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Extraordinary travel memoirs

use from Diego Garcia: Discovery Tour [Journey – Book 2] from  The talented writer Susan Joyce tells more of her memoirs, starting with her from Lullaby Illusion: Awakening Journey [Journey – Volume 1] from  . The result is a fascinating book that combines the types of memoirs and travel books and tells the author's further […]

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An excellent and reliable airline travel agency can offer you more choices and more services than what you can find on the Internet. Moreover, it has been found to be more convenient and comfortable for many flying customers to be able to talk to real people in actual locations. It is important to know that […]

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Wednesday, December 19, 2012

CP&T Issue Focuses on Personalized Medicine

The October 2012 issue of Clinical Pharmacology & Therapeutics focuses on individualized medicine including articles that discuss, reveal and tackle key issues in the field of PGx, and provides examples of current clinical implementation projects. Clinical Pharmacology & Therapeutics Volume 92, Issue 4 (October 2012)

Amongst these are articles by past and present members of the PGRN:
and articles we have announced in previous blogs:

Thursday, December 13, 2012

CPIC publishes guidelines on interpreting genetic test results for HLA-B*5801 when prescribing allopurinol therapy.

Allopurinol is an analog of the purine base hypoxanthine. It inhibits the conversion of hypoxanthine and xanthine to uric acid by XDH and is used in the treatment of gout.  Severe cutaneous adverse reaction, SCAR, also known as allopurinol hypersensitivity syndrome, is a rare serious and sometimes fatal side effect that occurs in an estimated 0.1 to 0.4% of allopurinol-treated patients.  SCAR is manifested by Stevens-Johnsons Syndrome (SJS), Toxic Epidermal Necrolysis (TEN) or drug reaction with eosinophilia and systemic symptoms (DRESS).

There is substantial evidence linking HLA-B*5801 with allopurinol-induced SCAR [see Articles: 15743917, 18192896, 19018717, 19696695, 21301380, 21393610, 21545408].  A recent meta-analysis pooling all the published studies gave the odds ratios for allopurinol induced SCAR in HLA-B*5801 carriers as 73 and 165 for studies using healthy controls and allopurinol tolerant controls, respectively [Article: 21906289].
A multinational team of rheumatologists, clinicians and pharmacogenomics researchers evaluated the evidence on HLA-B*5801 and allopurinol-induced SCAR. The CPIC guidelines recommend that allopurinol not be used in patients who are known carriers of HLA-B*5801.

To find out more:

Please click here to see excerpts from the guideline and access downloads of the article and supplement .

Please click here for a complete list of CPIC publications.

Friday, December 7, 2012

European Medicines Agency Drug Labels

European Public Assessment Reports (EPARs) for drugs published by the European Medicines Agency (EMA) that include pgx information are now available to view on PharmGKB. We add any pgx-containing EMA or FDA drug labels that come to our attention.

Like our FDA drug label information, we provide a summary and excerpt from the EMA drug report. A PDF of the EPAR with pgx information highlighted by our curators is available to download.

View our complete list of drug labels with pgx information.

View newly added EMA drug labels and related genes:

Monday, December 3, 2012

New PGRN Featured Project and PI for the Month of December

The PGRN website is featuring a new project and investigator of the month from the NWAP (Pharmacogenetics in Rural and Underserved Populations) group.

For detailed information, please visit the PGRN website.

PharmGKB welcomes Julia Barbarino to the team

We are pleased to welcome scientific curator Julia Barbarino to the PharmGKB team. Julia recently completed her master's in Medical Molecular Genetics from the University of Aberdeen, Scotland, where her research focused on epigenetic modifications of the apolipoprotein E gene and their role in human longevity. While undertaking her degree, she had the opportunity to receive lectures in pharmacogenomics, and is excited to be working with PharmGKB in this area of genetics. In addition to her master's degree, Julia also holds a degree in Biochemistry from UCLA.

Wednesday, November 21, 2012

New VIP gene summary for CYP2E1

A new VIP summary is available for CYP2E1, a member of the cytochrome P450 family of drug metabolizing enzymes. CYP2E1 is constitutively expressed in the liver but makes up less than 1% of the total hepatic P450 isoforms [Article: 20100563]. It metabolizes relatively few prescription drugs (approximately 2%), however its important in the toxicity of acetaminophen, the antituberculosis drug isoniazid, and the probe drug and muscle relaxant chlorzoxazone [Article: 18695978]. Pathways for acetaminophen and isoniazid are in development and will be released soon ( NEW: Acetaminophen Pathway, Pharmacokinetics is released 1/16/2013).

For more information on this VIP gene and its variants see the VIP tab for CYP2E1

Tuesday, November 6, 2012

PharmGKB welcomes Ugur Hodoglugil to the team

We are pleased to welcome scientific curator Ugur Hodoglugil to the PharmGKB team. Previously, Ugur has worked as research scientist on identifying the genetic determinants of complex traits (lipid and other metabolic phenotypes) and population structure at Gladstone Institutes, University of California San Francisco where he analyzed genome-wide scans data for quantitative trait locus analysis in families and studied the effects of variations of several candidate genes on lipid metabolism in unrelated individuals. He  performed different assays with transgenic/knockout mice and cell culture experiments to show functionality of the variants or the phenotype of gene(s) of interest. He has obtained his M.D. and Medical Pharmacology, Ph.D. degrees from Ankara, Turkey.

Monday, November 5, 2012

New PGRN Featured Project and PI for the Month of November

The PGRN website is featuring a new project and investigator of the month from the PAT (Pharmacogenomics of Arrhythmia Therapy) group.

For detailed information, please visit the PGRN website.

Saturday, November 3, 2012

From Genomics & Informatics to Precision Medicine

Several PharmGKB curators plan to attend UCSF's Institute for Human Genetics 2012 Symposium on Monday 5th Nov, entitled "From Genomics and Informatics to Precision Medicine".

Speakers include those from Genentech, Kaiser Permanente and prominent universities in the USA.

We hope to see you there!

Friday, November 2, 2012

PharmGKB team celebrates Halloween

The PharmGKB team joined the Halloween celebrations this week - take a look at our pumpkin carving skills!

ASHG Annual Meeting 2012 (6th-10th Nov)

The PharmGKB curators will be attending the American Society of Human Genetics Annual Meeting in San Francisco next week and look forward to a week of interesting talks and posters.

On Thursday 8th November (2:15-3:15pm) we will be presenting two posters - one focusing on the pharmacogenomic research undertaken by PharmGKB consortia, and the other focusing on the clinical interpretation and implementation of pharmacogenomics knowledge.

We hope to see you there!

Tuesday, October 9, 2012

Defining our lists of PGx information

With the increasing implementation of pharmacogenomics knowledge we are often asked "What is the difference between the CPIC gene list, VIP list and the Clinical Annotations list on PharmGKB?"

Here we clarify their contents:

VIP genes (purple layer of the PharmGKB Knowledge Pyramid)
This is a list of Very Important Pharmacogenes for which the PharmGKB curators have written a concise review about the gene from the published literature. These summaries are useful for research purposes and background knowledge. These are genes with a known role in the pharmacokinetics or pharmacodynamics of drugs but associations with VIP genes may not necessarily translate into therapeutic recommendations for the clinic. This list is added to as new VIP summaries are written and published, and VIP summaries are periodically reviewed and updated.

Clinical Annotations (blue layer of the PharmGKB Knowledge Pyramid)
The PharmGKB Clinical Annotations cover the full spectrum of pharmacogenetic associations between a particular genetic variant and a drug, from low levels of evidence (e.g. in vitro assays only) to those that are implemented in the clinic. The likely drug response is outlined for each genotype of the genetic variant. Clinical Annotations below Level 1A may not yet be clinically actionable.

CPIC Gene-Drug Pairs (top green layer of the PharmGKB Knowledge Pyramid)

This is a list of gene and drug combinations for which consensus genotype-based therapeutic recommendations for clinical practice can be made. CPIC guidelines are only written for pharmacogenetic associations that are clinically actionable. This list is updated as new CPIC guidelines are published or new suggestions for important gene-drug pairs are discussed by the CPIC group. Read more about CPIC and view the published CPIC genotype-based dosing guidelines.

Read more in the Overview of the PharmGKB
Read the recent PharmGKB publication

The PharmGKB Knowledge Pyramid

Monday, October 8, 2012

New pathway: Vemurafenib Pathway, Pharmacodynamics

We have added a new pathway: Vemurafenib PD pathway to our pathway collections.

Vemurafenib (marketed as ZELBORAF) is an oral BRAF inhibitor used to treat late-stage melanoma.  It specifically targets the mutant BRAF protein (V600E isoform) that is found in approximately half of all cases of melanoma. Vemurafenib is a personalized targeted therapy and it is only designed to be used in patients with the BRAF V600E mutation, but not for use in patients with wild-type BRAF melanoma.

