tag:blogger.com,1999:blog-10750568.comments2022-01-30T10:54:15.150-08:00Technology Times and TrialsMary Harrschhttp://www.blogger.com/profile/01812961655356354800noreply@blogger.comBlogger30125tag:blogger.com,1999:blog-10750568.post-23734657280178979412013-07-07T22:34:33.554-07:002013-07-07T22:34:33.554-07:00Nice post! Glad that you like their service. I bel...Nice post! Glad that you like their service. I believe that treating the customer so politely makes them so comfortable with your services. Anyway, thanks for sharing. Keep posting.Samsung Customer Care Numberhttp://customercaresupportnumber.com/noreply@blogger.comtag:blogger.com,1999:blog-10750568.post-1217412585622465472008-12-17T10:53:00.000-08:002008-12-17T10:53:00.000-08:00Interesting issue: highlights so many hot button a...Interesting issue: highlights so many hot button and crucial questions that are on the slippery slope of government and censorship.<BR/><BR/>I'm also interested in how the adult industry in Australia is responding by getting involved in politics themselves:<BR/><BR/>http://www.covenanteyes.com/blog/2008/12/10/sex-and-politics-australias-new-political-party-takes-on-the-mandatory-internet-filter/Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-10750568.post-60017333935501982712008-12-16T05:12:00.000-08:002008-12-16T05:12:00.000-08:00Sorry about that. I was using Scribefire to copy ...Sorry about that. I was using Scribefire to copy selected portions of the article and it grabbed a bunch of unseen HTML code that must have included that ad. I am usually trying to get as much done as possible in a short time so I don't view the blog after every post. I went in to the HTML code view and scrubbed the offending tags so hopefully you won't have any problem reading it now. Sometimes tools meant to help Bloggers be more productive are more trouble than they are worth.Mary Harrschhttps://www.blogger.com/profile/01812961655356354800noreply@blogger.comtag:blogger.com,1999:blog-10750568.post-9757890014417750452008-12-15T19:23:00.000-08:002008-12-15T19:23:00.000-08:00Very cheap is the fact this site has some advert i...Very cheap is the fact this site has some advert in place over top the blog so it is unreadable unless you copy it to a word pad, sad, sad, sad, sad.<BR/>Good Luck Oz because we are next on the hit list and in Ca it has already begun.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-10750568.post-63280738293141888742008-07-26T12:12:00.000-07:002008-07-26T12:12:00.000-07:00there are another idea too, you can add layer and ...there are another idea too, you can add layer and erase tool just to fit your need but with lower hardness and opacityAnonymousnoreply@blogger.comtag:blogger.com,1999:blog-10750568.post-27714521316149751752007-09-28T07:06:00.000-07:002007-09-28T07:06:00.000-07:00I want to thank You because you saved me a load of...I want to thank You because you saved me a load of headaches. I decided to go with Buy.com and got the same camera for only $20 more. I am glad my instincts made me search for reviews on the vendor I was going to purchase from. I thought something was not right when I saw the accessories were outrageously priced.Anonymoushttps://www.blogger.com/profile/06728167339081481295noreply@blogger.comtag:blogger.com,1999:blog-10750568.post-57346549564916750002007-08-08T06:50:00.000-07:002007-08-08T06:50:00.000-07:00Hi Mary! Glad to see you found our AR game stuff! ...Hi Mary! Glad to see you found our AR game stuff! My name is John Martin and I'm a game designer on the project at UW-Madison. I've been enthralled with this technology and its potential for connecting a wide range of ages (not just high school students) with the environments they move through. I'm currently working with 10-16 year olds in designing their own games and tours (regardingjohn.com/learn). I'd be happy to try to answer any questions you might have about any of the AR projects that our team at Madison works with (localgameslab.com)Anonymoushttps://www.blogger.com/profile/10642287545652299910noreply@blogger.comtag:blogger.com,1999:blog-10750568.post-49664300404296444812007-07-25T20:58:00.000-07:002007-07-25T20:58:00.000-07:00I think that Mr. Rockwell says it best http://www....I think that Mr. Rockwell says it best http://www.kenrockwell.com/tech/buy.htm<BR/><BR/>DaveGageGeekhttps://www.blogger.com/profile/16399066164611748225noreply@blogger.comtag:blogger.com,1999:blog-10750568.post-80111494086106916092007-07-17T11:32:00.000-07:002007-07-17T11:32:00.000-07:00Hartmut, you can download the prototype from:http:...Hartmut, you can download the prototype from:<BR/><BR/>http://interact.uoregon.edu/techweb/Timeline.fp7Mary Harrschhttps://www.blogger.com/profile/01812961655356354800noreply@blogger.comtag:blogger.com,1999:blog-10750568.post-1199289055131199572007-07-14T16:50:00.000-07:002007-07-14T16:50:00.000-07:00do you have a filemaker sample I could have. Hartm...do you have a filemaker sample I could have. <BR/>Hartmut77@yahoo.co.in<BR/><BR/>ThanksDave Phttps://www.blogger.com/profile/00737330564828537378noreply@blogger.comtag:blogger.com,1999:blog-10750568.post-26778782230570507832007-07-09T09:50:00.000-07:002007-07-09T09:50:00.000-07:00Thanks for you work and have a good weekThanks for you work and have a good weekdavid santoshttps://www.blogger.com/profile/08976825493652779441noreply@blogger.comtag:blogger.com,1999:blog-10750568.post-33816581445466167982007-07-01T06:18:00.000-07:002007-07-01T06:18:00.000-07:00Offering a product for a "false" price without cle...Offering a product for a "false" price without clearly stating it is dependent on the purchase of one or more accessories is not aggressive marketing - it is tacitly illegal. I received a letter back from our State Attorney General and his office forwarded my report on to the Federal Trade Commission for prosecution.Mary Harrschhttps://www.blogger.com/profile/01812961655356354800noreply@blogger.comtag:blogger.com,1999:blog-10750568.post-59546638815297347312007-07-01T06:03:00.000-07:002007-07-01T06:03:00.000-07:00That isn't really a scam; rather it is a form of a...That isn't really a scam; rather it is a form of aggressive marketing.