bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in health status and the use of services among the 80-84-year-old Finnish war veterans during 1992 and 2004
Authors: Leskinen M. Riita , Laatikainen Tiina K.M. , Tuomilehto Jaakko O.I. , Aulikki Nissinen M. , Peltonen Markku , Koistinen Pentti O.I. , Antikainen Riitta L.
Published: April 2010

Aim: The aim of this study was to compare the differences in health state, functional capacity and the use of social and health services among the 80—84-year-old Finnish Second World War veterans in 1992 and 2004 and to describe the possible effects of the improvements made based on the results after 1992. Methods: The Veteran Projects were conducted among the veterans using a postal questionnaire. In 1992, the questionnaire was sent to all veterans (n = 242,720) living in Finland, and in 2004 to 5750 veterans who had participated in the study in 1992. The comparable age groups of veterans aged 80—84 years were used. The data were analysed by descriptive statistics and binary logistic regression analysis. Analyses were conducted separately for men with and without disability and for all women. Results: The proportion of men with good self-reported health, painlessness, normal memory and vision and who were able to walk 500 m without difficulties, significantly increased, as did the proportion of women with normal memory and vision. The prevalence of many diseases increased, but diseases appeared to be less disabling in 2004 than 1992. The need for hospital care decreased and the use of rehabilitation services increased, but the increased use of rehabilitation services was not indicative of the ability to walk 500 m. Conclusions: Self-rated health and functional capacity improved and the need for hospital care decreased among veterans, although the prevalence of many diseases increased during the follow-up. Rehabilitation was not associated with the ability to walk 500 m without difficulties.
Never too late
Authors: Piquero Alex R. , Cullen Francis T. , Unnever James D. , Piquero Nicole L. , Gordon Jill A.
Published: April 2010

Policy decisions with respect to juvenile offenders oscillate between rehabilitation and punishment, and the effectiveness of these two approaches, including which one for which type of offender, has yet to be realized. Less studied is the extent to which the public favors one approach or the other generally, and whether the public believes that there is an age at which it may be too late to help a juvenile offender turn away from a life of crime. In this study, we explore whether optimism about juvenile rehabilitation is a near universal, shared belief, or whether there exist important variations across socio-demographic groups about whether juveniles can be rehabilitated (and if so at what age). Studying this issue is important because public attitudes have the potential to shape policy. In the domain of juvenile justice, the challenge is whether public opinion will breed unfettered punitiveness or, as we anticipate, will serve as an impetus for a richer and more progressive response to juvenile offenders. Using data from a random sample of Pennsylvania residents, our results point not toward a division over the beliefs about ‘saving children,’ but instead demonstrate a consensus — that optimism about juvenile rehabilitation is not something citizens argue over. Implications for public policies regarding juvenile offenders are addressed.
Victim movements at a crossroad
Authors: Christie Nils
Published: April 2010

Victim movements are growing in most western countries. This is a natural consequence of modernity. Neighbourhoods are weakened, state control moves in and victims might feel they are left behind, forgotten in the legal process. Now they demand a new entrance. This is easy to understand, but difficult to absorb in a penal process. Victim power might be a strong driving force towards the punitive society. And may be it is bad also for victims. Civil meetings between victims and the persons or systems that might have hurt them might be more constructive alternatives, both for victims and their communities. In such meetings there are no limits to what can be expressed. Here delivery of pain is not at the centre, but the question of what happened, how could you do this to me or mine, or to values dear to us? Victim movements stand at a crossroad. They might strengthen civil societies and their members, or create further damage.
Detained in occupied Iraq
Authors: Welch Michael
Published: April 2010

The war in Iraq has prompted some criminologists to examine such matters as the illegality of the invasion and subsequent occupation, controversial economic transformations, and the abuse — torture — of detainees at Abu Ghraib. For the most part, criminologists have neglected the problem of mass detention aimed at the civilian population: by 2007, the US military held more than 26,000 Iraqis in a network of large camps. Those civilians remained in long-term custody because the American commanders deemed them ‘imperative threats’ but not criminal nor terrorist. In an effort to shed critical light on that aspect of the occupation, this work interprets the official narratives used to justify the detention process and the role of American-styled reintegration programs. By doing so, the analysis draws on colonial theory in ways that deepen our understanding of social control and discipline in the new Iraq. Mindful of human rights, the discussion confronts important facets of enduring domination inherent in modern colonial projects.
Vibration-based Damage Identification Methods: A Review and Comparative Study
Authors: Wei Fan  , Pizhong Qiao
Published: April 2010

A comprehensive review on modal parameter-based damage identification methods for beam- or plate-type structures is presented, and the damage identification algorithms in terms of signal processing are particularly emphasized. Based on the vibration features, the damage identification methods are classified into four major categories: natural frequency-based methods, mode shape-based methods, curvature mode shape-based methods, and methods using both mode shapes and frequencies, and their merits and drawbacks are discussed. It is observed that most mode shape-based and curvature mode shape-based methods only focus on damage localization. In order to precisely locate the damage, the mode shape-based methods have to rely on optimization algorithms or signal processing techniques; while the curvature mode shape-based methods are in general a very effective type of damage localization algorithms. As an implementation, a comparative study of five extensively-used damage detection algorithms for beam-type structures is conducted to evaluate and demonstrate the validity and effectiveness of the signal processing algorithms. This brief review aims to help the readers in identifying starting points for research in vibration-based damage identification and structural health monitoring and guides researchers and practitioners in better implementing available damage identification algorithms and signal processing methods for beam- or plate-type structures.
Adaptive Fiber Bragg Grating Sensor Network for Structural Health Monitoring: Applications to Impact Monitoring
Authors: Kirikera Goutham R. , Balogun O. , Krishnaswamy Sridhar
Published: April 2010

