor cells to radiation while having nonoverlapping toxicities. Recent advances in molecular biology involving the identification of cellular receptors, enzymes, and pathways involved in tumor growth and immortality have resulted in the development of biologically targeted drugs. This review highlights the recent clinical data in support of newer generation cytotoxic chemotherapies and systemic targeted agents in combination with radiation therapy.
Recurrent genomic alterations in benign and malignant pheochromocytomas and paragangliomas revealed by whole-genome array comparative genomic hybridization analysis
Authors: Sandgren Johanna , Diaz de Ståhl Teresita , Andersson Robin , Menzel Uwe , Piotrowski Arkadiusz , Nord Helena , Bäckdahl Martin , Kiss Nimrod B , Brauckhoff Michael , Komorowski Jan , Dralle Henning , Hessman Ola , Larsson Catharina , Åkerström Göran , Bruder Carl , Dumanski Jan P , Westin Gunnar
Published: April 2010

Pheochromocytomas and abdominal paragangliomas are adrenal and extra-adrenal catecholamine-producing tumours. They arise due to heritable cancer syndromes, or more frequently occur sporadically due to an unknown genetic cause. The majority of cases are benign, but malignant tumours are observed. Previous comparative genomic hybridization (CGH) and loss of heterozygosity studies have shown frequent deletions of chromosome arms 1p, 3q and 22q in pheochromocytomas. We applied high-resolution whole-genome array CGH on 53 benign and malignant pheochromocytomas and paragangliomas to narrow down candidate regions as well as to identify chromosomal alterations more specific to malignant tumours. Minimal overlapping regions (MORs) were identified on 16 chromosomes, with the most frequent MORs of deletion (≥32%) occurring on chromosome arms 1p, 3q, 11p/q, 17p and 22q, while the chromosome arms 1q, 7p, 12q and 19p harboured the most common MORs of gain (≥14%). The most frequent MORs (61–75%) in the pheochromocytomas were identified at 1p, and the four regions of common losses encompassed 1p36, 1p32–31, 1p22–21 and 1p13. Tumours that did not show 1p loss generally demonstrated aberrations on chromosome 11. Gain of chromosomal material was significantly more frequent among the malignant cases. Moreover, gain at 19q, trisomy 12 and loss at 11q were positively associated with malignant pheochromocytomas, while 1q gain was commonly observed in the malignant paragangliomas. Our study revealed novel and narrow recurrent chromosomal regions of loss and gain at several autosomes, a prerequisite for identifying candidate tumour suppressor genes and oncogenes involved in the development of adrenal and extra-adrenal catecholamine-producing tumours.
Synthesis of special cement with fluidised bed combustion ashes
Authors: Selçuk N. , Soner İ. , Selçuk E.
Published: April 2010

Fluidised bed combustion (FBC) ashes containing a significant amount of free calcium oxide and calcium sulfate in addition to valuable inorganic acidic oxide ingredients such as silicon oxide, ferric oxide and aluminium oxide can be utilised as potential raw materials in the production of non-expansive belite-rich calcium sulfoaluminate cement, which is one of the special cement types having performance characteristics similar to those of ordinary Portland cement in addition to having lower energy requirements and carbon dioxide (CO2) emissions during manufacture. Therefore, in the present study, the possibility of synthesising the above-mentioned energy-saving green cement was investigated by adding FBC ashes in various proportions to the raw meal. For this purpose, a raw meal composed of a mixture of limestone, bauxite and gypsum together with FBC bottom ash and baghouse filter ash was prepared. It was sintered in a laboratory-scale muffle furnace at temperatures of 1200, 1250 and 1300°C for various holding times. The results of chemical and mineralogical analysis as well as microscopic examination revealed that FBC ashes have the potential to be used in the raw meal due to the formation of characteristic mineral phases of this type of cement, namely yeelimite, belite, ferrite and anhydrite, in the sample sintered at optimum temperature of 1250°C for 60 min.
Flexural rigidity and ductility of high-strength reinforced polyester polymer concrete beams
Authors: Park S.-K. , Jo B.-W. , Park D.-H. , Chun B.-S.
Published: April 2010