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-10750568.post-5666528884811101272007-06-23T08:29:00.000-07:002007-06-23T08:29:00.000-07:00it will demonstrate how words are pronounced ? a s...it will demonstrate how words are pronounced ? a sound is sometimes better in my opinion. <BR/>Nonetheless, thanks for sharing your experience on Garmin's navigation device. Here are some good resources about acquiring a new language by immersion, in essence "study abroad" that may be interesting to you. They include <STRONG><A HREF="http://www.exploringabroad.com/course-italy.htm" REL="nofollow">Italian Courses in Florence</A>, Milan, Rome</STRONG> Italy and more language courses such as french, german, arabic, chinese, greek in Europe, Asia, and South AmericaAnonymousnoreply@blogger.comtag:blogger.com,1999:blog-10750568.post-47001877416411463292007-06-16T17:26:00.000-07:002007-06-16T17:26:00.000-07:00Hi,I found that "resellerratings.com" is an excell...Hi,<BR/>I found that "resellerratings.com" is an excellent place to see how an online seller is rated by users.<BR/>I have been steered away from several by viewing reviews of various camera swindlers. <BR/>I have made several fine purchases from beachcamera.com, low prices and fast delivery. I am not affiliated.<BR/>Cheers,<BR/>RichardR&Vhttps://www.blogger.com/profile/00676786712954055194noreply@blogger.comtag:blogger.com,1999:blog-10750568.post-53794466637960123422007-05-15T01:46:00.000-07:002007-05-15T01:46:00.000-07:00This is a cool site and I find the posts really in...This is a cool site and I find the posts really interesting! Keep them coming and good luck! :)Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-10750568.post-1163403508765830862006-11-12T23:38:00.000-08:002006-11-12T23:38:00.000-08:00As a founder of one of the online video editing co...As a founder of one of the <A HREF="http://www.stashspace.com/" REL="nofollow" TITLE="Online Video Editing">online video editing</A> companies - <A HREF="http://www.stashspace.com" REL="nofollow" TITLE="Video Sharing">stashSpace.com</A> - I find it disheartening to see it suggested that people are abandoning high-quality video capture devices for the low-quality offered by digital still cameras and cellphones.<BR/><BR/>Videotape is by far still the highest-quality capture medium available on the market. Parents of the children in the play (as profiled above) will want to have this video content available in the future as a high-quality archive, and not just a low-quality mash-up as offered by the other video editing/sharing sites profiled in this post.<BR/><BR/>Our customers are able to easily record their digital video through our web-based video capture system (or upload existing digital video files) in an archival-quality version. Edits always keep the original high-quality video file intact for future reference. Movies can be delivered online, on DVD or on video iPod. Users who share their video with each other can also import scenes into their own movies for custom mash-ups.<BR/><BR/>Don't sacrifice quality just because your first experience with online video is limited by the features offered by other companies -- My suggestion for those people who have abandoned their camcorder? Dust it back off and make sure your special moments receive the high-quality they deserve.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-10750568.post-1161705156605151452006-10-24T08:52:00.000-07:002006-10-24T08:52:00.000-07:00Mary-In working on a presentation for the GaETC co...Mary-<BR/><BR/>In working on a presentation for the GaETC conference, I had included info that Google & Yahoo both would allow RSS for searches. I was dismayed when I found your post, but in poking around, realized that the RSS feed was offered when I was logged in on Google or My Yahoo, but not in regular searches.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-10750568.post-1157817523153916982006-09-09T08:58:00.000-07:002006-09-09T08:58:00.000-07:00Thanks for the neat site. I also find the switch f...Thanks for the neat site. I also find the switch for "looks" disturbing, and unfortunately harmful for the reputation and/or image of the Mac. When folks such as the person describe do this kind of switch, obtain no good advice, and don't seek more info., it does an amazing disservice. <BR/><BR/>Then again the NYT review is awful. I would expect much better research from them. I've used a Mac since they came out, owned one since a year after, have worked in technology, both in marketing and MIS, primarily with educating employees, and have also used PCs and Unix workstations. I still prefer a Mac, and just