bluuebunny/crossref_metadata_2025 huggingface dataset:
Forced vital capacity and forced expiratory volume in six seconds as predictors of reduced total lung capacity
Authors: Vandevoorde J. , Verbanck S. , Schuermans D. , Broekaert L. , Devroey D. , Kartounian J. , Vincken W.
Published: October 2007

The present study aims to derive guidelines that identify patients for whom spirometry can reliably predict a reduced total lung capacity (TLC). A total of 12,693 lung function tests were analysed on Caucasian subjects, aged 18–70 yrs.

Restriction was defined as a reduced TLC. Lower limits of normal (LLN) for TLC were obtained from the European Respiratory Society recommended reference equations. Reference equations from the National Health and Nutrition Examination Survey III were used for forced vital capacity (FVC) and forced expiratory volume in six seconds (FEV6). The performance of FVC and FEV6to predict the presence of restriction was studied as follows: 1) using two-by-two (2×2) tables; and 2) by logistic regression analysis. Both analyses were performed in obstructive (defined as forced expiratory volume in one second (FEV1)/FVC or FEV1/FEV6<LLN) and nonobstructive subgroups, and separately for males and females.

The 2×2 tables showed generally low positive and high negative predictive values for FVC or FEV6below their LLN in predicting a reduced TLC. Logistic regression analysis showed that in nonobstructive subjects, restriction can be positively predicted if FVC or FEV6is <55% predicted (males) or <40% pred (females). Restriction can be ruled out if FVC or FEV in six seconds is >100% pred (males) or >85% pred (females).

In obstructive patients, spirometry cannot reliably diagnose a concomitant restrictive defect, but it can rule out restriction for patients with forced vital capacity or forced expiratory volume in six seconds >85% pred (males) or >70% pred (females).
Airway abnormalities at flexible bronchoscopy in patients with chronic cough
Authors: Decalmer S. , Woodcock A. , Greaves M. , Howe M. , Smith J.
Published: October 2007

The algorithms utilised in the diagnosis of chronic cough advocate sequential investigations and treatment trials for asthma-like syndromes, post-nasal drip and gastro-oesophageal reflux disease; however, the role of bronchoscopy is unclear. In the present authors’ specialist clinic (North West Lung Centre Cough Clinic, Manchester, UK), flexible bronchoscopy is included in the diagnostic work-up of patients with chronic unexplained cough. In a retrospective review, the authors report on their experiences.

Over an 18-month period, patients followed a diagnostic algorithm that included: chest radiography; pulmonary function; methacholine challenge; ear, nose and throat examination; and empirical reflux treatment. Where diagnosis remained elusive, bronchoscopy was performed.

A total of 82 bronchoscopies were carried out for the sole indication of chronic cough. Patient age (mean±sd) was 54.9±11.22 yrs, with a median (range) cough duration of 5 (0.5–30) yrs. In nine (11%) subjects, a diagnosis was made on inspection or biopsy. These included seven cases of tracheobronchopathia osteochondroplastica (TPO), one case of elongated uvula and one case of endobronchial amyloidosis. All TPO patients had early changes, with a typical nodular appearance to the tracheal cartilage, without significant airway obstruction. These subtle changes could not have been predicted from less invasive procedures and would have been missed without bronchoscopy.

Flexible bronchoscopy is indicated in persistent unexplained cough and may reveal contributing pathology.
Smoking is associated with an age-related decline in exhaled nitric oxide
Authors: Sundy J. S. , Hauswirth D. W. , Mervin-Blake S. , Fernandez C. A. , Patch K. B. , Alexander K. M. , Allgood S. , McNair P. D. , Levesque M. C.
Published: October 2007

Age-related declines in forced expiratory volume in one second are accelerated in smokers. Smoking is associated with decreased exhaled nitric oxide fraction (FeNO). The aim of the present study was to determine the impact of age onFeNOin otherwise healthy smokers and nonsmokers.

FeNOand serum cotinine levels were measured in 994 healthy subjects aged 18–40 yrs. American Thoracic Society questionnaire data on smoking habits was used to validate serum cotinine levels as a surrogate marker for categorisation of smokers and nonsmokers in the cohort.

Serum cotinine levels were a good discriminator of smokers (n = 99) and nonsmokers (n = 895).FeNOlevels were significantly lower in otherwise healthy smokers compared with nonsmokers. There was an inverse correlation of serum cotinine levels withFeNO. No correlation of age withFeNOwas found in nonsmokers but an inverse correlation ofFeNOwith age in smokers was found.FeNOwas significantly lower in smokers aged 21–40 yrs compared with nonsmokers aged 21–40 yrs, but was not lower in smokers aged 18–20 yrs compared with nonsmokers of the same age.

Smoking was associated with decreased exhaled nitric oxide. The greatest smoking-related declines in exhaled nitric oxide occurred in older subjects. This suggests that smoking is associated with age-related declines in exhaled nitric oxide and justifies future mechanistic studies that address the impact of exhaled nitric oxide decline on lung function.
Airway responsiveness: associated features in infants with recurrent respiratory symptoms
Authors: Kotaniemi-Syrjänen A. , Malmberg L. P. , Pelkonen A. S. , Malmström K. , Mäkelä M. J.
Published: October 2007

Increased airway responsiveness (AR) is one of the main pathophysiological manifestations of asthma. The present study aimed to define the clinical features associated with increased AR in infants with recurrent lower respiratory tract symptoms.

