Gene Therapy

The best way of treating a cancer would be to find a way of genetically modifying the tumour cells, correcting the genetic defect. This technique is known as ‘gene therapy’, It is regarded as a potential revolution in medicine because gene therapy is aimed at treating or eliminating causes of disease, whereas most current drugs treat the symptoms.

Gene therapy for cancer accounts for the majority of gene therapy clinical trials. Targets for

this include replacement of tumor suppressor genes, ‘‘suicide genes’’ to activate prodrugs, antiangiogenic gene therapy, cytokine-based gene transfer, and delivery of drug resistance genes to hematopoietic stem cells to protect them from the bone marrow toxicity of chemotherapeutic agents.

Suicide gene therapy approaches include transfection of tumor cells with herpes simplex

virus-thymidine kinase (HSV-TK) to activate the prodrug ganciclovir and cytosine deaminase

to convert the nontoxic compound 5-fluorocytosine into cytotoxic 5-fluorouracil .

Suicide gene clinical trials have been carried out in prostate cancer, mesothelioma, and glioblastoma. Cytokine gene therapy approaches have included gene transfer via tumor-homing lymphocytes bearing genes encoding interleukins (IL-1B, IL-2, IL-4, IL- 12), GM-CSF, and interferon-g (IFN-g). Clinical trials include IL-12 delivered by a vaccinia virus vector for mesothelioma and GM-CSF and IFN-g delivered in retroviral vectors for melanoma. Some clinical responses have been observed in these trials with small numbers of patients.

The tumor suppressor gene p53 is the most commonly mutated gene in human cancers.

Hence, it is a good target for gene replacement  therapy. Re-expression of p53 in human colon cancer cell lines bearing a mutated gene inhibits tumor cell proliferation. In a murine model of p53-mutated colon cancer, injection of an adenoviral vector encoding the WT p53 gene into tumors resulted in tumor regression and enhanced survival . Clinical trials with p53 gene replacement have been initiated for a number of cancers including colon and

head and neck cancers. In general, the procedures were well tolerated. The main side effects were fever and transient liver enzyme abnormalities. One key question for this and other gene therapy approaches to cancer is how many cells in a tumor need to be transfected to get a therapeutic effect? There is some evidence for ‘‘bystander’’

effects from p53 transfection, probably due to an antiangogenesis effect.620 Other potential tumor suppressor gene targets for which there is at least preclinical demonstration of efficacy are PTEN, E-cadherin, C-CAM, BRCA-1, and pHyde.

TUMOUR SUPPRESSOR GENES

Tumour suppressor genes prevent excessive growth of a cell; the most well known ones are p53 and the retinoblastoma (Rb) gene.

Retinoblastoma Gene

Retinoblastoma gene is involved in the G1 checkpoint in the following way. It binds to a family of transcription factors known as the E2F family, thereby repressing their transcription of E2F-responsive genes, such as thymidine kinase (TK), needed for DNA replication, and cyclin E and A, needed for cell cycle progression. Rb is activated when cyclin D forms a complex with CDK4/6 (cyclin D/CDK4/6, hence making it active) this in turn phosphorylates Rb, which allows E2F to be released

p53

The p53 protein is essential for protecting us against cancer. More than half of human cancers have p53 mutations and therefore no functioning p53. p53 works by sensing DNA damage and halting the cell cycle (Figure 4.2). This is essential, because if DNA is damaged but still replicated in S phase, it could eventually manifest in the form of a protein mutation. By halting the cell cycle at the G1 checkpoint, this can be prevented. So how does this process work? Again, it comes back to the involvement of CDKs. First, in response to a variety of stress signals,

for example DNA damage, p53 switches from an inactive state to an active state. It then triggers transcription of the gene for p21, which is a CDK inhibitor. Because active CDKs are needed to progress through the cell cycle, an inactive CDK will cause the cycle to halt. The p53 protein is also involved at the G2 checkpoint in cases, for example, where DNA has been synthesized incorrectly. At this checkpoint, p53 binds to E2F (see Section ‘Retinoblastoma gene’) and prevents it from triggering transcription of proto-oncogenes, for example c-myc and c-fos, which are required for mitosis Proto-oncogenes are important promoters of normal cell growth and division; however, if they become mutated they are known as oncogenes and can have a detrimental effect. A single oncogene cannot cause cancer by itself but it can cause the cell cycle to lose its inhibitory controls, thereby increasing the rate of mitosis. When a cell loses control over mitosis, it can be the beginning of the pathway leading to the development of cancer