ordered a new iMac with a 24" screen. <BR/><BR/>The distinctions drawn in the article are awful. I've run a Mac on a mixed network with sharing plenty of peripherals. The problems that cropped up where on the Windows side and included trouble with networking, user screw ups galore, complete ignorance of the basics of the machine on their desktop (for Windows users, not Mac users), a variety of software that facilitated that by not following some standard interface design, viruses, spyware, adblockers, and all sorts of fixes that had to be done if one did something somewhere else, and constant panic attacks from users... you name it. Then again, Windows techs also had plenty of work because there was always enough running around to do to set up a Windows machine. It took much longer to do so, and keep an employee happy *and* productive (if they are not the same) on a Windows machine.<BR/><BR/>When it came to sharing files, most folks using MS Word on Windows had no trouble with those using it on the Mac. The same for Excel, Powerpoint (Marketing loved this stuff), Filemakers, etc. Hardly anything else was used (although from time to time people wanted that "beautiful picture screen saver" they saw on somebody else's computer.<BR/><BR/>In terms of hardware... being "less diverse" is not a negative. Diversity is neither a sign of strength, or excellence. It is a sign of market strategy. <BR/><BR/>Oh, why bother. Awful review by the NYT. Thanks again!Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-10750568.post-1148323062595295472006-05-22T11:37:00.000-07:002006-05-22T11:37:00.000-07:00its great to see the major tv networks as well as ...its great to see the major tv networks as well as smaller online television networks broadcasting programs over the net. check out these links for more similar news:<BR/><BR/>http://www.usatoday.com/money/media/2006-04-07-ethnic-media-usat_x.htm<BR/><BR/>http://www.iht.com/articles/2006/03/12/business/sliver.php<BR/><BR/>http://www.variety.com/article/VR1117934602?categoryid=1009&cs=1Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-10750568.post-1145580443009200292006-04-20T17:47:00.000-07:002006-04-20T17:47:00.000-07:00What a great tutorial. Jake really knows his stuf...What a great tutorial. Jake really knows his stuff! I can't wait to try this fast fix.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-10750568.post-1144561071019122072006-04-08T22:37:00.000-07:002006-04-08T22:37:00.000-07:00Hi, LibitinaI read your article where you mentione...Hi, Libitina<BR/><BR/>I read your article where you mentioned my site. I also read about you going to London. If you run into any trouble of actually creating the guide, feel free to contact me for help. It would be great to see what kind of PodGuide you were able to make of your visit.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-10750568.post-1137301324024777812006-01-14T21:02:00.000-08:002006-01-14T21:02:00.000-08:00Winning The Battle Against HIV-1 Winning The Batt...Winning The Battle Against HIV-1 <BR/> <BR/>Winning The Battle Against HIV-1: (MPTV-x , HAART-x) / <BR/>(MPTV-x , Mega-HAART-x) - Couples Formed of a <BR/>Multivalent-Polivalent-Therapeutic-Vaccine (MPTV-x) <BR/>and Its Corresponding HAART-x , or Mega-HAART- Regimen <BR/>, Respectively. <BR/><BR/>Iosif Secasan <BR/><BR/>Department of Urologic Surgery <BR/>Spitalul Judetean Resita / The Hospital of Resita <BR/>RO-1700, Resita <BR/><BR/>Dan I. Pop <BR/><BR/>Data International SRL <BR/>Str. Horia, Nr.6, Bl.6, Et.10, Ap.39 Resita-1700, <BR/>RO-1700, Romania <BR/>Phone: 0040-722-940299 E-mail : danpop77@yahoo.com <BR/><BR/>Ciprian C. Secasan <BR/><BR/>Department of Microbiology / Department of Urologic <BR/>Surgery <BR/>Spitalul Judetean Resita / The Hospital of Resita <BR/>RO-1700, Resita <BR/><BR/><BR/><BR/>Abstract : This article presents, for the first time <BR/>in Medical History, an entirely new <BR/>theory and practical solution to eradicate HIV-1, <BR/>based on HIV-1's ability and need to mutate under <BR/>HAART-x / Mega-HAART-x drugs pressure, and on the <BR/>sinergetical scissoring effect on HIV-1 of (MPTV -x , <BR/>HAART-x) - couples and (MPTV-x , <BR/>Mega-HAART-x)-couples, which are formed of : <BR/><BR/>1. a multivalent-polyvalent-therapeutic-vaccine (MPTV <BR/>-x) , made of whole-killed HIV-1 (or of particular <BR/>parts of HIV-1) bearing on its genome (biochemical <BR/>structure) the resistance-mutations-pattern (RMP-x) <BR/>that would be induced by the following , to come <BR/>HAART-x or Mega-HAART-x regimen <BR/><BR/>and of <BR/><BR/>2. the respective, corresponding HAART-x or <BR/>Mega-HAART-x regimen, respectively. <BR/><BR/>Key Words : <BR/><BR/>HAART (highly-active-anti-retroviral-therapy), HAART-x <BR/>regimen, Mega-HAART-x regimen, point-mutations (PM), <BR/>resistance-mutations-loci (RML-x), <BR/>resistance-mutations-sites (RMS-x), <BR/>resistance-mutations-pattern (RMP-x-), <BR/><BR/>multivalent-polyvalent-therapeutic-vaccine (MPTV -x), <BR/>(MPTV -x, HAART-x)-couples, <BR/><BR/>(MPTV-x,Mega-HAART-x)-couples, <BR/>drug-resistant-virus(DRV) , drug-sensitive-virus <BR/>(DSV); <BR/><BR/><BR/><BR/><BR/>Introduction: <BR/><BR/>Time has come for Science and Medicine to win the <BR/>battle against HIV and AIDS. Since a classical vaccine <BR/>against HIV-1 is hard to design or even define, and <BR/>since current HAART <BR/>(highly-active-anti-retroviral-therapy) and