text:
Establishing a Southern Swedish Malignant Melanoma OMICS and biobank clinicalcapability
© Welinder et al.; licensee Springer. 2013
Received: 12 November 2012
Accepted: 15 February 2013
Published: 27 February 2013
The objectives and goals of the Southern Swedish Malignant Melanoma (SSMM)are to develop, build and utilize cutting edge biobanks and OMICS platformsto better understand disease pathology and drug mechanisms. The SSMMresearch team is a truly cross-functional group with members from oncology,surgery, bioinformatics, proteomics, and genomics initiatives. Within theresearch team there are members who daily diagnose patients with suspectmelanomas, do follow-ups on malignant melanoma patients and remove primaryor metastatic lesions by surgery. This inter-disciplinary clinical patientcare ensures a competence build as well as a best practice procedure wherethe patient benefits.
Clinical materials from patients before, during and after treatments withclinical end points are being collected. Tissue samples as well as bio-fluidsamples such as blood fractions, plasma, serum and whole blood will bearchived in 384-high density sample tube formats. Standardized approachesfor patient selections, patient sampling, sample-processing and analysisplatforms with dedicated protein assays and genomics platforms that willhold value for the research community are used. The patient biobank archivesare fully automated with novel ultralow temperature biobank storage unitsand used as clinical resources.
An IT-infrastructure using a laboratory information management system (LIMS)has been established, that is the key interface for the research teams inorder to share and explore data generated within the project. The cross-sitedata repository in Lund forms the basis for sample processing, together withbiological samples in southern Sweden, including blood fractions and tumortissues. Clinical registries are associated with the biobank materials,including pathology reports on disease diagnosis on the malignant melanoma(MM) patients.
We provide data on the developments of protein profiling and targeted proteinassays on isolated melanoma tumors, as well as reference blood standardsthat is used by the team members in the respective laboratories. These pilotdata show biobank access and feasibility of performing quantitativeproteomics in MM biobank repositories collected in southern Sweden. Thescientific outcomes further strengthen the build of healthcare benefit inthe complex challenges of malignant melanoma pathophysiology that isaddressed by the novel personalized medicines entering the market.
Malignant melanoma Protein sequencing Proteomics Genes Antibodies mRNA Mass spectrometry BioinformaticsBackground
Malignant melanoma is a disease that is increasing in the industrialized world. InSweden approximately 2800 new cases are diagnosed every year and 500 patients die ofdisseminated melanoma every year. At the time of diagnosis 10-15% of these casesare considered advanced and this late discovery of the disease means a very poorprognosis. For malignant melanoma there is today no curative treatment when thetumor has disseminated, because malignant melanoma is relatively resistant to bothchemotherapy and radiotherapy [1]. The prevalence of mortality due to malignant melanoma is increasing andaccounts for 4% of all skin cancers. Melanoma is a malignancy ofpigment-producing cells (melanocytes) located predominantly in the skin, where itcauses the greatest number of skin cancer-related deaths worldwide. The increasingnumber of elderly people in society, i.e., above 65 years has a hugeimpact on the healthcare costs, and continues to escalate in the near future.Therefore new developments are essential for hospitals to improve healthcareefficiency as well as provide superior healthcare to patients. The current researchdevelopments and future healthcare solutions are expected to be closely linked tothe utility of biobank initiatives. A paradigm shift is under development, usingfuture 4P medicines, that is expected to introduce a paradigm shift in medicalpractice. The 4P Medicine is one of the most innovative future visions, thatcurrently is under development, with the objective to develop:personalized/predictive/preventive/participatory treatments [2].
Global access to biobank samples associated with clinical data, as well asstandardizations is key factors in order to serve the patients on a global scale.The number of biobanks is increasing as well as the number of samples that theselarge archives hold. In order to improve on efficiency and to optimize the sampleper biobank-freezer area, which includes robotic handling and processing ofindividual sample tubes, miniaturization is crucial. The miniaturization istechnology driven, which results in less sample consumption for each assay, as wellas a decrease in overall blood handling for the hospitals. Accordingly, this has adirect impact on biobank blood storage requirements, where the ultimate goal is toreach lowest cost per sample on a given −80°C storage units [3]. Currently biobank sources are being used more extensively in order toundertake large population based studies, from where new diagnostics and novel drugscan be developed. Biobanking was recently nominated as one out of ten most importantideas changing the world right now [4].
Today we have a lack of reliable diagnostic tools that can identify early malignantmelanoma as well as lack of sensitive methods/tools to follow the progression of thedisease, monitor the treatment or identify patients in high and low risk groups,respectively. A number of markers associated with malignant melanoma (e.g.S-100 and 5-S-cysteinyldopa) are under investigation, but their relevance tomelanoma progression, clinical outcome and the selection of optimal treatmentstrategies still needs to be established [5]. Recently mutations in B-RAF (v600E) have been identified as animportant driver of malignant melanoma. Inhibitors to B-RAF have likewisebeen shown to very favorably affect melanoma growth. More than 50%of melanomacases harbor mutations in the gene. In published phase III clinical studies [6, 7], the median progression free survival is 6 month mainly due todevelopment of resistance to the treatment. The Department of Oncology at SkåneUniversity Hospital has participated in clinical trials withB-RAF-inhibitors. Characterization of the somatic melanoma mutations inB-RAF (v600) will lead to a better understanding of developmentalpathways of melanoma. Possible targets for melanoma therapy are delineated withrelevant inhibitors already in research or on its way out in the clinic. In thisproject we aim to find new tumor markers for malignant melanoma with an ultimategoal to apply these findings in the clinic, with an ability to investigate drugimpact and mechanisms of drug action, as well as getting a better understanding ofMM pathophysiology. An ultimate goal for the SSMM is to organize the biobank patientsamples in a systematic way by harmonization in order to provide the highest qualityof the MM archive [8].
Clinical material
Metastatic tissue from malignant melanoma cancer patients was obtained from theSkåne University Hospital and other hospitals in the southern part ofSweden. Ethical approval was granted by the Lund University (approval number:DNR 1912007).
Cryostat thin slices, 10 μm of thickness, of lymph node metastases frompatients with malignant melanoma, stage III, participating in the South Swedishstudy, were prepared using a Leica CM5030 cryostat. Serial sec-tions were placedupon frosted end microscope slides (Menzel-Gläser) and air-dried followedby incubation at 37°C for 30 min. The slides were then stained withHematoxylin–Eosin.
Sample preparation
Proteins were extracted with AllPrep DNA/RNA/Protein Mini Kit (Qiagen) accordingto manufacture's instructions. The extracted proteins were precipitatedwith ice-cold acetone to a final concentration of 80% acetone. Samples wereincubated for 30 min at −20°C followed by centrifugation at16000 g for 2 minutes. The supernatant was removed, andthe protein pellets were allowed to air dry. The dried protein pellets wereresolved in 8 M urea in 50 mM ammonium bicarbonate (pH 7.6).Protein concentration was determined by the BCA method (Pierce). The proteinswere reduced with 10 mM dithiolthreitol (1 h at 37°C) andalkylated using 40 mM iodoacetamide (30 min, kept dark at roomtemperature). Following buffer exchange with 50 mM ammonium bicarbonatebuffer (pH 7.6) by using a 10 kDa cut-off spin filter (YM10 filter,AMICON). The samples were digested with sequencing grade trypsin (Promega) inratio 1:100 w/w (trypsin: protein) overnight at 37°C.
MRM assay development
Crude peptides were supplied by Thermo Scientific. Three mixtures were createdfrom the crude peptides, ca. 15 peptides in each and one mixture with aconcentration of 50 fmol/μL of each peptide. The transition lists werecreated in Skyline v1.2 software (MacCoss Lab). Primarily, high numbers oftransitions, all possible y-ion series that matches the criteria (fromm/z > precursor-2 to last ion-2, precursorm/z exclusion window: 20 Th), were selected for each peptide atboth 2+ and 3+ charge states. The peptide mixtures were analyzed by nanoLC-MS/MSusing a TSQ Vantage triple quadrupole mass spectrometer equipped with an Easyn-LC II pump (Thermo Scientific, Waltham, MA). The samples were injected onto anEasy C18-A1 pre-column (Thermo Scientific, Waltham, MA), and following on-linedesalting and concentration the tryptic peptides were separated on a75 μm × 150 mm fused silica column packed with ReproSil C18(3 μm, 120 Å from Dr. Maisch GmbH, Germany). Separationswere performed in a 45-min linear gradient from 10 to 35% acetonitrilecontaining 0.1% formic acid; at the flow rate of 300 nL/min. The MSanalysis was conducted in positive ion mode with the spray voltage anddeclustering potential were set to 1750 V and 0 V, respectively. Thetransfer capillary temperature was set to 270°C and tuned S-lens value wasused. SRM transitions were acquired in Q1 and Q3 operated at unit resolution(0.7 FWHM), the collision gas pressure in Q2 was set to 1.2 mTorr. The cycletime was 2.5 s in the non-scheduled methods and 1.5 s in the scheduledmethods. The best transitions (3–5 per precursor) were selected by manualinspection of the data in Skyline and scheduled transition lists were createdfor the final assays. The selected transitions were tested in real matrix alsoby spiking the heavy peptide mixtures into human malignant melanoma tissuedigests.
