Welcome to Fiveprime

StanleyKiernoziak

Wed, 06 Jun 2007 14:57:00 GMT

Violin maker in the shop of WilliamHarrisLee in [[Chicago]]. Made incredible and powerful [[Cello]]s, now makes mostly Violas

SiteUrl

Wed, 06 Jun 2007 11:09:00 GMT

http://www.fiveprime.org/

Google @ work 4 June 2007

Mon, 04 Jun 2007 13:17:00 GMT

*What have they learned
**Things are well and good in innovation world right now. Tech bubble...
**Consumer tech world is innovating at an incredible pace: tivo, youtube, second life, skype.
***slingbox is very easy to use.
**For perhaps the first time ever, user satisfaction is going up - NOS-Expectations are going up.
**Business space is lagging 2x graph of user satisfaction vs time.
**"Enterprise IT is falling behind" - head of sales at google.
**Flow is going backwards - now starts in consumer world and goes to business world.
**Gartner: "On average $80 spent in IT is dead money, not contributing to business change and growth"
*He reads "Business 2.0"
**80% of startups are in conumer space.
*Goal: Make applications that users love
*Google enterprise: Search, Geospacial, Apps
*Three lesson that enterprise IT can learn from Google.
**Fast is better than slow
***The world has sped up, how we deploy software hasn't changed
****define requirements; buy vs build, rfi/rfp; select vendor; do bakeoff; define implementation plan, customize application, build end user training plan, deploy
****users will give you a long list of requirement that they dont' need - YES
****buy the time you are done it's obsolet. If it takes you two years to roll out an app you are dead meat.
*IT projects have to be iterative and not big bank
**launch and improve
**fail quickly and learn
*Technology must be much simpler to implement
*Our platforms must be able to handle constant change.
**early failures allow you to divert resource
*SIMPLE IS BETTER THAN COMPLEX
**the way we have chosen to deploy applications have become insanely complex. "delivery models have insane complexity.
**new delivery models
***Appliance - one box
***SaaS "Software as a Service"
***Minimize customization - this one is hard to learn
*ASSUME CHAOS AND DEAL WITH IT
**you will never settle down to the normal state.
**in corporate IT, this means: Data has changed and it doesn't come in rows and columns. The world is now 80% unstructured i terms of data.
**Categorization? you can't keep up with the pace. You can't even look at it all right now.
*Manual categorization and hierarchies are dead - NOS - I don't agree.
*H in yahoo stands for Hierarchical
**Portal projects - no matter how he does them people hate them - how do we organize them? People don't agree with categorization.
**two innovations in Gmail: unlimited storage and good search
**categorizing email is biggest waste of time ever.
***perhaps he is right in terms of email
*LESSONS
**don't throw anything away
**encourage information to be published and Shared
*Stop categorizing information into hierarchies
**embrace search as a way of navigation
*Google portal
**hosted by goodle, but can be branded and domained.
*FINANCIAL PROPOSITION
**old world: 200-1000$ /per user for running email
**new world: $50/user/year

National Security and Homeland Security Presidential Directive

Wed, 23 May 2007 22:57:00 GMT

National Security and Homeland Security Presidential Directive

NATIONAL SECURITY PRESIDENTIAL DIRECTIVE/NSPD 51

HOMELAND SECURITY PRESIDENTIAL DIRECTIVE/HSPD-20

Subject: National Continuity Policy

Purpose

(1) This directive establishes a comprehensive national policy on the continuity of Federal Government structures and operations and a single National Continuity Coordinator responsible for coordinating the development and implementation of Federal continuity policies. This policy establishes "National Essential Functions," prescribes continuity requirements for all executive departments and agencies, and provides guidance for State, local, territorial, and tribal governments, and private sector organizations in order to ensure a comprehensive and integrated national continuity program that will enhance the credibility of our national security posture and enable a more rapid and effective response to and recovery from a national emergency.

Definitions

(2) In this directive:

(a) "Category" refers to the categories of executive departments and agencies listed in Annex A to this directive;

(b) "Catastrophic Emergency" means any incident, regardless of location, that results in extraordinary levels of mass casualties, damage, or disruption severely affecting the U.S. population, infrastructure, environment, economy, or government functions;

(c) "Continuity of Government," or "COG," means a coordinated effort within the Federal Government's executive branch to ensure that National Essential Functions continue to be performed during a Catastrophic Emergency;

(d) "Continuity of Operations," or "COOP," means an effort within individual executive departments and agencies to ensure that Primary Mission-Essential Functions continue to be performed during a wide range of emergencies, including localized acts of nature, accidents, and technological or attack-related emergencies;

(e) "Enduring Constitutional Government," or "ECG," means a cooperative effort among the executive, legislative, and judicial branches of the Federal Government, coordinated by the President, as a matter of comity with respect to the legislative and judicial branches and with proper respect for the constitutional separation of powers among the branches, to preserve the constitutional framework under which the Nation is governed and the capability of all three branches of government to execute constitutional responsibilities and provide for orderly succession, appropriate transition of leadership, and interoperability and support of the National Essential Functions during a catastrophic emergency;

(f) "Executive Departments and Agencies" means the executive departments enumerated in 5 U.S.C. 101, independent establishments as defined by 5 U.S.C. 104(1), Government corporations as defined by 5 U.S.C. 103(1), and the United States Postal Service;

(g) "Government Functions" means the collective functions of the heads of executive departments and agencies as defined by statute, regulation, presidential direction, or other legal authority, and the functions of the legislative and judicial branches;

(h) "National Essential Functions," or "NEFs," means that subset of Government Functions that are necessary to lead and sustain the Nation during a catastrophic emergency and that, therefore, must be supported through COOP and COG capabilities; and

(i) "Primary Mission Essential Functions," or "PMEFs," means those Government Functions that must be performed in order to support or implement the performance of NEFs before, during, and in the aftermath of an emergency.