PharmGKB Vemurafenib PD pathway describes the mechanism of action of vemurafenib and how it blocks tumor cell proliferation and survival via targeting BRAF V600E to effectively inhibit the MAPK signaling pathway.

View or download the pathway at Vemurafenib PD pathway.

View all pathways at PharmGKB.

Friday, October 5, 2012

PharmGKB welcomes Daniel Klein to the team

We are pleased to welcome curator Daniel Klein to the PharmGKB team. Daniel recently graduated from the University of California, San Diego. His background is physics (specializing in astrophysics) with minors in biology, chemistry, and psychology. During his senior year at UCSD, Daniel worked as a part-time curator for the PharmGKB. We thank UCSD for providing Daniel a broad introduction to pharmacogenomics during his graduate course which included lectures from such PGx notables including Darrell Abernethy and Richard Weinshilboum.

Friday, September 28, 2012

PGx Look Up Tables

The Translational Pharmacogenetics Project (TPP) is a PGRN-led initiative with the goal to operationalize the work of CPIC by translating widely accepted actionable pharmacogenetics discoveries into real-world clinical practice.

TPP creates "look up" tables by gene which contain phenotype and clinical decision support system information based on haplotypes and diplotypes. These tables are a work in progress and are offered on PharmGKB "as is" until the tables become formalized.

View the TPP lookup tables for:
Read more:
A Clinician-Driven Automated System for Integration of Pharmacogenetic Interpretations Into an Electronic Medical Record.
Hicks JK, Crews KR, Hoffman JM, Kornegay NM, Wilkinson MR, Lorier R, Stoddard A, Yang W, Smith C, Fernandez CA, Cross SJ, Haidar C, Baker DK, Howard SC, Evans WE, Broeckel U, Relling MV. Clin Pharmacol Ther. (2012) Sep 19. doi: 10.1038/clpt.2012.140.

Wednesday, September 26, 2012

New Haplotype features on PharmGKB

New features on the Haplotype tab (example: CYP2A6):
  • Details of the resources used to determine our curated haplotype maps and any important notes regarding the haplotypes are added by our curators.
  • Previously we only displayed dbSNP rsIDs within haplotypes - now you can view other genetic variants that currently have no known rsID.
  • Different colors denote the reference sequence, positions that differ from the reference and tag SNPs.
Haplotypes now also appear on gene and drug pages in the PGx Research table (example: CYP2A6 as pictured), with information including tag alleles and drugs that have been associated with the haplotype in our database.
  • To view individual haplotype pages: search for a gene or drug, click on the PGx Research tab, click on the haplotype name.
  • Individual haplotype pages now have extra tabs - Overview, PGx Research and VIP tab
  • PGx Research tab will appear if there are variant annotations for this haplotype
  • VIP tab will appear if there is a very important pharmacogene summary with a summary for this haplotype

    Wednesday, September 19, 2012

    PharmGKB Clinical Annotations Update and New Levels of Evidence

    We have launched an update of our Clinical Annotations, assessing new evidence available for each gene variant - drug association. Each Clinical Annotation is written by a PharmGKB curator and assigned a level of evidence. We have recently revised our criteria to provide 6 levels of evidence, from the highest (1A) to the lowest (4), detailed below:

    Level 1A - Annotation for a variant-drug combination in a CPIC or medical society-endorsed PGx guideline, or implemented at a PGRN site or in another major health system.
    Level 1B - Annotation for a variant-drug combination where the preponderance of evidence shows an association. The association must be replicated in more than one cohort with significant p-values, and preferably will have a strong effect size.
    Level 2A - Annotation for a variant-drug combination that qualifies for level 2B where the variant is within a VIP (Very Important Pharmacogene) as defined by PharmGKB. The variants in level 2A are in known pharmacogenes, so functional significance is more likely.
    Level 2B - Annotation for a variant-drug combination with moderate evidence of an association. The association must be replicated but there may be some studies that do not show statistical significance, and/or the effect size may be small.
    Level 3 - Annotation for a variant-drug combination based on a single significant (not yet replicated) association or annotation for a variant-drug combination evaluated in multiple studies but lacking clear evidence of an association.
    Level 4 - Annotation based on a case report, non-significant study or in vitro, molecular or functional assay evidence only.

    Clinical Annotations can be found on PharmGKB:

    We describe these new level of evidence criteria in the new published article:
    M Whirl-Carrillo, E M McDonagh, J M Hebert, L Gong, K Sangkuhl, C F Thorn, R B Altman and T E Klein. Clinical Pharmacology & Therapeutics (2012) 92: 414-417; doi:10.1038/clpt.2012.96
    Click here to download the PDF

    Tuesday, September 11, 2012

    Zidovudine Pathway Publication

    Zidovudine (ZDV, also known as azidothymidine (AZT)) is an important drug used for treatment of HIV infection. Belonging to the family of nucleoside analog reverse transcriptase inhibitor (NRTI), it is structurally related to the endogenous nucleoside thymidine. ZDV is a prodrug and must be activated by phosphorylation to exert its antiviral action.

    ZDV has three important pathways of clearance: 1) phosphorylation through cellular kinases to zidovudine triphosphate; 2) inactivation by glucouronidation; 3) reduction of the azido moiety.
    Zidovudine triphosphate inhibits the activity of HIV-1 reverse transcriptase by competing with the endogenous nucleotide thymidine triphosphate for incorporation into newly synthesized viral DNA, which leads to DNA chain termination.

    Few studies have evaluated pharmacogenomics with respect to zidovudine and antivirals overall. To find out more about how genetic variations in genes involved in the ZDV metabolism might influence efficacy and toxicity of zidovudine therapy read our publication PharmGKB summary: Zidovudine Pathway and visit the interactive pathway diagram at PharmGKB.

    PharmGKB summary: Zidovudine Pathway. Y. Ghodke, P. L. Anderson, K. Sangkuhl, J. Lamba, R. B. Altman, T. E. Klein. Pharmacogenet Genomics 2012. PMID: 22960662.

    View all pathways on PharmGKB.

    Tuesday, September 4, 2012

    Curators' Favorite Papers

    The current Curators' Favorite Papers highlight articles about the translation of pharmacogenomics into practice.  The article by Johnson et al. describes the design of a customized pharmacogenetics genotyping array. This broad pharmacogenetics panel is built for the personalized medicine programs of the University of Florida and Stanford University [PMID: 22910441]. The publication by O'Donnell et al. introduces the "The 1200 Patients Project", a pharmacogenetics implementation project established by a team at the University of Chicago [PMID: 22929923]. Chua and Kennedy review current state and future prospects of direct-to-consumer pharmacogenetics [PMID: 22934000].

    New PGRN Featured Project and PI for the Month of September

    The PGRN website is featuring a new project and investigator of the month from the PNAT (Pharmacogenomics of Nicotine Addiction Treatment) group.

    For detailed information, please visit the PGRN website.

    Thursday, August 30, 2012

    The 1200 Patients Project

    "The 1200 Patients Project" is a pharmacogenetics (PGx) implementation project established by a team at the University of Chicago who recruited 12 physicians to participate. The project is prospectively recruiting 1200 adults taking 1-6 prescription drugs, who are under the care of one of the participating physicians, and who give consent for pre-emptive genotyping of a panel of clinically-relevant PGx variants.

    A genomic prescribing system (GPS) on a web-based portal for physicians provides patient-specific clinically-relevant pharmacogenetic summaries for a drug, with stop light representations of level of risk for an adverse event or non-response. The physicians are monitored to examine whether they access the GPS during a patient's visit. The primary and secondary end points of the project are to assess whether they take the PGx information into consideration and whether this results in changes in prescriptions for patients who are at a high risk.

    The aim is to assess the effectiveness of a model in which PGx information is provided to physicians in an accessible format from which they can make informed decisions when they are in consultation with a patient.

    Read more:
    The 1200 Patients Project: Creating a New Medical Model System for Clinical Implementation of Pharmacogenomics. O'Donnell PH, Bush A, Spitz J, Danahey K, Saner D, Das S, Cox NJ, Ratain MJ. Clin Pharmacol Ther. 2012 Aug 29. doi: 10.1038/clpt.2012.117. [Epub ahead of print]

    Monday, August 27, 2012

    Development of a Customized PGx Genotyping Array using key variants in PharmGKB

    The University of Florida and Stanford University are undertaking a joint pharmacogenetics implementation project funded by the NIH, piloted first at Florida and replicated at Stanford. Initially, CYP2C19 genotype will be used to guide clopidogrel therapy, however a customized array of SNPs from 120 genes involved in drug response was designed for preemptive genotyping. This enables a patient's genotype information to be available in the future if or when a drug is to be prescribed. Read more in the Clinical Pharmacology & Therapeutics article available online.

