text:
Publications (549)4811.72 Total impact
- [Show abstract] [Hide abstract]
ABSTRACT: The phosphotungstate anion (PTA) is widely used to facilitate the precipitation of disease-causing prion protein (PrP(Sc)) from infected tissue for applications in structural studies and diagnostic approaches. However, the mechanism of this precipitation is not understood. In order to elucidate the nature of the PTA interaction with PrP(Sc) under physiological conditions, solutions of PTA were characterized by NMR spectroscopy at varying pH. At neutral pH, the parent [PW12O40](3-) ion decomposes to give a lacunary [PW11O39](7-) (PW11) complex and a single orthotungstate anion [WO4](2-) (WO4). To measure the efficacy of each component of PTA, increasing concentrations of PW11, WO4, and mixtures thereof were used to precipitate PrP(Sc) from brain homogenates of scrapie prion-infected mice. The amount of PrP(Sc) isolated, quantified by ELISA and immunoblotting, revealed that both PW11 and WO4 contribute to PrP(Sc) precipitation. Incubation with sarkosyl, PTA, or individual components of PTA resulted in separation of higher-density PrP aggregates from the neuronal lipid monosialotetrahexosylganglioside (GM1), as observed by sucrose gradient centrifugation. These experiments revealed that yield and purity of PrP(Sc) were greater with polyoxometalates (POMs), which substantially supported the separation of lipids from PrP(Sc) in the samples. Interaction of POMs and sarkosyl with brain homogenates promoted the formation of fibrillar PrP(Sc) aggregates prior to centrifugation, likely through the separation of lipids like GM1 from PrP(Sc). We propose that this separation of lipids from PrP is a major factor governing the facile precipitation of PrP(Sc) by PTA from tissue and might be optimized further for the detection of prions.ACS Chemical Biology 02/2015; · 5.44 Impact Factor - [Show abstract] [Hide abstract]
ABSTRACT: An increasing number of studies continue to show that the amyloid β (Aβ) peptide adopts an alternative conformation and acquires transmissibility; hence, it becomes a prion. Here, we report on the attributes of two strains of Aβ prions formed from synthetic Aβ peptides composed of either 40 or 42 residues. Modifying the conditions for Aβ polymerization increased both the protease resistance and prion infectivity compared with an earlier study. Approximately 150 d after intracerebral inoculation, both synthetic Aβ40 and Aβ42 prions produced a sustained rise in the bioluminescence imaging signal in the brains of bigenic Tg(APP23:Gfap-luc) mice, indicative of astrocytic gliosis. Pathological investigations showed that synthetic Aβ40 prions produced amyloid plaques containing both Aβ40 and Aβ42 in the brains of inoculated bigenic mice, whereas synthetic Aβ42 prions stimulated the formation of smaller, more numerous plaques composed predominantly of Aβ42. Synthetic Aβ40 preparations consisted of long straight fibrils; in contrast, the Aβ42 fibrils were much shorter. Addition of 3.47 mM (0.1%) SDS to the polymerization reaction produced Aβ42 fibrils that were indistinguishable from Aβ40 fibrils produced in the absence or presence of SDS. Moreover, the Aβ amyloid plaques in the brains of bigenic mice inoculated with Aβ42 prions prepared in the presence of SDS were similar to those found in mice that received Aβ40 prions. From these results, we conclude that the composition of Aβ plaques depends on the conformation of the inoculated Aβ polymers, and thus, these inocula represent distinct synthetic Aβ prion strains.Proceedings of the National Academy of Sciences 06/2014; · 9.81 Impact Factor - [Show abstract] [Hide abstract]
ABSTRACT: An increasing number of studies argues that self-propagating protein conformations (i.e., prions) feature in the pathogenesis of several common neurodegenerative diseases. Mounting evidence contends that aggregates of the amyloid-β (Aβ) peptide become self-propagating in Alzheimer's disease (AD) patients. An important characteristic of prions is their ability to replicate distinct strains, the biological information for which is enciphered within different conformations of protein aggregates. To investigate whether distinct strains of Aβ prions can be discerned in AD patients, we performed transmission studies in susceptible transgenic mice using brain homogenates from sporadic or heritable (Arctic and Swedish) AD cases. Mice inoculated with the Arctic AD sample exhibited a pathology that could be distinguished from mice inoculated with the Swedish or sporadic AD samples, which was judged by differential accumulation of Aβ isoforms and the morphology of cerebrovascular Aβ deposition. Unlike Swedish AD- or sporadic AD-inoculated animals, Arctic AD-inoculated mice, like Arctic AD patients, displayed a prominent Aβ38-containing cerebral amyloid angiopathy. The divergent transmission behavior of the Arctic AD sample compared with the Swedish and sporadic AD samples was maintained during second passage in mice, showing that Aβ strains are serially transmissible. We conclude that at least two distinct strains of Aβ prions can be discerned in the brains of AD patients and that strain fidelity was preserved on serial passage in mice. Our results provide a potential explanation for the clinical and pathological heterogeneity observed in AD patients.Proceedings of the National Academy of Sciences 06/2014; · 9.81 Impact Factor - [Show abstract] [Hide abstract]
ABSTRACT: Prions are self-propagating protein conformations that cause a variety of neurodegenerative disorders in humans and animals. Mouse models have played key roles in deciphering the biology of prions and in assessing candidate therapeutics. The development of transgenic mice that form prions spontaneously in the brain has advanced our understanding of sporadic and genetic prion diseases. Furthermore, the realization that many proteins can become prions has necessitated the development of mouse models for assessing the potential transmissibility of common neurodegenerative diseases. As the universe of prion diseases continues to expand, mouse models will remain crucial for interrogating these devastating illnesses.Journal of Biological Chemistry 05/2014; · 4.60 Impact Factor - [Show abstract] [Hide abstract]
ABSTRACT: Bank voles are uniquely susceptible to a wide range of prion strains isolated from many different species. To determine if this enhanced susceptibility to interspecies prion transmission is encoded within the sequence of the bank vole prion protein (BVPrP), we inoculated Tg(M109) and Tg(I109) mice, which express BVPrP containing either methionine or isoleucine at polymorphic codon 109, with 16 prion isolates from 8 different species: humans, cattle, elk, sheep, guinea pigs, hamsters, mice, and meadow voles. Efficient disease transmission was observed in both Tg(M109) and Tg(I109) mice. For instance, inoculation of the most common human prion strain, sporadic Creutzfeldt-Jakob disease (sCJD) subtype MM1, into Tg(M109) mice gave incubation periods of ∼200 days that were shortened slightly on second passage. Chronic wasting disease prions exhibited an incubation time of ∼250 days, which shortened to ∼150 days upon second passage in Tg(M109) mice. Unexpectedly, bovine spongiform encephalopathy and variant CJD prions caused rapid neurological dysfunction in Tg(M109) mice upon second passage, with incubation periods of 64 and 40 days, respectively. Despite the rapid incubation periods, other strain-specified properties of many prion isolates-including the size of proteinase K-resistant PrPSc, the pattern of cerebral PrPSc deposition, and the conformational stability-were remarkably conserved upon serial passage in Tg(M109) mice. Our results demonstrate that expression of BVPrP is sufficient to engender enhanced susceptibility to a diverse range of prion isolates, suggesting that BVPrP may be a universal acceptor for prions.PLoS Pathogens 04/2014; 10(4):e1003990. · 8.06 Impact Factor -
Article: Novel compounds lowering the cellular isoform of the human prion protein in cultured human cells
[Show abstract] [Hide abstract]
ABSTRACT: PurposePrevious studies showed that lowering PrPC concomitantly reduced PrPSc in the brains of mice inoculated with prions. We aimed to develop assays that measure PrPC on the surface of human T98G glioblastoma and IMR32 neuroblastoma cells. Using these assays, we sought to identify chemical hits, confirmed hits, and scaffolds that potently lowered PrPC levels in human brains cells, without lethality, and that could achieve drug concentrations in the brain after oral or intraperitoneal dosing in mice. Methods: We utilized HTS ELISA assays to identify small compounds that lower PrPC levels by ⩾30% on the cell surface of human glioblastoma (T98G) and neuroblastoma (IMR32) cells. Results: From 44,578 diverse chemical compounds tested, 138 hits were identified by single point confirmation (SPC) representing 7 chemical scaffolds in T98G cells, and 114 SPC hits representing 6 scaffolds found in IMR32 cells. When the confirmed SPC hits were combined with structurally related analogs, >300 compounds (representing 6 distinct chemical scaffolds) were tested for dose-response (EC50) in both cell lines, only studies in T98G cells identified compounds that reduced PrPC without killing the cells. EC50 values from 32 hits ranged from 65 nM to 4.1 μM. Twenty-eight were evaluated in vivo in pharmacokinetic studies after a single 10 mg/kg oral or intraperitoneal dose in mice. Our results showed brain concentrations as high as 16.2 μM, but only after intraperitoneal dosing. Conclusions: Our studies identified leads for future studies to determine which compounds might lower PrPC levels in rodent brain, and provide the basis of a therapeutic for fatal disorders caused by PrP prions.Bioorganic & medicinal chemistry 03/2014; · 2.82 Impact Factor - [Show abstract] [Hide abstract]
ABSTRACT: Prions are proteins that acquire alternative conformations that become self-propagating. Transformation of proteins into prions is generally accompanied by an increase in β-sheet structure and a propensity to aggregate into oligomers. Some prions are beneficial and perform cellular functions, whereas others cause neurodegeneration. In mammals, more than a dozen proteins that become prions have been identified, and a similar number has been found in fungi. In both mammals and fungi, variations in the prion conformation encipher the biological properties of distinct prion strains. Increasing evidence argues that prions cause many neurodegenerative diseases (NDs), including Alzheimer's, Parkinson's, Creutzfeldt-Jakob, and Lou Gehrig's diseases, as well as the tauopathies. The majority of NDs are sporadic, and 10% to 20% are inherited. The late onset of heritable NDs, like their sporadic counterparts, may reflect the stochastic nature of prion formation; the pathogenesis of such illnesses seems to require prion accumulation to exceed some critical threshold before neurological dysfunction manifests.Annual Review of Genetics 11/2013; 47:601-23. · 18.12 Impact Factor - [Show abstract] [Hide abstract]
ABSTRACT: Prions are proteins that adopt alternative conformations, which become self-propagating. Increasing evidence argues that prions feature in the synucleinopathies that include Parkinson's disease, Lewy body dementia, and multiple system atrophy (MSA). Although TgM83(+/+) mice homozygous for a mutant A53T α-synuclein transgene begin developing CNS dysfunction spontaneously at ∼10 mo of age, uninoculated TgM83(+/-) mice (hemizygous for the transgene) remain healthy. To determine whether MSA brains contain α-synuclein prions, we inoculated the TgM83(+/-) mice with brain homogenates from two pathologically confirmed MSA cases. Inoculated TgM83(+/-) mice developed progressive signs of neurologic disease with an incubation period of ∼100 d, whereas the same mice inoculated with brain homogenates from spontaneously ill TgM83(+/+) mice developed neurologic dysfunction in ∼210 d. Brains of MSA-inoculated mice exhibited prominent astrocytic gliosis and microglial activation as well as widespread deposits of phosphorylated α-synuclein that were proteinase K sensitive, detergent insoluble, and formic acid extractable. Our results provide compelling evidence that α-synuclein aggregates formed in the brains of MSA patients are transmissible and, as such, are prions. The MSA prion represents a unique human pathogen that is lethal upon transmission to Tg mice and as such, is reminiscent of the prion causing kuru, which was transmitted to chimpanzees nearly 5 decades ago.Proceedings of the National Academy of Sciences 11/2013; · 9.81 Impact Factor - [Show abstract] [Hide abstract]
ABSTRACT: There is not a single pharmaceutical that halts or even slows any neurodegenerative disease. Mounting evidence shows that prions cause many neurodegenerative diseases, and arguably, scrapie and Creutzfeldt-Jakob disease prions represent the best therapeutic targets. We report here that the previously identified 2-aminothiazoles IND24 and IND81 doubled the survival times of scrapie-infected, wild-type mice. However, mice infected with Rocky Mountain Laboratory (RML) prions, a scrapie-derived strain, and treated with IND24 eventually exhibited neurological dysfunction and died. We serially passaged their brain homogenates in mice and cultured cells. We found that the prion strain isolated from IND24-treated mice, designated RML[IND24], emerged during a single passage in treated mice. Although RML prions infect both the N2a and CAD5 cell lines, RML[IND24] prions could only infect CAD5 cells. When passaged in CAD5 cells, the prions remained resistant to high concentrations of IND24. However, one passage of RML[IND24] prions in untreated mice restored susceptibility to IND24 in CAD5 cells. Although IND24 treatment extended the lives of mice propagating different prion strains, including RML, another scrapie-derived prion strain ME7, and chronic wasting disease, it was ineffective in slowing propagation of Creutzfeldt-Jakob disease prions in transgenic mice. Our studies demonstrate that prion strains can acquire resistance upon exposure to IND24 that is lost upon passage in mice in the absence of IND24. These data suggest that monotherapy can select for resistance, thus intermittent therapy with mixtures of antiprion compounds may be required to slow or stop neurodegeneration.Proceedings of the National Academy of Sciences 10/2013; · 9.81 Impact Factor - [Show abstract] [Hide abstract]
