bluuebunny/crossref_metadata_2025 huggingface dataset:
Security threats categories in healthcare information systems
Authors: Narayana Samy Ganthan , Ahmad Rabiah , Ismail Zuraini
Published: October 2010

This article attempts to investigate the various types of threats that exist in healthcare information systems (HIS). A study has been carried out in one of the government-supported hospitals in Malaysia.The hospital has been equipped with a Total Hospital Information System (THIS). The data collected were from three different departments, namely the Information Technology Department (ITD), the Medical Record Department (MRD), and the X-Ray Department, using in-depth structured interviews. The study identified 22 types of threats according to major threat categories based on ISO/IEC 27002 (ISO 27799:2008). The results show that the most critical threat for the THIS is power failure followed by acts of human error or failure and other technological factors. This research holds significant value in terms of providing a complete taxonomy of threat categories in HIS and also an important component in the risk analysis stage.
Applying evidence in practice: A qualitative case study of the factors affecting residents’ decisions
Authors: Dalrymple Prudence W. , Lehmann Harold P. , Roderer Nancy K. , Streiff Michael B.
Published: October 2010

Patient care based on best available evidence is increasingly viewed as the hallmark of good quality medical diagnosis and treatment, yet its uptake is often slow and uneven and the reasons underlying the slow diffusion of evidence-based guidelines remain elusive. The authors report a qualitative study conducted at a major US teaching hospital which sought to discover the reasons why an evidence-based anticoagulation guideline appeared to be applied irregularly, with problematic results. Using a theoretical framework derived from Rogers’ work on the diffusion of innovation, this article describes the ways in which a group of residents evaluated and applied evidence in the context of caring for their patients. Future work in evidence-based practice can benefit from a greater emphasis on studies that use multi-method, qualitative designs to explore the complex ways in which people interact with information and the changes that ensue from its use.
Factors influencing the use of IT in the emergency department: A qualitative study
Authors: Ayatollahi Haleh , Bath Peter A. , Goodacre Steve
Published: October 2010

Investigating factors influencing the use of clinical information systems can help to develop a strategy to improve user acceptance of a given system or similar ones in the future. In this research, we investigated factors influencing the use of information technology in the emergency department (ED). We undertook a qualitative study in which data were collected using semi-structured interviews with the ED staff. In total, 34 interviews were conducted and data were analysed using framework analysis. The results showed that user characteristics and perception of task, technology, environment, and impact of technology could influence people’s use of IT in the ED. Of these, the usefulness of the systems, the impact of technology, IT training, and the feasibility of using IT by all members of staff seemed to be the main concerns. Addressing these factors in designing and implementing a system could help to introduce the change successfully and improve the acceptance of information technology.
An update on the efficacy and safety of aclidinium bromide in patients with COPD
Authors: Alagha Khuder , Bourdin Arnaud , Tummino Céline , Chanez Pascal
Published: October 2010

Aclidinium is a potent and selective muscarinic antagonist, which interacts rapidly with muscarinic receptors and shows subnanomolar affinity for the five human muscarinic receptors (M1–M5); its association rate for the M3 receptor is similar to that of ipratropium and 2.6 times faster than that of tiotropium. Aclidinium dissociates slightly faster from M2 and M3 receptors than tiotropium but much more slowly than ipratropium. A potent bronchodilatory activity has been observed after inhaled administration of aclidinium. Aclidinium undergoes rapid hydrolysis in the plasma into two major compounds, the alcohol (LAS34823) and the carboxylic acid (LAS34850) metabolites, resulting in low and transient systemic exposure to the active drug. The two major metabolites show no significant affinity for human muscarinic receptors. A potent bronchodilatory activity has been observed after inhaled administration of aclidinium. Clinical trials have provided evidence of sustained bronchodilation similar to that observed with tiotropium. Trial results have confirmed the positive safety profile of aclidinium, particularly in terms of a very low propensity to cause anticholinergic adverse events. Aclidinium is now moving to phase III clinical development for chronic obstructive pulmonary disease (COPD).
Malignant pleural effusion cells show aberrant glucose metabolism gene expression
Authors: Lin C-C. , Chen L-C. , Tseng V.S. , Yan J-J. , Lai W-W. , Su W-P. , Lin C-H. , Huang C-Y.F. , Su W-C.
Published: October 2010

Malignant pleural effusion (MPE) accompanying lung adenocarcinoma indicates poor prognosis and early metastasis. This study aimed to identify genes related to MPE formation.

Three tissue sample cohorts, seven from healthy lungs, 18 from stage I–III lung adenocarcinoma with adjacent healthy lung tissue and 13 from lung adenocarcinomas with MPE, were analysed by oligonucleotide microarray. The identified genes were verified by quantitative real-time PCR (qRT-PCR), immunohistochemical staining, and immunofluorescence confocal microscopy.