    Selecting SNPs for the array included one or more the following:

    1. There is a PharmGKB Clinical Annotation written between the SNP and a drug response, usually with high levels of evidence.
    2. It is a functional SNP within a VIP
    3. It is a known tag SNPs for an important PGx haplotype
    4. It is a SNP of interest to the research groups

    to give:
    252 PGx SNPs (listed in the Supplementary Information) + 2 sex markers + 2 SNPs for quality control

    Details of the genotyping array technology, validation, costs and turnaround times are outlined. Also discussed in the article are the current potential barriers to clinical implementation of pharmacogenetics, and how a preemptive genotyping approach can overcome some of these.

    J A Johnson, B M Burkley, T Y Langaee, M J Clare-Salzler, T E Klein and R B Altman. Clinical Pharmacology & Therapeutics (2012); advance online publication 22 August 2012. doi:10.1038/clpt.2012.125

    Wednesday, August 22, 2012

    New sortable PGx Research tables on PharmGKB

    Tables of our Variant Annotations found on the PGx Research tab (view on gene, drug, variant and haplotype pages) can now be sorted and filtered to allow you to see the most relevant information you want to see.

    example: If you want to see all variant annotations between the genetic variant rs1800462 (TPMT*2) and the drug mercaptopurine.
    • From our homepage search for 'rs1800462' and click on the PGx Research tab to see the table of Variant Annotations.
    • Add filter: select 'Drug'/ pick filter select 'contains'/ type mercaptopurine/ click add (pictured).
    • The list can then be sorted by each column e.g. significance, p value.
    • Click the configure icon (pictured) in the right hand corner above the table to add, remove or rearrange columns and save your desired settings to keep them for the next time you come to the website.

    Monday, August 20, 2012

    New features on the PharmGKB website

    Check out the new features we have launched at
    • Information is now more readily available, including haplotypes listed in the PGx Research Tab on gene and drug pages, and sortable tables.
    • Our Clinical Annotations and Variant Annotations have their own page and a new look
    • Variant Annotations from the published literature used by our curators to determine the level of evidence are listed with each Clinical Annotation (click 'Show Evidence' as pictured).
    We hope these new features help our users view the information they want more easily - we encourage feedback and questions to

    Wednesday, August 15, 2012

    Mining the pharmacogenomics literature

    Briefings in Bioinformatics Special Issue: Current Progress in Bioinformatics 2012 contains an editorial by Russ Altman discussing the current status of bioinformatics research.

    Among the articles in this special issue is a review on the current status of techniques for mining of the pharmacogenomics literature and includes descriptions of studies that have utilized the corpus of human-curated pharmacogenetic (PGx) articles in PharmGKB to train or assess the accuracy of machine-learning methods.

    "The PharmGKB repository comes perhaps closest to the vision of an all-embracing pharmacogenomics corpus. It represents a major step towards an interdisciplinary biomedical information store." quote from:

    Mining the pharmacogenomics literature -- a survey of the state of the art. Hahn U, Cohen KB, Garten Y, Shah NH. Brief Bioinform. 2012 Jul;13(4):460-94.

    At the PharmGKB we are currently working on a natural language processing (NLP) pipeline that would assist in the identification of relevant PGx articles for our curators to then manually curate.

    Friday, August 10, 2012

    New PGRN Featured Project and PI for the Month of August

    The PGRN website is featuring a new project and investigator of the month from the PARC (Pharmacogenomics and Risk of Cardiovascular Disease) group.

    For detailed information, please visit the PGRN website.

    Monday, August 6, 2012

    Curators' Favorite Papers

    Current Curators' Favorite Papers: The review by Alfirevic and Pirmohamed discusses genetic factors associated with drug-induced liver injury with a special focus on HLA gene variation [PMID: 22850601].  Parvez et al. reports that a common SNP on chromosome 4q25, which is associated with atrial fibrillation, modulates response to antiarrhythmic drugs [PMID: 22726630]. Savonarola et al. reviews the role of mutational analysis in anti-cancer targeted therapy [PMID: 22760589].

    Thursday, August 2, 2012

    A message about RFA-HG-12-016

    RFA-HG-12-016 "Clinically relevant genetic variants resource:  a unified approach for identifying genetic variants for clinical use (U01)."

    The PharmGKB team is excited to see this RFA because clinical genomics has great potential to impact medicine. PharmGKB catalogs genetic variation of relevance to drug response (pharmacogenomics) and moves research data to guidelines for clinical action.  We do not intend to apply for this RFA and we look forward to working with the grantee(s) under this program, who we presume will primarily focus on clinically actionable variants relevant to disease risk.

    Monday, July 16, 2012

    New PGRN Featured Project and PI for the Month of July

    The PGRN website is featuring a new project and investigator of the month from the PHAT (Pharmacogenetics of Asthma Treatment) group.

    For detailed information, please visit the PGRN website.

    Thursday, July 12, 2012

    Effect of a genetic variant associated with Multiple Sclerosis mirrors response to anti-TNF therapy

    Though anti-TNF therapy can be effective in the treatment of many auto-immune diseases including Rheumatoid Arthritis (RA), drugs that block TNF can promote or exacerbate Multiple Sclerosis (MS).

    A genetic variant (rs1800693) within the TNFRSF1A gene has been identified in multiple GWAS as being associated with MS but not associated with other auto-immune diseases, such as RA and Chrohn's disease. New findings show that allele G of rs1800693 (the risk allele for MS) alters exon splicing and results in a novel soluble TNFR1 protein that antagonizes TNF, mimicking the effect of anti-TNF therapeutics.

    Therefore, disease-associated genetic variants identified in GWAS may provide insight into mechanisms behind drugs that cause adverse effects associated with inducing or exacerbating disease symptoms, and may help inform treatment choice for common multifactorial diseases.

    Read the article in Nature Letters:
    TNF receptor 1 genetic risk mirrors outcome of anti-TNF therapy in multiple sclerosis
    Gregory, A.P. et al, Nature, Published online

    MS = Multiple Sclerosis
    Rheumatoid Arthritis
    TNF = tumor necrosis factor
    TNFR1 = tumor necrosis factor binding protein 1
    TNFRSF1A = tumor necrosis factor receptor superfamily, member 1A

    Tuesday, July 10, 2012

    New pathways on PharmGKB: Sorafenib PK and PD

    We have added two new pathways: Sorafenib PK and PD pathways to our pathway collections.

    Sorafenib (Nexavar, BAY 43-9006) is a cancer drug used to treat advanced renal cell carcinoma and unresectable hepatocellular carcinoma.  It blocks tumor cell proliferation and angiogenesis by targeting various types of serine/threonine and receptor tyrosine kinases.  PharmGKB sorafenib PD pathway describes its mechanism of action and PK pathway depicts candidate genes mediating the metabolism, transport of sorafenib and possible drug-drug interactions.

    View or download the pathways at Sorafenib PK and PD.

    View all pathways at PharmGKB.

    Monday, July 9, 2012

    New Relationships File Available

    PharmGKB has a new relationships file available for download. This file catalogs all the current relationships between drugs, genes, diseases, variants, and haplotypes in PharmGKB. These relationships are based on annotations generated by our curators.

    The new relationships file replaces and improves on the old relationships file. The entries in the old relationships file were based on co-occurence of gene, drug, and disease names within literature (primarily abstracts) and did not necessarily represent direct, curated relationships between entities.

    The relationships file has quite a few new features.
    • Includes relationships from our new annotations like clinical annotations, dosing guidelines, and drug label annotations
    • Each relationship indicates what types of annotation it comes from in the “Evidence” field.
    • PMIDs are now listed for relationships when available in the “PMIDs” field. This is a semi-colon(;) delimited list of PMIDs used to support the annotation.
    • The “Association” field gives a sense of whether an association is positive, negative, or ambiguous. Please see note below regarding associations in disease relationships.
    • Haplotype annotations are now included.
    • PK/PD flags for pharmacokinetic or pharmacodynamic relationships have been added back in.
    To get a copy of this file please sign into the site, agree to the PharmGKB Relationship Agreement on the Downloads page, and a copy of the file with supporting documentation will be sent to you.

    NOTE: Disease associations derived from a VariantAnnotation or ClinicalAnnotation are really referring to a variant that has an annotation with that “Disease” tag. These associations can be misleading because they are not necessarily indications that a variant is directly associated with a disease phenotype.

    Tuesday, July 3, 2012

    PharmGKB has an opening for a scientific curator

    PharmGKB is looking to fill a Curator position in the Department of Genetics at Stanford University.  We are specifically looking for someone with a clinical or pharmacology background to add to the curation team.

    This position works with a group of curators to collect and analyze information from the scientific literature as well as through direct submissions, abstracting this information in the required format(s), verifying for accuracy, compiling educated summaries of the literature, discovering new facts by analyzing the collected data and refining the submitted data.