ABSTRACT: To determine whether oral quinacrine increases survival in sporadic Creutzfeldt-Jakob disease (sCJD). This NIH/National Institute on Aging-funded, double-blinded, placebo-controlled, stratified randomization treatment trial was conducted at the University of California, San Francisco from February 2005 through May 2009 (ClinicalTrials.gov, NCT00183092). Subjects were randomized (50:50) to quinacrine (300 mg daily) or placebo with inpatient evaluations at baseline, and planned for months 2, 6, and 12. Subjects returning for their month-2 visit were offered open-label quinacrine. The primary outcome was survival from randomization to month 2. Of 425 patients referred, 69 subjects enrolled, 54 subjects were randomized to active drug or placebo, and 51 subjects with sCJD were included in survival analyses. Survival for the randomized portion of the trial (first 2 months) showed no significant difference between the 2 groups (log-rank statistic, p = 0.43; Cox proportional relative hazard = 1.43, quinacrine compared with placebo, 95% confidence interval = 0.58, 3.53). The quinacrine-treated group, however, declined less on 2 of 3 functional scales, the modified Rankin and Clinical Dementia Rating, than the placebo group during the first 2 months. This interventional study provides Class I evidence that oral quinacrine at 300 mg per day does not improve 2-month survival of patients with sCJD, compared with placebo. Importantly, this study shows that double-blinded, placebo-controlled, randomized treatment trials are possible in prion disease. Furthermore, the quantitative data collected on the course of sCJD will be useful for future trials. This study provides Class I evidence that quinacrine does not improve survival for people with sCJD when given orally at a dose of 300 mg per day for 2 months.Neurology 10/2013; · 8.30 Impact Factor - [Show abstract] [Hide abstract]
ABSTRACT: During prion diseases, a normally benign, host protein, denoted PrP(C), undergoes alternative folding into the aberrant isoform, PrP(Sc). We used ELISA to identify and confirm hits in order to develop leads that reduce PrP(Sc) in prion-infected dividing and stationary-phase mouse neuroblastoma (ScN2a-cl3) cells. We tested 52,830 diverse small molecules in dividing cells and 49,430 in stationary-phase cells. This led to 3100 HTS and 970 single point confirmed (SPC) hits in dividing cells, 331 HTS and 55 confirmed SPC hits in stationary-phase cells as well as 36 confirmed SPC hits active in both. Fourteen chemical leads were identified from confirmed SPC hits in dividing cells and three in stationary-phase cells. From more than 682 compounds tested in concentration-effect relationships in dividing cells to determine potency (EC50), 102 had EC50 values between 1 and 10μM and 50 had EC50 values of <1μM; none affected cell viability. We observed an excellent correlation between EC50 values determined by ELISA and Western immunoblotting for 28 representative compounds in dividing cells (R(2)=0.75; p <0.0001). Of the 55 confirmed SPC hits in stationary-phase cells, 23 were piperazine, indole, or urea leads. The EC50 values of one indole in stationary-phase and dividing ScN2a-cl3 cells were 7.5 and 1.6μM, respectively. Unexpectedly, the number of hits in stationary-phase cells was ∼10% of that in dividing cells. The explanation for this difference remains to be determined.Bioorganic & medicinal chemistry 09/2013; · 2.82 Impact Factor - [Show abstract] [Hide abstract]
ABSTRACT: The only small-molecule compound demonstrated to substantially extend survival in prion-infected mice is a biaryl hydrazone termed "Compd B." However, the hydrazone moiety of Compd B results in toxic metabolites, making it a poor candidate for further drug development. We developed a pharmacophore model based on diverse antiprion compounds identified by high-throughput screening and based on this model, we generated biaryl amide analogs of Compd B. Medicinal chemistry optimization led to multiple compounds with increased potency, increased brain concentrations, and greater metabolic stability, indicating that they could be promising candidates for antiprion therapy. Replacing the pyridyl ring of Compd B with a phenyl group containing an electron-donating substituent increased potency, while adding an aryl group to the oxazole moiety increased metabolic stability. In addition, we applied bioluminescence imaging, previously shown to detect prion disease onset in live mice earlier than clinical signs, and demonstrated it was possible to predict drug efficacy in two lines of prion-infected transgenic mice expressing a luciferase reporter long before extension in survival could be measured.Journal of Pharmacology and Experimental Therapeutics 08/2013; 347(2). · 3.89 Impact Factor -
Dataset: jm101250y si 001
- [Show abstract] [Hide abstract]
ABSTRACT: The prion diseases caused by PrP(Sc), an alternatively folded form of the cellular prion protein (PrP(C)), are rapidly progressive, fatal, and untreatable neurodegenerative syndromes. We employed HTS ELISA assays to identify compounds that lower the level of PrP(Sc) in prion-infected mouse neuroblastoma (ScN2a-cl3) cells and identified a series of arylamides. SAR studies indicated that small amides with one aromatic, or heteroaromatic ring, on each side of the amide bond are of modest potency. Of note, benzamide (7), with an EC50 of 2200 nM, was one of only a few arylamide hits with a piperazine group on its aniline moiety. The basic piperazine nitrogen can be protonated at physiologic pH, improving solubility, and therefore we wanted to exploit this feature in our search for a drug candidate. An SAR campaign resulted in several key analogs, including a set with biaryl groups introduced on the carbonyl side for improved potency. Several of these biaryl analogs have submicromolar potency, with the most potent analog 17 having an EC50 = 22 nM. More importantly, 17 and several biarylamides (20, 24, 26, 27) were able to traverse the BBB and displayed excellent drug levels in the brains of mice following oral dosing. These biarylamides may represent good starting points for further lead optimization for the identification of potential drug candidates for the treatment of prion diseases.ACS Medicinal Chemistry Letters 07/2013; 4(7):647-650. · 3.07 Impact Factor - [Show abstract] [Hide abstract]
ABSTRACT: During prion disease, cellular prion protein (PrPC) is refolded into a pathogenic isoform (PrPSc) that accumulates in the central nervous system and causes neurodegeneration and death. We used immunofluorescence, quantitative cryo-immunogold EM, and tomography to detect nascent, full-length PrPSc in the hippocampus of prion-infected mice from early preclinical disease stages onward. Comparison of uninfected and infected brains showed that sites containing full-length PrPSc could be recognized in the neuropil by bright spots and streaks of immunofluorescence on semi-thin (200-nm) sections, and by clusters of cryo-immunogold EM labeling. PrPSc was found mainly on neuronal plasma membranes, most strikingly on membrane invaginations and sites of cell-to-cell contact, and was evident by 65 days postinoculation, or 54% of the incubation period to terminal disease. Both axons and dendrites in the neuropil were affected. We hypothesize that closely apposed plasma membranes provide a favorable environment for prion conversion and intercellular prion transfer. Only a small proportion of clustered PrP immunogold labeling was found at synapses, indicating that synapses are not targeted specifically in prion disease.Neurobiology of aging 06/2013; 34(6):1621-1631. · 5.94 Impact Factor -
Article: Discovery and Preliminary SAR of Arylpiperazines as Novel, Brainpenetrant Antiprion Compounds.
[Show abstract] [Hide abstract]
ABSTRACT: Prion diseases are a group of fatal neurodegenerative disorders that include Creutzfeldt-Jakob disease (CJD) and kuru in humans, BSE in cattle, and scrapie in sheep. Such illnesses are caused by the conversion and accumulation of a misfolded pathogenic isoform (termed PrP(Sc)) of a normally benign, host cellular protein, denoted PrP(C). We employed high-throughput screening (HTS) ELISAs to evaluate compounds for their ability to reduce the level of PrP(Sc) in Rocky Mountain Laboratory (RML) prion-infected mouse neuroblastoma cells (ScN2a-cl3). Arylpiperazines were among the active compounds identified but the initial hits suffered from low potency and poor drug-likeness. The best of those hits, such as 1, 7, 13, and 19, displayed moderate antiprion activity with EC50 values in the micromolar range. Key analogs were designed and synthesized based on the SAR, with analogs 41, 44, 46, and 47 found to have sub-micromolar potency. Analogs 41 and 44 were able to penetrate the blood-brain barrier (BBB) and achieved excellent drug concentrations in the brains of mice after oral dosing. These compounds represent good starting points for further lead optimization in our pursuit of potential drug candidates for the treatment of prion diseases.ACS Medicinal Chemistry Letters 04/2013; 4(4):397-401. · 3.07 Impact Factor -
Article: 2-Aminothiazoles with Improved Pharmacotherapeutic Properties for Treatment of Prion Disease.
[Show abstract] [Hide abstract]
ABSTRACT: Recently, we described the aminothiazole lead (4-biphenyl-4-ylthiazol-2-yl)-(6-methylpyridin-2-yl)-amine (1), which exhibits many desirable properties, including excellent stability in liver microsomes, oral bioavailability of ~40 %, and high exposure in the brains of mice. Despite its good pharmacokinetic properties, compound 1 exhibited only modest potency in mouse neuroblastoma cells overexpressing the disease-causing prion protein PrP(Sc) . Accordingly, we sought to identify analogues of 1 with improved antiprion potency in ScN2a-cl3 cells while retaining similar or superior properties. Herein we report the discovery of improved lead compounds such as (6-methylpyridin-2-yl)-[4-(4-pyridin-3-yl-phenyl)thiazol-2-yl]amine and cyclopropanecarboxylic acid (4-biphenylthiazol-2-yl)amide, which exhibit brain exposure/EC50 ratios at least tenfold greater than that of compound 1.ChemMedChem 03/2013; · 3.05 Impact Factor - [Show abstract] [Hide abstract]
ABSTRACT: Prion diseases are neurodegenerative disorders characterized by the aberrant folding of endogenous proteins into self-propagating pathogenic conformers. Prion disease can be initiated in animal models by inoculation with amyloid fibrils formed from bacterially derived recombinant prion protein. The synthetic prions that accumulated in infected organisms are structurally distinct from the amyloid preparations used to initiate their formation and change conformationally on repeated passage. To investigate the nature of synthetic prion transformation, we infected mice with a conformationally diverse set of amyloids and serially passaged the resulting prion strains. At each passage, we monitored changes in the biochemical and biological properties of the adapting strain. The physicochemical properties of each synthetic prion strain gradually changed on serial propagation until attaining a common adapted state with shared physicochemical characteristics. These results indicate that synthetic prions can assume multiple intermediate conformations before converging into one conformation optimized for in vivo propagation.American Journal Of Pathology 03/2013; 182(3):866-74. · 4.60 Impact Factor - [Show abstract] [Hide abstract]
ABSTRACT: PURPOSE: To discover drugs lowering PrP(Sc) in prion-infected cultured neuronal cells that achieve high concentrations in brain to test in mouse models of prion disease and then treat people with these fatal diseases. METHODS: We tested 2-AMT analogs for EC(50) and PK after a 40 mg/kg single dose and 40-210 mg/kg/day doses for 3 days. We calculated plasma and brain AUC, ratio of AUC/EC(50) after dosing. We reasoned that compounds with high AUC/EC(50) ratios should be good candidates going forward. RESULTS: We evaluated 27 2-AMTs in single-dose and 10 in 3-day PK studies, of which IND24 and IND81 were selected for testing in mouse models of prion disease. They had high concentrations in brain after oral dosing. Absolute bioavailability ranged from 27-40%. AUC/EC(50) ratios after 3 days were >100 (total) and 48-113 (unbound). Stability in liver microsomes ranged from 30->60 min. Ring hydroxylated metabolites were observed in microsomes. Neither was a substrate for the MDR1 transporter. CONCLUSIONS: IND24 and IND81 are active in vitro and show high AUC/EC(50) ratios (total and unbound) in plasma and brain. These will be evaluated in mouse models of prion disease.Pharmaceutical Research 02/2013; · 4.74 Impact Factor -
Article: Genetics Without Genes
Publication Stats
51k | Citations | |
4,811.72 | Total Impact Points | |
Top Journals
University of California, San Francisco
- • Institute for Neurodegenerative Diseases
- • Department of Neurology
- • Department of Biochemistry and Biophysics
- • Division of Hospital Medicine
San Francisco, California, United States
Netherlands Cancer Institute
- Division of Cell Biology II
Amsterdam, North Holland, Netherlands -
University of Delaware
- Department of Chemical and Biomolecular Engineering
Newark, DE, United States
Mount Sinai School of Medicine
- Department of Neurology
Manhattan, NY, United States
Heinrich-Heine-Universität Düsseldorf
- Institute of Physical Biology
Düsseldorf, North Rhine-Westphalia, Germany
European Commission - Joint Research Centre
- Institute for Reference Materials and Measurements
Brussels, BRU, Belgium -
Kungliga Vetenskapsakademien
Tukholma, Stockholm, Sweden
University of Maryland, Baltimore
Baltimore, Maryland, United States -
University of Toronto
Toronto, Ontario, Canada
Gifu University
- School of Medicine
Gihu, Gifu, Japan
University of Oxford
- Department of Biochemistry
Oxford, ENG, United Kingdom -
Cold Spring Harbor Laboratory
Cold Spring Harbor, New York, United States
Molecular and Cellular Biology Program
Seattle, Washington, United States
McLaughlin Research Institute
Great Falls, Montana, United States
The Scripps Research Institute
- Department of Cell and Molecular Biology
La Jolla, CA, United States
University of California, Berkeley
- School of Public Health
Berkeley, California, United States -
San Diego Zoo
San Diego, California, United States
CSU Mentor
Long Beach, California, United States
Hadassah Medical Center
- Department of Neurology
Jerusalem, Jerusalem District, Israel -
University of Washington Seattle
- Department of Pathology
Seattle, WA, United States
Concordia University–Ann Arbor
Ann Arbor, Michigan, United States
The Jackson Laboratory
Bar Harbor, Maine, United States
Orlando Health
Orlando, Florida, United States
National Institute of Allergy and Infectious Diseases
Maryland, United States
Howard Hughes Medical Institute
Ashburn, Virginia, United States