AR was evaluated by performing a novel dosimetric methacholine challenge test.

Increased AR to methacholine, defined as a methacholine dose of ≤0.90 mg producing a 40% fall (PD40) in the maximal flow at functional residual capacity (V′max,FRC), was associated with atopy (odds ratio (OR) 4.1; 95% confidence interval (CI) 1.3–13.3), a history of physician-confirmed wheezing with respiratory syncytial virus (OR 32.9; 95% CI 2.5–428.8) or of a nonspecified aetiology (OR 4.9; 95% CI 1.1–22.5), functional residual capacity z-score ≥2 (OR 36.8; 95% CI 2.9–472.6), andV′max,FRCz-score (OR 0.5; 95% CI 0.2–0.9) at baseline, when compared with infants with only mild or no responsiveness to methacholine (PD40V′max,FRC>0.90 mg).

In conclusion, in recurrently symptomatic infants, increased airway responsiveness is associated with reduced baseline lung function, an atopic trait of the child, a history of physician-confirmed wheeze and viral aetiology of wheeze. Future intervention studies are needed to confirm the role of airway responsiveness in respiratory morbidity during infancy.
A method for generating uniform size-segregated pyrite particle fractions
Authors: Wolfe Amy L , Liu Ran , Stewart Brian W , Capo Rosemary C , Dzombak David A
Published: October 2007

Background

Standardized sample preparation techniques allow comparison of pyrite dissolution experiments under diverse conditions. Our objective was to assess dry and wet sieving preparation methodologies, and to develop a reproducible technique that yields uniformly size-distributed material within a limited size range of interest.

Results

Here, we describe a wet sieving preparation method that successfully concentrates pyrite particles within a 44–75 μm diameter range. In addition, this technique does not require a post-processing cleanup step to remove adhering particles, as those particles are removed during the procedure. We show that sample preparation methods not only affect the pyrite size distribution, but also apparent dissolution rates.

Conclusion

The presented methodology is non-destructive to the sample, uses readily available chemical equipment within the laboratory, and could be applied to minerals other than pyrite.
EST analysis on pig mitochondria reveal novel expression differences between developmental and adult tissues
Authors: Scheibye-Alsing Karsten , Cirera Susanna , Gilchrist Michael J , Fredholm Merete , Gorodkin Jan
Published: October 2007

Background

The mitochondria are involved in many basic functions in cells of vertebrates, and can be considered the power generator of the cell. Though the mitochondria have been extensively studied there appear to be only few expression studies of mitochondrial genes involving a large number of tissues and developmental stages. Here, we conduct an analysis using the PigEST resource [1] which contains expression information from 35 tissues distributed on one normalized and 97 non-normalized cDNA libraries of which 24 are from developmental stages. The mitochondrial PigEST resource contains 41,499 mitochondrial sequences.

Results

The mitochondrial EST (Expressed Sequence Tag) sequences were assembled into contigs which covers more than 94 percent of the porcine mitochondrial genome, with an average of 976 EST sequences per nucleotide. This data was converted into expression values for the individual genes in each cDNA library revealing differential expression between genes expressed in cDNA libraries from developmental and adult stages. For the 13 protein coding genes (and several RNA genes), we find one set of six genes, containing all cytochrome oxidases, that are upregulated in developmental tissues, whereas the remaining set of seven genes, containing all ATPases, that are upregulated in adult muscle and brain tissues. Further, the COX I (Cytochrome oxidase subunit one) expression profile differs from that of the remaining genes, which could be explained by a tissue specific cleavage event or degradation pattern, and is especially pronounced in developmental tissues. Finally, as expected cDNA libraries from muscle tissues contain by far the largest amount (up to 20%) of expressed mitochondrial genes.

Conclusion

Our results present novel insight into differences in mitochondrial gene expression, emphasizing differences between adult and developmental tissues. Our work indicates that there are presently unknown mechanisms which work to customize mitochondrial processes to the specific needs of the cell, illustrated by the different patterns between adult and developmental tissues. Furthermore, our results also provide novel insight into how in-depth sequencing can provide significant information about expression patterns.
Quantity of ethanol absorption after excessive hand disinfection using three commercially available hand rubs is minimal and below toxic levels for humans
Authors: Kramer Axel , Below Harald , Bieber Nora , Kampf Guenter , Toma Cyril D , Huebner Nils-Olaf , Assadian Ojan
Published: October 2007

Background

Despite the increasing promotion of alcohol-based hand rubs and the worldwide use of ethanol-based hand rubs in hospitals only few studies have specifically addressed the issue of ethanol absorption when repeatedly applied to human skin. The aim of this study was to assess if ethanol absorption occurs during hygienic and surgical hand disinfection using three different alcohol-based hand-rubs, and to quantify absorption levels in humans.

Methods

Twelve volunteers applied three hand-rubs containing 95% (hand-rub A), 85% (hand-rub B) and 55% ethanol (hand-rub C; all w/w). For hygienic hand disinfection, 4 mL were applied 20 times for 30 s, with 1 minute break between applications. For surgical hand disinfection, 20 mL of each hand rub was applied to hands and arms up to the level of the elbow 10 times for 3 minutes, with a break of 5 minutes between applications. Blood concentrations of ethanol and acetaldehyde were determined immediately prior and up to 90 minutes after application using head space gas chromatography.