Results and discussion
Biobanking malignant melanoma
Disease presentation and clinical sample collections are key strategic resourcesthat need to be installed in order to build on a disease understanding thatgenerates the next generation of modern treatments and diagnostics for MMpatients. In that respect, there are an increasing number of large-scalepopulation-based studies currently collecting vast numbers of clinical samplesinto biobank repositories [9]. These sample collections will be the source of much information inthe years to come. The UK Biobank has collected blood samples from 500,000participants in the study, which are stored in −80°C freezers in theUK Biobank in Manchester(http://www.ukbiobank.ac.uk/about-biobank-uk), whereas a Swedishinitiative with automated processing and robotic handling and sorting isgenerating millions of sample tubes over the years [5]. In this context, the human proteome initiative, that will map all ofour human proteins, are stakeholders in these biobank establishments [10].
Disease link-related data are one important deliverable that will be of highvalue and of cardinal importance for generating added values to:
Disease understanding
Novel Patient Diagnosis
New Drug Development
The strategy of the SSMM research group is to harvest the values in the clinicalMM materials that are built in our automated large-scale biobank. We willutilize blood fractions as a resource for biomarker and genomics studies as wellas tissues from drug treated patients, where the spatial drug distribution intissue is mapped by imaging mass spectrometry [11, 12]. In order to improve on both the efficacy and safety profiles ofnovel medicines, a detailed understanding of both drug characteristics, andmechanism of drug action is needed. The new generation of targeted personalizedmedicines are steadily increasing, in healthcare today with good treatmentprognosis. The pharmaceutical companies have filled up their productionpipelines, perusing clinical studies, and are expected to reach the market withthese novel chemical entities.
There is a necessity to use standardized methods for long-term cold storage thatshould include internal standards to measure spontaneous sample decay over time [17]. Standardization and best practice has reached a global status by the"NCI Best Practices for Biospecimen Resources" document from the NIHin the US (http://biospecimens.cancer.gov/practices/2011bp.asp).
Generally, storage and acquisition of sufficient numbers of study samples mighttake months or even many years to complete [18, 19]. For these reasons sustainable sample processing and its qualityassurance over time is mandatory. In this way we will ensure high quality of thepatient material that will make the comparative MM studies possible.
For each blood type, forty-eight blood fractions were generated as 70 μLaliquots. All of these processing steps were carefully controlled by thesoftware of the pipetting robot. There is a standard operating procedure (SOP)that is applied to the protocol with built in criteria and quality assuranceconditions. The successful completion of handling the primary tubes is followedby the completion of a 384-rack, shown in Figure 2.These steps were controlled by the liquid handling robot, linked and interfacedto the LIMS that provides registered data control of each step processed withinthe blood fractionation processing.
Pilot study with a toolbox concept
The sequencing of the human proteome will be performed with a Gene-Centricstrategy, where the Gene-Coded Proteins will be addressed, based on previousgenomics studies in MM [13, 14].
There is a future important ambition of future OMICS research, which relates todetermine how the annotated regions of the genome control the production ofprotein annotations. The research community currently links the Encyclopedia ofDNA Elements (ENCODE) consortium that reveals rapid progress in deciphering thehuman genome with the human proteome [20]. When adequate numbers of samples are stored, analysis will beperformed using standardized sample preparation and OMICS analysis with state ofthe art sample separation protocols. The technology developments withingenomics, proteomics and metabolomics are impressively fast. These advancementswill drive healthcare efficiency where the human genome map complemented by themap of human proteome will be used as key cornerstones [10].
In order to utilize gene-, and proteins as predictors of disease and/ortreatments as for drug responders, more experience and R&D inputs will berequested. For diagnostic quantifying of protein(s) in clinical studies, thereare currently no guidelines from the Food and Drug Administration (FDA) orEuropean Medicines Agency (EMEA). However, there are ongoing biomarker projects,where the FDA in collaboration with the Academics and pharmaceutical industryare looking into standardization procedures for future utilization. This incontrast to the pharmagenomics area whereas guideline for industry has beenintroduced recently(http://www.fda.gov/downloads/RegulatoryInformation/Guidances/ucm126957.pdf).
Protein sequence based assays
There has been an extensive progress made in the last decade within the area ofproteomics and protein expression analysis. An increasing number of target andbiomarker discovery studies are undertaken in both academia and industry usingshotgun sequencing, utilizing mass spectrometry technology [21].
In addition, today most drug targets are being validated by proteomics assays inthe pharma and biotech industries, providing evidence to the role of the targetwithin a given disease area.
In retrospect, one of the first reports that was presented on the ability to mapa protein expression in human blood plasma, was made with 2D gel electrophoresiswith intact proteins, in contrast to the protein digest protocol, followed byLC-MS, that is the most commonly used separation and mass spectrometry platformof today [22]. The marriage and the interface in-between high-resolutionchromatographic separation and mass spectrometry have been a critical part ofthe development of large-scale protein analysis. Today, the mass spectrometerhas become the real workhorse for protein sequencing and proteindeterminations.
Global expression analysis
In studies where the total protein expression is of interest to build on adisease staging profile, shotgun sequencing is utilized. This is a platformwhere the proteins are sequenced within a high-throughput scanning cycle. Theglobal expression studies are generally used in "Discovery phases"including a wide scale analysis of many housands of peptide sequences thatoriginates from digested proteins. This global protein expression analysis fieldis intimately associated with the area of proteomics research. Proteomics oftoday holds the post genomic research activities, in one big research community,where many of the successes will be expected to be deliver on the understandingof the complex disease pathophysiology. In one respect, the proteomics field hasplayed a significant role in opening up a number of doors that has beenimportant for other researchers, such as the clinical field. The current statusis an extensive discovery phase protein candidate delivery that has beenreported on by the proteomics society where still the extended validation ofcandidate proteins, still remains to be pursued.
Targeted analysis
Targeted protein analysis is dedicated to quantification where a specific andsmaller set of proteins is measured in dedicated assays. In the last years, MRMmultiplex assay have become very popular due to their generic concept and theability to generate multiplex quantifications. Currently, protein quantificationis preferably performed with an immuno-reagent base assay technique, where thereare a large number of methodologies available.
Within SRM or MRM assays, a series of transitions are made with the targetpeptides that are the precursors, being ionized after the LC-separation andinterfaced to MS. Looking back to decades of biological mass spectrometry andthe recent decade with proteomics studies, it is obvious that all the generatedprotein sequence data, compiled and built within databases is a great asset.These experimental reports provide in many instances not only sequences ofimportance, but also in numerous cases quantitative information regarding aspecific biology of clinical relevance. These data has been generated bothwithin Academia, as well as within pharma-, and biotech- industry.
The initial step of an MRM assay development usually relates to applying anin silico step, whereby we can use a selection process, followed byblast searching in protein databases where identified proteins in biologicalsamples can verify the utility of target peptides identified as candidates.Precursors and m/z of the peptide products are keys to the assaydevelopment and should be identify at an early stage. Best practice for rapidassay developments with MRM-MS instrumentations was recently presented [23]. In this respect, peptide libraries used as standards, are invaluabletools in order to funnel the large number of peptide candidates in the insilico processing step that helps make judgments of the most usefultarget peptide candidates for the assay [24, 25].
In order to make progress in the field of malignant melanoma treatment, theprocess of malignant melanoma spread has to be better understood. Identifyingthe expression patterns of proteins associated with melanoma progression mightbring some clarity and better understanding of the progression of malignantmelanoma.
Malignant melanoma pathophysiology
The cutaneous malignant melanoma is a neoplasm originating from the melanocytecells that can occur either de novo or from a pre-existing lesions;congenital, acquired, or atypical nevus. In addition, non-cutaneous primarysites of melanocytes also include the mucosal epithelium, retinas, andleptomeninges. There are four most common MM subtypes, that can be distinguishedby clinical and pathologic growth patterns:
Superficial Spreading
Lentigo Maligna
Acral Lentiginous
- 1)
Benign melanocytic nevi
- 2)
Melanocytic nevi with architectural and cytologic atypia (dysplastic nevi)
- 3)
Primary malignant melanoma, radial growth phase
- 4)
Primary malignant melanoma, vertical growth phase
- 5)
Metastatic malignant melanoma.
Data flow & IT-solutions
Within the consortium we have developed an IT-infrastructure, utilizing FDAapproved software for sample and data processing, as well as the link toclinical proteomic units at three hospitals/universities, and with nationalbiobank units.
Mass spectrometry imaging (MSI)
Drug characterization is an ever-increasing research area that currently holds acentral position in both drug developments as well as within hospitals wherepatients are being diagnosed. Classical X-ray is accompanied with MRI, PET andCT for many of the most common diseases including MM.
Mass spectrometry imaging (MSI) is a rapidly developing technique that providesdata on the spatial distribution of molecular profiles on a tissue sample. Interms of MM, the MSI can be used to provide evidence of drug presence in tissuemicroenvironments.
The distributions of drug and metabolite(s) are measured directly in patienttissue samples with a resolving power of 30 μm [26]. This technology platform enables direct drug measurement wherepharmaceuticals and metabolites can be analyzed, as a cold compound, without anylabeling. It has been gradually accepted that MSI provides rich molecularinformation provided by this mass spectrometry imaging platform. It interfaceswell with general histology, as the staining techniques of tissues arecompatible with MSI. This will provide complementary information, and thusoffers new possibilities in the clinical field. This ranges from new insightsinto the molecular changes associated with pathogenesis.
The Southern Swedish Malignant Melanoma research initiative is a stepping-stone inbridging the bioanalytical and clinical gap, providing an integrated platform andwork flow in order to build knowledge and understanding of the molecular andenvironmental basis of human diseases. The ultimate goals that these large andrecent investments into biobank initiatives are striving at are to provide a basisfor improving both diagnosis and treatment of disease in society. The research-, andhealthcare- societies will also need to support the development of integratedinformatics systems that allows for search routines on sample collections, andtypes, as well as data sets that has been generated from these cohorts. In the endof the day, both the Human Chromosome Initiative, as well as other global researchactivities are looking for tools that can bridge the data and deliverables that willbe of major use in future drug development and patient treatments. Unifying thedifferent disciplines will aid in the fulfilling of the big picture that some of uscall personalized medicine and systems biology.
The Human Proteome Project (HPP), which is a global initiative, will have animportant contribution by mapping all proteins coded by the human genome. Thisproteome initiative will provide public access to experimental data on the humanproteome, with annotations made in clinical material and in a large number of humandiseases. The purpose of this large initiative is to increase the knowledgeregarding the identification of disease markers, potential targets of therapy, aswell as the insight into variations of expression observed during development,health, and disease (http://www.HUPO.org).
Southern swedish malignant melanoma
Multiple reaction monitoring
Malignant melanoma
Liquid chromatography
Tandem mass spectrometry
Selected reaction monitoring
Food and drug Administration
Massspectrometry imaging
Laboratory intelligence managementsystem
The human proteome project.
This work was supported by grants from Mrs. Berta Kamprad Foundation, SwedishAcademy of Pharmaceutical Sciences, Swedish Research Council, the SwedishFoundation for Strategic Research, Vinnova, Ingabritt & Arne LundbergResearch Foundation, the Crafoord Foundation, Swedish Cancer Society(Cancerfonden) and ERC advanced grant (ERC-2011-AdG 294576-risk factorscancer).
Authors' Affiliations
- Newton Bishop JA: Molecular pathology of melanoma. Cancer Metastasis Rev 1997, 16: 141–154.View ArticlePubMedGoogle Scholar
- Tian Q, Price ND, Hood L: Systems cancer medicine: towards realization of predictive, preventive,personalized and participatory (P4) medicine. J Intern Med 2012, 271: 111–121.PubMed CentralView ArticlePubMedGoogle Scholar
- Utikal J, Schadendorf D, Ugurel S: Serologic and immunohistochemical prognostic biomarkers of cutaneousmalignancies. Arch Dermatol Res 2007, 298: 469–477.PubMed CentralView ArticlePubMedGoogle Scholar
- Park A: Ten Ideas Changing the World Right Now: Biobanks. Biobanks: Book Ten Ideas Changing the World Right Now; 2009.Google Scholar
- Marko-Varga G, Végvári Á, Welinder C, Lindberg H, Rezeli M, Edula G, Svensson KJ, Belting M, Laurell T, Fehniger TE: Standardization and Utilization of Biobank Resources in Clinical ProteinScience with Examples of Emerging Applications. J Proteome Res 2012, 11: 5124–5134.View ArticlePubMedGoogle Scholar
- Chapman PD, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, Dummer R, Garbe C, Testori A, Maio M: Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 2011, 364: 2507–2516.PubMed CentralView ArticlePubMedGoogle Scholar
- Hauschild A, Grob JJ, Demidov LV, Jouary T, Gutzmer R, Millward M, Rutkowski P, Blank CU, Miller WH, Kaempgen E: Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label,phase 3 randomised controlled trial. Lancet 2012, 380: 358–365.View ArticlePubMedGoogle Scholar
- Shaw PM, Patterson SD: The Value of Banked Samples for Oncology Drug Discovery and Development. JNCI Monographs 2011, 2011: 46–49.View ArticleGoogle Scholar
- Zatloukal K, Hainaut P: Human tissue biobanks as instruments for drug discovery and development:impact on personalized medicine. Biomark Med 2010, 4: 895–903.View ArticlePubMedGoogle Scholar
- Paik YK, Jeong SK, Omenn GS, Uhlen M, Hanash S, Cho SY, Lee HJ, Na K, Choi EY, Yan FF: The Chromosome-Centric Human Proteome Project for cataloging proteins encodedin the genome. Nat Biotechnol 2012, 30: 221–223.View ArticlePubMedGoogle Scholar
- Marko-Varga G, Végvári Á, Rezeli M, Prikk K, Ross P, Dahlbäck M, Edula G, Sepper R, Fehniger TE: Understanding Drug Uptake and Binding within Targeted DiseaseMicro-Environments in Patients: A New Tool for Translational Medicine. Clinical and Translational Medicine 2012, 1: 8.PubMed CentralView ArticlePubMedGoogle Scholar
- Végvári A, Rezeli M, Döme B, Fehniger TE, MarkoVarga G: Translation Science for Targeted Personalized Medicine Treatments. In Selected Presentations from the 2011 Sino-American Symposium on Clinical andTranslational Medicine. Edited by: Sanders S. Washington, DC): Science/AAAS; 2011:36–37.Google Scholar
- Harbst K, Staaf J, Lauss M, Karlsson A, Måsbäck A, Johansson I, Bendahl PO, Vallon-Christersson J, Törngren T, Ekedahl H: Molecular profiling reveals low- and high-grade forms of primary melanoma. Clin Cancer Res 2012, 18: 4026–4036.PubMed CentralView ArticlePubMedGoogle Scholar
- Jönsson G, Busch C, Knappskog S, Geisler J, Miletic H, Ringnér M, Lillehaug JR, Borg Å, Lönning PE: Gene expression profiling-based identification of molecular subtypes in stageIV melanomas with different clinical outcome. Clin Cancer Res 2010, 16: 3356–3367.View ArticlePubMedGoogle Scholar
- LaBaer J: Improving International Research with Clinical Specimens: 5 AchievableObjectives. J Proteome Res 2012, 11(12):5592–5601.PubMed CentralPubMedGoogle Scholar
- Malm J, Végvári Á, Rezeli M, Upton P, Danmyr P, Nilsson R, Steinfelder E, Marko-Varga G: Large Scale Biobanking of Blood - The Importance of High Density ProcessingProcedures. J Proteomics 2012, 76(1):116–124.View ArticlePubMedGoogle Scholar
- Otlowski MFA, Nicol D, Stranger MJA: Biobanks Information Paper 2010. Journal of Law and Information Science 2010, 20: 97–227.Google Scholar
- Hallmans G, Vaught JB: Best Practices for Establishing a Biobank. In Methods in Biobanking. Volume 675. Edited by: Dillner J. Totowa: Humana Press Inc; 2011:241–260. Methods in Molecular Biology Methods in Molecular BiologyView ArticleGoogle Scholar
- Vaught J, Rogers J, Carolin T, Compton C: Biobankonomics: Developing a Sustainable Business Model Approach for theFormation of a Human Tissue Biobank. JNCI Monographs 2011, 2011: 24–31.View ArticleGoogle Scholar
- Paik Y-K, Hancock WS: Uniting ENCODE with genome-wide proteomics. Nat Biotech 2012, 30: 1065–1067.View ArticleGoogle Scholar
- Huttenhain R, Soste M, Selevsek N, Rost H, Sethi A, Carapito C, Farrah T, Deutsch EW, Kusebauch U, Moritz RL: Reproducible Quantification of Cancer-Associated Proteins in Body FluidsUsing Targeted Proteomics. Sci Transl Med 2012, 4: 142ra94–142rs94.PubMed CentralView ArticlePubMedGoogle Scholar
- Végvári Á, Marko-Varga G: Clinical protein science and bioanalytical mass spectrometry with an emphasison lung cancer. Chem Rev 2010, 110: 3278–3298.View ArticlePubMedGoogle Scholar
- Picotti P, Rinner O, Stallmach R, Dautel F, Farrah T, Domon B, Wenschuh H, Aebersold R: High-throughput generation of selected reaction-monitoring assays forproteins and proteomes. Nat Methods 2010, 7: 43–46.View ArticlePubMedGoogle Scholar
- Picotti P, Aebersold R: Selected reaction monitoring-based proteomics: workflows, potential, pitfallsand future directions. Nat Methods 2012, 9: 555–566.View ArticlePubMedGoogle Scholar
- Deutsch EW, Lam H, Aebersold R: PeptideAtlas: a resource for target selection for emerging targetedproteomics workflows. EMBO Rep 2008, 9: 429–434.PubMed CentralView ArticlePubMedGoogle Scholar
- Fehniger TE, Végvári Á, Rezeli M, Prikk K, Ross P, Dahlbäck M, Edula G, Sepper R, Marko-Varga G: Direct demonstration of tissue uptake of an inhaled drug: proof-of-principlestudy using matrix-assisted laser desorption ionization mass spectrometryimaging. Anal Chem 2011, 83: 8329–8336.View ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), whichpermits unrestricted use, distribution, and reproduction in any medium, provided theoriginal work is properly cited.