text:
- Home
- Working with Chocolate
- Brazilian Chocolate
Brazilian Chocolate
Chocolate Diversity
Brazil offers a diverse range of cacao varieties and is one of the cradles of all cacao trees and hybrids. In fact when you look at all the hybrid types and flavors offered in Brazilian cacao you can find 140+ types.
Brazilian Chocolate Flavor Profile
Brazilian cacao has a strong flavor, so normally you will find Brazilian cacao used with other cacao types to create unique flavor profiles in chocolate. Brazilian cacao can have strong fruity, earthy or wet flavors. If one chooses the correct type of Brazilian cacao, it can offer a wonderful flavor that is truly unique and very uplifting. The predominate locations for Brazilian cacao production are Manaus North Central Amazon and Bahia Eastern Coastal.
Great Brazilian Selection
"Brazilian Bittersweet Dark Chocolate Chunk represents some of the best South American chocolate for baking."
-Master Chocolatier

subset: commoncrawl


text:
See items selected especially for you. Shop recommendations.
Exclusive finds with a new theme each month.
Shop: Pop-In
Our director of creative projects shares what she's into.
Read More
Stay updated with a steady stream of new info.
A cool mix of colors defines a classic sneaker detailed with a retro double-tongue.
Watch the video: Kids' Shoes Fit Fundamentals