even <BR/>Mega-HAART regimens are unable to clear an HIV-1 <BR/>infection , a combined strategy has to be adopted, in <BR/>order to achieve HIV-1 eradication. <BR/>This article presents an entirely new theory and <BR/>practical solution to eradicate the HIV-1 virus from <BR/>the body of HIV-1 infected persons, by combining HAART <BR/>(or Mega-HAART) with a multivalent-polivalent <BR/>-therapeutic-vaccine (MPTV), pre-administrated to <BR/>HAART, (or Mega-HAART respectively) and targeted <BR/>against the in-advance-known <BR/>resistance-mutations-sites (RMS) / <BR/>resistance-mutations-loci (RML) / point mutations(PM) <BR/>or even against entire resistance-mutations-pattern(s) <BR/>(RMP-s) of the following , to come HAART or Mega-HAART <BR/>regimen, respectively. <BR/>The polivalent, multivalent, or multivalent-polivalent <BR/>therapeutic vaccine (PTV-x, MTV-x, MPTV-x) made of <BR/>killed/highly inactivated HIV-1, bearing on its genome <BR/>blueprint the resistance-mutations-loci <BR/>(RML-x)/resistance-mutations-sites (RMS-x), the <BR/>point-mutations(PM-x), or the whole <BR/>resistance-mutations-pattern (RMP-x) that would be <BR/>generated by the following , to come , HAART-x , is <BR/>pre- administrated to HAART-x, and forms a couple with <BR/>it : (MPTV -x, HAART-x) or (MPTV-x, Mega-HAART-x) , <BR/>respectively. <BR/><BR/>A series, or repeated cycles of (MPTV -x, HAART-x) <BR/>couples, each couple encompassing a <BR/>multivalent-polivalent-therapeutic-vaccine (MPTV -x) <BR/>targeted against/ or encoding /or containing /the in - <BR/>advance - known resistance-mutations-loci (RML-x) / <BR/>resistance-mutations-sites (RMS-x) , <BR/>point-mutations(PM-x), or the whole <BR/>resistance-mutations-pattern (RMP-x) of the following, <BR/>to come HAART-x - regimen (or Mega-HAART-x -regimen , <BR/>respectively) may lead to the eradication of HIV-1 <BR/>from the body of a HIV-1 positive person. <BR/><BR/>The expansion of such a successful HIV-1 eradication <BR/>therapy may save all 40-50 million persons who are <BR/>HIV-infected worldwide and would solve the HIV/AIDS <BR/>crisis. <BR/><BR/><BR/><BR/>Materials and Methods : <BR/><BR/>The general HIV-1 eradication scheme in a series <BR/>and/or multi-cycle scenario is : <BR/><BR/>(MPTV-1, HAART-1), ----.> (MPTV-2, HAART-2), ----> <BR/>(MPTV-3,HAART-3),---->........(MPTV-x, <BR/>HAART-x)........---->(MPTV-n, HAART-n) -----> <BR/><BR/>--->(MPTV-1M, Mega-HAART-1),---->( MPTV-2M, <BR/>Mega-HAART-2), ---->(MPTV-3M, Mega-HAART-3)---->....( <BR/>MPTV-xM, Mega-HAART-x), ....---->(MPTV-nM, <BR/>Mega-HAART-n)---> -----> Eradication <BR/><BR/>clearly indicating that each multivalent, polivalent, <BR/>or multivalent-polivalent-therapeutic-vaccine (MPTV-x) <BR/>is pre-administrated to / (precedes) its corresponding <BR/>HAART-x - regimen <BR/><BR/>(or Mega-HAART-x - regimen respectively), and is <BR/>targeted against ( or encodes/or contains) the in <BR/>-advance-known resistance-mutations-loci (RML-x) / <BR/>resistance-mutations-sites (RMS-x), <BR/>point-mutations(PM-x), or even the whole <BR/>resistance-mutations-pattern (RMP-x) that would be <BR/>generated by the following , to come HAART-x - regimen <BR/>(or Mega-HAART-x-regimen, respectively) on HIV-1's <BR/>genome blueprint. <BR/><BR/>In other words, MPTV-x is preventing the emergence of <BR/>HAART-x - resistant - virus, acting in fact like a <BR/>typical VACCINE against the HIV-1 virus that would <BR/>otherwise emerge after HAART-x therapy. While MPTV-x <BR/>is preventing the emergence of HAART-x - resistant - <BR/>virus, HAART-x is reducing viral load, i.e. the <BR/>numbers of drug-sensitive- virus (DSV). <BR/><BR/>The synergetic scissoring effect of a (MPTV-x,HAART-x) <BR/>-couple on HIV-1 may be 1000 or even 10.000 times (3-4 <BR/>Log) more effective and potent than any current <BR/>HAART-x - regimen given alone, especially in terms of <BR/>reducing HIV-1 viral load. Considering that a typical <BR/>HAART-x regimen is currently able to reduce HIV-1 <BR/>viral load from 60.000 <BR/><BR/>copies/ml or higher, to 20 copies/ml or lower, a <BR/>(MPTV-x, HAART-x)-couple might be able to reduce viral <BR/>loads from 60.000 copies/ml or higher to 2-20 <BR/>copies/litre, whereas a succession of different <BR/>(MPTV-x, HAART-x)-couples, may lead to eradication of <BR/>HIV-1 from the body of HIV-1 positive persons. <BR/><BR/>In order to better illustrate the potential anti-HIV-1 <BR/>power of couples formed by a multivalent-polivalent <BR/>therapeutic vaccine (MPTV-x) and its corresponding <BR/>HAART-x - regimen , it can be estimated that a single <BR/>antiretroviral drug like AZT, (or e.g. Crixivan) , <BR/>would be as effective as 3-4 antiretroviral drugs ( <BR/>i.e. as effective as HAART ), provided that it is <BR/>preceded by a <BR/>multivalent-polivalent-therapeutic-vaccine (MPTV-x) <BR/>containing killed HIV-1 (or particular parts of HIV-1) <BR/>bearing on its genome (biochemical structure) the <BR/>resistance-mutations-pattern(RMP) of AZT. <BR/><BR/>Figure1/Table1 presents the RMS/RML for different <BR/>antiretroviral drugs and for 2 drug combinations, i.e. <BR/>their " point-mutations". The "point-mutations" <BR/>induced by a particular drug form/build the <BR/>resistance-mutations-pattern(RMP) of HIV-1 to that <BR/>drug. <BR/><BR/>Figure1/Table1 <BR/><BR/>Drug Class <BR/><BR/>Primary Resistance Mutations <BR/><BR/>Mutations With Additional