text:
Smoking decreases the response of human lung macrophages to double-stranded RNA by reducing TLR3 expression
© Todt et al.; licensee BioMed Central Ltd. 2013
Received: 3 May 2012
Accepted: 22 February 2013
Published: 9 March 2013
Cigarette smoking is associated with increased frequency and duration of viral respiratory infections, but the underlying mechanisms are incompletely defined. We investigated whether smoking reduces expression by human lung macrophages (Mø) of receptors for viral nucleic acids and, if so, the effect on CXCL10 production.
We collected alveolar macrophages (AMø) by bronchoalveolar lavage of radiographically-normal lungs of subjects undergoing bronchoscopies for solitary nodules (n = 16) and of volunteers who were current or former smokers (n = 7) or never-smokers (n = 13). We measured expression of mRNA transcripts for viral nucleic acid receptors by real-time PCR in those AMø and in the human Mø cell line THP-1 following phorbol myristate acetate/vitamin D3 differentiation and exposure to cigarette smoke extract, and determined TLR3 protein expression using flow cytometry and immunohistochemistry. We also used flow cytometry to examine TLR3 expression in total lung Mø from subjects undergoing clinically-indicated lung resections (n = 25). Of these, seven had normal FEV1 and FEV1/FVC ratio (three former smokers, four current smokers); the remaining 18 subjects (14 former smokers; four current smokers) had COPD of GOLD stages I-IV. We measured AMø production of CXCL10 in response to stimulation with the dsRNA analogue poly(I:C) using Luminex assay.
Relative to AMø of never-smokers, AMø of smokers demonstrated reduced protein expression of TLR3 and decreased mRNA for TLR3 but not TLR7, TLR8, TLR9, RIG-I, MDA-5 or PKR. Identical changes in TLR3 gene expression were induced in differentiated THP-1 cells exposed to cigarette smoke-extract in vitro for 4 hours. Among total lung Mø, the percentage of TLR3-positive cells correlated inversely with active smoking but not with COPD diagnosis, FEV1% predicted, sex, age or pack-years. Compared to AMø of never-smokers, poly(I:C)-stimulated production of CXCL10 was significantly reduced in AMø of smokers.
Active smoking, independent of COPD stage or smoking duration, reduces both the percent of human lung Mø expressing TLR3, and dsRNA-induced CXCL10 production, without altering other endosomal or cytoplasmic receptors for microbial nucleic acids. This effect provides one possible mechanism for increased frequency and duration of viral lower respiratory tract infections in smokers.
Trial registration
ClinicalTrials.gov NCT00281190, NCT00281203 and NCT00281229.
KeywordsLung Cigarette smoking Effects Toll-like receptors Macrophages Alveolar
Viral respiratory infections are major risk factors for exacerbations of chronic obstructive pulmonary disease (COPD) and asthma [1, 2], contributing to enormous societal costs due to healthcare utilization and reduced productivity. The frequency and duration of viral respiratory infections is increased by cigarette smoking [3–6] through multiple mechanisms, including reduced mucociliary clearance, impaired production of epithelial defensins, and decreased neutrophil chemotaxis {reviewed in [7, 8]}. Smoking also negatively impacts host defense by alveolar macrophages (AMø), a key phagocyte and source of inflammatory mediators. Acting via both nicotinic cholinergic receptors [9] and uncharacterized mechanisms [10], smoking decreases pro-inflammatory cytokine release by human AMø [11–13]. Cigarette smoke extract (CSE) also blunts the ability of AMø to be activated by IFN-γ produced by T cells and natural killer (NK) cells [14]. Whether smoking has additional effects predisposing to viral respiratory infections is unknown.
We hypothesized that cigarette smoke could also reduce the ability of AMø to detect and activate innate responses to respiratory viruses. Cells recognize viruses by sensing double-stranded (ds) RNA using TLR3, which is expressed on endosomes and in some cell types, on the cell surface [15, 16]. The other endosomal microbe-associated molecular pattern (MAMP) receptors, TLR7, TLR8 and TLR9, are also important for recognizing single stranded RNA and bacterial DNA with unmethylated CpG dinucleotides, respectively. Alternatively, dsRNA can also be recognized via cytosolic sensors, such as double-stranded RNA-dependent protein kinase R (PKR), retinoic acid-inducible gene I (RIG-I), or melanoma differentiation-associated gene 5 (MDA-5) [17].
Experimentally, the response to dsRNA is measured using the synthetic analogue polyinosinic acid:cytidylic acid (poly(I:C)), which stimulates secretion of the chemokine CXCL10 (formerly IP-10) [18–20], in some cell types in an entirely TLR3-dependent fashion [21]. CXCL10 is important to recruit and activate neutrophils, lymphocytes and NK cells [22–24], which are crucial to limit viral replication. At concentrations 100-fold higher than needed for chemotactic activity, CXCL10 also has defensin-like antimicrobial activities [25] and can enhance Mø killing of intracellular Leishmania[26].
The purpose of this study was to determine the effect of smoking on endosomal and cytoplasmic receptors for nucleic acids. Our results demonstrate the susceptibility in human AMø of TLR3, but not of other receptors tested, to smoke-induced down-regulation.
Research subjects
Studies and consent procedures were performed in accordance with the Declaration of Helsinki at the VA Ann Arbor Healthcare System (all bronchoscopies and some clinically-indicated lung resections) and the University of Michigan Health System (some clinically-indicated lung resections, including all lung transplants and lung volume reduction surgeries) and were approved by their Institutional Review Boards (FWA 00000348 & FWA 00004969, respectively). All subjects understood the purpose of the study and gave written consent before any research procedures. All subjects underwent a complete history and physical examination by a Pulmonologist, spirometry, chest imaging, prospective collection of medication history, and complete blood count with differential, coagulation studies and chemistry panel.
Bronchoalveolar lavage (BAL) cohort
We recruited 13 healthy never-smoker volunteers and 23 subjects with a smoking history who either were scheduled to undergo bronchoscopy in the evaluation of solitary pulmonary nodules (n = 16) or who volunteered (n = 7). Among the 23 subjects who had ever smoked, 18 were active smokers (<six months since quitting) and 5 were former smokers (>six months since quitting). Of those with any smoking history, subjects (n =10) with ≥10 pack years, a ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) >0.7, normal spirometry, and no clinical diagnosis of COPD represent control smokers. Subjects (n =13) with a smoking history, FEV1/FVC <0.7 and abnormal spirometry were considered to have COPD. All subjects were without evidence of lung infection, interstitial lung disease or collagen vascular disease.
Importantly, not all types of experiments were performed on cells from every subject in this cohort, and conversely, some subjects were used for more than one type of experiment. The characteristics of the BAL subjects used in each type of experiments are summarized in Tables in the Results sections; demographic and clinical data for this entire cohort are shown in Additional file 1: Table S1.
Lung tissue cohort
Lung tissue was collected from consented subjects undergoing clinically-indicated resections for pulmonary nodules, lung volume reduction surgery, or lung transplantation (n = 25). Using the same definitions as in the BAL cohort, this cohort comprised seven control smokers and 18 subjects with COPD. This cohort was used exclusively for flow cytometric analysis of total lung Mø. Characteristics of this cohort are summarized in the Results section, and demographic and clinical data for individual subjects are shown in Additional file 2: Table S2.
BAL procedure and cell preparation
BAL was performed in the right middle lobe and lingula of the volunteers and in whichever of these sites was contralateral to the nodule in the clinically-indicated bronchoscopies, in which the research BAL was performed as early as feasible, and always before any biopsies or brushings. We instilled 100 ml normal saline per site, using a 30 ml syringe and gentle manual suction. BAL fluid was filtered through sterile gauze to remove mucous, and cells were washed thrice with PBS, with centrifugation between washes.