    Qualifications required:

    PharmD, PhD, MD
    Three - five years relevant experience
    In-depth training and knowledge of pharmacology, genetics, molecular biology, and/or bioinformatics
    In-depth training and knowledge of pharmaceuticals including dosing, interactions and use.
    Familiar with disease areas including cancer, cardiovascular disease and asthma as well as publicly available biological databases
    Strong analytical, organization and communication (English written and oral) skills
    Detail oriented
    Desired Qualifications:
    Seven years relevant experience
    Experience with relational databases, data integration and statistics preferred
    Enjoys public speaking

    Please apply here if you are interested in this position.

    Friday, June 29, 2012

    Genetic contribution of response to opioids

    Opioids  are commonly prescribed for pain relief, yet many individuals suffer adverse side effects such as nausea, dizziness and sedation.

    A study published in this month's Anesthesiology set out to establish the relative contribution of genetic and environmental factors in opioid response. 114 monozygotic and dizygotic twin pairs were recruited, and were given either alfentanil then placebo, or placebo then alfentanil. Significant heritability was shown for respiratory depression, nausea and disliking of the drug. Almost 60% of the variation in nausea response was attributed to genetic effects. Genetic effects also accounted for around 25% of the variance in disliking of the drug, and 30% of the variance in respiratory depression decreases. Genetic and/or environmental effects were attributed to liking of the drug, sedation, dizziness and pruritus.

    Aversive and Reinforcing Opioid Effects: A Pharmacogenomic Twin Study. Angst M.S. et al. Anesthesiology. 2012 Jul;117(1):22-37. Read the article

    PGx of opioids
    Discovering the specific genetic variants behind these side effects may help identify patients most at risk before prescribing opioids...

    Variants within the CYP3A5 and OPRM1 gene have been associated with alfentanil drug metabolism and dosage, respectively; view these variant annotations on PharmGKB.

    To avoid toxicity, CPIC have published therapeutic dosing guidelines for codeine based on an individual's CYP2D6 genotype; view these dosing guidelines on PharmGKB.

    Numerous genetic variants in many different genes have been associated with response to or dosage of methadone; view these variant annotations on PharmGKB.

    Tuesday, June 26, 2012

    Helix Group & PharmGKB Retreat

    Much fun and team-building was had at the Stanford Helix Group & PharmGKB retreat in San Diego last week - including sea kayaking, insightful talks and a lively discussion with guest speaker Philip Bourne

    Helix Group & PharmGKB team members kayaking in San Diego

    Curators' Favorite Papers

    The current Curators' Favorite Papers are about pharmacogenomics of antidepressant drugs. Narasimhan and Lohoff review recent findings on the pharmacogenetics of antidepressant drugs and discuss possible future clinical implementations [PMID: 22380000]. The study by de Klerk et al. investigates the association of ABCB1 variants with adverse effects of antidepressants in a large cohort of patients with major depressive disorder. The authors report a significant association between the number of selective serotonin reuptake inhibitors-related adverse drug effects and two ABCB1 SNPs (rs2032583 and rs2235040) [PMID: 22641028]. Sasayama et al. present evidence that polymorphisms in the CUX1 gene (rs365836 and rs201522) may be associated with response to antidepressant treatment based on a genome-wide approach followed by a candidate SNP analysis [PMID: 22584459].


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Obtaining SDWinPEx64.iso – HP WinMagic Decryption Tool

Posted by

This Windows pre-boot execution environment ISO can be used on encrypted HP drives to recover the data or fix the Windows install. You’ll need to know the decryption key or the encryption login password for a user on the machine.

SDWinPEx64.iso ordinarily needs to be obtained from HP support, but I’ve hosted a copy here for those who don’t have a valid support subscription. You can get it at https://phil.lavin.me.uk/downloads/SDWinPEx64.iso

There’s a decent guide here for fixing a corrupted BCD: http://tom.meinlschmidt.org/2015/06/16/bcd-boot-troubles-and-winmagic-encryption/

  1. Bless you. This has been happening quite frequently and end up doing a full recovery. This saved me tons of time!! Thanks!!!

    1. I don’t remember the exact details of the recovery process, to be honest… but I don’t actually recall that being required. I think we just booted the ISO and unlocked each partitions, then ran the normal Windows fix tools.

  2. I cannot say thank you enough to you for posting this. It really saved a lot of time for me. Please continue posting these kinds of help for users like me. Again many thanks and God Bless you!

  3. Hi all,
    When I used the WinPe, I can see the drive that is encrypted,but the bottom of “unlock” is unable. The status of the drive C is encrypted.
    Do you have any idea?
    thank you

  4. This worked for me: The boot partition was corrupt in some way and so I had a computer that is encrypted and not fixable. So, downloaded the utility as mentioned above. I could not get the qdir utility to do anything for me except show me the files…i.e. I didn’t see how to move them to a new drive. I ran the SD Recovery Plugin. I selected Crypto Status tab and below I selected the first slot and clicked -login. I did that for the next couple slots also, not knowing which was my real physical drive until after. You will notice one status is then different from the others. I then went back to File Browser window and the one drive that showed as empty before was now 450gb of a viewable file system tree. Not figuring out how to copy the files within the file brower gui, I opened a DOS cmd prompt and used xcopy to copy all needed folders to the new/clean install of Win7/drive. example c:\> md temp (enter -create place to send files)
    c:\> g: (enter) < xcopy users\mike\*.* c:\temp\mike /s/e
    —–and the same with the QBData folder, etc.
    once the files were on the new pc, I could move them to a proper location.
    ****The SDWinPEx64.iso was a life saver **** Thanks so much!

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text:
Follow CBSPHILLY Facebook  | Twitter

MEMPHIS (CBS Local) – An Uber driver in Tennessee didn’t react too kindly to being told he was driving the wrong way and wound up allegedly hitting his passenger with a baseball bat, police say.

According to Memphis police, John Pearson called for an Uber ride home on May 31. When driver Juan Magdalenas arrived, Pearson claimed the ride turned rocky from the beginning.

Woman Reportedly Leaves Mascara On Too Long, Almost Loses Her Eyesight

“When the Uber driver got there, he was a little agitated. He asked me if I was going to throw up in his car,” Pearson said, via WREG. Things reportedly went downhill quickly when the customer told the 44-year-old driver he was going in the wrong direction.

“I said, ‘Hey man, I live the other direction,’ and he said, ‘Get out! Get out of my car! Get another Uber!'” After Magdalenas left his passenger at a local car wash, Pearson admits to kicking the car’s bumper, which triggered the driver’s attack.

“He slammed on his brakes and immediately got out an aluminum baseball bat and came and swung at me, and I put my arm up to block it and he smashed me on my wrist,” Pearson explained.

“This is a regrettable and concerning incident. The driver was removed from the app and we are looking into the matter,” Uber said in a statement on June 5. The five-star rated customer says Uber should be doing more after learning that Magdalenas has allegedly been connected to multiple assaults in the past.

IHOP Restaurant Announces It’s Changing Its Name To IHOB

Magdalenas claims that there was no assault and that the two only argued during the trip.


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Here is the LET Board Exam Result September 2019 Including the Full List of Passers for Elementary and Secondary Level

UPDATED (11/28/2019) LET RESULT 2019 – Here is the Licensure Exams for Teachers LET Board Exam Result September 2019 (Elementary and secondary level) – UPDATED (11/28/19)

The Professional Regulation Commission is about to release the LET Teachers Board Exam Result September 2019 including the list of passers, top 10 passers, top performing and performance of schools.

The official results of 2019 Licensure Examination for Teachers will be available on this website after it will be released. PRC would release the examination results within forty-four (44) working days after the board examinations.

LET Board Exam Result

PRC Board of Professional Teachers headed by its Chairman, Dr. Rosita L. Navarro, Vice Chairman Dr. Paz I. Lucido, and its members Dr. Paraluman R. Giron and Dr. Nora M. Uy administered the licensure examination on September 29, 2019.

The teacher’s licensure examination has been given at PRC testing centers in Manila, Bacolod, Baguio, Batanes, Butuan, Cagayan de Oro, Catarman, Cebu, Kidapawan, Davao, General Santos, Iloilo, Laoag, Legazpi, Lucena, Masbate, Marinduque, Occidental Mindoro, Oriental Mindoro, Palawan, Pagadian, Pampanga, Romblon, Rosales, Tacloban, Tuguegarao and Zamboanga.

Target Date of Releasing Results

PRC is expected to release the LET Board Exam Results on November 29, 2019 (Tuesday). However, the LET results might be released earlier or later than the expected date.

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16 July 2019

Free For All Tuesday - No. 441

So what questions or discussion points have you got for us today?

It doesn't matter if you are a beginner or a more experienced user of organisers, we want to hear your thoughts, questions, opinions etc.

We are here to answer your questions.

Make today the one day you post a comment or a question.

It is Tuesday after all so fire away.