Results

The median of absorbed ethanol after hygienic hand disinfection was 1365 mg (A), 630 mg (B), and 358 mg (C). The proportion of absorbed ethanol was 2.3% (A), 1.1% (B), and 0.9% (C). After surgical hand disinfection, the median of absorbed ethanol was 1067 mg (A), 1542 mg (B), and 477 mg (C). The proportion of absorbed ethanol was 0.7% (A), 1.1% (B), and 0.5% (C). The highest median acetaldehyde concentration after 20 hygienic hand disinfections was 0.57 mg/L (hand-rub C, after 30 min), after 10 surgical hand disinfections 3.99 mg/L (hand-rub A, after 20 minutes).

Conclusion

The overall dermal and pulmonary absorption of ethanol was below toxic levels in humans and allows the conclusion that the use of the evaluated ethanol-based hand-rubs is safe.
Proteome analysis of human gastric cardia adenocarcinoma by laser capture microdissection
Authors: Cheng Yan , Zhang Jun , Li Yang , Wang Yan , Gong Jun
Published: October 2007

Background

The incidence of gastric cardiac adenocarcinoma (GCA) has been increasing in the past two decades in China, but the molecular changes relating to carcinogenesis have not been well characterised.

Methods

In this study, we used a comparative proteomic approach to analyse the malignant and nonmalignant gastric cardia epithelial cells isolated by navigated laser capture microdissection (LCM) from paired surgical specimens of human GCA.

Results

Twenty-seven spots corresponding to 23 proteins were consistently differentially regulated. Fifteen proteins were shown to be up-regulated, while eight proteins were shown to be down-regulated in malignant cells compared with nonmalignant columnar epithelial cells. The identified proteins appeared to be involved in metabolism, chaperone, antioxidation, signal transduction, apoptosis, cell proliferation, and differentiation. In addition, expressions of HSP27, 60, and Prx-2 in GCA specimens were further confirmed by immunohistochemical and western blot analyses.

Conclusion

These data indicate that the combination of navigated LCM with 2-DE provides an effective strategy for discovering proteins that are differentially expressed in GCA. Such proteins may contribute in elucidating the molecular mechanisms of GCA carcinogenesis. Furthermore, the combination provides potential clinical biomarkers that aid in early detection and provide potential therapeutic targets.
The odor of origin: kinship and geographical distance are reflected in the marking pheromone of male beewolves (Philanthus triangulum F., Hymenoptera, Crabronidae)
Authors: Kaltenpoth Martin , Kroiss Johannes , Strohm Erhard
Published: October 2007

Background

Pheromones play an important role for mate finding and courtship in many insects. In species where males are the signaling sex, females are expected to choose among potential mates with regard to the emitter's quality and/or genetic compatibility. One important aspect is the balance between negative and positive effects of in- vs. outbreeding. In the present study, we aimed to assess the potential of the territory marking pheromone of European beewolves as an indicator for genetic compatibility in the context of female choice.

Results

We analyzed the sex pheromone composition of male European beewolves (Philanthus triangulum F., Hymenoptera, Crabronidae) from eight different locations across Central Europe (six in Germany, one in England, and one in Italy). The pheromone constitutes a complex blend of various long-chain hydrocarbons (alkanes, alkenes, alcohols, ketones, and a carbon acid). We demonstrate that pheromone composition differs significantly among distant populations (regional scale), among subpopulations (local scale) and between families within subpopulations. The differences in the pheromone blend are positively correlated with geographical distances as might be expected according to an isolation-by-distance model. On a local scale, family membership has a larger effect on pheromone composition than subpopulation affiliation, while the reverse is true for the regional scale.

Conclusion

Our results show that male pheromones can contain information on both kinship and geographical origin that may be used by females to choose adaptively among potential mates on the basis of their genetic distance.
Responses of cancer cells with wild-type or tyrosine kinase domain-mutated epidermal growth factor receptor (EGFR) to EGFR-targeted therapy are linked to downregulation of hypoxia-inducible factor-1α
Authors: Lu Yang , Liang Ke , Li Xinqun , Fan Zhen
Published: October 2007

Background

Searching for novel molecular markers that dependably predict or indicate responses of human cancer cells to epidermal growth factor receptor (EGFR)-targeted therapy is strongly warranted. The purpose of the current study was to evaluate hypoxia-inducible factor-1α (HIF-1α) as a novel response marker compared with previously explored markers following treatment with an EGFR-blocking monoclonal antibody (cetuximab) and a small-molecule EGFR tyrosine kinase inhibitor (gefitinib) in a group of cancer cell lines containing wild-type or tyrosine kinase domain-mutated EGFR.

Results

We found that, compared with previously studied response markers, including EGFRper seand three EGFR downstream signal molecules (ERK, Akt, and STAT3), which showed variable post-treatment changes in levels of phosphorylation and no consistent link of the changes to therapeutic responses, HIF-1α showed a selective decrease in protein levels only in responsive cell lines. To demonstrate a critical role of HIF-1α downregulation by EGFR-targeted treatment, we introduced a constitutively expressed HIF-1α mutant (HIF-1α/ΔODD) that is resistant to cetuximab-induced downregulation in a cetuximab-responsive cell line (A431); we found that the HIF-1α/ΔODD-transfected cells remained sensitive to cetuximab-induced inhibition of Akt and ERK phosphorylation but were remarkably less responsive to cetuximab-induced growth inhibition compared with corresponding control cells.