Policy

(3) It is the policy of the United States to maintain a comprehensive and effective continuity capability composed of Continuity of Operations and Continuity of Government programs in order to ensure the preservation of our form of government under the Constitution and the continuing performance of National Essential Functions under all conditions.

Implementation Actions

(4) Continuity requirements shall be incorporated into daily operations of all executive departments and agencies. As a result of the asymmetric threat environment, adequate warning of potential emergencies that could pose a significant risk to the homeland might not be available, and therefore all continuity planning shall be based on the assumption that no such warning will be received. Emphasis will be placed upon geographic dispersion of leadership, staff, and infrastructure in order to increase survivability and maintain uninterrupted Government Functions. Risk management principles shall be applied to ensure that appropriate operational readiness decisions are based on the probability of an attack or other incident and its consequences.

(5) The following NEFs are the foundation for all continuity programs and capabilities and represent the overarching responsibilities of the Federal Government to lead and sustain the Nation during a crisis, and therefore sustaining the following NEFs shall be the primary focus of

the Federal Government leadership during and in the aftermath of an emergency that adversely affects the performance of Government Functions:

(a) Ensuring the continued functioning of our form of government under the Constitution, including the functioning of the three separate branches of government;

(b) Providing leadership visible to the Nation and the world and maintaining the trust and confidence of the American people;

(c) Defending the Constitution of the United States against all enemies, foreign and domestic, and preventing or interdicting attacks against the United States or its people, property, or interests;

(d) Maintaining and fostering effective relationships with foreign nations;

(e) Protecting against threats to the homeland and bringing to justice perpetrators of crimes or attacks against the United States or its people, property, or interests;

(f) Providing rapid and effective response to and recovery from the domestic consequences of an attack or other incident;

(g) Protecting and stabilizing the Nation's economy and ensuring public confidence in its financial systems; and

(h) Providing for critical Federal Government services that address the national health, safety, and welfare needs of the United States.

(6) The President shall lead the activities of the Federal Government for ensuring constitutional government. In order to advise and assist the President in that function, the Assistant to the President for Homeland Security and Counterterrorism (APHS/CT) is hereby designated as the National Continuity Coordinator. The National Continuity Coordinator, in coordination with the Assistant to the President for National

Security Affairs (APNSA), without exercising directive authority, shall coordinate the development and implementation of continuity policy for executive departments and agencies. The Continuity Policy Coordination Committee (CPCC), chaired by a Senior Director from the Homeland Security Council staff, designated by the National Continuity Coordinator, shall be the main day-to-day forum for such policy coordination.

(7) For continuity purposes, each executive department and agency is assigned to a category in accordance with the nature and characteristics of its national security roles and

responsibilities in support of the Federal Government's ability to sustain the NEFs. The Secretary of Homeland Security shall serve as the President's lead agent for coordinating overall

continuity operations and activities of executive departments and agencies, and in such role shall perform the responsibilities set forth for the Secretary in sections 10 and 16 of this directive.

(8) The National Continuity Coordinator, in consultation with the heads of appropriate executive departments and agencies, will lead the development of a National Continuity Implementation Plan (Plan), which shall include prioritized goals and objectives, a concept of operations, performance metrics by which to measure continuity readiness, procedures for continuity and incident management activities, and clear direction to executive department and agency continuity coordinators, as well as guidance to promote interoperability of Federal Government continuity programs and procedures with State, local, territorial, and tribal governments, and private sector owners and operators of critical infrastructure, as appropriate. The Plan shall be submitted to the President for approval not later than 90 days after the date of this directive.

(9) Recognizing that each branch of the Federal Government is responsible for its own continuity programs, an official designated by the Chief of Staff to the President shall ensure that the executive branch's COOP and COG policies in support of ECG efforts are appropriately coordinated with those of

the legislative and judicial branches in order to ensure interoperability and allocate national assets efficiently to maintain a functioning Federal Government.

(10) Federal Government COOP, COG, and ECG plans and operations shall be appropriately integrated with the emergency plans and capabilities of State, local, territorial, and tribal governments, and private sector owners and operators of critical infrastructure, as appropriate, in order to promote interoperability and to prevent redundancies and conflicting lines of authority. The Secretary of Homeland Security shall coordinate the integration of Federal continuity plans and operations with State, local, territorial, and tribal governments, and private sector owners and operators of critical infrastructure, as appropriate, in order to provide for the delivery of essential services during an emergency.

(11) Continuity requirements for the Executive Office of the President (EOP) and executive departments and agencies shall include the following:

(a) The continuation of the performance of PMEFs during any emergency must be for a period up to 30 days or until normal operations can be resumed, and the capability to be fully operational at alternate sites as soon as possible after the occurrence of an emergency, but not later than 12 hours after COOP activation;

(b) Succession orders and pre-planned devolution of authorities that ensure the emergency delegation of authority must be planned and documented in advance in accordance with applicable law;

(c) Vital resources, facilities, and records must be safeguarded, and official access to them must be provided;

(d) Provision must be made for the acquisition of the resources necessary for continuity operations on an emergency basis;

(e) Provision must be made for the availability and redundancy of critical communications capabilities at alternate sites in order to support connectivity between

and among key government leadership, internal elements, other executive departments and agencies, critical partners, and the public;

(f) Provision must be made for reconstitution capabilities that allow for recovery from a catastrophic emergency and resumption of normal operations; and

(g) Provision must be made for the identification, training, and preparedness of personnel capable of relocating to alternate facilities to support the continuation of the performance of PMEFs.

