Meeting Four
1) How to communicate on the IRC
• /me i am hungry.
The above will appear in the chat and your name is beside it.
• Can chat with each other individually. Right click on the person’s name to set up a private conversation
• Instead of setting up a private window with the person, you can directly send a msg that only that person can see.
Type /msg I am hungry.
Only the person intended can see your message.
• /join #libreoffice
This allows you to join a channel and if that channel is not existing, a new channel will be created.
IRC has no central control server unlike google chat. A company wouldn’t use a central control server because information are supposed to be confidential. IRC server can be run in your own company server, you can just download it. It’s open source but for the google chat, msn, you are not having a server within your company. It’s outside and you need to have an account.
However, some network might block the IRC chatting.
The Economic model of Open Source
Question: Why do ppl create open source software if you don’t collect payment in the first place?
Out of goodwill.
The internet is an enabling technique that makes open source possible.
Red hat: As a developer, they uses internet to work on open source projects and writes code.
1) Web 2.0
There is an element of Web2.0 in facebook.
The igoogle is your personalized google homepage. Go to igoogle.com, which is a good example of Web2.0. This is where you can customize the google webpage. They are using Web2.0.
There are some smarts inside the browser itself and allows some editing to occur. You just click any box and then you can drag it from one place to another and the page will not refresh.
I have shifted the two box.
2) Red Hat is providing the recipe and the ingredients for free but its providing services to help you cook but with charges. Hence, this is how Red Hat earns money-they provide services.
3) Google
How do Google make money? (what is the business model for Google) : Advertisements. Once you click on the advertisements, they pay google the money.
Search engine optimization (SEO) : Giving you search that are relevant to what you might be looking for. E.g. if you search NTU, Nanyang technological university comes up instead of National Taiwan University. Hence, this is probably looking from the point that you are from Singapore. Hence, this is optimization.
Google is not on the open-source business but they are using open source code to create a business. Google don’t sell you anything but they sell you an experience, using open source tool. Their entire engine that runs behind is using Linux. They provide the algorithm but not the code. They using GPL V2 hence they need not release the changes if they were providing a service. This is different from GPLV3 which requires you to release the code.
Could they have done this if they were using a proprietary software instead of open source? No. They would have a hard time to pull that off.
4) For every 1 dollar that open source business gets, 5 dollars is denied for proprietary business even though they does exactly the same job.
5) Microsoft is trying to defeat the competition from the open source software.
6) Skype : How does it works?
When your computer runs a skype software. The software makes a supernodes. They are not doing VOIP (voice over IP). They are transferring your voice through many machines and bouncing to the person’s PC through many ppl’s PC. Hence, there is no privacy at all since it is passing through many PC. You don’t know how much of your computer bandwidth is being used even when you are not using skype, you have it installed though. It might be using some of your computer’s processing power or bandwidth of the internet you are using even without you knowing it. Hence, the more Skype users there are, the better the quality your voice gets carried over because they could spread the power out.
So is there any private conversation?
There is. PGP Pretty good private. They encrypts your conversation and others won’t know about it’s contents and everything. It is open source, so will ppl decrypt it?
PGP works on PKI (Public Key Infrastructure). Your EZ link card is a PKI. When you tab the card, the device will activate your card and query within the few ms whether or not you have enough money in the card. The way it is encrypted is using PKI.
7) Go to opensource.com
Intellectual property - Copyrights, Patents and Trademarks
1) Patents
It is valid for 17 years. You can grant permission to others (involving or not, $) to the person to use it.
Reasonable and non-discriminatory licensing (RAND)
-IPOS (Intellectual property of Singapore) will grant you a patent in your name to do something. In the next 17 years, someone needs to give money or not to do the same thing. This is called RAND.
-If you really want to use a patented piece of software, can you make the price reasonable and non-discriminatory (RAND)? Non-discriminatory means you can use it (the patented software) for whatever purpose after you have got the permission to use it.
-Then what is the reasonable price? It depends on the party involved.
-FRAND: Free and reasonable and non-discriminatory licensing. Means that hopefully it is FOC.
-If you take a power plug as an example :
Anybody can make the plug, you don’t have to pay anyone for permission to make it. That must be some patent for the plug because it has some different design or something that makes it different from other plugs. Means that, they have a patent pending for this. However, you can make it in a different way, different design. But if this design has been around for more than 17 years, you could just make it, no need permission.
-GIF is a patented FORMAT on how to save an image. And if you want to use GIF, you have to pay the company. Then there came another format, PNG (portable Network Graphics) for you to save the image. But now, GIF is expired alr, so not an issue today. JPEG is another one.
-If you want to save your image as a JPEG, the camera company had already paid royalties to the company in order to allow you to save your image as JPEG bcos the patent haven expire.
-But with software, it is more tricky. Example, moving the mouse on the screen. This can be patented. Another example is, when you click on a logo to bring you to another site, this action can be patented.
-Go to patentlysilly.com to see the different patents.
-In general, Open source does not like software patents because ppl misuse it.
-Go to openinventionnetwork.com. If you join them, you have a right to the entire license they have. If a third party sue you for using some software that this third party have, you can also sue this third party which uses the software that openinventionnetwork.com has. Hence, you and the third party will have cross-licensing, meaning allowing each other to use the software without inputting patent.
Copyright
-GPL: applied to software. To run a piece of software, you need a manual.
-GFPL: GNU free document license. Means, this is for a document, not for a software.
-But what about music, photos, pictures? These evolve under creative commons. Why need this? Bcos there is a problem with ppl remixing music. Does the person have permission to remix the music? It becomes a huge problem if you want to remix music. Hence, ppl come up with creative commons, granting you permission right from the start without needing you to ask for permission later.
Creative commons:
- Our vision is nothing less than realizing the full potential of the Internet — universal access to research and education, full participation in culture — to drive a new era of development, growth, and productivity.
Why CC?
The idea of universal access to research, education, and culture is made possible by the Internet, but our legal and social systems don’t always allow that idea to be realized. Copyright was created long before the emergence of the Internet, and can make it hard to legally perform actions we take for granted on the network: copy, paste, edit source, and post to the Web. The default setting of copyright law requires all of these actions to have explicit permission, granted in advance, whether you’re an artist, teacher, scientist, librarian, policymaker, or just a regular user. To achieve the vision of universal access, someone needed to provide a free, public, and standardized infrastructure that creates a balance between the reality of the Internet and the reality of copyright laws. That someone is Creative Commons.
Our mission
Creative Commons develops, supports, and stewards legal and technical infrastructure that maximizes digital creativity, sharing, and innovation.
The open source way
http://www.theopensourceway.org/book/
http://www.theopensourceway.org/book/The_Open_Source_Way-Introduction-Essential_terminology_or_Read_this_even_if_you_think_you_know_what_it_means.html
What needs to happen before an open source community thrives.
Community
A phrase that relates to open source. Community can overlap. It is a starting point when you want to build something with an open source. The project that we want to do will only succeed if you are building a community that other ppl can also contribute. If not, the contribution you had made will end with you.
When people talk about community, they may be talking about very different things:
• People who use something
• People who like something
• People who advocate for a technology
• People who enable others to use something
• People who contribute to improve something
• ... and so on.
When we talk about community in the The Open Source Way, we mean the community of contributors who are a superset to all other communities. The ones who, by getting things done, make it possible for many, many more to get much, much more done.
This is the group of people who form intentionally and spontaneously around something important to them. It includes the people who use or benefit from the project, those who participate and share the project to wider audiences, and the contributors who are essential to growth and survival.