The structural behaviours were analysed for reinforced polymer concrete. The analysis included load–deflection and moment–curvature responses, ductility index, and flexural rigidity. Ductility indexes computed on the basis of deflections and curvatures were higher than those of high-strength cement concrete. The prediction equation for the effective moment of inertia proposed by ACI 318 is not applicable to high-strength polymer concrete, because the ACI 318 equation does not reflect the high effective moment of inertia of high-strength polymer concrete. Therefore, an empirical equation was proposed to estimate the effective moment of inertia of simply supported reinforced polymer concrete beams. The predicted deflections using the proposed formula agree well with the experimental deflections of the tested polymer concrete beams.
Durability of light steel framing in residential applications
Authors: Lawson R. M. , Popo-Ola S. O. , Way A. , Heatley T. , Pedreschi R.
Published: April 2010

This paper presents a summary and analysis of research findings on the durability of galvanised cold-formed steel sections used in housing in order to deduce their design life. These cold-formed sections are produced from pre-galvanised strip steel. It reviews reports and publications from research projects carried out by Corus and the Steel Construction Institute on zinc-coated, cold-formed steel products. New data have also been gathered from measurements on houses and similar buildings that have used galvanised steel components. The data also extend to over-cladding applications in building renovation. The performance of galvanised (zinc-coated) steel components within warm-frame applications is very good. The research leading to this paper shows that the predicted design life of the standard G275 coating, based on the measured loss of zinc from the strip steel, is over 200 years, provided that the building envelope is well insulated and properly maintained. The evidence for this conclusion is based on measurement of zinc loss on light steel frames in various applications and locations. A formula for the loss of zinc over time in areas subject to low condensation risk is presented.
Study on the effect of granite powder on concrete properties
Authors: Thomas F. K. , Partheeban P.
Published: April 2010

An experimental study on high-performance concrete made with granite powder as fine aggregate and partial replacement of cement with admixtures subjected to water curing was carried out. The percentage of granite powder added by weight was 0, 25, 50, 75 and 100% as a replacement of the sand used in concrete and cement was partially replaced with 7·5% silica fume, 10% fly ash, 10% slag and 1% superplasticiser. The water-to-binder (w/b) ratio was 0·40. The effects of curing water temperature at 26 and 32°C for 1, 7, 14, 28, 56 and 90 days on the compressive strength, split tensile strength, modulus of elasticity, drying shrinkage, hydration and water penetration of concrete were studied. The test results showed clearly that granite powder of marginal quantity, used as partial sand replacement, has beneficial effects on the compressive strength and split tensile strength, modulus of elasticity. The highest compressive strength was achieved in samples containing 25% granite powder. The overall performance revealed that granite powder can be utilised as a partial replacement of natural sand in high-performance concrete.
Parole Release Decisions: Impact of Positive and Negative Victim and Nonvictim Input on a Representative Sample of Parole-Eligible Inmates
Authors: Caplan Joel M.
Published: April 2010

This study analyzed administrative data from the New Jersey State Parole Board to determine the extent to which victim and nonvictim input impacted parole release decisions. Positive and negative input, in both verbal and written forms, was studied for a representative sample of 820 parole-eligible adult inmates. Victim input was not found to be a significant predictor of parole release; measures of institutional behavior, crime severity, and criminal history were significant. Though insignificant, verbal input had a greater effect than written input. Results suggest that the impact of victim input is not generalizable across different types of offenders or across different paroling jurisdictions. It can no longer be assumed that victim rights laws and public participation at parole guarantee victim-desired outcomes.
Social Indicators and Physical Abuse of Women by Intimate Partners: A Study of Women in Zambia
Authors: Okenwa Leah , Lawoko Stephen
Published: April 2010