text:
Section 4: Custodial trustee's acceptance
Section 4. (a) Obligations of a custodial trustee, including the obligation to follow directions of the beneficiary, shall arise under this chapter upon the custodial trustee's acceptance, express or implied, of the custodial trust property.
(b) The custodial trustee's acceptance may be evidenced by a writing stating in substance:
I, ___ (name of custodial trustee) acknowledge receipt of the custodial trust property described below or in the attached instrument and accept the custodial trust as custodial trustee for ___ (name of beneficiary) under the Massachusetts Uniform Custodial Trust Act. I undertake to administer and distribute the custodial trust property pursuant to the Massachusetts Uniform Custodial Trust Act. My obligations as custodial trustee are subject to the directions of the beneficiary unless the beneficiary is designated as, is, or becomes incapacitated. The custodial trust property consists of ___
Dated ______________________________________
(Signature of Custodial Trustee)
(c) Upon accepting custodial trust property, a person designated as custodial trustee under this chapter shall be subject to personal jurisdiction of the court with respect to any matter relating to the custodial trust.

subset: commoncrawl


text:
Do you have a question? Post it now! No Registration Necessary
posted on
May 17, 2010, 8:39 pm
May 17, 2010, 8:39 pm
Have a neighbor w/ garage door troubles.
Can someone explain (from a voltmeter's perspective) how these things
I can get it to work right if I aim the electric eye sensors directly
into each other and tape them up, but if I try to actually aim them
across the opening, the door will not close. (It may not open either,
but I never tested that..)
With both eyes disconnected, the terminals on the back of the main
unit read about 12 volts. With one eye connected, that drops to about
7.8 volts, and with both sensors, it drops to about 7.3 volts or so.
However, I can't really see much meter deflection whether the eyes are
aimed or not, even when they are taped together.
However, when taped directly together (so that one sees directly into
the other and there is no possible chance for misalignment!!), the
door does indeed work correctly.
I'm assuming these electric eyes are current mode??
That might at least explain the lack of a discernable voltage when
aligned, not-aligned...?
There are no polarity markings on the electric eyes, and opening up
both showed a full-wave bridge (4 diodes anyway that look suspiciously
like a bridge!), so I'm assuming polarity does not matter. (?)
Either way, the voltage magnitudes did not change much when trying the
wires reversed.
Any ideas what could be going on here?
Can this really be just an alignment problem, or to you think the eyes
are defective?
They are newly replaced (before I got involved). I have no idea where
the orignal ones went off to.
Thanks in advance!!
It's a Sears unit, "Genie", I think?
Pretty hefty size door. 2-car with hurricane braces. Probably a 3/4
Re: Garage Door Opener - Electric Eye
Oh, I should also have added...
Each electric eye has an LED.
I suspect one is a transmitter and the other is a receiver. (?)
Anyway, the one with the GREEN LED is on all the time.
The other one (receiver?) has a RED LED which toggles on or off
depending on whether the beam is obstructed.
RED 3D% Clear, RED off 3D% obstructed.
Please note that the LED's behave this way when (I'm pretty damn
certain) they are aimed correctly, yet the door will not close.
(It also might not open, but I didn't test that). And as I mentioned
previously, the DC voltage doesn't seem to change much, if at all
regardless of what the LED's are doing.
Re: Garage Door Opener - Electric Eye
In today's world, nothing is simple!
A common scheme is to pulse the led, and measure the drop on the
receiver's power suppply. This is done by wiring both to the same
(current limited) power source, sending a pulse and looking at the
current drawn. Too little current, and the system knows the sensor eye
is blocked, enough current and it knows the sensor is seeing the pulse
from the LED. Pulsing is used to both allow comphensation for ambient
light, and to provide a basic reference point for the blocked sensor
mode (OK, these are basically the same thing...)
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Not the hoodie your refering to, but some of the shirts cracked me up.
I have to say, now that I'm a good ways into the campaign, this game is going to be tough to top. The action is top-of-the-line, there are some amazing missions, and they aren't holding back on the story telling. No spoilers, but there are some damn depressing parts sprinkled into the ongoing epicness. I'd be surprised if we aren't looking at our GOTY...
Yeah i know its nerdy. But I am a big nerd. And they do have a hoodie like that. I saw it over in the Bioware store. Just go to masseffect.com and click on the store. They had it listed for 74 bucks.
That's cool. I just wanted to know if you guys liked it. As for the logo, no problem. Hit me up in a PM with details and I will bang it out for ya.
Sent from my Galaxy Nexus
Last edited by DisturbedShifty; 03-08-2012 at 01:36 PM.
Havent gotten into the main game at all, been to busy but finally sitting down the next 2 days to hammer away at it. Gotta say, despite how gritty the game is, im very VERY thankful they havent toned down the humor at all. I chuckled when talking to the(to avoid spoilers being vague) turian on board during his conversation with Shepard:
Turian: "Thanks for having me on board. Garrus is working on the weapons. Something about calibrations....."
Shepard: "Sounds like him".
Anyways, im down for online this weekend if anyone wants to try and set up a Finheaven group. Honestly dont have to much of a preferance which day or time. Suppose anyone who is interested just start posting and we can work out the details.
So since I pretty much started with ME2, I never got the opportunity to import a ME1 saved file into ME2. I know I made my choices in the digital comic, it just didn't have a huge impact as I now know it does.
This part will contain a contain a spoiler, so click the box to continue:
I think that's what drew me into the series so much. You start becoming emotionally attached to these characters. Bioware probably does the best job of any company as far as developing their characters and making you become emotionally invested in their interests. It was the same with Dragon Age...
I am loving every minute of this game, I just did the sidequest where:Spoiler


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Editor's note: Signal Chain Basics is an ongoing and popular series; click here for a complete, linked list of all installments.)
In Signal Chain Basics Part 56 we discussed the fundamental relationships between jitter and phase noise. Now in Part #61, we discuss practical aspects of jitter transfer and capabilities as well as the limitations of phase noise measurement techniques.
Clock jitter and edge rate
Figure 1 shows three waveforms represented by a generic equation. The equation includes a phase noise term f(t) and an amplitude noise term ?(t). For each of the three frequencies evaluated, f(t) = 0 and ?(t) is a pseudo random function generating a constant envelope of noise for each waveform.
Figure 1 illustrates an exploded view of the crossing of Vth for each of the three waveforms, along with distributions of locations where Vth could be crossed.
Figure 1: Time-jitter induction versus signal-edge rate
(click here to enlarge).
Figure 1 emphasizes that noise sources other than intrinsic jitter can cause timing jitter errors. Faster edge rates diminish the effect that voltage noise on a clock signal has on clock jitter performance. This phenomenon is not solely a characteristic of the clock signal. Rather, this mechanism is apparent in devices that receive the clock signal or measure jitter performance.
Clock performance measurements
Engineers often evaluate lab results that dont make sense; and clock performance measurement is particularly problematic. For example, you can use an oscilloscope and a phase noise analyzer (PNA) to measure random jitter. However, the results are sometimes radically different. To better understand these results, a few experiments are identified in Figure 2. The results are tabulated in Table 1.
Figure 2: Random-jitter measurement experiments
Table 1: Results of random-jitter measurement experiments from Figure 2.
For example, the ONET1191P is a limiting amplifier which is optimized for high-speed applications. We used this amplifier to decrease the rise and fall time of the clock signal, which in this case is from about 200 ps to 35 ps.
Notice that the application of this amplifier has different results for the scope versus the PNA. The PNA results are as expected (for example, adding the limiting amplifier (LA) adds noise). However, the LA improves the results delivered by the oscilloscope significantly.
These results are related to the edge rate and jitter transfer mechanism shown in Figure 1. Instead of the clock signal containing the noise component, the front end of the oscilloscope provides the noise (error) source. Equation 1 shows an expression for the jitter noise floor of an oscilloscope. It comprises the jitter of the scopes time base, the noise of the scopes front end (Vnoise), and the slew rate of the signal under test.
Equation 1: Oscilloscope jitter noise floor.
Please join us next month when we will show you how to design your own simple I2C isolator.
For more information about clock solutions from TI, visit: www.ti.com/clocks-ca.
Editor's note: Liked this? Want more?
If you are interested in "analog" issues such as signal input/output (sensors and transducer, real-world I/O); interfacing (level shifting, drivers/receivers); the signal chain; signal processing (op amps, filters, ADCs and DACs); and signal integrity, then go to the Planet Analog home page here for the latest in design, technology, trends, products, and news. Also, sign up for our weekly Planet Analog Newsletter here.


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Here's a tasty assortment of baked potato recipes to complement your meal. Add toppings and your baked potato can be a meal in itself. Baked potatoes are easy to prepare yet versatile and nutritious. Learn how to bake a potato in several ways.
Baked potatoes are also great fixed on the grill or in the microwave. With a filling or topping, a baked potato becomes a complete meal in itself.
Potatoes are always a great choice for highly nutritional dishes at extremely low cost.
Select evenly-shaped potatoes and scrub them well. One medium to large potato is one serving.
Oven Baked Potatoes
Place clean potatoes directly on the baking rack or in a baking pan. Bake at 350 - 375 degrees for 90 minutes.
When the baked potatoes are cooked (prick with a fork to check for tenderness), make a crosswise slit in the top of each potato and squeeze gently to open out the cut area. Place a pat of butter in the opening if desired. Serve immediately.
300 Best Potato Recipes: A Complete Cook's Guide: Potatoes are just about everyone's favorite side dish. This book includes dozens of recipes, and ways to cook potatoes, for every part of a meal from breakfast through appetizer, main course, and even dessert.Microwave Baked Potatoes
Microwaving your potatoes will save time however a baked potato made in the microwave oven will not have a crispy skin.
Scrub the potatoes, then dry and prick each one several times with a fork.(a baking potato can explode in the microwave if the skin is not pricked). Cook one potato for 6 minutes on full power. If your microwave oven does not have a turntable, turn half way through cooking. Allow to stand for 1 - 2 minutes before serving.
If you are preparing more than one potato at a time, increase the cooking time accordingly.
You will get even better result with microwave baked potatoes with the Microwave Baked Potato Cooker BagA baked potato can be far more than a side dish. With some additions, even using leftovers, you can turn a single potato into a complete meal. If you need something more, add a salad, some fruit, wonderful bread or whatever "rounds out" a meal for you.
Try these baked potato variations:
Even more about How to Bake a Potato
A baked potato is nature's "mini-casserole." This edible, self-contained dish can hold an unending variety of hearty stuffings. Slice lengthwise to open your baked potato and make it into a meal. Here are just a few delicious ways to do it:
These mini-meals are tastier and healthier than any fast food you could purchase. Potatoes are cheap nutrition and using small amounts of meats, cheeses and leftovers offer infinite possibilities for a meal for one or a meal for a family or crowd.
We know that everyone has a favorite potato recipe because, in most families, potatoes are served several times each week. What are your favorite potato recipes? Share them!
Click below to see potato recipes from other visitors to this page...
Stuffed Baked Fingerling Potatoes Not rated yet
2 lbs Idaho® Fingerlings, such as Purple Peruvian or Ruby Crescent
4 oz Andouille Sausage, finely diced
4 Ramps, or Green Onions, finely …
Philly Cheese Steak Potato Not rated yet
Bake potatoes for 1 hr or until tender when pierced with fork.
Cook very thinly sliced steak to your desire. Cut steak in small pieces.
Sautee onion …
Don't know what to call this -- Onion baked potatoes? Not rated yet
This is very flavourful and yummy and healthy without adding calories or irritating delicate digestions with fats.
- Preheat the oven to 370 degrees …
Oven Baked Potato Not rated yet
Oven Baked Potato Recipe
6 med. potatoes, sliced
1/2 tsp. salt
Dash of pepper
Dash of garlic salt
1 1/2 tsp. instant minced onion
1/4 c. butter …
Reuban Baked Potato Recipe Not rated yet
6 large Russet or Idaho potatoes
Toppings: strips of deli corned beef, sauerkraut, shredded Swiss cheese, Thousand Island dressing.
Mediterranian Baked Potato Recipe Not rated yet
6 large Russet or Idaho potatoes
Toppings: chopped tomato, sliced olives, finely chopped red onion, oregano, feta cheese and plain yogurt. …
Ham and Cheese Baked Potato Recipe Not rated yet
6 large Russet or Idaho potatoes
Strips of cooked ham
Shredd cheese
Preheat oven to 450 degrees F.
Scrub potatoes …
Chili Baked Potato Recipe Not rated yet
6 large Russet or Idaho potatoes
Leftover or canned chili for topping
Shredded cheese
Sour cream
Preheat oven to …
Easy Baked Potato Recipe Not rated yet
6 large Russet or Idaho potatoes
Toppings of your choice
Preheat oven to 450 degrees F.
Scrub potatoes and pat …
Baked Potatoes with Garlic Cheese and Chorizo Sausage Topping Not rated yet
4 potatoes
9 ozs. chorizo sausage, sliced
1 lb. canned tomatoes, drained,
1 tbsp. plus 1 tsp. brown sugar
1 tsp. cider vinegar
3 ozs.
Twice Baked Bacon Horseradish Baked Potatoes Not rated yet
4 large russet baking potatoes, washed
11/2 cups bottled bacon dressing
3 tablespoons real bacon bits
1/4 cup bottled creamy horseradish dressing, …
Fun With Potatoes - Mr. Potato Head
About Me and Best Potato Recipes
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Feb 08, 17 02:15 PM
Share your best potato soup recipes with readers of the Best Potato Recipes website. We have lots of ours for you and know you have some potato soups we have not yet tried.
Dec 24, 16 02:13 PM
Make ahead mashed potatoes are a time saver when you want a mashed potato recipe that does not need to be fixed last minute. It is the best mashed potato recipe for holiday meals.
Dec 10, 16 09:03 PM
Learn how to cook sweet potatoes for all of your favorite sweet potato recipes. Cooking sweet potatoes is very much like how you cook any other type of potato.