BAL cells (>95% AMø by Wright-Giemsa-stained cytospins) were either immediately processed for flow cytometry and immunohistochemistry or were cultured briefly to purify AMø by adherence. For this purpose, cells were resuspended in complete medium (RPMI 1640 containing 25 mM HEPES, 2 mM l-glutamine, 1 mM pyruvate, 100 U/ml penicillin/streptomycin, 10% heat-inactivated AB human serum (all from Invitrogen, Carlsbad, CA), and 55 μM 2-ME (Sigma Chemical, St. Louis, MO), and were plated at 2 × 105 cells/well in sterile 24-well plates. Cells were incubated for 1.5 h in 5% CO2 at 37°C, washed to remove nonadherent cells, then incubated in AIM-V serum-free medium (Invitrogen) under experimental conditions. For TLR3 stimulation, adherence-purified AMø were cultured in AIM-V alone or with poly(I:C) at 50 μg/ml for 24 h.
Lung sample preparation
Lung tissue was dissected free of any areas containing nodules, cancers or evidence of infection by a Pathologist before being released to the study. Lung sections weighing approximately 3 g were dispersed using a Waring blender in a biosafety cabinet without enzyme treatments, which we have previously shown produces single cell suspensions of high viability and functional capacity [27, 28]. Cells were filtered through a 40 μm strainer to remove debris and were resuspended in staining buffer (2% FBS in PBS) for flow cytometery.
Differentiation and treatment of THP-1 cells
THP-1 cells obtained from ATCC (Manassas, VA) were grown according to the supplier's guidelines. Cells were plated at 4 × 105 cells/well in 24-well plates, and after adherence, were differentiated by exposure to 150 ng/ml phorbol myristate acetate (PMA) and 0.01 μM vitamin D3 for 48 hrs, and then were washed with fresh complete medium before exposure to various concentrations of cigarette smoke-extract (CSE) for 4 hr. Fresh CSE was prepared by bubbling the mainstream smoke of two University of Kentucky Tobacco Health Research Institute standardized cigarettes (lot 2R4F), using a Jaeger-Baumgartner Cigarette Smoking Machine (C.H. Technologies, New Jersey) driven by dry compressed air, into 20 ml RPMI 1640; the result was defined as 10% CSE. CSE was filter-sterilized using a 0.22 μm membrane and was used the same day.
Quantitative real-time PCR
RNA was isolated using RiboPure kits (Applied Biosystems, Foster City, CA), TURBO DNA-free (Applied Biosystems) to remove genomic DNA, and Retroscript kits (Applied Biosystems) for reverse-transcription. We performed quantitative real-time PCR using the Stratagene Mx3000P (LaJolla, CA), with human glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as the endogenous reference, and commercial primer-probe sets (Taqman chemistry, Applied Biosystems). Transcript levels were reported relative to a calibrator of unstimulated THP cells, or AMø from never smokers, as appropriate, as calculated on the thermocycler.
Flow cytometry
BAL cells were resuspended in 100 μL staining buffer {1% FA Buffer (BD Bioscience, San Jose, CA), 1% FCS, 0.01% sodium azide} per tube. We used antibodies against the following antigens (clones in parentheses): CD45 (2D1) (eBioscience, San Diego, CA), TLR3 (40C1285.6), TLR7 (polyclonal), TLR9 (26C593.2) (Imgenex Corp., San Diego, CA), and TLR8 (303F1.14) (Dendritics, Lyon, France). To detect intracellular receptor expression, cells were treated with Fixation and Permeabilization Buffers (eBioscience). In all experiments, we used isotype-matched controls, analyzed cells on an LSR II flow cytometer (BD Bioscience), and collected a minimum of 10,000 CD45+ events per sample, using FACS Diva software with automatic compensation, and FlowJo analysis software (Tree Star, Inc., Ashland, OR). Details of instrument setup have been described recently [29].
Cytospins were immersed in cold acetone followed by methanol plus hydrogen peroxide. The slides were stained with biotinylated anti-human TLR3 (Imgenex) or isotype control antibodies, followed by Universal ABC peroxidase complex and 3-amino-9-ethylcarbazole peroxidase substrate. Slides were counter-stained with hematoxylin and photographed using an Olympus BX51 digital camera.
CXCL10 analysis
CXCL10 levels were determined using Biosource Multiplex Assays (Invitrogen) and a Luminex 200™ (Luminex Corporation, Austin, TX).
Statistical analyses
Statistical analysis was performed using GraphPad Prism (GraphPad, La Jolla, CA) except as specified. We used the nonparametric unpaired Mann–Whitney test to determine differences between two groups (smokers versus never-smokers; healthy subjects versus COPD subjects) in mRNA and flow cytometry data; the nonparametric Kruskal-Wallis one-way ANOVA to compare multiple conditions on THP cells in vitro; and ANOVA with Bonferroni's Multiple Comparison post-hoc testing to determine differences between smokers and never-smokers in stimulated cytokine secretion. We used Spearman non-parametric analysis to correlate TLR3 mRNA and protein expression with clinical variables and performed linear regression using SPSS (IBM Corp.; Armonk, NY). A two-tailed p value of < 0.05 was considered significant.
TLR3 expression is selectively decreased in AMø of smokers
Characteristics of BAL subjects used for RNA studies
Subjects, n
Sex ratio, M/F
Age, years (SD)
65.5 (7.2)
37.7 (12)
Smoking, pack-years (SD)
65.5 (23.1)
0 (0)
Smoking status (Former/Current)
FEV1, % pred. (SD)
57 (22.1)
101 (8.7)
58.5 (15.6)
86.8 (4.9)
ICS use (yes/no)
Characteristics of BAL subjects used for flow cytometry studies
Subjects, n
Sex ratio, M/F
Age, years (SD)
60.3 (8.9)
42.2 (13.7)
Smoking, pack-years (SD)
47.4 (33.7)
0 (0)
Smoking status (Former/Current)
FEV1, % pred. (SD)
83.5 (23.6)
100.7 (10.5)
72.5 (14.3)
84.2 (5.7)
ICS use (yes/no)
Thus, these secondary analyses supported a significant effect of smoking on AMø expression of TLR3. However, due to the distribution of our subjects, we were unable to exclude the possibility that our findings resulted from the preponderance of women in the never-smoker group and of men among the smokers in this cohort, or from the significant difference in ages between the volunteer and clinical subjects.
Reduced TLR3 expression in lung Mø correlates with smoking status but not COPD stage
Characteristics of surgical lung tissue subjects
Smokers with COPD
Smokers without COPD
Subjects, n
Sex ratio, M/F
Age, years (SD)
61.8 (9.4)
54.4 (9.1)
Smoking, pack-years (SD)
60.3 (41.4)
44.5 (23.9)
Smoking status (Former/Current)
FEV1, % pred. (SD)
41.8 (27.7)
95.4 (11.2)
42.5 (18.6)
76.0 (5.2)
ICS use (yes/no)
Exposure to CSE specifically reduces expression of TLR3 mRNA transcripts by differentiated human THP-1 cells
AMø of smokers show reduced CXCL10 production in response to poly(I:C) stimulation in vitro
Characteristics of BAL subjects used for in vitro stimulation studies
Subjects, n
Sex ratio, M/F
Age, years (SD)
60 (11)
39.5 (12.1)
Smoking, pack-years (SD)
47.4 (35.2)
0 (0)
Smoking status (Former/Current)
FEV1, % pred. (SD)
66.6 (30.6)
106.5 (12)
61.8 (19)
81.0 (7.5)
ICS use (yes/no)
We demonstrate that smoking reduces expression by human lung Mø of TLR3, a receptor for microbial dsRNA and endogenous danger signals. Relative to AMø of never-smokers, AMø of current smokers showed reduced TLR3 mRNA and protein, and lower secretion of CXCL10 in response to the viral dsRNA analogue poly(I:C). Smoking did not significantly reduce AMø expression of other receptors for viral nucleic acids in the cytoplasm (RIG-I, MDA-5 or PKR) or endosome (TLR7, TLR8 or TLR9). In a separate cohort, TLR3 protein expression by total lung Mø was also reduced in active smokers, relative to former smokers. TLR3 protein expressed as the percentage of postive lung Mø did not correlate significantly in either cohort with a diagnosis of COPD, FEV1% predicted or total history of smoking expressed as pack-years. The direct nature of the smoking effect was shown in vitro using differentiated cells of the human Mø line THP-1. These findings identify a new mechanism by which smoking impairs anti-viral lung host defenses.
