Our son Harvey parry who is now 3, caught meningitis meningococcal septicemia at the age 15 months, after spending 4 months in intensive care he had to have both his legs and 3 fingers on his right hand amputated.

The NHS supplied our son with 8 pairs of prosthetic legs, each one was uncomfortable for Harvey to wear. See videos of Harvey's media campaign at harveyparry-appealfund.com/media/Media-compaign.htm.

The consultant who amputated Harvey’s legs advised us that if we did not want Harvey to lose even more of his remaining legs, we need a high quality pair of prosthetic legs, not the NHS legs which were causing his legs damage.

We had no choice but to go private, we found a company in New York Long Island www.astepaheadonline.com.

Since going private our Primary Care Trust Enfield have withdrawn all support services i.e. physiotherapy, occupational therapy etc. They have told us that they will not fund legs from the USA even if they are better than the ones supplied by the NHS. I have asked our Primary Care Trust Enfield on many occasions for a costing of Harvey’s prosthetic legs, I had to use the Freedom Of Information Act to force them to reveal the cost.  The total cost provided by Enfield PCT of Harvey parry's prosthetic legs/maintenance to date is £26,942.14. http://www.whatdotheyknow.com/request/costing_request_for_harvey_parry#incoming-19232

Even after this expense Harvey still does not have a working/comfortable pair of legs from the NHS.  The cost spent by Enfield PCT would of paid for 1 pair of American legs from StepAhead Prosthetics.

Why can't the government fund us for Harvey's American Legs, they work, are very practical, he wears them all day with no discomfort.  Funding Harvey’s legs in the USA would set a president which would open the flood gates for parents dissatisfied with NHS prosthetic legs.

Harvey will receive his second pair of legs from StepAhead Prosthetics in May 2009, Thank you to all the people who have worked hard to make this happen.

We badly need your support in order to give Harvey a better life with comfortable prosthetics, physiotherapy, occupational therapy, rehabilitation aids etc.

Since Harvey has had his new prosthetics from New York his confidence and personality has blossomed, he can now wear prosthetic legs all day with no pain or discomfort.

You can donate at harveyparry-appealfund.com via PayPal on the left under the menu. If you have any fundraising ideas, you can obtain sponsor forms from harveyparry-appealfund.com/pages/fundraising.htm.

Harvey Parry Appeal Fund Line 0208 482 1603
Email: Harvey@harveyparry-appealfund.com

Website optimization starts with content.  If the content is irrelevant, the website will not last long in the rankings, no matter how many keywords are included.  The best way to get relevant content is to get an expert to write the content.  General content may be more friendly to beginners, but in the search optimization arena, content is what is going to keep readers coming back and webmasters linking to the page.  Many search engines use link counters to rank sites.  If enough people like and value the site, they will link to it from their own site as an example of expert help for visitors seeking more detailed information than they can provide, or are willing to provide.  Often, general-interest sites will link to expert sites, thereby also driving their own traffic up as the initial portal to those expert sites and improving their own rankings in the optimization listings.  The quality of the sites linked is also a major factor in the rankings, as quality sites such as Microsoft and Google are going to be more effective "heavy hitters" than a link to Bob's House of Website Optimizing. 

When the content is being created, keywords are the "anchors" that search engines hook onto, but just filling your content with keywords risks being dismissed as a spam site, as many spammers merely fill a page with keywords, hoping to hook anyone searching for anything.  These kind of pages are usually removed quickly, but they exist nonetheless.  Specific keywords are the key--instead of Search Engine, use Search Engine Optimization for Google, or combinations of the key words or phrases.  Optimization for Search Engines in one area, then Optimizing for higher Search Engine rankings in another increases the chances of an engine ranking your website content a little higher than it may have otherwise.

The guidelines for content also go for Meta tags such as the title.  Title is very important, as it is one of the bigger spots for an engine to catch, as well as the hook that draws a surfer in once the rankings have been displayed.  A recommended length is 50-80 characters (including spaces), with keywords located near the beginning in case the window is resized on the screen.  A good example would be "Search Engine Optimization tips and tricks for Google", instead of "How to do important SEO for websites." 

Search Engine Optimization--what to avoid:  Don't use huge strings of keywords without relevant content--you may be labeled as a spammer and blacklisted off the engine(s) you're trying to climb.  Stay away from pop-ups, excessive load times (by keeping the page clean and using fast hosting servers), and lots of flash animation, as this takes time to load and also detracts from the readability of the site.

More specific information can be found by typing "Search Engine Optimization" into any major search engine like Google or Yahoo and following the links.  Good luck!