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Pilots are human. They make mistakes – statistically not as often as most mortals – but they do screw up from time to time. No pilot wants to run out of fuel and land on a busy highway. No pilot wants to be involved in an accident. In fact, most of pilot training involves avoiding such troubles. It's drilled into them that they be prepared for any flight condition, take every precaution, follow checklists and procedures and be ready for any emergency. It's part of being a pilot.
That being said, highly trained, exceptionally prepared airline pilots have managed to land on the wrong runway at the wrong airfield at least one hundred and fifty times in the past twenty years.
When a misstep leads to a mishap, pilots are subject to investigation by the FAA (Federal Aviation Administration) and if serious enough, the NTSB (National Transportation Safety Board). In that case, the airman becomes the subject of investigation "relating to the approval, denial, suspension, modification or revocation "of his or her certificate. No pilot wants that!
Momma Never Said There Would Be Days Like This.
Since pilots love being in control and fear losing their certificates more than anything, imagine their frustration if, while under investigation, they were denied access to air traffic data or to any flight data that could help defend their actions. Imagine how helpless they would feel if they had no access to what was being said about them – or if they really could not voice any objections until the case was closed and they could appeal. Doesn't sound very American, does it? Well, that's the way it was in America until recently.
How Many Senators Does It Take To Right A Wrong?
Legislation to protect a pilot's rights began the day Oklahoma Senator and private pilot James Inhofe landed his twin engine Cessna on a closed Texas runway in October, 2010 and became the subject of an FAA investigation. The Senator admits landing on the closed runway was a mistake, especially since it had construction crews on it at the time. He will also tell you he didn't realize the runway at Port Isabel-Cameron Country, Texas was closed or that people were working on it. Apparently he hadn't noticed, read or heeded the NOTAM (Notice to Airman) about the runway closure.
The problem for the Senator was not the mistake but the mistreatment that followed. Senator Inhofe learned firsthand what American pilots go through when under investigation by the Federal Government. The U.S. Senator felt as though he had no rights and no say in the way the investigation was conducted. The result of the infraction was mandatory remedial training which further fueled the Senator's ire. Good thing, too! Because the whole incident got him angry enough to write a Pilot's Bill of Rights, get it approved with bipartisan support from 65 U.S Senators and get it signed into law by President Obama before the end of summer in 2012.
It Took An Act Of Congress!
In the old days, the National Transportation Safety Board used to defer to the FAA for interpretation of their own rules when it came to determining the ramifications of pilot error. The Pilot's Bill of Rights or as Congress calls it "Public Law 112-153", eliminates the deference to the FAA and gives both FAA or NTSB equal weight in deciding the fate of the airman's certificate. While that doesn't sound very helpful, it does provide for more than one view of the situation and could have an impact if the NTSB were to find an interpretation of the FAA rules capricious or arbitrary as it relates to an individual case.
Far better news for pilots is that the NTSB is now required to follow Federal Rules of Evidence and Federal Rules of Civil procedure. You heard right. They have to play by the Federal rule book and follow Federal Court rules "to the extent they are practicable." This begs the question what rule of law was in place before Congress acted?
What The Bill Does For Pilots They Could Not Do For Themselves Before.
Before the law, the only way a pilot could appeal was to take his case to the U.S. Court of Appeals. That's a costly trip to Washington that could take months, maybe even years.
Now, however, the airman can take his or her case to a U.S. District Court which is a venue that's a lot cheaper, closer to home and less time consuming.
The real improvements come in the way the FAA must inform airmen they are under review.
- They must inform an airman under investigation of the nature of their offense
- They must inform the airman that an oral or written response is expected, but if that the airman chooses not to respond no adverse inference will be taken
- They must inform the airman that "releasable" portions of the report will be made available to them
- They must inform the airman that they are entitled to air traffic data (including ATC data from contract towers), ATC tapes, radar data, controller statements as well as any other investigative reports the FAA may possess that would facilitate the airman's defense (NOTE: ATC data is recorded and stored from 5 to 45 days before being destroyed or discarded, making it imperative that a Letter of Investigation be sent in a timely fashion and that any requests for data be made by an airman expeditiously.)
- The FAA must give airman access to all relevant information for 30 days before an enforcement action can move forward.
There are several other issues the law currently addresses:
- It calls for improvement in the method of presenting NOTAMs like the one pointing out the closed runway which the Senator obviously missed.
- It mandates the FAA improve its medical certification process and its associated forms. The law mandates further clarity so applicants can understand what medical restrictions they may or may not have and what their reporting responsibilities clearly are.
- And lastly, as we mentioned earlier, the FAA must adhere to Federal rules when it comes to evidence and other civil law procedures.
At present Senator Inhofe and others in the aviation community are pushing for additional changes to the law. Among the things he wants is an adherence to Federal Law when it comes to Customs and Border Patrol searches of GA aircraft. He wants to extend the Bill of Rights to other members of the aviation community, such as charter operators. He also wants the law to clearly state that if the FAA fails to notify an airman of an investigation, the FAA cannot press charges. Senator Inhofe is seeking up to nine additional changes to the law.
One more important thing. The phrase "airman" does not only refer to pilots. Maintenance crews hold airman certificates, too. Until this law was passed, maintenance people had just as little right to investigative information and data as pilots did. This law does for maintenance professionals what it does for pilots. It gives them the right to know why they're being investigated and allows them access to public data they can use to defend their certificates.
The way airmen were treated while under investigation in the past was a mistake. The Pilot's Bill of Rights Law fixes the mistake. We can thank Congress for that. As to why it took Congress so long? Well, I guess you can say they're only human, too.


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TRUEbalance blood glucose test strips from Home Diagnostics are cutting edge diabetic testing strips that ensure accuracy and precision. Featuring Home Diagnostic's TRUEfill™ patented beveled tip design which reduces re-testing, TRUEbalance diabetes test strips require no coding and are ideal for home glucose testing or when you're on the go.
This offer includes 48 boxes of test strips (50 strips per box) and 12 FREE meter kits.


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EXPLORE UNA-USA.ORG: Learn how UNA-USA connects Americans with the United Nations through local Chapters, grassroots advocacy, and education.
Advocacy Agenda Find a Chapter Model UN Human Rights UNA-USA/Seton Hall Study Program Upcoming Events Members receive access to a range of exclusive benefits such as events at the UN and across the United States, as well as opportunities to advocate, host Model UN conferences, and connect young professionals to UN experts.
Join UNA-USA For Members Model UN Resources Advocacy Resources Young Professionals Student Alliance Council of Organizations Learn how the UN is making an impact and how UNA-USA Chapters are sharing the UN with communities around the U.S. through our online news magazines The InterDependent and World Bulletin.
The InterDependent From the Executive Director World Bulletin UN Dispatch News & Publications |
BookTalkUNA: However Long the NightNew York City ChapterThursday, May 2, 2013 When Molly Melching arrived at the University of Dakar in Senegal to study in the fall of 1974, she planned on staying for only six months. Those six months would then turn into many decades, as she became deeply involved in humanitarian work. She founded Tostan (which means breakthrough in Wolof), an organization helping social and economic development in African communities through multidisciplinary education based on respect for human rights. Author Aimee Molloy follows Melching's fascinating life helping the women and communities of West Africa, delineating her groundbreaking strategies that have led to more education for women, increased health care, human rights and greater awareness of the dangers of female genital cutting - a tradition that has been deeply entrenched within the culture. In coordination with the government of Senegal, Tostan is working toward the goal of eradicating the practice by 2015 and is on-track to enable it. Tostan's approach is to bring human rights-based education to a community and enable a community-led process of discussion and shared understanding to optimize practices of health, governance, education, project management and environmental protection. Through an outreach model called organized diffusion, villagers share their knowledge and decision-making with their extended family and social network, across neighboring villages and entire regions. Tostan understands that true change can come only from within. In HOWEVER LONG THE NIGHT we see how this attitude empowers the communities of West Africa and how Melching's relationship with these communities not only brings about new outlooks on life but also profoundly affects Melching herself. Alongside Melching's story are the stories of the African women embracing Tostan's vision and breaking down cultural traditions that have been holding them back. The power of their transformative journeys, and those of millions of Africans who have been impacted by their work, comes alive on the page. This is the story of how lasting change can start with one woman and how the connections within a community and between communities can lead to a better world. ADMISSION: FREE for UNA MEMBERS - Reservation REQUIRED CLICK HERE TO MAKE YOUR RESERVATION ONLINE $15.00 for non-members and guests CLICK HERE TO PURCHASE YOUR TICKET(S) ONLINE SPACE IS LIMITED! Not a UNA-member? Join for just $25.00 and attend most events at a reduced rate or free! Just visit www.unanyc.org/join_us WHERE AND WHEN Steelcase, Inc. 4 Columbus Circle (58th Street and 8th Avenue) Thursday, May 2, 2013 6:30 - Reception 7:00 - Presentation 8:00 - Book Signing Questions? Please call (212) 907-1353 or e-mail us at email@example.com Labels: New York City Chapter |