20 up- or down-regulated genes with a two-fold change in MPE cancer cells compared to healthy tissues were differentially expressed from early- to late-stage lung cancer. Of 13 genes related to cellular metabolism, aldolase A (ALDOA), sorbitol dehydrogenase (SORD), transketolase (TKT), and tuberous sclerosis 1 (TSC1) were related to glucose metabolism. qRT-PCR validated their mRNA expressions in pleural metastatic samples. Immunohistochemical staining confirmed aberrant TKT, ALDOA, and TSC1 expressions in tumour cells. Immunofluorescence confirmed TKT co-localisation and co-distribution of ALDOA with thyroid transcription factor 1-positive cancer cells. TKT regulated the proliferation, vascular endothelial growth factor secretionin vitroandin vivovascular permeability of cancer cell.

Glucose metabolic reprogramming by ALDOA, SORD, TKT and TSC1 is important in MPE pathogenesis.
Epigenetic mechanisms and the relationship to childhood asthma
Authors: Kabesch M. , Michel S. , Tost J.
Published: October 2010

Epigenetic mechanisms mediate genomic adaption to the environment and epigenetic alterations can contribute to the development of disease phenotypes, as can genetic variants. A variety of molecular mechanisms are involved in epigenetic regulation, including post-transcriptional histone modifications, histone variants, ATP-dependent chromatin remodelling complexes, polycomb/trithorax protein complexes, small and other noncoding RNAs (small interfering RNA and micro RNAs) and DNA methylation. Epigenetic mechanisms have been identified in cancer but very little is known about these effects in complex diseases such as asthma. Epigenetic mechanisms have been found to play a primordial role in T-cell differentiation and novel aspects of asthma and allergy development are now investigated by systematic epigenetic studies. Here we give an introduction to epigenetics, review the existing literature in relation to asthma and asthma-related mechanisms and hypothesise on feasible approaches for the study of epigenetics in asthma in the future.
Role of pulmonary infection in the development of chronic lung disease of prematurity
Authors: Beeton M.L. , Maxwell N.C. , Davies P.L. , Nuttall D. , McGreal E. , Chakraborty M. , Spiller O.B. , Kotecha S.
Published: October 2010

We studied the role of ante- and post-natal infection in the development of chronic lung disease (CLD) of prematurity.

192 newborn infants (61 term and 131 pre-term of <34 weeks gestation: 88 with respiratory distress syndrome, 35 developed CLD and eight died) were recruited. 16S ribosomal RNA (rRNA) genes were identified by PCR of DNA isolated from 840 gastric and lung fluid samples.Ureaplasmaspp. were also cultured.

Presence of 16S rRNA genes (OR 1.6, 95% CI 1.2–2.2) andUreaplasmaspp. (OR 3.6, 95% CI 1.7–7.7) was significantly associated with the development of CLD. This association remained if the 16S rRNA genes andUreaplasmaspp. were first identified within the first 3 days of life (OR 2.4 (95% CI 1.4–4.1) and 3.8 (95% CI 1.4–10.0), respectively) or if first identified after 3 days of age (OR 1.7 (95% CI 1.1–2.8) and OR 5.1 (95% CI 1.3–19.8), respectively). Peak lung fluid interleukin (IL)-6 and IL-8 were significantly associated with presence of microbes (p<0.0001 and p = 0.0001, respectively) and development of CLD (p = 0.003 and 0.001, respectively).

Both early and late microbial presence in neonatal lung fluid samples was significantly associated with the development of CLD suggesting that both ante- and post-natal infection play a role in the development of CLD.
Discoidin domain receptor 1 regulates bronchial epithelial repair and matrix metalloproteinase production
Authors: Roberts M.E. , Magowan L. , Hall I.P. , Johnson S.R.
Published: October 2010

Discoidin domain receptor (DDR)1 is an extracellular matrix (ECM)-sensing receptor tyrosine kinase, which is activated by collagen and expressed in bronchial epithelium. DDR1 is responsible for maintaining the normal structure of skin and kidney epithelia and we hypothesised that DDR1 plays a regulatory role in bronchial epithelial integrity by transducing signals from the airway ECM.

Effects of DDR1 depletion were studied using RNA interference in primary human bronchial epithelial cells (HBECs) and BEAS-2B cells. The effects of overexpression of DDR1a and DDR1b in BEAS-2B cells were studied using a plasmid vector. We measured the effects on epithelial repair using a scratch wounding model, and levels of matrix metalloproteinases (MMPs) by gelatin zymography (MMP-2 and -9) and ELISA (MMP-7).

We showed that knockdown of DDR1 slowed epithelial repair by 50%, which was associated with a reduction in levels of MMP-7, whilst DDR1 overexpression enhanced epithelial repair. DDR1 knockdown reduced proliferation of HBECs, but had no significant effect on adhesion to collagen I or other matrix substrates.

These data suggest that ECM signallingviaDDR1 regulates aspects of bronchial epithelial repair, integrity and MMP expression in the airways.
Targeting of c-kit+ haematopoietic progenitor cells prevents hypoxic pulmonary hypertension
Authors: Gambaryan N. , Perros F. , Montani D. , Cohen-Kaminsky S. , Mazmanian M. , Renaud J-F. , Simonneau G. , Lombet A. , Humbert M.
Published: October 2010

Haematopoietic c-kit+ progenitor cells may contribute to pulmonary vascular remodelling and pulmonary hypertension (PH). Stromal derived factor-1 (SDF-1/CXCL12) and its receptors CXCR4 and CXCR7 have been shown to be critical for homing and mobilisation of haematopoietic c-kit+ progenitor cells in the perivascular niche.