text:
US 5273309 A Abstract The air bag assembly, including the inflator and the stored air bag are mounted on the vehicle pillar adjacent the front seat back. Upon deployment, the air bag unfurls from a housing mounted on the pillar and extends along the door between the end of the seat and the door. The air bag assembly can include either an air bag which unfurls forwardly for the front seat occupant, or which unfurls rearwardly for the rear seat occupant, or air bags for both the front and rear occupants. The air bags maybe inflated by a single inflator, or separate inflators may be provided for the front and the rear seats. A sensor may be mounted on either the door or the pillar to provide an input signal to the air bag actuating electrical circuit.
Claims(3) 1. In combination, a motor vehicle having a passenger compartment accessible through front and rear doors, a first pillar to which a front door is hingedly mounted, a second pillar located rearward of the first pillar and to which the front door is latched in a closed position and to which the rear door is hingedly mounted, said second pillar being provided with inner and outer panels, an occupant front seat adjacent the front door and an occupant rear seat adjacent the rear door, an air bag assembly including an inflator mounted on the inner panel of the second pillar for inflating a first air bag facing forward and a second air bag facing rearward, a plastic molding mounted on the inner panel of the second pillar to conceal the air bag assembly and having a first door facing forward and a second door facing rearward, said inflator being actuable to unfurl the first air bag to an inflated position extending through the front door between the front seat occupant and the front door, as permitted by opening of the first door of the plastic molding and unfurl the second air bag to an inflated position extending along the rear door between the rear seat occupant and the rear door as permitted by opening of the second door of the plastic molding.
2. The combination of claim 1 further characterized by the first air bag and the second air bag being inflatable by a common gas generator.
3. The combination of claim 1 further characterized by the first air bag and the second air bag having separate gas generators so that either the first air bag or the second air bag may be actuated independently of the other.
Description The invention relates to a vehicle air bag and more particularly an air bag mounted on the pillar to which the door is latched and having an air bag which deploys into the space between the seated occupant and the door. It is well known in motor vehicles to provide an air bag deployed by a gas generator to cushion an occupant. The prior art has recognized that such an air bag may be mounted on a vehicle door to provide such cushioning in a side impact situation. It would be desirable to provide a side air bag without necessitating the direct mounting of the air bag on the vehicle door where interference may result with door handles, window handles, and arm rests. According to the present invention, the air bag assembly, including the inflator housing and the stored air bag are mounted on the vehicle pillar adjacent the front seat back. Upon deployment, the air bag unfurls from the housing mounted on the pillar and extends along the door between the end of the seat and the door. The air bag assembly may include an air bag for the front seat, an air bag for the rear seat, or air bags for both the front and rear seats. The front and rear air bags maybe inflated by a single inflator or separate inflators may be provided for the front and the rear seats. A sensor may be mounted on either the door or the pillar to provide an input signal to the air bag actuating electronic control circuit. FIG. 1 is a side elevation view of a vehicle according to the invention and having the front and rear doors partially broken away to show the front and rear seat air bags in the deployed condition; FIG. 2 is a section view taken in the direction of arrows 2--2 of FIG. 1 showing the mounting of the air bag assembly on the pillar; FIG. 3 is an engaged plan view of a typical inflator having front and rear seat air bags shown in the stored condition and a single inflator for inflating both the air bags; FIG. 4 is a view similar to FIG. 3 but showing the air bags inflated; and FIG. 5 is a elevation view of the air bag assembly having separate inflators for the front and rear air bags showing one air bag stored and the other inflated. Referring to FIG. 1 it is seen that a conventional motor vehicle 10 includes a front seat 12 accessible through a front door 14, and a rear seat 16 accessible through a rear door 18. The front door 14 is conventionally hinged on a front pillar 20 of the vehicle and latched to a second pillar 22 of the vehicle. The rear door 18 is hingedly mounted on the second pillar 22 and is latched to the rearmost pillar 24 of the vehicle body. The front door 14 carries a side panel 25 located adjacent the front seats 12 and the rear door 18 carries a side panel 27 located adjacent the rear sear 16. As best seen in FIGS. 1 and 2, the pillar 22 is comprised of an outer panel 24 and an inner panel 26 which are suitably welded or otherwise connected together in spaced apart relation. The outer panel 24 may be an outside panel of the motor vehicle body, or may alternatively be concealed behind the edges of the doors 14 and 18. As seen in FIGS. 2 and 3, an air bag assembly 30 is mounted on the inner panel 26 by nut and bolt assemblies 32. The pillar 22 and air bag assembly 30 are concealed by plastic molding 34. FIG. 3 shows a typical air bag assembly 30 which includes an inflator 38, front seat air bag 40 and a rear seat air bag 42. The air bags 40 and 42 are rolled to a stored condition and respectively concealed behind break away doors 43 and 45 of the plastic molding which conceals the air bag from view. The doors 43 and 45 are molded integrally into the plastic molding and defined by a series of weakening indentations 47 molded into the plastic molding 34 to promote tearing of the plastic and a hinge indentation 49 which enables the doors to hinge open. A control wire 44 is connected to the inflator 38 and extends to suitable electronic control circuitry for initiating the actuation of the air bag. The electronic control circuitry preferably includes a sensor 46 shown in FIG. 2 mounted on the pillar 22. Referring to FIGS. 1 and 4, it is seen that the actuation of the air bag assembly 30 by the electronic control circuitry will cause the inflator 38 to generator inflation gas which unfurls the front occupant bag 40 and the rear occupant bag 42 to their deployed positions of FIG. 1 in which the air bags extend between the seated occupants and the adjacent vehicle door. Each air bag 40 and 42 has a vent hole 46 at the end thereof to control the pressure within the bag. FIG. 5 shows an alternative arrangement of the air bag assembly in which the front air bag 40 has an inflator 48 with control wire 52 and the rear air bag 42 has a separate inflator 50 with a control wire 54. The control wires 52 and 54 are preferably connected with separate electronic control circuitry which will actuate the front air bag 40 if an occupant is seated in the front seat 12 and separately actuates the rear seat bag 42 if an occupant is present on the rear seat 16. It will be understood that although FIG. 1 shows a air bag of relatively long narrow shape, other air bag shapes may be employed within the ordinary skill of the art in order to obtain the desired results. Although the vehicle of FIG. 1 is shown as a four-door vehicle having front and rear doors, it will be understood that the invention is equally applicable to a coupe vehicle having only front doors, and in which case the pillar mounted air bag for the rear seat will deploy along the side panel of the vehicle body. It will also be appreciated that although the air bag shown in the drawings includes both a front occupant air bag and a rear occupant air bag, the pillar mounted air bag assembly can include only one air bag. In the preferred embodiment of FIG. 1 the air bag assembly is mounted on the pillar at an elevation just vertically below the side windows. However, it is understood that the air bag assembly may be mounted higher or lower as desired. Thus it is seen that the invention provides a new and improved side impact air bag for a motor vehicle in which the air bag assembly is mounted on the pillar between the front and rear seats. Patent Citations
Referenced by
Legal Events
Rotate |


text:
Write a review and win a £250 Amazon.co.uk gift certificate!
All you have to do is submit a review of a campsite or holiday park you have visited to be in with a chance to win. Find out more
Site name | Location | Date stayed | Date reviewed | Booked on Pitchup.com | Summary |
Church Stile Farm Holiday Park | Cumbria, North West England | Jul 2013 | Jul 2013 | Confirmed | Review regarding The Shepards Hut |


text:
This Register does not include everything everyone wants to know about the 1853 to 1861 No Arrows New Orleans Branch Mint Liberty Seated Half Dollars. Specifically, little information is included on condition census and there is no pricing information. Alternatively, Bugert has included estimated rarity ratings. The detailed die marriage data and accompanying photographs will allow the collector of this series to attribute die marriages, identify potentially new die marriages, and help detect counterfeits. Finally, the last few pages include a checklist of O-Mint die marriages for the collector working on a full die marriage collection.
Binding: Spiral Bound Paperback
Edition: 1st Edition
Publication Date: January 2014
Size: 8.5x11
Pages: 508
Customers Also Bought
Heavy Duty Single Row Slab/Crown Box |
The Official Red Book: A Guide Book of United States Coins 2015 |
Meghrig Soft Vinyl 2x2 Coin Flips -- Box of 1000 |
Inserts For Two Pocket Flips - 2x2 |


text: Taotribe via Amazon offers the Doosl Bluetooth Receiver in Silver or Black, model no. DSER101, for $29.99. Coupon code "JMK5F7KC" cuts the price to $21.99. Plus, Prime members qualify for free shipping. (Non-members can spend $35 to qualify for free shipping; otherwise, it adds $6.07.) That's $28 off list and the lowest total price we could find. Features include automatic call-back, built-in charger, and a range of 30 feet.


text:
Photograph by Mike Theiss, National Geographic
Published May 19, 2011
As many as six major hurricanes could form in the Atlantic Basin during a busy 2011 summer storm season, forecasters announced today.
Twelve to 18 named tropical storms with winds of at least 39 miles (63 kilometers) an hour could form in the Atlantic Basin, which includes the Gulf of Mexico and the Caribbean Sea, according to National Oceanic and Atmospheric Administration (NOAA) head Jane Lubchenco.
Six to ten of those named storms could intensify into hurricanes—meaning they'd have winds of at least 74 miles (119 kilometers) an hour, Lubchenco said during a press briefing.
And three to six of the hurricanes could develop winds exceeding 110 miles (177 kilometers) an hour, which would make the storms major hurricanes. The Atlantic hurricane season runs from June 1 to November 30.
(Watch hurricane videos.)
Warm Waters, La Niña Foretell Busy Hurricane Season
The busy hurricane forecast is based on several factors, such as Atlantic water temperatures that are about 2 degrees Fahrenheit (1.1 degrees Celsius) above normal.
Hurricanes draw their strength from ocean waters that have been warmed to at least 80 degrees Fahrenheit (27 degrees Celsius).
Another variable is a weather phenomenon known as La Niña, which exists when waters in the central and eastern tropical Pacific Ocean are cooler than normal. This condition diminishes upper-level winds over the Atlantic, which often disrupt hurricane formation during the summer.
(Read about a possible link between La Niña and April's monster tornado in Alabama.)
U.S. Not So Lucky This Year?
Overall NOAA and emergency-management officials are concerned that U.S. East and Gulf Coast residents may have been lulled into a false sense of security during the 2010 hurricane season.
Although 2010 was the third most active hurricane season on record, with 19 named storms, no hurricanes made landfall in the U.S.
"The U.S. was lucky last year," Lubchenco said. "We cannot count on the same luck this year."
The NOAA forecast for an active hurricane season followed a similar prediction from Colorado State University meteorologists.
In April, CSU forecasters Phil Klotzbach and William Gray had predicted 16 named storms, 9 hurricanes, and 5 major hurricanes.
Popular Stories
Finding Homes for Children Orphaned by Ebola
More than ten thousand West African children have lost one or both parents to Ebola. Now the search begins to find them new homes.
Tiny Frogs Contain Big Evolutionary Surprise
Recent DNA testing has revealed that the Philippine limestone frogs are actually more closely related to tree and ground frogs on their own islands than they are to each other.
Beautiful Antique Photos—From Potato Starch
Almost 30 years before Kodachrome, two French brothers invented a way to take color photos.
The Future of Food
Why Food Matters
How do we feed nine billion people by 2050, and how do we do so sustainably?
Download: Free iPad App
We've made our magazine's best stories about the future of food available in a free iPad app.


text:
Movies On-Demand
Current Filter: Mohanlal
Drishyam Malayalam Movie Online
- Mohanlal, Meena, Ansiba Hassan, Baby Esther, Kalabhavan Shajon, Asha Sarath and Siddique. Directed by Jeethu Joseph. Music by Anil Johnson. 2013 Drishyam Malayalam Movie Online.
Posted Jun 05 2014 @ 02:11 am
Drishyam @ Wikipedia86ratings.
Red Wine Malayalam Movie Online
- Mohanlal, Fahad Fazil, Asif Ali, Saiju Kurup, Jayaprakash, Mia and Meghana Raj. Directed by Salam Bappu. Music by Bijibal. 2013 Red Wine Malayalam Movie Online.
Posted Jan 02 2014 @ 04:43 pm
Red Wine @ Wikipedia15ratings.
Mr. Fraud Malayalam Movie Online
- Mohanlal, Dev Gill, Vijay Babu, Mia George, Manjari Phadnis and Pallavi Purohit. Directed by B. Unnikrishnan. Music by Gopi Sunder. 2014 Mr. Fraud Malayalam Movie Online.
Posted Aug 29 2014 @ 01:38 am
Mr. Fraud @ Wikipedia14ratings.
Lokpal Malayalam Movie Online
- Mohanlal, Kavya Madhavan and Meera Nandan. Directed by Joshiy. Music by Ratheesh Vegha. 2013 Lokpal Malayalam Movie Online.
Posted Jul 07 2013 @ 01:58 pm
Lokpal @ Wikipedia10ratings.
Oru Naal Varum Malayalam Movie Online
- Mohanlal, Sreenivasan and Sameera Reddy. Directed by T. K. Rajeev Kumar. Music by M. G. Sreekumar. 2010 Oru Naal Varum Malayalam Movie Online.
Posted Mar 25 2013 @ 07:02 pm
Oru Naal Varum @ Wikipedia15ratings.
Shikkar Malayalam Movie Online
- Mohanlal, Samuthirakani, Ananya and Sneha. Directed by M. Padmakumar. Music by M. Jayachandran. 2010 Shikkar Malayalam Movie Online.
Posted Sep 16 2013 @ 11:35 pm
Shikkar @ Wikipedia7ratings.