A passive structural health monitoring (SHM) system for locating foreign-object impact using a network of fiber Bragg grating (FBG) sensors that monitor high frequency dynamic strains is described. The FBG sensor signals are adaptively demodulated using a two-wave mixing (TWM) spectral demodulator. Strains applied on the FBG sensors are encoded as wavelength shifts of the light reflected by the FBG sensor which are then converted into phase shifts and demodulated by the TWM interferometer. The demodulator adaptively compensates for low frequency drifts caused by large quasi-static strain and temperature drift and allows only high frequency signals to pass through. The FBG sensor network is mounted on a plate, and the structure is subjected to artificial impacts generated by dropping small ball bearings. Owing to the directional sensitivity of the FBG sensors, an FBG sensor-pair configuration is used at each sensing location. The impact signals from multiple FBG sensors are simultaneously acquired at frequencies of up to 180kHz. Using time-frequency wavelet analysis, the group velocity dispersion curve of the detected Lamb wave modes is obtained from the measured transient responses of the sensors, and this is used to determine the location of the impact.
Instantaneous Identification of Degrading Hysteretic Oscillators Under Earthquake Excitation
Authors: Ceravolo Rosario , Demarie Giacomo Vincenzo , Erlicher Silvano
Published: April 2010

This article presents a technique for the structural identification of hysteretic oscillators that are characterized by degradation in stiffness. The main assumption of the proposed procedure is that it is possible to replace the expression of the time derivative of the restoring force with a polynomial approximation, characterized by time-varying coefficients. The work aims at generalizing a method that the authors have proposed for hysteretic nondegrading systems: system parameters are evaluated from instantaneous estimates of the time-varying coefficients. The instantaneous estimation, based on optimization techniques, is made possible through the temporal localization of frequency components, i.e., the representation in the joint time—frequency domain. A numerical application consisting of the instantaneous identification of a Bouc-Wen model with stiffness degradation under earthquake excitation is presented and discussed. Although the sensitivity of the estimation to exogenous noise is greater than in the nondegrading case, the global accuracy of the identification is satisfactory.
Trends in the application of dynamic allocation methods in multi-arm cancer clinical trials
Authors: Pond Gregory R , Tang Patricia A , Welch Stephen A , Chen Eric X
Published: April 2010

Background Dynamic allocation (DA) methods which attempt to balance baseline prognostic factors between treatment arms, can be used in multi-arm clinical trials to sequentially allocate patients to treatment. Although some experts express concern regarding the validity of inference from trials using DA, others believe DA methods produce more credible results.

Purpose A review of published multi-arm cancer clinical trials was conducted to explore the frequency of DA use in oncology.

Methods Multi-arm phase III clinical trials of at least 100 patients per arm, published in 13 major oncology journals from 1995—2005 were manually reviewed. Information about reported use of DA methods, or randomization via random permuted blocks (PB), was extracted along with trial characteristics.

Results Of 476 published clinical trials, 112 (23.5%) reported using some form of DA method, while 103 (21.6%) reported using PB methods. Most trials (403 or 84.7%) reported stratifying on at least one baseline factor. The mean number of stratification factors was 2.70 per trial, and 78.6% of DA trials reported 3 or more stratification factors compared with 30.2% of non-DA trials (p < 0.001). The frequency of DA use increased over time, with 20.2%, 21.3%, 25.8%, 28.8% and 38.9% of trials reported use in 1995—2001, 2002, 2003, 2004, and 2005, respectively. Use of DA methods was more frequently reported in trials involving an academic co-operative group (28.4% vs. 13.8%), however, no difference was observed between industry-funded and other-funded trials (24.0% vs. 23.2%) or geographical region (19.7% of North American trials, 26.2% of European trials and 21.7% of multinational/other trials).

Limitations As a retrospective analysis, the true frequency of DA use is likely underreported. Few trials gave complete details of the allocation method used, thus it is possible some manuscripts reported incorrect allocation methods. Journals were selected which were assumed to publish most large, multi-arm clinical trials in cancer from 1995—2005, however, some trials were likely reported in journals other than what was reviewed.