We administered AMD3100, a CXCR4 antagonist, and CCX771, a CXCR7 antagonist, to chronic hypoxia exposed mice in order to study the role of c-kit+ progenitor cells in PH. CXCL12, CXCR4 and CXCR7 protein expression, haemodynamic parameters, right ventricular mass, extent of vascular remodelling and perivascular progenitor cell accumulation were studied.

Chronic hypoxia-exposed mice showed increased total lung tissue expression of CXCR4, CXCR7 and CXCL12 after development of PH. This was associated with significantly increased right ventricular systolic pressure and evidence of right ventricular hypertrophy, vascular remodelling and perivascular c-kit+/sca-1+ progenitor cell accumulation. CCX771 administration did not abrogate these effects. In contrast, administration of AMD3100, whether alone or combined with CCX771, prevented vascular remodelling, PH and perivascular accumulation of c-kit+/sca-1+ progenitor cells, with a synergistic effect of these agents.

This study offers important pathophysiological insights into the role of haematopoietic c-kit+ progenitors in hypoxia-induced vascular remodelling and may have therapeutic implications for PH.
Current data on predictive markers for anti-angiogenic therapy in thoracic tumours
Authors: Reinmuth N. , Thomas M. , Meister M. , Schnabel P.A. , Kreuter M.
Published: October 2010

The fact that growth and spread of tumours are dependent on angiogenesis has led to the investigation of the role of anti-angiogenic agents in the therapeutic strategies for thoracic tumours such as nonsmall cell lung cancer or mesotheliomas. Since various angiogenic factors may contribute to the regulation of angiogenesis in the individual tumour, in the era of increasing amounts of clinically tested agents it is of utmost importance to properly select patients that may benefit from a specific therapy. Due to the complex nature of tumour angiogenesis, various biomarkers may be applicable. For example, the profile of activated angiogenic pathways in endothelial cells may be determined in order to make conclusions about the relevance of inhibiting a given pathway by a selected agent. Moreover, changes in protein expression in stromal and tumour cells, as well as structural alterations in the vasculature, may be used for predicting and monitoring the clinical effects of such a therapy. In this review, the current data from clinical studies evaluating predictive markers for anti-angiogenic agents in thoracic cancers are summarised. Besides giving clinical examples, the rationales for investigating various parameters based on pre-clinical studies are described.
Iron deficiency is common in idiopathic pulmonary arterial hypertension
Authors: Ruiter G. , Lankhorst S. , Boonstra A. , Postmus P.E. , Zweegman S. , Westerhof N. , van der Laarse W.J. , Vonk-Noordegraaf A.
Published: October 2010

The aims of this study were to assess the prevalence of iron deficiency in idiopathic pulmonary arterial hypertension (IPAH) and investigate whether oral iron supplementation has effects in iron-deficient patients.

Iron parameters were measure for all IPAH patients attending our centre (VU University Medical Center, Amsterdam, the Netherlands) between May 2009 and February 2010. Iron data were related to clinical parameters, including 6-min walking distance (6MWD), and haemodynamic parameters measured during right heart catheterisation. In a subset of iron-deficient patients, the uptake of iron from the bowel was studied after administering oral iron for 4 weeks.

Iron deficiency was found in 30 (43%) out of 70 patients. 6MWD was reduced in iron-deficient patients compared with iron-sufficient patients (mean±sd390±138versus460±143 m; p<0.05) irrespective of the existence of anaemia. In a subset of 18 patients that received oral iron, ferritin levels were significantly increased, although eight patients only slightly increased their iron storage.

This study shows that iron deficiency is frequently present in IPAH and is associated with a lower exercise capacity. The small response to oral iron in 44% of the treated patients suggests impaired iron absorption in these patients.
Tuberculosis contact investigation in low prevalence countries: a European consensus
Authors: Erkens C.G.M. , Kamphorst M. , Abubakar I. , Bothamley G.H. , Chemtob D. , Haas W. , Migliori G.B. , Rieder H.L. , Zellweger J-P. , Lange C.
Published: October 2010

Contact investigation to identify individuals with tuberculosis and latent infection withMycobacterium tuberculosisis an important component of tuberculosis control in low tuberculosis incidence countries. This document provides evidence-based and best-practice policy recommendations for contact tracing among high- and medium-priority contacts in a variety of settings. It provides a basis for national guidelines on contact investigation and tuberculosis outbreak management, and should support countries and tuberculosis control managers in evaluating and revising national policies. A review of existing guidelines, a literature search, several meetings and consultation with experts were used to formulate and grade recommendations for action during contact investigation.

Available tests to identify individuals with latent infection withM. tuberculosisare designed to identify immune response against mycobacterial antigens and have variable predictive value for the likelihood to develop active tuberculosis in different populations. Contact investigation should therefore be limited to situations with a clear likelihood of transmission or to those with a higher probability of developing active tuberculosis, for instance, young children and immunocompromised persons. A risk assessment-based approach is recommended, where the need to screen contacts is prioritised on the basis of the infectiousness of the index case, intensity of exposure and susceptibility of contacts.
A systematic study of genome context methods: calibration, normalization and combination
Authors: Ferrer Luciana , Dale Joseph M , Karp Peter D
Published: October 2010

Background

Genome context methods have been introduced in the last decade as automatic methods to predict functional relatedness between genes in a target genome using the patterns of existence and relative locations of the homologs of those genes in a set of reference genomes. Much work has been done in the application of these methods to different bioinformatics tasks, but few papers present a systematic study of the methods and their combination necessary for their optimal use.