Contributors are the oxygen. Without it, the animal chokes and dies.
1.4.5. Leaderless organizations (e.g. Wikipedia)
Hence, even if the leader disappears, the community can continue to survive on its own.
A leaderless organization is decentralized, meaning it does not rely upon a central authority for leadership, strategy, or tactics. Being decentralized makes it easier to heal, faster to respond and innovate, and more able to grow in scale.
An example of a large leaderless organization is the Internet. Not just the set of agreements that makes the structure work, but all the way down to the wire protocols that route around damage in the network, such as when a backhoe slices through a fiber link between two ISPs.
In projects, Wikipedia is a decentralized organization, while the Encyclopaedia Brittanica is a classic centralized organization.
The idea of the leaderless organization is put forth in the book The Starfish and The Spider.
1.4.8. Open collaboration tools
These are examples of open collaboration tools used in the open source communities. The same or similar tools apply to any online community of practice.
• What is a wiki?
• What is a mailing list?
• What is IRC?
For any kind of community building, you need to have ppl communicate with one another. You can create a mailing list, start up a wiki page , blog about what you are doing.
1.4.9.2. Fundamental rule - be radically transparent
There is no such thing as too much information. Everything you can legally say, you should be saying.
Don't use this as an excuse to be verbose or disorganized.
Verbal diarrhea: Incoherent comments
1.4.9.3. Fundamental rule - explain what you know and how you know it
In the general category of being honest, spend some time with revealing sources and means. Bad numbers are everywhere in software and communities. Make sure your numbers are real and provable. Explain your source of information that makes you certain that the way you are doing things are correct.
This also falls in the general methodology of thinking like a scientist.
Evolution – Expect some changes along the way
Release early release often
Fail early fail quickly
2.4. Principles for Cultivating Communities of Practice
In his book Cultivating Communities of Practice, Etienne Wenger proposes seven principles for successfully cultivating communities of practice. Anyone who is responsible for moving a community forward towards its goals should consider reading it.
2.4.1. Design for evolution
When starting a new community effort, it's difficult to know what form it will take. Volunteers are not employees; they can only be influenced, never ordered. Some may take passionately to the proposed project; others may only be able to give some of their time.
Be ready for that. Concentrate on simple lists that encourage accountability. Know who's doing what. Maintain a flexibility of structure, so that if someone to have an idea that takes your effort in a completely different direction, you don't have to change all your rules. Only have as much "governance" as you need at the time, never more.
Also: volunteers leave. It's a fact of life. Make it easy to hand off tasks to newcomers, and work to generate newcomers, so that your old-timers don't feel obliged to continue doing work that they no longer have the time or inclination to do.
At teachingopensource.org, there are a number of working groups. Some of them are active; some of them are not. Creating a new working group is deliberately kept simple; identify a "leader" in charge of moving things forward, and claim a wiki page, and you're all set. Working groups are evaluated periodically by the entire group, and if it's generally agreed that no progress is being made -- often because the leader doesn't have the time required -- the working group either finds a new leader, or is disbanded. Simple process, until more complex process is needed.
2.4.3. Invite different levels of participation
Not everyone in the community will contribute at the same level with the same kind of contribution. Nobody will contribute equally.
Often, the hard tasks at the center of a domain can only be tackled by the insiders -- but if only the hardest tasks get focus, and only by experts, then those new to the domain do not have opportunities to gain expertise.
One of the important concepts espoused by Wenger is legitimate peripheral participation. It is, essentially, the idea of apprenticeship; the key difference is that, rather than being apprenticed to an individual, a new practitioner can be apprenticed to the entire community of practice.
In a volunteer community especially, people who join are going to be invested in learning more and doing more, and it's important to identify work that matches the newbie's skills, invites them to stretch those skills, and provides people who can help them develop those skills as required.
As an example, learning to package software is not easy -- but some software is easier to package than others. Newbie Fedora packagers are invited to learn how to package fonts, since they are simple and very uniform in how they are packaged. There are also lots and lots of fonts out there that need to be packaged. It's a perfect "on-ramp" for newbie packagers, and because there are so many fonts to be packaged, there are plenty of opportunities for newbies to be immediately useful.
Experts are great but they are hard to find. Experts are great, but they're hard to find. The way to find more experts is to invest in a process that continually creates more experts.
Appendix
RAND is a type of licensing typically used during standardization processes. When joining a standardization body, companies normally agree that if they receive any patents on technologies which become essential to the standard they agree to allow other groups attempting to implement the standard to use those patents and they agree that the charges for those patents shall be reasonable. RAND licenses allow a competitive market to develop between multiple companies making products which implement a standard.
Having created a RAND-based standard does mean that the known exclusive rights can be licensed from their right holders at published RAND conditions. If at a later time exclusive rights beyond this will get visible or even claimed, this does not at all mean that those parts will be available under RAND conditions but the requested charges can be rather unreasonable instead. The acting standardisation group often has few options for reacting to this, other than creating a newer version of the standard that works around the parts now known to be problematic (if this is possible at all). For example, see the case of the de facto GIF standard or the JPEG standard, which was severely damaged by suddenly surfacing patents.
The second, more subtle, limitation of RAND licenses in standardisation is that the term does not say anything about the relation of the license to the product cost. With this a right that was found to fit, e.g. into a medical device, can have a rather high price per unit via its published RAND conditions. Now finding a second case, e.g. in a cheap consumer device, will not necessarily change the RAND licensing terms in any way.
Almost all free software licenses are RAND, but a RAND license is not necessarily compatible with free software licenses. If a standards body requires the use of a RAND license, free software developers must check the terms of the specific license chosen by the rights holder in order to determine if the standard may be used in free software. A particular RAND license could be incompatible with free software in several ways, such as requiring licensing fees, only applying to complete implementations of the licensed standard, limiting use to particular fields, or restricting redistribution. Some free software advocates argue that standards bodies should use a different term, such as "uniform fee only" (UFO), because they believe a license that charges for a patent license is inherently non-reasonable, and thus the term RAND is misleading.
One very successful area where RAND is in use is in the GSM and UMTS mobile phone standards where many different manufacturers compete to provide handsets and base stations. This is possible because the systems are based on open standards and because the patents required to implement this are mostly available under RAND terms. This situation is claimed, for example by the 3GPP to lead to strong price competition and lower market prices for this equipment both to consumers and to operators. This compares very well to other standards such as CDMA, where single companies may have almost complete control over particular areas of technology and manufacturing.
In contrast to the situation for GSM, the World Wide Web Consortium considered standardising on RAND principles, but, after considerable resistance from many different sources, abandoned this strategy in order to aim for royalty free licensing.
As the word "reasonable" is absolutely free in interpretation, standards of the RAND type can be used to keep small and mid-sized businesses away from the market. This can easily lead to oligopolies, where few big enterprises share the markets. Customers then have to pay inflated prices and technological and economical progress is decelerated.
The RAND-Z (RAND with zero royalty) or or RAND-RF (RAND Royalty Free) licensing means that the company promises to license the technology at no charge, but implementers still have to get the licenser's permission to implement. The licenser may not make money off the deal but can still stop some type of products or requre some type of reciprocity or do more subtle things like drag out the licensing process.
Improving in progress
Definition of Photoaging
The deterioration of biological functions and ability to manage metabolic stress is one of the major consequences of the ageing process. Aging is a complex, progressive process which also leads to functional and esthetic changes in the skin. This process could result from both intrinsic, such that it is genetically determined, as well as extrinsic processes which include environmental factors.