(12) In order to provide a coordinated response to escalating threat levels or actual emergencies, the Continuity of Government Readiness Conditions (COGCON) system establishes executive branch continuity program readiness levels, focusing

on possible threats to the National Capital Region. The President will determine and issue the COGCON Level. Executive departments and agencies shall comply with the requirements and

assigned responsibilities under the COGCON program. During COOP activation, executive departments and agencies shall report their readiness status to the Secretary of Homeland Security or the Secretary's designee.

(13) The Director of the Office of Management and Budget shall:

(a) Conduct an annual assessment of executive department and agency continuity funding requests and performance data that are submitted by executive departments and agencies as part of the annual budget request process, in order to monitor progress in the implementation of the Plan and the execution of continuity budgets;

(b) In coordination with the National Continuity Coordinator, issue annual continuity planning guidance for the development of continuity budget requests; and

(c) Ensure that heads of executive departments and agencies prioritize budget resources for continuity capabilities, consistent with this directive.

(14) The Director of the Office of Science and Technology Policy shall:

(a) Define and issue minimum requirements for continuity communications for executive departments and agencies, in consultation with the APHS/CT, the APNSA, the Director of the Office of Management and Budget, and the Chief of Staff to the President;

(b) Establish requirements for, and monitor the development, implementation, and maintenance of, a comprehensive communications architecture to integrate continuity components, in consultation with the APHS/CT, the APNSA, the Director of the Office of Management and Budget, and the Chief of Staff to the President; and

(c) Review quarterly and annual assessments of continuity communications capabilities, as prepared pursuant to section 16(d) of this directive or otherwise, and report the results and recommended remedial actions to the National Continuity Coordinator.

(15) An official designated by the Chief of Staff to the President shall:

(a) Advise the President, the Chief of Staff to the President, the APHS/CT, and the APNSA on COGCON operational execution options; and

(b) Consult with the Secretary of Homeland Security in order to ensure synchronization and integration of continuity activities among the four categories of executive departments and agencies.

(16) The Secretary of Homeland Security shall:

(a) Coordinate the implementation, execution, and assessment of continuity operations and activities;

(b) Develop and promulgate Federal Continuity Directives in order to establish continuity planning requirements for executive departments and agencies;

(c) Conduct biennial assessments of individual department and agency continuity capabilities as prescribed by the Plan and report the results to the President through the APHS/CT;

(d) Conduct quarterly and annual assessments of continuity communications capabilities in consultation with an official designated by the Chief of Staff to the President;

(e) Develop, lead, and conduct a Federal continuity training and exercise program, which shall be incorporated into the National Exercise Program developed pursuant to Homeland Security Presidential Directive-8 of December 17, 2003 ("National Preparedness"), in consultation with an

official designated by the Chief of Staff to the President;

(f) Develop and promulgate continuity planning guidance to State, local, territorial, and tribal governments, and private sector critical infrastructure owners and operators;

(g) Make available continuity planning and exercise funding, in the form of grants as provided by law, to State, local, territorial, and tribal governments, and private sector critical infrastructure owners and operators; and

(h) As Executive Agent of the National Communications System, develop, implement, and maintain a comprehensive continuity communications architecture.

(17) The Director of National Intelligence, in coordination with the Attorney General and the Secretary of Homeland Security, shall produce a biennial assessment of the foreign and domestic threats to the Nation's continuity of government.

(18) The Secretary of Defense, in coordination with the Secretary of Homeland Security, shall provide secure, integrated, Continuity of Government communications to the President, the Vice President, and, at a minimum, Category I executive departments and agencies.

(19) Heads of executive departments and agencies shall execute their respective department or agency COOP plans in response to a localized emergency and shall:

(a) Appoint a senior accountable official, at the Assistant Secretary level, as the Continuity Coordinator for the department or agency;

(b) Identify and submit to the National Continuity Coordinator the list of PMEFs for the department or agency and develop continuity plans in support of the NEFs and the continuation of essential functions under all conditions;

(c) Plan, program, and budget for continuity capabilities consistent with this directive;

(d) Plan, conduct, and support annual tests and training, in consultation with the Secretary of Homeland Security, in order to evaluate program readiness and ensure adequacy and viability of continuity plans and communications systems; and

(e) Support other continuity requirements, as assigned by category, in accordance with the nature and characteristics of its national security roles and responsibilities

General Provisions

(20) This directive shall be implemented in a manner that is consistent with, and facilitates effective implementation of, provisions of the Constitution concerning succession to the Presidency or the exercise of its powers, and the Presidential Succession Act of 1947 (3 U.S.C. 19), with consultation of the Vice President and, as appropriate, others involved. Heads of executive departments and agencies shall ensure that appropriate

support is available to the Vice President and others involved as necessary to be prepared at all times to implement those provisions.

(21) This directive:

(a) Shall be implemented consistent with applicable law and the authorities of agencies, or heads of agencies, vested by law, and subject to the availability of appropriations;

(b) Shall not be construed to impair or otherwise affect (i) the functions of the Director of the Office of Management and Budget relating to budget, administrative, and legislative proposals, or (ii) the authority of the Secretary of Defense over the Department of Defense, including the chain of command for military forces from the President, to the Secretary of Defense, to the commander of military forces, or military command and control procedures; and

(c) Is not intended to, and does not, create any rights or benefits, substantive or procedural, enforceable at law or in equity by a party against the United States, its

agencies, instrumentalities, or entities, its officers, employees, or agents, or any other person.