Effect <BR/><BR/>RTIs <BR/><BR/>AZT (Retrovir®) <BR/><BR/>M41L, T215Y, T215H <BR/><BR/>D67N, K70R, K219Q, K219E <BR/><BR/>3TC (Epivir®) <BR/><BR/>M184V, M184T, M184I <BR/><BR/>ddI (Videx®) <BR/><BR/>L74V <BR/><BR/>K65R, L74V, V75T, M184V <BR/><BR/>ddC (HIVID) <BR/><BR/>K65R <BR/><BR/>T69D, L74V, V75T, MI84V, Y215C <BR/><BR/>Abacavir (Ziagen) <BR/><BR/>K65R, L74V, Y115F, M184V <BR/><BR/>D4T (Zerit®) <BR/><BR/>V75T <BR/><BR/>150T <BR/><BR/>PFA <BR/><BR/>E89G, E89K, L921 <BR/><BR/>W88G, W88S, S156A, Q161L, H208Y <BR/><BR/>NNRTIs <BR/><BR/>Nevirapine (Viramune®) <BR/><BR/>K103N, Y181C, Y181I <BR/><BR/>A98G, L100I, V106A, V108I, Y188C, G190A <BR/><BR/>Delavirdine (Rescriptor®) <BR/><BR/>K103N, K103T, Y181C <BR/><BR/>P23L <BR/><BR/>Efavirenz (Sustiva) <BR/><BR/>Y188L <BR/><BR/>L100I, K101E, K103N, V108I, V179D, Y181C <BR/><BR/>Protease Inhibitors <BR/><BR/>Indinavir (Crixivan®) <BR/><BR/>M46I, M46L, V82A, I84V <BR/><BR/>L10I, L10R, K20M, K20R, L24I, V32I, I54V, A71V, A71T, <BR/><BR/>L90M <BR/><BR/>Nelfinavir (Viracept®) <BR/><BR/>D30N, M46I, A71V, I84V <BR/><BR/>M36I, V77I, N88D, L90M <BR/><BR/>Saquinavir (Fortavase®) <BR/><BR/>G48V, L90M <BR/><BR/>L10I, I54V, I84V <BR/><BR/>Ritonavir (Norvir®) <BR/><BR/>V82A, V82F, V82S, I84V <BR/><BR/>K20R, L33F, M46I, I54L, I54V, A71T, A71V, L90M <BR/><BR/>Resistance to Multiple Drugs <BR/><BR/>AZT + ddI/ddC <BR/><BR/>A62V, V75I, F77L, F116Y <BR/><BR/>Q151M (all 4 mutations required for significant <BR/><BR/>resistance) <BR/><BR/>AZT + 3TC <BR/><BR/>M184V + R211K + L214F <BR/><BR/>G333D, G333E <BR/><BR/>A large database containing nearly all published HIV-1 <BR/>reverse-transcriptase and protease sequences, and that <BR/>allows for mutations searching can be found at : <BR/>http://hivdb.stanford.edu/ <BR/><BR/>HIV-1 recombination and mutation (1-6), including <BR/>"resistance-mutation", are important mechanisms by <BR/>which HIV-1 evades drug or immune pressures. HIV-1- <BR/>strains that are resistant to an antiretroviral drug <BR/>present multiple " point-mutations"(PM), which act in <BR/>synergy to confer the resistant phenotype to that <BR/>drug, and we may define these "point-mutations" (PM-x) <BR/>as resistance-mutations-loci (RML-x) or <BR/>resistance-mutations-sites (RMS-x), whereas their <BR/>ensemble may be termed resistance-mutations-pattern <BR/>(RMP-x). <BR/><BR/>Multidrug resistant HIV-1 strains arise in patients <BR/>treated with HAART-x or Mega-HAART-x, either through <BR/>direct mutation or through recombination of variants <BR/>that are resistant to single drugs. <BR/><BR/>Paradoxically, and luckily at the same time, <BR/>point-mutations (PM) that confer drug - resistance <BR/>offer us targets for vaccine(s) and especially for <BR/>therapeutic vaccines(TV-s) development. The <BR/>drug-induced point-mutations (PM), or <BR/>resistance-mutations-loci <BR/>(RML-x)/resistance-mutations-sites (RMSx), or even the <BR/>entire resistance-mutations-patterns (RMP-x-s) may be <BR/>contained/encoded/encompassed in a multivalent, <BR/>polivalent or <BR/>multivalent-polivalent-therapeutic-vaccine (MPTV-x) <BR/>aimed to prevent the emergence of HAART-x - resistant <BR/>HIV-1 virus. <BR/><BR/>In HIV-1 infection, the infected hosts apparently <BR/>cannot solve the problem of identifying an antigen <BR/>that is conserved among the variants and quasispecies, <BR/>and thereby neutralize the infection. Paradoxically <BR/>and luckily again, both HAART and Mega-HAART regimens <BR/>are not only reducing HIV-1 viral loads to 50 <BR/>copies/ml or less, but are also UNIFYING HIV-1's <BR/>diversity, by "artificially" creating a common factor <BR/>among the remaining/surviving 50 copies/ml of <BR/>drug-resistant-virus(DRV), in form of <BR/>resistance-mutations-loci (RML-x) / <BR/>resistance-mutations-sites (RMS-x) or point-mutations <BR/>(PM), which together build the <BR/>resistance-mutations-pattern (RMP-x). <BR/><BR/>Each point-mutation (PM) taken separately, and even <BR/>entire resistance-mutations-patterns (RMP-x-s) are <BR/>both excellent targets for therapeutic vaccines (TV), <BR/>and at the same time can be used as a simple, or <BR/>polyvalent, or multivalent, or multivalent-polyvalent <BR/>-therapeutic- vaccines (MPTV -x) respectively, namely <BR/>in form of whole-killed or highly - inactivated HIV-1 <BR/>virus (Remune-like and/or Remune- modified bearing the <BR/>HAART-x or Mega-HAART-x mutations ) , bearing on its <BR/>genome blueprint the resistance-mutations-pattern(s) <BR/>(RMP-x-s) of the following , next , to come HAART-x or <BR/>Mega-HAART-x - regimen. <BR/><BR/>Interestingly and noteworthy, within each (MPTV -x, <BR/>HAART-x)-couple, and by analogy within each <BR/>(MPTV-x,Mega-HAART-x)-couple, the <BR/>multivalent-polyvalent therapeutic vaccine (MPTV -x) <BR/>acts in fact like a true vaccine, like a CLASSICAL <BR/>VACCINE against the HAART-x-resistant HIV-1 virus (or <BR/>Mega-HAART-x- resistant HIV-1 virus), by preventing <BR/>its emergence. <BR/><BR/>Each antiretroviral drug and each HAART-x - or <BR/>Mega-HAART-x - regimen divides the HIV-1 viral <BR/>population in : <BR/><BR/>1. drug-sensitive-virus (DSV) , which is killed off by <BR/>HAART-x or Mega-HAART-x respectively, <BR/><BR/>and <BR/><BR/>2. drug-resistant-virus(DRV), whose emergence can be <BR/>prevented by the multivalent-polyvalent therapeutic <BR/>vaccine (MPTV -x) which is pre-administrated to its <BR/>corresponding <BR/><BR/>HAART-x regimen or Mega-HAART-x regimen, respectively. <BR/><BR/>If a pre - HAART-x administrated <BR/>multivalent-polyvalent therapeutic vaccine (MPTV -x) <BR/>manages to prevent the emergence of <BR/>drug-resistant-virus(DRV), HIV-1 can be eradicated , <BR/><BR/>since the following HAART-x-regimen will eliminate the <BR/>drug-sensitive- virus(DSV). <BR/><BR/><BR/>Results : <BR/><BR/>Infection and immunity are two sides of the same coin. <BR/>Therefore it is reasonable and scientifically sound to <BR/>vaccinate an HIV-1 positive person with killed HIV-1 <BR/>virus resistant to <BR/><BR/>a specific HAART-x regimen, before HAART-x treatment ; <BR/>and with killed wild-type HIV-1 (eventually collected <BR/>from the patients' blood before HAART-x treatments <BR/>onset) at the end of all HAART-x or Mega-HAART-x <BR/>therapies, especially when a long-term structured <BR/>-treatment - interruption (STI) is planned or <BR/>intended. <BR/><BR/>This vaccination with whole, killed, wild-type HIV-1 <BR/>virus should be done shortly before HAART-x or <BR/>Mega-HAART-x therapy is stopped ( or interrupted ), <BR/>since it is well known that some wild-type HIV-1 may <BR/>still be hidden in certain organs or tissue reservoirs <BR/>and since it is also well-known that eventually <BR/>surviving HAART-resistant- HIV-1 virus tends to revert <BR/>to wild-type HIV-1 virus , after HAART-treatment is <BR/>stopped. <BR/><BR/>Two Latin sayings describe the rationale of using <BR/>(MPTV -x, HAART-x)-couples and <BR/>(MPTV-x,Mega-HAART-x)-couples in eradication of HIV-1. <BR/>"Divide et Impera" perfectly describes the role and <BR/>action of HAART-x and Mega-HAART-x regimens, which <BR/>divide the <BR/><BR/>HIV-1 viral population in drug-sensitive-virus(DSV), <BR/>which is eliminated/cleared by HAART-x and <BR/>Mega-HAART-x -regimens respectively, and <BR/>drug-resistant-virus(DRV) , whose emergence is <BR/>prevented by the multivalent-polyvalent therapeutic <BR/>vaccine <BR/><BR/>(MPTV -x) which is pre-administrated to HAART-x or <BR/>Mega-HAART-x respectively, according to the main <BR/>principle of prevention, vaccination and homeopathy <BR/>"Similia Similibus Curentur". <BR/><BR/>The golden standard for multivalent-polyvalent <BR/>therapeutic vaccines (MPTV-x)-s to be used in (MPTV <BR/>-x, HAART-x)-couples or (MPTV <BR/>-x,Mega-HAART-x)-couples, should be whole , killed <BR/>HIV-1 virus or whole, highly inactivated HIV-1 virus <BR/>(e.g. Remune-like and Remune-RMP-x- modified), bearing <BR/>on its genome blueprint the <BR/>resistance-mutations-pattern(s) (RMP-x-s), that would <BR/>be generated by the following, to come <BR/>HAART-x-regimen. <BR/><BR/>On the other hand, the ultimate aim of pathogen <BR/>(HIV-1) -genome sequencing is the development of <BR/>vaccines. The genome sequence is the"parts list", and <BR/>each gene or gene product should be tested for its <BR/>potential usefulness in anti-HIV-1 vaccine and <BR/>therapeutic vaccine development. <BR/><BR/>The process of HIV-1 eradication may be divided in 3 <BR/>steps by monitoring HIV-1 viral load decreases : <BR/><BR/>STEP 1 would mean a viral load decrease from <BR/>60.000copies/ml or highr to 5-50 copies/ml; <BR/><BR/>STEP 2 would mean a viral load decrease from 5-50 <BR/>copies/ml to 5-50 copies/litre and <BR/><BR/>STEP 3 would mean a further viral load decrease from <BR/>5-50 copies/litre to zero copies/litre, i.e. <BR/>eradication of HIV-1. Current HAART and Mega-HAART-x <BR/>regimens make STEP1 possible for prolonged periods of <BR/>time. STEP 2 and STEP 3 can only be accomplished by <BR/>using (MPTV -x, HAART-x)-couples and/or (MPTV -x, <BR/>Mega-HAART-x) -couples in series and / or cycles. <BR/><BR/>(MPTV -x) , the multivalent-polyvalent therapeutic <BR/>vaccines, can be defined and designed in many ways, <BR/>depending on the drugs that are chosen as partners in <BR/>the (MPTV -x, HAART-x)-couples and <BR/>(MPTV-x,Mega-HAART-x)-couples. <BR/><BR/>When a combination of reverse-transcriptase inhibitors <BR/>(RTI-s) is chosen as a first-line drug - <BR/>treatment,(MPTV -x) may contain at least 2 main <BR/>components : <BR/><BR/>1. whole killed HIV-1 virus bearing the <BR/>point-mutations (PM) of each reverse-transcriptase <BR/>inhibitor and of their combination (Figure1/Table1) <BR/>and <BR/><BR/>2. an HIV-1 reverse-transcriptase enzyme bearing the <BR/>point-mutations of the following, to come, to be used <BR/>reverse-transcriptase inhibitors (RTI-s). <BR/><BR/>When a combination of protease inhibitors is chosen, <BR/>,(MPTV-x) may also have 2 main components: <BR/><BR/>1. whole killed HIV-1 virus bearing the <BR/>point-mutations (PM) of each protease inhibitor and of <BR/>their combination(Figure1/Table1) and <BR/><BR/>2. an HIV-1 protease enzyme bearing the <BR/>point-mutations (PM) that would be induced by the <BR/><BR/>following, to come protease inhibitors (PI-s) in the <BR/>absence of pre-administrated MPTV -x. <BR/><BR/>When a combination of reverse-transcriptase and <BR/>protease - inhibitors is chosen as the HAART-x <BR/>component of the (MPTV-x, HAART-x)-couple, MPTV -x may <BR/>contain at least 3 main components : <BR/><BR/>1. whole killed / inactivated HIV-1 virus bearing the <BR/>point-mutations (PM) of each reverse-transcriptase and <BR/>of each protease inhibitor (Figure1/Table1), as well <BR/>as the point-mutations (PM) with additional effect; <BR/><BR/>2.an