Photoaging is a process of ageing of the skin attributed to continuous, long-term exposure to ultraviolet (UV) radiation of approximately 245-290nm, natural or synthetic, on an intrinsically aged skin. Photoaging is thus also known as aging of the skin of the face, ears, neck and hands, caused by UVA and UVB rays.
Effects of UV light
UV and Molecular and Genetic Changes
UVB ray is considered as a primary mutagenthat can only penetrate through the epidermal or outermost layer of the skin, resulting in DNA mutations. These DNA mutationsarise due to chemical changes, the formation of cyclobutane pyrimidine dimers and photoproducts formed between adjacent pyrimidine bases. These mutations may be clinically related to specific signs of photoaging such as wrinkling, increasing in elastin and collagen damage.
The epidermal layer does not contain any blood vessels or nerve endings but melanocytes and basal cells are embedded in this layer. Upon exposure to UVB rays, melanocytes will produce melanin, a pigment that gives the skin its colour tone. However, UVB will cause the formation of freckles and dark spots, both of which are symptoms of Photoaging. With constant exposure to UVB rays, signs of Photoaging might appear and precancerous lesions or skin cancer may develop.
UVA rays are able to penetrate deeper into the skin as compared to UVB rays. Hence, in addition to the epidermal layer, the dermal layer will also be damaged. The dermis is the second major layer of the skin and it comprises of collagen, elastin, and extrafibrillar matrix which provides structural support to the skin. However, with constant UVA exposure, the size of the dermis layer will be reduced, thereby causing the epidermis to start drooping off the body. Due to the presence of blood vessels in the dermis, UVA rays could lead to dilated or broken blood vessels most commonly visible on the nose and cheeks. UVA can also damage DNA indirectly through the generation of reactive oxygen species (ROS) which includes superoxide anion, peroxide and singlet oxygen. These ROS damage cellular DNA as well as lipids and proteins (1).
UV and Pigmentation
UV exposure could also lead to inflammation and vasodilation which is clinically manisfested as sunburn. UV radiation activates the transcription factor, NF-κB, which is the first step in inflammation. NF-κB activation will result in the increase of proinflammatory cytokines eg interleukin 1 (IL-1), IL-6 vascular endothelial growth factor and tumor necrosis factor, TNF-α. This would then attract neutrophils which lead to an increase in oxidative damage through the generation of free radicals.
Additionally, UV radiation would cause the down-regulation of an angiogenesis inhibitor, thrombospondin-1, and the up-regulation of an angiogenesis activator which is platelet-derived endothelial cell growth factor, in keratinocytes. These enhance angiogenesis and aid in the growth of UV-induced neoplasms.
UV and Immunosupression
It has also been reported that UV radiation would lead to local and systemic immunosuppression, due to DNA damage and altered cytokine expression. This has implications in cutaneous tumor surveillance. The langerhan cells would undergo changes in terms of quantity, morphology and functions due to UV exposure and eventually becomes depleted. One of the reasons suggested to account for the presence of immunosuppression mediated by the body is due to the need to suppress or prevent an autoimmune response to inflammatory products resulting from UV-mediated damage.
UV and degradation of collagen
UV exposure would also lead to the activation of receptors for epidermal growth factor, IL-1 and TNF-α in keratinocytes and fibroblasts, which then activates signalling kinases throughout the skin via an unknown mechanism. The nuclear transcription factor activator protein, AP-1, which controls the transcription of matrix metalloproteinases (MMP), is expressed and activated. MMP-1 is a major metalloproteinases for collagen degradation. This entire process is aided by the presence of reactive oxygen species (ROS) that inhibits protein-tyrosine phosphatases via oxidation, thereby resulting in the up-regulation of the above mentioned receptors. Another transcription factor NF-κB, which is also activated by UV light, also increases the expression of MMP-9.
The up-regulation of MMP can occur even after minimal exposure to UV, hence, exposure to UV radiation which is inadequate to cause sunburn can thus facilitate the degradation of skin collagen and lead to presumably, eventual photoaging. Thus, collagen production is reduced in photoaged skin due to the process of constant degradation of collagen mediated by MMPs.
In addition, the presence of damaged collagen would also down-regulate the synthesis of new collagen. The impaired spreading and attachment of fibroblasts onto degraded collagen could be one of the contributing factors to the inhibition of collagen synthesis.
UV and Retinoic acids and Photodamage
Retinoic acid (RA) is essential for normal epithelial growth and differentiation as well as for maintenance of normal skin homeostasis. UV radiation decreases the expression of both retinoic acid receptors (RARs) and retinoid X receptors (RXRs) in human skin, thereby resulting in a complete loss of the induction of RA-responsive genes. It also would lead to an increase in activity of AP-1 pathway, increasing MMP activity and thus also resulting in a functional deficiency of vitamin A in the skin.
Signs, symptoms and histopathology
The early symptoms of Photoaging includes the following:
Dyspigmentation and the formation of wrinkles around regions of skin commonly exposed to sun, namely the eyes, mouth and forehead.
Spider veins on face and neck
Loss of colour and fullness in lips
Symptoms of Photoaging attributed to prolonged exposure to UV
Wrinkles deepen and forehead frown lines can be seen even when not frowning.
Telangiectasias most commonly seen around the nose, cheeks and chin.
Skin becomes leathery and laxity occurs.
Solar Lentigines (age spots) appears on the face and hands.
Possibly pre-cancerous red and scaly spots (actinic keratoses) appear.
Cutaneous malignancies
In addition to the above symptoms, photoaging could also result in an orderly maturation of keratinocytes and an increased in the cell population of the dermis where abundant; hyperplastic, elongated and collapsed fibroblasts and inflammatory infiltrates are found.
Photodamage could also be characterised as the disorganisation of collagen fibrils which constitute most of the connective tissue and the accumulation of abnormal, amorphous, elastin-containing material.
Endogenous Defence Mechanism against UV radiation
The endogenous defence mechanisms provide protection of the skin from damages induced by UV.
Epidermal thickness
UV exposure which would lead to an increase in epidermal thickness could help protect from further UV damage.
Pigment
It has been reported in many cases that fairer individuals who has lesser melanin pigment show more dermal DNA photodamage, infiltrating neutrophils, keratinocyte activation, IL-10 expression and increased MMPs after UV exposure. Therefore, the distribution of melanin provides protection from sunburn, Photoaging, and carcinogenesis by absorbing and scattering UV rays.
Repair of DNA mutation and apoptosis
The damage of DNA due to exposure of UV rays will lead to expression of p53, thereby leading to eventual arrest of the cell cycle. This allows DNA repair mediated by endogenous mechanisms like the nucleotide excision repair system. In addition, apoptosis occurs if the damage is too severe. However, the apoptotic mechanisms decline with age and if neither DNA repair mechanism nor apoptosis occurs, cutaneous tumorigenesis may result.
Tissue inhibitors of MMPs (TIMPs)
TIMPs regulate the activity of MMP. UV rays have been shown in many studies that it would induce TIMP-1.
Antioxidants
The skin consists of several antioxidants which include vitamin E, coenzyme Q10, ascorbate, carotenoids, superoxide dismutase, catalase and glutathione peroxidase. These antioxidants provide protection from ROS produced during normal cellular metabolism. However, too much exposure to UV rays could lead to a significant reduction in the antioxidant supply, leading to oxidative stress. Hence, these antioxidants are essential in the skin's defense mechanism against UV radiation and photocarcinogenesis.
Treatment of Photoaging
Treatment and intervention for photoaging can be classified into a unique paradigm based on disease prevention.
