The invention shows a transmission system with a transmitter function, a transmitting fiber and a receiver function where the transmitter function comprising lightsources (1), modulators (2) and a multiplexer (3), and the receiver comprising at least a demultiplexer (5), filters and electrical receivers where the channels for left side filtering are modulated with modulators with a negative chirp and for right side filtering with modulators with positive chirp.

The invention relates to the field of transmitting digital data by optical means. It is more particularly concerned with transmission at high bit rates on long-haul fiber optic links, based on wavelength division multiplexing (WDM).
More specifically, the invention is related to a modulation scheme for a signal transmitted via a WDM transmission line with alternating left side and right-side filtering for adjacent channels at the receiver, with channels with alternating channel spacing of A and B, , channels for right side filtering being modulated by a modulator with positive chirp and channels for left side filtering being modulated by a modulator with a negative chirp.
The invention is also related to a transmission system with a transmitter function, a transmitting fiber and a receiver function: where the transmitter function comprising laser sources, external modulators and a multiplexer where the receiver comprising at least a demultiplexer, filters and receivers and the channels for left side filtering are modulated with modulators with a negative chirp and for right side filtering with modulator with positive chirp.
At the transmitter end, each channel is modulated by passing into a modulator of a given chirp. As compared to using a chirp-free (zero-chirp) device, using a negative-chirp modulator is similar to passing into a small section of fiber with negative dispersion (e.g. of DCF fiber). Conversely, using a positive-chirp modulator is similar to passing into a small section of fiber with positive dispersion (e.g. of Standard Single-Mode Fiber G652).
After modulation, the optical spectrum of a given channel consists of a carrier and two optical sidebands apart the carrier. The lower-wavelength sideband is referred to next as "left side" and the higher-wavelength sideband is referred to as "right-side".
Such transmission scheme uses an optical transmitter connected to an optical receiver by the fiber. The transmitter generally modulates the power of an optical carrier wave from a laser oscillator as a function of the information to be transmitted. NRZ or RZ modulation is very frequently used and entails varying the power of the carrier wave between two levels: a low level corresponding to extinction of the wave and a high level corresponding to a maximum optical power. The variations of levels are triggered at times imposed by a clock rate and this defines successive time cells allocated to the binary data to be transmitted. By convention, the low and high levels respectively represent the binary values "0" and "1". The maximum transmission distance is generally limited by the ability of receivers to detect without error these two power levels after the modulated wave has propagated in the optical link. The usual way to increase this distance is to increase the ratio between the average optical power of the high levels and that of the low levels, this ratio defining the "extinction ratio" which is one of the characteristics of the modulation.
For a given distance and a given extinction ratio, the information bit rate is limited by chromatic dispersion generated in the fibers. This dispersion results from the effective index of the fiber depending on the wavelength of the wave transported, and it has the consequence that the width of the transmitted pulses increases as they propagate along the fiber. This phenomenon is characterized by the dispersion coefficient D of the fiber, which is defined as a function of the propagation constant β by the equation D=−(2πc/λ2)d2β/dω2, where λ and ω are respectively the wavelength and the angular frequency of the wave.
The value and sign of the dispersion coefficient D depend on the type of fiber and the transmission wavelength. For example, for the "standard" monomode fibers routinely used, and for λ=1.55 μm, the coefficient D is positive and has a value of 17 ps/(nm.km). In contrast, the coefficient D is zero for λ=1.30 μm. The coefficient D can generally be positive, zero or negative depending on the wavelength and the type of fiber used.
If the coefficient D has a non-zero value, to compensate the phenomenon of pulse widening in the case of NRZ or RZ modulation, it has already been proposed to modulate the phase φ (and therefore the frequency or the angular frequency) of the carrier wave in a manner that correlates to the modulation of the power. The phase φ (corresponds to the convention whereby the electric field of the carrier wave is represented as a function of time t by a complex expression of the type: Ap exp (jωot) and the field of a transmitted wave S of amplitude A is represented by: S=A exp [j(ωot+φ)], where ωo is the angular frequency of the carrier wave and φ is the phase of the transmitted wave.
To be more precise, to compensate chromatic dispersion, and if the coefficient D is positive, the phase must decrease on the rising edges of the pulses and increase on their falling edges. The modulated wave is then said to feature a transient negative "chirp". If, in contrast, the coefficient D is negative, the phase modulation must be reversed and the transient "chirp" is positive.
A transient "chirp" parameter α is introduced to characterize this modulation, and is defined by the equation α=2P(dφ/dt)/(dP/dt), where P is the power of the modulated wave and φ is its phase in radians. For the previously mentioned standard fibers and for values of λ close to 1.55 μm, for example, the value of the parameter α must be constant and substantially equal to −1 if by approximation a is regarded as constant. In an optimized system the chip of the modulator can compensate the chromatic dispersion of the fiber.