HIV-1 reverse-transcriptase bearing the <BR/>point-mutations (PM) that would be induced by the <BR/>reverse-transcriptase inhibitors (RTI-s) to come; <BR/><BR/>3. an HIV-1 protease enzyme, bearing the <BR/>point-mutations (PM) that would be induced by the <BR/>following, to come, to be used protease inhibitors. <BR/><BR/>In addition to the reverse-transcriptase inhibitors <BR/>(RTI-s) and protease inhibitors(PI-s), fusion <BR/>inhibitors like T 20 and T-1249, and integrase <BR/>inhibitors like S-1360 and L870,810 (7) may be soon <BR/>added to current HAART-x and Mega-HAART-x regimens. ( <BR/>The integrase enzyme is essential for HIV to integrate <BR/>its proviral DNA into the host cell chromosome. S-1360 <BR/>,e.g., , is a low molecular weight molecule, for oral <BR/>use, that inhibits the integrase enzyme in <BR/><BR/>HIV-1.) <BR/><BR/>An HIV-1 integrase- enzyme, bearing the <BR/>point-mutations (PM), that would be induced in HIV-1-s <BR/>genome by integrase inhibitors (II), may be introduced <BR/>as a fourth component of a multivalent-polyvalent <BR/>therapeutic vaccine (MPTV -x) against HIV-1, along <BR/>with : <BR/><BR/>1. whole killed/inactivated HIV-1 virus bearing the <BR/>point-mutations (PM) of each reverse-transcriptase <BR/><BR/>inhibitor, of each protease inhibitor <BR/>(Figure1/Table1), and of each integrase inhibitor , as <BR/>well as the <BR/><BR/>point-mutations (PM) with additional effect; <BR/><BR/>2. An HIV-1 reverse-transcriptase bearing the <BR/>point-mutations (PM) , RMS/RML -s that would be <BR/>induced by the reverse-transcriptase- inibitors <BR/>(RTI-s) to come; <BR/><BR/>3.An HIV-1 protease bearing the point-mutations(PM) <BR/>,RMS/RML, and even the whole RMP that would be induced <BR/>by the following, to come protease inhibitors. <BR/><BR/>Most importantly in this article , the <BR/>multivalent-polyvalent therapeutic vaccines (MPTV -x) <BR/><BR/>may be defined and consist minimally of 3 enzymes : <BR/><BR/>1. an HIV-1 reverse-transcriptase enzyme, <BR/><BR/>2. an HIV-1 protease enzyme and <BR/><BR/>3. an HIV-1 integrase enzyme , <BR/><BR/>each of the 3 enzymes bearing the point-mutations <BR/>(PM), resistance-mutations-loci (RML-x), <BR/>resistance-mutations-sites (RMS-x) or even the entire <BR/>resistance-mutations-patterns (RMP-x-s) of the <BR/>following , to come HAART-x regimen or Mega-HAART-x <BR/>regimen, respectively. <BR/><BR/>The rationale to use the 3 viral enzymes : <BR/>reverse-transcriptase, protease and integrase as <BR/>components of a multivalent-polyvalent therapeutic <BR/>vaccine (MPTV -x) against HIV-1 is based on the fact <BR/>that all currently approved antiretroviral drugs are <BR/>either reverse-transcriptase inhibitors, or protease <BR/>inhibitors or integrase inhibitors, and only these <BR/>drugs are able to generate HIV-1 strains bearing on <BR/>their genomes the point-mutations(PM), <BR/>resistance-mutations-loci (RML-x), <BR/>resistance-mutations-sites (RMS-x), <BR/>resistance-mutations-patterns (RMP-x-s) listed in <BR/>Table1/Figure1. <BR/><BR/><BR/>Discussion : <BR/><BR/><BR/>This entirely new approach to treat HIV-1 infections <BR/>with (MPTV -x, HAART-x)-couples and <BR/>(MPTV-x,Mega-HAART-x)-couples, can be adapted and used <BR/>to treat all possible <BR/><BR/>hard - to - treat infectious diseases for which at <BR/>least one effective drug has been developed, and may <BR/>lead to the eradication of many (otherwise resistant) <BR/>microbes, pathogens, viruses and fungi from the body <BR/>of infected persons. <BR/><BR/>Especially hard- to- treat infectious diseases, like <BR/>tuberculosis (TB) and malaria , may be eradicated and <BR/>drug-resistant pathogens eliminated when (MPTV -x, <BR/>drugs-x ) -couples are carefully and wisely selected <BR/>and used rationally. <BR/><BR/>This (MPTV -x, HAART-x)-couple-approach may also be <BR/>used in the treatment of cancer. <BR/><BR/>In cancer, the role of the MPTV -x can be taken by <BR/>killed cancer cells bearing on their DNA the <BR/>mutation-points(PM) of the anti-cancer drugs to be <BR/>used in chemotherapy. <BR/><BR/><BR/>Conclusions : <BR/><BR/>An entire industry of multivalent therapeutic vaccines <BR/>(MTV-x), polivalent therapeutic vaccines (PTV-x), and, <BR/>of course, multivalent-polyvalent therapeutic <BR/>vaccines (MPTV-x)-s against HIV-1 will probably emerge <BR/>after the publication of this article. These <BR/>multivalent-polyvalent therapeutic vaccines (MPTV-x)-s <BR/>will be used together with their corresponding <BR/>HAART-x and Mega-HAART-x regimens in (MPTV <BR/>-x,HAART-x)-couples and (MPTV <BR/>-x,Mega-HAART-x)-couples, respectively, <BR/><BR/>Using an "ad conventium" terminology, a polivalent <BR/>therapeutic vaccine (PTV-x) should have the capacity <BR/>to prevent the emergence of the primary <BR/>resistance-mutations-pattern (RMP) for at least one <BR/>antiretroviral drug and up to a HAART or Mega-HAART <BR/>-regimen. <BR/><BR/>A multivalent therapeutic vaccine (MTV-x) should have <BR/>the capacity to prevent the emergence of at least 2 <BR/>successive resistance-mutations-patterns (RMP-s) for <BR/>at least one drug, and up to a HAART or Mega-HAART <BR/>-regimen, whereas a multivalent-polyvalent therapeutic <BR/>vaccine (MPTV -x) should be able to prevent the <BR/>emergence of primary , secondary and even multiple <BR/>successive HIV-1 resistance-mutations-patterns (RMP-s) <BR/>for a HAART or