Primary prevention
Primary prevention aims to reduce the risk factors before a disease or condition occurs. Primary prevention method involves mainly sun protection that comes in many forms like sun avoidance, protective clothing, and sunscreens.
The UV exposure would be the strongest between 10am and 4pm and sun avoidance between this period of time is highly encouraged. If one cannot avoid exposure to the sun, clothing, hats and sunglasses that protects one from sun exposure should be fully utilised. Wide spectrum sun screens that have a sun protection factor (SPF) of at least 30 should be used when one gets frequent sun exposure.
Secondary protection
Secondary protection refers to early detection of disease, potentially while still asymptomatic, to allow positive interference to prevent, delay or attenuate the symptomatic clinical condition. This includes the following:
·Retinoids e.g. Tretinoin
·Antioxidants e.g. Tropical vitamin C, oral supplements, CoQ10, Lipoic acid
·Estrogens
·Growth factors and cytokines.
Tertiary prevention
Lastly, tertiary prevention is the treatment of an existing symptomatic disease process to ameliorate its effects or delay its progress. Such tertiary prevention includes the use of chemical peels, resurfacing techniques like micro-dermabrasion, the use of ablative and non-ablative laser systems, radiofrequency technology, the use of exotoxin Botulinum toxins and soft tissue augmentation, also known as fillers.
Summary of article: “Photoaging: Mechanism and repair”
Brief Introduction
The deterioration of biological functions and ability to manage metabolic stress is one of the major consequence of the aging process (1). Aging is a complex, progressive process which also leads to functional and esthetic changes in the skin (1). This process could result from both intrinsic, such that it is genetically determined, as well as extrinsic processes which include environmental factors (1).
Definition of Photoaging
Photoaging is the resulting effect of continuous, long-term ultraviolet (UV) exposure and sun damage on an intrinsically aged skin (1). Most often, fairer individuals are most severely affected. For photoaged skin, there would be a significant reduction in many functions of the skin (1).
Signs, symptoms and histopathology
The clinical signs and symptoms for a photoaged skin include dyspigmentation, laxity, a yellow hue, wrinkles, telangiectasia, leathery appearance, and cutaneous malignancies (1).
Additionally, photoaging could also result in an orderly maturation of keratinocytes and an increased in the cell population of the dermis where abundant, hyperplastic, elongated and collapsed fibroblasts and inflammatory infiltrates are found (1).
Photodamage could also characterised as the disorganisation of collagen fibrils which constitute most of the connective tissue and the accumulation of abnormal, amorphous, elastin-containing material (1). Fine wrinkles is another one of the prominent feature of a photoaged skin (1).
Effects of UV light on keratinocytes
UV and Molecular and Genetic Changes
UV radiation of appopximately 245 – 290 nm is maximally absorbed by DNA, where UVB is considered as a primary mutagen (1). UVB results in DNA mutations that arise due to chemical changes, the formation of cyclobutane pyrimidine dimers and photoproducts formed between adjacent pyrimidine bases (1). These mutations may be clinically related to specific signs of photoaging such as wrinkling, increasing in elastin and collagen damage (1).
UVA can also damage DNA indirectly through the generation of reactive oxygen species (ROS) which includes superoxide anion, peroxide and singlet oxygen. These ROS damage cellular DNA as well as lipids and proteins (1).
UV and Pigmentation
UV exposure could also lead to inflammation and vasodilation which is clinically manisfested as sunburn (1). UV radiation activates the transcription factor, NF-κB, which is the first step ininflammation. NF-κB activation will result in the increase of proinflammatory cytokines eg interleukin 1 (IL-1), IL-6 vascular endothelial growth factor and tumor necrosis factor, TNF-α (1). This would then attract neutrophils which leads to an increase in oxidative damage through the generation of free radicals (1).
Additionally, UV radiation would cause the downregulation of an angiogenesis inhibitor, thrombospondin-1, and the upregulation of an angiogenesis activator which is platelet-derived endothelial cell growth factor, in keratinocytes (1). These enhance angiogenesis and aid in the growth of UV-induced neoplasms (1).
UV and Immunosupression
It has also been reported that UV radiation would lead to local and systemic immunosuppression, due to DNA damage and altered cytokine expression (1). This has implications in cutaneous tumor surveillance (1).
UV and Extracellular Matrix
UV exposure would also lead to the activation of receptors for epidermal growth factor, IL-1 and TNF-α in keratinocytes and fibroblasts, which then activates signalling kinases throughout the skin (1). The nuclear transcription factor activator protein, AP-1, which controls the transcription of matrix metalloproteinases (MMP), is expressed and activated (1). MMP-1 is a major metalloproteinases for collagen degradation. NF-κB, which is also activated by UV light, also increases the expression of MMP-9 (1).Exposure to UV radiation which is inadequate to cause sunburn can thus facilitate the degradation of skin collagen and lead to presumably, eventual photoaging (1).
UV and Retinoic acids and Photodamage
Retinoic acid (RA) is essential for normal epithelial growth and differentiation as well as for maintenance of normal skin homeostasis (1). UV radiation decreases the expression of bothretinoic acid receptors (RARs) and retinoid X receptors (RXRs) in human skin which results in a complete loss of the induction of RA-responsive genes (1). It also would lead to an increase in activity of AP-1 pathway, increasing MMP activity and thus also resulting in a functional deficiency of vitamin A in the skin (1).
Endogenous Defense Mechanism Against UV radiation
Epidermal thickness
UV exposure which would lead to an increase in epidermal thickness could help protect from further UV damage (1).
Pigment
It has been reported in many cases that fairer individuals (lesser melanins) show more dermal DNA photodamage, infiltrating neutrophils, keratinocyte activation and IL-10 expression, increased MMPs after UV exposure (1). Therefore, the distribution of melanin provides protection from sunburn, photoaging and carcinogenesis by absorbing and scattering UV rays (1).
Repair of DNA mutation and apoptosis
When DNA is damaged by UV rays exposure, p53 transcription isactivated and cell will be arrested in the G1 phase so as to allow DNA repair by endogenous mechanisms like the nucleotide excision repair system (1). If the damage is too severe and cannot be repaired, it might trigger apoptosis to occur (1).
Tissue inhibitors of MMPs (TIMPs)
TIMPs regulate the activity of MMP. UV rays has been shown in many studies that it would induce TIMP-1 (1).
Antioxidants
The skin consists of several antioxidants which include vitamin E, coenzyme Q10, ascorbate, carotenoids, superoxide dismutase, catalase and glutathione peroxidase (1). These antioxidants provide protection from ROS produced (1). However, too much exposure to UV rays could lead to a significant reduction in the antioxidant supply, leading to oxidative stress (1). Hence, these antioxidants are essential in the skin's defense mechanism against UV radiation and photocarcinogenesis (1).
Treatment of Photoaging
Treatment and intervention for photoaging can be classified into a unique paradigm based on disease prevention (1).
Primary prevention is to reduce the risk factors before a disease or condition occurs that includes photoprotection or sun protection (1).
Secondary protection refers to early detection of disease, potentially while still asymptomatic, to allow positive interference to prevent, delay or attenuate the symptomatic clinical condition (1). This include the usage of retinoids, antioxidants, estrogens and growth factors or cytokines (1).
Lastly, tertiary prevention is the treatment of an existing symptomatic disease process to ameliorate its effects or delay its progress (1). Such tertiary prevention includes the use of chemical peels, resurfacing techniques like microdermabrasion, the use of ablative and nonablative laser systems, radiofrequency technology, the use of exotoxin Botulinum toxins and soft tissue augmentation, also known as fillers (1).