Our findings address the intersection of two highly prevalent clinical issues, host defense against respiratory viruses and smoking. Respiratory viruses are implicated, alone or as mixed infections, in most COPD exacerbations, including those of greatest severity [31, 32]. Viral respiratory infections are also the leading cause of asthma exacerbations in adults and children [33, 34], including those requiring hospitalization [35]. Although only some smokers develop COPD, those who continue to smoke sustain more frequent respiratory infections and faster lung function decline [36]. Smoking is also a key contributor to morbidity in asthma [37]. Asthmatic smokers experience worse symptom control, greater risk of hospitalization, and increased resistance to the therapeutic effects of inhaled corticosteroids [38–41]. Finally, even in individuals with normal spirometry, smoking is an independent risk factor for increased number and severity of respiratory infections [3]. Hence, these results provide another rationale to urge all smokers to quit smoking absolutely, regardless of pulmonary function or specific diagnosis.
Optimal defense against respiratory viruses requires coordination of multiple elements of innate and adaptive immunity [42], especially prompt production by epithelial cells of types I (alpha/beta) and III (lambda) IFNs [43–45]. Appropriate contributions by AMø are likely also important [42]. In response to viruses, AMø produce measurable amounts of type I IFNs [46] and of the type III IFN lambda 1 (IL-29) [47]. Human monocyte-derived Mø (MDMø) produce mRNA for type III IFNs in response to stimultation via TLR3 or TLR4 [48] or to viruses [47, 49]. A specific anti-viral role of AMø has been confirmed experimentally by cellular depletion in two animal models [50, 51], but in a murine model of respiratory syncytial virus pneumonia, AMø depletion reduced early antiviral responses, increased viral load, but had no effect on late outcomes [52]. Hence, the significance of the current findings may vary with the particular viral pathogen. Additional studies will be needed to determine whether the effect we found on TLR3 expression translates into defective responses by the AMø of smokers to intact respiratory viruses.
These results expand the known effects of cigarette smoking on AMø function, which are clearly complex. Two studies using Affymetrix Human Genome U133 Plus 2.0 GeneChips found AMø from human smokers to have distinctive, globally altered gene expression profiles relative to non-smokers [53, 54]. Interestingly, TLR3 is not mentioned as a differentially expressed gene in either study. Disparity from our results likely relates to the difference in methodology; importantly, we showed very reduced TLR3 protein expression. The more pronounced reduction we found in TLR3 protein relative to mRNA implies the possibility of post-transcriptional smoking-induced downregulation, an important issue for future studies.
AMø of human smokers are often described as being "activated" [55–57], but both they and AMø from COPD patients show impaired bacterial uptake and killing [58, 59]. Production of TNF-α and IL-6 by AMø of smokers (and COPD patients, which often mixed current and former smokers) equaled or exceeded that of non-smokers, but was strikingly less inhibitable by steroids [60, 61]. Increased secretion of IL-8 and other neutrophil-attracting chemokines by AMø of human smokers has been shown in most [62, 63] but not all [64] studies. Thus, smoking appears to make AMø less likely to respond efficiently to pathogens but more likely to enhance sustained inflammation.
TLR3 has been shown experimentally to be essential for optimal protection against some but not all viruses, even those with a dsRNA genome [17]. Moreover, under some circumstances TLR3 may be responsible for exaggerated inflammation [65], and anti-TLR3 blocking antibody is being developed for therapeutic use [66]. Importantly, TLR3 is a receptor not only for microbial dsRNA, but also for dsRNA from necrotic host cells [67], an example of an endogenous danger-associated molecular pattern. This finding assumes increased significance based on the recognition of increased apoptotic cell death in emphysema [68] and decreased clearance of apoptotic cells by AMø of smokers [69–71], a defect postulated to foster lung injury and emphysema progression [71, 72]. Hence, the putative detrimental effect of reduced TLR3 expression by AMø of smokers on antiviral defenses might be partially offset by reduced responsiveness to necrosis-induced lung inflammation, an intriguing possibility that will require considerably greater investigation. Our finding that the percentage of TLR3-positive AMø was increased in former smokers when compared to active smokers agrees with the partial resolution of other smoking-induced AMø defects on smoking cessation [73]. These data are also congruent with the observation that smoking but not COPD decreases AMø expression of TLR2, but not of TLR4 [74]. The molecular mechanisms for down regulation by active smoking of TLR3 (this study) and TLR2 [74] remain unclear.
Our data partially differ from those of Koarai and colleagues, who recently reported increased TLR3 expression by AMø of smokers that correlated positively with smoking history and inversely with DLCO but not FEV1 % predicted [30]. Our results agree in finding no differences in AMø TLR3 expression among smokers based on the presence or absence of spirometrically-defined COPD. That study examined paraffin-fixed sections using a polyclonal anti-TLR3 antibody and immunohistochemistry, whereas we analyzed freshly isolated cells using the same monoclonal antibody in both of our cohorts. Hence, the disparity regarding TLR3 expression results might relate to antigen availability. Our studies differ in the cell type used for in vitro exposure to CSE (in that study MDMø), incubation time (24 hr vs. 4 hr in the current study) and CSE concentration (5% vs. a significant effect at 1.25% in the current study). These disparities make comparison difficult, as do multiple differences in design and endpoints of the experiments testing poly(I:C)-stimulated mediator production. One other study found that CSE reduced mRNA expression by MDMø of TLR8 and MDA5 and that MDMø of smokers had reduced mRNA expression of RIG-I and MDA-5, relative to MDMø of never-smokers [75]. That study does not mention TLR3 expression, which presumably was not altered in either case. Differences from our results likely reflect disparity both in cell type studied and possibly in methodology, as those results were obtained by Affimetrix assay.
The current findings are interesting in regard to two recent murine studies. Gaschler and colleagues found attenuated in vitro secretion of TNF-α, IL-6 and CCL5 in response to poly(I:C) by AMø from smoke-exposed mice, but did not find decreased TLR3 expression [76]. That disparity from our results may reflect a species difference. Kang and colleagues found that cigarette smoke selectively augmented airway and alveolar inflammation induced by viral MAMPs and influenza virus, as measured by induction of type I IFN, IFN-γ, IL-18 and IL-12/IL-23 p40 and PKR activation [77]. Further analysis using knockout mice indicated a role for both acute TLR3-dependent and chronic TLR3-independent pathways, as well as a pathway dependent on mitochondrial antiviral signaling protein (MAVS), IL-18Rα, IFN-γ and PKR [77]. That important study, however, did not measure TLR3 expression by AMø, and its findings likely reflect the interaction of multiple cell types in vivo.
Considerable evidence indicates the importance of CXCL10 in antiviral host defense but also in development or prevention of certain lung diseases [78, 79]. CXCL10 is one of three chemokines, along with CXCL9 and CXCL11, that are highly induced by IFN-γ, as well as by types I and III IFNs [49, 80]. Of note, however, CXCL10 production is also induced directly by infection of human AMø by rhinovirus, of murine AMø by RSV and of human MDMø by influenza or HIV [19, 20, 81–83], making this cytokine a suitable endpoint to test the functional importance of the observed TLR3 downregulation. A key action of CXCL10 is inflammatory cell recruitment, acting via CXCR3, which is found on Mø, CD8+ T cells, activated CD4+ T cells (especially TH1 cells), NK cells and plasmacytoid dendritic cells [84]. CXCR3 is essential for recruitment of antigen-specific CD4+ T cells to the lungs in a murine model of parainfluenza pneumonia [85]. In a model of Coxsackievirus infection, CXCL10 was shown to limit viral replication via NK cell recruitment [24].
Markedly reduced induction of CXCL10 in AMø from smokers is of interest in the context of other recent human studies. CXCL10 is one of several M1-associated genes down-regulated in AMø of healthy smokers and even more so, in smokers with COPD, relative to healthy never-smokers [54]. Although significantly increased CXCL10 concentrations have been found in the sputum of COPD patients, when compared with nonsmokers but not with smokers without obstruction [86], the origin of that chemokine is unclear, as it is also produced by epithelial cells that significantly outnumber Mø in the airways. Both by showing the role of reduced TLR3 expression and by studying AMø, we extend a study of gene expression by MDMø, which found reduced expression of CXCL10 at baseline in smokers relative to never-smokers, and also that CSE reduced IFN-γ-induced CXCL10 production by MDMø of never-smokers [75].