cPanel History

cPanel was originally designed as the control panel for Speed Hosting,  a now-defunct web hosting company. The original author of cPanel, J. Nick Koston, had a stake in Speed Hosting. Web King quickly began using cPanel after their merger with Speed Hosting. After Speed Hosting and Webking merged, the new company moved their servers to Virtual Development Inc. (VDI), a now-defunct hosting facility. Following an agreement between J. Nick Koston and VDI, cPanel was only available to customers hosted directly at VDI. At the time there was little competition in the control panel market with the main choices being VDI and Alabanza. cPanel 3 was released in 1999; its main features over cPanel 2 were an automatic upgrade and the Web Host Manager.

cPanel 3 tended to be buggy and did not have a good user interface. The interface improved when Carlos Rego of WizardsHosting made what became the default theme of cPanel. Eventually due to internal problems between VDI and J. Nick Koston, cPanel split into two separate programs called cPanel and WebPanel. WebPanel was the version run by VDI. Without the lead programmer, VDI was not able to continue any work on cPanel and eventually stopped supporting it completely. J. Nick Koston kept working on cPanel while also working at BurstNET. Eventually Nick left BurstNET on good terms to focus fully on cPanel. cPanel has been updated and improved over the years. It is now a stable and reliable control panel......

Basics of cPanel Web hosting

20.04.2011 | Author: dwssruthi | Posted in Internet

CPanel is by far the most preferred web hosting control panel in the market today. It is in no doubt very popular among web administrators, end users and resellers. Its simplicity and functionality is well known to web masters. It makes standard activities like uploading, processing emails and data gathering to be accomplished fast and efficiently.

CPanel web hosting is the best in the industry; it allows you to be fully in control of your website. Regular updates are done automatically, they actually require very minimal or no supervision at all. CPanel also forwards incoming mails automatically into specified accounts. These accounts are accessible from the web administrator’s email. This fact makes cPanel web hosting control panel user friendly to most website administrators.

Fitting an Internet site may sometimes be troublesome involving a lot of valuable information, reports and at times junk. A significant fact about cPanel web hosting is that it makes management of this information within your website simple.

What you need to understand is cPanel enables you track down what information your website gives out. Updates are very easy to install without affecting the general output of the website. This is necessitated by cPanel’s ability to control these operations on auto-pilot. You may set your website as “Under Construction” to maximize security. In this, you do not expressly need a web administrator since these tasks can be accomplished in just a few hours.

What basically slows down websites is numerous of unresolved data files or some of which do not exist at all. Web hosting with cPanel enables you to make traction and delete them. This means, your site will experience more traffic due to its efficiency in satisfying the customer’s interests as well as responses.

The cPanel web hosting program also allows you to fully monitor your website. You can view the number of visitations made. The traffic of clients to your site is a leading factor to whether or not you should make any changes...

Reseller web hosting

Reseller hosting is a form of web hosting wherein the account owner has the ability to use his/her allotted hard drive space and bandwidth to host websites on behalf of third parties. The reseller purchases the host's services wholesale and then sells them to customers, possibly for a profit. A certain portion of hard drive and bandwidth is allocated to the reseller account. The reseller may rent a dedicated server from a hosting company, or resell shared hosting services. In the latter case, the reseller is simply given the permission to sell a certain amount of disk space and bandwidth to his own customers without renting a server from a web hosting company he signed for a reseller account with.

The typical web hosting reseller might be a web design firm, web developer or systems integrator who offers web hosting as an add-on service. Reseller hosting is also an inexpensive way for web hosting entrepreneurs to start a company. Most reseller hosting plans allow resellers to create their own service plans and choose their own pricing structure. In many cases, resellers are able to establish their own branding via customized control panels and name servers.