Conclusions DA methods are frequently used in multi-arm cancer clinical trials. The use of DA appears to becoming more common over time and are used more frequently when an academic cooperative group is involved. No relationship between industry funded trials or geographic region and allocation method was observed. Clinical Trials 2010; 7: 227—234. http://ctj.sagepub.com
To What Extent is the Experience of Empathy Mediated by Shared Neural Circuits?
Authors: Decety Jean
Published: April 2010

This paper selectively reviews the neurophysiological evidence for shared neural circuits (supposedly implemented by mirror neurons) as the mechanism underlying empathy. I will argue that while the mirror neuron system plays a role in motor resonance, it is not possible to conclude that this system is critically involved in emotion recognition, and there is little evidence for its role in empathy and sympathy. In addition, there is modest support from neurological observations that lesion of the regions involved in the mirror neuron system leads to dysfunction in empathy, whereas damage of the ventromedial prefrontal cortex is associated with such impairment. To significantly advance our understanding of the mechanisms underlying empathy, research needs finer conceptualization, better designed paradigms, and integration with knowledge from lesion studies.
Toward a Microdevelopmental, Interdisciplinary Approach to Social Emotion
Authors: Immordino-Yang Mary Helen
Published: April 2010

Social emotions about others’ minds, for example, admiration for virtue and compassion for social pain, play a critical role in interpersonal relationships, motivation, and morality. However, historical biases toward studying emotions as automatic reactions generated within a solitary individual limit our ability to study emotions about others’ minds, which are inherently complex, social, and subjective. Here, I argue that a microdevelopmental approach, that is, considering these emotions as dynamic, context-dependent mental constructions actively organized from simpler cognitive and affective psychological components, may help to overcome the difficulties of studying these emotions by providing new perspectives on: reliably inducing these emotions; parsing the ensuing experiences into component psychological processes organizing over time; and relating these component processes to patterns of brain activation.
RAGE and ICAM-1 cooperate in mediating leukocyte recruitment during acute inflammation in vivo
Authors: Frommhold David , Kamphues Anna , Hepper Ingrid , Pruenster Monika , Lukić Ivan K. , Socher Ines , Zablotskaya Victoria , Buschmann Kirsten , Lange-Sperandio Baerbel , Schymeinsky Jürgen , Ryschich Eduard , Poeschl Johannes , Kupatt Christian , Nawroth Peter P. , Moser Markus , Walzog Barbara , Bierhaus Angelika , Sperandio Markus
Published: April 2010

The receptor for advanced glycation end products (RAGE) contributes to the inflammatory response in many acute and chronic diseases. In this context, RAGE has been identified as a ligand for the β2-integrin Mac-1 under static in vitro conditions. Because intercellular adhesion molecule (ICAM)-1 also binds β2-integrins, we studied RAGE−/−, Icam1−/−, and RAGE−/−Icam1−/− mice to define the relative contribution of each ligand for leukocyte adhesion in vivo. We show that trauma-induced leukocyte adhesion in cremaster muscle venules is strongly dependent on RAGE and ICAM-1 acting together in an overlapping fashion. Additional in vivo experiments in chimeric mice lacking endothelium-expressed RAGE and ICAM-1 located the adhesion defect to the endothelial compartment. Using microflow chambers coated with P-selectin, CXCL1, and soluble RAGE (sRAGE) demonstrated that sRAGE supports leukocyte adhesion under flow conditions in a Mac-1– but not LFA-1–dependent fashion. A static adhesion assay revealed that wild-type and RAGE−/− neutrophil adhesion and spreading were similar on immobilized sRAGE or fibrinogen. These observations indicate a crucial role of endothelium-expressed RAGE as Mac-1 ligand and uncover RAGE and ICAM-1 as a new set of functionally linked adhesion molecules, which closely cooperate in mediating leukocyte adhesion during the acute trauma-induced inflammatory response in vivo.
Rac2 GTPase deficiency depletes BCR-ABL+ leukemic stem cells and progenitors in vivo
Authors: Sengupta Amitava , Arnett Jorden , Dunn Susan , Williams David A. , Cancelas Jose A.
Published: April 2010

Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disease (MPD) initiated by p210-BCR-ABL–mediated transformation of hematopoietic stem cells (HSCs). Inhibition of the ABL kinase alone is not sufficient to eradicate leukemic stem cells (LSCs). We have previously shown that the deficiency of Rac2 GTPase signaling, but not Rac1, in p210-BCR-ABL–transduced hematopoietic cells prolonged survival of mice with MPD. Here we demonstrate that absence of Rac2 GTPase prolongs survival of HSC-initiated, inducible Scl/p210-BCR-ABL (Scl/p210) binary transgenic mice, it induces apoptosis, and, unlike in normal HSC and progenitor (HSC/P), impairs LSC and progenitor (LSC/P) proliferation in vivo. As a result, Rac2 deficiency causes functional exhaustion of the LSC pool in vivo. This defect is not due to impaired interaction with the hematopoietic microenvironment as reflected by its unaltered adhesion, migration, and homing to recipient organs. In summary, Rac2 deficiency exhausts the LSC pool in vivo through impairment of oncogene-induced proliferation and survival signals.
Iron control of erythroid development by a novel aconitase-associated regulatory pathway
Authors: Bullock Grant C. , Delehanty Lorrie L. , Talbot Anne-Laure , Gonias Sara L. , Tong Wing-Hang , Rouault Tracey A. , Dewar Brian , Macdonald Jeffrey M. , Chruma Jason J. , Goldfarb Adam N.
Published: April 2010