No comments:

Post a Comment


text:
I read it is unethical to hire someone because it breaks the second categorical imperative which is to treat people as an ends. If by hiring someone to do something you are treating them as a means to get a job done and therefore it is unethical. Are there any counters to this?

  • one example i've seen is taxi drivers, you're not treating a taxi driver as a means by paying them to take you somewhere – another_name Apr 7 '19 at 3:44

You're missing an important word. The second formulation of the categorical imperative in the Groundwork is:

Act in such a way that you always treat humanity, whether in your own person or in the person of any other, never simply as a means, but always at the same time as an end.

The key phrase here is "never simply." Kant has no problem with entering into mutually beneficial rational contracts.

Maybe stated in another way, using someone as a mere means is abusing their rationality by getting them to act in a way inconsistent with how they would act when fully informed.

In fact in the Metaphysics of Morals, this is how Kant understands sex and marriage, because Kant views sex as using another person as the means to your gratification, and he thinks this is only justifiable insofar as you both rationally consent to the arrangement -- and make it permanent.

For instance, Kant sees it as an abuse of a ticket seller to pay with a credit card you know is stolen. Or conversely, to sell seats you know you don't have the rights to.

For Kant, employment itself should be a rationally entered into arrangement between the employer and employee where they understand what they agree to.

http://www.utm.edu/staff/jfieser/class/300/categorical.htm http://alexanderpruss.com/145/KantOnMarriage.html

See Also

Kant's second formulation

  • An object lesson in how to answer here. I must take notice. . – PeterJ Apr 6 '19 at 11:45

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text:
How is perception formed? By perception I mean 'thought' or 'idea' of the World. What I see by itself does not contribute anything to thought. Only an acknowledgement can contribute to structuring of thought.

If, according to Tractatus, logic is innate, and we cannot think illogically, then we must think logically. And if mathematics is a method of logic, then shouldn't it be the case that we 'compute' thought of the world?

My sense of the world must be computed on the basis of available data, and expectations. Intuition then resolves to ability to acutely apply logical analysis on input, and computing what is the case. Of course some people may have poor perception, but that should be because of their inability to rigorously solve the input; the basic method remains the same -computing the world.

As an example consider the following case: If I were to ask you what would tomorrow be like, you would be able to tell a fairly accurate picture by taking into consideration your present world, and probabilistically computing tomorrow. You would be able to tell me lot of things -your family matters, work, politics, etc. On the other hand, if I ask you same about a decade down the line, you will only tell me most likely things -that in world this may happen, I may be doing this job or this might be the state of nation and so on -basically saying things with highest likelihood. So is there some sort of 'computation' or structured mechanism of intuition at play when I think of the world?

  • I added an edit below the <HR> to respond to yours. – J D Aug 26 '19 at 19:21
  • This is so broad even a book wouldn't cover it, and more suitable for Psychology & Neuroscience SE. Could you read Wikipedia and specify what the philosophical question is. – Conifold Aug 26 '19 at 22:21
  • Unrelated to your underlying question, but mathematics is not a method of logic; you got it completely backwards. Mathematics is founded on logic, and in particular classical first-order logic. You can have logic without mathematics, but you cannot have mathematics without logic. And if you truly want to understand logic, you have to actually put in some hard work into studying and practicing first-order logic, and cannot rely on philosophy texts. – user21820 Oct 15 '19 at 19:06
  • Related to your question, Tractatus is mostly nonsense; logic is not innate. FOL may intrinsically underlie reality, but humans need to actually think quite carefully to come up with FOL, or may even have to learn it from someone else. If you do a proper study of logic including learning to use a concrete deductive system for FOL, then you will know what I mean. It takes effort for almost all non-logicians to refrain from thinking illogically. For logicians, they have made a habit to think logically, so it is different for them. – user21820 Oct 15 '19 at 19:08
  • @user21820 Are you saying Tractatus is non-sense because it's author said so, or is non-sense because it is a useless piece of text (and serves absolutely no purpose)? – Ajax Oct 15 '19 at 20:34

Since we are talking about understanding thought, it should be first noted that this is a philosophically challenging topic in it's own right. And a good path would be to study Cartesian duality, Gilbert Ryle's work, as well as the work of Jaegwon Kim. You'd also have to study what we know about the anatomy and physiology of perception.

Now, to respond to your question from the philosophical angle, yes, human's are capable of logic, but a lot of thought is (EDIT) alogical. Human beings are not logic engines, but rely heavily on their emotions to draw even logical conclusions. (See Thinking, Fast and Slow by Nobel-prize winner Daniel Kahneman for the relatively current state of science on logic and decision making).

But, I'm going to dip your toes in the waters that I prefer which is artificial intelligence, in which there are two camps of thinking historically that are recently trying to reconcile their differences, connectionism and computationalism. A connectionists tries to simulate thoughts from the neuron up, and the computationalist attacks the problems by using the logics humans use, such as Boolean logic or Aristotelian syllogism, etc. Ultimately, what the camps have discovered over the last 70 years is that central to the question of what characterizes human thought, it is the creation and use of meaning.

Wittegenstein comes in two flavors, Tractatus and Philosophical Investigations, and the early Wittegenstein who was a close intellectual ally of Bertrand Russell, diverged largely on the question of meaning after exploring logical thoroughly. In his later work, he is famous for his declaration that logic and words are essentially games played by agents, and that human thought is much more than traditional logic whose rules fall short of the rules used by people. He went on to recognize "family resemblances" in meanings, and other manners of thinking that anticipated cognitive semantics and other findings in cognitive science.

Your question shows your attempts to develop your own ontology, invoking words like input, structure, and computed. The best way to answer your question is to get a good book on the psychology of perception, so you don't have to reinvent the wheel. On my shelf is Perception by Julian E. Hochberg, but it's dated. He seems to have another book copyrighted in 2007. But I'm no expert in the field.

Ultimately, you have to find what in these works appeals to your metaphysics. For me, currently I'm working works by the linguist George Lakoff who along with several allies expresses a theory regarding meaning based on conceptual metaphors and ends with a metaphysics that rejects traditional views on concepts, categories, and computation of the mind based on his views on embodied cognition.

EDIT: To answer your question, which seems to me, does the mind compute, then the answer is yes metaphorically. How does it compute? I would argue that the four important ways the mind functions is intuitively, deductively, inductively, and abductively. Intuition is showcased in Blink by Malcom Gladwell, and the latter three topics are handled in the study of logic increasing in terms of complexity and sophistication. It should be noted that computers excel at deduction, but tend to struggle with induction and abduction, as both types of logic require a better handle on the meaning of the topics reasoned. Computer science has the field of expert systems to implement more heuristic forms of computation and mimic to a better degree how humans 'compute'.

If you want to understand reasoning beyond formal logic, a good introduction would be Stephen Toulmin's Uses of Argument where he floats some ideas about how jurisprudential reckoning, and hence generalized inference functions.

  • @J D Thanks for pointers. – Ajax Aug 26 '19 at 19:27
  • I feel compelled to say that neither the later Wittgenstein nor Kahneman refutes the impossibilty of illogical thought. The point is not anthropological, but logical. The thought is something like this: A contradiction does not specify a way for things to be, so there is no such thing as thinking that things are that way. – Michael Amundsen Aug 26 '19 at 22:18
  • @MichaelAmundsen I've gone and edited to replace illogical with alogical. It might be a categorical mismatch to consider thought and logic as largely overlapping. Most cognitive function of the brain is not logic and has nothing to do with reason at all. I took Ajax's question as referring to the intuitions by which we arrive at our often unexamined metaphysical presuppositions to be 'thought' given his characterization. Illogical thought: two intuitions find themselves promoting presumptions that lead to contradiction. Illogical thought is not only possible, it is human nature. – J D Aug 27 '19 at 19:05

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Submission #6193561 is currently offline

Submitted Sep 11th 2019 2:05 PM by cleanmx   (Current time: Jan 17th 2020 4:09 PM UTC)

Verified: Is a phish

As verified by Vasily1 Netsafe Romantic emidaniel k0t
Is a phish
Is NOT a phish
Server: 31b7753895bd


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PIA01882: Viking Lander 2 (Gerald A. Soffen Memorial Station) Imaged from Orbit
 Target Name:  Mars
 Is a satellite of:  Sol (our sun)
 Mission:  Mars Reconnaissance Orbiter (MRO)
 Spacecraft:  Mars Reconnaissance Orbiter (MRO)
Viking Lander 1
Viking Lander 2
 Instrument:  HiRISE
 Product Size:  5039 x 4356 pixels (w x h)
 Produced By:  University of Arizona/HiRISE-LPL
 Full-Res TIFF:  PIA01882.tif (21.98 MB)
 Full-Res JPEG:  PIA01882.jpg (4.702 MB)

Click on the image above to download a moderately sized image in JPEG format (possibly reduced in size from original)

Original Caption Released with Image:

Click here for annotated version of PIA01882 Viking Lander 1 (Thomas A. Mutch  Memorial Station) Imaged from Orbit
Annotated Version

Click here for annotated Viking 2 back shell of  PIA01882Click here for annotated Viking 2 heat shield of  PIA01882Click here for annotated Viking 2 Lander of  PIA01882
Viking 2 Back ShellViking 2 Heat ShieldViking 2 Lander

NASA's Viking Lander 2 landed on Mars on Sept. 3, 1976, in Utopia Planitia. The lander, which has a diameter of about 3 meters (10 feet), has been precisely located in this image from the High Resolution Imaging Science Experiment on NASA's Mars Reconnaissance Orbiter. Also, likely locations have been found for the heat shield and back shell. The lander location has been confirmed by overlaying the lander-derived topographic contours on the high-resolution camera's image, which provides an excellent match. Viking Lander 2 was one element of an ambitious mission to study Mars, with a four-spacecraft flotilla consisting of two orbiters and two landers. Four cutouts from this image are shown. The first is an overview showing the relative locations of the lander and candidate back shell and heat shield, and the others are enlargements of each of these components. Large boulders, dunes, and other features visible in Viking Lander 2 images can be located in the high-resolution camera's image. The polygonal pattern of the surface is typical at these latitudes and may be due to the presence of deep subsurface ice.

