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Excessive proinflammatory cytokine and chemokine responses of human monocyte-derived macrophages to enterovirus 71 infection
Viral diseases
The levels of proinflammatory cytokine or chemokine in blood and cerebrospinal fluid are thought to be one of predictors for clinical severity of enterovirus 71 (EV71) infection, yet the cellular sources or signalling mechanism remain undefined. Here, we focused on the response of human primary monocyte-derived macrophages (MDMs) to EV71 virus and its possible mechanisms.
Human primary MDMs were infected by EV71 virus
Effective infection and viral replication were detected in EV71-infected MDMs. The titters of progeny virus released from EV71-infected MDMs gradually increased from 6-h to 48-h point of infection (POI.). Proinflammatory cytokines: IL-1, IL-6, TNF-α but not IFN-α and γ were induced in MDMs by EV71. EV71 infection significantly increased the release of IL-8, IP-10 and RANTES at 12-h or 24-h POI. Upregulation of TLR2, TLR7 and TLR8 mRNA expression rather than TLR3, TLR4, TLR6, TLR9, TLR10, RIG-I, MDA5 were found at different time points in EV71-infected MDMs.
Our findings suggested that macrophages are not only the important target cells but also the effectors during EV71 infection, and they may play an important role in the pathogenesis of EV71 infection. And the proinflammatory cytokine and chemokine responses in EV71-infected MDMs may be mediated by the activation of differential pattern of TLRs.
Enterovirus 71, a positive-stranded RNA virus, is highly infectious and can cause hand-foot-and-mouth disease (HFMD), herpangina, neurological diseases with potentially more serious complications such as encephalitis, aseptic meningitis, brain stem encephalitis (BE) in infants and young children. Many of patients died from fulminant pulmonary edema (PE) or hemorrhage, which was based on nervous system injury
Although the pathogenesis of neurogenic PE caused by EV71 remains unclear, host factors especially host immune response rather than EV71 itself or its genotype may be one of important determinants for the disease severity
Previous studies have identified that the immune cells such as human peripheral blood mononuclear cells, human T cell line (Jurkat), monocytic cells, human immature dendritic cells can be infected with EV71
Effective infection and viral replication of EV71 in human MDMs
We first determined the infectivity of MDMs to EV71 by immunofluorescence staining of viral VP1. As evidenced by the expression of viral VP1+ at 12-h POI. (data not shown), human MDMs could be infected by EV71 virus. Furthermore, the infection showed a dose-dependent for infectious dose, as evidenced by an increase of VP1 expression at 24-h POI. along with a MOI of 0.1, 0.5, 1 and 5. (Figure
Figure 1
A dose-dependent infection of EV71 virus in human monocyte-derived macrophages (MDMs)
A dose-dependent infection of EV71 virus in human monocyte-derived macrophages (MDMs). Immunofluorescence staining of EV71 VP1 in mock- or EV71-infected MDMs was assayed at 24-h POI. A. mock, B. UV-inactivated EV71 infection, C. EV71 infection at a MOI of 0.1, D. EV71 infection at a MOI of 0.5, E. EV71 infection at a MOI of 1, F. EV71 infection at a MOI of 5.
Figure 2
Viral replication of EV71-infected human MDMs
Viral replication of EV71-infected human MDMs. Viral gene copies were quantified by real-time RT-PCR. Supernatants from infected cells were collected at designated time points post inoculation of EV71 at a MOI of 5 and the viral titter was measured by TCID50 analysis on Vero cells. A. the change of VP1 gene. The number of gene copy was normalized to 104copies of β-actin and expressed as mean ± standard error (SEM) from eight independent experiments, and each experiment was performed in triplicates. B. viral titters of EV71-infected MDMs cultures. The data were expressed as mean ± SEM from 8 independent experiments.
Enhanced proinflammatory cytokine responses of human MDMs to EV71
We subsequently determine the functional response of human MDMs to live EV71 or UV-irradiated EV71. Significant higher level of TNF-α was rapidly induced by live EV71 infection other than mock or UV-irradiated EV71 at the 12-h POI. (72.34 ± 52.56 pg/ml vs. 6.68 ± 7.67 pg/ml, 31.74 ± 20.26 pg/ml, respectively,
Figure 3
Proinflammatory cytokines IL-1β, IL-6 and TNF-α induced in EV71 infected MDMs
Proinflammatory cytokines IL-1β, IL-6 and TNF-α induced in EV71 infected MDMs. MDMs were infected with or without EV71 (live or UV-inactivated) at MOI of 5. Culture supernatants were harvested at 12-h and 24-h after infection to measure the indicated cytokines by CBA as described in Methods section. Data are expressed as mean ± SEM from eight independent experiments performed in triplicates. (*,
Enhanced production of IL-8, RANTES and IP-10 from human MDMs infected with EV71
Chemokines include a large superfamily and play multiple roles in shaping the innate and adaptive immune responses during viral infection. We measured the levels of the chemokines including CXCL-10/IP-10, CCL-2/MCP-1, CXCL-9/MIG, CXCL-8/IL-8, and CCL-5/RANTES in the supernatants at 12-h and 24-h POI. At early time points (12-h POI.), enhanced production of IL-8 and RANTES was detected in EV71-infected MDMs than in mock-infected MDMs (
Figure 4
Chemokines induced in MDMs infected with EV71 and (or) UV-inactivated EV71
Chemokines induced in MDMs infected with EV71 and (or) UV-inactivated EV71. MDMs were infected with or without EV71 (live or UV-inactivated) at MOI of 5 for 12-h and 24-h. The chemokines including IP-10, MCP-1, RANTES, IL-8, MIG concentration in the supernatants at 12-h and 24-h was measured by CBA. Data are expressed as mean ± SEM from eight independent experiments performed in triplicates. (*, P < 0.05 and **, P < 0.01).
Up-regulation of TLR2, TLR7 and TLR8 mRNA expression in EV71 infected- MDMs
In order to investigate the involvement of TLRs and RLHs in EV71-infected MDMs, we screened the TLR2, TLR3, TLR4, TLR6, TLR7, TLR8, TLR9, TLR10, RIG-1, Mda-5 mRNA expression by real-time quantitative RT-PCR. The results showed that the mRNA expression of TLR2 appeared to be significantly enhanced in EV71-infected human MDMs from 6-h to 24-h POI. Increased mRNA expressions of TLR2 were also observed in UV-inactivated virus-infected MDMs at 12-h to 24-h POI. as compared with mock (
Figure 5
A higher mRNA expression of TLR2, TLR7 and TLR8 were induced in MDMs infection with EV71
A higher mRNA expression of TLR2, TLR7 and TLR8 were induced in MDMs infection with EV71. The mRNA expression of TLR2, TLR3, TLR4, TLR6, TLR7, TLR8, TLR9, TLR10, RIG-1 and MDA-5 were performed by SYBR green real-time RT-PCR. The relative change of mRNA expression was analyzed using △△CT method. To standardize results for variability in cDNA quantity, we expressed them with target gene/β-actin as 1 in mock at 6-h POI. Data are expressed as mean ± SEM from eight independent experiments performed in triplicates (*,
Macrophages, which are shown to support the infection of various viruses including HIV-1, influenza viruses, and poliovirus and so on, play a critical role in presentation of antigens, pathogen clearance, and induction of inflammation during the early phase of viral infection
It is controversial whether TNF-α was involved in fatal EV71 infection. Significant or minor change of blood TNF-α in EV71 patient with both encephalitis and PE was reported by different clinical studies
Macrophages or plasmacytoid DCs, specialized in secreting large amounts of type I IFN after virus infection, play an important role in viral infection. However, minor change of IFN-α in EV71-infected MDMs was detected in our study. It is likely that the 3C protein of EV71 virus inhibits type I interferon activation by viral nuclear acid or RIG-I signalling
TLRs and RLHs recognize distinct ligands and trigger host immune response in different virus infection
As documented previously, younger children less than 5-year-old were the most susceptible groups to EV71 and usually presented with severe infection
In summary, effective viral replication in EV71-infected MDMs and excessive inflammatory cytokine and chemokine responses of MDMs to the virus were demonstrated for the first time in our study. The results indicate that macrophages are an important target for EV71, and they can trigger pro-inflammatory response and chemokine response against viral infection. However, inordinate macrophages response may be detrimental to the infected host due to exacerbate virus inflammation and pathology. TLR2, TLR7 and TLR8 may participate in the induction of cytokines/chemokines in EV71-infected MDMs. These data suggested that MDMs may play an important role in the pathogenesis of EV71 infection
Isolation and culture of monocyte-derived macrophages
The study was approved for human subject protection by the Ethics Committee of National Institute for Viral Disease Control and Prevention, China CDC. Following informed consent was written by participants.