The problem chirping of a laser source can be solved to some extent by employing an external modulation technique. Among other external modulators, an absorption type modulator exhibits smaller chirping compared to semiconductor lasers; however, not zero. On the other hand, if a Mach-Zehnder modulator, which uses optical interference as its operational principle, is used as an external modulator operating in a push-pull modulation scheme, the wavelength chirping can be entirely removed theoretically. Accordingly, Mach-Zehnder modulators are expected to be key external modulators for use in ultra high-speed and long distance optical communication systems.
Some known Mach-Zehnder modulators have dielectric substances such as LiNbO3. On the other hand, semiconductor Mach-Zehnder modulators are considered to be advantageous over the dielectric type Mach-Zehnder modulators, in view of the integration capability with optical elements such as semiconductor lasers or semiconductor optical amplifiers and electric elements such as FETs, as well as in view of their smaller dimensions and lower power consumption.
A Mach-Zehnder modulator of this kind comprises an interferometer structure with an input optical guide that splits into two branches that are combined to form an output guide. Electrodes apply respective electric fields to the two branches. The semiconductor Mach-Zehnder modulator generally uses changes in the refractive index generated upon a reverse-bias voltages applied to a p-n junction. When the input optical guide receives a carrier wave of constant power, two partial waves propagate in the two branches and then interfere at the output. The output guide then supplies a wave whose power and phase depend on the values of the electrical control voltages applied to the electrodes. Phase shifts of approximately 180° can be produced at the times when the instantaneous power of the transmitted wave is zero.
If the modulated control signal is applied to only one of the electrodes and the other electrode receives a fixed bias voltage, the optical signal output by the modulator features a non-zero transient "chirp" which can be positive or negative, depending on the sequence of binary data encountered and whether the edge is a rising or falling edge.
In the U.S. Pat. No. 6,122,414 experiments show that push-pull modulation achieves a small waveform distortion due to pulse compression and thus maintains a half-value width better than a single arm modulation. From the results, it is considered that the push-pull modulation can provide a double or triple transmission distance compared to the single arm modulation.
A push-pull driven semiconductor Mach-Zehnder modulator generally requires a pair of drivers for applying drive voltages to electrodes of the respective phase modulators and a timing generator for driving the phase modulators exactly in opposite phases. It is difficult to accurately adjust the timing by the timing generator, especially at higher frequencies, for example, over 2.5 Gb/s, which fact renders the operation of the phase modulator arms to be difficult at such high frequencies.
The invention solves the problems of high bit rate transmission at least higher than 10 Gbit/s—using a single arm modulator for modulation and simultaneously an optimize modulation scheme for reducing bandwidth.
A modulation scheme know as VSB (vestigial side band modulation) is explained in "5.12 Tbit/s Transmission over 3×100 km of Teraliight fiber" Bigo, S. et al., paperPD2, PP40-41,ECOC 2000.
The two side bands of a NRZ spectrum generally contain redundant information. It is therefore tempting to filter out one of them in order to increase spectral efficiency, a technique known as VSB. However VSB is difficult to implement at the transmitter because the suppressed side bands rapidly reconstruct through fiber non linearities.
So a VSB filtering at the receiver side is proposed.

Modulation scheme and transmission system for NRZ signals with left and right side filtering


Astaxanthin is a potent antioxidant, over 500 times more powerful than Vitamin E and 10 times stronger than other carotenoids such as zeaxanthin, lutein, canthaxanthin and beta-carotene. Astaxanthin has also been shown to enhance and modulate the immune system. Disclosed is a method and treatment for retarding and preventing sunburns. The method comprises administering a source of astaxanthin in a therapeutically effective amount to prevent and retard sunburns.

This invention relates to the treatment and prevention of sunburns by UV light exposure. More particularly the invention relates to a method for prevention of sunburns using, as a basis, the protective properties of astaxanthin. Most particularly, the invention relates to prevention of sunburns using orally administered astaxanthin.
Tanning is pigmentation of the skin due to the synthesis and dispersion of melanin in the epidermis. It is of great cosmetic and societal significance and a key physiological defense against sun-induced injuries such as sunburn, photocarcinogenesis and photoaging. However, during recent decades, there has been a dramatic increase in skin cancers, including melanoma, due to habitual sun exposure. At present, in the United States, about one in 75 individuals are projected to develop malignant melanoma during their lifetime. Unfortunately, progress in preventing sun-related injuries has been slow, in part due to lack of understanding of the molecular mechanisms involved in pigmentation.