Reseller hosting does not require extensive knowledge of the technical aspects of web hosting. Usually, the data center operator is responsible for maintaining network infrastructure and hardware, and the dedicated server owner configures, secures, and updates the server. A reseller is responsible for interfacing with his/her own customer base, but any hardware, software and connectivity problems are typically forwarded to the server provider from whom the reseller plan was purchased. Being a profitable reseller firm usually involves extensive advertising to get customers. While the monthly fees with major hosts are only a few dollars a month, it's a low margin business, and resellers must devote large advertising budgets to compete with established competitors. However, web hosting is one of the biggest online businesses, because every website needs hosting.

Web host Reselling Model

 Resellers face several significant challenges, and not least of these is technical support. While resellers can reasonably expect that they will be given some support by their parent hosting companies, in almost all cases they are responsible for directly fielding the complaints of their own customers.

In other words, if a reseller's client calls to complain about downtime, it is the reseller who must address the matter - even if "addressing" it just means complaining to the original host. This is a source of frequent complaint among resellers, because they feel that while they cannot directly remedy many of the most common hosting problems (bandwidth, space limitations, downtime, etc.), they are the ones who have to deal with end users whose sites are down, or are loading too slowly.

Ideally, however, resellers should not operate according to the same business model as hosting companies. Although resellers may market themselves as hosts (indeed, some deliberately foster an appearance of being first-generation hosting companies), they are ultimately a sales and services company, not a technology provider. Resellers do not actually own the server space that they are selling, and their two principal responsibilities consist of recruiting new customers and servicing those accounts once they are established.

Resellers are valuable to hosting companies because they are middle men; they concentrate their resources on sales and support, and the hosting company, freed from the need to employ a bank of CSRs, can funnel its resources into technology. If resellers could hand off their sales and support duties to the original host, then there would be no reason for the host to even include them in the business model!

Ultimately, however, this system tends toward greater efficiency, particularly because resellers are often based in countries other than their host. For example, when a British host's server goes down, the company's French reseller might receive complaints from each of its twenty clients - but would then lodge a single complaint with the hosting company. Alone, the original hosting company might not have been equipped to offer support to twenty French-speaking end users ... but through the reseller, it is.

How to resell web hosting

So you would like to get into the lucrative business of being a web hosting provider. Welcome to the club. There are many companies and individuals trying to break into the web hosting resellers market today. Reselling web hosting services offers you the ability to start your own internet-based business selling web space, but without the hassles or monetary expense of managing your own equipment.

But now that you’ve made that decision, what do you do? Where do you even start when it comes to creating a new business for this purpose? I hope to provide you with guidelines that can help you to achieve your goals.

The first thing to do is decide on what it is you wish to offer. Some resellers just want to offer hosting solutions for a cheap price hoping that they can make money on quantity. Alternatively, other resellers are design firms who have decided to offer hosting to augment their design offerings as well as open the door for additional customers. There are many reasons for becoming a reseller, and a multitude of options that can be offered to your customers. It is a very good idea to know who your prospective customer is before you even get started.

In addition to deciding on what it is you wish to offer, the next step is to consider how you want to offer it. Many resellers offer different flavors of reseller hosting. Here are a couple of the more common varieties:

Agent Partners

This is when you become a "partner" with a web host, and resell their services. It is your job to find the customers, and when they sign up they become customers of your web host. You earn a recurring commission on the services they purchase. It is well known that you are not the actual hosting provider, just a partner.

Private Label

If you would like your customers to believe that you are the actual provider, or do not wish for them to know whose services you resell then this is the option for you. The actual provider will supply you with the information you need and the appropriate tools to transparently offer their services as your own. It is not common knowledge that you are a reseller or whose services you resell.

Once you have decided who you will cater to and what kind of image you would like to portray, the next step would be to begin to research hosting providers who can accommodate your wishes. For example, if you wish to offer services for ASP developers, you will need to find a hosting provider who offers windows-based hosting and who can offer the reseller program you desire.

Selecting a provider may not be as simple as it sounds. There are many hosts available to choose from, some better than others. It is highly recommended that you find some references from the ones that match your intentions, to help narrow down your selection.