Peripheral blood obtained from 8 healthy blood donors aged from 20 to 40 years old. Peripheral blood mononuclear cells (PBMCs) were isolated by a Ficoll-Paque density gradient (Pharmacia Biotech, Uppsala, Sweden) to remove erythrocytes, platelets, and cell debris. Monocytes were isolated by plastic adherence, harvested, counted and seeded on tissue culture plates in RPMI 1640 (Invitrogen Life Technologies, Great Island, NY, USA) medium supplemented with 10% heat-inactivated autologous plasma at 106cells/ml. The purity of monocytes was determined by flow cytometry with anti-CD14 monoclonal antibody (Mab, PharMingen, San Diego, CA, USA) and was consistently above 90%. The monocytes were reseed with 2-5 × 105 cells per well onto a 24 well culture plate, and were allowed to differentiate into MDMs for 10–14 days
Infection of MDMs with EV71
Enterovirus 71 virus was propagated in RD cells (obtained from ATCC) in DMEM containing 2% fetal bovine serum (FBS, Invitrogen, Grand Island, NY, USA) and incubated at 35°C with 5%CO2. When 80% of the cells showed the typical enteroviral cytopathic effect (CPE), the infected cells were harvested after being frozen and thawed for three times. Cell debris was removed by centrifugation and filtration using a 0.22 μm membrane filter (Millipore, Billerica, CA). EV71 viruses were inactivated using ultraviolet radiation 3000 mj/cm2, 30 mins on ice (UV-inactivated EV71). Differentiated MDMs were infected by EV71 and UV-inactivated EV71 at MOI (multiplicity of infection) of 0.1, 0.5, 1 and 5. This is taken to be 0-h point of infection (POI.) for the experiments described below. Virus titters were performed by measuring the 50% tissue culture infective dose (TCID50) on Vero cells and calculated by using the Reed and Muench formula.
Immunofluorescence assay of viral VP1 protein in infected cells
MDMs were fixed with methanol: acetone (1:1) for 5 min. The cell monolayer was incubated by anti-EV71 VP1 monoclonal antibody (MAB979, Millipore, Billerica, CA) at room temperature for 60 min, and followed by labelling FITC-conjugated goat anti-mouse IgG for 1-h. After being completely washed, the cells were observed under a fluorescence microscope.
Quantification of mRNA by real-time RT-PCR
Infected MDMs cultured in macrophage serum-free medium (Invitrogen, Grand Island, NY, USA) were harvested at 2-h, 6-h, 12-h, 24-h and 48-h POI. Total RNAs were extracted using QIAGEN RNeasy mini kit(QIAGEN, Hilden, Germany). Reverse transcription was performed on DNase-treated total RNA. The cDNA was synthesized from mRNA with oligo(dT)12–18 primer and Superscript II reverse transcriptase (Invitrogen, Grand Island, NY, USA). Specific primers and probes used in the real-time PCR assay were listed in Table
Measurement of cytokines
Concentration of cytokines from culture supernatants were determined by Cytometric Bead Array(CBA). IL-1β, IL-6, TNF-α, IFN-α, IFN-γ, IP-10, IL-8, RANTES, MCP-1, MIG Flex Set reagents (BD Biosciences, San Diego, CA) were used to measure cytokines by flow cytometry according to the manufacturer's protocol. The results are presented as the means of assays performed in duplicate wells. Data were analyzed by using FCAP Array 0.1 and BD Cytometric Bead Array 1.4 software assay. The theoretical limits of detection were listed as follows: IL-1β(2.3 pg/ml), IL-6 (1.6 pg/ml), TNF-α (1.2 pg/ml), IFN-α (1.5 pg/ml), IFN-γ(1.8 pg/ml), IP-10 (0.5 pg/ml), IL-8 (1.2 pg/ml), RANTES (0.002 pg/ml), MCP-1 (1.3 pg/ml), MIG (1.1 pg/ml).
Statistical analysis
Statistical significance was determined by Two-Way ANOVA or the Mann–Whitney rank sum tests. All analyses were performed using the Statistical Package for Social Sciences (SPSS13.0) software (SPSS Inc, IL, USA). A probability
(EV71): Enter virus; (TLRs): 71Toll-like receptors; (RIG-I): Retinoic acid-inducible gene I; (RLHs): RIG-I-like helicases; (MDMs): Monocyte-derived macrophages; (MDA5): Melamoma differentiation associated gene 5; (HFMD): Hand-foot-and-mouth disease; (BE): Brain stem encephalitis; (PE): Pulmonary edema; (CNS): Central nervous system; (BBB): Blood brain barrier; (MOI): Multiplicity of infection; (CSF): Cerebrospinal fluid; (PBMCs): Peripheral blood mononuclear cells.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
Conceived and designed the experiments: ZD, YJ, XG and JZ. Performed the experiments: XG and JZ. Analyzed the data: XG and JZ. Contributed reagents/materials/analysis tools: WZ, NL, JL and LL. Wrote the paper: XG, JZ, WZ and ZD. All authors read and approved the final manuscript.
This work was supported by China Mega-Project for Infectious Disease (2011ZX10004-001) and the National Basic Research Program (973) of China (2010CB534004).