(22) Revocation. Presidential Decision Directive 67 of October 21, 1998 ("Enduring Constitutional Government and Continuity of Government Operations"), including all Annexes thereto, is hereby revoked.

(23) Annex A and the classified Continuity Annexes, attached hereto, are hereby incorporated into and made a part of this directive.

(24) Security. This directive and the information contained herein shall be protected from unauthorized disclosure, provided that, except for Annex A, the Annexes attached to this directive are classified and shall be accorded appropriate handling, consistent with applicable Executive Orders.

GEORGE W. BUSH

5 May 2007 $35 price target for BMY?

Sat, 05 May 2007 12:52:00 GMT

Deutsche Bank upgrades Bristol-Myers Squibb (NYSE: BMY) from Hold to Buy with a $35 price target. The firm said, "BMY's 1Q07 EPS indicate a sustained EPS recovery may be ahead Solid sales, higher than expected gross margins, and lower expenses drove a substantial earnings beat in BMY's 1Q07 EPS. The new management team has been focusing on improving shareholder value in a multitude of ways which could bear substantial fruit over the coming years. Due to these factors we now expect
that BMY's operating leverage from its growing new product portfolio may be substantially greater than we had originally believed."

Total comments on support for Sanofi M&A

Sat, 05 May 2007 12:46:00 GMT

PARIS, May 4 (Reuters) - French oil major Total (TOTF.PA: Quote, Profile, Research, which is a major shareholder in drugs group Sanofi-Aventis (SASY.PA: Quote, Profile, Research, said it could support a merger or acquisition deal for Sanofi if it felt it was in Sanofi's best interests.

"We will support any deal proposed by Sanofi if we have the feeling it's good for Sanofi," Total Chief Financial Officer Robert Castaigne told Total's annual shareholder meeting on Friday.

Awesome Stools

Sun, 29 Apr 2007 07:45:00 GMT

La Palma "LEM" 370-500 euros online.

http://www.ambientedirect.com/en/eur/lap_lem_hocker_en.php

Nathan's Amsterdam Music Exploring (Instruments and Bows)

Sun, 29 Apr 2007 07:43:00 GMT

Shop of Andras Post, Mozartkade, Amsterdam
C. (or L.) Bausch Bow, Dresden ca 1870. very nice e4500

Shop of Matthieu Besseling
Berman bow circa 1800, school of Knopf e2200

Gold mounted bow german circa 1870 e2600

Matthiew Besseling's cello was nice but a bit tight sounding - he says he has the sound post tight to increase the consistency of the instrument in all ranges - it was indeed consistent and there was essentially no wolf at all to the instrument! e20,000

Tiddlywikify

Fri, 13 Apr 2007 11:50:00 GMT

See [[X::Tiddlywikify - A simple Perl Module for writing Tiddlywikis]]

Time Travel Spammer

Thu, 12 Apr 2007 20:58:00 GMT

Greetings,

We need a vendor who can offer immediate supply. I’m offering $5,000 US dollars just for referring a vender which is (Actually RELIABLE in providing the below equipment) Contact details of vendor required, including name and phone #. If they turn out to be reliable in supplying the below equipment I’ll immediately pay you $5,000. We prefer to work with vendor in the Boston/New York area.

1. The mind warper generation 4 Dimensional Warp Generator # 52 4350a series wrist watch with z80 or better memory adapter. If in stock the AMD Dimensional Warp Generator module containing the GRC79 induction motor, two I80200 warp stabilizers, 256GB of SRAM, and two Analog Devices isolinear modules, This unit also has a menu driven GUI accessible on the front panel XID display. All in 1 units would be great if reliable models are available

2. The special 23200 or Acme 5X24 series time transducing capacitor with built in temporal displacement. Needed with complete jumper/auxiliary system

3. A reliable crystal Ionizor with unlimited memory backup.

4. I will also pay for Schematics, layouts, and designs directly from the manufature which can be used to build this equipment from readily available parts.

If your vendor turns out to be reliable, I owe you $5,000.

google ajax trial

Tue, 10 Apr 2007 11:01:00 GMT

obviously the interaction with Tiddlywiki is not working

SEO TiddlyWiki Plugin

Mon, 26 Mar 2007 21:43:00 GMT

!Purpose / But

I wrote this Search Engine Optimization plugin to improve ~TiddlyWiki website's ranking on Google, Yahoo, etc. Basically, it does two things:
1) For each tiddler and each tag of this one, it creates a html file with the tiddler's content and named according to the tiddler's title. The html file is written in a way that it can be easily crawled by a search engine (short and with html format, not ~TiddlyWiki's format), but if it is opened (which will be the case if it appears in the results of a search engine), it redirects to the ~TiddlyWiki with the corresponding tiddler opened.
2) It creates the sitemap.xml and urllist.txt files for Google and Yahoo which included generated html files.

J'ai écrit ce plugin d'optimisation pour les moteurs de recherche pour améliorer l'indexation d'un ~TiddlyWiki par Google, Yahoo, etc.
Le plugin fait deux choses :
1) Pour chaque tiddler et chaque tag de celui-ci, il créé un fichier html avec le contenu du tiddler et nommé selon le titre du tiddler. Le fichier html est écrit de sorte qu'il soit facilement indexable par un moteur de recherche (court et avec un balisage html et non un balisage ~TiddlyWiki), mais que s'il est ouvert (ce qui sera le cas s'il apparaît dans les résultats d'un moteur de recherche), il redirige vers le ~TiddlyWiki avec le tiddler correspondant ouvert.
2) Il créé les fichiers sitemap.xml et urllist.txt pour Google et Yahoo, qui inclue les fichiers html générés.