Human red cell differentiation requires the action of erythropoietin on committed progenitor cells. In iron deficiency, committed erythroid progenitors lose responsiveness to erythropoietin, resulting in hypoplastic anemia. To address the basis for iron regulation of erythropoiesis, we established primary hematopoietic cultures with transferrin saturation levels that restricted erythropoiesis but permitted granulopoiesis and megakaryopoiesis. Experiments in this system identified as a critical regulatory element the aconitases, multifunctional iron-sulfur cluster proteins that metabolize citrate to isocitrate. Iron restriction suppressed mitochondrial and cytosolic aconitase activity in erythroid but not granulocytic or megakaryocytic progenitors. An active site aconitase inhibitor, fluorocitrate, blocked erythroid differentiation in a manner similar to iron deprivation. Exogenous isocitrate abrogated the erythroid iron restriction response in vitro and reversed anemia progression in iron-deprived mice. The mechanism for aconitase regulation of erythropoiesis most probably involves both production of metabolic intermediates and modulation of erythropoietin signaling. One relevant signaling pathway appeared to involve protein kinase Cα/β, or possibly protein kinase Cδ, whose activities were regulated by iron, isocitrate, and erythropoietin.
Netrin-4 induces lymphangiogenesis in vivo
Authors: Larrieu-Lahargue Frederic , Welm Alana L. , Thomas Kirk R. , Li Dean Y.
Published: April 2010

Netrin-4, a laminin-related secreted protein is an axon guidance cue recently shown essential outside of the nervous system, regulating mammary and lung morphogenesis as well as blood vascular development. Here, we show that Netrin-4, at physiologic doses, induces proliferation, migration, adhesion, tube formation and survival of human lymphatic endothelial cells in vitro comparable to well-characterized lymphangiogenic factors fibroblast growth factor-2 (FGF-2), hepatocyte growth factor (HGF), vascular endothelial growth factor-A (VEGF-A), and vascular endothelial growth factor-C (VEGF-C). Netrin-4 stimulates phosphorylation of intracellular signaling components Akt, Erk and S6, and their specific inhibition antagonizes Netrin-4–induced proliferation. Although Netrin receptors Unc5B and neogenin, are expressed by human lymphatic endothelial cells, suppression of either or both does not suppress Netrin-4–promoted in vitro effects. In vivo, Netrin-4 induces growth of lymphatic and blood vessels in the skin of transgenic mice and in breast tumors. Its overexpression in human and mouse mammary carcinoma cancer cells leads to enhanced metastasis. Finally, Netrin-4 stimulates in vitro and in vivo lymphatic permeability by activating small GTPases and Src family kinases/FAK, and down-regulating tight junction proteins. Together, these data provide evidence that Netrin-4 is a lymphangiogenic factor contributing to tumor dissemination and represents a potential target to inhibit metastasis formation.
Pegylated arginase I: a potential therapeutic approach in T-ALL
Authors: Hernandez Claudia P. , Morrow Kevin , Lopez-Barcons Lluis A. , Zabaleta Jovanny , Sierra Rosa , Velasco Cruz , Cole John , Rodriguez Paulo C.
Published: April 2010

Adult patients with acute lymphoblastic T cell leukemia (T-ALL) have a very poor prognosis and few effective therapeutic options. Therefore, novel therapies that increase the efficacy of the treatments and that prolong T-ALL patient survival are needed. Malignant T cells require high concentrations of nutrients to sustain their increased rate of proliferation. In this study, we determined whether L-Arginine depletion by the pegylated form of the L-Arginine-metabolizing enzyme arginase I (peg-Arg I) impairs the proliferation of malignant T cells. Our results show that peg-Arg I depleted L-Arginine levels in vitro and in vivo. In addition, treatment of malignant T-cell lines with peg-Arg I significantly impaired their proliferation, which correlated with a decreased progression into the cell cycle, followed by the induction of apoptosis. Furthermore, peg-Arg I impaired the expression of cyclin D3, a fundamental protein in T-ALL proliferation, through a global arrest in protein synthesis. Injection of peg-Arg I plus chemotherapy agent Cytarabine prolonged survival in mice bearing T-ALL tumors. This antitumoral effect correlated with an inhibition of T-ALL proliferation in vivo, a decreased expression of cyclin D3, and T-ALL apoptosis. The results suggest the potential benefit of L-Arginine depletion by peg-Arg I in the treatment of T-cell malignancies.
Anxiety- and depressive-like responses and c-fos activity in preproenkephalin knockout mice: Oversensitivity hypothesis of enkephalin deficit-induced posttraumatic stress disorder
Authors: Kung Jen-Chuang , Chen Tsung-Chieh , Shyu Bai-Chuang , Hsiao Sigmund , Huang Andrew Chih Wei
Published: April 2010

The present study used the preproenkephalin knockout (ppENK) mice to test whether the endogenous enkephalins deficit could facilitate the anxiety- and depressive-like symptoms of posttraumatic stress disorder (PTSD). On Day 1, sixteen wildtype (WT) and sixteen ppENK male mice were given a 3 mA or no footshock treatment for 10 seconds in the footshock apparatus, respectively. On Days 2, 7, and 13, all mice were given situational reminders for 1 min per trial, and the freezing response was assessed. On Day 14, all mice were tested in the open field test, elevated plus maze, light/dark avoidance test, and forced swim test. Two hours after the last test, brain tissues were stained to examine c-fosexpression in specific brain areas. The present results showed that the conditioned freezing response was significant for different genotypes (ppENK vs WT). The conditioned freezing effect of the ppENK mice was stronger than those of the WT mice. On Day 14, the ppENK mice showed more anxiety- and depressive-like responses than WT mice. The magnitude of Fos immunolabeling was also significantly greater in the primary motor cortex, bed nucleus of the stria terminalis-lateral division, bed nucleus of the stria terminalis-supracapsular division, paraventricular hypothalamic nucleus-lateral magnocellular part, central nucleus of the amygdala, and basolateral nucleus of the amygdala in ppENK mice compared with WT mice. In summary, animals with an endogenous deficit in enkephalins might be more sensitive to PTSD-like aversive stimuli and elicit stronger anxiety and depressive PTSD symptoms, suggesting an oversensitivity hypothesis of enkephalin deficit-induced PTSD.
SNP-RFLPing 2: an updated and integrated PCR-RFLP tool for SNP genotyping
Authors: Chang Hsueh-Wei , Cheng Yu-Huei , Chuang Li-Yeh , Yang Cheng-Hong
Published: April 2010