Neural pathogenesis of enterovirus 71 infection
Fatal enterovirus 71 encephalomyelitis
An epidemic of enterovirus 71 infection in Taiwan. Taiwan Enterovirus Epidemic Working Group
Enterovirus 71 infection: an experience in Korea, 2009
Enterovirus 71 outbreak in the People's Republic of China in 2008
Direct detection of enterovirus 71 (EV71) in clinical specimens from a hand, foot, and mouth disease outbreak in Singapore by reverse transcription-PCR with universal enterovirus and EV71-specific primers
Enterovirus 71 from fatal and nonfatal cases of hand, foot and mouth disease epidemics in Malaysia, Japan and Taiwan in 1997–1998
Genetic analysis of enterovirus 71 isolated from fatal and non-fatal cases of hand, foot and mouth disease during an epidemic in Taiwan, 1998
Proinflammatory cytokine reactions in enterovirus 71 infections of the central nervous system
Cerebrospinal fluid cytokines in enterovirus 71 brain stem encephalitis and echovirus meningitis infections of varying severity
Acute chemokine response in the blood and cerebrospinal fluid of children with enterovirus 71-associated brainstem encephalitis
Biology of adult human microglia in culture: comparisons with peripheral blood monocytes and astrocytes
Enterovirus 71 infection induces Fas ligand expression and apoptosis of Jurkat cells
Enterovirus 71 infection of human dendritic cells
Enterovirus 71 infection of monocytes with antibody-dependent enhancement
Human cardiac inflammatory responses triggered by Coxsackie B viruses are mainly Toll-like receptor (TLR) 8-dependent
TLR8 and TLR7 are involved in the host's immune response to human parechovirus 1
Human rhinovirus recognition in non-immune cells is mediated by Toll-like receptors and MDA-5, which trigger a synergetic pro-inflammatory immune response
Rotavirus and coxsackievirus infection activated different profiles of toll-like receptors and chemokines in intestinal epithelial cells
Variance estimation in the reed-muench fifty per cent end-point determination
Infection of primary human microglia and monocyte-derived macrophages with human immunodeficiency virus type 1 isolates: evidence of differential tropism
Dendritic cells and macrophages are productively infected by poliovirus
Differential expression of chemokines and their receptors in adult and neonatal macrophages infected with human or avian influenza viruses
Different proinflammatory reactions in fatal and non-fatal enterovirus 71 infections: implications for early recognition and therapy
Pathogenesis of enterovirus 71 brainstem encephalitis in pediatric patients: roles of cytokines and cellular immune activation in patients with pulmonary edema
Elevation of nasal viral levels by suppression of fever in ferrets infected with influenza viruses of differing virulence
Retrograde axonal transport: a major transmission route of enterovirus 71 in mice
TNF-alpha opens a paracellular route for HIV-1 invasion across the blood–brain barrier
Cytokines and chemokines induced by influenza virus infection
The 3C protein of enterovirus 71 inhibits retinoid acid-inducible gene I-mediated interferon regulatory factor 3 activation and type I interferon responses
Interleukin-8 in cerebrospinal fluid from patients with septic and aseptic meningitis
Innate immune recognition of viral infection
Age-related changes in expression of CXCR4 and CCR5 on peripheral blood leukocytes from uninfected infants born to human immunodeficiency virus type 1-infected mothers
Acute encephalitis caused by intrafamilial transmission of enterovirus 71 in adult
Pre-publication history
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By Harry R. Weber And Joshua Freed, AP Airlines Writers
Delta Air Lines has completed the integration of its frequent flier program with that of its subsidiary, Northwest Airlines, Chief Executive Richard Anderson said Thursday.
The combined program has more than 70 million members.
Separately, another airline executive said that about half of the old Northwest Airlines planes that will get Delta's colors have been repainted, and the rest will be finished by mid-2010.
Atlanta-based Delta, which became the world's biggest airline operator with its acquisition in October 2008 of Eagan, Minn.-based Northwest, remains on course to obtain a single operating certificate by the end of this year.
Anderson said in a recorded message to employees that the changeover in the frequent flier program occurred Wednesday night.
"It's all SkyMiles now," Anderson said. "We have a single frequent flier program now, with a single database with a single technology platform."
The changeover means that Northwest frequent flier members have had their WorldPerks converted to SkyMiles and will have SkyMiles issued to them in the future for eligible travel and credit card purchases, Delta spokesman Paul Skrbec said.
He said frequent flier members would be notified, and that process would continue through October.
Representation and seniority list integration has been resolved for pilots of the two carriers and for several other work groups. The issues remain unresolved for the two biggest work groups, which include flight attendants and ground workers.
Anderson told employees in his recording that he hopes the issues are resolved soon. He urged the unions that represent pre-merger Northwest employees in those groups to not delay a vote.
"Everyone of you is entitled to prompt resolution of representation issues," he told all Delta employees.
Meanwhile, Delta has painted about 138 of the 250 Northwest planes that are getting a new paint job, said William Lentsch, Delta's senior vice president for Minnesota operations. That doesn't count smaller planes for Northwest's regional operations Compass and Mesaba airlines.
Northwest planes that are being retired, such as some of its aging DC-9s, aren't getting the Delta colors, he said.
Minnesota lawmakers called Lentsch to testify at a committee hearing for an update. They're especially interested because Delta has agreed to keep 10,000 jobs here through 2016 and 400 flights a day at Minneapolis-St. Paul International Airport.
Lentsch also said that Delta:
• Employs about 13,000 Minnesotans, and that most of the job transfers to Delta's Atlanta headquarters are finished. He said he doesn't expect them to get close to the 10,000 floor anytime soon;
• Is meeting its commitment for 400 flights a day at the Minneapolis airport.
Northwest ticket and gate agents in Minneapolis and Detroit are getting week-long training on Delta's new, integrated computer systems, he said.
The integration is happening at a time when the industry is shrinking dramatically because of a sharp drop in business travel and steeply discounted leisure travel. He said the airline industry's capacity is down about 7% compared with a year ago — the steepest drop since 1942, the first full year the U.S. was fighting in World War II.
The industry is in "a very weak revenue environment," Lentsch said. "We don't see any real near-term recovery on the revenue side."
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University of Bern, School of Dental Medicine, Department of Preventive, Restorative and Pediatric Dentistry, CH-3010 Bern, Switzerland
Nordstrasse 26, CH-8200 Schaffhausen, Switzerland
Address all correspondence to: Martina Eichenberger, University of Bern, Department of Preventive, Restorative and Pediatric Dentistry, School of Dental Medicine, CH-3010 Bern, Switzerland, Tel: 0041 316 322570; Fax: 0041 316329875; E-mail: email@example.com
We evaluated the near visual acuity of 40 dentists and its improvement by using different magnification devices. The acuity was tested with miniaturized E-optotype tests on a negatoscope under the following conditions: 1. natural visual acuity, 300 mm; 2. single lens loupe, 2×, 250 mm; 3. Galilean loupe, 2.5×, 380 mm; and 4. Keplerian loupe, 4.3×, 400 mm. In part 1, the influence of the magnification devices was investigated for all dentists. The Keplerian loupe obtained the highest visual acuity (4.64), followed by the Galilean loupe (2.43), the single lens loupe (1.42), and natural visual acuity (1.19). For part 2, the dentists were classified according to their age (</≥40 years). The younger dentists' group achieved a significantly higher visual acuity with all magnification devices (p<0.001). For part 3, the dentists were grouped according to their natural visual acuity. The group with the higher natural visual acuity achieved significantly higher visual acuity with all magnification devices than did the group of dentists with the lower natural visual acuity (p<0.01). It can be concluded that near visual acuity varies highly between individuals and decreases during the lifetime. Independent of age or natural vision, visual acuity can be significantly improved by using magnification devices.
The conviction that visual acuity has an essential influence on the precision of manual work is well-known and widespread in many professions. Dentistry, with its small operating field and its demands for manual skills and precision, is particularly suited to the use of optical magnification. For decades, loupes have been used by dentists to improve precision,1- 2 as well as for ergonomic reasons.2- 7 Since the 1990s, the operating microscope has been promoted as a necessary part of dental equipment.