There have been increasing incidence and mortality rates due to melanoma in most countries where they are being recorded. The highest incidences occur in areas with the highest flux of solar radiation such as the southern US, regions near the equator or at higher elevations. Ultraviolet radiation (UVR) increases about 4% for every 1000 feet in elevation. Lighter-skinned individuals are affected more frequently and severely. Significant transmission of UVR may occur through some types of clothing resulting in sunburned skin. The initial approach in many countries has been to develop some form of early detection program in an attempt to diagnose and treat at a curable stage the melanomas that are occurring now. The long-term morbidity and mortality associated with chronic sun exposure is related primarily to the development of cutaneous neoplasms, including basal cell carcinoma and malignant carcinoma.
Primary prevention of melanoma is a more long-term approach to the problem which many countries are now considering and a number are actively pursuing. A survey conducted at Galveston beach showed that the likelihood of sunburn increased with increasing duration of sun exposure, with 100% of subjects experiencing sunburn after 4.5 hours of exposure. Men exhibited a significantly higher frequency of sunburn, employed fewer sun-protective measures, and demonstrated less knowledge concerning sun safety information and skin cancer than women. The information suggests a need for greater educational efforts directed toward changing public attitudes about preventing sunburn, especially those of men, that currently lead to high-risk sunbathing behavior (McCarthy et al. 1999).
Sunburns are an acute inflammation reaction of the skin and tissue just beneath it that follows excessive exposure of the skin to UVR. The affected area becomes red, hot, tender, and swollen and in severe cases blisters may form. The ultraviolet spectrum can be divided in UVA (320-400 nm), UVB (290-320 nm) and UVC (200-290 nm), wavelengths less than 290 nm are filtered out in the outer atmosphere and are not encountered at sea level. About 65% of the total UVR reaches the earth between 10 AM and 2 PM. UVB radiation are high intensity rays absorbed by the surface of the skin and the primary cause of sunburns, erythema and intermediate skin damage. UVA rays are lower intensity but penetrate below the skin surface causing long-term damage such as premature wrinkling. UVA comprises the majority of the total UVR reaching the surface of the earth (about 90% at midday) and accounts for a significant percentage of the acute and chronic cutaneous effects. UVC and UVB produce damage primarily by the formation of cyclobutane pyrimidine dimers of DNA. Pyrimidine dimers are 80-90% of the UV-light induced DNA photoproducts, with the remainder being pyrimidine (6,4) pyrimidone (Franklin and Haseltine, 1986).
Recent concern about stratospheric ozone depletion has contributed to the desire for the primary prevention approach. There are epidemiological data associating the risk of melanoma with increased exposure to sunlight in people with fair skin. The exact spectrum of radiation in sunlight which is responsible for these tumors is not known, although the ultraviolet range is believed to be most important, particularly UVB but probably also UVA. Studies show that sunburns in childhood result in increased risk of melanoma later in life. Protecting children is especially important since more than half of a person exposure occurs before the age of 20. It is estimated that approximately 80% of the skin changes commonly thought of as skin aging (premature wrinkles, leathery skin, 30 freckles, dark spots) are actually due to sun exposure and not to the actual age of the skin. The aging process affects the skin""s ability to protect itself. The rate of cell protection and turnover slows down with age, making cell repair less effective. The outer layer epidermis of the skin becomes thinner and melanocytes gradually lose their pigment producing ability, thereby reducing protection for the skin.
Skin cancer is the most common type of cancer, about 800,000 cases occur in the US each year. Most skin cancers are either basal cell or squamous type and tend to grow and spread slowly. Nearly 95% can be cured. Malignant melanoma is a much more serious form of skin cancer and is now increasing by about 4% per year. Melanoma was diagnosed in approximately 38,300 Americans in 1996. The overall five-year survival rate for melanoma is 85%. The five-year survival rate for localized disease is 93% and about 82% of melanomas are diagnosed in this earlier stage. The second-most common form of skin cancer, squamous cell carcinoma, appears as nodules or red scaly patches, and can spread if untreated. While the cure rate is relatively high, squamous cell carcinoma results in at least 1,200 deaths per year (Park and Gilchrest. 1999).
Less intense or shorter-duration exposure to UVR results in an increase in skin pigmentation that provides some protection against further UVR-induced damage. The increased skin pigmentation occurs in two phases, immediate pigment darkening and delayed tanning. Intermediate pigment darkening occurs during exposure to UVR and results from oxidation and redistribution of existing melanin. This reaction may fade rapidly or persist for several days. Delayed tanning results from increased synthesis of epidermal melanin and requires 24-72 hours to become visible. With repeated exposure to UVR, the skin thickens due to epidermal hyperplasia and thickening of the stratum corneum.