Meeting Four
1) How to communicate on the IRC
• /me i am hungry.
The above will appear in the chat and your name is beside it.
• Can chat with each other individually. Right click on the person’s name to set up a private conversation
• Instead of setting up a private window with the person, you can directly send a msg that only that person can see.
Type /msg I am hungry.
Only the person intended can see your message.
• /join #libreoffice
This allows you to join a channel and if that channel is not existing, a new channel will be created.
IRC has no central control server unlike google chat. A company wouldn’t use a central control server because information are supposed to be confidential. IRC server can be run in your own company server, you can just download it. It’s open source but for the google chat, msn, you are not having a server within your company. It’s outside and you need to have an account.
However, some network might block the IRC chatting.
The Economic model of Open Source
Question: Why do ppl create open source software if you don’t collect payment in the first place?
Out of goodwill.
The internet is an enabling technique that makes open source possible.
Red hat: As a developer, they uses internet to work on open source projects and writes code.
1) Web 2.0
There is an element of Web2.0 in facebook.
The igoogle is your personalized google homepage. Go to igoogle.com, which is a good example of Web2.0. This is where you can customize the google webpage. They are using Web2.0.
There are some smarts inside the browser itself and allows some editing to occur. You just click any box and then you can drag it from one place to another and the page will not refresh.
I have shifted the two box.
2) Red Hat is providing the recipe and the ingredients for free but its providing services to help you cook but with charges. Hence, this is how Red Hat earns money-they provide services.
3) Google
How do Google make money? (what is the business model for Google) : Advertisements. Once you click on the advertisements, they pay google the money.
Search engine optimization (SEO) : Giving you search that are relevant to what you might be looking for. E.g. if you search NTU, Nanyang technological university comes up instead of National Taiwan University. Hence, this is probably looking from the point that you are from Singapore. Hence, this is optimization.
Google is not on the open-source business but they are using open source code to create a business. Google don’t sell you anything but they sell you an experience, using open source tool. Their entire engine that runs behind is using Linux. They provide the algorithm but not the code. They using GPL V2 hence they need not release the changes if they were providing a service. This is different from GPLV3 which requires you to release the code.
Could they have done this if they were using a proprietary software instead of open source? No. They would have a hard time to pull that off.
4) For every 1 dollar that open source business gets, 5 dollars is denied for proprietary business even though they does exactly the same job.
5) Microsoft is trying to defeat the competition from the open source software.
6) Skype : How does it works?
When your computer runs a skype software. The software makes a supernodes. They are not doing VOIP (voice over IP). They are transferring your voice through many machines and bouncing to the person’s PC through many ppl’s PC. Hence, there is no privacy at all since it is passing through many PC. You don’t know how much of your computer bandwidth is being used even when you are not using skype, you have it installed though. It might be using some of your computer’s processing power or bandwidth of the internet you are using even without you knowing it. Hence, the more Skype users there are, the better the quality your voice gets carried over because they could spread the power out.
So is there any private conversation?
There is. PGP Pretty good private. They encrypts your conversation and others won’t know about it’s contents and everything. It is open source, so will ppl decrypt it?
PGP works on PKI (Public Key Infrastructure). Your EZ link card is a PKI. When you tab the card, the device will activate your card and query within the few ms whether or not you have enough money in the card. The way it is encrypted is using PKI.
7) Go to opensource.com
Intellectual property - Copyrights, Patents and Trademarks
1) Patents
It is valid for 17 years. You can grant permission to others (involving or not, $) to the person to use it.
Reasonable and non-discriminatory licensing (RAND)
-IPOS (Intellectual property of Singapore) will grant you a patent in your name to do something. In the next 17 years, someone needs to give money or not to do the same thing. This is called RAND.
-If you really want to use a patented piece of software, can you make the price reasonable and non-discriminatory (RAND)? Non-discriminatory means you can use it (the patented software) for whatever purpose after you have got the permission to use it.
-Then what is the reasonable price? It depends on the party involved.
-FRAND: Free and reasonable and non-discriminatory licensing. Means that hopefully it is FOC.
-If you take a power plug as an example :
Anybody can make the plug, you don’t have to pay anyone for permission to make it. That must be some patent for the plug because it has some different design or something that makes it different from other plugs. Means that, they have a patent pending for this. However, you can make it in a different way, different design. But if this design has been around for more than 17 years, you could just make it, no need permission.
-GIF is a patented FORMAT on how to save an image. And if you want to use GIF, you have to pay the company. Then there came another format, PNG (portable Network Graphics) for you to save the image. But now, GIF is expired alr, so not an issue today. JPEG is another one.
-If you want to save your image as a JPEG, the camera company had already paid royalties to the company in order to allow you to save your image as JPEG bcos the patent haven expire.
-But with software, it is more tricky. Example, moving the mouse on the screen. This can be patented. Another example is, when you click on a logo to bring you to another site, this action can be patented.
-Go to patentlysilly.com to see the different patents.
-In general, Open source does not like software patents because ppl misuse it.
-Go to openinventionnetwork.com. If you join them, you have a right to the entire license they have. If a third party sue you for using some software that this third party have, you can also sue this third party which uses the software that openinventionnetwork.com has. Hence, you and the third party will have cross-licensing, meaning allowing each other to use the software without inputting patent.
Copyright
-GPL: applied to software. To run a piece of software, you need a manual.
-GFPL: GNU free document license. Means, this is for a document, not for a software.
-But what about music, photos, pictures? These evolve under creative commons. Why need this? Bcos there is a problem with ppl remixing music. Does the person have permission to remix the music? It becomes a huge problem if you want to remix music. Hence, ppl come up with creative commons, granting you permission right from the start without needing you to ask for permission later.
Creative commons:
- Our vision is nothing less than realizing the full potential of the Internet — universal access to research and education, full participation in culture — to drive a new era of development, growth, and productivity.
Why CC?
The idea of universal access to research, education, and culture is made possible by the Internet, but our legal and social systems don’t always allow that idea to be realized. Copyright was created long before the emergence of the Internet, and can make it hard to legally perform actions we take for granted on the network: copy, paste, edit source, and post to the Web. The default setting of copyright law requires all of these actions to have explicit permission, granted in advance, whether you’re an artist, teacher, scientist, librarian, policymaker, or just a regular user. To achieve the vision of universal access, someone needed to provide a free, public, and standardized infrastructure that creates a balance between the reality of the Internet and the reality of copyright laws. That someone is Creative Commons.
Our mission
Creative Commons develops, supports, and stewards legal and technical infrastructure that maximizes digital creativity, sharing, and innovation.
The open source way
http://www.theopensourceway.org/book/
http://www.theopensourceway.org/book/The_Open_Source_Way-Introduction-Essential_terminology_or_Read_this_even_if_you_think_you_know_what_it_means.html
What needs to happen before an open source community thrives.
Community
A phrase that relates to open source. Community can overlap. It is a starting point when you want to build something with an open source. The project that we want to do will only succeed if you are building a community that other ppl can also contribute. If not, the contribution you had made will end with you.
When people talk about community, they may be talking about very different things:
• People who use something
• People who like something
• People who advocate for a technology
• People who enable others to use something
• People who contribute to improve something
• ... and so on.
When we talk about community in the The Open Source Way, we mean the community of contributors who are a superset to all other communities. The ones who, by getting things done, make it possible for many, many more to get much, much more done.
This is the group of people who form intentionally and spontaneously around something important to them. It includes the people who use or benefit from the project, those who participate and share the project to wider audiences, and the contributors who are essential to growth and survival.