Surprisingly, very little scientific research about the visual acuity of dentists, the influence of the different optical devices, and the relationship between visual acuity and precision in dental work has been published so far. An electronic search in the PubMed and Embase databases using the keywords "loupes," "magnification," or "visual acuity," and their combinations yielded no more than 70 original articles, when endodontic publications were excluded and the search was limited to dental journals. The literature about optical magnification in dentistry is dominated by case reports and expert opinions that mostly praise the advantages of optical magnification),2,6,8- 10 thus representing a body of evidence with the lowest possible evidence level. There is an obvious gap between the subjective conviction of the advantages of magnification for dental work and its scientific evidence. Burton and Bridgman11 examined the visual acuity of a group of dentists and dental students in New Zealand and showed a huge individual variability and also an influence of age on visual performance. Several other studies investigated the influence of age and showed a loss of accommodation (presbyopia) and low contrast sensitivity under testing conditions with low illumination with increasing age.8,12- 15 Studies about loupes in restorative dentistry and adjacent tooth damage showed ambiguous results and suggest that the use of the tested magnification devices does not, per se, lead to better quality processes or results.1,16- 17 Studies comparing the impact of different magnifications on diagnostic accuracy showed little18- 19 or no diagnostic gain.19 On the contrary, the use of loupes or clinical microscopes provokes an increase in false positive results, despite an increase in sensitivity.20- 21
Loupes are classified according to their different optical construction into single lens loupes, Galilean loupes, and Keplerian loupes. Dependent on the optical construction, different magnification factors are possible. A typical magnification factor for Galilean loupes is 2.5× with an upper limit of 3.2×. Keplerian loupes allow a free choice of the magnification factor. However, due to practical reasons, it is commonly between 3.5× and 4.5×.
The diversity of loupe systems, the variability in natural visual acuity, and the influence of age and adjustments suggest that the impact of loupes on dental treatment quality might be more complex than expected.
The aim of the present study was to evaluate with a new visual test the effect of different magnification devices on the near visual acuity of a group of dentists and to analyze how this effect is influenced by the dentist's age and natural visual acuity.
Forty dentists from the Dental School of Bern, Switzerland, were enrolled in the testing procedure (age distribution, Table 1). Miniaturized visual tests with E-optotypes, well-known to opticians, allowed a test of the visual acuity at a typical dental working distance (Fig. 1). The miniaturization of these tests was achieved by precision pictures on diapositive films (Kodachrome 64, KODAK, Rochester, New York). The dimension of the E-optotypes ranged from 0.05 to 0.58 mm. The transparent tests were fixed behind a fenestrated black cardboard (0.5 mm) and mounted on a negatoscope.
Visual test with E-optotypes (5.2 × 2.8 mm).
The visual test was carried out under four different conditions, whereby the negatoscope was at eye-level and the chin could be supported on the hands. There was no special training with the different loupe systems.
The loupes were mounted to a headband, allowing the wearing of individual eyeglasses in all groups. During all visual tests, the position of the loupes, the eye-object-distance, and the reading of the E-optotypes were supervised by the same expert. The smallest line that could be read without mistakes was registered.
The values of the recorded lines of the E-optotypes were converted in visual acuity units by the following formula: Visual acuity = 1/angular visual acuity.
The angular visual acuity is defined as the smallest angle, in minutes, under which two adjacent points can be separately recognized. In the visual tests, these points are two adjacent arbors of the E ( = 1/5 the size of E). First, the angle epsilon (ɛ) had to be calculated with the formula 1. ɛ = tan−1(d/a), and then the visual acuity was calculated according to the formula 2. visual acuity = 1/(ɛ×60) (Fig. 2).22- 23
Schematic illustration for calculating visual acuity.
For part 1 of the study, the influence of the different magnification systems on the visual acuity was investigated for all tested dentists. In part 2, the same dentists were divided into two subgroups: group A included those with age<40 years and group B included those with age ≥ 40 years. The age cut-off of 40 years was chosen because literature reports this to be the age at which natural changes in the eye begin.13- 14 For part 3, the dentists were classified by their natural visual acuity as assessed in part 1: group C presented a natural visual acuity of 1.1 or more and group D presented a value <1.1. The cut-off value of 1.1 was chosen according to the test results with the aim to obtain two evenly divided groups.
For statistical analysis, the software SAS 9.1.3 (SAS Institute Inc., Cary, North Carolina) was used. The significance level was set at α = 0.05. Descriptive statistical analysis was carried out to determine the means and medians as well as the nonparametrical 95% confidence intervals (CIs) for all dentists and for the subgroups A to D. The influence of the respective groups of dentists and different loupe systems on the visual acuity was analyzed using two nonparametric repeated measures ANOVA models, namely F1_LD_F1 models after Brunner, Domhof, and Langer,24 followed by Wilcoxon Mann Whitney tests and Wilcoxon signed rank tests with Bonferroni–Holm correction for multiple comparisons as post-hoc tests.
The mean visual acuities, medians, and 95% CIs for all tested dentists are presented in Table 2. The highest visual acuity was obtained with the Keplerian system, followed by the Galilean system, the single lens loupe, and finally, the natural visual acuity. Statistical analysis revealed significant differences between all tested conditions (p<0.001) (Table 2).
The mean visual acuities, medians, and 95% CI for groups A and B (< and ≥40 years, respectively) are presented in Table 3. There was a moderate correlation between the participants' age and their visual acuity (Cohen's kappa 0.53). For all tested conditions, significant differences between the two groups were detected. Both groups profited from magnification of the single lens loupe and even more from the sophisticated optics of the Galilean and Keplerian loupe (Table 3).
The mean visual acuities, medians, and 95% CI for the groups C and D (natural visual acuity ≥1.1 and <1.1, respectively) are presented in Table 4. Statistical analysis detected significant differences between groups C and D for all tested conditions. Without magnification, group C achieved significantly better visual acuity than group D (p<0.001); this was also true when using the single lens loupe (p<0.001), the Galilean loupe (p<0.001), and the Keplerian loupe (p<0.01) (Table 4). Group C showed a significantly higher visual acuity without magnification than did group D with the help of a single lens loupe (p<0.01), but a lower visual acuity than was found in group D assisted by a Galilean or Keplerian loupe (p<0.0001).
The body of evidence for using magnification devices in dentistry is weak: in particular, near vision in the dental working distance has rarely been tested. This might be due to the fact that the tests commonly used for near vision, such as the reading type test of the British Faculty of Ophthalmologists, are obviously not sensitive enough for dental purposes, and a commonly accepted visual test that would fulfill the necessary optical requirements is not available.
Near vision, as assessed by the above-mentioned reading type test, was assessed in a group of dentists and showed adequate near visual acuity in 93.5%,15 99.91%,25 and 100%.26 This test is composed of passages of text at known type-face sizes from N5 upward. N5 is a historic dimension unit that is equivalent to 0.9 mm for lower case letters in Times Roman.27 If almost all of the test subjects can read the smallest line, then this test seems to be inadequate for dental purposes. A comparison of N5 with the range of E-sizes used in this study could support this conclusion. Only one study used miniaturized Snellen tests, which do show the variability in dentist's natural near vision.11 Snellen charts are well-known from optician's acuity tests and consist of randomly arranged letters in downsizing lines. This test allows an objective acuity measurement but has the disadvantage that some letters are easier to recognize than others. Only tests with E-optotypes or Landolt-Rings allow a more objective measurement of visual acuity and the calculation of the vision angle.
For the present study, E-optotypes ranging from 0.05 to 0.58 mm were chosen. As 39 out of 40 participating dentists were able to read the biggest line without magnification aids, and as all of them failed to read the smallest line even when using the biggest magnification factor, we consider the selected test size to be adequate.
The miniaturization of these tests in an adequate and precise dimension was one of the challenges of this study. In summary, the use of a miniaturized common and validated test in the chosen dimensions seems to be adequate to measure near visual acuity for dental purposes. The aim of a further study should be the comparison of this miniaturized test with the common test applied by an optician.