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Amon Sûl-stone
The Stone of Amon Sûl was a palantír that rested on the Arnorian Tower of Amon SûlIn T.A. 1409 the watchtower was burned and destroyed when Angmar's forces invaded Arnor. Arthedain's last King, Arvedui, saved the palantír as well as the Annúminas-stone,when Arthedain was overrun by Angmar in Third Age 1974.
With these and other heirlooms, he fled into the far north, where he was given shelter by the Lossoth. At last a ship from the Grey Havens came to rescue Arvedui, but after he had boarded, its hull was crushed by the ice, and all aboard were lost. The Stone of Annúminas, along with that of Amon Sûl, were lost in the shipwreck, and sank.
The Palantíri | |
Stones of Arnor | † Annúminas-stone (Annúminas) · Elostirion-stone (Elostirion - Valinor) · † Amon Sûl-stone (Amon Sûl - Fornost) |
Stones of Gondor | † Osgiliath-stone (Osgiliath) · † Ithil-stone (Minas Ithil - Barad-dûr) · Anor-stone (Minas Tirith) · Orthanc-stone (Orthanc - Minas Tirith) |
Other | Master-stone (Tower of Avallonë) |


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Sponsored by
Roger Williams University Justice System Training & Research Institute,
and the New England Association of Chiefs of Police, Inc.
Wednesday, September 14 – Friday, September 16, 2016
Registration 8:00 am - 8:30 am (September 14 th )
Presentation 8:30 am - 4:30 pm
Roger Williams University Baypoint Inn & Conference Center
144 Anthony Road, Portsmouth, RI
This three-day seminar is designed to provide practical information for police administrators or mid-level
managers responsible for the supervision and management of a Field Training & Evaluation Program
(FTEP). Based on the "San Jose Model," topics will include: Overview of the Field Training and
Evaluation Program; Field Training Officer (FTO) selection, retention, and evaluation; establishing and
maintaining the "Rook Book"; remediation – identification and facilitation; trouble shooting your FTO
Program; as well as ethical and liability issues.
It is recommended that students enrolling in this course have prior experience as an FTO or familiarity
with the San Jose Model.
The cost for the seminar is $435.00 which includes materials, continental breakfast, breaks, and lunch.
Checks should be made payable to the Roger Williams University Justice System Training & Research
Institute, 144 Anthony Road, Portsmouth, RI. Lodging information for out-of- state attendees is
available. Telephone inquiries should be made to Liz Campo, Administrative Assistant to the School of
Justice Studies at (401) 254-3731 or e-mail email@example.com or fax (401) 254-3351.
**We require 72 hours cancellation prior to the seminar or you will be charged the required fee.**


text:
View Poll Results: Critique of Episode 14 | |||
10 out of 10: Near Perfect... | 103 | 45.98% | |
9 out of 10 : Excellent... | 58 | 25.89% | |
8 out of 10 : Very Good... | 19 | 8.48% | |
7 out of 10 : Good... | 16 | 7.14% | |
6 out of 10 : Average... | 10 | 4.46% | |
5 out of 10 : Below Average... | 1 | 0.45% | |
4 out of 10 : Poor... | 5 | 2.23% | |
3 out of 10 : Bad... | 3 | 1.34% | |
2 out of 10 : Very Bad... | 1 | 0.45% | |
1 out of 10 : Tortuous... | 8 | 3.57% | |
Voters: 224. You may not vote on this poll |
Thread Tools |
2012-10-09, 09:10 | Link #421 | |
Anime Watcher
Join Date: Apr 2009
Location: Sanford, Maine
Age: 28
2012-10-09, 09:26 | Link #422 | |
Moe Kyun~!
However, take note that the genre is NOT shonen, but seinen. That means one thing: this is not action oriented. This was supposed to focus more on the AI/World/State/KiritoxAsuna side of things, not how the fight with the Skullreaper will go for say... an entire episode. Well... Heathcliff, let's just say he's one hell of a schemer -- it seems that from the starting design up to the excecution he's got it all planned out -- I wouldn't be so surprised if Heathcliff actually initially designed the game to gather and try to interpret "image" thoughts. Heck the WMG in the TvTropes of SAO is very interesting and presents that very point, you should check it out (if you don't mind the spoilers of course...)
2012-10-09, 09:44 | Link #423 | |
Senior Member
Join Date: Apr 2006
On a side note, shounen manga doesn't necessarily have to be action oriented. There are many shounen manga series that focus on things other than fighting.
2012-10-09, 09:54 | Link #424 | |
Spoiler for Comparison to Accel World:
I feel I'm nowhere near close to say wanting to drop it, but there is an element of disappointment that I just can't shake, and this is coming from somebody that disregarded all hype and promises made by LN fans going in. So anyway if I were to give this first cour a rating out of 10 it would probably be something like a 6.5. A little better than average, but a lot of little things that imo easily addressable issues that hold it back when it could have easily been much greater, similar to how I felt about the latest Gundam show actually. Last edited by relentlessflame; 2012-10-09 at 20:47. Reason: added spoiler tags for comparison |
2012-10-09, 10:23 | Link #427 | |
Deploying Funnel Cakes
Join Date: Jan 2008
Let's not forget seinen manga/anime can have a good amount of action and suspense in it... - Darker than Black - Cowboy Bebop - Trigun - Black Lagoon - Jormungand - Ghost in the Shell: Stand Alone Complex |
2012-10-09, 10:24 | Link #428 | ||
Join Date: Sep 2010
Location: InterWebs
Spoiler for Comparison to Accel World:
Last edited by relentlessflame; 2012-10-09 at 20:48. Reason: Spoiler tags for comparisons... |
2012-10-09, 15:51 | Link #432 | |
Senior Member
Join Date: Nov 2007
Location: Tennessee
Age: 29
Have to disagree with Kirito and Asuna being cheesy and sappy though, Kazu-kun-kun; to me it just feels like a lovely, sweet romance between two people that have a genuinely meaningful relationship, it doesn't feel... I dunno, wanky like the kind of teenage relationships you mention. Pictures such as the one in the image thread where Kirito, Asuna, and Yui are dressed up for Halloween together resonate with me well because, rather than being an eyerollingly overdone teenage couple with no real substance, they feel more like young adults, giving off the 'newlywed' vibe of a relationships whose closeness and tenderness is genuine and well-earned. Yay I can argue without being a jerkoff now because I'm no longer a sleep-deprived wreck, thank you Clonidine |
2012-10-09, 16:10 | Link #433 | |
Senior Member
Join Date: Apr 2006
And I like it!!
2012-10-09, 16:47 | Link #435 | |
Anime Watcher
Join Date: Apr 2009
Location: Sanford, Maine
Age: 28
Kinda like what we see between Kirito & Asuna, they arent all over each other in public like they are in their house/alone. And I love it. |
2012-10-09, 17:41 | Link #438 |
I don't really see Asuna as his equal and I don't think she does either, but she's definitely one of the stronger characters in the game no doubt. She's indicated multiple times though that she's come to rely on him for his knowledge of the game and for his kindness towards her when she was basically alone. He essentially saved her and set her on the path towards becoming a front liner...but she's not his equal by any stretch. The only thing she seems to beat him at is cooking skill, but the lack of ability to dual wield pretty much instantly makes her nowhere close in terms of combat ability. Even Kayaba stated that for all intents and purposes he set Kirito up as the hero of the game and he expected nobody else but Kirito to be the one to face him at the final level, though of course that never happened.
Klein....I don't ever remember doing much of anything. That said there is some decent teamwork going on between Kirito and Asuna at times, but really the rest of the supporting cast just kind of feels like it's there to fall by the way side so that Kirito can save them, though from the sounds of Kayaba's speech it almost sounds like he might have been manipulating things so that this would be the case all along. Last edited by relentlessflame; 2012-10-09 at 20:51. |
2012-10-09, 17:46 | Link #439 | |
Yummy, sweet and unyuu!!!
Join Date: Dec 2004
He never was the focus in the boss room, even when he pulled the duel sword skill out, without Klein and Asuna he would have died. I think this is a hard one to categorise as it is pretty grey in a lot of areas, as his motives were never that clear cut. If anything Kayaba wanted Kirito to fulfil the role of a traditional action hero, this imho by giving the duel wield skill and wanting to face off against him. In terms of his heroism: In the beginning he avoided people as it would slow him down, which he regretted through out the 2 years. He went a bit suicidal after the Black Cats incident and would rather die first then see (or was it cause) others die. Finally after coming to terms with that, he would rather run away with Asuna then put her in danger. Him facing off against Kayaba on his own was imho an accumulation of those experiences and his death blow a sign of his love for Asuna. More importantly his style of play is to leave himself a large margin of safety. Which I guess he would have regretted even more if the real heroic one wasn't there beside him... Asuna that is, she is the one who jumps into danger without any regard for margins or her own safety to save people she doesn't know. I found his actions very human like which is one of the reasons why I like this show so much.
2012-10-09, 18:33 | Link #440 | ||||||||
Thread Tools | |