!How to install / Comment l'installer

1) Create two tiddlers like these one (same name and content):
[[SEOTiddlyWikiPlugin]] [[SEOTiddlyWikiConfig]]
NB: double-clic on each tiddler to get edit mode and copy-paste their content.
2) Fill in shadow tiddlers SiteUrl, SiteTitle and SiteSubtitle.
3) Edit this tiddler and see the code behind the following link to understand how to launch the process, once the plugin installed: Generate SEO files.
4) See http://www.google.com/webmasters/sitemaps/ to register your sitemap.xml file.

Tips
1) Feel free to modify html template [[SEOTiddlyWikiConfig]].
2) Use tag //excludeSearch// to disallow the export of a tiddler.

Limitation
If you remove a tiddler after an export, you have to manually remove the corresponding html file.

1) Créez un tiddler comme ceux-ci (même nom et contenu) :
[[SEOTiddlyWikiPlugin]] [[SEOTiddlyWikiConfig]]
NB: double-cliquez sur chaque tiddler pour le passe en mode d'édition et copier-coller leur contenu.
2) Remplissez les tiddlers cachés SiteUrl, SiteTitle et SiteSubtitle.
3) Editez le contenu de ce tiddler pour voir le code derrière le lien suivant et comprendre comment lancer le processus une fois le plugin installé : Générer les fichiers SEO.
4) Voyez http://www.google.com/webmasters/sitemaps/ pour enregistrer votre fichier sitemap.xml.

Astuces
1) N'hésitez pas à modifier le modèle html [[SEOTiddlyWikiConfig]].
2) Utilisez le tag //excludeSearch// pour interdire l'export d'un tiddler.

Limitation
Si vous supprimez un tiddler après un export, vous devez manuellement effacer le fichier html correspondant.

!Sample results / Exemple de résultats

http://www.google.com/search?q=site:superphysique.net
http://www.superphysique.net/
http://www.superphysique.net/super%20physique/quotes.htm
http://www.superphysique.net/gallery/dusan.htm
http://www.superphysique.net/materials/strength-cycles.htm
http://www.superphysique.net/materials/external-resources.htm
http://www.superphysique.net/gallery/jerome.htm
http://www.superphysique.net/gallery/eric.htm
http://www.superphysique.net/super%20physique/copyright.htm
http://www.superphysique.net/super%20physique/about-a-propos.htm
http://www.superphysique.net/tiddlywiki/seo-tiddlywiki-plugin.htm
http://www.superphysique.net/gallery/benjamin.htm
http://www.superphysique.net/gallery/fabrice.htm
http://www.superphysique.net/gallery/yann.htm
http://www.superphysique.net/super%20physique/updates.htm
http://www.superphysique.net/gallery/jean-louis.htm
http://www.superphysique.net/gallery/rudy.htm

!Report a bug / Reporter un bug

<>

!Copyright

This work is licensed under a Creative Commons Attribution 2.5 License.

Panel discussion on genomics, 2001

Fri, 16 Mar 2007 21:36:00 GMT

Moderated by Adrienne Burke, Editor-in-Chief of Genome Technology magazine, panelists included: NathanSiemers, Group Leader Bioinformatics/Applied Genomics, Bristol-Myers Squibb Pharmaceutical Research Institute; Christian Stoekert, Jr., Senior Research Investigator, Center for Bioinformatics, University of Pennsylvania; Neil Winegarden, M.Sc., Manager of Commercialization and External Contracts, Ontario Cancer Institute Microarray Centre; and Jeffrey Paul Woessner, Director, DNA Technologies, Paradigm Genetics.

At the beginning of the hour-long discussion, each panelist presented his perspectives on problems encountered while analyzing disparate gene sequence and expression data and explored approaches currently on the drawing boards of vendors and standards consortiums such as the National Center for Genome Resources (NCGR).

There was general agreement between panelists with Nathan Siemers' assertion that a "Tower of Babel" exists within the research community. However, Chris Stoeckert cautioned that while many organizations were working on standards, no single approach to "data normalization" would be a desired since "there is currently no one best way" to normalize data. At best, Stoeckert asserted, many obstacles to sharing expression data could be overcome with a controlled vocabulary and "repository of research methods" defined in a commonly understood language.

Neil Winegarden recommended that a way should be found to link or couple processed expression data with raw data to permit researchers to check the validity of analysis methods or results by referring back to expression data contained in original TIF files. Although network bandwidths do not yet support the increased volume of data transfer this idea suggests, Winegarden expects this to become feasible as bandwidth grows and computing capabilities evolve. Jeff Woessner suggested that a "common-error model" not yet developed could be used to judge data quality. Presently, error-models tend to treat all data as equally significant and that saturation, or results beyond a measurement tool's range, was a big problem.

The panelists generally agreed that the industry is still immature and expected that progress will be made over time towards inexpensive, off-the-shelf solutions.

C&E News Article with NathanSiemers, 2002

Fri, 16 Mar 2007 21:34:00 GMT

EMPLOYMENT
January 7, 2002
Volume 80, Number 1
CENEAR 80 01 pp. 47-53
ISSN 0009-2347

CAREERS IN BIOINFORMATICS
Field is not significantly affected by economic downturn; qualified people are still hard to find

CELIA M. HENRY, C&EN WASHINGTON

With the ever-expanding reach of genomics and proteomics and the large amounts of data that their associated techniques generate, biology is becoming an increasingly quantitative science. The need is growing for scientists--whether they be trained as molecular biologists, biochemists, or chemists--who can speak the languages of both the computational and biological sciences.
8001new_about

The field of bioinformatics is one way to deal with this explosion of data. Unfortunately for neophytes trying to understand the field, bioinformatics means different things to different people. At its core, however, the field is simply the intersection of biology and the computational sciences, which include mathematics, statistics, and computer science.