Conclusion

Our data indicates that downregulation of HIF-1α is associated with positive therapeutic responses of cancer cells to EGFR-targeted therapy and suggest further investigation using HIF-1α as an indicator of tumor response to EGFR-targeted therapy in preclinical studies and in the clinical setting.
Primary presacral neuroendocrine tumor associated with imperforate anus
Authors: Kim Tad , Grobmyer Stephen R , Liu Chen , Hochwald Steven N
Published: October 2007

Background

Presacral masses are unusual growths that have a limited differential diagnosis, typically not including neuroendocrine tumors (NETs). Classically, NETs are well-differentiated gastroenteropancreatic tumors of probable benign behavior. These tumors are associated with a typical morphologic pattern and involve the distal colon, rectum, and genitourinary tract; they are considered less aggressive, frequently asymptomatic, and rarely cause carcinoid syndrome, even when metastatic. Neuroendocrine tumors of the presacral region are extremely rare and few have been described in the literature. They have not been previously reported as being associated with imperforate anus.

Case presentation

We present an interesting case of a woman with a history of imperforate anus that was found to have a primary neuroendocrine tumor of the presacral region with no rectal wall involvement.

Conclusion

We argue that this is a primary gastroenteropancreatic neuroendocrine tumor which likely originated from cells of hindgut origin that underwent an abnormal migration during embryonic development.
Efficacy of adjuvant chemotherapy according to hormone receptor status in young patients with breast cancer: a pooled analysis
Authors: van der Hage Jos A , Mieog J Sven D , van de Vijver Marc J , van de Velde Cornelis JH ,   cooperating investigators of the European Organization for Research and Treatment of Cancer
Published: October 2007

Introduction

Breast cancer at a young age is associated with an unfavorable prognosis. Very young patients with breast cancer therefore are advised to undergo adjuvant chemotherapy irrespective of tumor stage or grade. However, chemotherapy alone may not be adequate in young patients with hormone receptor-positive breast cancer. Therefore, we studied the effect of adjuvant chemotherapy in young patients with breast cancer in relation to hormone receptor status.

Methods

Paraffin-embedded tumor material was collected from 480 early-stage breast cancer patients younger than 41 years who participated in one of four European Organization for Research and Treatment of Cancer trials. Using immunohistochemistry on the whole series of tumors, we assessed estrogen receptor (ER) status and progesterone receptor (PgR) status in a standardized way. Endpoints in this study were overall survival (OS) and distant metastasis-free survival (DMFS). The median follow-up period was 7.3 years.

Results

Overall, patients with ER-positive tumors had better OS rates (hazard ratio [HR] 0.63; P = 0.02) compared with those with ER-negative tumors. However, in the subgroup of patients who received chemotherapy, no significant difference in OS (HR 0.87; P = 0.63) and DMFS (HR 1.36; P = 0.23) was found between patients with ER-positive tumors or those with ER-negative tumors. These differences were similar for PgR status.

Conclusion

Young patients with hormone receptor-positive tumors benefit less from adjuvant systemic chemotherapy than patients with hormone receptor-negative tumors. These results confirm that chemotherapy alone cannot be considered optimal adjuvant systemic treatment in breast cancer patients 40 years old or younger with hormone receptor-positive tumors.
Identification of the scavenger receptors SREC-I, Cla-1 (SR-BI), and SR-AI as cellular receptors for Tamm-Horsfall protein
Authors: Pfistershammer Katharina , Klauser Christoph , Leitner Judith , Stöckl Johannes , Majdic Otto , Weichhart Thomas , Sobanov Yuri , Bochkov Valery , Säemann Marcus , Zlabinger Gerhard , Steinberger Peter
Published: October 2007

Tamm-Horsfall protein (THP) is expressed exclusively in the kidney and constitutes the most abundant protein in urine. An important role for THP in antibacterial host defense but also in inflammatory disorders of the urogenital tract has been suggested. In line with this, THP has been shown recently to potently activate macrophages and dendritic cells (DC) via the toll-like receptor 4 (TLR4) pathway. We show here that THP interacts specifically with surface structures on DC and provides evidence that they are distinct from TLR4. Using retroviral expression cloning, we have identified one such receptor as the scavenger receptor (SR) expressed by endothelial cells I (SREC-I). In addition, we found that two other receptors for acetylated low-density lipoprotein (AcLDL), namely scavenger receptors AI (SR-AI) and Cla-1 (SR-BI), also serve as receptors for THP. SREC-I/THP interaction is of high affinity (16.8±6.8 nM), whereas Cla-1 and SR-AI have lower affinities for THP (396 nM±114 nM and 802 nM±157 nM, respectively). The interaction of THP with these molecules is fully blocked by AcLDL. However, AcLDL only partially blocks binding of THP to DC, and a series of experiments did not support a role in DC activation for SR interacting with THP and AcLDL. Thus, our data point to the existence of additional receptors for THP, which mediate TLR4-dependent DC activation. Interaction and up-take of THP by SR might play an important role in local host defense and could contribute to inflammatory kidney diseases associated with THP-specific antibody responses.
Differential expression of β2-integrins and cytokine production between γδ and αβ T cells in experimental autoimmune encephalomyelitis
Authors: Smith Sherry S , Barnum Scott R
Published: October 2007