Background

PCR-restriction fragment length polymorphism (RFLP) assay is a cost-effective method for SNP genotyping and mutation detection, but the manual mining for restriction enzyme sites is challenging and cumbersome. Three years after we constructed SNP-RFLPing, a freely accessible database and analysis tool for restriction enzyme mining of SNPs, significant improvements over the 2006 version have been made and incorporated into the latest version, SNP-RFLPing 2.

Results

The primary aim of SNP-RFLPing 2 is to provide comprehensive PCR-RFLP information with multiple functionality about SNPs, such as SNP retrieval to multiple species, different polymorphism types (bi-allelic, tri-allelic, tetra-allelic or indels), gene-centric searching, HapMap tagSNPs, gene ontology-based searching, miRNAs, and SNP500Cancer. The RFLP restriction enzymes and the corresponding PCR primers for the natural and mutagenic types of each SNP are simultaneously analyzed. All the RFLP restriction enzyme prices are also provided to aid selection. Furthermore, the previously encountered updating problems for most SNP related databases are resolved by an on-line retrieval system.

Conclusions

The user interfaces for functional SNP analyses have been substantially improved and integrated. SNP-RFLPing 2 offers a new and user-friendly interface for RFLP genotyping that can be used in association studies and is freely available at http://bio.kuas.edu.tw/snp-rflping2.
Genome-wide comparison between IL-17 and combined TNF-alpha/IL-17 induced genes in primary murine hepatocytes
Authors: Sparna Titus , Rétey Julia , Schmich Kathrin , Albrecht Ute , Naumann Katrin , Gretz Norbert , Fischer Hans-Peter , Bode Johannes G , Merfort Irmgard
Published: April 2010

Background

Cytokines such as TNF-alpha and IL-1beta are known for their contribution to inflammatory processes in liver. In contrast, the cytokine IL-17 has not yet been assigned a role in liver diseases. IL-17 can cooperate with TNF-alpha to induce a synergistic response on several target genes in different cell lines, but no data exist for primary hepatocytes. To enhance our knowledge on the impact of IL-17 alone and combined with TNF-alpha in primary murine hepatocytes a comprehensive microarray study was designed. IL-1beta was included as this cytokine is suggested to act in a similar manner as the combination of TNF-alpha and IL-17, especially with respect to its role in mRNA stabilization.

Results

The present microarray analysis demonstrates that primary murine hepatocytes responded to IL-17 stimulation by upregulation of chemokines and genes, which are functionally responsible to increase and sustain inflammation. Cxcl2, Nfkbiz and Zc3h12a were strongly induced, whereas the majority of the genes were only very moderately up-regulated. Promoter analysis revealed involvement of NF-kappaB in the activation of many genes. Combined stimulation of TNF-alpha/IL-17 resulted in enhanced induction of gene expression, but significantly synergistic effects could be applied only to a few genes, such as Nfkbiz, Cxcl2, Zc3h12 and Steap4. Comparison of the gene expression profile obtained after stimulation of TNF-alpha/IL-17 versus IL-1beta proposed an "IL-1beta-like effect" of the latter cytokine combination. Moreover, evidence was provided that modulation of mRNA stability may be a major mechanism by which IL-17 regulates gene expression in primary hepatocytes. This assumption was exemplarily proven for Nfkbiz mRNA for the first time in hepatocytes. Our studies also suggest that RNA stability can partially be correlated to the existence of AU rich elements, but further mechanisms like the RNase activity of the up-regulated Zc3h12a have to be considered.

Conclusions

Our microarray analysis gives new insights in IL-17 induced gene expression in primary hepatocytes highlighting the crosstalk with the NF-kappaB signaling pathway. Gene expression profile suggests IL-17 alone and in concert with TNF-alpha a role in sustaining liver inflammatory processes. IL-17 might exceed this function by RNA stabilization.
Reconstruction of xylose utilization pathway and regulons in Firmicutes
Authors: Gu Yang , Ding Yi , Ren Cong , Sun Zhe , Rodionov Dmitry A , Zhang Weiwen , Yang Sheng , Yang Chen , Jiang Weihong
Published: April 2010

Background

Many Firmicutes bacteria, including solvent-producing clostridia such as Clostridium acetobutylicum, are able to utilize xylose, an abundant carbon source in nature. Nevertheless, homology searches failed to recognize all the genes for the complete xylose and xyloside utilization pathway in most of them. Moreover, the regulatory mechanisms of xylose catabolism in many Firmicutes except Bacillus spp. still remained unclear.