As shown by the results, the natural visual acuity varies highly between individuals. Dentists may compensate for visual deficiencies by using different magnification devices, such as the tested loupes. Even a single lens loupe leads to better visual performance, but the small, physically-determined working distance of 250 mm is ergonomically compromising. Therefore, single lens loupes are not normally recommended because of their inappropriate ergonomics and optical aberrations.6,28 Nevertheless, this optical system was tested as it is still a common magnification device in dental practice thanks to its light weight and low cost. Improved optics such as the Galilean and Keplerian loupes, are more convenient as they allow an individualization of the working distance and, in part, the magnification factor. The tested Galilean system was chosen as a reference of Galilean systems, with the common magnification of 2.5× and the possibility of attachment to a headband that allows for the wearing of glasses. This system enabled improved visual acuity at the typical working distance for dentists. In previous publications, Galilean loupes have been especially recommended for dental students, dental hygienists, and periodontists and as a good entry point for those unfamiliar with magnification.8,28 In the present study, the Keplerian loupe with a magnification of 4.3× achieved the best visual acuity at the typical working distance for dentists. This is mainly due to the higher magnification factor, but perhaps also to the absence of chromatic and optical aberrations. A direct comparison between a Galilean and a Keplerian system with the same magnification factor was not possible because Keplerian loupes with 2.5× are not on the market because of their heavier weight and more complicated construction. However, the significant difference between the tested Galilean and Keplerian loupe is remarkable. This result indicates that in studies of loupes, the choice of the tested loupe system is important.
Many previous studies have reported presbyopia and a loss of visual acuity with increasing age. This was confirmed in the present study, as a lower natural visual acuity was found for the older dentists (≥40 years), which may be due to changes in the eye that begin at this age.13- 14 Dentists suffering from presbyopia can compensate for their visual deficiencies by using magnification devices, but they may not achieve the visual acuity that they had at a younger age. The younger dentists in this study obtained significantly higher visual acuity than did the older dentists, independent of the tested magnification device. The Keplerian loupe even showed the highest differences between the two age groups, which may be due to the complexity of this optical system. With increasing magnification, the depth of the field becomes smaller, allowing fewer tremors of the hand or head, which might be more difficult for older dentists. Moreover, the lower contrast sensitivity that was reported for older dentists (>40 years) may be a factor that negatively influences the visual acuity, especially with a decreasing size of the E-optotypes).12,14 Another reason for the high difference between the older and the younger group of dentists with Keplerian loupes may be the fact that younger people are more adaptive, allowing them to handle a complex loupe system more easily.
In part 3 of this study, the dentists were classified according to their natural visual acuity (</≥1.1) to determine if both groups benefited in the same degree from magnification devices, what could be confirmed in this study. Nevertheless, it is apparent that there are individuals that can achieve a higher acuity without any magnification than others with the assistance of the Galilean loupe. Only when using the Keplerian loupe did all dentists achieve a higher visual acuity than anyone did with natural vision.
Magnification devices, the dentist's age, and their natural visual acuity all have a significant influence on visual performance in the dental working distance. Dentists should be aware of their own visual performance and of the methods available to compensate their visual deficiencies. Magnification devices are recommended for dentists with low natural visual acuity and for dentists with good visual acuity. By using magnification aids such as Galilean or Keplerian loupes, dentists with low natural visual acuity can see better than can dentists with high natural visual acuity without magnification aids.
The authors thank Philippe Ducreux (Lunea-Group, France), Professor Andreas Ettemeyer (NTB Interstaatliche Hochschule für Technik Buchs, Buchs, Switzerland), Martin Roost (Roost-Optik, Schaffhausen, Switzerland), and René Seiler (Fischer & Loeliger Optik, Bern, Switzerland) for their support with optical issues. The authors also thank Stefanie Hayoz (Institute of Mathematical Statistics, University of Bern, Switzerland) for the statistical analysis.
Martina Eichenberger ; Philippe Perrin ; Klaus W. Neuhaus ; Ueli Bringolf and Adrian Lussi"Influence of loupes and age on the near visual acuity of practicing dentists", J. Biomed. Opt. 16(3), 035003 (March 16, 2011). ; http://dx.doi.org/10.1117/1.3555190
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ESPN College GameDay is headed to Columbia, SC! GameDay hosts, college football fans and students will take over the University of South Carolina Horseshoe this Saturday, October 6, 2012, as the South Carolina Gamecocks take on the Georgia Bulldogs.
GameDay, presented by The Home Depot will air live at 9:00 am ET on ESPNU and 10:00 am on ESPN with host Chris Fowler, analysts Lee Corso, Kirk Herbstreit, Desmond Howard and David Pollack, and host/reporter Samantha Steele and Tom Rinaldi.
The Home Depot will offer a chance to win tickets to the game and backstage passes at College GameDay at The Home Depot College GameDay Event, at their 5200 Fernandina Rd location from 4:00 to 6:00 pm on Friday, October 5.
Game day shuttles will run from the State Fairgrounds to USC campus between 8:30 am and 1:30 pm on Saturday. Find out more about GameDay shuttles.
Are you ready for another 'Famously Hot' GameDay in Columbia? Let us know by dropping us a line on Twitter or Facebook if we'll see you at the Horseshoe getting 'Famously Hot & Cocky'! Keep following our blog this week as we round-up of things you won't want to miss while you're in town for ESPN College GameDay, let you in on a special giveaway for Gamecocks at GameDay and more! Hint: Gamecocks, did you get a 'Famously Hot' sweatband at the Mizzou game?
These are modern times, y'all, and Columbia SC is redefining Southern for a new era. Stay up-to-date on all things Columbia -- from events and festivals to delicious restaurant eats and sweet treats. Here, we curate the newest and most buzzworthy things to do during your stay in The Real Southern Hot Spot.
ESPN College GameDay heads to Columbia, SC
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1. Some track(s) to reduce takeout rates on something other than Pick-4s or Superfectas
2. Exchange wagering to finally come to California harness racing, and then quickly come to New Jersey.3. Free 'basic' program pages available on American Racetrack websites. I have no problem with people having to pay for advanced programs but if we want people to even sample the sport, we need to give them something to look at. Names don't cut it.
4. 4NJBets.com (or put in your ADW) to cover some additional tracks (such as Fraser Downs). While we are at it, how about some foreign harness racing. No, I don't expect it to be on television, but over the Internet, how expensive can it be? At least the classics such as the Prix d'Amerique and the Elitlopp. .
5. A Fair Start Rule (Definitely not holding my breath on this one).
6. Legislators coming to their sense in Illinois and pass the ADW bill. Why we are at it, why do you insist on a sunset provision?
7. Racetracks and their own ADWs show some love to the little player. Look, I understand the larger players pay the bills but the smaller player deserve some type of rebates. Instead of 3% back, give them 1% back. Instead of crediting them it back daily, do it quarterly. The point is give them something tangible back; something to let them know you appreciate their business. And please, make it a wagering credit, a free program after spending $250 doesn't cut it.
8. Stop this nonsense of having state governments assessing domestic market fees on out of state ADWs to get the customers YOU LOST back. If your ADW offered rebates like the out of state ADWs, you wouldn't need the state to get your customers back. Compete for your customers and win them back. Instead of having the state tax out of state ADWs, lobby them to give you a percentage of the pari-mutuel tax for rebates.
9. An understanding of the criteria for getting licensed in California. Do they check on prior records or are they that desperate for warm bodies that a warm body is the criteria?
10. How about a percentage of the takeout going towards horse retirement/placement in second careers when they are done and publicize the fact it's being done. In some jurisdictions some money is being used exactly for that but it's treated like a state secret; that's not smart.
11. Horsemen who worry more about how many people are in the stands than they do about how much slot revenue they may get or not get.