Once you have selected a provider you need to decide what you want your website to consist of. If you are skilled in web design, then you have an edge in this arena. Most do not, however, and need to employ web designers to build their site for them.

By becoming familiar with the options available by your provider, and by researching other web reseller’s websites, you can build a site map of how your web site should be architected. If you will be having a web design firm handle creation of the website for you, this is imperative if you would like receive an all-inclusive quote.

Be sure you know what it is you want from your designer. Some of them will offer services such as logo design and banner ad creation, as well. Ask for example work and references. It is also helpful if your designer has experience with web hosting sites. First impressions are everything when it comes to web hosting customers, so this is very important. You want to make sure to select a firm that can deliver what it is you need, with professional quality and at a fair price.

Once your site it created, your final step is advertising. You can have a professionally designed website and outstanding hosting plans to sell, but without proper advertising your potential customers will never know you exist. There are many ways to advertise on the internet. These include submitting your website to search engines, doing direct advertising with select web sites, and banner advertising with different exchanges. You will need to weigh the benefits of each along with your budget.

By following the above guidelines, you should be well on your way to a constructive and profitable web hosting venture. This is not to say that these guidelines are a sure-fire way to become an instant success. Any successful business requires effort and dedication. But by taking these guidelines and applying the right amount of good old-fashioned hard work and determination, you have the makings of lucrative venture.

How to Choose A Reseller Hosting Plan

As the web hosting industry continues to boom, many small firms resell backbone web hosting packages under their own private labels. Thousands of companies resell hosting packages to consumers, providing specialty services and their own expert support.

Backbone web hosts are happy to provide small firms the tools and discounts necessary to resell their web hosting plans. This allows the backbone providers to gain customers they normally wouldn't have had, and the resellers to succeed by earning significant profits. These discounted plans can be quite impressive, in some cases up to 50% less than the regular cost to direct backbone customers. Depending on which additional features your firm provides such as web design, specialized advice, or other types of services you can set the price accordingly. Resellers are often considered individuals who have multiple domains and wish to receive discounts by hosting several of them at a single hosting provider.

If you are planning to resell web hosting packages, there are certain things you'll want to prepare for. First, a reliable provider is key factor for successful reselling. Second, most hosts will require you to provide customer technical support -- so it's wise to ensure you have the necessary time or staff to handle this. As a reseller, your web host will provide you online administration tools, however you will be responsible for using these tools online. Many hosting companies also offer resellers more advanced tools than they provide to general users.

As a reseller you can sell the following types of services under your own private-label:

    - General web site hosting

    - Virtual storefront hosting

    - Dedicated Server hosting

    - Co-located server hosting

    - Additional portal services (e-mail, chat, etc.)

Keeping these in mind, take the time to find a reliable web host providing reseller web hosting plans. Your web host's reliability will affect yours. If their servers are frequently down, it will end up hurting your company significantly -- customers will look to you to find out why "their" server is down. Look for leading web hosts that can fix problems quickly, and meet the needs of customers efficiently. As a reseller it will be your duty to handle hosting problems directly through your web hosting service. If you end up with a difficulty in fixing a client's problem, you'll have to turn to the backbone provider for help. Inquire with the web host whether there are any additional support call costs beyond a certain volume each month.

When looking for a web host providing reseller capabilities, browse company showcases, and read up on monthly rankings. Typically, the most reliable web hosting providers are also going to have the most reliable reseller opportunities. When you resell web hosting plans your web host will provide you with a special discount. Up to a 30% discount is typical - anything above that is exceptional. Keep in mind, the difference in reseller discounts provided to you will make a huge difference in the amount of money your company earns over time. Also be sure to find well-priced web hosting packages to resell in the first place. The industry standard for basic web hosting plans is $19.95 a month for 25-100MB, with 5 GB of data transfer. The other factor to remember is whether you are looking for UNIX or NT-based hosting -- NT is typically higher priced. If you are an international reseller check to make sure your Internet business can contact them during your local working hours -- some companies may not offer 24 hour support.