Results

We present a thorough study of the four main families of genome context methods found in the literature: phylogenetic profile, gene fusion, gene cluster, and gene neighbor. We find that for most organisms the gene neighbor method outperforms the phylogenetic profile method by as much as 40% in sensitivity, being competitive with the gene cluster method at low sensitivities. Gene fusion is generally the worst performing of the four methods. A thorough exploration of the parameter space for each method is performed and results across different target organisms are presented.

We propose the use of normalization procedures as those used on microarray data for the genome context scores. We show that substantial gains can be achieved from the use of a simple normalization technique. In particular, the sensitivity of the phylogenetic profile method is improved by around 25% after normalization, resulting, to our knowledge, on the best-performing phylogenetic profile system in the literature.

Finally, we show results from combining the various genome context methods into a single score. When using a cross-validation procedure to train the combiners, with both original and normalized scores as input, a decision tree combiner results in gains of up to 20% with respect to the gene neighbor method. Overall, this represents a gain of around 15% over what can be considered the state of the art in this area: the four original genome context methods combined using a procedure like that used in the STRING database. Unfortunately, we find that these gains disappear when the combiner is trained only with organisms that are phylogenetically distant from the target organism.

Conclusions

Our experiments indicate that gene neighbor is the best individual genome context method and that gains from the combination of individual methods are very sensitive to the training data used to obtain the combiner's parameters. If adequate training data is not available, using the gene neighbor score by itself instead of a combined score might be the best choice.
Data-driven assessment of eQTL mapping methods
Authors: Michaelson Jacob J , Alberts Rudi , Schughart Klaus , Beyer Andreas
Published: October 2010

Background

The analysis of expression quantitative trait loci (eQTL) is a potentially powerful way to detect transcriptional regulatory relationships at the genomic scale. However, eQTL data sets often go underexploited because legacy QTL methods are used to map the relationship between the expression trait and genotype. Often these methods are inappropriate for complex traits such as gene expression, particularly in the case of epistasis.

Results

Here we compare legacy QTL mapping methods with several modern multi-locus methods and evaluate their ability to produce eQTL that agree with independent external data in a systematic way. We found that the modern multi-locus methods (Random Forests, sparse partial least squares, lasso, and elastic net) clearly outperformed the legacy QTL methods (Haley-Knott regression and composite interval mapping) in terms of biological relevance of the mapped eQTL. In particular, we found that our new approach, based on Random Forests, showed superior performance among the multi-locus methods.

Conclusions

Benchmarks based on the recapitulation of experimental findings provide valuable insight when selecting the appropriate eQTL mapping method. Our battery of tests suggests that Random Forests map eQTL that are more likely to be validated by independent data, when compared to competing multi-locus and legacy eQTL mapping methods.
Carbohydrate antigens in nipple aspirate fluid predict the presence of atypia and cancer in women requiring diagnostic breast biopsy
Authors: Deutscher Susan L , Dickerson Marie , Gui Gerald , Newton Jessica , Holm Jeffrey E , Vogeltanz-Holm Nancy , Kliethermes Beth , Hewett John E , Kumar Senthil R , Quinn Thomas P , Sauter Edward R
Published: October 2010

Background

The goal of this prospective study was to determine (a) concentrations of the carbohydrate biomarkers Thomsen Friedenreich (TF) antigen and its precursor, Tn antigen, in nipple discharge (ND) collected from women requiring biopsy because of a suspicious breast lesion; and (b) if concentration levels predicted pathologic diagnosis.

Methods

Adult women requiring biopsy to exclude breast cancer were enrolled and ND obtained. The samples from 124 women were analyzed using an anti-TF and anti-Tn monoclonal antibodies in direct immunoassay.

Results

The highest median concentration in ND for TF and Tn was in women with ductal carcinomain situ(DCIS). TF was higher in women with 1) cancer (DCIS or invasive) vs. either no cancer (atypia or benign pathology, p = .048), or benign pathology (p = .018); and 2) abnormal (atypia or cancer) versus benign pathology (p = .016); and was more predictive of atypia or cancer in post- compared to premenopausal women. Tn was not predictive of disease. High TF concentration and age were independent predictors of disease, correctly classifying either cancer or abnormal vs. benign pathology 83% of the time in postmenopausal women.

Conclusions

TF concentrations in ND were higher in women with precancer and cancer compared to women with benign disease, and TF was an independent predictor of breast atypia and cancer. TF may prove useful in early breast cancer detection.
Molecular determinants of improved cathepsin B inhibition by new cystatins obtained by DNA shuffling
Authors: Valadares Napoleão F , Dellamano Márcia , Soares-Costa Andrea , Henrique-Silva Flávio , Garratt Richard C
Published: October 2010

Background

Cystatins are inhibitors of cysteine proteases. The majority are only weak inhibitors of human cathepsin B, which has been associated with cancer, Alzheimer's disease and arthritis.