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At a glance
• Trapper Mining officials want the U.S. government to decrease the mine's required royalty payments on production.
• If the request is approved, it could allow the mine to operate for a longer time by making it economically viable to dig for deeper coal.
• Ray DuBois, Trapper Mining president and general manager, said current operational plans go through 2014, though the mine could remain open for a few years after that without lower royalty payments.
• If the request is approved, the mine's lifespan could be extended to about 2023.
Trapper Mining officials want the coal mine to stay open, said Ray DuBois, Trapper Mining president and general manager.
However, economic conditions could cause the mine to close early unless the federal government gives Trapper a break on its royalty payments.
The U.S. government owns the mineral rights to the mine's coal and charges a royalty fee on the mine's production.
DuBois said he wants the government to reduce its fee, which may be the only way to make it economically viable to dig for deeper coal.
The more coal workers can dig for, the longer the mine stays open, DuBois said.
Mine officials have an operations plan that runs through 2014, he said, which includes a previously granted request for a lower royalty rate.
The Bureau of Land Management reduced Trapper's royalty payment from a standard 12.5 percent to 8 percent shortly after a landslide struck the mine in fall 2006. However, the request was for only half the mine's coal reserves, and that half is running out, DuBois said.
His company's request would extend the 4.5 percent reduction for the rest of the mine's coal reserves for the next eight years, or up to 22 million tons.
"We're not just blowing smoke when we say if we can get some relief here, we can actually extend the life of the mine," DuBois told the Moffat County Commission at its Tuesday meeting.
He appeared before the commission to ask for the local government's support on his company's request.
A portion of the federal government's mineral lease revenue goes back to states and counties. Federal authorities already have recommended the request be granted, but they want local officials' input because it would directly affect their budgets, too.
The commissioners unanimously approved signing a letter to Gov. Bill Ritter asking him to support the rate reduction, citing Trapper's importance to the area's economy.
"We've had that (year) of 2014 for quite a while, and now it's not that long out," Commissioner Tom Gray said. "It's a no-brainer for me to do this."
Trapper Mining is the county's eighth-largest property taxpayer, accounting for 5 percent of all assessed value in the county.
DuBois also told the Commission he could hire 15 to 20 additional employees if his company's request is approved, which would help the local economy remain stable during the country's recession.
Trapper Mining's relief request is not based on its own financial hardships, DuBois said.
The 2006 landslide illustrated burdensome geologic conditions that exist south of Craig, most notably the steep grade of the mine's pits. It costs money to work and ensure safety in such conditions, and there also are issues with fractures in the hills' rock structure, ground water containment and rock formations in the coal seams, DuBois said.
Those conditions are not "standard" for open-pit mines, he added, which is why a standard royalty rate should be amended.
The issue now awaits Ritter's opinion.
However, DuBois said Trapper will not last forever, even with the rate reduction.
Mine officials are eyeing 2023 as an approximate closure date if the U.S. government lowers its royalty on the remaining coal, DuBois said.
It's hard to say when the mine might close without a lower royalty, he added, but it would take "a few years" off its life.


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Last month's EmployNews reported a decision from the National Labor Relations Board, Copper River of Boiling Springs, LLC, in which the Board upheld use by an employer of a policy that prohibits expressions of negativity toward customers and coworkers. Earlier this month, a different NLRB panel reached the opposite conclusion in a similar case involving a non-unionized employer's policies and procedures.
In Hills and Dales General Hosp., employees challenged three employer policies: (1) a prohibition against "negative comments about our fellow team members"; (2) a requirement that employees "represent [the employer] in the community in a positive and professional manner at every opportunity"; and (3) a requirement that employees "will not engage in or listen to negativity or gossip." The plaintiffs contended that all three requirements constitute unfair labor practices because they interfere with employees' ability to organize and to engage in concerted activity.
In response, the employer sought to introduce evidence regarding the adoption and enforcement of the policies. It contended that they were adopted with employee involvement and recommendations, and that there was no indication that the policies were ever used in any manner that would have a chilling effect on concerted activity. The NLRB panel refused to consider this extraneous evidence, concluding that on their face, all three policies were overbroad and ambiguous to the extent that they violate Section 8(a)(1) of the NLRA.
The Board concluded that the polices could, on their face, be read by employees to threaten disciplinary action if they raised complaints within or outside of the hospital with regard to the terms and conditions of their employment. This language violates the NLRA regardless of the employer's motivations or actual use of the policies.
It is very difficult to reconcile this decision with that of the Copper River panel. At the present time, the fate of these cases appears to depend on the composition of the NLRB panel that hears the cases. Absent guidance from the full Board and eventually federal courts, employers have little assurance over the legality of these types of employee behavioral expectation policies.
See more »
DISCLAIMER: Because of the generality of this update, the information provided herein may not be applicable in all situations and should not be acted upon without specific legal advice based on particular situations.
© Parker Poe Adams & Bernstein LLP | Attorney Advertising
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Just another Perl shrine | |
PerlMonks |
Loss of a Legendby dreadpiratepeter (Priest) |
on Oct 13, 2011 at 15:11 UTC ( #931268=perlmeditation: print w/replies, xml ) | Need Help?? |
For anyone who hasn't heard, Dennis Ritchie died. For you young kids, he was the creator of C and the co-creator of Unix, without which there is no Perl. I don't know that I can think of anyone who had a bigger influence on my career. He will be missed. -pete "Worry is like a rocking chair. It gives you something to do, but it doesn't get you anywhere."
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For the first time in its twenty-five year history, Asia-Pacific Economic Cooperation (APEC) looks to promote coherent advertising standards across the 21 Pacific Rim member economies in order to promote trade, writes Will Gilroy
In June 2004, when the EU grew from fifteen to twenty-five member states, the European Commission challenged the European advertising industry to create 'a better system of advertising self-regulation for a bigger Europe.' The primary incentive of the Commission was to be able to afford acceding citizens to the European Union from countries as diverse as Cyprus, Hungary and Latvia the same consumer protection that they were given in Germany, UK and France.
This led to a flurry of activity from the industry coordinated by the European Advertising Standards Alliance. Industry self-regulatory infrastructures were quickly established from Lisbon to Nicosia and Tallinn to Ljubljana on the basis of the EASA Charter Ten Best Practice Principles, an agreed checklist of core components which make for effective industry-led advertising standards.
Today, nearly every member state of the EU has a Self-Regulatory Organisation (SRO) in place which monitors, polices and enforces advertising codes of conduct and provides consumers and industry with an independent body which can process complaints and competitor disputes. It has been a remarkable achievement in such a short space of time and is testament to the European advertising industry's ability to take its responsibilities seriously.
Ten years on, the global industry has a greater responsibility still. In 2012, APEC launched the Advertising Regulatory Capacity Building Mentoring (ARCAM) programme in order to identify best practice in advertising standards and identify ways in which they might be able to seek greater regulatory convergence across APEC economies.
The rationale was very different to that of the European Union. Rather than looking at the world through the prism of consumer protection, APEC is an organisation charged with promoting trade and there is growing acknowledgment within that advertising regulation that does not meet best practice constitutes a barrier to trade and is likely to reduce competitiveness and economic output. Conversely, increasing coherence of advertising standards across APEC markets would reduce the cost of doing business as well as non-tariff barriers to trade.
APEC also recognises that there are currently significant shortcomings in many APEC markets, particularly in the emerging markets of East and South East Asia. Foreign companies entering the market are often faced with swathes of red tape and a myriad of idiosyncrasies and legal uncertainties. Entering Vietnam, Indonesia or China can prove a daunting prospect for US or European companies not used to the local ropes.
But the economic prize is too great. Six of the top ten contributors to global ad spend growth (USA, China, Indonesia, Japan, Korea and Russia) between 2013 and 2016 will be APEC economies. APEC accounts for approximately 54% of the world's gross domestic product and about 44% of world trade. APEC countries represent 40% of the world's population.
By creating clear industry standards and more transparent processes for the approval and airing of advertising content and giving industry a greater stake in policing itself, APEC would make it less costly for local companies to bring product to market and simpler for foreign companies to ensure compliance with local standards. All this would likely lead to increased trade and competition and higher advertising spend, which APEC knows to be intrinsically correlated to economic growth.
On top of this, it would be laying the framework for the EU's noble ambition and afford greater protection to APEC consumers. Realistically, the APEC process is not going to increase consumer rights in US, Canada or Australia where they are already well enshrined – but it might just provide a blueprint for a system which over time improves consumer protections in China and Vietnam, for instance, while properly weighing the interests of companies and their ability to drive economic growth – which is ultimately the most sustainable form of consumer welfare in an emerging economy.
Indeed, a reality check is needed. APEC represents 21 countries, very few of which have a great deal in common. For those who bemoan the lack of EU consensus and homogeneity, the reality of having to drive an APEC agenda on a daily basis would likely paralyse them with shock. Nor do the member countries hand over decision-making or sovereignty in the same way that EU member states do. APEC represents a light-touch, aspirational vision, created in part as a reaction to the advent of other global trading blocs around the world.
But that is not to say that greater convergence of advertising standards between APEC countries is a pipe dream. In November 2012, the Australian Advertising Standards Bureau (ASB) hosted a Dialogue on Best Practice in Advertising Standards in Hanoi at which WFA keynoted with P&G on the importance of advertising to the economy. This coincided with the Vietnamese government's own review of the Vietnamese Ad Law in which they foresee the potential development of industry-led codes of conduct and an independent 'Advertising Appraisal Council.'
Two years later, the Chinese Advertiser Association (again alongside the Australians on account of ASB's tireless work) will be hosting a two day workshop in Beijing on August 8th and 9th 2014 alongside other global industry partners including WFA, EASA and the International Chamber of Commerce.
A great deal of the focus will be given to fostering a better understanding of global best practice in advertising standards and how they can be customised to a Chinese reality. Crucially, this has the support from Chinese government and Chinese industry during the year that China hosts APEC.
With APEC's initiative, it is hard not to see growing momentum and appetite for industry involvement in setting clear and transparent standards and processes in countries such as Vietnam, Indonesia and China. Not least as these governments witness how the more evolved industry-led set-ups in India, the Philippines and Singapore can incentivise foreign direct investment.
Time will tell if the fruits of our labours can be properly reaped. It will not happen overnight. A great responsibility falls on industry to make the case for governments to revisit their advertising frameworks so that they can deliver systems which better serve consumers, businesses and the broader economy. But the first steps have been taken.
For your company to be involved in the APEC Advertising Standards Forum and Mentoring Workshop in Beijing on August 8th and 9th, 2014, please contact Will Gilroy (firstname.lastname@example.com)