Intimate partner physical abuse (IPPA) of women is a societal problem with sinister implications on health. IPPA has been integrally linked to social status though the direction of association remains elusive, not the least in sub-Saharan Africa. This article investigated the association between IPPA and social status of women in Zambia. Data comprising 3,969 currently partnered women were retrieved from the 2001 Zambian Demographic and Health Survey and analyzed using chi-square test and logistic regression. IPPA augmented with low education, income-generating activity, access to information, autonomy over household health issues, and having tolerant attitudes toward IPPA. Tolerant attitude toward IPPA and illiteracy were independent risk factors for IPPA. Educational interventions are recommended to prevent IPPA in Zambia.
Disseminating Evidence-Based Practice Projects: Poster Design and Evaluation
Authors: Forsyth Diane McNally , Wright Tracy L. , Scherb Cindy A. , Gaspar Phyllis M.
Published: April 2010

The international emphasis on evidence-based practice (EBP) as a basis for quality care has elevated the importance of EBP dissemination. The doctor of nursing practice (DNP) degree has created opportunities for nurses to implement EBP projects in collaboration with academic and clinical teams. Findings from such innovative efforts ought to be widely distributed, yet such projects have unique dissemination needs that are not readily met by traditional research-based presentation venues. Current literature focuses on presentation approaches for research-based poster content and evaluation rather than EBP posters. To facilitate timely and quality dissemination of EBP projects, there is a need for clear criteria identifying the essential information to be shared, how to share it effectively, and how to evaluate the end product. Thus far, the challenge to better accommodate EBP poster presentations has been unmet. The purposes of this article are to provide suggestions for EBP poster creation and to describe the process of developing a Poster Evaluation Rubric for Evidence-Based Practice (PER-EBP). The PER-EBP tool, developed by the authors, provides a guide for EBP poster creation and criteria for EBP poster evaluation by self and others. Examples of an EBP literature review and a DNP student poster are provided.
Long QT Syndrome: A Case Report, Genomics, and Clinical Implications
Authors: Yao Jiaming , Hickey Kathleen
Published: April 2010

Long QT syndrome (LQTS) is a hereditary disorder in which the majority of affected individuals present with QT prolongation on electrocardiograms (ECGs), arising from delayed ventricular repolarization. This commonly arrhythmia-associated genetic syndrome can lead to sudden cardiac death (SCD) and increased propensity for arrythmogenic syncope. The authors describe the case of a young patient who presented with episodes of syncope, prolonged QTc interval on ECG, and family history of SCD. He subsequently received an ICD for protection against SCD based on his prior clinical history. The article discusses the clinical manifestations, electrocardiographic (ECG) findings, management of LQTS, and role of the clinician in testing, teaching, and counseling the affected patients and families.
Evaluating the “Innovativeness Quotient” (IQ) in a Collaborative Model
Authors: Maxworthy Juli C.
Published: April 2010

The health care quality and patient safety movement has evolved rapidly during the past 10 years largely as a result of the Institute of Medicine (IOM) report, “To Err is Human.” Patient safety teams are using a collaborative model to improve patient outcomes. Diffusion of improvement-oriented innovations is a major challenge facing health care. Utilizing a tool to measure innovativeness, a 39-hospital patient safety collaborative was evaluated for their “Innovativeness Quotient.” Findings showed that 75.5% of the members of the collaborative who completed the survey were innovators/early adopters compared to 16% as described for the general population. The application and implications of this project are described.
Modeling and Experimental Determination of Salt Accumulation Induced by Root Water Uptake
Authors: Nishida Kazuhiro , Shiozawa Sho
Published: April 2010