Results

Starting from the sequences of oryzacystatin-1 and canecystatin-1, a shuffling library was designed and a hybrid clone obtained, which presented higher inhibitory activity towards cathepsin B. This clone presented two unanticipated point mutations as well as an N-terminal deletion. Reversing each point mutation independently or both simultaneously abolishes the inhibitory activity towards cathepsin B. Homology modeling together with experimental studies of the reverse mutants revealed the likely molecular determinants of the improved inhibitory activity to be related to decreased protein stability.

Conclusion

A combination of experimental approaches including gene shuffling, enzyme assays and reverse mutation allied to molecular modeling has shed light upon the unexpected inhibitory properties of certain cystatin mutants against Cathepsin B. We conclude that mutations disrupting the hydrophobic core of phytocystatins increase the flexibility of the N-terminus, leading to an increase in inhibitory activity. Such mutations need not affect the inhibitory site directly but may be observed distant from it and manifest their effects via an uncoupling of its three components as a result of increased protein flexibility.
Anti-inflammatory properties of the PI3K pathway are mediated by IL-10/DUSP regulation
Authors: Günzl Philipp , Bauer Kathrin , Hainzl Eva , Matt Ulrich , Dillinger Barbara , Mahr Benedikt , Knapp Sylvia , Binder Bernd R , Schabbauer Gernot
Published: October 2010

Activation of the PI3K/PTEN signaling pathway down-regulates pro-inflammatory gene expression via up-regulation of DUSP1.

Resolution of inflammation is an important hallmark in the course of infectious diseases. Dysregulated inflammatory responses may have detrimental consequences for the affected organism. Therefore, tight regulation of inflammation is indispensable. Among numerous modulatory signaling pathways, the PI3K/PTEN signaling pathway has been proposed recently to be involved in the regulation of innate immune reactions. Here, we attempted to elucidate molecular mechanisms that contribute to the modulatory properties of the PI3K signaling pathway in inflammation. PTEN-deficient macrophages, which harbor constitutively active PI3Ks, were analyzed in response to gram-negative bacteria and PAMPs such as LPS. PTEN-deficient cells showed reduced inflammatory cytokine production, which was accompanied by reduced MAPK signaling activation in early- as well as late-phase activation. Simultaneously, we found increased levels of the MKP DUSP1, as well as the anti-inflammatory cytokine IL-10. Our data suggest that differential DUSP1 regulation coupled with enhanced IL-10 production contributes to the anti-inflammatory properties of the PI3K pathway.
Regulatory T cells suppress antigen-driven CD4 T cell reactivity following injury
Authors: MacConmara Malcolm P , Tajima Goro , O'Leary Fionnuala , Delisle Adam J , McKenna Ann M , Stallwood Christopher G , Mannick John A , Lederer James A
Published: October 2010

Injury initiates local and systemic host responses and is known to increase CD4 Treg activity in mice and humans. This study uses a TCR transgenic T cell adoptive transfer approach and in vivo Treg depletion to determine specifically the in vivo influence of Tregs on antigen-driven CD4 T cell reactivity following burn injury in mice. We report here that injury in the absence of recipient and donor Tregs promotes high antigen-driven CD4 T cell expansion and increases the level of CD4 T cell reactivity. In contrast, CD4 T cell expansion and reactivity were suppressed significantly in injured Treg-replete mice. In additional experiments, we found that APCs prepared from burn- or sham-injured, Treg-depleted mice displayed significantly higher antigen-presenting activity than APCs prepared from normal mice, suggesting that Tregs may suppress injury responses by controlling the intensity of APC activity. Taken together, these findings demonstrate that Tregs can actively control the in vivo expansion and reactivity of antigen-stimulated, naïve CD4 T cells following severe injury.
Suppressing LPS-induced early signal transduction in macrophages by a polyphenol degradation product: a critical role of MKP-1
Authors: Tucsek Zsuzsanna , Radnai Balazs , Racz Boglarka , Debreceni Balazs , Priber Janos K , Dolowschiak Tamas , Palkovics Tamas , Gallyas Ferenc , Sumegi Balazs , Veres Balazs
Published: October 2010

Macrophages represent the first defense line against bacterial infection and therefore, play a crucial role in early inflammatory response. In this study, we investigated the role of MAPKs and MKP-1 activation in regulation of an early inflammatory response in RAW 264.7 macrophage cells. We induced the inflammatory response by treating the macrophages with LPS and inhibited an early inflammatory response by using ferulaldehyde, a water-soluble end-product of dietary polyphenol degradation that we found previously to exert its beneficial anti-inflammatory effects during the early phase of in vivo inflammation. We found that LPS-induced ROS and nitrogen species formations were reduced by ferulaldehyde in a concentration-dependent manner, and ferulaldehyde protected mitochondria against LPS-induced rapid and massive membrane depolarization. LPS induced early suppression of MKP-1, which was accompanied by activation of JNK, ERK, and p38 MAPK. By reversing LPS-induced early suppression of MKP-1, ferulaldehyde diminished MAPK activation, thereby inhibiting NF-κB activation, mitochondrial depolarization, and ROS production. Taken together, our data suggest that ferulaldehyde exerts its early anti-inflammatory effect by preserving the mitochondrial membrane integrity and shifting the expression of MKP-1 forward in time in macrophages.
HIV inhibits early signal transduction events triggered by CD16 cross-linking on NK cells, which are important for antibody-dependent cellular cytotoxicity
Authors: Lichtfuss Gregor F , Meehan Aislin C , Cheng Wan-Jung , Cameron Paul U , Lewin Sharon R , Crowe Suzanne M , Jaworowski Anthony
Published: October 2010