As chance would have it, this image is blurred in some places due to the abrupt motion associated with the restart of the orbiter's high-gain antenna tracking during the very short image exposure. This is the first time after acquiring hundreds of pictures that a High Resolution Imaging Science Experiment image has been unintentionally smeared; overall performance has been excellent.

A prime motivation for early viewing of the Viking sites is to calibrate imagery taken from orbit with the data previously acquired by the landers. In particular, determining what sizes of rocks can be seen from Mars Reconnaissance Orbiter aids the interpretation of data now being taken to characterize sites for future landers, such as the Phoenix Mars Lander mission to be launched in 2007.

Images from the High Resolution Imaging Science Experiment and additional information about the Mars Reconnaissance Orbiter are available online at: http://www.nasa.gov/mro or http://HiRISE.lpl.arizona.edu.

For information about NASA and agency programs on the Web, http://www.nasa.gov.

NASA's Jet Propulsion Laboratory, a division of the California Institute of Technology in Pasadena, manages the Mars Reconnaissance Orbiter for NASA's Science Mission Directorate, Washington. Lockheed Martin Space Systems is the prime contractor for the project and built the spacecraft. The High Resolution Imaging Science Experiment camera was built by Ball Aerospace Corporation and is operated by the University of Arizona.

Image Credit:
NASA/JPL-Caltech/University of Arizona

Image Addition Date:


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PHP cURL functions tutorial

cURL is a library which allows you to connect and communicate to many different types of servers with many different types of protocols. Using cURL you can:

  • Implement payment gateways’ payment notification scripts.
  • Download and upload files from remote servers.
  • Login to other websites and access members only sections.

PHP cURL library is definitely the odd man out. Unlike other PHP libraries where a whole plethora of functions is made available, PHP cURL wraps up a major parts of its functionality in just four functions.

A typical PHP cURL usage follows the following sequence of steps.

curl_init – Initializes the session and returns a cURL handle which can be passed to other cURL functions.

curl_opt – This is the main work horse of cURL library. This function is called multiple times and specifies what we want the cURL library to do.

curl_exec – Executes a cURL session.

curl_close – Closes the current cURL session.

Below are some examples which should make the working of cURL more clearer.

Download file or web page using PHP cURL

The below piece of PHP code uses cURL to download Google’s RSS feed.

As you can see, curl_setopt is the pivot around which the main cURL functionality revolves. cURL functioning is controlled by way of passing predefined options and values to this function.

The above code uses two such options.

  • CURLOPT_URL: Use it to specify the URL which you want to process. This could be the URL of the file you want to download or it could be the URL of the script to which you want to post some data.
  • CURLOPT_RETURNTRANSFER: Setting this option to 1 will cause the curl_exec function to return the contents instead of echoing them to the browser.

Download file or web page using PHP cURL and save it to file

The below PHP code is a slight variation of the above code. It not only downloads the contents of the specified URL but also saves it to a file.

Here we have used another of the cURL options, CURLOPT_FILE. Obtain a file handler by creating a new file or opening an existing one and then pass this file handler to the curl_set_opt function.

cURL will now write the contents to a file as it downloads a web page or file.

4 thoughts to “PHP cURL functions tutorial”

  1. Excellent cURL tutorial. Just what I needed… A quick run-through of the basic cURL options without getting bogged down in the PHP manual 🙂 Thanks!

  2. the script Download file or web page using PHP cURL and save it to file is not running on my system.
    What can be the problem?

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FAQ – What do I do after a car accident?

December 29, 2014 | By R. Brendan Dummigan of Pickett Dummigan LLP

Millions of car accidents occur every year in the United States. Thankfully, many of them are minor; unfortunately, not all of them are. Getting involved in a car crash can be a shocking, confusing, and stressful experience. However, it is important to control your anxiety and remember your obligations and rights in order to protect […]

Merry Multicultural Christmas

December 24, 2014 | By R. Brendan Dummigan of Pickett Dummigan LLP

The Chinese American Citizen’s Alliance invited one of our attorneys to join the holiday celebration at the Asian Health & Services Center on Tuesday, December 23, 2014. The AHSC is an organization dedicated to serving the healthcare needs of Asian immigrants and citizens in the Portland metropolitan area. This specific event was focused on bringing […]

Heaters Too Hot to Handle

December 19, 2014 | By R. Brendan Dummigan of Pickett Dummigan LLP

The Consumer Product Safety Commission (CPSC) estimates that over 25,000 residential fires and more than 300 deaths are caused each year by space heaters. Some of these fires could have been prevented had the heaters been used correctly. As the temperature gets colder, more and more people are starting to use space heaters to keep […]

The Legacy of the Lewis & Clark Legal Clinic – #ClinicLegacy #ClinicPledge

December 10, 2014 | By R. Brendan Dummigan of Pickett Dummigan LLP

by Ron K. Cheng, a former clinic student, now lawyer. The Lewis and Clark Legal Clinic is closing its doors on December 31, 2014. I was shocked and dismayed when closure of this important program was announced. The Lewis & Clark Legal Clinic has provided decades of legal representation to poor communities and individuals that […]

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Programming simplified!

PicoLisp is a programming language, or really a programming system, including a built-in database engine and a GUI system!

It's simple and lightweight and encourages clean, concise code - just like every other language.

PicoLisp introductory overview

   (+ 1 2 3)

   -> 6

   (setq Foo (1 2 3))

   -> (1 2 3)

   (and Foo (reverse @) (cons 4 @))

   -> (4 3 2 1)

Conditional statements

   (if (= 'this 'that) "This is that" "This isn't that")

   -> "This isn't that"

   (let (Foo "bar")
         ((not Foo) "No foo for you")
         ((lst? Foo) (map 'my-list-function Foo))
         ((= Foo "bar") "Foobar")
         "Nothing is true" ) )

   -> "Foobar"

Create functions

   (de hello ()
      (prin "Hello, world.") )

   -> Hello, world.

   (de double (Number)
      (* 2 Number))
   -> double

   (double 12)
   -> 24

Load libraries

   (load "@lib/http.l" "@lib/xhtml.l")

Serve web pages

   (load "@lib/http.l" "@lib/xhtml.l")

   (de hello-web ()
      (html 0 "Hello Web" "@lib.css" NIL
         (<h1> NIL "Hello, web")
         (<p> NIL
            "This is my first PicoLisp website" ) ) )

   (server 8080 "!hello-web")

Install PicoLisp

Install on Linux

You came here to play with another programming language, right? If you're using a Debian-based Linux (like Ubuntu or Mint), simply install it with:
   $ sudo apt-get install picolisp
and check out the tutorial.

Otherwise, grab the latest version - [picoLisp.tgz] - unpack it, follow the instructions from the INSTALL file, and then check out the tutorial.

Install on Windows Sybsystem for Linux (WSL)

See here: Install PicoLisp on Windows 10

Install on macOS

It is not possible to install picolisp on macOS, or even to build it without significant modifications to the code. The easiest way to access it on your machine is to install it on a lightweight Linux system and to remotely access it with ssh or similar solutions.

PicoLisp features

Maybe you like to do a little research before diving in. In that case...
  1. An integrated database
  2. Awesome C / Java interop
  3. It's really simple
Besides, it's free (MIT/X11 License). The documentation is pretty great, too.

Integrated Distributed Database Engine

Build large, distributed databases with fewer headaches and fewer dependencies.

Database functionality is built into the core of the VM, making PicoLisp a language for querying and manipulating databases.

For that, PicoLisp includes a built-in application framework and Prolog engine so you can create, organize, inspect and change (and even build a fancy UI for) your data - all with a uniform and concise syntax.