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William King is the director of Wholesale Pages: http://www.wholesalepages.co.uk , Aid and Trade: http://www.aidandtrade.com , Daily Trader: http://www.dailytrader.com and Pakistan Property Portal http://www.zameen.com/ . He has 18 years of experience in the marketing and trading industries and has been helping retailers, entrepreneurs and startups with their product sourcing, promotion, marketing and supply chain requirements.

Our son Harvey parry who is now 3, caught meningitis meningococcal septicemia at the age 15 months, after spending 4 months in intensive care he had to have both his legs and 3 fingers on his right hand amputated.

The NHS supplied our son with 8 pairs of prosthetic legs, each one was uncomfortable for Harvey to wear. See videos of Harvey's media campaign at harveyparry-appealfund.com/media/Media-compaign.htm.

The consultant who amputated Harvey’s legs advised us that if we did not want Harvey to lose even more of his remaining legs, we need a high quality pair of prosthetic legs, not the NHS legs which were causing his legs damage.

We had no choice but to go private, we found a company in New York Long Island www.astepaheadonline.com.

We raised £40,000 which we used to purchase his 1 st pair of prosthetics legs from A Step Head prosthetics in June. See the video dairy & media coverage of this at harveyparry-appealfund.com/pages/new%20york/New-York-Trip-Harveys-New-Legs.htm. Harvey spent about 8 weeks in New York. The training was fantastic and put our NHS to shame.

In October Harvey attended the Mobility clinic at A Step Ahead to have physiotherapy, and maintenance on the legs we bought in June 2008. See the videos of Harvey at harveyparry-appealfund.com/pages/new%20york/New-York-Trip-2.htm

Harvey has had these legs for 6 months now. The sockets are starting to get tight & need replacing. We have raised £9,538 so far but we need to raise £30,000 to replace the pair he has.

We are asking you if you can contribute to Harvey’s Appeal fund by sponsorship or donation or even by using your status to bring awareness of our plight.

Since going private our Primary Care Trust Enfield have withdrawn all support services i.e. physiotherapy, occupational therapy etc. They have told us that they will not fund legs from the USA even if they are better or cheaper than the ones supplied by the NHS.

We badly need your support in order to give Harvey a better life with comfortable prosthetics, physiotherapy, occupational therapy, rehabilitation aids etc.

Since Harvey has had his new prosthetics from New York his confidence and personality has blossomed, he can now wear prosthetic legs all day with no pain or discomfort.

You can donate at harveyparry-appealfund.com via PayPal on the left under the menu. If you have any fundraising ideas, you can obtain sponsor forms from harveyparry-appealfund.com/pages/fundraising.htm.

Harvey Parry Appeal Fund Line 0208 482 1603
Email: Harvey@harveyparry-appealfund.com

I would like to introduce you to a revolutionary new way to 'smoke' whilst remaining healthy and stay within the law. These cigarettes are a healthy alternative to traditional cigarettes, same cigarette taste, still with nicotine but with none of the 4000 toxins usually found in a cigarette.

Electronic cigarettes have been available for approximately 3 years now but have always been a little cumbersome, well with the fourth generation of e-cigarettes that hurdle has finally been overcome.

For those of you who are new to electronic cigarettes let us explain exactly what they are: An e-cigarette consists of a battery an atomiser and a cartridge chamber that holds a small amount of nicotine and water.

When you draw on an electronic cigarette a smokers cravings are satisfied due to the taste of tobacco, the smoke like vapour emitted, the actual holding of a cigarette, the glow at the end and an intake of nicotine so it can be used as an alternative to a cigarette.

The process of drawing on the Smart Smoker ™ operates a micro switch which heats up an element within the atomiser to produce a very realistic looking 'smoke' which is in fact just a completely harmless vapour with no harmful chemicals, and vaporises into the air within a few seconds, the pleasant odour also disappears with this vapour so you will have no smell on your clothes or indeed in your car or home!

The Smart Smoker ™ can be used legally anywhere as there is no passive smoke, no health concerns and of course nothing flammable.

The renewable cartridges are available in 4 strengths, Normal, Medium, Low and no nicotine and are normally despatched within 48 hours of ordering, usually same day, a cartridge will last approximately the same time as 15 normal cigarettes so you will also save aprox 80% of your costs as a bonus.