12. Require horsemen to wager. Of course, not on their horses but they should be required to wager at least $1,000 over a year using a card which can be used to track the wagers. You would be surprised how many horse owners and others don't bet the races. I won't speculate why but maybe if they wagered on the races they would appreciate what the gambler goes through. Maybe then they would understand why we are not happy with the way things are.
13. Judges to finally recognize the lunacy of transferring horses to a second trainer when the regular trainer gets suspended and stop approving them.
14. The end of seeing horses consistently race lackluster in eliminations and then turn into bear cats the following week.
15. Get rid of earning your post position based on your finish in the elimination. You say it's not fair to draw the outside when you win the elimination, but you had no problem when someone else drew the outside in the elimination and had to race their heart out hoping to advance to the final. Earning post positions is utter bull, well you get the idea. If a random draw is good enough for an elimination, it should be good enough for the final.
16. Consistency when it comes to exclusions. I'm all for a private track operator to show 'undesirable' people the door, but while it is a good tool for the operator, you can't help but wonder why one person gets to race while someone else is banished to the hinterlands when the individuals seem to be having similar situations. It gives the appearance of playing favorites which hurts credibility.
17. Cooperation between area tracks so that simulcast viewers could watch a race every 5 minutes, instead of 3 races going off at the same time and then waiting 15 minutes for another 3 races that go off at the same time.
18. Continuing on a cooperation and coordination theme, do we need to have Harrah's, Meadowlands, Pocono Downs, and Yonkers Raceway all racing at the same time? First of all there is not that much demand for the product and secondly, you are watering down the racing stock available at each track. Coordinate the meets instead of slugging it out against each other and not only will the racing be better but your handles will increase (especially if you get rid of your extortion-like takeout rates Pennsylvania).
19. Races to go off at post time with the countdown clock like they have in Sweden and the WEG tracks. If the race is held up, it should be no more than two minutes (Remember USTA Rule 16 Section 10?)
§ 16.10 Holding Horses Before Start.—Horses may be held on the backstretch not to exceed 2 minutes awaiting post time except when delayed by an emergency..
20. Exciting camera angles like they have in France. Gosh, if there is anything less exciting in sports presentation-wise than horse racing, I would like to know it. How about some camera angles from the inside of the track and close ups of horses in the turns. Make the presentation of the race like the bettor is actually in it.
21. Free Wi-Fi. Block the wagering sites except your own if you wish, but maybe I want to be able to check on things at the other tracks.
22. In the future, should any more tracks get alternate gaming, have racing and/or gaming commissions require permit holders to upgrade the racing-side of the facilities and not just backstretch improvements. No, I don't expect each track to make the grandstand look as luxurious as the casino part of the facility but just the same, some amount of upgrading of the grandstand is reasonable. I'm sick and tired of walking through some beautiful casino into a grandstand that looks like Newark, NJ after the race riots. Remember, you sold alternative gaming as a way to save horse racing so asking you to do something more than applying a fresh coat of paint is not unreasonable.


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You Can't Teach an Old Dog New Tricks, But New Ordinance Will Make It Cheaper to Try
Back to the animal shelter for a second ...
One other thing interim assistant city manager Joey Zapata and I touched on briefly yesterday was an item on the council's agenda for next week involving the lowering of adoption fees at Dallas Animal Services. Because right now, it's kinda pricey for some: $85 for a dog, and $55 for a cat. Now, of course, that's a package deal: Those costs cover everything from vaccinations to sterilization to the microchip implant, which you don't just get at Baylor. Still. Not for everyone.
Council hopes to change that with a new ordinance that makes it a little less expensive -- for some, all the time; for everyone else, some of the time:
The proposed ordinance would amend Section 7-2.7 of the Dallas City Code to reduce the adoption fees to $43 for a dog and $27 for a cat if: (1) the dog or cat is at least six years of age; (2) the ultimate owner of the dog or cat will be a person who is 65 years of age or older as of the date of adoption; or (3) the adopter adopts two or more dogs and/or cats on the same date and as part of the same transaction and the adopter will be the ultimate owner of all of the animals adopted in the transaction.
The proposed ordinance would also allow the director to designate and advertise promotional adoption periods during which the adoption fees will be reduced to $43 for a dog and $27 for a cat. These promotional adoption periods may not exceed seven consecutive days, and no more than eight promotional adoption periods may be designated during a calendar year.
The new ordinance is on the other side. Jump. Now, roll over. Now, play dead.
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me and my mom where organizing everything for the baby , when my water broke , my mom grabbed the beg and told me too grab a jaket bc we leaving for the hospital . I told her " no I am not ready to have her I didn't finish organize and I thing got emotionaly ready for this " so my mom grabed my hand and said " yeah right you better hurry up before the pain kicks in bc then you will deff be emotionaly ready "
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Another day removed from that ugly Toronto street brawl and CC Sabathia is admitting he let his temper get the best of him.
The New York Yankees pitcher told TMZ Sports that he let haters get under his skin in trying to get in the mix of what turned into a wild street brawl outside of EFS nightclub early Saturday morning. The Yankees had just taken the first game of a three-game weekend series with the Blue Jays.
Sabathia had to be held back by a friend and pushed into a car...which was probably a good thing for those fighting, considering the Yankees pitcher stands six foot, seven inches and nearly 300 pounds. But overall, Sabathia thinks he made a bad decision trying to fight.
"They caught me at a bad time," Sabathia said of hecklers who he said got personal with him. "It was literally 25 seconds of me and then I was gone."
When it was all said and done, Sabathia says explaining it to his child was harder than explaining it to the Yankees.
"That's the toughest part: 'Dad had a bad night,'" Sabathia said. "'Made a bad decision. Sometimes these things happen.'"
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Andrew Frankel is a former Hasbro designer.
He is known to have created the deco for numerous Transformers, particularly store exclusives.
Frankel had also previously worked on NASCAR, Jurassic Park, Batman, and Star Wars toylines. At one point he was brand manager of Hasbro's G.I. Joe line, and helped develop the two direct-to-video G.I. Joe CGI movies.
Between 2001 and 2002, Frankel edited the scripts for the Robots in Disguise cartoon series to include references to characters and events from earlier Transformers series, after the scripts had been submitted to Hasbro for broadcast approval. He was also credited as a creative consultant for the Armada and Energon cartoons.
Robots in Disguise
- Like some others who have worked on the G.I. Joe and Star Wars toylines at Hasbro, Frankel's likeness was used as the inspiration for some action figures of both lines, in his case the headsculpts of the 3' 3/4 inch G.I. Joe Sideswipe and the Star Wars twelve-inch AT-ST driver figures. The Juggler, General Frankel was also named after him.
- Before working for Hasbro, Frankel was a frequent participant in online Transformers fandom discussions. He went by the nickname "Sideswipe" but was more commonly referred to as "Swiper".


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World Thinking Day ~ Today!
Today is World thinking day! ... My girl scout troop participated in a great event to help think about the world last night. Each troop in our Service unit picked a different country and gave information on the country and provided "tastes" of food from that country. The girls had a great time and the food was great!
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- slumber party
- noun Date: 1925 an overnight gathering especially of teenage girls usually at one of their homes
New Collegiate Dictionary. 2001.