text:
Azarenka into 3rd round in Qatar; Stephens out
Updated: February 13, 2013, 3:42 PM ET
Associated Press
DOHA, Qatar -- Fresh off winning a second consecutive Australian Open, top-ranked Victoria Azarenka breezed into the third round of the Qatar Open with a 6-2, 6-3 victory over Romina Oprandi on Wednesday.
The defending champion was joined by fourth-ranked Agnieszka Radwanska and Caroline Wozniacki. Radwanska beat Australian qualifier Anastasia Rodionova 6-3, 6-2, and Wozniacki downed Sorana Cirstea of Romania 7-6 (7), 6-0.
American Sloane Stephens, who upset Serena Williams in the ...
Read full story
You must be signed in to post a comment
You are fully responsible for the content you post. Content that includes profanity, personal attacks or antisocial behavior (such as "spamming" or "trolling"), or other inappropriate content or material will be removed. We reserve the right to block any user who violates our terms of use, including removing all content posted by that user.


text:
Results: 471 - 480 of 585
News + Politics
Blowing Smoke: A History of Tobacco and U.S. Politicians
President Obama and John Boehner, the newly elected Speaker of the House, don't share much in common--except maybe a Zippo read more
January 19, 2011
News + Politics
Welcome to Congress!
A complete guide to the "Take America Back" class of 2010 read more
January 2011
Symbol of the Year: #
Hashtags on Twitter have changed the way we think, communicate, process information. # for president! read more
December 13, 2010
- Tags:
- Entertainment,
- Humor,
- Year in Culture,
The Year in Wang
Yet again--seven centuries and counting!--it was the male body part of the year. But in 2010, the penis truly blew up: junk as far as the eye could see. An exhaustive list of sightings read more
December 13, 2010
- Tags:
- Entertainment,
- Humor,
- Year in Culture,
News + Politics
The Gravest Show on Earth
American politics have always been a freakish spectacle. But 2010 was the year when the circus didn't just come to townit took over the whole darn country read more
December 2010
5 Commandments of Flying
Workplace Maverick Steven Slater offers suggestions for how not to act like an ass in the skies read more
December 2010
- Tags:
- Humor,
- News,
- Steven Slater,
- JetBlue
The 50 Worst States in America
American States, like Americans themselves, are fond of trumpeting their superlatives. To hear them tell it, they're all first in something: Corn growth, coal production, giant-est giant-ball-of-twine, blah, blah, blah. But something's not adding up, States: If you're all so great, how come the country's giving off the distinct odor of failure? read more
December 02, 2010
- Tags:
- Humor,
- Worst States,
- America
News + Politics
An Open Letter to the Tea Party Candidates
Congratulations on taking the country back! Yeah, we know, it's not official yet. But that's a mere technicality, like the Sixteenth and Seventeenth Amendments. read more
November 2010
Scary Sex: Your Halloween Hook-Up Guide
What does a woman's costume say about how she is in bed? From Snooki's fetishes to Gaga's turn-ons, everything you need to know about the 15 women you could bring home this weekend read more
October 28, 2010
News + Politics
The Year in Fearmongering
In midterm elections, the best way to get people out to vote is to scare them to death. As ever, a handful of republicans raised it to an artform read more
October 28, 2010
- Tags:
- Politics,
- Humor,
- Ana Marie Cox
Results: 471 - 480 of 585
News + Politics
How To
Food + Travel
- David Chang's Kitchen: Don't Get All "Fresh" with Me
- David Chang's Kitchen: Your Idea of Bologna is Total Baloney
- Chart: The Family Tree of Bourbon Whiskey
- Recipe: Semi-Summer Salad - Chef Jeff Taibe of Oak + Almond
- The Great Franco-Italian Pasta Experiment
- How to Pick from an Overpriced Restaurant Wine List


text:
Brand Skagen
Style 981XLGLD
Style Casual
Gender Men's
Strap Width 20 mm
Case Brushed and polished gold tone ion plated stainless steel
Dial Color White
Hands Gold tone and luminous hour and minute. Gold tone second
Markers Gold tone Arabic numeral at 12:00. White and gold tone indices
Clasp Type Buckle
Strap Color Brown
Strap Material Genuine Leather
Case Shape Round
Weight 48g
Movement Swiss quartz
Crystal Mineral
Case Diameter 39 mm
Case Thickness 9 mm
Water Resistant 3 ATM/30 meters/99 feet
Calendar Date display at 3:00
Strap Length Up to 8.75 inches
Case Back Screw-down ion plated stainless steel
Crown Push/Pull
Material Genuine Leather
Your {{bm.networkName}} URL:
Commission for this product: 5% Commission
Shop Features
- Today's Daily Deals
- Otterbox Cases - Up to 75% Off
- Best Selling Intimates
- $12.99 Tennis Bracelets
- Mac: Microsoft Software Sale
- St. Patrick's Day Savings
- Plus Size Solid Dolman Tops
- White Mark Fit n' Flare Dress
- Lighten Your Load
- Monogrammed Initial Pendants
- iPads, iPhones & Macs
- Eternity Fashion Bangles
- Eco-Friendly Pet Beds
- School Spirit Sale
- A Good Pun is its Own Reword
- Light it up: Top Flashlights
- Robert Matthew Handbags
- Egyptian Comfort Luxury Sheets
- Plus Size Palazzo Pants
- Board Game Blowout
- Find Your Zen
- Neoprene Face Mask Event
- FMD by Fossil Watches
- Wilson & New Balance Clearance
- Fragrance Blowout Event
- Travel
- iPhone/iPad Accessories
- Garden & Outdoors
- Bed & Bath
- Speakers & Headphones
Skagen Men's White Dial Brown Genuine Leather
A fashionable addition to any wardrobe
Original Price:
Free Shipping!
Questions? We're Here to Help!
Our awesome customer service department is ready for your questions! Although we are a small company (22 of us total), we will do everything we can to answer your questions and take care of any problems.


text:
Clé de Peau Beauté
Satin Eye Color - 119
Product Actions
Satin Eye Color is a luxuriously smooth powder eye shadow accentuates eyes with brilliant, sumptuous color.
Available in 119
Style # 502938341
Available in 119
Style # 502938341
Need Help? Have Questions? Contact Us.
Please call 1.888.222.7639 to speak with a Customer Service Representative.
We're here to help you:
Monday - Friday, 9 AM - 9 PM (ET)
Saturday - Sunday, 11:30 AM - 8 PM (ET)
If you prefer email, we can be reached anytime at firstname.lastname@example.com.
Our Shipping & Returns Policy can be viewed here.


text:
Electrosonic Helps âBeyond All Boundariesâ? Deliver Unique Theatrical Experience at Expanded National World War II Museum
Visitors to the National World War II Museum in New Orleans are moved and excited by its unique new immersive film attraction, "Beyond All Boundaries," which not only tells the story of the "war that changed the world" but also breaks boundaries of its own in 4D cinema experiences. Electrosonic was responsible for the design and integration of the Audio Visual and show control system for what Tom Brokaw called "the most significant cinematic piece on World War II."
A large-scale immersive production that harnesses 21st century technology, "Beyond All Boundaries" plunges viewers into the Greatest Generation's journey from Pearl Harbor into the heat of battle to the final victory of D-Day. It premiered November 6 in the 250-seat Solomon Victory Theater, part of the museum's recent $300 million expansion.
Tom Hanks narrates (and executive produced) the 35-minute "Beyond All Boundaries" which features Brad Pitt, Kevin Bacon, Patricia Clarkson, Gary Sinise and other A-list actors voicing Americans on the front lines and homefront. As part of the 4D experience, the theater's seats shake from rumbling tanks, it snows during The Battle of the Bulge, and the nose of B-52 bomber set piece flies in front of the screen during a bombing raid as its wings are projected around it. The production plays to audiences eight times a day.
The Hettema Group was responsible for the concept, design and production and called in Electrosonic to consult on AV design for its debut production, "Beyond All Boundaries." Phil Hettema, president of The Hettema Group and a former senior vice president of attraction development for Universal Studios, served as show producer and creative director. Mousetrappe, Inc. furnished media design and productionwith Doug Yellen as producer and Darin Ulmer as production and media designer
"Beyond All Boundaries" is projected onto a 115 x 28-foot curved scrim, or transparent gauze, screen with three Christie Roadster S+20K DLP(tm) projectors edge blending the images to create the compelling wartime visuals. "The main criterion was to create a very large projection experience that would encompass audio, moving scenery and layered effects," says Jane Hall, manager of Electrosonic's Design Consulting Group.
In front of the scrim is a pit from which artifacts – a giant radio set, a concentration camp watch tower, the gun turret of a warship – emerge at appropriate moments in the show. Behind the scrim various objects, such as tank traps, can be illuminated, and another giant projection screen is set back about 20 feet from the main scrim. This configuration creates truly dimensional, complex images with visuals projected onto the scrim bleeding through to the set pieces and second screen. Sequences depicting the fire bombing of Dresden, Asian jungles and the bombing of Japan are especially powerful with the double-screen arrangement which can be augmented with lighting and smoke effects.
Electrosonic did a mock up with a single projector to determine the best scrim material to use, Hall explains. "When only a front image needs to be seen, a black velour curtain is dropped behind the scrim to make it opaque," she points out. Electrosonic also spent a lot of time working with 3D computer models of the theater, reports project manager Steve Calver. "We needed to see how everything would fit and be positioned in the theater, how the projectors would be out of the sight of the audience and out of the way of other props yet be easily accessible for maintenance and retain their signal integrity and network connectivity."
The main screen projectors were installed on a custom projection mount in the ceiling of the projection booth and aligned to achieve a single focal point so edge blending could be resolved on different surfaces. "That's very different from typical edge blending," Calver notes.
Five Christie DS+10KM projectors are used to create edge-butted images for the second concentric screen 20ft upstage of the primary scrim. A Christie Roadster HD10K-M, mounted at back of house, projects onto three small panels that rise up out of the pit in front of the scrim providing captions and other supporting images for the main screen.
For the six-minute preshow which sets the stage with a look at life in prewar America, all of the plasma monitors are driven by eight Electrosonic MS9500GL MPEG2 HD video players. "Beyond All Boundaries" is sourced from five Electrosonic ES9600 dual-channel JPEG-2000 players that provide 10 channels of 24p HD. Overall show control is supplied by a Medialon running Show Manager V5. with integrated AMX touch panels for GUI based operation and maintenance access. .
"John Bush, our Medialon programmer, worked three months programming the system on site to make sure everything performed as a perfectly timed, integrated system," says Calver. "In the end there were over 1100 Medialon tasks that coordinated communications and timing between show control and the various subsystems for moving sets, special effects, lighting, audio and video. That took a lot of testing and adjusting to accomplish."
An extensive audio system was also required to reinforce wartime sound effects and an original musical score by Hollywood composer Bruce Broughton. Electrosonic hired SoundWorks System Integrators, a local professional integrator in New Orleans to help build, install, and commission this very dynamic sound system. The Electrosonic-designed system features a digital Peavey Nion-6 digital signal processors, QSC amps and Renkus Heinz PNX series speakers.
"Beyond All Boundaries" is "a real theatrical production in a large-scale sense," Calver emphasizes. "It's amazingly well done, the kind of show you'd expect to see at a leading theme park."
At Electrosonic Linda Danet was the sales consultant, Mike Dwyre was site supervisor, Tom Brighton handled the video encoding for the preshow and film and supported all the onsite video editing and mixing, John Groper and Stan Gilson were engineers, and John Notarnicola and Nir Elnekave were projectionists. Andy Batwinas from the Design Consulting Group worked with The Hettema Group on early conceptual design and design parameters.
Nick Mueller, President of the museum, developed the concept to create an immersive theatrical experience for the museum. Bob Farnsworth was project Director for the museum.
Electsosonic worked with a variety of specialty contractors including Elliott Metal Fabrication for the custom design and fabrication of the projection mounts, Visual Terrain who provided lighting design, LA Propoint and Rando Production who provided all mechanical and special effects, and Technical Supervision was provided by It's Alive Co. New Orleans-based SoundWorks fabricated audio racks and handled the audio installation.
About Electrosonic
Electrosonic is an international audio-visual company with a strong reputation for working on complex projects, both large and small, and has through its 45 year history developed lasting partnerships with customers and suppliers. Electrosonic brings a unique breadth of experience to each project; backed by solid engineering skills, project management and quality production facilities. Beyond complete integrated systems, Electrosonic can provide a wide range of services including consultancy, technical design, maintenance and operational support.
Learn more about Electrosonic. Visit http://www.electrosonic.com
Metric Halo Supports SCA Spring Fling
Sergio Mendes and will.i.am have a (Governors) Ball with DPA Microphones
StrandVision Offers Personal Finance Tips in Latest Set of Employee Digital Signage Communications Animated Templates
Ashly Saves the Day at Rocky Mountain Classical Academy
StoreStreams to Offer Turnkey In-Store Radio to Businesses
Audinate Announces âAudio over IP in Broadcast with Danteâ Event in London
Renkus-Heinz Helps Conquer Audio Challenges in Canadian Museum for Human Rights
Additional Danley Speakers Handle Seating Expansion at Life Pentecostal Church
Landmark Manhattan Center Studios Upgrades To Dual Yamaha CL5 Digital Audio Consoles