Overview of Benefits

• 80% Cheaper than real cigarettes
• No carcinogenic/cancerous toxins
• A healthier alternative
• Proven to work with smokers
• Legal to smoke in public areas
• No lighting, no burning, no tar and no real smoke. No cancerous substances (during the burning of tobacco there are approx. 40 cancerous substances), no ashtrays, no cigarette butts, no horrible smells and no air pollution (no CO2).
• No tobacco
• Can lower the strength of nicotine over time in your electronic cigarette to ease your nicotine addiction.

A revolutionary electronic cigarette designed as a healthier smoking alternative to traditional tobacco cigarettes. Using advanced technology, the Fifty-One™ allows one the freedom to smoke virtually anywhere, without the flame, ash, tar, or carbon monoxide found in traditional tobacco cigarettes.

As the Fifty-One™ is completely free of tobacco, this product likewise does not contain the thousands of harmful carcinogens typically found in tobacco products. With no offensive second-hand smoke, the Fifty-One™ offers a safer, healthier environment to both you and the non-smoking community.

Simply put, there is no longer a need for anyone to breathe the unwanted, dangerous second-hand smoke produced
by traditional tobacco cigarettes.The Fifty-One™ consists of a two-part unit, including a lithium ion battery and a nicotine cartridge, and it uses high- frequency patented technology to atomize nicotine and produce only a smoke-like "vapor".

Cartridges are offered at nicotine levels ranging from 8mg to 0mg, and in a variety of tasteful flavors for a more enjoyable smoking experience.The Fifty-One™ offers all of the nicotine you crave, without the over 4,000 toxins found in traditional tobacco
cigarettes.

With countless advantages over traditional cigarettes, this premier electronic smoking device offers both the smoking and non-smoking community a new approach for effectively dealing with the problems associated with harmful second-hand smoking which allows you to smoke virtually anywhere.

Buy this revolutionary electronic cigarette Here

RNA interference (RNAi) is the process of mRNA degradation that is induced by double-stranded RNA in a sequence-specific manner. RNAi has been observed in all eukaryotes, from yeast to mammals. The RNAi pathway is thought to be an ancient mechanism for protecting the host and its genome against viruses and rogue genetic elements that use double-stranded RNA (dsRNA) in their life cycles. They have also been shown to play a role not only in mRNA and dsRNA stability/degradation, but also in regulation of translation, transcription, chromatin structure, and genome integrity. In plants and animals, RNA silencing has been adapted to play a critical role in regulation of cell growth and differentiation using a class of small RNAs. In the RNA interference process, the dsRNAs get processed into 20-25 nucleotide (nt) small RNAs by an RNase III-like enzyme called Dicer. Then, the small RNAs assemble into endoribonuclease-containing complexes known as RNA-induced silencing complexes (RISCs), unwinding in the process. The small RNA strands subsequently guide the RISCs to complementary RNA molecules, where they cleave and destroy the cognate RNA (effecter step). Cleavage of cognate RNA takes place near the middle of the region bound by the siRNA strand. The small RNAs that provide target specificity to the silencing machinery includes short interfering RNAs (siRNAs), repeat-associated siRNAs (rasiRNAs), and microRNAs (miRNAs) and is distinguished by their origin. siRNAs are processed from dsRNA precursors made up of two distinct strands of perfectly base-paired RNA, while miRNAs originate from a single, long transcript that forms imperfectly base-paired hairpin structures. siRNAs were originally identified as intermediates in the RNAi pathway after induction by exogenous dsRNA; however, endogenous sources of siRNAs have now been recognized. The endogenous siRNAs are derived from repetitive sequences within the genome, and are termed repeat-associated siRNAs, or rasiRNAs. miRNAs were discovered through their critical roles in development and cellular regulation, and represent a large class of evolutionarily conserved RNAs. miRNAs have always been recognized as being of endogenous origin. RNA interference has emerged as a natural mechanism for silencing gene expression over the past decade. This ancient cellular antiviral response can be harnessed to allow specific inhibition of the function of any chosen target genes, including those involved in causing diseases such as cancer, AIDS, and hepatitis. It is already proving to be an invaluable research tool, allowing much more rapid characterization of the function of known genes. More importantly, the technology considerably bolsters functional genomics to aid in the identification of novel genes involved in disease processes. Last but not the least the technology can be harnessed as a novel therapeutic agent and is suitable for combating viral diseases, cancers and inflammatory diseases.