Results

A comparative genomic approach was used to reconstruct the xylose and xyloside utilization pathway and analyze its regulatory mechanisms in 24 genomes of the Firmicutes. A novel xylose isomerase that is not homologous to previously characterized xylose isomerase, was identified in C. acetobutylicum and several other Clostridia species. The candidate genes for the xylulokinase, xylose transporters, and the transcriptional regulator of xylose metabolism (XylR), were unambiguously assigned in all of the analyzed species based on the analysis of conserved chromosomal gene clustering and regulons. The predicted functions of these genes in C. acetobutylicum were experimentally confirmed through a combination of genetic and biochemical techniques. XylR regulons were reconstructed by identification and comparative analysis of XylR-binding sites upstream of xylose and xyloside utilization genes. A novel XylR-binding DNA motif, which is exceptionally distinct from the DNA motif known for Bacillus XylR, was identified in three Clostridiales species and experimentally validated in C. acetobutylicum by an electrophoretic mobility shift assay.

Conclusions

This study provided comprehensive insights to the xylose catabolism and its regulation in diverse Firmicutes bacteria especially Clostridia species, and paved ways for improving xylose utilization capability in C. acetobutylicum by genetic engineering in the future.
Do coder characteristics influence validity of ICD-10 hospital discharge data?
Authors: Hennessy Deirdre A , Quan Hude , Faris Peter D , Beck Cynthia A
Published: April 2010

Background

Administrative data are widely used to study health systems and make important health policy decisions. Yet little is known about the influence of coder characteristics on administrative data validity in these studies. Our goal was to describe the relationship between several measures of validity in coded hospital discharge data and 1) coders' volume of coding (≥13,000 vs. <13,000 records), 2) coders' employment status (full- vs. part-time), and 3) hospital type.

Methods

This descriptive study examined 6 indicators of face validity in ICD-10 coded discharge records from 4 hospitals in Calgary, Canada between April 2002 and March 2007. Specifically, mean number of coded diagnoses, procedures, complications, Z-codes, and codes ending in 8 or 9 were compared by coding volume and employment status, as well as hospital type. The mean number of diagnoses was also compared across coder characteristics for 6 major conditions of varying complexity. Next, kappa statistics were computed to assess agreement between discharge data and linked chart data reabstracted by nursing chart reviewers. Kappas were compared across coder characteristics.

Results

422,618 discharge records were coded by 59 coders during the study period. The mean number of diagnoses per record decreased from 5.2 in 2002/2003 to 3.9 in 2006/2007, while the number of records coded annually increased from 69,613 to 102,842. Coders at the tertiary hospital coded the most diagnoses (5.0 compared with 3.9 and 3.8 at other sites). There was no variation by coder or site characteristics for any other face validity indicator. The mean number of diagnoses increased from 1.5 to 7.9 with increasing complexity of the major diagnosis, but did not vary with coder characteristics. Agreement (kappa) between coded data and chart review did not show any consistent pattern with respect to coder characteristics.

Conclusions

This large study suggests that coder characteristics do not influence the validity of hospital discharge data. Other jurisdictions might benefit from implementing similar employment programs to ours, e.g.: a requirement for a 2-year college training program, a single management structure across sites, and rotation of coders between sites. Limitations include few coder characteristics available for study due to privacy concerns.
Anopheles culicifacies breeding in brackish waters in Sri Lanka and implications for malaria control
Authors: Jude Pavilupillai J , Dharshini Sangaralingam , Vinobaba Muthuladchumy , Surendran Sinnathamby N , Ramasamy Ranjan
Published: April 2010

Background

Anopheles culicifacies is the major vector of both falciparum and vivax malaria in Sri Lanka, while Anopheles subpictus and certain other species function as secondary vectors. In Sri Lanka, An. culicifacies is present as a species complex consisting of species B and E, while An. subpictus exists as a complex of species A-D. The freshwater breeding habit of An. culicifacies is well established. In order to further characterize the breeding sites of the major malaria vectors in Sri Lanka, a limited larval survey was carried out at a site in the Eastern province that was affected by the 2004 Asian tsunami.

Methods

Anopheline larvae were collected fortnightly for six months from a brackish water body near Batticaloa town using dippers. Collected larvae were reared in the laboratory and the emerged adults were identified using standard keys. Sibling species status was established based on Y-chromosome morphology for An. culicifacies larvae and morphometric characteristics for An. subpictus larvae and adults. Salinity, dissolved oxygen and pH were determined at the larval collection site.

Results

During a six month study covering dry and wet seasons, a total of 935 anopheline larvae were collected from this site that had salinity levels up to 4 parts per thousand at different times. Among the emerged adult mosquitoes, 661 were identified as An. culicifacies s.l. and 58 as An. subpictus s.l. Metaphase karyotyping of male larvae showed the presence of species E of the Culicifacies complex, and adult morphometric analysis the presence of species B of the Subpictus complex. Both species were able to breed in water with salinity levels up to 4 ppt.