text:
Tech Helproom
It's free to register, to post a question or to start / join a discussion
Which desktop to buy ?
Likes # 0
Posted May 10, 2010 at 4:08PM
I run a small business and use my current PC (Acer Aspire) for large parts of the day. I don't tend to do anything too fancy; the majority of what I do is based on Office, or doing work online and of course sending and receiving emails. I tend to be online much of the day.
Sadly, my Acer is slowing down significantly and I feel it is time to buy a new PC.
I bought the July 2010 edition of PC Adviser as it had the Best Buys in the sub £500 category, which I reckoned was where I wanted to be. I confess I hadn't heard of the companies which came top (Eclipse, Chillblast) and usually prefer to deal with better known brands. There also seemed quite a lot of stuff about graphics cards and I don't do gaming, so wondered whether I wasn't really their market. In addition, I got the impression they are perhaps aimed at an enthusiast, which I'm not. I just need the PC for various office functions.
I feel I need a decent sized hard disk (My Acers is only 115GB, so probably anything will be better than that) and a good amount of RAM ( Acer has 480MB only). I don't particularly need a new monitor, but may have if its included at a reasonable price. A DVD RW (is that type of thing standard now ?) would be good, plus lots of USB ports.
What do you think I should buy ? Wouldn't really want to spend over £500.
Likes # 0
Posted May 10, 2010 at 7:06PM
How about a Dell?
click here
To see an Inspiron 570 - it's right up your street in terms of specification. It comes without a monitor, but if your current monitor was purchased at the same time as your computer it may be time to think about a new flat panel if the budget would stretch to it.
My recommendation is that you build yourself a machine on the Dell site, and see how it goes - it's an easy process, you can add/remove things until you're comfortable with the cost.
Good luck - feel free to ask for further help and/or advise if you need it.
Reply to this topic
This thread has been locked.
Check out PC Advisor's other tech forums
Top 5 Most Popular
HP Spectre x360 review: Hands-on with the MacBook Air and Lenovo Yoga 3 Pro rival
19 best new phones you should be most excited about in 2015: best new phones coming from Apple, Samsung, Sony, HTC, LG, Xiaomi and others
Sony Xperia Z3 vs Sony Xperia Z4 comparison: What's new in Sony's latest Z-series flagship?
21 best antivirus for PC and laptop UK: 2015's best antivirus for protection, performance value, and best free antivirus
Fitbit Charge HR review: the fitness tracker with an always-on heart-rate monitor


text:
Your phone will know where you are — even if you don't. Get driving directions, detailed maps, traffic alerts (on select phones) and one-click rerouting.
iPhone 4S on 3G data network too slow to be useful
No more frustration now,eft sprint a couple of weeks ago and the iphone family as well! CRICKET 4g LTE is my new family and not only am I getting > ...beeay , Regular Visitor
has this outage been fixed? I never recieved the old texts that I should have recieved last night.Customer Service (Updated Mar 3, 2015)


text:
At All German Auto, we strive to restore, enhance, and optimize the performance of your German car in order to provide you with the outmost and satisfactory potential of your car.
We appreciate the feedback of our customers and we will do anything in our power to keep our customers satisfied with our service.
I took my 2011 X5 with an N63 engine to All German Auto to get the valve guide seals fixed. They were able to complete the job at a fraction of the cost of the dealer, by using their custom in house designed N63 Valve Stem Seal Tool. My BMW was smoking quite a bit before the repair. I was adding a quart of oil every 500 miles and have now driven 2300 miles without having to add any engine oil so far. Great customer service! They know what they are doing and they are truly German car specialists.
One of the best decisions I made was to continue service for my VW Bug at All German Auto. The previous owner always used All German so I figured why change anything. My car is 14 years old. I was in today for a battery and with All German's help I plan to keep my car as long as I can. Troy gets my car to the mechanic as soon as I get there and everyone is really so professional!
Wow! I live in Austin and emailed Martin about my E66 compressor plug issue. Not only did he reply, but he found/sent me the required compressor plug UPS FREE OF CHARGE!! The part arrived and the car is working perfectly. Martin even took the time today to follow up and make sure my problem was solved. Customer Service/Attention to Detail.... Thank You Martin!!
Dinan package is great, couldn't believe the difference from stock - really happy with attention to detail and performance/handling.
I've been a truck mechanic for 30+ years. I'm hesitant on taking my car to a shop because I now first hand there are many hit & miss part changers out there but few first rate diagnosticians working on vehicles. These BMWs require the attention of a first rate diagnostic tech and I feel more then confident on the abilities of the All German Auto team. They repaired my car at a reasonable cost and returned it cleaner then I dropped it off. The shop is very clean, well organized and well equipped with the tools necessary to repair these highly engineered German vehicles.
Absolutely great service on my 745. From the moment I called to getting the car back completely ready for what I needed, I knew I was in good hands. Martin, and the rest of the AGA team, really exceeded my expectations and have earned a lifelong customer. Thanks AGA!
Anthony Howard is the Man! He was a great help in selling my Land Cruiser and getting me into my new Lexus GX 470. Anthony is refreshing to deal with in this tough auto business! He is professional, thorough, patient and honest. He gained my trust from the start. He was prompt at returning my calls, had answers to my many questions and gave information to me to make a good decision. He is definitely an asset to All German Auto and we will call him to find my wife's next new car. I highly recommend All German Auto because of him and will refer my friends and relatives to you. Thank you!
my car is always thoroughly checked over and runs as it was designed to run after being serviced at AGA. keep up the good work. I am one very satisfied driver!
You guys ROCK. I am so impressed with your service, knowledge, pricing and responsiveness… You have a customer for Life. Well done.
Hi There!
All work was performed in a timely manner and to my satisfaction. Biggest thing for me is that I "trust" AGA to work on my M cars and older BMW's and get things right. I'm pretty picky who works on my cars! Have always been highly satisfied with AGA! Enjoy checking out all the other cool cars there and their S62 powered off road toy. Keep up the good work...
Thank You! Dan
More information about formatting options


text:
What everyone seems to ignore about this kerfuffle is that insurance companies have the right, without the consent of the insured, to settle as it chooses. Most would settle for small amounts like those alleged to save legal expenses that could become egregious.
Why this is news and accusations of rape by a person who stood up and said so was "only about sex" and not worthy of report when Bill Clinton was accused, and is big news when a black conservative is accused by unnamed sources.
AT Systems, Inc. corporate trainers ( an armored car transport company, now Garda, LTD of Quebec, Canada) said during mandatory employee sex harassment training in 2004 that the average sexual harassment case costs the company $300,000. My understanding is they had a large number of them in the years prior to this mandatory in-house employee training.
Mind you, the security and especially the armored car business, are comprised of mostly male employees. Very few women want these kinds of jobs, unless they are back office clerks or cash counters. Often times, a disgruntled employee or "gold digger" is the type of employee most apt to file a formal, written sexual harassment complaint. Again, there are a bunch of them (complainers) in the armored car and security businesses. I am not so sure guys have any particular motivation to harass except to generate such "settlements" as were allegedly paid on behalf of Herman Cain.
This is extortion, plain and simple. These women simply want more than they originally bargained for.
Some of you are assuming that the women with whom these settlements were made are the source of the information. These events don't happen in a vacuum, there would have been witnesses interviewed by HR or corporate counsel as they assessed the complaints. They were not subject to the confidentiality agreement. As Cain's visibility increased doubtless there were dinner conversations by these witnesses, nothing salacious stays private.
Cain's mistake, when this issue surfaced, was not to have an appropriate response. He could easily said that on a couple of occasions people took what he said in a way he didn't intend, that he was sorry for that and wished all involved an appropriate resolution, These matters are handled by HR and counsel and he is subject to the confidentiality agreements so he cannot comment further.
His big mistake was attacking the women and commenting on what happened. They are entitled to defend themselves.
It would be a bigger mistake for his representatives to sue the press. Cain would be required to testify and reveal details which he thought had long since been put to rest.
So Mr. Bradley, according to you victims of sexual harassment are disgruntled gold diggers. How do you describe rape victims? Attention-seeking nymphomaniacs?
Certainly you are whacked out of your mind "not worth of a report when Bill Clinton was accused..."
You must be kidding, right? Alternatively, you must be playing the "how can I be a racist, when I come to the defense of a black man" card. Moron.
What is the actual allegation, Cain made a couple of woman feel "uncomfortable"?
To the Editor -- please spare the readers from "a brief primer on the topic" by Ashby.
I actually appreciate the brief primers...
The Law Blog covers the legal arena's hot cases, emerging trends and big personalities. It's brought to you by lead writer Jacob Gershman with contributions from across The Wall Street Journal's staff. Jacob comes here after more than half a decade covering the bare-knuckle politics of New York State. His inside-the-room reporting left him steeped in legal and regulatory issues that continue to grab headlines.
Comment or tip? Write to email@example.com or email@example.com
The First Amendment rights of judges are a hot topic these days.
Plaintiffs' lawyers dodged a bullet last year when the U.S. Supreme Court spared a quarter-century-old precedent that had served as the legal linchpin of the modern investor class-action case. Despite that win, a new report suggests that securities class actions have lost some of their firepower.
In a week in which images of Prophet Muhammad were connected to acts of terror and defiant expressions of freedom, a sculpture of the prophet of Islam inside the U.S. Supreme Court has drawn little notice.
Alan Dershowitz has vowed to slap a defamation suit against the two lawyers who claimed in a court document that Florida financier Jeffrey Epstein arranged sexual liaisons for him with an underage prostitute. Those lawyers have beaten him to the punch.
The salacious allegations against Prince Andrew and Alan Dershowitz that surfaced in a federal lawsuit involving convicted sex offender Jeffrey Epstein have generated international attention. Drawing less coverage is the lawsuit itself -- a case with the potential to expand the rights of crime victims during federal investigations.
Content engaging our readers now, with additional prominence accorded if the story is rapidly gaining attention. Our WSJ algorithm comprises 30% page views, 20% Facebook, 20% Twitter, 20% email shares and 10% comments.