Nathan O. Siemers, associate director of applied genomics at Bristol-Myers Squibb in Hopewell, N.J., calls bioinformatics "a mixture of the mundane and the sublime." The mundane includes data integration, data formatting and conversion (also known as parsing), and automation--"doing a relatively straightforward analysis a million times over the course of a few days and then dealing with the volume of results you get and turning them into something useful," Siemers says.

It's when the useful parts start to emerge that the sublime aspects surface. "Some of the most exciting stuff is working with large bodies of sequence and gene-expression data," he says, "seeing the patterns that come out and how they reproduce biology, in some cases extremely well."

FOR MANY PEOPLE, bioinformatics is focused on analyzing genomic data, but for others it's much broader. Originally confined to the early stages of drug discovery, bioinformatics is lending its power to all aspects of clinical development, a trend that will only continue. "In industry, I see bioinformatics evolving from primarily supporting early discovery to becoming more embedded in all stages of the drug discovery process," Siemers says. "We're already established in pharmacogenomics, trying to tie efficacy and side effects in a clinical setting back to underlying genetic variation in our patients."

Much bioinformatics work at Bristol-Myers currently focuses on RNA measurements, such as gene-expression profiling, Siemers says. However, proteomics is catching up. "It will probably take another couple of years before the volumes of data from those [proteomics] efforts really equal that of the RNA profiling chips," he says.

Abgenix, located in Fremont, Calif., is also taking a broader view of bioinformatics. Its informatics group is subdivided into a software development group, a computational biology group, and even a library information science group. "We're involved in the same types of genomics data analysis that you have in a typical bioinformatics group, but we're also involved in lab automation and algorithm development for the various high-throughput assays, preclinical assays, and process development," says Keith Joho, director of bioinformatics. "We're putting together an integrated bioinformatics approach that not only encompasses that very beginning part--the genomics data analysis--but really covers the spectrum of drug discovery up to going into the clinic."

Rosetta Inpharmatics, a subsidiary of Merck located in Kirkland, Wash., takes a quantitative and computational biology approach to bioinformatics, according to Eric Schadt, a chief scientist and head of the computational genomics program.

At Rosetta, bioinformatics falls under the larger umbrella of informatics, headed by Roland Stoughton, and is divided into three groups. A custom data analysis group headed by Hongyue Dai and Yudong D. He develops solutions to process large sets of RNA expression array data and integrates these data with other sources of information. These individuals must take the data from thousands of arrays--millions of measurements--and "recognize the patterns within those millions of measurements that really elucidate the processes of interest in the system under study," Schadt says. The individuals in that group tend to have doctorates in mathematics or statistics.

The second group is the computational genomics program, which Schadt describes as being closer to classic bioinformatics. That group does sequence-based analyses, such as annotating genes and proteins, searching for motifs in proteins, or predicting genes in genomic sequence. However, that group is also "directly involved in driving the biology and thinking of innovative ways to integrate expression, genetics, genomic, and other data of interest for the purposes of discovery." Most of the people in that group have a Ph.D. in math, statistics, or biology. Schadt himself has a Ph.D. in biomathematics. The third group, headed by Mihai Margarint, focuses on software engineering and provides advanced software development support to the other two research teams.

ALTHOUGH BIOLOGISTS first come to mind when talking about bioinformatics, chemists are also welcome. "Chemists who are more biologically oriented, like biochemists, play a big role in helping us piece together pathways and understand protein function," Schadt says. "Also, their training, especially in areas like physical chemistry, tends to be more quantitative. They're more adept at the sort of analyses we do than a classically trained biologist, who typically doesn't get the math and statistical training that chemists often get."

In fact, the small number of biologists working within the informatics team at Rosetta "tend to be those biologists with strong programming, database, or quantitative skills, which are skills many graduate programs in biology haven't integrated into their curricula," Schadt says. In contrast, physical chemists and physicists tend to be more skilled in developing and applying numerical algorithms to mine data. "I think the need for people who are trained more quantitatively just grows and grows as more people in the biological sciences accept that biology is becoming more of a quantitative science. The quantitative training will continue to enable research in this field to be more competitive," he says.

At Large Scale Biology Corp. in Vacaville, Calif., Gary M. Wolfe, vice president of informatics systems, prefers to pull bioinformaticists from the physical sciences because they tend to have a "good mathematical foundation." They may be required to develop user interfaces for existing algorithms or to develop algorithms of their own. "I'd rather get individuals who are heavy-duty experienced scientists with a strong programming background," Wolfe says. "Then it's pretty straightforward to write a Web interface to the BLAST [sequence alignment] algorithm. But that individual on another day could put together a sophisticated algorithm to analyze mass spec data."

Wolfe believes strongly that a bioinformatics platform must effectively integrate laboratory information management systems with data analysis and discovery applications. The data generated must be stored and tracked in a relational database. "Once the data are in some ordered format, it becomes straightforward to write programs for analyzing the data, and generally speaking, this enables us to create a discovery platform," Wolfe says. "However, to create such a platform, it is necessary to have individuals with excellent systems analysis and programming skills."

However, Wolfe says, it's not possible to take just any person with a programming background or mathematical background and have them program for bioinformatics applications. "They have to have an interest and experience in the life sciences. That can come from previous work they've done in a company or even their graduate or undergraduate training."
"The need for people who are trained more quantitatively grows as more people in the biological sciences accept that biology is becoming more of a quantitative science."