Our study has several limitations. One is the absence of never-smokers from our surgical cohort, who were recruited before clinically-indicated resections. Another is the predominance in our BAL cohort of female never-smokers (11 of 13 subjects) versus a predominance of male current smokers with preserved lung function (eight of nine subjects) and COPD patients (11 of 11 subjects). Concerns that differences in sex or age could confound our BAL results should be reduced by the congruent effect of smoking in our surgical cohort, which comprised 40% female subjects and which showed no significant effect of age on TLR3 expression by lung Mø. Moreover, at equivalent levels of tobacco exposure, women appear to be at greater risk of lung function impairment {reviewed in [87]}, the opposite of what would be expected if the current finding were a male-specific effect. Although we cannot formally exclude the possibility that differences in subject age explain the reduced expression of CXCL10 in response to TLR3, we consider that possibility unlikely, as serum levels of CXCL10 increase with age [88, 89]. Other limitations are the absence of DLCO measurements, which precludes comparison of our results with those of Koarai and colleagues [30] on this point, and that because post-bronchodilator FEV1 values were not available on all subjects, we have presented and analyzed exclusively pre-bronchodilator FEV1 values.
Active smoking reduces expression of TLR3 by human lung Mø, assayed both as AMø harvested by BAL and as a mixture of AMø and interstitial lung Mø from surgical tissue. This effect occurs via both down-regulation of mRNA transcripts, which can be induced in vitro within four hours, and from a more pronounced effect on TLR3 protein expression, which appears to be at least partially reversible on smoking cessation. Reduction in lung Mø TLR3 expression may be one mechanism contributing to the increased incidence of viral respiratory infections in smokers and to viral induction of acute exacerbations of COPD. Defining the effect of smoking on the phenotype of human AMø and other lung cell types is a crucial step in the translation of basic science into therapies.
Subjects were recruited via observational studies registered with ClinicalTrials.gov as NCT00281190, NCT00281203 and NCT00281229. These data were presented in part at the International Scientific Conference of the American Thoracic Society, May 17, 2010 in New Orleans, LA, and have been published in abstract form Am J Respir Crit Care Med 2010; 181: A3875.
Supported by R01 HL082480 (JLC, FJM), R01 HL056309 (JLC) and U01 HL098961 (JMB, JLC) from the USPHS; a Career Development Award (CMF) and a Merit Review Award (CMF) and a Research Enhancement Award Program (SWC, JMB, JLC) from the Biomedical Laboratory Research & Development Service, Department of Veterans Affairs. These investigations were also supported in part by the Tissue Procurement Core of the University of Michigan Comprehensive Cancer Center, Grant P30 CA46952, and by the Lung Tissue Research Consortium (Clinical Centers), Grant N01 HR046162.
Current e-mail addresses: James M. Beck, M.D.: http://email@example.com.
- AMø:
Alveolar macrophage(s)
Bronchoalveolar lavage
Chronic obstructive pulmonary disease
Cigarette smoke extract
- Ds:
Forced expiratory volume in 1 second
Forced vital capacity
Glyceraldehyde-3-phosphate dehydrogenase
- Mø:
Melanoma differentiation-associated gene 5
- MDMø:
Monocyte-derived macrophage(s)
Natural killer
Double-stranded RNA-dependent protein kinase
Phorbol myristate acetate
- poly(IC):
Polyinosinic acid:cytidylic acid
Retinoic acid-inducible gene I
Toll-like receptor 3.
The authors thank Drs. Peter Mancuso, Michal A Olszewski and Martin R Stämpli for providing helpful discussions and suggestions; Catherine Meldrum, R.N. for human subjects recruitment; Lisa McCloskey, R.R.T. and Tricia Geal, R.R.T. for human subjects recruitment and assistance in bronchoscopies; Bradley T Todd, and Angela M Preston, M.P.H. for generating cigarette smoke extract; Catherine Spino, Sc.D. and Glen Feak for database support; and Mary Freer, M.B.A., Tameka Lewis, Joyce O'Brien, Rebecca Weeks and Sara Whisenant for administrative support.
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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


text:
Three thousand dead in New York as
Two towers tumble to the ground,
Many more to die soon
As a holy war is sworn.
"You're for us or against us!"
Is Junior Bush's feeble chant,
So most nations in the world
Give vent to evil cant.
"We're real nice people, gosh"
Is Junior Bush's speech,
"Why don't youse people like us?"
Is his feeble beseech.
Has he forgotten the evil
U.S. presidents have bestowed,
On Far and Middle Eastern lands
You reap what you shall sow.
From nineteen forty-eight to now
America sowed only evil,
Playing Monopoly with real lands
Sanctifying devils.
Rightful leaders were kidnapped
And imprisoned for three decades,
Evil Shahs were put into power
To uphold America's oil enclave.
An evil empire arose
In Arabia's darkest hour,
Rightful leaders were killed off
Maniacs put into power.
Three million? Or three-hundred million
Arabs died along the way,
So, who can blame the Orient
For hating the U.S.A.?
So America's need for oil
Could finally be sated,
The U.S. lied and killed and cheated
And rightfully is hated.
So when Junior asks
"Why hate us? Hey we're real nice!"
Don't give in to his trick
Of convenient short-sight.
© Copyright 2011
Philip Roberts, Melbourne, Australia
© Copyright 2017 Philip Roberts. All rights reserved.
Status: Finished
Genre: Literary Fiction
Poem / Horror
Short Story / Horror
Short Story / Horror
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text:
Government Revenue from Financial Repression
This paper presents an analysis of the theoretical underpinnings and the relevance of the phenomenon of financial repression from a public-finance perspective. The analysis explicitly accounts for the interaction between capital controls and financial repression. The proposed empirical estimate of the revenue from financial repression is based on the difference between the domestic and the foreign cost of borrowing of the government. The correlations of the revenue from financial repression with inflation, exchange rates and per-capita income are discussed.
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|Date of creation:
|Jan 1991
|Publication status:
|published as American Economic Review, Vol. 83, no. 4 (1993): 953-963.
|Contact details of provider:
| Postal: National Bureau of Economic Research, 1050 Massachusetts Avenue Cambridge, MA 02138, U.S.A.
Phone: 617-868-3900
Web page: http://www.nber.org
More information through EDIRC
References listed on IDEAS
Please report citation or reference errors to , or , if you are the registered author of the cited work, log in to your RePEc Author Service profile, click on "citations" and make appropriate adjustments.:
- Giovannini, Alberto, 1985. "Saving and the real interest rate in LDCs," Journal of Development Economics, Elsevier, vol. 18(2-3), pages 197-217, August.
- Dixit, Avinash, 1985. "Tax policy in open economies," Handbook of Public Economics, in: A. J. Auerbach & M. Feldstein (ed.), Handbook of Public Economics, edition 1, volume 1, chapter 6, pages 313-374 Elsevier.
- Dornbusch, Rudiger & Reynoso, Alejandro, 1989.
"Financial Factors in Economic Development,"
American Economic Review,
American Economic Association, vol. 79(2), pages 204-209, May.
- Rudiger Dornbusch & Alejandro Reynoso, 1989. "Financial Factors in Economic Development," NBER Working Papers 2889, National Bureau of Economic Research, Inc.
- Lizondo, Jose Saul, 1983. "Foreign exchange futures prices under fixed exchange rates," Journal of International Economics, Elsevier, vol. 14(1-2), pages 69-84, February.
- Gordon, R.H. & Levisohn, J., 1989.
"The Linkage Between Domestic Taxes And Borber Taxes,"
Working Papers
244, Research Seminar in International Economics, University of Michigan.
- Roger H. Gordon & James A. Levinsohn, 1990. "The Linkage between Domestic Taxes and Border Taxes," NBER Chapters, in: Taxation in the Global Economy, pages 357-396 National Bureau of Economic Research, Inc.
- Easterly, William R., 1989. "Fiscal adjustment and deficit financing during the debt crisis," Policy Research Working Paper Series 138, The World Bank.