text: Hi Everyone, My friend has access to a machine lab and said he could make me rollers for a grain mill. Does anyone have a CAD drawing of the rollers and even an assembly that we could use? I understand that doing it in a lathe might be easier, but if the drawings are available, we'll take them. Thanks!


text:
PoliticsKurdish rebels prepare for peace Kurdish leaders have given a cautious welcome to the recent PKK ceasefire declaration, knowing that much work remains. Richard Hall | 11 Apr 2013 19:48 GMT | Politics, US & Canada, Australia, Iran, Iraq Murat Karayilan has led the PKK since the capture of Abdullah Ocalan in 1999 [Richard Hall/Al Jazeera]Qandil, Iraq - On a bright day in the Turkish city of Diyarbakir late last month, hundreds of thousands gathered to celebrate the Kurdish New Year and the beginning of spring. While long political speeches are customary for the occasion, there was one in particular that stirred the crowd - a message from the jailed leader of the Kurdistan Workers Party (PKK), Abdullah Ocalan. "Let guns be silenced, let ideas speak," Ocalan said in the letter, read out by Kurdish politician Pervin Buldan. The historic announcement from the head of the Kurdish rebel group, who is revered among many of Turkey's Kurds, called for an end to violence and declared a ceasefire in the decades-old conflict between the PKK and the Turkish state - a conflict that has left around 40,000 people dead. " Let guns be silenced, let ideas speak. " - Abdullah Ocalan, PKK leader There were cheers from the throngs in Diyarbakir, but two weeks later, in a small stone house across the border in northern Iraq, the PKK's military leader, Murat Karayilan, suggested rumblings of discontent among the group's fighters. "The thinking of the leadership of the PKK is in line with Ocalan," Karayilan told Al Jazeera. "But the PKK is a very large organisation. We cannot say that the middle ranks all feel the same way. We are having a problem convincing all of our comrades." Rank and file Despite his incarceration, Ocalan inspires a fierce loyalty in the organisation he founded in 1974. But important though his call may be, it will mean little if it is not welcomed by the PKK fighters here in the Qandil Mountains that straddle the border between Iraq and Iran. Before Ocalan went public with his proposal, Karayilan said, it was put to the rank and file of the PKK. It was discussed, debated and argued over at a series of meetings here in the mountains. It was during these discussions that a rare voicing of dissent began to emerge among some of the fighters. Word got back to Ocalan, who made his frustration clear by passing messages through the handful of Kurdish politicians who are allowed to visit him in jail. The problem, according to Karayilan, in convincing the fighters that now should be the time to lay down their arms is that the PKK "has never been stronger". There is also mistrust over Turkey's willingness to reciprocate Ocalan's call for peace. "We have been trying to solve the issue peacefully since 1992 - this is nothing new," said Karayilan. "We have announced ceasefires before and, on one occasion, we even withdrew our forces from Turkey. But we couldn't get anywhere because of Turkey." Incarceration Ocalan has been held on the island of Imrali in the Sea of Marmara since his 1999 capture by Turkish security forces in Kenya. For the first decade, he was held in solitary confinement, unable to communicate with the outside world. In his absence, Karayilan has headed the organisation. PKK leader calls for peace in Nowruz address To convince the middle ranks, he told Al Jazeera that Ocalan's prison conditions must be relaxed, so that he is able to communicate with his troops more easily. Even then, there is no guarantee that the rank and file will concede. Ceasefires have been called on four previous occasions, and they have all broken down. Nevertheless, Karayilan displayed a guarded optimism about the burgeoning peace process. "People are tired of clashes and divisions," he said. "They are tired of it. There has to be a new way in the region." Much more than a declaration of a ceasefire, he continued, Ocalan's New Year message was a grand vision, "a new approach to the problems in the Middle East". The PKK's leadership claim that there are several thousands of fighters in the organisation. Designated a terrorist organisation by the US and the UK, the group reportedly has roughly 3-4,000 members based in Iraq, sheltered by the impassable mountains along the border. Repeated Turkish raids on the mountains have failed to dislodge them from their hideouts. There are reportedly a further 1,500-2,000 in Turkey, where the group has carried out attacks on Turkish soldiers. The PKK has also been blamed for planting bombs that have killed civilians. Leaving the mountains? A small band of fighters are present on this overcast evening in the Qandil. They are mostly young, former students. Many female fighters make up the group's ranks, and are present in its leadership. What will become of these guerrillas, who until a month ago were ready to die for their cause? That question is more easily asked than answered. Most of the PKK's members are well-versed in Ocalan's writings and seldom stray from the party line. Roj Welat, a PKK official and its foreign affairs spokesman, is older than most of his comrades. He joined in 1993 after living in Australia for many years. Having lived abroad for so long, he is better placed than most to imagine a future away from the mountains, but even he is reticent. "It is very early to be able to answer this question," he told Al Jazeera. "But since you have asked, I can say that, if the peace process develops and the mentality of violence is put aside in Turkey and the rest of the Middle East, then there will be work of a different kind to be done for the development of democracy and freedom. Inside Story: Turkey and the PKK - a chance for peace? "In short, there will be plenty of work still to be done." Karayilan is less guarded when talking of the future. "If we have to leave the mountains, the PKK will continue its work to establish a free society," he said. "Not all of our comrades are from Turkey. The others will go back to their respective parts of Kurdistan and continue the fight for freedom there." Talk of leaving the mountains is a delicate subject for the PKK. Kurds have called the mountains home for thousands of years. For these fighters, however, they hold an even deeper resonance. It is here that they find shelter from the Turkish jets that stalk the skies and the army that outguns them. The impenetrable passes, thick forests and deep valleys provide refuge as well as a home. So how do they feel about the possibility of leaving them behind? "I have been in the mountains for 21 years, both in north and south Kurdistan," Karayilan said. "There may be some difficulties. We love the mountains. But a lot has changed since I joined the PKK all those years ago. Back then a person could be arrested simply for calling themself as a Kurd." Ronahi Serhat, also a member of the PKK's executive council and a fighter with the organisation for the past 20 years, sat alongside Karayilan, in front of a yellow flag bearing a portrait of Ocalan. She spoke with a similar reverie of her time in the hills. "You feel so free," she says of the guerrilla life. Shifting ground A little more than a year ago, in another house not far from where we met that evening, her outlook was very different. The mountains were then under intense bombardment from the Turkish airforce - a response to an attack in which 26 Turkish soldiers were killed by rebels at police and army posts in south-east Turkey. Back then, Serhat displayed little optimism. "We are not in the mountains by choice, it is a necessity," she said at the time. "We believe in a peaceful solution. If the environment is right, we are ready to put down our arms, but such an environment does not exist in Turkey right now." "A lot has changed since I joined the PKK all those years ago. Back then a person could be arrested simply for calling themself as a Kurd." - Murat Karayilan, PKK leader But for the past few weeks, the bombs have fallen silent and the PKK's leadership - following Ocalan's lead - is speaking in positive tones. And while the atmosphere in the Qandil has improved, conditions in Turkey also seem now more suited to talks. Recep Erdogan, prime minister of Turkey, faces a nationalist opposition which fears any talks could lead to a renewal of Kurdish demands for an independent state. Opposition leader Devlet Bahceli has accused the prime minister of "treason" for negotiating with the man dubbed the "chief terrorist". Turkey's justice minister, and one of the founding members of Erdogan's Justice and Development Party, urged caution when commenting on the ceasefire announcement and the potential success of a peace deal. "There are no guarantees," Sadullah Ergin told reporters. "But we know what is going to happen if it does not." Erdogan has held firm in the face of opposition, saying he would pursue talks "even if it costs me my political career". His dream of transforming Turkey into a presidential republic, with him in the top job, cannot be achieved without the Kurdish Peace and Democracy Party. This support will not be forthcoming without the Kurdish issue being solved. Among the details that will have to be ironed out during the peace process will be the hundreds, if not thousands, of people detained in Turkish prisons on charges of links to the PKK. Erdogan has overseen the granting of greater language rights to Turkey's 20 million Kurds since coming to power in 2003, but they are still calling for greater autonomy in areas of the south-east where they maintain a majority. Requests for further official comment from Turkish authorities for this report were unanswered by time of publication. Perhaps most significantly, however, is that the two men with the power to end the conflict are now talking to each other. And, just as importantly, and though tentative they may be, the fighters of the mountains are also talking about reconciliation. "There will need to be a period of repair," Karayilan said. "Much like there was in South Africa." "The Turkish state has killed a lot of people. Thousands of civilians lost their lives to unknown assailants. Villages were destroyed and people went missing. We have also killed. Both sides have a lot to forgive." Follow Richard Hall on Twitter: @_RichardHall Source: Al Jazeera
Kurds hope Newroz brings peace in Turkey Optimism for ceasefire between PKK and Turkish army intensifies amid Kurdish New Year celebrations. Politics, Europe, Turkey
Iraq-Kurd tensions on the boil Inability to resolve issues arising out of autonomy for the region may prove costly. Politics, Iraq
The other side of Somalia's pirates Poisoned waters and illegal fishing drove Somalis into sea piracy to feed families, according to relatives. Human Rights, Poverty & Development, Environment
The most powerful mafia you've never heard of Italy's 'Ndrangheta crime syndicate is believed haul in more revenue than many Fortune 500 companies. Italy, Crime, Europe
New Afghan militia sets its sights on ISIL 'Marg' vigilante group vows to safeguard northern Afghanistan from armed factions amid reports of ISIL infiltration. War & Conflict, Asia, Afghanistan
Devastation and disease after deadly Malawi floods Tens of thousands stranded after southern Africa country's record floods face rising risk of disease outbreak. Humanitarian crises, Africa, Malawi
The SystemProsecutorial MisconductThe System examines two cases where prosecutorial misconduct may have led to wrongful imprisonment. Crime, Law, United States
Talk to Al JazeeraPrince Ali of Jordan: 'Bring back FIFA's reputation'The FIFA presidential candidate explains why he is challenging Sepp Blatter and how he plans to reform the organisation.Sport, Middle East, FIFA
Al Jazeera WorldAhalil: Music of the Red OasisThe music of the Algerian Sahara, known as Ahalil, is a key part of a way of life that has survived for centuries.Arts & Culture, Algeria, Music
People & PowerKilling the BallPeople & Power investigates how a match-fixer and his syndicate corrupted global football.Sport, Football, Corruption