The expression of β2-integrins on γδ T cells in naïve mice or those with experimental autoimmune encephalomyelitis (EAE) remains poorly characterized. We compared β2-integrin expression and cytokine production between γδ and αβ T cells over the acute course of EAE. We observed that unlike in αβ T cells, β2-integrin expression on γδ T cells increased significantly from baseline, peaked at Day 10, and remained unchanged in the draining lymph nodes or declined in the spleen and CNS by Day 15. In addition, IFN-γ- and TNF-α-producing γδ T cells infiltrated the CNS rapidly and produced significantly more of these cytokines than αβ T cells throughout the course of EAE. These results suggest unique roles for β2-integrins in the trafficking of γδ versus αβ T cells during EAE and that γδ T cells infiltrate the CNS rapidly, producing cytokines, which modulate acute disease.
Neutrophil adhesion to E-selectin under shear promotes the redistribution and co-clustering of ADAM17 and its proteolytic substrate L-selectin
Authors: Schaff Ulrich , Mattila Polly E , Simon Scott I , Walcheck Bruce
Published: October 2007

E-selectin is expressed by the vascular endothelium and binds flowing neutrophils in the blood to facilitate their recruitment into the underlying tissue at sites of inflammation. L-selectin on neutrophils is engaged by E-selectin and undergoes rapid clustering and then coalescence in the trailing edge of polarizing cells. These processes are believed to increase the valency and capacity of L-selectin to signal CD18 integrin activity. Neutrophils, upon exiting the microvasculature, down-regulate their surface L-selectin through ectodomain shedding by a disintegrin and metalloprotease 17 (ADAM17). We reasoned that neutrophil tethering and rolling on E-selectin might initiate a coordinate change in the membrane distribution of ADAM17 as well. We found that ADAM17 indeed underwent a dramatic cell surface redistribution to the trailing edge of neutrophils rolling on purified E-selectin when activated by a chemoattractant under shear flow; however, its lateral migration occurred at a slower rate than L-selectin. ADAM17 and L-selectin also redistributed in the same manner in neutrophils attached to IL-1β-stimulated HUVEC under shear flow. In contrast, the coalescence of L-selectin on the surface of neutrophils by antibody cross-linking did not promote the redistribution of ADAM17, suggesting that these molecules do not constitutively associate in the plasma membrane. Together, our findings reveal that neutrophil activation upon E-selectin adhesion initiates active transport of ADAM17 and L-selectin to the cell uropod, thus providing additional insight into the molecular mechanisms that regulate L-selectin during leukocyte extravasation.
Genome-wide analysis of DNA methylation patterns
Authors: Zilberman Daniel , Henikoff Steven
Published: October 2007

Cytosine methylation is the most common covalent modification of DNA in eukaryotes. DNA methylation has an important role in many aspects of biology,including development and disease. Methylation can be detected using bisulfite conversion, methylation-sensitive restriction enzymes, methyl-binding proteins and anti-methylcytosine antibodies. Combining these techniques with DNA microarrays and high-throughput sequencing has made the mapping of DNA methylation feasible on a genome-wide scale. Here we discuss recent developments and future directions for identifying and mapping methylation, in an effort to help colleagues to identify the approaches that best serve their research interests.
SHP-2 is required for the maintenance of cardiac progenitors
Authors: Langdon Yvette G. , Goetz Sarah C. , Berg Anna E. , Swanik Jackie Thomas , Conlon Frank L.
Published: October 2007

The isolation and culturing of cardiac progenitor cells has demonstrated that growth factor signaling is required to maintain cardiac cell survival and proliferation. In this study, we demonstrate in Xenopus that SHP-2 activity is required for the maintenance of cardiac precursors in vivo. In the absence of SHP-2 signaling, cardiac progenitor cells downregulate genes associated with early heart development and fail to initiate cardiac differentiation. We further show that this requirement for SHP-2 is restricted to cardiac precursor cells undergoing active proliferation. By demonstrating that SHP-2 is phosphorylated on Y542/Y580 and that it binds to FRS-2, we place SHP-2 in the FGF pathway during early embryonic heart development. Furthermore, we demonstrate that inhibition of FGF signaling mimics the cellular and biochemical effects of SHP-2 inhibition and that these effects can be rescued by constitutively active/Noonan-syndrome-associated forms of SHP-2. Collectively, these results show that SHP-2 functions within the FGF/MAPK pathway to maintain survival of proliferating populations of cardiac progenitor cells.
Characterization of a natural heterodimer between MLV genomic RNA and the SD′ retroelement generated by alternative splicing
Authors: Maurel Stéphan , Houzet Laurent , Garcia Eric L. , Telesnitsky Alice , Mougel Marylène
Published: October 2007