Contributors are the oxygen. Without it, the animal chokes and dies.
1.4.5. Leaderless organizations (e.g. Wikipedia)
Hence, even if the leader disappears, the community can continue to survive on its own.
A leaderless organization is decentralized, meaning it does not rely upon a central authority for leadership, strategy, or tactics. Being decentralized makes it easier to heal, faster to respond and innovate, and more able to grow in scale.
An example of a large leaderless organization is the Internet. Not just the set of agreements that makes the structure work, but all the way down to the wire protocols that route around damage in the network, such as when a backhoe slices through a fiber link between two ISPs.
In projects, Wikipedia is a decentralized organization, while the Encyclopaedia Brittanica is a classic centralized organization.
The idea of the leaderless organization is put forth in the book The Starfish and The Spider.
1.4.8. Open collaboration tools
These are examples of open collaboration tools used in the open source communities. The same or similar tools apply to any online community of practice.
• What is a wiki?
• What is a mailing list?
• What is IRC?
For any kind of community building, you need to have ppl communicate with one another. You can create a mailing list, start up a wiki page , blog about what you are doing.
1.4.9.2. Fundamental rule - be radically transparent
There is no such thing as too much information. Everything you can legally say, you should be saying.
Don't use this as an excuse to be verbose or disorganized.
Verbal diarrhea: Incoherent comments
1.4.9.3. Fundamental rule - explain what you know and how you know it
In the general category of being honest, spend some time with revealing sources and means. Bad numbers are everywhere in software and communities. Make sure your numbers are real and provable. Explain your source of information that makes you certain that the way you are doing things are correct.
This also falls in the general methodology of thinking like a scientist.
Evolution – Expect some changes along the way
Release early release often
Fail early fail quickly
2.4. Principles for Cultivating Communities of Practice
In his book Cultivating Communities of Practice, Etienne Wenger proposes seven principles for successfully cultivating communities of practice. Anyone who is responsible for moving a community forward towards its goals should consider reading it.
2.4.1. Design for evolution
When starting a new community effort, it's difficult to know what form it will take. Volunteers are not employees; they can only be influenced, never ordered. Some may take passionately to the proposed project; others may only be able to give some of their time.
Be ready for that. Concentrate on simple lists that encourage accountability. Know who's doing what. Maintain a flexibility of structure, so that if someone to have an idea that takes your effort in a completely different direction, you don't have to change all your rules. Only have as much "governance" as you need at the time, never more.
Also: volunteers leave. It's a fact of life. Make it easy to hand off tasks to newcomers, and work to generate newcomers, so that your old-timers don't feel obliged to continue doing work that they no longer have the time or inclination to do.
At teachingopensource.org, there are a number of working groups. Some of them are active; some of them are not. Creating a new working group is deliberately kept simple; identify a "leader" in charge of moving things forward, and claim a wiki page, and you're all set. Working groups are evaluated periodically by the entire group, and if it's generally agreed that no progress is being made -- often because the leader doesn't have the time required -- the working group either finds a new leader, or is disbanded. Simple process, until more complex process is needed.
2.4.3. Invite different levels of participation
Not everyone in the community will contribute at the same level with the same kind of contribution. Nobody will contribute equally.
Often, the hard tasks at the center of a domain can only be tackled by the insiders -- but if only the hardest tasks get focus, and only by experts, then those new to the domain do not have opportunities to gain expertise.
One of the important concepts espoused by Wenger is legitimate peripheral participation. It is, essentially, the idea of apprenticeship; the key difference is that, rather than being apprenticed to an individual, a new practitioner can be apprenticed to the entire community of practice.
In a volunteer community especially, people who join are going to be invested in learning more and doing more, and it's important to identify work that matches the newbie's skills, invites them to stretch those skills, and provides people who can help them develop those skills as required.
As an example, learning to package software is not easy -- but some software is easier to package than others. Newbie Fedora packagers are invited to learn how to package fonts, since they are simple and very uniform in how they are packaged. There are also lots and lots of fonts out there that need to be packaged. It's a perfect "on-ramp" for newbie packagers, and because there are so many fonts to be packaged, there are plenty of opportunities for newbies to be immediately useful.
Experts are great but they are hard to find. Experts are great, but they're hard to find. The way to find more experts is to invest in a process that continually creates more experts.
Appendix
RAND is a type of licensing typically used during standardization processes. When joining a standardization body, companies normally agree that if they receive any patents on technologies which become essential to the standard they agree to allow other groups attempting to implement the standard to use those patents and they agree that the charges for those patents shall be reasonable. RAND licenses allow a competitive market to develop between multiple companies making products which implement a standard.
Having created a RAND-based standard does mean that the known exclusive rights can be licensed from their right holders at published RAND conditions. If at a later time exclusive rights beyond this will get visible or even claimed, this does not at all mean that those parts will be available under RAND conditions but the requested charges can be rather unreasonable instead. The acting standardisation group often has few options for reacting to this, other than creating a newer version of the standard that works around the parts now known to be problematic (if this is possible at all). For example, see the case of the de facto GIF standard or the JPEG standard, which was severely damaged by suddenly surfacing patents.
The second, more subtle, limitation of RAND licenses in standardisation is that the term does not say anything about the relation of the license to the product cost. With this a right that was found to fit, e.g. into a medical device, can have a rather high price per unit via its published RAND conditions. Now finding a second case, e.g. in a cheap consumer device, will not necessarily change the RAND licensing terms in any way.
Almost all free software licenses are RAND, but a RAND license is not necessarily compatible with free software licenses. If a standards body requires the use of a RAND license, free software developers must check the terms of the specific license chosen by the rights holder in order to determine if the standard may be used in free software. A particular RAND license could be incompatible with free software in several ways, such as requiring licensing fees, only applying to complete implementations of the licensed standard, limiting use to particular fields, or restricting redistribution. Some free software advocates argue that standards bodies should use a different term, such as "uniform fee only" (UFO), because they believe a license that charges for a patent license is inherently non-reasonable, and thus the term RAND is misleading.
One very successful area where RAND is in use is in the GSM and UMTS mobile phone standards where many different manufacturers compete to provide handsets and base stations. This is possible because the systems are based on open standards and because the patents required to implement this are mostly available under RAND terms. This situation is claimed, for example by the 3GPP to lead to strong price competition and lower market prices for this equipment both to consumers and to operators. This compares very well to other standards such as CDMA, where single companies may have almost complete control over particular areas of technology and manufacturing.
In contrast to the situation for GSM, the World Wide Web Consortium considered standardising on RAND principles, but, after considerable resistance from many different sources, abandoned this strategy in order to aim for royalty free licensing.
As the word "reasonable" is absolutely free in interpretation, standards of the RAND type can be used to keep small and mid-sized businesses away from the market. This can easily lead to oligopolies, where few big enterprises share the markets. Customers then have to pay inflated prices and technological and economical progress is decelerated.
The RAND-Z (RAND with zero royalty) or or RAND-RF (RAND Royalty Free) licensing means that the company promises to license the technology at no charge, but implementers still have to get the licenser's permission to implement. The licenser may not make money off the deal but can still stop some type of products or requre some type of reciprocity or do more subtle things like drag out the licensing process.
Improving in progress
Definition of Photoaging
The deterioration of biological functions and ability to manage metabolic stress is one of the major consequences of the ageing process. Aging is a complex, progressive process which also leads to functional and esthetic changes in the skin. This process could result from both intrinsic, such that it is genetically determined, as well as extrinsic processes which include environmental factors.