New Collegiate Dictionary. 2001.
slumber party — slumber parties N COUNT A slumber party is an occasion when a group of young friends spend the night together at the home of one of the group. [AM] … English dictionary
slumber party — slumber .party n AmE a children s party when a group of children sleep at one child s house … Dictionary of contemporary English
slumber party — slumber ,party noun count an occasion when a group of children all sleep at the house of one child: SLEEPOVER, PAJAMA PARTY … Usage of the words and phrases in modern English
slumber party — ☆ slumber party n. a house party at which young teenage girls, dressed in nightclothes, spend much of the night in talk, eating, games, etc … English World dictionary
slumber party — noun an overnight party of girls who dress in nightclothes and pass the night talking • Hypernyms: ↑party * * * noun, pl ⋯ ties [count] US : a party where one or more people (usually girls) stay overnight at one person s house : ↑sleepover My 12… … Useful english dictionary
Slumber Party — Infobox musical artist Name = Slumber Party Background = group or band Origin = Detroit, Michigan, USA Genre = Slow Core Noise rock Psychedelia Indie rock Years active = 1998 present Label = Kill Rock Stars Dulcitone Top Quality Rock Roll URL =… … Wikipedia
slumber party — UK / US noun [countable] Word forms slumber party : singular slumber party plural slumber parties mainly American an occasion when a group of children all sleep at the house of one child … English dictionary
slumber party — pyjama party, party where guests sleep at one s house (usually children) … English contemporary dictionary
slumber party — a social gathering typically of teenagers held at the home of one of them for the purpose of sleeping there overnight. Also called pajama party. [1920 25] * * * … Universalium
slumber party — noun a party where everyone is dressed in pyjamas, or otherwise dressed for bed … Wiktionary
slumber party — noun N. Amer. a party, typically for teenage girls, in which all the guests stay overnight … English new terms dictionary


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Coach Leads a School Without a Gym to Basketball Glory
Published: April 2, 1989
(Page 2 of 2)
Mr. Hurley recalls that as a young boy he imagined tumbling out of his home on Linden Avenue and altering his identity. He dreamed of being Bob Cousy of the Celtics. The playground was the Boston Garden. He would practice making shots that won games. ''I'd use my imagination and be anywhere,'' he said. ''I always knew where to find a good game. I took my ball and went.'' No Varsity Letter
The practice turned him into a good player at St. Peter's Preparatory High School, but that was it. As a 5-foot-10-inch point guard, he was unable to contribute at St. Peter's College. He averaged 20 points a game for the freshman team, but never stitched on a varsity letter.
Curtailing his career was a painful blessing. It gave Mr. Hurley freedom to coach. As a junior in college, he coached the St. Anthony junior varsity. Three years later, he was varsity coach.
While he was the junior varsity mentor, he married Chris Ledzion. Their third date was a three-hour elementary school basketball game. In Mr. Hurley's first varsity season, the team was 27-2 and won a state championship. The next year, St. Anthony was 30-0 and won another state crown. It was also the season when Bobby Jr., still a baby, clinging to a miniature basketball, began making appearances at practices. Bobby was recently named one of the top 10 players in the country by Parade magazine.
As Bobby went from crawling to walking and dribbling behind his back, the state championships continued to pile up. With Mr. Hurley in the backcourt, St. Anthony added four more state titles and won 91 of its last 93 games.
''We're going to miss that guy,'' Mr. Hurley said. ''He always made the big shot.''
Point guard was the elder Hurley's own position. It is Bobby Jr.'s position, and next season his younger brother, Danny, a sophomore, will inherit it. The players change, but the coach remains. Asked About a Change
Mr. Hurley is often asked about leaving St. Anthony for a more lucrative job. He admits to being flattered by the attention, and his penetrating blue eyes gleam at talk of handling a Division I college team.
After a few seconds, he returns to reality. Not the reality of whether he could do it, but the reality of what he said he would miss. It is the pleasure of molding the lives of wayward youths and giving them a better chance than they could have expected without him.
And it is the pleasure of doing it in his own backyard, with his sons on the team, with his wife keeping score and with his 8-year-old daughter, Melissa, as a water girl. It is the pleasure of coaching one of the best teams in the country in the city where he first dreamed of basketball. Mr. Hurley believes he belongs at St. Anthony, and he is in no hurry to leave.
''This past season was filled with memories that will last a lifetime,'' Mr. Hurley said. ''We were the best in the United States. The taste was phenomenal and I don't want to lose it. I don't want to be coaching for my livelihood as opposed to coaching for the love of it. I coach because I love it. I don't see any reason why I would ever leave.''
Photo of Bob Hurley, coach of the St. Anthony High School basketball team, with team members during a game (NYT/Barton Silverman)


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Four ways to enjoy beer more, courtesy Rackhouse Pub's GABF Beer Judge School
Presenter Gwen Conley and Rackhouse Pub owner Chris Rippe.
With the Great American Beer Festival in town and everyone talking about beer, describing a brew as "good" or just saying "I like it" no longer feels like enough. That's why an oversold crowd of sixty or so swillers packed the Rackhouse Pub for yesterday's Beer Judge School.
For those who aren't ready to debate whether "skunky" is a legitimate description of beer, here are four easy ways to become a better beer-drinker:
1) Press your tongue to the top of your palette: Don't have a great sense of taste? Can't figure out where your drinking buddies are getting those green apple notes from? Pressing your beer-soaked tongue to the roof of your mouth will allow you to taste more.
2) Sniff your beer: According to Gwen Conley, quality assurance and brewing operations director of Port Brewing and the Lost Abbey, 80 to 90 percent of what we think of as taste is actually smell. She recommends short sniffs so that your snout doesn't get worn out as quickly. If you're presented with an especially unappetizing beer, you don't want to inhale too deeply, either.
3) And sniff your armpit: When your nose does get worn out, Conley suggests that you sniff an armpit. Your own, which has a smell that's neutral to you.
4) Use your right brain, not your left: While there's nothing empirically wrong with describing beer as "good" or "bad," what's the fun in that? Does the beer remind you of a Caribbean vacation? Is it because there are tropical fruit notes? Push yourself to really describe a beer. (And just FYI, those fruity flavors are the result of a detectable amount of ester which is produced by yeast.)
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100% Kona Coffee › best coffee › Best Kona Coffee › feature › Hawaiian Coffee › honolulu coffee › Honolulu Coffee Experience Center › Kona Blend Coffee › kona coffee › Kona Coffee Beans › Kona Coffee Farm › Kona Coffee Hawaii › Kona Coffee Honolulu › news › sprudge ›
It's exciting to be featured in one of most famous daily coffee news Sprudge.com
It's Aloha Friday here on Sprudge, and that means no work til Monday. It also means we da kine to take a look at the latest location from Honolulu Coffee Company, purveyors of fine Hawaiian-grown specialty coffee. This new shop is to be the brand's flagship, and will be home to a cafe, bakery, roastworks and QC lab. So whether you're in Honolulu as a haole for a little mele kalikimaka come Christmastime, or you're lucky enough to be a local stuck in paradise traffic, ... more
© 2017 Honolulu Coffee


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I was with my husband at the Hotel and we enjoyed the beach. The food was very good. It was my honeymoon #25. The hotel is wonderful for family and love. We were at de Sambil mall for shopping. We ate a very good food and very cheap. All the retail stores are excelent.
- Official Description (provided by the hotel):
- Situated along Margarita Island's magnificent northeastern coast, Playa el Agua, the newest addition to our family of 4-star luxury boutique hotels - Agua Dorada Beach Hotel by Lidotel - is a tranquil beach haven nestled upon the shores of the Caribbean Sea. The hotel is conveniently located 25km from the main city of Porlamar and 35km from the Porlamar International Airport (PMV).Offering the same amenities as larger resorts in the area, our modestly-sized property allows us to provide our guests with an exceptional level of personalized service not easily found at our other hotels or resorts in the area. Our safe and secure environment provides travelers with a completely harmonious experience within a tropical setting.Find your inner self as you take a siesta on one of our beachside relaxation beds or leave your footprints-in-the-sand along the pristine shoreline as you walk for miles in pure bliss. If you are a traveler that likes adventure, our beachfront location also allows for a variety of motorized and non-motorized water sports and activities. ... more less
- Reservation Options:
- TripAdvisor is proud to partner with Orbitz, Expedia, Hotels.com, Travelocity, HotelQuickly, TripOnline SA, Cheap Tickets, Evoline ltd and Hotwire so you can book your Agua Dorada Beach Hotel by LIDOTEL reservations with confidence. We help millions of travelers each month to find the perfect hotel for both vacation and business trips, always with the best discounts and special offers.