Murine leukemia virus (MLV) specifically packages both genomic RNA (FL RNA) and a subgenomic RNA, which we call SD′. SD′ RNA results from alternative splicing of FL RNA. It is reverse-transcribed, and its DNA copy, integrated into the host genome, constitutes a splice donor-associated retroelement. FL and SD′ RNAs share a common 5′-UTR that includes the packaging/dimerization signal (Psi). To investigate whether the mechanism of copackaging of these two RNAs involves RNA heterodimerization, we examined the spontaneous dimerization capacity of the two RNAs as large synthetic RNAs transcribed in vitro. We showed that SD′ RNA not only formed homodimers with similar efficiency as the FL RNA, but that FL and SD′ RNAs also formed FL/SD′ heterodimers via Psi sequences. Comparison of the thermostabilities determined for these different dimeric species and competition experiments with Psi RNA fragments indicate the recruitment of similar dimer-linkage interactions within the Psi region. To validate these results, the dimeric state of the SD′ RNA was analyzed in MLV particles. RNA capture assays performed with the FL RNA as bait revealed that SD′, and not the host packageable U6 or 7SL RNAs, was associated with the FL RNA in virions. Heterodimerization of SD′ RNA with FL RNA may argue for the recent concept of a nuclear dimerization at or near the site of transcription and raises the new hypothesis of RNA dimerization during splicing. Furthermore, FL/SD′ heterodimerization may have leukemogenic consequences by influencing the pool of genomic dimers that will undergo recombinogenic template switching by reverse transcriptase.
Dicer-1, but not Loquacious, is critical for assembly of miRNA-induced silencing complexes
Authors: Liu Xiang , Park Joseph K. , Jiang Feng , Liu Ying , McKearin Dennis , Liu Qinghua
Published: October 2007

Double-stranded RNA-binding proteins (dsRBPs), such as R2D2 and Loquacious (Loqs), function in tandem with Dicer (Dcr) enzymes in RNA interference (RNAi). In Drosophila, Dcr-1/Loqs and Dcr-2/R2D2 complexes generate microRNAs (miRNAs) and small interfering RNAs (siRNAs), respectively. Although R2D2 does not regulate siRNA production, R2D2 and Dcr-2 coordinately bind siRNAs to promote assembly of the siRNA-induced silencing (siRISC) complexes. Conversely, Loqs enhances miRNA production. It is uncertain if Dcr-1 and Loqs facilitate miRNA loading onto the miRISC complexes. Here we used loqs knockout (KO) flies to characterize the physiological functions of Loqs in the miRNA pathway. Northern analysis revealed consistent accumulation of precursor (pre)-miRNAs in loqsKO flies. However, the lack of Loqs had differential effects on mature miRNAs: some are diminished, whereas others maintain wild-type levels. Importantly, the data suggest that miRNA production is not the rate-limiting step of the miRNA pathway. We show that Dcr-1, but not Loqs, is critical for assembly of miRISCs by using dcr-1 or loqs null egg extract. Consistent with this, recombinant Dcr-1 could efficiently interact with miRNA duplex in the absence of Loqs. Together, our results indicate that Loqs plays a prominent role in miRNA biogenesis, but is largely dispensable for miRISC assembly. Thus, Loqs and R2D2 represent two distinct functional modes for dsRBPs in the RNAi pathways.
Risk Stratification for Heart Failure and Death in an Acute Coronary Syndrome Population Using Inflammatory Cytokines and N-Terminal Pro-Brain Natriuretic Peptide
Authors: Kavsak Peter A , Ko Dennis T , Newman Alice M , Palomaki Glenn E , Lustig Viliam , MacRae Andrew R , Jaffe Allan S
Published: October 2007

Background: Inflammation in acute coronary syndrome (ACS) can identify those at greater long-term risks for heart failure (HF) and death. The present study assessed the performance of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1 (MCP-1) (cytokines involved in the activation and recruitment of leukocytes) in addition to known biomarkers [e.g., N-terminal pro-brain natriuretic peptide (NT-proBNP)] for predicting HF and death in an ACS population.

Methods: In a cohort of 216 ACS patients, NT-proBNP (Elecsys®; Roche) and IL-6, IL-8, and MCP-1 (evidence investigator™; Randox) were measured in serial specimens collected early after symptom onset (n = 723). We collected at least 2 specimens from each participant: an early specimen (median 2 h; interquartile range 2–4 h) and a later specimen (9 h; 9–9 h), and used the later specimens’ biomarker concentrations for risk stratification.

Results: An increase in both IL-6 and NT-proBNP was observed but not for IL-8 or MCP-1 early after pain onset. Kaplan–Meier analysis demonstrated that individuals with increased NT-proBNP (>183 ng/L) or cytokines (IL-6 > 6.4 ng/L; above upper limit of normal for IL-8 or MCP-1) had a greater probability of death or HF in the following 8 years (P <0.05). In a Cox proportional hazard model adjusted for both CRP and troponin I, increased IL-6, MCP-1, and NT-proBNP remained significant risk factors. Combining all 3 biomarkers resulted in a higher likelihood ratio for death or HF than models restricted to any 2 of these biomarkers.