We investigated salt accumulation processes induced by root water uptake above the groundwater table. We compared experimentally determined results from a pot experiment with those predicted by a numerical simulation. Spring wheat (Triticum aestivum L.) was grown in sand‐filled pots, and a constant groundwater table of saline water was maintained. We measured physiological factors of wheat such as daily transpiration rate, leaf water potential, and root length distribution. Water content and salt distribution in the pots were determined. We developed a numerical model for salt accumulation that was based on physical models of water and solute movement in the soil and included a root water uptake term and a stomatal behavior model. The root water uptake rate was calculated using an Ohm's law type model; the transpiration rate as a function of leaf water potential and all soil physical properties regarding water and solute movement in soil were measured independently. Observed and calculated results showed that the salt accumulation pattern changes dynamically with changes in root water uptake patterns and vice versa. In the lower root zone, salt content was at a quasi‐steady state, and salt accumulation did not proceed even though root water uptake occurred there; concentrated salt was transported upward by soil water flux induced by root water uptake in the upper zone. Salt accumulated mainly in the upper root zone where root water uptake ceased due to the lower water potential of the soil. The site of salt accumulation moved downward as salt accumulation proceeded and soil water potential decreased
Hydropedological Implications of Ferromanganiferous Nodules in Rice‐Growing Plinthitic Ultisols under Different Moisture Regimes
Authors: Jien Shih-Hao , Hseu Zeng-Yei , Chen Zueng-Sang
Published: April 2010

Rice (Oryza sativaL.)‐growing soils with plinthite and abundant ferromanganiferous nodules (≥60 g kg−1) were selected to evaluate the formation mechanisms of ferromanganiferous nodules and to determine the relationships among the characteristics of ferromanganiferous nodules under different moisture regimes in soils. Depth to water table, water potential, and redox potential (Eh) were monitored at different soil depths during 2004 and 2005. The results show that the greatest quantity of ferromanganiferous nodules (91–492 g kg−1) were found in plinthic horizons, which had reducing conditions for a moderate amount of time (about 47% of the year). This was especially true for nodules >20 mm in diameter. Micromorphological observation of ferromanganiferous nodules revealed that co‐presentation of secondary Fe and Mn oxides and oriented clay is more apparent in coarser nodules than finer nodules. Based on the micromorphological observation, we deduced that nodules were formed when Mn(II) first precipitated within micropores or coated the coarse nuclear grain surface. Later, reduced Fe, Mn, and illuvial clay continued reoxidizing and precipitating on the initial Mn nodules, which then grew to a larger size. The Fe activity ratio (oxalate‐ to dithionite‐extractable Fe) is suggested as a good index for prediction of the annual duration of reducing conditions in the soils examined in this study. Furthermore, the dithionite‐extractable Mn/Fe ratio in nodules is a good indicator for prediction of the soil depths where the water table fluctuated, because Mn accumulated and was well crystallized at these depths.
Performance of Slow‐Release Formulations of Alachlor
Authors: Undabeytia Tomás , Sopeña Fátima , Sánchez-Verdejo Trinidad , Villaverde Jaime , Nir Shlomo , Morillo Esmeralda , Maqueda Celia
Published: April 2010

Alachlor [2‐chloro‐N‐(2,6‐diethylphenyl)‐N‐(methoxymethyl)acetamide] is a widely used herbicide that has been identified as a groundwater contaminant. Several slow‐release formulations (SRFs) of this herbicide have been examined for their capacity to reduce its leaching and enhance weed control. A field experiment was performed to determine alachlor leaching and bioefficacy in (i) a commercial formulation, Alanex, and (ii) SRFs based on ethylcellulose (EC) microencapsulation or phosphatidylcholine (PC)–montmorillonite complexes. Alachlor distribution within the top 30 cm of the soil layer was modeled with the pesticide‐leaching model PEARL, using release constants for the SRFs obtained from in vitro experiments. Compared with the commercial formulation, leaching to the 20‐ to 30‐cm depth was reduced by 33% for EC and 25% for PC–clay formulations, but only in the latter was herbicide bioefficacy retained. The poor bioefficacy of the EC formulations can be explained by their very slow release properties, which may nevertheless confer an advantage under prolonged heavy rainfall. The model yielded good predictions for the residual amounts of herbicide at 59 and 99 d after treatment (DAT). At 191 DAT, the amounts of alachlor at 0‐ to 20‐cm depth were overestimated by 13 to 23%, indicating limitations of the model at longer times, attributed to (i) the adaptation time of the microbial population for herbicide degradation, and (ii) the effect of herbicide sequestration in the soil matrix, a phenomenon denoted as “aging.