- Fischer, Stanley, 1982. "Seigniorage and the Case for a National Money," Journal of Political Economy, University of Chicago Press, vol. 90(2), pages 295-313, April.
- Corbo, Vittorio & de Melo, Jaime, 1987. "Lessons from the Southern Cone Policy Reforms," World Bank Research Observer, World Bank Group, vol. 2(2), pages 111-142, July.
- Heady, Christopher J. & Mitra, Pradeep K., 1987. "Distributional and revenue raising arguments for tariffs," Journal of Development Economics, Elsevier, vol. 26(1), pages 77-101, June.
- Giovannini, Alberto, 1988. "International Capital Mobility and Tax Evasion," CEPR Discussion Papers 231, C.E.P.R. Discussion Papers.
- Fry, Maxwell J., 1982. "Models of financially repressed developing economies," World Development, Elsevier, vol. 10(9), pages 731-750, September.
- Diamond, Peter A & Mirrlees, James A, 1971. "Optimal Taxation and Public Production: I--Production Efficiency," American Economic Review, American Economic Association, vol. 61(1), pages 8-27, March.
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text:
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- Test Services Offered: Erosion (Blowing Sand), Corrosion Testing / Chemical Exposure, Flow / Pressure Testing, Humidity, Seismic / NEBS Testing, Stress Screening / HASS, Thermal Cycling / Shock, Transportation Test, UV Exposure (Weathering / Solar Radiation), Vacuum / Decompression (Altitude Simulation), Wind &
- Accelerated (HALT / HASS): Yes
Supplier: E-Labs, Inc.
Description: an issue from smallto large we can accommodate most any size unit. We can simulate such profilesas the road shock to the shock of a torpedo hitting a submarine or the side ofa ship. Combined Environments Vibration Testing We have the flexibility to turn any of our vibration systemsinto combined
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- Capabilities: Testing / Simulation, Component / Product Comparisons, Engineering Verification Testing, In-Process In-Line Testing, Performance Testing, Research and Development, Test Fixtures / Equipment
- Forms Tested: Components / Parts, Products, Samples
- Dynamics Test Services Offered: Acceleration, Aging / Life Testing (HALT), Crash Safety, Drop / Impact Testing, Shock Testing, Transportation Test, Stress Screening / HASS, Vibration (Random / Sine), Specialty / Other
- Accelerated (HALT / HASS): Yes
Supplier: Intertek
Description: , fixture resonance evaluation, custom fixture design and fabrication, reproduction of sample road and/or event data, shock response spectrum (SRS) testing, buzz, squeak, and rattle (BSR) testing and more. Testing sites across the U.S. -including Grand Rapids and Plymouth, Michigan; Cortland, New
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- Capabilities: Testing / Simulation, Component / Product Comparisons, Engineering Verification Testing, Performance Testing, Research and Development, Test Fixtures / Equipment
- Forms Tested: Components / Parts, Products, Samples
- Dynamics Test Services Offered: Acceleration, Aging / Life Testing (HALT), Drop / Impact Testing, Shock Testing, Transportation Test, Stress Screening / HASS, Vibration (Random / Sine), Specialty / Other
- Accelerated (HALT / HASS): Yes
Supplier: IHS Product Design
Description: PROCEDURE FOR PERFORMING ROAD SIMULATION TESTSShow More
Standards and Technical Documents - GUIDE ON METHODS FOR EVALUATING FIRE HAZARD TO OCCUPANTS OF PASSENGER ROAD VEHICLES -- NFPA 556
Description: the properties of passenger road vehicles, including the materials, components and systems, and the development of hazardous conditions in the vehicle. This approach can include small-scale testing, full-scale testing of systems or entire vehicles, and computer modeling techniques in specified, well-definedShow More
Supplier: ASTM International
Description: Simulation of Obstacles in a Longitudinal Road Profile Based on the Weibull Distribution Volume 39, Issue 3 (May 2011) This paper solves the question of the generation of a longitudinal road profile with randomly distributed local obstacles. For the simulation of local road obstacles, threeShow More
Standards and Technical Documents - Standard Specification for Smoothness of Pavement in Weigh-in-Motion (WIM) Systems, Single User PDF Download -- M331-13-UL
Description: extensive simulations of truck dynamic loading over measured profiles. Acceptable index levels are based on ensuring to a 95 percent level of confidence that the WIM system roughness will not produce errors that exceed the tolerance level limits recommended by ASTM E 1318. The profiler test vehicleShow More
Standards and Technical Documents - Road vehicles -- Sled test procedure for the evaluation of restraint systems by simulation of frontal collisions -- ISO 7862:2004
Description: ISO 7862:2004 specifies a sled test procedure for the evaluation of restraint systems in road vehicles by the simulation of frontal collisions. Its main purposes are to improve test methods for evaluating restraint system efficacy and harmonize existing test methods -- especially to enableShow More
Supplier: Spectral Dynamics, Inc.
Description: on Random Road Simulation Rotating Machinery Analysis Sine on Random Star Analyzer Sine
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- Number of Analog Input Channels: 4, 6, 8, 16, Other
- Number of Analog Output Channels: Other
- Test Types: Random, Sine, Sine on Random, Random on Random, Classical Shock, Shock Response Spectrum (SRS), Other
- Analog to Digital Converter (ADC) Size: 24 bit
Find Suppliers by Category Top
Featured Products Top
E-Labs, Inc.
Shock & Vibration Testing ISO:17025 Accredited
E-Labs has additional mechanical shock testing machines. Using these shock testing facilities we can achieve custom shock levels to meet our customers' needs. At our lab, the test item size is never an issue from small to large we can accommodate most any size unit. We can simulate such profiles as the road shock to the shock of a torpedo hitting a submarine or the side of a ship. Combined Environments Vibration Testing. We have the flexibility to turn any of our vibration systems into combined... (read more)
Browse Shock and Vibration (Dynamics) Testing Services Datasheets for E-Labs, Inc.
TECAT Performance Systems
WISER Sensors
default 's shifting is used for validations. Because of these challenges, it is impossible to compare GEM with absolute measurements of fueling. Only relative comparisons are meaningful. " TECAT 's WISER system was created to solve challenges like these, and will give OEMs the ability to correlate real-world test results with simulation outputs. In other words, TECAT 's WISER system serves as the bridge between simulation results and the real world. In fact, being that bridge - between the algorithm... (read more)
Browse Torque Sensors Datasheets for TECAT Performance Systems
Conduct Research Top
Simulation Replaces Prototyping
As simulation gets more realistic, prototyping becomes an expensive last resort. The spindle from a front suspension, designed by Audi, shows fatigue damage predicted by simulation. Audi engineers model the front end of a new car as part of the suspension, then run it through simulated test driving
Defect prevention and elimination: Where the rubber hits the road(map)
yield improvement efforts do not become meaningful until an action can be taken to adjust or change something that ultimately adversely affects yield. Modeling, simulation, inspection, testing, failure analysis, and the like are necessary and meaningful only when they support root-cause assessment
Runnin' full throttle
and decelerate the engine under load to reproduce aerodynamic and mechanical forces. After 32 laps, the program pauses for a simulated pit stop while the test cell is refueled. Jaques Lazier #2, Eddie Cheever Jr. #51, and Sam Hornish Jr. #4, race side-by-side at the Yamaha Indy 400 at California Speedway
More Information Top
Steering Measurement, Analysis and Simulation on 6DOF Road Test Simulator
Road test simulation technology has been widely used in vehicle development and durability evaluation to reduce product development time and lower cost [1].
Elementary Investigation into Road Simulation Experiment of Powertrain and Components of Fuel Cell Passenger Car
Figure 2 Concept of fuel cell passenger car road simulation test ROAD SIMULATION TEST OF FUEL CELL VEHICLE AND POWERTRAIN SYSTEM ROAD LOAD SAMPLING The fuel cell passenger car road simulation test was carried out on a 4-poster hydraulic servo road …
Chassis Handbook
Strassensimulationsprüfstand ( road simulation test rig) STC .
A case study of increasing market competitiveness through shortening the research and development cycle
Prediction from vehicle fatigue curve perfects procedure for equipment endurance testing, and not only serves as reference for future vehicle development and road test simulation , but also provides greater accuracy of measurement for analysis and comparison under various load conditions, servings as …
Proceedings of the FISITA 2012 World Automotive Congress
According to small cycle operating mode, the road simulation test criterion is formed.