Guide To Reseller Hosting

 If you are in the market for a web host, chances are that in the course of your research, you have come across some resellers. There are positive and negative aspects to purchasing your web space from a reseller - however, as long as you have made yourself aware of what to look for and what to avoid you should not have many problems by trusting your site to a reseller, in fact, a good reseller host can save you money and offer you more services than a traditional host.
Like any hosting plan, reseller packages come in all shapes and sizes, but are usually tailored to emphasize the strengths of the parent host. Depending on the size of the parent company, resellers range from offering a robust services for advanced web developers to lower-cost solutions for individuals, SOHOs and SME's. However, there are a few things one should know before signing on with a reseller.
What Is A Reseller Host?
Reseller hosting is the provision of web hosting services to third-party companies that in turn act as web hosts for other organizations - acting as the host for the client site and serving its pages to users. Many resellers augment their hosting packages with Web design and management services in order to provide additional value to their clients.When you purchase a package from a reseller, your web site will be stored on the parent host's equipment, and served via their high speed lines. The reseller from whom you purchased the package will be the one who interacts with the parent host on your behalf. You will make your payments to the reseller, receive technical support from the reseller, and generally rely on the reseller to act as your host in all areas of maintaining your site.
How Do I Know That I'm Dealing With A Reseller?
You may never know! The majority of resellers hide the fact that they are reselling, and the only way to know for sure is to seek out the information yourself. Many resellers insist that the parent hosting provider provide personalized DNS servers in order to protect their identity. In general however, the best way to find out if a host is a reseller is to ask them - most resellers will admit to you that they are just that, and will reveal who they resell for. Other ways to find out if a hosting business is really a reseller is to run trace routes, domain lookups, and visit various hosting forums, and resources.
Does It Matter Who The Parent Provider Is?
Definitely! It is very helpful to know who the business is reselling for. Once you have that information, you can easily compare the features and price of the true host to those services being offered by the reseller.
Why Not Skip The Middleman And Purchase An Account With The Parent Provider?
This is the first question you should ask any potential reseller. This will give the reseller a chance to outline the extra services that they offer (which may not be listed on their web site). Since the reseller should be well informed about the parent provider's service, they will be able to give you a cost-to-service comparison between the two. What may pay only for basic web space at the parent provider may get you many extra features by signing on with a reseller, including (but not limited to):

- Web and graphic design
- Database design and maintenance
- Search engine promotion
- Managed services
- Web-based applications
- Internet training

Furthermore, resellers are also familiar with the parent providers configurations, abilities, and points of contact, which means that in many cases they are able to provide you more support and assistance with your account. The majority of resellers serve a smaller client base than the parent, which means they can offer you higher quality and more personal support than the parent can provide. Additionally, resellers often receive large discounts from the parent provider since they are purchasing more services than a single domain client - which translates into robust service at a lower price than the parent would charge.
If The Parent Provider Is A Known And Trusted Brand, Is The Reseller?
Not necessarily. When looking at the parent provider's services, be sure to carefully examine what they offer to their reseller clients. This will give you an idea if the reseller is marketing what they can actually offer, and also give you an estimate of what the reseller is paying to the parent provider in fees every month.
This is critical, as if a reseller fails to make their payments to the true host - regardless of whether or not you have made you payment to the reseller - your site will be shut down. Since resellers do not have to invest the same amount of capital as the parent - as the reseller acts more as a sales and technical contact, rather than providing infrastructure - a reseller can go out of business much faster and easier than a true host can. Since reseller accounts can be purchased from the parent online, it can be simple for a reseller to use a false name, have no business license, collect funds from those that purchase their services, and disappear, leaving you out in the cold. Wise shopping is a necessity when deciding upon a reseller - same as any other business.
Does The Plan Have The Features You Need?
Look at your requirements and determine if the Reseller plan can meet them. For instance, does the reseller meet your needs in terms of storage and data transfer? Do you need Real Audio, Video or chat capability? Do you need robust E-Commerce solutions with secure servers, shopping carts and transaction software? If you see a plan you like but it doesn't include something you need, don't be afraid to ask them for it. Resellers are always adding new features, and they may already have what you need in the works.
Does The Plan Fit Your Budget?
No matter what your budget you need to consider your (ROI) Return on Investment. The initial costs of the reseller plan is certainly a big factor but other aspects must be considered too. For instance, you might want to consider future discounts for multiple signups and referrals - which can add up to significant savings. Can you save money on the development by selecting a Web Host company that provides pre-installed features? This way you won't have to develop them, this cuts down on your direct costs in terms of time and expenses:
Will Their Equipment Handle Your Sites?
Before you make your decision, you must make sure the reseller's parent provider can handle your client sites smoothly during peak periods. Find out if their systems are redundant with reliable uninterruptible backup power supplies in case of power outages. Make sure they perform daily backups of the data. Look at their Internet connections to ensure they have both the speed and the bandwidth you need. The last thing your client needs is for the servers to go down. You will get the blame, not the reseller.
When choosing a reseller, always remember that there are more resellers on the Internet than true hosts, so ask the right questions and do your homework. Regardless of whether your site is hosted by a reseller or a true provider, the bottom line is that you will need to be able to know for certain that your web site is being served as it needs to be