Conclusions

The study demonstrates the ability of An. culicifacies species E, the major vector of falciparum and vivax malaria in Sri Lanka, to oviposit and breed in brackish water. The sibling species B in the An. subpictus complex, a well-known salt water breeder and a secondary malaria vector in the country, was also detected at the same site. Since global warming and the rise in sea levels will further increase of inland brackish water bodies, the findings have significant implications for the control of malaria in Sri Lanka and elsewhere.
A retroviral mutagenesis screen identifies Cd74 as a common insertion site in murine B-lymphomas and reveals the existence of a novel IFNγ-inducible Cd74 isoform
Authors: Pyrz Magdalena , Wang Bruce , Wabl Matthias , Pedersen Finn Skou
Published: April 2010

Background

Insertional mutagenesis screens in the mouse are an acknowledged approach to identify genes involved in the pathogenesis of cancer. The potential of these screens to identify genes causally involved in tumorigenesis is not only limited to the murine host, but many of these genes have also been proven to be involved in the oncogenic process in man.

Results

Through an insertional mutagenesis screen applying murine leukemia viruses in mouse, we found thatCd74was targeted by proviral insertion in tumors of B-cell origin. This locus encodes a protein playing crucial roles in antigen presentation and B-cell homeostasis, and its deregulation is often associated with cancer in man. The distribution of insertions within theCd74locus prompted the identification of an alternative transcript initiated in intron 1 ofCd74encoding an N-terminally truncated Cd74 isoform in tissues from un-infected mice, and transcriptional activation assays revealed a positive effect on the novel intronic promoter by a formerly described intronic enhancer in theCd74locus. Furthermore, we show that the new Cd74 isoform is IFNγ inducible and that its expression is differentially regulated from the canonical Cd74 isoform at the transcriptional level.

Conclusions

We here identifyCd74as a common insertion site in murine B-lymphomas and describe a novel IFNγ-inducible murine Cd74 isoform differentially regulated from the canonical isoform and expressed under the control of an intronic promoter. The distribution and orientation of proviral insertion sites within theCd74locus underscores the causal involvement of the isoforms in the murine B-lymphomagenic process.
Identification of responsive gene modules by network-based gene clustering and extending: application to inflammation and angiogenesis
Authors: Gu Jin , Chen Yang , Li Shao , Li Yanda
Published: April 2010

Background

Cell responses to environmental stimuli are usually organized as relatively separate responsive gene modules at the molecular level. Identification of responsive gene modules rather than individual differentially expressed (DE) genes will provide important information about the underlying molecular mechanisms. Most of current methods formulate module identification as an optimization problem: find the active sub-networks in the genome-wide gene network by maximizing the objective function considering the gene differential expression and/or the gene-gene co-expression information. Here we presented a new formulation of this task: a group of closely-connected and co-expressed DE genes in the gene network are regarded as the signatures of the underlying responsive gene modules; the modules can be identified by finding the signatures and then recovering the "missing parts" by adding the intermediate genes that connect the DE genes in the gene network.

Results

ClustEx, a two-step method based on the new formulation, was developed and applied to identify the responsive gene modules of human umbilical vein endothelial cells (HUVECs) in inflammation and angiogenesis models by integrating the time-course microarray data and genome-wide PPI data. It shows better performance than several available module identification tools by testing on the reference responsive gene sets. Gene set analysis of KEGG pathways, GO terms and microRNAs (miRNAs) target gene sets further supports the ClustEx predictions.

Conclusion

Taking the closely-connected and co-expressed DE genes in the condition-specific gene network as the signatures of the underlying responsive gene modules provides a new strategy to solve the module identification problem. The identified responsive gene modules of HUVECs and the corresponding enriched pathways/miRNAs provide useful resources for understanding the inflammatory and angiogenic responses of vascular systems.
Descriptive study of stress and satisfaction at work in the Saragossa university services and administration staff
Authors: Tricas Moreno Jose Miguel , Salavera Bordas Carlos , Lucha Lopez Ma Orosia , Vidal Peracho Concepcion , Lucha Lopez Ana Carmen , Estebanez de Miguel Elena , Bernues Vazquez Luis
Published: April 2010

Background

The notion of stress in connection with the work environment became an important topic during the 1970's, when the first studies on the subject were published and the term of work stress was first coined. In 1974, Freudenberger proposed the term burnout to refer to the condition of physical and emotional exhaustion, as well as the associated negative attitudes, resulting from the intense interaction in working with people. The aim of our study is to examine burnout and job satisfaction in Saragossa University Services and Administration Staff (SAS) and detect the main factors which could contribute to too much stress, because job stress has emerged as a major psychosocial influence on mental health, associated with burnout.

Methods

24 people from the Services and Administration Staff in the University of Saragossa participated in the study. The research was carried out during the implementation of a module on Stress Management organised by the University of Saragossa and commissioned to the Unit for Research in Physical Therapy (University School of Health Sciences) from that University. This research is an exploratory research to improve the stress management program. A personal interview was carried out and additionally, participants were given the Maslach Burnout Inventory and the Scale of Satisfaction at Work of Warr, Cook & Wall.

Results

However using small sample this is worth to state that participants present most of them low burnout levels in the burnout scale. Only in one person high exhaustion level was reflected, even though other seven showed mean levels; in the professional self-esteem section, most of them showed high self-esteem, with two cases of low self-esteem and five with mean level.

With regard to satisfaction people participating in the study show mean levels in intrinsic as much as in extrinsic factors and general satisfaction.

Conclusions

Services and Administration Staff from the University of Saragossa shows low burnout levels linked with high professional self-esteem and low emotional exhaustion and depersonalization.

It has been found also medium levels in work satisfaction probably related with the continuous quality improvement efforts in the academics environment to create protective factors in decreasing levels of job stress.