Bio-Medical Materials and Engineering
At present, road simulation test is the main method of motorcycle's reliability test, which tests motorcycle's quality and useful life by simulating actual road roughness and reappearing motorcycle's driving environment on the simulation test bed.
Optimized energy management control for the Toyota Hybrid System using dynamic programming on a predicted route with short computation time
The road tests simulated are done on urban and highway driving conditions, realized on a second generation Toyota Prius (MY06) in Paris and its suburban between July and August 2008.
Engineered Technologies in Materials Science, Geotechnics, Environment and Mechanical Engineering
Road simulation test is a sort of indoor experiment technology emerged in the 1960s.


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Capt. Bill Pike Blog
Tops In ToolsBy Capt. Bill Pike | Posted 2012-09-17 17:15
I recently had a job to do onboard Betty Jane that seemed virtually impossible. There are a couple of seven-foot-long cosmetic trim pieces over each of her fuel tanks and I needed to remove each of them so I could get at and replace the hose clamps on the fuel fills.Read Post
The Transformation of Betty's DecksBy Capt. Bill Pike | Posted 2012-09-10 16:58
There are all sorts of ways a teak deck can be spiffed up. And all sorts of levels to which the spiffed-upness can be taken. I recently opted to exalt my Grand Banks trawler Betty Jane's woodsy pavement (both on her main deck and her flying bridge) to the highest level I could afford, both money-wise and time-wise. Check out the photo above. You can be the judge of how successful the month-long ordeal actually was.Read Post
Ahhhh, The Boating WeekendBy Capt. Bill Pike | Posted 2012-09-04 16:13
There are all sorts of boating weekends, of course. Sometimes you leave the dock, sometimes you don't. Sometimes you cook a meal or two onboard, sometimes you don't.Read Post
The Sky Gets Even FriendlierBy Capt. Bill Pike | Posted 2012-08-27 16:34
Read Post
Dolphin Delight (w/Cool Video)By Capt. Bill Pike | Posted 2012-08-20 15:43
Musta been last year, although DANG! it doesn't seem that long ago. I was helping deliver a Kadey Krogen 48 AE up the eastern coast of the United States, from Stuart, Florida, to Annapolis, Maryland.Read Post
How to Tie a Bowline Like a ProBy Capt. Bill Pike | Posted 2012-08-14 11:04
Read Post
A Grand Old BoatBy Capt. Bill Pike | Posted 2012-08-02 11:29
I don't think I'd ever seen anything quite like it before. There was a light rain falling at the time--as there often is in the Pacific Northwest--and I was walking down the long dock at Skyline Marina in Anacortes, Washington. And the vision ahead seemed like pure romance, or maybe pure cinematic romance is more like it. I swear. Had Humphrey Bogart himself swung open the watertight door of the buff-colored superstructure and stepped out into the chilly air to study the sky and pull up the collar of his pea coat, I wouldn't have been a bit surprised.Read Post
For good or for bad, sometimes the world works in mysterious ways.By Capt. Bill Pike | Posted 2012-06-04 12:43
Who'da Thunk?
Okay, I'll admit it. I've become a tad cynical over the years. So when the Deepwater Horizon exploded catastrophically on April 20, 2010, killing 11 crewmen, I cynically watched developments on TV, day after day, feeling steadily more dismal over the resultant oil spill and what it was gonna do to the Gulf Coast and, more particularly (and selfishly perhaps), Panama City, Florida, the place where my wife and I were keeping our Grand Banks trawler Betty Jane. Having spent several of my youthful years working on oil-field boats in the Gulf, a job that put me cheek-by-jowl with big oil companies like BP, I figured I knew the score. Everybody was gonna lose … except BP!Read Post
Well, I'll Be Blessed. And Betty, Too!By Capt. Bill Pike | Posted 2012-05-03 16:49
A few weekends ago, I was elbow deep in Betty Jane's annual oil-change (a day-long extravaganza that usually entails, besides the oil deal, a total swap-out of coolant and filters) when I heard something strange and seemingly far off.
A bagpipe? Playing The Marine's Hymn?Read Post
Fright NightBy Capt. Bill Pike | Posted 2012-02-07 09:06


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|Message view
|« Date » · « Thread »
|« Date » · « Thread »
|Andrew Wilson <and...@www.elsevier.co.uk>
|Re: my scoreboard file is world writeable
|Wed, 02 Aug 1995 20:06:57 GMT
> A further thought on scoreboard file security --- one way to fix this > would be to put the scoreboard file in $(SERVERROOT)/logs by default, or > at least to allow people to put it there if they wanted. Permissions on > that directory could then prevent mischief from the hoi polloi... > > Is this a show-stopper, or can it wait for TNR? Question is can people's messing with the scoreboard file compromise the server. If people can damage the file and kill the server then we'll end up on bugraq by the end of the week ;) That would not be a good thing. > rst Ay.
|View raw message


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Magento customisation
This project was awarded to itconsultindia for $60 AUD.Get free quotes for a project like this
Project Budget$30 - $250 AUD
Total Bids1
Project Description
We're looking for a SENIOR and EXPERIENCED magento developer to complete the following tasks on our site:
1. Upgrade our magento ver 184.108.40.206 to ver 188.8.131.52.
The site is customise with various modules. This includes GoMage Light checkout, Aitoc Review Booster, Aheadworks Ajax Cart Pro, Aheadworks Facebook Link. As well, we have a variety of custom modules installed.
[url removed, login to view] order tracking functionality without requiring the customer to log in his account. Please see sample here: [url removed, login to view]
3. For out of stock products, we have a "Notify Me When It's Available" link where the customer can sign up to be notified once the product is back in stock. It is currently not functioning properly and does not properly email the customer automatically. We need this fixed.
4. Install functionality that will automatically display "Customers Who Bought This Product Also Purchased". On the product description page, We need a list of 6 products that other customers have purchased with the displayed product. This list should automatically populate in accordance to sales data.
5. Install this blog extension: [url removed, login to view]
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- Choking
- Facial swelling
- Shortness of breath
What causes choking, facial swelling and shortness of breath? 3 possible conditions
See a list of possible causes in order from the most common to the least.
This condition is considered a medical emergency. Urgent care may be required.
Anaphylaxis can occur when you have a severe reaction to certain allergens. Learn what the symptoms are and what to do if this happens.
This condition is considered a medical emergency. Urgent care may be required.
A head injury is an injury to your brain, skull, or scalp. All head injuries should be treated seriously and assessed by a doctor.
Food allergies are overblown responses by the immune system to foods that aren't typically harmful - like eggs and peanuts. Continue reading and learn more about food allergies, and how to prevent or treat sever...
Please consult a healthcare professional if you have health concerns.
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Tahiryonline.com is hosted by: Shaw Telecom G.P.
Hosting report about Tahiryonline.com. Tahiryonline.com is currently hosted at Shaw Telecom G.P.. The IP 220.127.116.11 links to a server in Calgary, Canada. The company behind this all is Shaw Communications.
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LAKELAND, FL (November 13, 2013) -- A new traffic signal on a steel mast will be installed on Sleepy Hill Road at the at the Sleepy Hill Middle School driveway. Preliminary foundation work has started and signal installation is scheduled to begin the first week of December.
This project is being funded by the Polk County School Board and construction will be performed by the City of Lakeland's Public Works Traffic Operations and Construction & Maintenance Divisions.
The signal will operate only during school hours when school is in session to allow traffic to exit the school. The signal will feature a "protected pedestrian phase" permitting students to safely cross Sleepy Hill Road while opposing traffic is stopped. The project also includes marked crosswalks with ADA compliant pedestrian ramps and school crossing signs.
No road closures or traffic detours will be required, however intermittent lane closures are likely and will be restricted to the time period between 9 a.m. – 2 p.m. so access to the school will not be inconvenienced. The traffic signal work should be completed by mid-December and the signal will be allowed to operate in the "flash mode" until students return from winter break on January 6, 2014 when the signal will be fully operational.