And when it's time to scale, PicoLisp has you covered - creating networks of distributed databases is built into the core as well. It's simple and powerful, and makes few assumptions about your application architecture.

Native C calls and Java interop

The intention of PicoLisp is to avoid writing extensive libraries. So we give you easy, transparent access to all your favorite software.

Leverage any C library function, manipulate C data structures in memory, call lisp functions from your C code - all that interactively from the REPL.

   # call the 'MD5' function from 'libcrypto.so'

   (let Str "The quick brown fox jumped over the lazy dog's back"
         (mapcar '((B) (pad 2 (hex B)))
            (native "libcrypto.so" "MD5"
               '(B . 16) Str (length Str) '(NIL (16)) ) ) ) )

   -> "E38CA1D920C4B8B8D3946B2C72F01680"

Interface directly to a running JVM, giving you dynamic access to everything Java.
   # a simple Swing UI

   (let [Frame (java "javax.swing.JFrame" T "Bye-Frame")
         Button (java "javax.swing.JButton" T "OK") ]
      (java Frame 'add "South" Button)
      (java Button 'addActionListener
         (interface Button "java.awt.event.ActionListener"
            'actionPerformed '((Ev) (bye)) ) )
      (java Frame 'setSize 100 60)
      (java Frame 'setVisible T) )
Now that's swingin' harder than a Charlie Parker record!

See the article Interfacing with Other Software for details.

PicoLisp is easy to understand and adapt.

Beneath the surface of the language lies the PicoLisp virtual machine. At the lowest level, the VM operates on a single data structure - the cell.

      | CAR | CDR |

A cell is just a pair of pointers, 'CAR' and 'CDR'.

All functions and data in the system are stored in cells, which simply point to each other to form arbitrarily complex structures.

From these cells, we contruct three base data types - Numbers, Symbols, and Lists - and from those, the rest of our universe.

So once you grok the underlying cell structure (which you pretty much already have), you just need to explore a small but powerful set of functions that do cool things with those cells.

It's that simple!

It's lisp, afterall. It's a language best suited for reprogramming itself.

Into functional programming? Rock on. OOP? PicoLisp has an elegant, unobtrusive, totally optional object system. Explore a syntax of nested function calls, bend the language to the task at hand, metaprogram yourself to the moon. We'll help you build a rocket.

PicoLisp programs are often much shorter than equivalent programs written in other languages. Examples of various programming tasks and their solutions can be found at rosettacode.org.

PicoLisp uses very little memory, on disk as well as in memory (heap space).

The tarball size of the whole system - including the interpreter, database, HTTP server, HTML and JavaScript application framework, and the debugger - is just a few hundred kilobytes.

If the following command makes sense for your setup, go ahead and run it.

   $ sudo apt-get install picolisp

If not, you'll have to build it from source. But that's easy, too!

Grab the tarball - [picoLisp.tgz] - unpack it, and follow the instructions from the INSTALL file.

Learn more - documentation overview

The documentation page has many examples and tutorials to get you started.

26may19   shoshin


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secular leftism is the no-standards club, and it gets this directly from the christinsanity it evolved out of. christianity requires merely mouthing you accept jesus p faggot as your personal savior; SJW requires that you mouth whatever lies the cult is currently circulating. words are taken more seriously than any behavior or reality among both these noxious cults.

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Work in the sunny BOP!

Pipe Masters Limited is a Plumbing, Drainage and Gasfitting company established at the end of 2015. We currently employ 8 full time tradesman and due to our large increase in work load due to the strong client base we have formed, we require an additional qualified tradesman to join our fun team. We carry out all types of work from maintenance, residential, shop fitouts to small commercial projects.

Depending on the tradesman skillset we can offer work across the plumbing/gasfitting/drainlaying and heating disciplines and would consider anyone who could add valve to these areas of the trade. We work on many high end projects as well as group housing so there is opportunity for most skill sets. We are also keen to actively extend the skillset for someone who is willing to learn.

We are looking for someone who:

  • Is a combination of either a qualified and registered Plumber/Gasfitter or Plumber/Drainlayer.
  • We have a small digger so someone who can operate excavators would be a bonus
  • Holds a current NZ Plumbers, Drainlayers and Gasfitters Board licence
  • Can work as part of a team or unsupervised.
  • Well presented and most importantly a good sense of humour

Benefits include:

  • Competitive wages package dependent on qualifications/experience
  • Uniform
  • Vehicle
  • Cellphone
  • Tool allowance
  • Fun team environment with an active social club
  • We work all online using Simpro software so no needing to fill out piles of paperwork and jobcards

Check out our: facebook or instagram to see what we are all about and the jobs we have completed.Applications for this position need to have NZ residence. To apply, email

Competitive wages package 0%
Uniform 0%
Vehicle & Cellphone 0%
Tool allowance 0%

How we get things done in the BOP

They say experience is what you get just after you need it. Thankfully we have been there, done that, got the tee shirt and we have showed others along the way. Having experience is one thing, but having a ‘make it happen’ ethos and a smart team of tradesmen running around with the latest technology gives us enough to be dangerous.  Have a read below to see how we are viewed in the market place.

Our Team

Pipe Masters is a team from our suppliers to our staff on the ground, it takes a team to deliver a service. At Pipe Masters, we are focused on continuous improvement, making sure we learn fast and carry ourselves into tomorrow, more experienced and better than today.

Our Processes

Pipe Masters processes are based on utilising a combination of the latest cloud based management and accounting software to the ability to pick up the phone and talk to someone for the personal touch. Our systems work fluidly to keep quotes moving into jobs, moving into invoices.

Our Mission

Pipe Masters mission is to ‘partner’ with our clients to complete plumbing, gas and drainage projects ensuring along the way the key values of quality workmanship, communication and trust are held in the highest regard.

Our Location

Pipemasters is located in Mount Maunganui (BOP) but services the greater western bay.
From Waihi to Te Puke we cover all areas in between. Our vans can be found on both sides of the bridge on any given day.
We're not just plumbers, we're professionals.

Pipe Masters Core values are:

  • Quality
  • Communication
  • Trust

We hope to deliver on every job with these values dressed in a ‘nothing is a problem’ type attitude. At Pipe Masters Ltd we understand that no matter how good we are, there is always room for improvement – Its a need to improve that sets us apart from those happy to remain stagnant.

What Our Customers Say…

Need a Plumber or Gas Fitter?

Pipe Masters provide the best plumbing solutions in Tauranga. Feel free to get in touch with our team to discuss your next project. Good honest Kiwis saving you time and money.


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Pipenv & Virtual Environments

This tutorial walks you through installing and using Python packages.

It will show you how to install and use the necessary tools and make strong recommendations on best practices. Keep in mind that Python is used for a great many different purposes, and precisely how you want to manage your dependencies may change based on how you decide to publish your software. The guidance presented here is most directly applicable to the development and deployment of network services (including web applications), but is also very well suited to managing development and testing environments for any kind of project.

This guide is written for Python 3, however, these instructions should work fine on Python 2.7—if you are still using it, for some reason.

☤ Make sure you’ve got Python & pip

Before you go any further, make sure you have Python and that it’s available from your command line. You can check this by simply running:

$ python --version

You should get some output like 3.6.2. If you do not have Python, please install the latest 3.x version from python.org or refer to the Installing Python section of The Hitchhiker’s Guide to Python.

If you’re newcomer and you get an error like this:

>>> python
Traceback (most recent call last):
  File "<stdin>", line 1, in <module>
NameError: name 'python' is not defined

It’s because this command is intended to be run in a shell (also called a terminal or console). See the Python for Beginners getting started tutorial for an introduction to using your operating system’s shell and interacting with Python.

Additionally, you’ll need to make sure you have pip available. You can check this by running:

$ pip --version
pip 9.0.1

If you installed Python from source, with an installer from python.org, via Homebrew or via Linuxbrew you should already have pip. If you’re on Linux and installed using your OS package manager, you may have to install pip separately.

If you plan to install Pipenv using Homebrew or Linuxbrew you can skip this step. The Homebrew/Linuxbrew installer takes care of pip for you.

☤ Installing Pipenv

Pipenv is a dependency manager for Python projects. If you’re familiar with Node.js’ npm or Ruby’s bundler, it is similar in spirit to those tools. While pip can install Python packages, Pipenv is recommended as it’s a higher-level tool that simplifies dependency management for common use cases.

☤ Homebrew Installation of Pipenv

Homebrew is a popular open-source package management system for macOS. For Linux users, Linuxbrew is a Linux port of that.

Installing pipenv via Homebrew or Linuxbrew will keep pipenv and all of its dependencies in an isolated virtual environment so it doesn’t interfere with the rest of your Python installation.