Measurement of NK cell cytolytic activity in the setting of chronic viral infection is important for determining viral pathogenicity. Mobilization of LAMP-1 (CD107a) to the NK cell surface is a surrogate marker for cytotoxic granule release and hence, NK cell cytotoxicity. We have developed a convenient, rapid, whole blood flow cytometric assay for measuring CD107a mobilization in response to CD16 cross-linking, a surrogate for NK cell ADCC activity ex vivo, which can be performed using small volumes of patient whole blood. Using this assay, we show that CD107a mobilization, in response to CD16 cross-linking, is triggered in CD56dim but not CD56bright NK cells, requiring Syk/Zap70 tyrosine kinase activity, and that there is a significant correlation between CD107a mobilization and pSyk/Zap70 in response to CD16 cross-linking. We compared whole blood from treatment-naïve, HIV-infected patients with age- and sex-matched HIV-uninfected control subjects and found a significant reduction in CD16-dependent pSyk/Zap70 (median=32.7% compared with 67.8%; P=0.0002) and CD107a mobilization (median=9.72% compared with 32.9%; P=0.046) in NK cells. Reduction of both correlated strongly with reduced CD16 surface expression on NK cells of HIV-infected individuals (P<0.01). These data suggest that ADCC is inhibited in NK cells from therapy-naïve, HIV-infected individuals at the level of early events in CD16 signal transduction, associated with low CD16R expression, and our method is a useful and reliable tool to detect pathological defects in NK cell degranulation.
Quantitative analysis of water-content estimation errors using ground-penetrating radar data and a low-loss approximation
Authors: Giroux Bernard , Chouteau Michel
Published: October 2010

Expressions are derived to quantify the error when estimating permittivity that results from using the low-loss approximation under lossy conditions and to examine the repercussions on estimating water content [Formula: see text]. Values are computed under a range of porosity, clay-content, water-quality, and frequency conditions. Although in most cases the error is negligible, it can be significant for some hydrogeophysical applications involving cross-hole measurements or low-frequency surface ground-penetrating radar (GPR). For instance, when the loss tangent [Formula: see text] equals 0.5, corresponding to an effective conductivity of [Formula: see text], a dielectric constantof 11, and a frequency of [Formula: see text], the relative error on dielectric permittivity is approximately 6%. If the conductivity doubles or the frequency is halved, the loss tangentdoubles but the error grows to 21%. In addition, considering a situation where the porosity is 20% and [Formula: see text], the use of the low-loss approximation leads to a 10% deviation from [Formula: see text]. In the context of water-content estimation, we therefore suggest to perform attenuation tomography, in addition to velocity tomography for crosshole data, or estimate the quality factor [Formula: see text] for surface GPR data to compute the loss tangent over the probed area. If proven necessary, the parameters sought can then be determined more accurately using a lossy formulation. We also propose to supplement GPR measurements with electrical-resistivity tomography to constrain the borehole GPR amplitude data-processing steps required by attenuation tomography or to complement the characterization of the survey area and improve the knowledge brought by [Formula: see text] estimates alone.
Properties of precipitation-induced multilayer surface waveguides derived from inversion of dispersive TE and TM GPR data
Authors: van der Kruk J. , Jacob R. W. , Vereecken H.
Published: October 2010

Precipitation events result in a high water content of the shallow subsurface. When the water remains in the shallow subsurface, a shallow low-velocity layer can be generated which acts as a waveguide when the contrasts in permittivity are large enough. The electromagnetic waves emitted by ground-penetrating radar (GPR) systems are trapped within these thin surface layers and show pronounced dispersion, which depends on the velocities and thicknesses of the surface waveguide layers and the velocity of the material below it. Conventional traveltime techniques cannot be reliably applied because the different phases cannot be clearly identified. Recently developed techniques for inverting dispersed waveforms in transverse electric (TE) and transversemagnetic (TM) GPR data are used to provide information on the thickness and permittivity of a single-layer low-velocity waveguide induced by precipitation events. Repeated measurements at one location after two precipitation events show that, for increasing soil water content and increasing thickness of the low-velocity waveguide, an increased number of higher-order modes can be identified in the phase-velocity spectrum. The TE and TM inversion techniques are extended for multilayered waveguides, and inversion of synthetic and experimental data events show that the properties of a two-layer waveguide can be reliably reconstructed when at least two modes can be used in the inversion. The misfits between the picked and the synthetic dispersion curves are significantly reduced compared to a single-layer wave-guide inversion.
Detection of subsurface soil cracks by vertical anisotropy profiles of apparent electrical resistivity
Authors: Greve Anna K. , Acworth R. Ian , Kelly Bryce F.
Published: October 2010