CITY OF LAKELAND TO LAUNCH TRAKiT
Users can track building permits, inspections, site plans, land use/zoning applications
LAKELAND, FL (October 29, 2013) -- The City of Lakeland is pleased to announce the launch of TRAKiT, a comprehensive and centralized software solution that allows unparalleled flexibility in automating and coordinating the construction permitting process. TRAKiT will go live Thursday, November 14, 2013 after more than a year of planning and implementation.
The Building Inspection, Business Tax and Code Enforcement offices will be CLOSED Wednesday, November 13th to ensure a seamless transition for customers. All offices will reopen to the public at 8:00 a.m. on Thursday the 14th.
The customer friendly web based system tracks all building permits, inspections, business tax receipts, site plan reviews as well as annexation/land use/zoning applications allowing users to manage projects more efficiently. TRAKiT also allows users to track and review code enforcement violations.
Once live, TRAKiT's web-based eTRAKiT module will allow citizens, business owners, contractors, architects, and engineers to apply for select permits, view the status of projects, permits, and code cases, and request permit inspections. Customers will also have the ability to pay permit, planning through eTRAKiT, and in-person via credit card, a payment method which was previously unavailable.
As with any project of this magnitude, there could be unanticipated challenges during the transition to the new software and while staff will be working diligently to minimize impacts, customer patience and indulgence are appreciated as the City moves to this enhanced customer service solution.
Lakeland Firefighters Respond to Lake Bentley Shores Condominium Fire
Four Injured, Including One Firefighter
Lakeland --- At approximately 1:10 AM, on Friday, November 8, 2013, the Lakeland Fire Department (LFD) responded to a structure fire at Lake Bentley Shores Condominiums located at 1920 E. Edgewood Drive, Lakeland, FL. The fire effected building L, a two story building that housed eight apartment units.
Upon arrival, Lakeland Firefighters found heavy black smoke showing on both the lower and upper level of building L. Firefighters entered building L, quickly extinguishing the fire and evacuating residents. The fire originated in a back bedroom of unit 7 in building L. The cause of the fire is currently under investigation but investigators believe that it was not intentionally set.
Resident Lamarcus Carter, 58, resident of unit L7 where the fire originated sustained smoke inhalation and was transported to Lakeland Regional Medical Center (LRMC). A relative of Lamarcus and additional resident of Unit L7, Ross Carter, 23, was transported by helicopter to Tampa General Hospital for burns and smoke inhalation. Their current medical conditions are unknown to LFD. Fred Cottonjim, 77, a neighbor of the Carters sustained unknown non-fire related injuries while trying to evacuate and was also transported to LRMC for treatment.
In addition to the three residents injured and transported, Firefighter Alex Sanchez, 32, displayed signs of heat exhaustion as a result of fighting the blaze. He was transported to and treated at LRMC where he was released soon after at approximately 5:00 AM. Sanchez was one of several firefighters that entered the structure to both extinguish the fire and evacuate residents.
The Lakeland Fire Department responded with eight apparatuses and 18 personnel. The scene was cleared by 6:30 AM.
LAKELAND,FL (November 7, 2013) - The City of Lakeland has partnered with the Florida Department of Environmental Protection (FDEP) and Illinois Tool Works (ITW) to remove the hydrilla in Lake Wire. Hydrilla is an invasive water plant that found its way into Florida waterways following release from aquariums in the 1960's.
The contractor working for the City of Lakeland, Texas Aquatic Harvesting will be on site at Lake Wire November 15th with actual hyrdrilla removal starting the week of November 18th. The work is expected to take up to 30 days from the start of the project.
Roadways around Lake Wire will not be blocked during the project. Sidewalks will remain open with very minimal impact as hydrilla is hauled away. ITW was the owner of the former Florida Tile property located on the west side of Lake Wire. The hydrilla harvesting program and work plan for Lake Wire recently received approval from the FDEP and incorporates an agreement between ITW and the City. ITW will pay $22,500 each year for the next three years to have the invasive water plant harvested from Lake Wire as a mandated lake clean-up effort.
Hydrilla has not been removed from Lake Wire since 2004. The invasive species is a great water filtering plant but it has a tendency to choke water ways with its rapid growth. As an invasive species, hydrilla has become the most serious aquatic weed problem for Florida and one of the most serious for most of the United States.
The City of Lakeland's Division of Lakes & Stormwater will be overseeing the hydrilla harvesting project. For more information, call Curtis Porterfield, Manager of Lakes & Stormwater at 863-834-8439.


text:
- Published
Synthetic Aperture Focusing for a Single Element Transducer undergoing Helix Motion
Publication: Research - peer-review › Journal article – Annual report year: 2011
- Published
Three-Dimensional Synthetic Aperture Focusing Using a Rocking Convex Array Transducer
Publication: Research - peer-review › Journal article – Annual report year: 2010
- Published
Synthetic Aperture Beamforming in Ultrasound using Moving Arrays.
Publication: Research › Ph.D. thesis – Annual report year: 2009
I E E E Transactions on Ultrasonics, Ferroelectrics and Frequency Control
ISSNs: 0885-3010
Additional searchable ISSN (Electronic): 1525-8955
I E E E, United States
ISI indexed (2013): ISI indexed yes, BFI (2015): BFI-level 2, Scopus rating (2015): 0.91 1.455
Local database
- Completed
3D Synthetic Aperture Imaging and Implementation
Project: PhD
Local database
Technical University of Denmark (DTU)
Local database
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Excess Liquidity and Effectiveness of Monetary Policy; Evidence from Sub-Saharan Africa
This paper examines the pattern of excess liquidity in sub-Saharan Africa and its consequences for the effectiveness of monetary policy. The paper argues that understanding the consequences of excess liquidity requires quantifying the extent to which commercial bank holdings of excess liquidity exceed levels required for precautionary purposes. It proposes a methodology for measuring this quantity and uses it to estimate a nonlinear structural VAR model for the CEMAC region, Nigeria and Uganda. The study suggests that excess liquidity weakens the monetary policy transmission mechanism and thus the ability of monetary authorities to influence demand conditions in the economy.
If you experience problems downloading a file, check if you have the proper application to view it first. In case of further problems read the IDEAS help page. Note that these files are not on the IDEAS site. Please be patient as the files may be large.
|Date of creation:
|01 May 2006
|Contact details of provider:
| Postal: International Monetary Fund, Washington, DC USA
Phone: (202) 623-7000
Fax: (202) 623-4661
Web page: http://www.imf.org/external/pubind.htm
More information through EDIRC
|Order Information:
|Web: http://www.imf.org/external/pubs/pubs/ord_info.htm
References listed on IDEAS
Please report citation or reference errors to , or , if you are the registered author of the cited work, log in to your RePEc Author Service profile, click on "citations" and make appropriate adjustments.:
- David B. Gordon & Eric M. Leeper, 1992.
"The dynamic impacts of monetary policy: an exercise in tentative identification,"
FRB Atlanta Working Paper
92-13, Federal Reserve Bank of Atlanta.
- Gordon, David B & Leeper, Eric M, 1994. "The Dynamic Impacts of Monetary Policy: An Exercise in Tentative Identification," Journal of Political Economy, University of Chicago Press, vol. 102(6), pages 1228-1247, December.
- David B. Gordon & Eric M. Leeper, 1993. "The dynamic impacts of monetary policy: an exercise in tentative identification," FRB Atlanta Working Paper 93-5, Federal Reserve Bank of Atlanta.
- Fabio C. Bagliano & Carlo A. Favero, "undated".
"Measuring Monetary Policy with VAR Models: an Evaluation,"
Working Papers
132, IGIER (Innocenzo Gasparini Institute for Economic Research), Bocconi University.
- Bagliano, Fabio C. & Favero, Carlo A., 1998. "Measuring monetary policy with VAR models: An evaluation," European Economic Review, Elsevier, vol. 42(6), pages 1069-1112, June.
- Bagliano, Fabio-Cesare & Favero, Carlo A., 1997. "Measuring Monetary Policy with VAR Models: An Evaluation," CEPR Discussion Papers 1743, C.E.P.R. Discussion Papers.
- Sims, Christopher A., 1992.