COMPUTER SKILLS are very important for work in bioinformatics, especially UNIX and the programming languages C and PERL, Wolfe says. He focuses on these particular languages because most bioinformatics programs are written in C and because PERL is powerful for text processing and is flexible with Web applications.

Schadt agrees that ideal bioinformaticists will be strongly grounded in math, statistics, and computer science. In addition, they will have at least some level of biological understanding. "The ones who are the most productive are the ones who can set up databases themselves, write scripts and programs themselves to process data or assemble data in a meaningful way, and then statistically summarize those data for the purposes of biological discovery. As the bar gets raised, I think a better understanding of biology, having the ability to identify the really pressing questions, is going to be required to be really competitive."

Joho says the ideal preparation varies because bioinformatics requires a variety of people. "The key would be that you have to be very good in one area--for instance, an accomplished biologist or biomathematician--but you should also have some additional training in another area. For example, a mathematician who has a good biology background is very valuable, as is a biologist who has a computer science or mathematics background."

At Consensus Pharmaceuticals in Medford, Mass., the best candidates will have strong biology backgrounds, "because the computer skills are broadly available in a variety of candidates," says John L. Krstenansky, vice president of chemistry. "You have to know how to interpret the data and know what's really meaningful if you're generating algorithms."

Krstenansky considers people with purely computer science backgrounds or who have been out of the science for a while not to have "the scientific strength" needed to build a strong bioinformatics program. "You need a strong chemistry or biology background that cannot be achieved without formal training. You must be able to be recognized as a contributing scientist in that area of science. That's the kind of depth of understanding and currency in the field that I think is essential."

The bioinformatics needs at Consensus lie outside the "mainstream bioinformatics" of genomic data, Krstenansky says. The company, which is based on a library-screening technology for identifying ligands to various enzymes or receptors, needs people who can assess information to identify "new biology." Therefore, Consensus is particularly interested in candidates with a strong background in biochemistry and an understanding of cellular biology.

Although Krstenansky anticipates that the bioinformatics effort at Consensus will grow, he doesn't see it reaching the size of the company's biology and chemistry groups. "Your primary need is people generating the real materials and the raw data to be analyzed," he says. "If things are being done right, you should need fewer people proportionately to do the analysis of the data or to create the tools for the analysis of the data."

SOME COMPANIES focus on providing bioinformatics software to other companies. One such company is Accelrys, located in San Diego. The "ideal profile" for someone in bioinformatics at Accelrys is someone who has at least a master's degree in biology in addition to a computer science degree, according to Judith M. Ohrn, vice president of human resources. "That's really nirvana," she says. If they can't find someone with training in both biology and computer science, they will hire a strong computer scientist who can pick up the biology on the job. "Normally you find with scientists who are good engineers or good computer scientists a certain fundamental knowledge about biology and an aptitude to learn what they need to learn."

Universities are grappling with the issue of what to include in a bioinformatics program. C. Fred Fox, a professor of microbiology and molecular genetics who is actively involved with the bioinformatics program at the University of California, Los Angeles, asks: "What training must these people have so they can sustain a career without going stale?" At UCLA, students must fulfill the requirements for a degree in one of the 13 participating departments--including math, statistics, and biochemistry--and then take additional courses to earn the bioinformatics certificate. Programs are being set up at both the master's and Ph.D. levels. The Ph.D. certificate program has already been training students for three years and should soon receive its final approval from the faculty senate.

The main issue in preparing for a career in bioinformatics isn't whether an individual is a biologist or computer scientist first, says Michael N. Liebman, director of computational biology at the Abramson Family Cancer Research Institute at the University of Pennsylvania. He spent 12 years working on bioinformatics in the pharmaceutical industry. "You can come in with a molecular biology background and learn computer science. You can come in with a computer science background and learn molecular biology. The issues that really need to be addressed are how do you solve complex problems and how do you work in teams."

Liebman complains that students are not usually taught how to identify the right question about a problem. "They're taught how to apply methodologies if the question is presented to them," he says. "You don't need an algorithm to run faster. You first need to ask if it's the right algorithm and if it's solving the right problem."

Liebman calls bioinformatics a "moving target." People who are training for a career should not expect that the qualifications for the jobs advertised today will also be what is needed in the future. "You really have to look for a training program that's looking ahead to see what the longer term issues are and not just turning somebody out for an industrial position."

Opinions vary over the value of specialized bioinformatics programs. For example, Wolfe worries that such programs teach very little in each of the underlying areas. "I'm a real proponent of the fundamentals," he says. "The fundamentals are math, chemistry, and physics. With that, you've created a great foundation."

Schadt believes that graduates of master's-level programs may find their career choices limited by not having a doctorate. "If you're at all passionate about the science, it's a very tough world to be in where you're at the low end of the totem pole, really servicing the scientific efforts," he says. "It's incredibly difficult to drive projects at the scientific level without having jumped through the Ph.D. hoop."

No matter what their educational background, people need to be nimble and willing to seize fast-moving opportunities. "If you're going to be in this field, it's a really dynamic field with small windows of opportunity," Wolfe says. "If you can't keep up with the Joneses and keep moving and keep learning new things, then it's not a good place to be. That's just the baggage that goes along with the fact that this field is progressing so fast and will be around for a long time."

EVEN WITH THE downturn in the economy, the demand for bioinformaticists does not seem to have significantly diminished. "The field is somewhat insulated because there is still such a high demand for skilled bioinformaticists," Wolfe says. "The fact is that there is a lot of money going into genomics and proteomics these days; I assume that the demand for bioinformatics will only grow over the coming years."