Once you have installed Homebrew or Linuxbrew simply run:

$ brew install pipenv

To upgrade pipenv at any time:

$ brew upgrade pipenv

☤ Pragmatic Installation of Pipenv

If you have a working installation of pip, and maintain certain “toolchain” type Python modules as global utilities in your user environment, pip user installs allow for installation into your home directory. Note that due to interaction between dependencies, you should limit tools installed in this way to basic building blocks for a Python workflow like virtualenv, pipenv, tox, and similar software.

To install:

$ pip install --user pipenv

This does a user installation to prevent breaking any system-wide packages. If pipenv isn’t available in your shell after installation, you’ll need to add the user base’s binary directory to your PATH.

On Linux and macOS you can find the user base binary directory by running python -m site --user-base and adding bin to the end. For example, this will typically print ~/.local (with ~ expanded to the absolute path to your home directory) so you’ll need to add ~/.local/bin to your PATH. You can set your PATH permanently by modifying ~/.profile.

On Windows you can find the user base binary directory by running python -m site --user-site and replacing site-packages with Scripts. For example, this could return C:\Users\Username\AppData\Roaming\Python36\site-packages so you would need to set your PATH to include C:\Users\Username\AppData\Roaming\Python36\Scripts. You can set your user PATH permanently in the Control Panel. You may need to log out for the PATH changes to take effect.

For more information, see the user installs documentation.

To upgrade pipenv at any time:

$ pip install --user --upgrade pipenv

☤ Crude Installation of Pipenv

If you don’t even have pip installed, you can use this crude installation method, which will bootstrap your whole system:

$ curl https://raw.githubusercontent.com/kennethreitz/pipenv/master/get-pipenv.py | python

☤ Installing packages for your project

Pipenv manages dependencies on a per-project basis. To install packages, change into your project’s directory (or just an empty directory for this tutorial) and run:

$ cd myproject
$ pipenv install requests

Pipenv will install the excellent Requests library and create a Pipfile for you in your project’s directory. The Pipfile is used to track which dependencies your project needs in case you need to re-install them, such as when you share your project with others. You should get output similar to this (although the exact paths shown will vary):

Creating a Pipfile for this project...
Creating a virtualenv for this project...
Using base prefix '/usr/local/Cellar/python3/3.6.2/Frameworks/Python.framework/Versions/3.6'
New python executable in ~/.local/share/virtualenvs/tmp-agwWamBd/bin/python3.6
Also creating executable in ~/.local/share/virtualenvs/tmp-agwWamBd/bin/python
Installing setuptools, pip, wheel...done.

Virtualenv location: ~/.local/share/virtualenvs/tmp-agwWamBd
Installing requests...
Collecting requests
  Using cached requests-2.18.4-py2.py3-none-any.whl
Collecting idna<2.7,>=2.5 (from requests)
  Using cached idna-2.6-py2.py3-none-any.whl
Collecting urllib3<1.23,>=1.21.1 (from requests)
  Using cached urllib3-1.22-py2.py3-none-any.whl
Collecting chardet<3.1.0,>=3.0.2 (from requests)
  Using cached chardet-3.0.4-py2.py3-none-any.whl
Collecting certifi>=2017.4.17 (from requests)
  Using cached certifi-2017.7.27.1-py2.py3-none-any.whl
Installing collected packages: idna, urllib3, chardet, certifi, requests
Successfully installed certifi-2017.7.27.1 chardet-3.0.4 idna-2.6 requests-2.18.4 urllib3-1.22

Adding requests to Pipfile's [packages]...
P.S. You have excellent taste! ✨ 🍰 ✨

☤ Using installed packages

Now that Requests is installed you can create a simple main.py file to use it:

import requests

response = requests.get('https://httpbin.org/ip')

print('Your IP is {0}'.format(response.json()['origin']))

Then you can run this script using pipenv run:

$ pipenv run python main.py

You should get output similar to this:

Your IP is

Using $ pipenv run ensures that your installed packages are available to your script. It’s also possible to spawn a new shell that ensures all commands have access to your installed packages with $ pipenv shell.

☤ Virtualenv mapping caveat

  • Pipenv automatically maps projects to their specific virtualenvs.
  • The virtualenv is stored globally with the name of the project’s root directory plus the hash of the full path to the project’s root (e.g., my_project-a3de50).
  • If you change your project’s path, you break such a default mapping and pipenv will no longer be able to find and to use the project’s virtualenv.
  • You might want to set export PIPENV_VENV_IN_PROJECT=1 in your .bashrc/.zshrc (or any shell configuration file) for creating the virtualenv inside your project’s directory, avoiding problems with subsequent path changes.

☤ Next steps

Congratulations, you now know how to install and use Python packages! ✨ 🍰 ✨


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#TuneTuesday | Calon Lan

Piper playing in front of garden

This past Saturday, I played for a memorial service in Cambridge. For this service, the tune “Calon Lan” was requested by the deceased to be played at his funeral as he had really enjoyed the Welsh boys choir Only Boys Aloud singing it on the show, Britain’s Got Talent.

As I had never played this tune before, I relied on Google to find the sheet music for it. Luckily, this tune is a traditional Welsh hymn that is also commonly sung at Welsh rugby games, so it was fairly easy to find and not copyrighted. I enjoy learning new tunes for gigs as it adds to my repertoire and increases customer satisfaction.

Enjoy and stay “tuned” for next week’s #TuneTuesday!

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• Top European Quality for disposable and diagnostic

DEHP-free PVC sets with double scale flow regulator List of components:
  • Drip chamber (PVC DEHP FREE)
  • Microdrip (steel INOX)
  • Air Filter (coloured ABS + Pore Membrane)
  • 2 ways spike (white ABS)
  • Cap for spike (Low Density Polyethylene)
  • Tube 3x4,1 (PVC DEHP FREE)
  • Roller house (ABS)
  • Roller wheel (Polystyrol)
  • Flow regulator double scale (ABS and silicone for rings)
  • Y connector with injection site (clean ABS and latex-free)
  • Male Luer lock (clean ABS)
  • Vented cap for male L.L. (Low Density Polyethylene)
100 pieces per carton size cm.39x23,5x39H Click for more


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Back to the Product Directory index

Quik App

How often do you hear the phrase “No Experience Needed?” Moreover, how often is that actually the case? Well, you are in luck. With Quik you don’t need experience to create and edit beautiful videos. Quik is an intuitive and user-friendly app that makes it super easy to create awesome videos with just a few quick steps. Quik helps you quickly search footage found via Facebook, Instagram, Photo Library, or GoPro Plus to find the most captivating moments and images. From there you can quickly add transitions and effects to your masterpiece with just a few taps, sync your movie to work with the music of choice or use any number of the endless tools Quik offers to customize your video, and easily to share it with friends. Job description: video editor, no experience needed. And . . . you’re hired.

Yep. We use cookies. Just like everybody else. Cool? Click OK.


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Homalomena Lemon Lime

incl. vat

Homalomena Lemon Lime is the rare cousin of the increasingly popular Homalomena Rubescens variety, due to its ease of care, disease resistance and tolerance to low light conditions and stress. It’s a genus of flowering plants from the family Aracea, just like our beloved Monstera or Philodendron.

This plant comes in a pot 15cm size and is about 45cm tall.

In stock

Categories: , ,

Care tips

 Homalomena houseplants do well in medium to low light exposures but truly thrive in medium light conditions. An over abundance of sun can scorch the foliage, causing burnt spots on the leaves.

Re-pot only when it has become root-bound in its existing container. Smaller pots help prevent over-watering. Plant a homalomena in a well-aerated houseplant soil that drains quickly.

Water well and and keep the soil moist, not soggy wet. Dry soil will turn the foliage yellow and spartan. Low humidity will cause browning along the leaf edges. Don’t let homalomena to dry out.

Toxic to animals and humans when ingested.

Delivery Time.

Germany 1-3 days

For all other countries delivery time can range from 3-10 days.

At the moment we are processing the orders on Mondays only – so if you order from us on a Wednesday it won’t be processed until the following Monday.

An example picture gives a trustworthy image of the plant with good care. The plant at the example picture is not the plant that will be delivered. This is an example, so variations are possible. The eventually delivered plant may differ in for example size, number of flower branches, etc.


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Poster The Conspirator 2010

The Conspirator 2010

Watch The Conspirator (2010) : Full Movie Online Free Mary Surratt is the lone female charged as a co-conspirator in the assassination trial of Abraham Lincoln. As the whole nation turns against her, she is forced to rely on her reluctant lawyer to uncover the truth and save her life.

  • Released: Sep 10, 2010
  • Runtime: 122 minutes
  • Genre: , ,
  • Stars: James McAvoy, Robin Wright, Evan Rachel Wood, Kevin Kline, Alexis Bledel, Justin Long, Tom Wilkinson, Norman Reedus, Toby Kebbell, Jonathan Groff, Danny Huston
  • Production Company: Wildwood Enterprises, American Film Company
Download : MKV
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