Photoaging is a process of ageing of the skin attributed to continuous, long-term exposure to ultraviolet (UV) radiation of approximately 245-290nm, natural or synthetic, on an intrinsically aged skin. Photoaging is thus also known as aging of the skin of the face, ears, neck and hands, caused by UVA and UVB rays.
Effects of UV light
UV and Molecular and Genetic Changes
UVB ray is considered as a primary mutagenthat can only penetrate through the epidermal or outermost layer of the skin, resulting in DNA mutations. These DNA mutationsarise due to chemical changes, the formation of cyclobutane pyrimidine dimers and photoproducts formed between adjacent pyrimidine bases. These mutations may be clinically related to specific signs of photoaging such as wrinkling, increasing in elastin and collagen damage.
The epidermal layer does not contain any blood vessels or nerve endings but melanocytes and basal cells are embedded in this layer. Upon exposure to UVB rays, melanocytes will produce melanin, a pigment that gives the skin its colour tone. However, UVB will cause the formation of freckles and dark spots, both of which are symptoms of Photoaging. With constant exposure to UVB rays, signs of Photoaging might appear and precancerous lesions or skin cancer may develop.
UVA rays are able to penetrate deeper into the skin as compared to UVB rays. Hence, in addition to the epidermal layer, the dermal layer will also be damaged. The dermis is the second major layer of the skin and it comprises of collagen, elastin, and extrafibrillar matrix which provides structural support to the skin. However, with constant UVA exposure, the size of the dermis layer will be reduced, thereby causing the epidermis to start drooping off the body. Due to the presence of blood vessels in the dermis, UVA rays could lead to dilated or broken blood vessels most commonly visible on the nose and cheeks. UVA can also damage DNA indirectly through the generation of reactive oxygen species (ROS) which includes superoxide anion, peroxide and singlet oxygen. These ROS damage cellular DNA as well as lipids and proteins (1).
UV and Pigmentation
UV exposure could also lead to inflammation and vasodilation which is clinically manisfested as sunburn. UV radiation activates the transcription factor, NF-κB, which is the first step in inflammation. NF-κB activation will result in the increase of proinflammatory cytokines eg interleukin 1 (IL-1), IL-6 vascular endothelial growth factor and tumor necrosis factor, TNF-α. This would then attract neutrophils which lead to an increase in oxidative damage through the generation of free radicals.
Additionally, UV radiation would cause the down-regulation of an angiogenesis inhibitor, thrombospondin-1, and the up-regulation of an angiogenesis activator which is platelet-derived endothelial cell growth factor, in keratinocytes. These enhance angiogenesis and aid in the growth of UV-induced neoplasms.
UV and Immunosupression
It has also been reported that UV radiation would lead to local and systemic immunosuppression, due to DNA damage and altered cytokine expression. This has implications in cutaneous tumor surveillance. The langerhan cells would undergo changes in terms of quantity, morphology and functions due to UV exposure and eventually becomes depleted. One of the reasons suggested to account for the presence of immunosuppression mediated by the body is due to the need to suppress or prevent an autoimmune response to inflammatory products resulting from UV-mediated damage.
UV and degradation of collagen
UV exposure would also lead to the activation of receptors for epidermal growth factor, IL-1 and TNF-α in keratinocytes and fibroblasts, which then activates signalling kinases throughout the skin via an unknown mechanism. The nuclear transcription factor activator protein, AP-1, which controls the transcription of matrix metalloproteinases (MMP), is expressed and activated. MMP-1 is a major metalloproteinases for collagen degradation. This entire process is aided by the presence of reactive oxygen species (ROS) that inhibits protein-tyrosine phosphatases via oxidation, thereby resulting in the up-regulation of the above mentioned receptors. Another transcription factor NF-κB, which is also activated by UV light, also increases the expression of MMP-9.
The up-regulation of MMP can occur even after minimal exposure to UV, hence, exposure to UV radiation which is inadequate to cause sunburn can thus facilitate the degradation of skin collagen and lead to presumably, eventual photoaging. Thus, collagen production is reduced in photoaged skin due to the process of constant degradation of collagen mediated by MMPs.
In addition, the presence of damaged collagen would also down-regulate the synthesis of new collagen. The impaired spreading and attachment of fibroblasts onto degraded collagen could be one of the contributing factors to the inhibition of collagen synthesis.
UV and Retinoic acids and Photodamage
Retinoic acid (RA) is essential for normal epithelial growth and differentiation as well as for maintenance of normal skin homeostasis. UV radiation decreases the expression of both retinoic acid receptors (RARs) and retinoid X receptors (RXRs) in human skin, thereby resulting in a complete loss of the induction of RA-responsive genes. It also would lead to an increase in activity of AP-1 pathway, increasing MMP activity and thus also resulting in a functional deficiency of vitamin A in the skin.
Signs, symptoms and histopathology
The early symptoms of Photoaging includes the following:
Dyspigmentation and the formation of wrinkles around regions of skin commonly exposed to sun, namely the eyes, mouth and forehead.
Spider veins on face and neck
Loss of colour and fullness in lips
Symptoms of Photoaging attributed to prolonged exposure to UV
Wrinkles deepen and forehead frown lines can be seen even when not frowning.
Telangiectasias most commonly seen around the nose, cheeks and chin.
Skin becomes leathery and laxity occurs.
Solar Lentigines (age spots) appears on the face and hands.
Possibly pre-cancerous red and scaly spots (actinic keratoses) appear.
Cutaneous malignancies
In addition to the above symptoms, photoaging could also result in an orderly maturation of keratinocytes and an increased in the cell population of the dermis where abundant; hyperplastic, elongated and collapsed fibroblasts and inflammatory infiltrates are found.
Photodamage could also be characterised as the disorganisation of collagen fibrils which constitute most of the connective tissue and the accumulation of abnormal, amorphous, elastin-containing material.
Endogenous Defence Mechanism against UV radiation
The endogenous defence mechanisms provide protection of the skin from damages induced by UV.
Epidermal thickness
UV exposure which would lead to an increase in epidermal thickness could help protect from further UV damage.
Pigment
It has been reported in many cases that fairer individuals who has lesser melanin pigment show more dermal DNA photodamage, infiltrating neutrophils, keratinocyte activation, IL-10 expression and increased MMPs after UV exposure. Therefore, the distribution of melanin provides protection from sunburn, Photoaging, and carcinogenesis by absorbing and scattering UV rays.
Repair of DNA mutation and apoptosis
The damage of DNA due to exposure of UV rays will lead to expression of p53, thereby leading to eventual arrest of the cell cycle. This allows DNA repair mediated by endogenous mechanisms like the nucleotide excision repair system. In addition, apoptosis occurs if the damage is too severe. However, the apoptotic mechanisms decline with age and if neither DNA repair mechanism nor apoptosis occurs, cutaneous tumorigenesis may result.
Tissue inhibitors of MMPs (TIMPs)
TIMPs regulate the activity of MMP. UV rays have been shown in many studies that it would induce TIMP-1.
Antioxidants
The skin consists of several antioxidants which include vitamin E, coenzyme Q10, ascorbate, carotenoids, superoxide dismutase, catalase and glutathione peroxidase. These antioxidants provide protection from ROS produced during normal cellular metabolism. However, too much exposure to UV rays could lead to a significant reduction in the antioxidant supply, leading to oxidative stress. Hence, these antioxidants are essential in the skin's defense mechanism against UV radiation and photocarcinogenesis.
Treatment of Photoaging
Treatment and intervention for photoaging can be classified into a unique paradigm based on disease prevention.