Imgenex (San Diego) recently launched the pSuppressorAdeno construction kit for adenovirus mediated gene knockdown. The kit provides the ability to infect a broad range of cell types, including many primary cell lines as well as dividing and nondividing cells, according to a company official. The kit also offers the flexibility to validate sequences using the nonviral expression plasmid prior to construction of adenoviruses, notes Sujay K. Singh, Ph.D., president and CEO of Imgenex, which markets plasmid-based RNA interference (RNAi) products. “One of the greatest advantages is the ability of recombinant adenovirus vectors to reduce gene expression both in vitro and in vivo,” he adds. RNAi, initially considered a bizarre attribute of petunias and later a gene-silencing mechanism in worms, is creating a stir as one of the hottest new technologies in molecular biology. It is revolutionizing the field of functional genomics.

IMGENEX India Pvt Ltd. the only biotech company in Orissa and one of its kinds in Eastern India. IMGENEX India started in Oct as an outsourcing branch of  IMGENEX Corporation San Diego, USA.  Find out more information about   RNA interference.

All the cellular processes in living cells such as growth, development, morphogenesis and cellular differentiation are a product of gene expression programs involving complicated transcriptional regulation of several genes. This process of transcriptional regulation is tightly controlled and coordinated by proteins called transcriptional regulators. These transcriptional regulators and factors are DNA-binding proteins that bind to the promoter or enhancer sequences on the DNA and facilitate either transcriptional repression or activation.

There are three principal types of transcription factors. These include basal transcription factors, upstream transcription factors and inducible transcription factors. The basic structure of every transcriptional factor mainly contains a DNA-binding domain and an activator domain. DNA-binding motifs found in transcription factors include zinc-finger, helix-loop-helix, helix-turn-helix, leucine zipper and high-mobility groups, based on which transcription factors are classified. The activator domain of these transcription factors interacts with components of transcription machinery such as RNA polymerases and associated transcription regulators.

Regulation of transcriptional factors is a complex mechanism that ensures exact spatio-temporal expression of genes. In response to a specific cellular stimulus, these trans-regulatory factors are activated in a sequential manner. Upon activation, these factors recruit transcriptional co-regulators such as histones that function as co-activators or co- repressors and aid in modifying chromatin structure. Altered activation of these regulators is often associated with various pathologies such as chronic disorders and malignancies. Recent studies are concentrating on developing improved disease treatment strategies through identification of different transcription factor-binding patterns and blocking them.

There are several families of trans-regulatory factors that control critical cellular signaling cascades involved in cell proliferation, survival, lineage development and cellular differentiation. These include Rel/NF-kB family, AP-1 family, STAT family of transcription factors, homeodomain proteins, DNA-binding proteins, POU transcription factors, nuclear hormone receptor family, p53 family and E2F family.

IMGENEX India Pvt Ltd. the only biotech company in Orissa and one of its kinds in Eastern India. IMGENEX India started in Oct as an outsourcing branch of IMGENEX Corporation, San Diego, USA.Find out more information about   Transcriptional Factors.

Early development and differentiation of nascent T cells that migrate from bone marrow to become mature, naïve T cells, which are capable of responding to antigen takes place inside the thymus. Around 10¹⁰ TCR (T cell receptor) variations are generated in developing T lymphocyte clones through a random process of somatic cell gene reorganization. During this process, often T-cells recognizing self-antigens are generated. Due to the ability of these self-reactive T-cells to elicit an autoimmune attack, they are permanently removed by the thymus through negative selection and clonal deletion. But, some of them manage to escape the thymic defenses and harbor themselves in the peripheral lymphoid organs. In periphery, T lymphocytes undergo further differentiation into effectors of various immune functions.

One of many immunotolerance mechanisms that immune system has developed to distinguish between self and non-self antigens is regulatory T cells or Tregs. These cells are recently characterized specialized T-cell subsets that actively suppress a variety of immune responses. Researchers have broadly classified Tregs into natural and adaptive Tregs. Natural Tregs are CD4⁺CD25⁺ T-cells that originate in the thymus and play a significant role in immune homeostasis and protection against autoimmunity. Adaptive Tregs are non-regulatory CD4⁺ T-cells that have up-regulated CD25 expression during pathological and inflammatory conditions such as cancers and infections.

Although the principal immunosuppressive mechanism of Tregs remains elusive, several in vivo experimental models have indicated that Tregs secrete large amounts of immunosuppressants including IL-9, IL-10 and TGF-β upon activation. These lymphokines are capable of inhibiting activation of Th1, Th2 cells and CTLs required for cell-mediated immunity, inflammation and antibody production. Certain recent experimental data and results even indicate that IL-2-IL-2R signaling is vital for development, maintenance, survival, expansion and suppressive activity of Tregs. Increased expression of certain other characteristic markers including CTLA-4, glucocorticoid-inducible tumor necrosis factor receptor (GITR) and OX40 has been identified on Tregs whose function inside these cells is still not clear. The TCRs displayed on Tregs are capable of recognizing and interacting with any peptide-MHC class II ligand having certain range of avidity. But, the contribution of TCR signaling and role of TCR-ligand interactions towards regulatory T-cell development needs to be determined.