To date, an understanding of crack dynamics has been fundamentally hampered by the lack of available techniques to observe or monitor crack dynamics below the soil surface. A new technique relates the growth of soil cracks to a progressive increase in the electrical anisotropy of the soil. Although a single measurement of anisotropy is possible using a surface array of electrodes, the use of four strings of electrodes installed vertically at the corners of a square provides a valuable picture of the crack pattern at depth. In addition, time-lapse electrical surveys allow the growth of cracks to be clearly monitored. The electrical anisotropy is defined as the ratio of the [Formula: see text]-to-[Formula: see text] apparent resistivity for the square array and is determined for each coplanar set of four electrodesusing one electrode from each of the four vertical strings. In a laboratory, we measured the electrical anisotropy in a sand-filled lysimeter with a plastic sheet, introduced to represent an electrically insulating crack. Measurements were then repeated in a cracking-soil-filled lysimeter. Finally, measurements were made in a field where a flood-irrigated sorghum crop was grown on cracking soil. Measurements under all three conditions demonstrate that the lateral and vertical extents of cracking in a soil profile strongly influence the electrical anisotropy. The larger the cumulative cracking volume, the higher the electrical anisotropy. Soil-moisture changes after crack closure have a minor influence on the measured anisotropy, as have sorghum roots. These experiments demonstrate that electrical-anisotropy profiles are a valuable tool for monitoring crack dynamics within a soil profile.
A tracer test in a shallow heterogeneous aquifer monitored via time-lapse surface electrical resistivity tomography
Authors: Monego Martina , Cassiani Giorgio , Deiana Rita , Putti Mario , Passadore Giulia , Altissimo Lorenzo
Published: October 2010

We illustrate a case study of a saline tracer test in a shallow, highly heterogeneous aquifer, monitored by means of surface time-lapse ERT. The test was aimed at identifying the system’s hydraulic properties. Some of the expected limitations of the method — particularly caused by the strong decrease in ERT resolution with depth — and the consequent problems with mass balance and moment calculation could be partly balanced by the use of direct measurements of groundwater electrical conductivity and tracer concentration at one selected location. The vast heterogeneity of the system, ranging in lithology from clay to gravel at a scale of meters to tens of meters, reflects itself in the tracer migration and distribution over time: The tracer is trapped in the low-permeability regions and from these it is slowly released over time. High-resolution surface ERT proves effective at picturing this system behavior over time. The extreme heterogeneity is also a challenge in the attempt to translate bulk electrical conductivity into estimates of groundwater electrical conductivity and, hence, solute concentration because surface conductivity in fine sediments has an important role. The test results could be used to identify some of the key parameters for solute transport, namely, mean groundwater velocity and aquifer dispersivity at the scale of the test by means of transport model calibration.
Compensating for temperature variations in time-lapse electrical resistivity difference imaging
Authors: Hayley Kevin , Bentley L. R. , Pidlisecky A.
Published: October 2010

Variations in temperature during time-lapse electrical resistivity imaging (ERI) surveys introduce changes in electrical conductivity (EC). When the goal of the time-lapse ERI survey is to image changes in EC due to changes in saturation or pore water salinity, compensation must be made for the effect of temperature variations. A temperature-compensation method can approximate time-lapse ERI data with the effect of temperature variations removed. First uncompensated ERI data are inverted. The inversion model then is adjusted to a standard temperature image. Forward simulations are performed using the uncompensated inversion and the standard temperature equivalent model. The temperature-compensated simulated resistance data are subtracted from the uncompensated simulated resistance data, forming data correction terms. The data correction terms then are subtracted from the measured data to yield temperature-compensated data. Using the temperature-compensated data, inversions have been carried out on two synthetic data sets and a field example. Differencing two temperature-compensated data inversions is found to be superior to differencing two postinversion standard temperature equivalent images. Temperature compensation on the data allows temperature corrections to be applied to time-lapse difference inversion schemes and hydrogeophysical inversion where postinversion temperature-correction methods are not easily applied.
Textural controls on low-frequency electrical spectra of porous media
Authors: Kruschwitz Sabine , Binley Andrew , Lesmes David , Elshenawy Ahmed
Published: October 2010

The results from several laboratory studies of the relationships between electrical polarization and physical properties of porous media have prompted interest in the potential use of low-frequency electrical spectra to qualitatively or quantitatively map variation in hydrogeologic properties in the field. Compiling several published and unpublished data sets, supported by new measurements, we have examined the low-frequency electrical spectra of a range of natural and artificial porous media to assess the generality of proposed relationships between electrical and physical properties. Our work confirms a significant positive correlation between the magnitude of electrical polarization (quantified as imaginary conductivity at a specific frequency) and the surface-area/pore-volume ratio [Formula: see text]. Analyzing the parameters of ageneralized Cole-Cole resistivity relaxation model fitted to many electrical spectra, we observe two apparent controls on the electrical relaxation. For samples with abundant relatively large pore throats, we observe a distinct increase in the time constant of the model with modal pore-throat size, in accordance with classical electrical relaxation models. However, for media with pore structures dominated by small pore throats, the diffusion-length scales do not appear to be controlled by modal pore-throat size. We conclude that for such media, the microstructure of the network of small pores leads to some connectivity of diffusion paths; thus, these samples exhibit relatively large time constants. There is potential value in addition to limitations when using electrical spectra to estimate physical properties of porous media, and we see the need for more appropriate generalized theories of electrical polarization in hydrogeologic media.
Always on the bright side of life: anti-adhesive properties of insect ommatidia grating
Authors: Peisker Henrik , Gorb Stanislav N.
Published: October 2010