Mega-HAART - regimen. <BR/><BR/>Ideally, a multivalent-polyvalent therapeutic vaccine <BR/>(MPTV -x) should be able to prevent the emergence of a <BR/>very high or even unlimited number of successive <BR/>resistance-mutations-patterns (RMP-s) and/or it should <BR/>be able eradicate HIV-1 by acting sinergetically with <BR/>their corresponding HAART-x or Mega-HAART-x regimens, <BR/>within these (MPTV -x, HAART-x)-couples, or (MPTV-x, <BR/>Mega-HAART-x)-couples, respectively. <BR/><BR/>ADVENTRX Pharmaceuticals intends to begin human <BR/>trials for EradicAide (8) , an HIV therapeutic <BR/>vaccine, composed of six synthetic peptides, which <BR/>stimulate a killer <BR/><BR/>T-cell response to clear HIV-infected cells. A unique <BR/>feature of this treatment is that it is designed to <BR/>not elicit an antibody response. It is <BR/>antibody-negative. Such a therapeutic vaccine may also <BR/>be added to (MPTV -x, HAART-x)-couples and <BR/>(MPTV-x,Mega-HAART-x)-couples , as an adjuvant <BR/>therapeutic vaccine(ATV) to (MPTV -x, HAART-x)-couples <BR/>and (MPTV-x,Mega-HAART-x)-couples, respectively. <BR/><BR/>Also, the Remune vaccine of the The Immune Response <BR/>Corporation, Inc. (9) may be considered ( and used ) <BR/>as an adjuvant therapeutic vaccine(ATV) to (MPTV -x, <BR/>HAART-x)-couples and to (MPTV-x,Mega-HAART-x)-couples <BR/>. Studies have shown that inactivated, gp120-depleted <BR/>whole virus immunogen (Remune) boosts immune responses <BR/>to HIV-1. <BR/><BR/>Both therapeutic vaccines (TV) mentioned above , <BR/>(EradicAide and Remune), as well as others that are in <BR/>advanced development and clinical trials, may <BR/>eventually be adjusted, modified and adapted to be <BR/>used in one formulation prior to HAART-x (or <BR/>Mega-Haart-x) onset, and in a different formulation <BR/>during HAART-x or Mega-Haart-x treatment. In other <BR/>words, they may be used both in (MPTV -x, <BR/>HAART-x)-couples and (MPTV-x,Mega-HAART-x)-couples , <BR/>and/or as adjuvant therapeutic vaccines(ATV). <BR/><BR/>Affymetrix (10) , a leading US company in DNA-chip <BR/>technology has developed GeneChip oligonucleotide <BR/>probe arrays that are manufactured using a high <BR/>resolution photolitographic fabrication process <BR/>adapted from the semiconductor industry, for HIV-1 <BR/>mutations determinations. <BR/><BR/>The Authors of this article believe that an entire <BR/>industry of standardized multivalent-polyvalent <BR/>therapeutic vaccines (SMPTV-x)-s will emerge, to act <BR/>complementary and sinergetically with HAART-x and/or <BR/>Mega-HAART-x - regimens in order to eradicate HIV-1. <BR/><BR/>The Authors of this article are very interested to <BR/>collaborate with pharmaceutical companies interested <BR/>to produce (SMPTV -x)-s for use in (MPTV -x, HAART-x) <BR/>-couples and (MPTV -x , Mega-HAART-x)-couples aimed <BR/>and designed to eradicate HIV-1, cancer (11) , and <BR/>other infectious diseases. <BR/><BR/>References: <BR/><BR/>1. Hahn B.H. , Robertson D.L. , McCutchan F.E. , Sharp <BR/>P.M. , Recombination and diversity of HIV: <BR/>implications for vaccine development. Neuvieme <BR/>Colloque Des Cent Gardes , <BR/><BR/>1994, 87-94 ; <BR/><BR/>2. Robertson D.L. , Sharp P.M. , McCutchan F.E. , Hahn <BR/>B.H. , Recombination in HIV-1, Nature 1995 : 374 <BR/>:124-126; <BR/><BR/>3. Robertson D.L. , Hahn B.H. , Sharp P.M. , <BR/>Recombination in Aids viruses, J.Mol.Evolution , 1995, <BR/>40, 249-259; <BR/><BR/>4. Sharp P.M., Robertson D.L., Hahn B.H. , Cross - <BR/>species transmission and recombination of ' AIDS ' <BR/>viruses. , Phil. Trans. R. Soc., London B , 1995, 349 <BR/>: 41-47; <BR/><BR/>5. M. L. Kalish et al, Recombinant Viruses and Early <BR/>Global HIV-1 Epidemic, Emerging Infectious Diseases, <BR/>Vol.10, No.7, July 2004; <BR/><BR/>6. I.S. Secasan, D.I. Pop , Fighting HIV with HIV, <BR/>Medical Hypotheses,1998 Jan;50(1):39-42 <BR/>Churchill-Livingstone, ISSN 0306-9877; <BR/><BR/>7. Young, S.D., et al. L870,810: Discovery of a potent <BR/>HIV integrase inhibitor with potential clinical <BR/>utility, Presented at The XIV International AIDS, <BR/>Conference, Barcelona, Spain. <BR/><BR/>8. <BR/>http://www.adventrx.com/products/antiv_eradicaide.htm <BR/><BR/>9. http://www.imnr.com : The Immune Response <BR/>Corporation, Inc. web-site <BR/><BR/>10. http://www.affymetrix.com/index.affx <BR/><BR/>11. Iosif Secasan, Dan I. Pop, Ciprian C. Secasan: <BR/>Potentially New And Innovative Treatments For <BR/>Superficial, Muscle-Invasive, And Metastatic <BR/>Transitional Cell Carcinoma (TCC) Of The Bladder. The <BR/>Internet Journal of Oncology. 2005. Volume 2 Number 2.Dan I. Pophttps://www.blogger.com/profile/15179854691127395735noreply@blogger.comtag:blogger.com,1999:blog-10750568.post-1135384189861516502005-12-23T16:29:00.000-08:002005-12-23T16:29:00.000-08:00good insight! additional thoughts:http://www.blogl...good insight! additional thoughts:<BR/><BR/>http://www.bloglines.com/blog/ski?id=61Jeff SKI Kinseyhttps://www.blogger.com/profile/02805285208294459012noreply@blogger.comtag:blogger.com,1999:blog-10750568.post-1129129228482638302005-10-12T08:00:00.000-07:002005-10-12T08:00:00.000-07:00Thanks for the article.BTW have you looked at Alph...Thanks for the article.<BR/><BR/>BTW have you looked at Alpha Five - I hear they have version 7 coming very soon with a lot of expanded features for web database publishing?Anonymousnoreply@blogger.com