Several elegant experiment using transgenic mice and retrovirus mediate over expression studies, researchers have identified FoxP3, a transcription factor, to be a specific molecular marker essential for the development and function of Tregs. The primary evidence regarding the involvement of FoxP3 in the development of Tregs was provided by the experiments of Sakaguchi et al, (ref ?) in patients suffering from IPEX, a rare and fatal human autoimmune disorder. In these patients, mutated FoxP3 gene causes improper development of Tregs resulting in hyperactivation of T-cells reactive to self-antigens. Recently, experiments have clearly shown that retroviral mediated introduction of FoxP3 into conventional CD4+ T-cells converts them into regulatory T-cells.

The emergence of regulatory T-cells and role of FoxP3 as a critical player in the negative control of a of various normal and pathological immune responses holds great promise for the development of novel therapies useful for the treatment of autoimmune diseases in humans. However, there are several questions that remain to be answered including the basic biology of the Tregs, various ligands responsible for thymic selection of these cells, the exact function of FoxP3 in relation with various markers present on Tregs and most importantly, the mechanisms by which Tregs exert their suppressive effects. A better understanding of manipulating FoxP3 and Tregs would enable us to harness the tremendous therapeutic potential in various clinical situations including Type I diabetes, Multiple sclerosis, GVHD, rheumatoid arthritis, allergy, and cancers.

IMGENEX India Pvt Ltd. the only biotech company in Orissa and one of its kinds in Eastern India. IMGENEX India started in Oct as an outsourcing branch of IMGENEX Corporation, San Diego, USA.  Find out more information about Regulator T-cells(Treg).

Immunology is a broad branch of biomedical science that covers the study of all aspects of the immune system in all organisms. The immune system is the body's defense against infectious organisms and other invaders. Through a series of steps called the immune response, the immune system attacks organisms and substances that invade our systems and cause disease. The immune system is made up of a network of cells, tissues, and organs that work together to protect the body. The immune system is the body’s natural defence in combating organisms. The immune system usually have two lines of defence: the innate immune system representing a non-specific (no memory) response to antigen (substance to which the body regards as foreign or potentially harmful) and the adaptive immune system, which displays a high degree of memory and specificity. The innate system represents the first line of defence to an intruding pathogen and includes various cells like the natural killer (NK) cells, mast cells dendritic cells and phagocytes. Besides there are molecules like complement, acute phase proteins (APP) and interferons (IFNs) which work in concert with the cells of the innate immune system and which foster close functional links with their adaptive counterpart. The adaptive immune system is further divided into humoral and cellular components.  Cell-mediated immunity, also known as delayed-type hypersensitivity (DTH) or Type IV Hypersensitivity, is an immune response that does not involve antibodies but rather involves the activation of macrophages, natural killer cells (NK), antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen. The humoral immune response (HIR) is the aspect of immunity that is mediated by secreted antibodies, produced in the cells of the B lymphocyte lineage (B cell). When activated by foreign antigen, B cells undergo proliferation and mature into antibody secreting plasma cells which posses the ability to secrete soluble proteins (antibodies). Antibodies which are classified into five different types (known as isotypes), namely IgM, IgG, IgA, IgE and IgD, have two roles to play - the first is to bind antigen and the second is to interact with host tissues and effector systems in order to ensure removal of the antigen. Thus the immune system generally is protective, however the same immunologic mechanisms that defend the host at times may result in severe damage to tissues and, occasionally, may cause death.

Conceptualizing the natural antigen- antibody development & interaction, Imgenex Corp. develops and commercializes novel reagents for the scientific study of human biology and disease and for the production of new diagnostic assays and potential therapies of such diseases. These novel reagents include antibodies, gene and protein expression systems, and arrays of various cells and tissues for use in studies of functional genomics. Areas of biological interest at IMGENEX include cancer, apoptosis (programmed cell death), molecular signaling pathways, cellular aging, and metabolic and infectious diseases.

IMGENEX India Pvt Ltd. the only biotech company in Orissa and one of its kinds in Eastern India. IMGENEX India started in Oct as an outsourcing branch of IMGENEX Corporation, San Diego, USA. Find out more information about immunology.