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Many car manufacturers promote certified used vehicles on a dedicated Web site. For example, Ford Motor Co.'s site is FordCPO.com.
Now the independent service contract providers are getting in the game.
Among the first is The Warranty Group, a Chicago-based vendor of independent service contracts. The company intends to roll out a Web portal to promote its QCertified used-vehicle warranty program.
The Web site, QCertified.com, will launch soon after the National Automobile Dealers Association convention this month, says Rob Mancuso, a senior vice president with The Warranty Group.
Dealers will be able to post inventory that's Qcertified for free. The site will be advertised through search-engine and social media marketing campaigns as well as postings on eBay and Craigslist.
About 40 dealers are signed up so far, Mancuso says. Most are in the Midwest, but the site will post vehicles from around the country.
QCertified.com won't launch with the muscle of AutoTrader.com, and prospects gravitate toward the biggest selection. But the new site's inventory likely will grow -- postings are free.


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(b) If a merger or share exchange is abandoned under subsection (a) of this section after articles of merger or share exchange have been filed with the secretary of state but before the merger or share exchange has become effective, a statement that the merger or share exchange has been abandoned in accordance with this section, executed on behalf of a party to the merger or share exchange by an officer or other duly authorized representative, is to be delivered to the secretary of state for filing prior to the effective date of the merger or share exchange. Upon filing, the statement is to take effect and the merger or share exchange is to be deemed abandoned and may not become effective.
Note: WV Code updated with legislation passed through the 2016 Regular Session
The West Virginia Code Online is an unofficial copy of the annotated WV Code, provided as a convenience. It has NOT been edited for publication, and is not in any way official or authoritative.


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Kaitlyn Spees
Year: | SO |
Hometown: | Oakland |
High School: | Bishop O'Dowd |
Previous College: | Scripps |
Major: | Biology |
Personal bests: 5K - 19:15 (UCR '11); 6K - 24:31 (P-P '11)
Kaitlyn Spees is the human version of Homeward Bound's shadow. Like the loyal dog who climbed out of a muddy pit and limped his way home, Kaitlyn has accomplished enormous feats in her short time here at CMS. A sophomore at Scripps from Oakland, California, Kaitlyn has cut minutes off her times and proved herself as a dedicated athlete. And like Shadow, she can bark. When not splashing through Walnut Creek's muddy crossings, she can be found reciting Shakespeare or crafting works of art.


text: Silsbee looking ahead to the regional finals Back to Article Comments Need to Register? X Remember Me Forgot your password? SETX Sports PN-G baseball tops Nederland, stays perfect in 22-5A Lamar softball sweeps Alcorn State in doubleheader West Sabine head football coach resigns Lamar's win streak at five games LU announces notable speakers for coaches clinic Super Gold Boys Basketball Team Top Stories Updated: Kountze woman killed in Hardin Co. accident Beaumont cop under criminal, internal investigation Storms with possible hail approach Beaumont area Grand jury indicts 3 in auto burglaries SO: Unlucky man caught keying cars at casino Report: Teens taking selfies hit by plane, killed Authorities: Cops shoot one of their own during celebration Accused Lumberton booster embezzler tells judge she is indigent LIT announces new workplace safety courses PAPD: Man broke into home, assaulted resident


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Android Tweaker Is A Great Modding Alternative To Pimp My ROM [Review]
A while back, we reviewed Pimp My ROM that offered Android users possibly the largest collection of various system performance enhancement tweaks, hacks and mods bundled into a single package. Ranging from Kernel-based tweaks to internet & network-based mods, the tool allows both intermediate and advanced users to tinker with a lot of settings of their rooted Android devices. New to the scene, Android Tweaker by XDA-Developers senior member iGio90 is a similar tool that could prove to be a tough competitor to Pimp My ROM and other Android tweaking solutions currently available in the market. As with Pimp My ROM, Android Tweaker is equipped with loads of tweaks allowing you to play around with various performance-related settings of your Android device. Needless to say, the app is meant to work with rooted Android devices only. A good thing about Android Tweaker is that it is fully compatible with almost all Android devices, versions, kernels and ROMs (both stock & custom). Let's explore this handy utility in detail after the break.
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text: I Don't Know If This Mass Effect Rap Is Awful or AmazingKirk Hamilton4/05/12 8:45pmFiled to: Listen hereMass EffectMass effect 3Kotaku melodic55EditPromoteShare to KinjaToggle Conversation toolsGo to permalink I think I've been spending too much time on the internet. I laughed for pretty much this entire video, even though I'm fairly certain it's the most objectively bad music I've heard in a long time. Advertisement It's to the point that I don't really know what to make of it anymore, so I'm putting it up during Kotaku Melodic and I'll let you guys make up your own minds. It… there aren't words, really.Poor Jacob. Advertisement (Fair warning: It has a ton of spoilers for all three Mass Effect games.)Reply55 repliesLeave a reply


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At DelVal, you don't have to be a music major to be an active performer.
Just ask the education major who performed the second movement of Mozart's Clarinet Concerto at graduation, the biology major who plays first alto saxophone in the band, the horticulture major who performed under Moses Hogan at the Pennsylvania Collegiate Choral Festival, or the agribusiness major who starred in the chorale's production of Gilbert and Sullivan's Trial by Jury.
We believe the performing arts play an important role in your undergraduate education. That's why we encourage you to develop your creative skills by participating in one of our outstanding music organizations. At DelVal, you do not need to choose between music and chemistry lab. You can do both.


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Identifying with columnist
Comments: Re: On Being retired Gord Turner November 22
I can truly identify with Gord Turner about retirement since I arrived at the same spot little more than five years ago . Inside I feel no different than I did when I was 20 even though my outside doesn't move nearly half as fast as it did back then. Some of the things that excited me in my early years still hold the same magic for me today, though there are memories that make me shudder and wonder how it is that I am still breathing today.
It seems that not long ago I was struggling to find an opening into my career and now I am contemplating what changes retirement has brought to my life. One niggling bother is the fact that the years are creeping up on me and age has to be taken into consideration. This has led me to the question "How old am I ...Really?'. In trying to find the answer I stumbled across a short quiz helped clarify a good number of things. I would encourage the reader to take pencil in hand and determine for yourself what age they truly are.
The True Age Quiz
Scoring Explanation - In each space write
1 if this situation never occurs.
2 if this occasionally happens to you.
3 if this regularly happens in your life.
4 if this is a common occurrence.
5 if this happens without a second thought. . .
Physical Clues
_1. Your ears are growing more hair than your head.
_2. No matter who walks into the room, you no longer hold in your stomach.
_3. Your back goes out more often than you do.
_4. Reading the newspaper comfortably will require lengthening of your arms.
_5. You are truly interested in the details of other people's operations.
Clothing and Accessories
_6. The end of your tie has not seen the top of your pants for a long while.
_7. You can survive without sex but not without your glasses.
_8. You are very comfortable wearing black socks and sandals.
_9. Your wardrobe is a eclectic mixture of love beads, leisure suits and Armani ties.
_10.You wear sweat pants so you can breathe rather than because you planned an athletic activity.
Tools and Toys
_11. You have purchased a compass for the dash of the car.
_12. You take exceptional pride of your lawnmower.
_13. Neighbours have taken to borrowing tools from you.
_14. You are buying a metal detector so that you can enjoy the beach.
_15. Laying on the floor in front of the television has not occurred in at least two decades.
Activities and Pastimes
_16. Discussion about pension plans has ended in a heated argument more than once.
_17. You can fully explain what the word 'Equity' means.
_18. Speed limits are no longer viewed as a 'challenge'.
_19. Going to work holds more appeal than booking off sick.
_20. People shake you awake from your nap thinking that you're dead.
Social Life
_21. Your neighbours never even notice that you've had a 'wild' party at your place.
_22. When you talk about 'good grass' you are referring to someone's lawn.
_23. Going bowling without drinking is a common occurrence.
_24. A phone call at 9 PM is always accompanied by the question 'Did I wake you ?'.
_25. You enjoy the hip tunes they use for elevator music.
Scoring Explanation
The final tally will give you a combination of chronological and biological age, in other words your "True" age. Find the category you fall into below for further explanation.
0-20 Either you are being exceedingly dishonest or have yet to be born. In either case, Why are you taking this quiz?!!
21-40 There is nothing to concerned about. The terms 'mid-life crisis' and 'pension' are little more than vague notions that will happen to everyone else at some point in the distant future.
41-60 You may be in the throes of mid-life or perhaps your denial factor around ageing is such that only a motorcycle or sports car can alleviate the problems you face.
61-80 Mid-life crisis is behind you and a good pension is in front of you. Life is to good to even consider yourself 'old'.
81 - 100 Your mortality is staring you in the face. Please drop the author an e-mail.... I need to chat with people I have a lot in common with.
Ryan Lengsfeld
Nelson, BC