Conclusion: IL-6, MCP-1, and NT-proBNP are independent predictors of long-term risk of death or HF, highlighting the importance of identifying leukocyte activation and recruitment in ACS patients.
Interfacing health care and innovation: Traditional medicinal knowledge in Nigeria
Authors: Sampath Padmashree Gehl , Oyelaran-Oyeyinka Banji
Published: October 2007

Traditional medicinal knowledge and related innovations are deeply embedded within the context of knowledge use and exchange of health services in developing countries. Traditional medicine systems cater to the health needs of a majority of people in the developing world, and there
is a clear link between such practice and feedback innovations based on traditional medicinal knowledge. Understanding these interlinkages calls for an interface between innovation systems and health systems, and this is perhaps why this issue has not received the kind of attention it deserves
in either strands of literature. This paper uses field level data collected during a survey of the biopharmaceutical innovation system in Nigeria in 20032004 to highlight these interlinkages. By way of results obtained in the survey, it derives the scope for policy intervention in order to
harness the role of traditional medicinal knowledge for both biopharmaceutical innovation and health care infrastructure in Nigeria.
Universities, poverty and technology management: Developing export markets for West African micro-enterprises
Authors: Conlon Jane , Humphreys John
Published: October 2007

To ensure that the benefits of economic development reach the African poor, action on income redistribution is necessary. In the mid-1990's, international aid funding was refocused from higher education into areas thought to be more directly compatible with the emergent poverty reduction
priority. Recent rehabilitation of higher education is exemplified by the report of the Commission for Africa, which asked the international community to commit US 5 billion to revitalise Africa's institutions of higher education with a view to developing professional elites as the basis for
global competitiveness and good government. Universities can make direct contributions to poverty reduction but not as a consequence of their traditional activities. Such contributions can be achieved through technology management projects whose benefits are directly relevant to the income
of poor communities. An example of such a project is described involving the development of export trading for garment manufacturing micro-enterprises. Resolving issues relating to design, standardisation and quality control and scaling up has enabled the development of export markets, which
directly connect the spending power of affluent European populations with poor communities in Ghana.
Leadership for sustainable innovation
Authors: Bossink Bart A.G
Published: October 2007

This article explores and explains the effects of a manager's leadership style on sustainable, that is environment friendly, innovation processes. It uses an analytical framework, based on the literature, to investigate a manager's influence on sustainable innovation in the Dutch building
sector. An empirical research project observes a manager in a series of sustainable innovation processes in four building projects. The research shows that a manager's charismatic, instrumental, strategic, or interactive leadership style substantially contributes to the development of sustainable
innovation processes. It also shows that the exchange of knowledge and information in the organisation affects the sustainable innovation process. It concludes that a manager's performance of an innovation leadership style is (un)successful where it is (not) combined with the management of
knowledge.
Product innovation through management of collaborative design in concurrent engineering
Authors: Girard Philippe , Legardeur Jrmy , Merlo Christophe
Published: October 2007

The control of engineering design processes is a complex problem that takes place within conflicting contexts combining technical, economic and social aspects. This paper presents the results of a study on the development of new methods and tools for the control of manufactured product
design. In discussing these approaches, the paper shows their limitations with respect to the control of design coordination and collaboration, especially when the sociotechnical aspects of the design process are studied. A design control model and collaboration taxonomy that would enhance
decisions concerning the coordination of design projects is presented. The tools discussed are the result of empirical studies based on the experiences of different industrial companies. The paper concludes by highlighting how these tools can be used for routine-based as well as innovative
project operations.
Reviews
Authors: Morawczynski Olga , Hanlin Rebecca
Published: October 2007

The Cell Phone: An Anthropology of Communication, Heather Horst and Daniel Miller (2006) Berg, 224 pp., ISBN 1845204018 (pbk), 16.99

The Oxford Handbook of Innovation Jan Faberberg, David C. Mowery and Richard R. Nelson (2006) Oxford: Oxford University
Press, xviii + 656 pp., ISBN 0-19-928680-9 (pbk), 30.00
Institutional change and innovation capacity: Contrasting experiences of promoting small-scale irrigation technology in South Asia
Authors: Hall Andy , Clark Norman , Naik Guru
Published: October 2007

The most effective approach to agricultural technology promotion and innovation is still a source of considerable debate, and nowhere more so than in the context of agricultural engineering hardware. Contemporary perspectives on agricultural innovation stress the importance of institutional
change and give emphasis to the need to develop innovation capacity in systems terms, rather address limitations of technology transfer mechanisms. This paper illustrates using the case of manual irrigation technology treadle pumps in Bangladesh and India. It identifies five elements of this
capacity: (1) a sector coordination mechanism; (2) a developmental rather than technical organising principle for sector development; (3) habits and practices (institutions) of key organisations; (4) interaction as a learning and knowledge transmission mechanism; (5) market demand as key incentive
for innovation and (6) policies and institutional innovations to ensure adequate stakeholder participation. The paper concludes by suggesting that identifying new sources of institutional innovation is the most pressing task for initiatives that seek to make more effective use of knowledge
and technology in development.
Extended theatre composition in telematized environments
Authors: Petersen Kjell Yngve
Published: October 2007

In the pursuit of a dramaturgy of telematics as a compositional practice, the author builds a position on technology as externalized technique, develops a dramaturgic strategy with notions of an extended theatre practice and reports on a realized telematized performance where a practical implementation was explored.

The theatrical site is viewed as a construct of attention, generated by the performers through the performance composition. The composition determines the audience experience, orchestrated by how the construction of the site manages their perspectives, and how the performers are situated in the consciousness site of the audience.