Primary prevention
Primary prevention aims to reduce the risk factors before a disease or condition occurs. Primary prevention method involves mainly sun protection that comes in many forms like sun avoidance, protective clothing, and sunscreens.
The UV exposure would be the strongest between 10am and 4pm and sun avoidance between this period of time is highly encouraged. If one cannot avoid exposure to the sun, clothing, hats and sunglasses that protects one from sun exposure should be fully utilised. Wide spectrum sun screens that have a sun protection factor (SPF) of at least 30 should be used when one gets frequent sun exposure.
Secondary protection
Secondary protection refers to early detection of disease, potentially while still asymptomatic, to allow positive interference to prevent, delay or attenuate the symptomatic clinical condition. This includes the following:
·Retinoids e.g. Tretinoin
·Antioxidants e.g. Tropical vitamin C, oral supplements, CoQ10, Lipoic acid
·Estrogens
·Growth factors and cytokines.
Tertiary prevention
Lastly, tertiary prevention is the treatment of an existing symptomatic disease process to ameliorate its effects or delay its progress. Such tertiary prevention includes the use of chemical peels, resurfacing techniques like micro-dermabrasion, the use of ablative and non-ablative laser systems, radiofrequency technology, the use of exotoxin Botulinum toxins and soft tissue augmentation, also known as fillers.
Summary of article: “Photoaging: Mechanism and repair”
Brief Introduction
The deterioration of biological functions and ability to manage metabolic stress is one of the major consequence of the aging process (1). Aging is a complex, progressive process which also leads to functional and esthetic changes in the skin (1). This process could result from both intrinsic, such that it is genetically determined, as well as extrinsic processes which include environmental factors (1).
Definition of Photoaging
Photoaging is the resulting effect of continuous, long-term ultraviolet (UV) exposure and sun damage on an intrinsically aged skin (1). Most often, fairer individuals are most severely affected. For photoaged skin, there would be a significant reduction in many functions of the skin (1).
Signs, symptoms and histopathology
The clinical signs and symptoms for a photoaged skin include dyspigmentation, laxity, a yellow hue, wrinkles, telangiectasia, leathery appearance, and cutaneous malignancies (1).
Additionally, photoaging could also result in an orderly maturation of keratinocytes and an increased in the cell population of the dermis where abundant, hyperplastic, elongated and collapsed fibroblasts and inflammatory infiltrates are found (1).
Photodamage could also characterised as the disorganisation of collagen fibrils which constitute most of the connective tissue and the accumulation of abnormal, amorphous, elastin-containing material (1). Fine wrinkles is another one of the prominent feature of a photoaged skin (1).
Effects of UV light on keratinocytes
UV and Molecular and Genetic Changes
UV radiation of appopximately 245 – 290 nm is maximally absorbed by DNA, where UVB is considered as a primary mutagen (1). UVB results in DNA mutations that arise due to chemical changes, the formation of cyclobutane pyrimidine dimers and photoproducts formed between adjacent pyrimidine bases (1). These mutations may be clinically related to specific signs of photoaging such as wrinkling, increasing in elastin and collagen damage (1).
UVA can also damage DNA indirectly through the generation of reactive oxygen species (ROS) which includes superoxide anion, peroxide and singlet oxygen. These ROS damage cellular DNA as well as lipids and proteins (1).
UV and Pigmentation
UV exposure could also lead to inflammation and vasodilation which is clinically manisfested as sunburn (1). UV radiation activates the transcription factor, NF-κB, which is the first step ininflammation. NF-κB activation will result in the increase of proinflammatory cytokines eg interleukin 1 (IL-1), IL-6 vascular endothelial growth factor and tumor necrosis factor, TNF-α (1). This would then attract neutrophils which leads to an increase in oxidative damage through the generation of free radicals (1).
Additionally, UV radiation would cause the downregulation of an angiogenesis inhibitor, thrombospondin-1, and the upregulation of an angiogenesis activator which is platelet-derived endothelial cell growth factor, in keratinocytes (1). These enhance angiogenesis and aid in the growth of UV-induced neoplasms (1).
UV and Immunosupression
It has also been reported that UV radiation would lead to local and systemic immunosuppression, due to DNA damage and altered cytokine expression (1). This has implications in cutaneous tumor surveillance (1).
UV and Extracellular Matrix
UV exposure would also lead to the activation of receptors for epidermal growth factor, IL-1 and TNF-α in keratinocytes and fibroblasts, which then activates signalling kinases throughout the skin (1). The nuclear transcription factor activator protein, AP-1, which controls the transcription of matrix metalloproteinases (MMP), is expressed and activated (1). MMP-1 is a major metalloproteinases for collagen degradation. NF-κB, which is also activated by UV light, also increases the expression of MMP-9 (1).Exposure to UV radiation which is inadequate to cause sunburn can thus facilitate the degradation of skin collagen and lead to presumably, eventual photoaging (1).
UV and Retinoic acids and Photodamage
Retinoic acid (RA) is essential for normal epithelial growth and differentiation as well as for maintenance of normal skin homeostasis (1). UV radiation decreases the expression of bothretinoic acid receptors (RARs) and retinoid X receptors (RXRs) in human skin which results in a complete loss of the induction of RA-responsive genes (1). It also would lead to an increase in activity of AP-1 pathway, increasing MMP activity and thus also resulting in a functional deficiency of vitamin A in the skin (1).
Endogenous Defense Mechanism Against UV radiation
Epidermal thickness
UV exposure which would lead to an increase in epidermal thickness could help protect from further UV damage (1).
Pigment
It has been reported in many cases that fairer individuals (lesser melanins) show more dermal DNA photodamage, infiltrating neutrophils, keratinocyte activation and IL-10 expression, increased MMPs after UV exposure (1). Therefore, the distribution of melanin provides protection from sunburn, photoaging and carcinogenesis by absorbing and scattering UV rays (1).
Repair of DNA mutation and apoptosis
When DNA is damaged by UV rays exposure, p53 transcription isactivated and cell will be arrested in the G1 phase so as to allow DNA repair by endogenous mechanisms like the nucleotide excision repair system (1). If the damage is too severe and cannot be repaired, it might trigger apoptosis to occur (1).
Tissue inhibitors of MMPs (TIMPs)
TIMPs regulate the activity of MMP. UV rays has been shown in many studies that it would induce TIMP-1 (1).
Antioxidants
The skin consists of several antioxidants which include vitamin E, coenzyme Q10, ascorbate, carotenoids, superoxide dismutase, catalase and glutathione peroxidase (1). These antioxidants provide protection from ROS produced (1). However, too much exposure to UV rays could lead to a significant reduction in the antioxidant supply, leading to oxidative stress (1). Hence, these antioxidants are essential in the skin's defense mechanism against UV radiation and photocarcinogenesis (1).
Treatment of Photoaging
Treatment and intervention for photoaging can be classified into a unique paradigm based on disease prevention (1).
Primary prevention is to reduce the risk factors before a disease or condition occurs that includes photoprotection or sun protection (1).
Secondary protection refers to early detection of disease, potentially while still asymptomatic, to allow positive interference to prevent, delay or attenuate the symptomatic clinical condition (1). This include the usage of retinoids, antioxidants, estrogens and growth factors or cytokines (1).
Lastly, tertiary prevention is the treatment of an existing symptomatic disease process to ameliorate its effects or delay its progress (1). Such tertiary prevention includes the use of chemical peels, resurfacing techniques like microdermabrasion, the use of ablative and nonablative laser systems, radiofrequency technology, the use of exotoxin Botulinum toxins and soft tissue augmentation, also known as fillers (1).