text:
March 25, 2014, 12:20 AM | posted by in Filmmakers
Did you ever think that cleaning your sink, washing your floor or dusting your furniture could be toxic? Toxic chemicals are in use every day in our homes.
"This issue was not on my radar," says documentarian Dana Nachman, who at the time was a television news producer. "Someone I interviewed for [a TV news] series told me that products are not vetted by any government agency before they get onto store shelves and into our homes."
She was shocked. So much so that she turned the topic into the film, "The Human Experiment."
The film focuses on the impact of man-made chemicals on human health and examines the U.S. regulatory system that allows these chemicals on the market without any testing for health effects. The film's website states, for example, that two of the sudsing agents used in some all-purpose cleaners contain substances that when in contact with nitrites "react to form nitrosamines – carcinogens that readily penetrate the skin."
She is still shocked by what she finds out -- even after more than four years of working on the film and researching the topic.
Her audiences are shocked as well, and angered. But she also knows that watching the film is empowering. She now makes healthier decisions for her family and so can her audiences.
"People tend to go straight home and throw away products," she says.
Although most are moved to action, her main goal is to inform and educate. "I … want to make sure that they have the resources they need to make changes so that they don't feel helpless and just throw their hands up after seeing the film."
The film is narrated by actor and activist Sean Penn, who is also the executive producer. The two were introduced by a mutual friend and worked together on Nachman's previous film, "Witch Hunt."
"The fact that he thinks we are good enough filmmakers to align with really gives us a boost, for sure," she says.
She admits, though, that sometimes the life of a filmmaker isn't always that exciting. "… These films take a very long time to make and often you feel like you are all alone in the dark at difficult times of production," she says. "So when you do get emails from people who the film resonated with or awards from film festivals it does feel good!"
— Anne M. DiTeodoro
Download Related PDF [1.1 MB]
Related Screenings:
03/25/14 @ 6:45 PM – The Human Experiment
03/26/14 @ 1:50 PM – The Human Experiment
Check out the latest festival highlights and goings on in the print edition of The Daily.
We are 24 hours away from #CIFF39 tix going on sale at http://t.co/P6JKL99BP2! Use code TWITTER to receive $2 off each ticket purchase.
about 13 hours ago . Reply . Retweet . Favorite
We are just over 24 hours away from #CIFF39 tickets going on sale to the general public at clevelandfilm.org! Use code "Facebook" to receive $2 off each ticket purchase. Let's hear it, what's on your film schedule?
about 15 hours ago . Link
Between Two Films.
CIFF 38 Daily Buzz Day 13 Wrap Up
Meet the Filmmaker with Michele Josue, Judy & Dennis Shepard from "Matt Shepard is a Friend of Mine"
Tickets On Sale to the General Public Friday, March 6th
CIFF39 tickets will go on sale to the general public Friday, March 6th at 11:00 a.m.
Tickets on Sale to Members Friday, February 27th
CIFF39 tickets go on sale to MEMBERS ONLY February 27th at 11:00 a.m. Join or renew today!


text:
Village Environmental News
Village Celebrates Arbor Day Jan. 16
Village hosted a celebration at Palmetto Bay Park Jan. 16, during which Boy Scout Troop 20 honored Florida State's recognition of Arbor Day by planting a live oak tree. See our Facebook photo album.
Resident Survey on Thalatta Programs
We recently asked residents to share input on events at Thalatta Estate and future programming, too. Stay tuned for results of the recent survey.
How to Save $100k in Taxpayer Dollars
Since Mayor Flinn introduced paperless production of e-Currents in 2008, the Village has saved $100,000 in taxpayer dollars by eliminating the cost -- and environmental impact -- of print newsletters.
FPL Relocating Royal Palms
FPL is relocating 25 mature trees in Palmetto Bay that were planted years ago by Miami-Dade County under power lines. Removal and relocation work starts Jan. 16 along the east side of Franjo Road.
YGrene Offers PACE Financing
Commercial property owners in Palmetto Bay are obtaining financing to make big improvements in their properties that lower utility bills, reduce repair costs, and increase property value. Read more.
Everything "Green" in Village Video
Check out this Earth Week video to see how Palmetto Bay recognizes Earth Day in a big way, with a full week of events each year -- leaving our Villagers "greening" from cheek to cheek.
Mangrove Kayak Adventure Program
The monthly Mangrove Kayak Adventure program at Thalatta Estate has concluded but will be back in 2015 due to resounding popularity. Contact Parks Admin for further info -- and see photos.
Garden Club Honors Homeowner
The board of the Palmetto Bay Garden Club formally presented the Garden of the Year Award to Dr. Lloyd Wruble at their May 27 meeting. Read more, and get news coverage in the Palmetto Bay News.
Program Lures 65 Kids to Fishing Event
"Get a Kid Fishing" was the big fish tale of the season as 65 kids and family members gathered at Thalatta Estate July 11 for a full day of fishing and boating-skills training. See photo gallery.


text:
Planning board agrees to work on steep slope ordinance
Published 10:21pm Sunday, February 17, 2013Planning board members were all in favor of having the building inspector make the engineer decisions through an ordinance, with their main reason being the ordinance can contain a slope trigger.
Planning board members said an ordinance can give the building inspector a trigger of when to go out to a site saving the county time and money and avoiding having to do a pre-site inspection on every building regardless of slope.
An ordinance would also give a local avenue for property owners to appeal a building inspector's decision as well as to give exemptions such as for agriculture, forestry, altering or replacing a single-family dwelling and for minor construction.
Homeowners already have an appeal process for a building inspector decision through the state for a range of decisions made on construction.
Polk County Building Inspector Steve Jones told the planning board it was up to them, but he'd rather go the route of writing a pre-site inspection rather than an ordinance.
But planning board members said they'd feel more comfortable with an ordinance.
"I still think something should be on the books," said planning board member Christel Walter.
"And it's really for the protection of the homeowner and people that live around (the construction)."
Walter also said the ordinance drafted is "benign."
"It's benign because it's only establishing that threshold," Walter said. "It's still up to (the building inspector's) discretion. I hope the commissioners will be OK with this. I think we have to move in that
Another topic discussed last week amongst the planning board was the potential liability issue of not having an ordinance. A couple of the planning board members and a resident mentioned the county being cautioned last year by former county attorney Mike Egan that without an ordinance the county would not be protected under state law if a slope failed due to construction.
Egan told commissioners last year both the county and the building inspector could be liable if, for example, the building inspector said an engineer wasn't needed and a slope failed causing damage. It is unclear how liable the county would remain with the current draft steep ordinance leaving the decision up to the building inspector whether or not to require the property owner to have an engineer design the building.
"And as you recall attorney Mike Egan cautioned against an employee making those type decisions," said Tryon resident and former county commissioner Renée McDermott. "Under North Carolina law, Egan said when an employee is making discretionary decisions neither the county or the employee is covered under North Carolina law. The inspector and the county could both be held liable and I'm sure you wouldn't want that."
Planning board members Lee Bradley and Susan Welsh also mentioned Egan's caution.
"At least in theory (an ordinance) relieves a lot of liability," Bradley said.


text:
Town Square
Obama's Red Line
Original post made by Red Line Obama, Another Pleasanton neighborhood, on Dec 6, 2012
This hollow Red Line blustering is about as effective as Obama repeatedly telling Amadi Nut Job that if Iran keeps developing nuclear weapons, that will not be tolerated. Have you noticed how scared Nut Job is?
Probably about as effective as Obama repeatedly telling North Korea that firing test rockets would not be tolerated - they seem really scared too. That little tin-horn dictator is probably hiding under his bed clutching his teddy.
Here's a wake-up call for Obama -- while he has been fiddling, the Genie escaped the bottle. Assad has gone ahead and prepared the Sarin gas. Obama might want to have his chemical suit and gas mask handy in case Addad holds back a few cannisters for other purposes.
Obama might want to read about how Ronald Reagan got Ahmadi Nut Job's attention 32 years ago when Nut Job personally held the American hostages captive; and how he got Muammar Gaddafi's attention in just a few hours time. P. S. It wasn't by repeatedly drawing a new Red Line in the sand.
Comments (4)
a resident of Another Pleasanton neighborhood
on Dec 6, 2012 at 2:01 pm
Dear Red Line Obama,
I'm very impressed with your line of thinking and the way you so elegantly express your thoughts. If you aren't currently in a classroom, you certainly belong in one. Have you thought about starting up your own school? Just a thought.... Keep up the good work!
a resident of Another Pleasanton neighborhood
on Dec 6, 2012 at 3:51 pm
Well, he-whose-name-is-not-really-Cholo, I bet you'd enjoy very much being in a classroom taught by Red Line Obama.
Thank you for your prescient remarks. I'm certain they'll find great traction among the readership. Please keep up the good work!
a resident of Livermore
on Dec 6, 2012 at 5:46 pm
Ned is a moser.
a resident of Livermore
on Dec 6, 2012 at 9:11 pm
Who is a moser"
Web Link
Don't miss out on the discussion!
Sign up to be notified of new comments on this topic.
Steve Glazer for State Senate
By Roz Rogoff | 2 comments | 1,713 views
Pleasanton resident will have his hands full trying to keep the Oakland teams
By Tim Hunt | 1 comment | 947 views
The House of Representatives performs historys first repeat hara-kiri
By Tom Cushing | 0 comments | 282 views