The surface of some insect eyes consists of arrays of cuticular protuberances, which are 50–300 nm in diameter, and are termed corneal nipples or ommatidia gratings. They were widely reported to reduce the reflectance for normally incident light, contributing to camouflage by reducing glare to predators, while furthermore enhancing the intake of light, which is especially important for nocturnal insects. Our preliminary observations suggest a third function: in contrast to the rest of the body, ommatidia of various insects remain clean, even in a heavy contaminated environment. In order to prove such an anti-contamination hypothesis of these structures, we measured the adhesive properties of polymer moulds of insect ommatidia, and compared these data with control surfaces having the same curvature radii but lacking such a nanostructure. A scanning electron microscope (SEM) study and force measurements using an atomic force microscope (AFM) on the eye surfaces of three different insect species, dragonfly Aeshna mixta (Odonata), moth Laothoe populi (Lepidoptera) and fly Volucella pellucens (Diptera), were undertaken. We revealed that adhesion is greatly reduced by corneal grating in L. populi and V. pellucens when compared with their smooth controls. The smooth cornea of A. mixta showed no statistically significant difference to its control. We assume that this anti-adhesive phenomenon is due to a decrease in the real contact area between contaminating particles and the eye's surface. Such a combination of three functions in one nanostructure can be interesting for the development of industrial multifunctional surfaces capable of enhancing light harvesting while reducing light reflection and adhesion.
Lifespan and oxidative stress show a non-linear response to atmospheric oxygen inDrosophila
Authors: Rascón Brenda , Harrison Jon F.
Published: October 2010

Oxygen provides the substrate for most ATP production, but also serves as a source of reactive oxygen species (ROS), which can induce cumulative macromolecular oxidative damage and cause aging. Pure oxygen atmospheres (100 kPa) are known to strongly reduce invertebrate lifespan and induce aging-related physiological changes. However, the nature of the relationship between atmospheric oxygen, oxidative stress, and lifespan across a range of oxygen levels is poorly known. Developmental responses are likely to play a strong role, as prior research has shown strong effects of rearing oxygen level on growth, size and respiratory system morphology. In this study, we examined (1) the effect of oxygen on adult longevity and (2) the effect of the oxygen concentration experienced by larvae on adult lifespan by rearing Drosophila melanogaster in three oxygen atmospheres throughout larval development (10, 21 and 40 kPa), then measuring the lifespan of adults in five oxygen tensions (2, 10, 21, 40, 100 kPa). We also assessed the rate of protein carbonyl production for flies kept at 2, 10, 21, 40 and 100 kPa as adults (all larvae reared in normoxia). The rearing of juveniles in varying oxygen treatments affected lifespan in a complex manner, and the effect of different oxygen tensions on adult lifespan was non-linear, with reduced longevity and heightened oxidative stress at extreme high and low atmospheric oxygen levels. Moderate hypoxia (10 kPa) extended maximum, but not mean lifespan.
Binding and cleavage of CRISPR RNA by Cas6
Authors: Carte Jason , Pfister Neil T. , Compton Mark M. , Terns Rebecca M. , Terns Michael P.
Published: October 2010

The CRISPR–Cas system provides many prokaryotes with acquired resistance to viruses and other mobile genetic elements. The core components of this defense system are small, host-encoded prokaryotic silencing (psi)RNAs and Cas (CRISPR-associated) proteins. Invader-derived sequences within the psiRNAs guide Cas effector proteins to recognize and silence invader nucleic acids. Critical for CRISPR–Cas defense is processing of the psiRNAs from the primary transcripts of the host CRISPR (clustered regularly interspaced short palindromic repeat) locus. Cas6, a previously identified endoribonuclease present in a wide range of prokaryotes with the CRISPR–Cas system, binds and cleaves within the repeat sequences that separate the individual invader targeting elements in the CRISPR locus transcript. In the present study, we investigated several key aspects of the mechanism of function of Cas6 in psiRNA biogenesis. RNA footprinting reveals thatPyrococcus furiosusCas6 binds to a 7-nt (nucleotide) sequence near the 5′ end of the CRISPR RNA repeat sequence, 14 nt upstream of the Cas6 cleavage site. In addition, analysis of the cleavage activity ofP. furiosusCas6 proteins with mutations at conserved residues suggests that a triad comprised of Tyr31, His46, and Lys52 plays a critical role in catalysis, consistent with a possible general acid–base RNA cleavage mechanism for Cas6. Finally, we show thatP. furiosusCas6 remains stably associated with its cleavage products, suggesting additional roles for Cas6 in psiRNA biogenesis.