"Interpreting the macroeconomic time series facts : The effects of monetary policy,"
European Economic Review,
Elsevier, vol. 36(5), pages 975-1000, June.
- Christopher A. Sims, 1992. "Interpreting the Macroeconomic Time Series Facts: The Effects of Monetary Policy," Cowles Foundation Discussion Papers 1011, Cowles Foundation for Research in Economics, Yale University.
- Emilio Sacerdoti, 2005. "Access to Bank Credit in Sub-Saharan Africa; Key Issues and Reform Strategies," IMF Working Papers 05/166, International Monetary Fund.
- Agenor, Pierre-Richard & Aizenman, Joshua & Hoffmaister, Alexander W., 2004.
"The credit crunch in East Asia: what can bank excess liquid assets tell us?,"
Journal of International Money and Finance,
Elsevier, vol. 23(1), pages 27-49, February.
- P.R. Agenor & J. Aizenman & A. Hoffmaister, 2000. "The Credit Crunch in East Asia: What can Bank Excess Liquid Assets Tell us?," NBER Working Papers 7951, National Bureau of Economic Research, Inc.
- Agenor, Pierre-Richard & Aizenman, Joshua & Hoffmaister, Alexander, 2000. "The credit crunch in East Asia : what can bank excess liquid assets tell us ?," Policy Research Working Paper Series 2483, The World Bank.
- Nathan S. Balke, 2000. "Credit and Economic Activity: Credit Regimes and Nonlinear Propagation of Shocks," The Review of Economics and Statistics, MIT Press, vol. 82(2), pages 344-349, May.
- Bernanke, Ben S & Blinder, Alan S, 1992.
"The Federal Funds Rate and the Channels of Monetary Transmission,"
American Economic Review,
American Economic Association, vol. 82(4), pages 901-921, September.
- Ben S. Bernanke & Alan S. Blinder, 1989. "The federal funds rate and the channels of monetary transmission," Working Papers 89-10, Federal Reserve Bank of Philadelphia.
- Ben Bernanke, 1990. "The Federal Funds Rate and the Channels of Monetary Transnission," NBER Working Papers 3487, National Bureau of Economic Research, Inc.
- Savvides, Andreas, 1998. "Inflation and monetary policy in selected West and Central African countries," World Development, Elsevier, vol. 26(5), pages 809-827, May.
- Ang, Andrew & Bekaert, Geert, 2002.
"Regime Switches in Interest Rates,"
Journal of Business & Economic Statistics,
American Statistical Association, vol. 20(2), pages 163-182, April.
- Andrew Ang & Geert Bekaert, 1998. "Regime Switches in Interest Rates," NBER Working Papers 6508, National Bureau of Economic Research, Inc.
- Calza, Alessandro & Sousa, João, 2005.
"Output and inflation responses to credit shocks: are there threshold effects in the euro area?,"
Working Paper Series
0481, European Central Bank.
- Calza Alessandro & Sousa João, 2006. "Output and Inflation Responses to Credit Shocks: Are There Threshold Effects in the Euro Area?," Studies in Nonlinear Dynamics & Econometrics, De Gruyter, vol. 10(2), pages 1-21, May.
- Koop, Gary & Pesaran, M. Hashem & Potter, Simon M., 1996. "Impulse response analysis in nonlinear multivariate models," Journal of Econometrics, Elsevier, vol. 74(1), pages 119-147, September.
- Jakob E Christensen, 2004. "Domestic Debt Markets in Sub-Saharan Africa," IMF Working Papers 04/46, International Monetary Fund.
- Baldacci, Emanuele & Hillman, Arye L. & Kojo, Naoko C., 2004.
"Growth, governance, and fiscal policy transmission channels in low-income countries,"
European Journal of Political Economy,
Elsevier, vol. 20(3), pages 517-549, September.
- Naoko C. Kojo & Arye L. Hillman & Emanuele Baldacci, 2003. "Growth, Governance, and Fiscal Policy Transmission Channels in Low-Income Countries," IMF Working Papers 03/237, International Monetary Fund.
- Pesaran, H.M. & Potter, S.M., 1995.
"A Floor and Ceiling Model of U.S. Output,"
Cambridge Working Papers in Economics
9407, Faculty of Economics, University of Cambridge.
- Pesaran, M. Hashem & Potter, Simon M., 1997. "A floor and ceiling model of US output," Journal of Economic Dynamics and Control, Elsevier, vol. 21(4-5), pages 661-695, May.
- Dollar, David & Hallward-Driemeier, Mary, 2000. "Crisis, Adjustment, and Reform in Thailand's Industrial Firms," World Bank Research Observer, World Bank Group, vol. 15(1), pages 1-22, February.
- Stiglitz, Joseph E & Weiss, Andrew, 1981. "Credit Rationing in Markets with Imperfect Information," American Economic Review, American Economic Association, vol. 71(3), pages 393-410, June.
- Bruce E. Hansen, 1996.
"Sample Splitting and Threshold Estimation,"
Boston College Working Papers in Economics
319., Boston College Department of Economics, revised 12 May 1998.
- Bruce E. Hansen, 2000. "Sample Splitting and Threshold Estimation," Econometrica, Econometric Society, vol. 68(3), pages 575-604, May.
- Stéphane Cossé & Johannes Mueller & Jean Le Dem & Jean A. P. Clément, 1996. "Aftermath of the CFA Franc Devaluation," IMF Occasional Papers 138, International Monetary Fund.
- Adam, Christopher, 1999. "Financial Liberalisation and Currency Demand in Zambia," Journal of African Economies, Centre for the Study of African Economies (CSAE), vol. 8(3), pages 268-306, October.
- repec:eme:jespps:v:21:y:1994:i:2:p:3-37 is not listed on IDEAS
- Simon M. Potter, 1993.
"A Nonlinear Approach to U.S. GNP,"
UCLA Economics Working Papers
693, UCLA Department of Economics.
- Potter, Simon M, 1995. "A Nonlinear Approach to US GNP," Journal of Applied Econometrics, John Wiley & Sons, Ltd., vol. 10(2), pages 109-125, April-Jun.
- Ben S. Bernanke & Ilian Mihov, 1998. "Measuring Monetary Policy," The Quarterly Journal of Economics, Oxford University Press, vol. 113(3), pages 869-902.
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|Conveyor or transmission belts or belting, of vulcanised rubber...
|Air or vacuum pumps, air or other gas compressors and fans; ventilating or recycling hoods incorporating a fan, whether or not fitted with filters...
|Mechanical appliances (whether or not hand-operated) for projecting, dispersing or spraying liquids or powders; fire extinguishers, whether or not charged; spray guns and similar appliances; steam or sandblasting machines and similar jet projecting machin...
|Electro-magnets; permanent magnets and articles intended to become permanent magnets after magnetisation; electromagnetic or permanent magnet chucks, clamps and similar holding devices; electromagnetic couplings, clutches and brakes; electromagnetic lifti...
|Philips do Brasil Ltda Varginha MG 37066440
|Philco Eletronicos S.A. Manaus AM 69075215
|Semp Toshiba Amazonas S.A. Manaus AM 69075090
|H-Buster da Amazônia Indústria e Comércio S. S.A. MANAUS AM 69047000
|Audiomotor Comercial e Indústrial Ltda Brasopolis MG 37530000
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This section gives information on Children and Young People statistics, including data on looked after children, children on the child protection register, young people in secure accommodation, and early learning and childcare data.
The equality evidence for these topics is available on the Scottish Government Equality Evidence website and evidence finder.
If you can't find what you're looking for, use the Search Statistics page.
The Looked After Children Data Strategy 2015 is available here.
The consultation seeking the views on the current and anticipated future use and needs of Early Learning and Childcare (ELC) data closed on the 6th of January 2016. Findings and a link to the online questionnaire can be found here.
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Education Outcomes for Looked After Children, 2014-15
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Protecting children and young people
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Applied CCM
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"Gabran (Gabriele Ranica) since the Seventies has played in groups of progressive music, jazz and of contemporary improvisation. The interest for electronic music on tape and for computer music was born toward the beginning of the Eighties. The search and the improvisation are at the base of its job."
[Vist the artist's MySpace page.]