Schadt's experience has been that several bioinformatics companies have instituted hiring freezes. However, he says, "the bioinformatics-based groups are less affected" because "special allowances can be made to hire in hotshot types." In the short term, he says, lower level bioinformaticists will be the most affected, including people with master's or Ph.D. degrees with little or no experience.

"But for any of these big companies that have a freeze on hiring, there are other big companies and smaller start-ups that are more eager than ever to pick up bioinformatics types," Schadt says. "The bottom line, I believe, is that the bioinformatics field will not feel any real pain unless the economy gets really bad."

Schadt believes that the bioinformatics field will continue to be insulated from all but major economic shocks for several reasons. It is still a relatively new field, and there are not enough qualified people to fill all the positions. Plus, companies and academic centers continue to realize the need for bioinformaticists and thus create new positions.

Even though the human genome has been sequenced, don't expect the need for bioinformaticists to vanish anytime soon. "I couldn't think of a better place to be in the next five to 10 years," Wolfe says. "Five years from now, people are going to look back at even the year 2000, give a little chuckle, and say, 'If these people had the data we're working with today, they could have done this, this, and this.' Ten years from now, they're going to be saying the same thing about the year 2005, let alone 2000."

Flickr Search Tool

Sun, 11 Mar 2007 16:26:00 GMT

I've been working on a [[Flickr|http://www.flickr.com]] search tool - it's up and powerful in terms of minimizing web paging.

Give it a try: [[Flickr Hive Mind|http://www.fiveprime.org/flickr_hvmnd.cgi]]

Update - that little Flickr Search on the left menu column is now enabled to use the Flickr Hive Mind tool.

Moennig Violins

Tue, 20 Feb 2007 18:40:00 GMT

He won't take my StanleyKiernoziak [[cello]] in for repairs. Very lame.

2039 Locust Street, Philadelphia PA 19103 | moennig@juno.com
tel: 800-523-4051 or 215-567-4198 | fax: 215-567-4175

Plavix trial ends

Fri, 16 Feb 2007 12:18:00 GMT

Feb. 15 (Bloomberg) -- Bristol-Myers Squibb Co. and Sanofi- Aventis SA's bid to protect the blood-thinning drug Plavix from generic competition moved closer to resolution with the end of a patent trial over the medicine.

Apotex Inc., a generic-drug maker, spent the past four weeks trying to convince U.S. District Judge Sidney Stein in New York that the patent is invalid and unenforceable. Stein today told both sides to submit written arguments to him, putting off a ruling for at least six weeks, said Evan Chesler, lead lawyer for Bristol-Myers and Sanofi.

``Apotex is confident in its position,'' Robert Silver, a lawyer for the Weston, Ontario-based company, said today in an e-mail. ``We believe there is overwhelming evidence to support our defenses and look forward to a favorable decision.''

New York-based Bristol and Paris-based Sanofi want to prevent the erosion of profits from Plavix, the world's second- best selling drug in 2005 behind Pfizer Inc.'s Lipitor cholesterol pill. The companies are still trying to recover from closely held Apotex's flooding of the market with a six-month supply of generic Plavix during a three-week period in August.

Stein today told Apotex's attorneys to submit post-trial arguments within two weeks from tomorrow. Bristol-Myers will have two weeks to present its argument and Apotex will get two more weeks to prepare a rebuttal, said Chesler, a partner with New York-based law firm Cravath, Swaine & Moore. He declined to comment on the case.

Compound Patent

Investors are betting Bristol-Myers and Sanofi will win the case, since the patent covers the main compound in Plavix, clopidogrel bisulfate. Eli Lilly & Co. and Pfizer have successfully fended off challenges to compound patents on their top medicines.

Robert Breisblatt, a lawyer for Apotex, claimed the key ingredient in Plavix was covered by a patent that expired in 2003. Chesler maintained that the earlier patent covered a whole class of compounds, and the discovery of clopidogrel bisulfate was a surprise.

Bolstering Sanofi and Bristol-Myers was an earlier ruling by Stein that Apotex hadn't raised a ``substantial question'' of the validity of the patent. That ruling, which was upheld by an appeals court that specializes in U.S. patent law, forced Apotex to stop shipping generic Plavix until the trial's completion.

``We obtained the preliminary injunction and we won the appeal,'' Sanofi Chief Executive Officer Gerard Le Fur said at a Feb. 13 press conference. ``For these reasons, we remain very optimistic about events surrounding the Plavix suit.''

Top Seller

Bristol-Myers spokesman Tony Plohoros said his company also is confident of victory. Plavix is the second-biggest drug for Sanofi and the top seller for Bristol-Myers, accounting for a third of its 2005 revenue. The companies share the profits.

SEOTiddlyWikiPlugin

Wed, 14 Feb 2007 21:10:00 GMT

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SEOTiddlyWikiConfig

Wed, 14 Feb 2007 20:58:00 GMT

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Bring in the investment bankers!

Thu, 01 Feb 2007 13:32:00 GMT

Where there's smoke, the old saying goes, there's fire.

And something is certainly smoldering at Bristol-Myers Squibb, which the Financial Times reported yesterday has hired several investment banks in advance of an expected takeover offer from Sanofi Aventis.
Advertisement

The report, quoting unnamed bankers in Paris, said the drug maker hired Lehman Bros. to work alongside Citigroup and Morgan Stanley.

The idea, the report said, is to spark a bidding war for Bristol- Myers by attracting rival bids from GlaxoSmithKline, AstraZeneca, Pfizer, Schering-Plough or Merck.

Earlier this week, a French newsletter reported Sanofi and Bristol-Myers were in negotiations and had signed a pre-merger agreement. The Financial Times report said French bankers denied the companies signed an agreement, but were in talks on merging the company.