These results show that not only personality or temperament have an influence on burnout and stress, also the job conditions are related with these diseases. These aspects should be taken into account in the design of stress prevention programme at work.
Rapid and Direct Transport of Cell Surface APP to the Lysosome defines a novel selective pathway
Authors: Lorenzen Angela , Samosh Jonathan , Vandewark Kenneth , Anborgh Pieter H , Seah Claudia , Magalhaes Ana C , Cregan Sean P , Ferguson Stephen SG , Pasternak Stephen H
Published: April 2010

Background

A central feature of Alzheimer's disease is the cleavage of the amyloid precursor protein (APP) to form beta-amyloid peptide (Aβ) by the β-secretase and γ-secretase enzymes. Although this has been shown to occur after endocytosis of APP from the cell surface, the exact compartments of APP processing are not well defined. We have previously demonstrated that APP and γ-secretase proteins and activity are highly enriched in purified rat liver lysosomes. In order to examine the lysosomal distribution and trafficking of APP in cultured cells, we generated constructs containing APP fused to a C-terminal fluorescent protein tag and N-terminal HA-epitope tag. These were co-transfected with a panel of fluorescent-protein tagged compartment markers.

Results

Here we demonstrate using laser-scanning confocal microscopy that although APP is present throughout the endosomal/lysosomal system in transfected Cos7 and neuronal SN56 cell lines as well as in immunostained cultured mouse neurons, it is enriched in the lysosome. We also show that the Swedish and London mutations reduce the amount of APP in the lysosome. Surprisingly, in addition to its expected trafficking from the cell surface to the early and then late endosomes, we find that cell-surface labelled APP is transported rapidly and directly from the cell surface to lysosomes in both Cos7 and SN56 cells. This rapid transit to the lysosome is blocked by the presence of either the London or Swedish mutations.

Conclusions

These results demonstrate the presence of a novel, rapid and specific transport pathway from the cell surface to the lysosomes. This suggests that regulation of lysosomal traffic could regulate APP processing and that the lysosome could play a central role in the pathophysiology of Alzheimer's disease.
Estimation of the penetration angle of a man-made tunnel using time of arrival measured by short-pulse cross-borehole radar
Authors: Kim Sang-Wook , Kim Se-Yun , Nam Sangwook
Published: April 2010

The relatively fast propagation of electromagnetic signals through empty man-made tunnels has played a key role in detecting deep underground tunnels using a short-pulse cross-borehole radar system. Our cross-borehole radar system measured the pulse signatures of an obliquely penetrating tunnel using eight different borehole pairs at a test site in Korea. Compared to the arrival times of the first peaks, the arrival times of the first received signals at an appropriate amplitude level provided an increasingly clear indication of the empty tunnel as its penetration angle became more oblique. A quadratic relationship between the arrival time of the first received signal and the oblique angle of the empty tunnel was obtained in pure granite.
Increased Incidence of Visceral Metastases in Scottish Patients With BRCA1/2-Defective Ovarian Cancer: An Extension of the Ovarian BRCAness Phenotype
Authors: Gourley Charlie , Michie Caroline O. , Roxburgh Patricia , Yap Timothy A. , Harden Sharon , Paul Jim , Ragupathy Kalpana , Todd Radha , Petty Russell , Reed Nick , Hayward Richard L. , Mitchell Paul , Rye Tzyvia , Schellens Jan H.M. , Lubinski Jan , Carmichael James , Kaye Stan B. , Mackean Melanie , Ferguson Michelle
Published: April 2010

Purpose

To compare the frequency of visceral relapse of BRCA1/2-deficient ovarian cancer to that of nonhereditary controls.

Patients and Methods

All patients diagnosed in Scotland with epithelial ovarian cancer (EOC) or primary peritoneal cancer (PPC) and a germline BRCA1/2 mutation were identified. Those with previous malignancy were excluded. Each remaining patient who experienced relapse was matched with two nonhereditary controls.

Results

Seventy-nine patients with EOC/PPC and germline BRCA1/2 mutations were identified. Fifteen had inadequate clinical data, two had carcinosarcoma, 27 had previous breast cancer, and 16 were in remission. Of the remaining 19 patients who were BRCA1/2 deficient, 14 patients (74%) developed visceral metastases compared with six (16%) of 38 patients in the control group. The percentages of liver, lung, and splenic metastases were 53%, 32%, and 32%, respectively, in the patients compared with 5%, 3%, and 5%, respectively, in the controls. When events occurring outside the matched follow-up period were omitted, the percentages of visceral, liver, lung, and splenic metastases were 58%, 42%, 16%, and 32% in the patients compared with 5%, 0%, 0%, and 3% in controls (P < .001, P < .001, P = .066, and P = .011, respectively). In an independent validation set, the corresponding percentages of visceral, liver, lung, and splenic metastases were 63%, 46%, 13%, and 17% in the patients compared with 11%, 4%, 2%, and 2% in controls (P < .001, P < .001, P = .153, and P = .052, respectively).

Conclusion

Although sporadic EOC commonly remains confined to the peritoneum, BRCA1/2-deficient ovarian cancer frequently metastasizes to viscera. These data extend the ovarian BRCAness phenotype, imply BRCA1/2-deficient ovarian cancer is biologically distinct, and suggest that patients with visceral metastases should be considered for BRCA1/2 sequencing.