How to know if a Web Host is a Reseller

 Web hosting resellers have been around for almost as long as the Web hosting business itself. In the beginning, Web hosting companies who had made large capital investments in servers and infrastructure began recruiting third-party companies as a type of commissioned sales force to help them recoup their investment faster. These third-party companies were given incentives to "resell" hosting services with volume discounts, advanced technical support and private labeling that made the primary host completely transparent to the reseller’s customers. In general, the more hosting customers that a reseller can deliver for the primary host, the greater the discount the reseller receives and the more money they can make marking up the hosting service to end users. Interestingly enough, many of today’s large primary hosting companies actually began as resellers and later bought their own servers and added support staff by reinvesting their profits.

Today, there are thousands of resellers operating under their own brand names who would prefer that their hosting customers never know they are really reselling another company’s hosting services. Should you be concerned with whether your hosting company is a reseller? The answer is yes and no. Resellers can sometimes offer you more attentive and personalized support because they don’t have as many customers to deal with as the primary hosting company they are reselling for. Resellers also can offer value-added benefits to their customers by including other services in their hosting packages such as search engine promotion, Web design, database management and other Web-based applications. And even though resellers are acting as middlemen, their hosting packages may be priced as low as, or even lower, than the primary host’s retail hosting packages depending on the volume discount they receive and the margin they need.

The majority of resellers are legitimate businesses offering a good value to their hosting customers through an established and reliable primary hosting company. But just because the primary hosting company is reputable and trustworthy doesn’t automatically mean all of their resellers are. If for any reason a reseller can’t pay or chooses not to pay their hosting bills, they can be shutdown by their primary host with no warning to you. It’s also highly unlikely that you would have any recourse with the primary host (if you can even find out who they are) since your hosting contract is with the reseller. Resellers don’t have any real capital investment in equipment and infrastructure so it’s very easy for them to go out of business for any reason. They’ll just resurface tomorrow under a different name and start reselling hosting for another hosting company -- leaving their existing customers with a pile of headaches and nobody to turn to for help.

So how do you know if you are dealing with a primary hosting company or a reseller? The first rule of thumb is to ask! A reputable reseller will most likely be honest and even tell you who their primary hosting company is. If the reseller is truly offering value for their hosting customers, their hosting packages should hold up even to direct comparisons with the primary host’s retail packages. But, if a reseller really doesn’t want anyone to know they are a reseller, it can be hard to know for sure. You could ask to visit their data center in person and see what they say. You can also try domain lookups, running trace routes or go into hosting forums for info on them.

The bottom line is that you need to very inquisitive and careful when choosing a reseller for a hosting company, just as you should with any new supplier with whom you are contemplating a contractual relationship. Regardless of whether your host is a reseller or not, the most important thing is that you reliably get the Web services you need for a fair market price. Make sure your host’s systems are redundant to avoid problems during peak periods and have uninterrupted power supplies in case of a power failure. Find out if their Internet connections offer the speed and bandwidth you need. And make absolutely sure that all of your data is backed up daily so if you ever have a problem, you can get up and running quickly with another hosting provider.