In the performed event the performers articulate as a collective extended entity, incorporating the transformation of the performance site via the articulation strategies implemented in the staging. Telematics is argued to be a technology facilitating specific modes of thinking, generating specific modes of actions and presence, which enable new performance sites and new modes of situating performance.
Brave BioArt 2: shedding the bio, amassing the nano, and cultivating posthuman life
Authors: Vita-More Natasha
Published: October 2007

This article will address an overview of BioArt, biomedia and its practitioners, developed through a series of semi-structured, qualitative interviews and openended discussions with more than fifteen experts in the field. BioArt is approached from the perspective of scientific exploration,
visual design in interactivity and installation, and social commentary and political activism. Of consequence is the fact that BioArt is relatively new, its nomenclature is without a codified definition, and bioartists have varied views on the parameters of its biomedia. Regardless, BioArt
has been escalating as a fecund medium with the potential for spawning visionary and critical practices and theories. In lieu of a slippery slope in which artists rely on freedom of expression in substantiating artworks, the burden of proof is placed on artists to be creative and objective
in understanding what it means to tamper with biology and alter life forms. Issues of ethics have already affected artists' practices and venues for exhibition, and as BioArt continues to develop, research practice has become a necessary field of study. In addition, as biomedia evolve and
emergent technologies partner with current biotechnologies, there is concern if the concept of BioArt is ambiguous in light of the fact that biotechnology is dovetailing nanotechnology, artificial general intelligence and cognitive science. Herein there is a need for practice-based scenarios
for questioning constructive and destructive viewpoints about BioArt and, more particularly, concerning the future of life forms.
Evaluation of the First Mode of Vibration and Base Fixidity in Resonant-Column Testing
Authors: Khan Zahid H. , Cascante Giovanni , El-Naggar M. Hesham
Published: October 2007

In resonant column testing (ASTM standard), the shear strain distribution along the height of a specimen is assumed linear and fixed at the base. To investigate these assumptions, specimens of dry sand, mine tailings, and cemented sand are tested at different confinement and shear strain levels. The measured mode shapes for dry sands and mine tailings are linear at low and high strain levels; however, for a stiff cemented-sand specimen the first mode shape presents slippage at the end platens. Resonant frequencies decrease up to 50 % while the damping ratios increase up to 200 % because of this slippage. The coupling between the specimen and end-platens is enhanced using three different agents: gypsum cement, portland cement, and epoxy resin. The epoxy resin produces the best coupling, whereas portland and gypsum cements are effective only at low confinements and strain levels. Even after eliminating the slippage at the end-platens, the shear wave velocity of aluminum and PVC probes decreases with the increase in specimen stiffness because of the lack of base fixidity. To correct this apparent reduction, a new model and calibration procedure based on a two-degree-of-freedom system are proposed.
Estimation of Osmotic Suction from Electrical Conductivity and Water Content Measurements in Unsaturated Soils
Authors: Abedi-Koupai Jahangir , Mehdizadeh Hasan
Published: October 2007

Salt-affected soils are a common feature of an arid-zone landscape. Osmotic suction arises from the salt content in the soil pore fluid. In this research osmotic potential was obtained by measuring total and matric suction via the filter paper technique. The filter paper technique has been widely adopted for measuring soil water potential in the recent years and now is a U.S. standard.

One thousand and twenty samples of clay, silty clay loam, sandy clay loam, and loam having different levels of soil water content, between the field capacity (F.C.) and permanent wilting point (P.W.P.) defined as the soil water content below which plants wilt permanently, and ten levels of soil salinity were tested. The measuring tests were repeated three times and aimed at measuring the osmotic suction. By stepwise multiple regression analysis, four new empirical relations were obtained to estimate the osmotic suction as a function of soil water content and the electrical conductivity of saturation extracts (ECe).The results also indicate that the estimation of osmotic suction using the filter paper technique is inexpensive, relatively simple, and applicable to wide ranges of soil salinity.
Specimen Size Limitations inJ-RCurve Testing—Standards Versus Reality
Authors: Wallin Kim
Published: October 2007

Testing standards contain limitations on allowable J and crack growth, related to specimen size. In the case of unirradiated pressure vessel steel, it is usually possible to extract specimens of sufficient size to allow a standard determination of the J-R curve. However, in the case of irradiated materials, especially irradiated internals, it is normally not possible to use specimens that would provide valid results according to the standard requirement. This raises the question as to the relevance of the standard requirements. The size requirements stem from the dawn of elastic-plastic fracture mechanics. They have remained practically unchanged ever since, even though the understanding of elastic-plastic fracture mechanics and ductile fracture has evolved considerably. In this paper, the state-of-art understanding of the ductile fracture process, and elastic-plastic fracture mechanics is combined with experimental test results to derive new more realistic size requirements for J-R curve testing. It is shown that a considerable relaxation of the standard requirements is possible without affecting the reliability of the test result. This enables an effective and reliable testing of irradiated materials and structures whose dimensions inhibit the extraction of large specimens.
Violence today
Authors: Wieviorka Michel
Published: October 2007

In this paper, the author seeks to approach contemporary violence in its most different expressions, including the use of the most recent developments in biology, bacteriology, chemistry and nuclear physics. The central idea is that violence changes, and with it the way it is perceived and how we react to it. The text, besides putting violence into a historical context, analyzes 1) the big transformation(s) in the world: the end of the cold war, the new industrial structure and its consequences for the decline of the labor movement, globalization and the new forms of victimization; 2) in the second part, the author points to new approaches and characterizes novel contemporary subjects.