- Also Known As:
- Agua Dorada Beach Hotel By LIDOTEL Margarita Island/Playa El Agua, Venezuela


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Mischa arrived at LAX this week with her dog Ziggy and a new look. Her airport attire is definitely more tame than her hot club wear (she traded those daisy dukes for pinstripe pants) - and it looks like she hit the salon to lighten up and perhaps add extensions to those long locks. We like this outfit, but her pup is definitely the best accessory. To get Mischa's look, just click here.
Join The Conversation
Mischa's great! LOVE HER!!!
Ziggy is so cute! I love her hair and her top here.
i still don't get why we pay attention to this girl anymore...anyone?
Where was she coming from?
like the outfit and the sunglasses
Ok... she looks MUCH better in these pics!! "Aint nobody out there swift like this."
I tottaly agree Krisua.
She can look nice in ads (due to airbrushing, i imagine), but in general, I don't think she's very pretty and her cankles (which aren't showing here, thanks the lord) are so disgusting.
She looks like a mixture of paris and britney here!!!
oh, the dog is so cute! I love her pants!
i think her face is slightly taking the shape of of her sunglasses, DROOPY!!! she looks better when she keeps them on L!VE !N LOVE ;)
Awww. Ziggy is adorable. Mischa looks pretty with those sunglasses. Her jeans are kind of cute.
whoa is it just me or does that not look like her? i mean i know its her, but something about her face in those photos is weird
i like the jeans!
it was sorta a boring day.. I didn't do anything to tick anyone off..
sorry... my little guy had a school trip. Karate.. what did I miss?
OHSURI!!!!! WHERE HAVE YOU been all day ?
Shes been dressing alot better lately, I love those jeans!
I don't like her at all.. why is she famous again. I agree with Jennav.. I heart Ziggy too!!
OMG, pinstriped jeans??? I remember those (vaguely) from when I was little. My babysitter had them in the 80's... Is this a trend I am totally missing??
The dog has legs for a reason! lol. I am kinda getting tired of celebs carrying their dogs around with one arm. On another note though, I love her shirt.
She always looks so effortlessly great...and what a cute pooch!
She just seems so dorky to me.
her puppy is too cute!
She looks so pretty! And I heart Ziggy!!!
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Training of principals is inadequate, with scant attention given to firing ineffective teachers, three new studies conclude. Eleven of the most popular college textbooks for training prospective school principals fail to focus on critical personnel decisions such as firing bad teachers, reports a study released in May by Frederick M. Hess and Andrew P. Kelly of the American Enterprise Institute. "Not one text provided a single positive reference to the possible benefit of removing an ineffective teacher," the study states. A separate AEI study faulted 31 graduate education courses particularly in the area of faculty management to foster greater academic achievement by students. A study by Arthur E. Levine, president of Teachers College, Columbia University, and released in March, concluded that "the majority of [educational administration] programs range from inadequate to appalling."
Strip-searching a whole class held unconstitutional. The U.S. Court of Appeals for the 6th Circuit, in Cincinnati, held in April that a strip search of students at a Michigan high school violated the Fourth Amendment's bar to unreasonable searches. The search in question took place after a girl reported that $364 had been stolen from her gym bag during a physical education class. Boys and girls were searched in separate locker rooms. The teachers did not touch the students.


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HP DL380 G6 G7 DL385 G6 G7 Complete Rail Kit w/ Cable Management Arm 487267-001
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- Item Category: Tools
- Source: eBay
- Sold Date: Oct 09, 2015
- Channel: Auction House
Up for sale, Qty- 1 487267-001 HP Complete Rail Kit, inner and outer rails, also with cable management arm for Proliant DL380 G6 DL380 G7 DL385p G5 DL385 G6Picture is actual Hardware. Good Luck


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Shauk hai ~full song (Guru) ~A.R.Rahman ~haunting melody MP3
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You'll worry less about day-to-day problems and focus on what is most important. As you become more mindful, you will be a more effective, successful and fulfilled leader. That's worth twenty minutes a day, isn't it?
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Gust MEES's curator insight, June 18, 2015 10:12 AM
People with high emotional intelligence tend to do better at work. So what habits do they have that set them apart?
Learn more:
- http://www.scoop.it/t/21st-century-learning-and-teaching/?tag=EQ
Chris Wejr's curator insight, April 14, 2015 9:35 AM
Although this is about business, there are some key links to some hurdles to overcome in our schools.
Ivon Prefontaine, PhD's curator insight, April 21, 2015 9:36 PM
In a day and age of more connectivity, is it not surprising that isolation appears on this list?
Dr. Deborah Brennan's curator insight, June 18, 2015 5:29 PM
Pessimism, fear, pressure, isolation, and narrow-mindedness all kill creativity - and all can be present in struggling schools. No wonder America continues to have schools that year after year fail to succeed. We need creative problem solving - therefore, we must build school cultures that minimize the fear, pressure, and pessimism that come with being in a struggling school.
Graeme Reid's curator insight, July 28, 2015 9:02 PM
As you become more mindful, you will be a more effective, successful and fulfilled leader.
Ivon Prefontaine, PhD's curator insight, April 22, 2015 9:17 PM
The Anne Lamott quote is accurate. We need a break from just doing and sometimes need to just be.


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The hearing has been scheduled for 9 a.m. on Wednesday, Oct. 31 at the municipal building off Blue Mill Road. Attorneys will answer questions and present their arguments to the committee although no new witnesses or evidence will be presented for the appeal, Arnold Mytelka, the attorney representing Harding Township, said on Monday. The Zoning Board of Adjustment surprised Sand Spring Road residents and environmentalists in May by approving a variance allowing the Animal Inn, a dog boarding facility, to increase its size to nearly 14,800-square-feet in an area of sensitive wetlands and a district currently zoned for single family residences.
Twenty-two residents filed a variance appeal to the Township Committee in July, objecting to the board's approval of the application. Residents are concerned the Animal Inn expansion not only violates several provisions of the township's Master Plan, but will also increase traffic on Sand Spring Road, lower property values, and set a precedent for future commercial development in their residential neighborhood.
The Township Committee also will meet at 9 a.m., Friday, Nov. 2, to announce and discuss their decision, said Mytelka. After the committee's oral decision, officials will prepare a resolution which sets out the reasons behind the decision in writing, he said. The resolution will be considered for adoption at a Township Committee meeting at 8 p.m., Wednesday, Nov. 28.
The committee's decision could be appealed to the Superior Court in Morristown.
Mytelka said the Oct. 31 hearing will be analogous to an appellate court hearing as opposed to a trial court hearing with witnesses.
Prior to the hearing, the Township Committee will have reviewed transcripts from the Board of Adjustment hearings on the Animal Inn during the past two years. The committee also will have looked over exhibits and reviewed briefs filed b y the applicant and the objectors, said Mytelka. In the Board of Adjustment's 5-2 decision granting the variance to the Morris Animal Inn in the spring, several members argued the expansion would not pose a substantial detriment to the public good or to the township's zoning or master plans.