The minimal single dose of UVR (energy per unit area) required to produce erythema on exposed skin is known as minimal erythema dose (MED). Moderate to severe sunburn occurs at 3-8 MED""s. UVR penetrates moist skin more effectively than dry skin. MED""s are greater on the limbs than on the face, neck and trunk. Exposure to solar radiation has beneficial benefits of stimulating cutaneous synthesis of vitamin D. However, when skin is subjected to excessive radiation in the ultraviolet range (less than 400 nm), deleterious effects such as sunburn or xe2x80x98solar erythemaxe2x80x99 can occur. Solar erythema is associated with microscopic changes in the skin that are detectable within 30 minutes of UVR exposure. The most characteristic changes include formation of epidermal sunburn cells, damaged keratinocytes with hyaline cytoplasm and pyknotic nuclei. Epidermal Langerhans cells and mast cells may decrease while the relative percentage of hypogranulated or degranulated cells may increase. Superficial blood vessels show endothelial swelling, perivenular edema and a mixed perivascular infiltrate. The precise biochemical pathways that lead to the sunburn reaction are not fully understood, but appear to involve multiple mediators including histamine, prostaglandins and cytokines. Sunburns may cause exacerbation of other skin diseases, and trigger recurrence of herpes simplex, lupus, porphyria or other cutaneous disorders. Chronic sunburns and exposure to the sun can lead to multiple deleterious effects including premature aging and wrinkling of the skin (dermatoheliosis), development of pre-malignant lesions (solar keratoses) and various malignant tumors (e.g. basal cell, squamous cell and melanoma). Large freckles known as xe2x80x98age spotsxe2x80x99 and scaly growths (actinic keratoses) may develop into skin cancer.
Free radicals of oxygen have been shown to result from and mediate deleterious effects of ultraviolet radiation on the skin. One study showed that the number of sunburn to cells was decreased by treatment with the antioxidant tocopherol, and may result from both direct protection from free radicals and indirect protection by means of increased epidermal thickness. (Ritter E.F. et al, 1997). There is additional evidence that ultraviolet radiation induces the formation of reactive oxygen species and these are implicated as toxic intermediates in the pathogenesis of photoaging. One study examined whether repeated topical treatment with benzoyl peroxide, a source of free radicals, produced the same cutaneous effects as chronic ultraviolet B radiation. These results indicate that repeated administration of benzoyl peroxide produces skin changes in the hairless mouse that qualitatively resemble those produced by ultraviolet B and suggest that common mechanisms may be involved (Ibbotson S.H. et al., 1999).
Exposure of the skin to UVR triggers a chain reaction within skin cells that generates lipid peroxides and other high-energy free radicals. These molecules damage cellular components such as DNA, thereby increasing the risk of skin cancer development. Although the body utilizes an array of antioxidants such as vitamin E, vitamin C, selenium and superoxide dismutase to scavenge these free radicals, they can become quickly depleted under the severe stress of UVR exposure. One study showed that when a 10% solution of vitamin C was applied to the skin of volunteers, the amount of ultraviolet light needed for them to bum increased by an average of 22%. Once they did burn, half of the volunteers experienced much less severe bums than those without the vitamin C solution. In studies with laboratory animals, researchers found that vitamin E acetate, which converts to vitamin E in the body, prevented inflammation, skin sensitivity and skin damage when applied up to 8 hours following UVB exposure. In one human study, supplementation of dietary vitamin E and vitamin C elicited a 21% higher tolerance of MED than the control group (Eberlein-Konig B. et al. 1998).
A double-blind randomized study was designed to examine the influence of the antioxidant, melatonin, on the anti-erythema effect. Topical treatment of the skin with melatonin 15 min before UV irradiation proved to almost completely suppress the development of an UV-induced erythema. In contrast, no significant protective effects of melatonin were observed when it was applied after UV irradiation. The researchers concluded that topically applied melatonin has a clear-cut protective effect against UV-induced erythema. Free radical scavenging of UV-generated hydroxyl radicals and interference with the arachidonic acid metabolism are possible mechanisms of the melatonin action (Bangha E. et al, 1997).
There is some evidence that oral beta-carotene supplementation may lower skin-cancer rates in animals, but there is limited evidence of its effect in human beings (Roth and Krinski, 1985.). One double blind placebo-controlled study examined the effect of beta-carotene supplementation on the human sunburn response. However, the data suggested that oral beta-carotene supplementation is unlikely to modify the severity of cutaneous photodamage in normal individuals to a clinically meaningful degree (Garmyn M. et al. 1995). In a community-based randomized trial, individuals were assigned to four treatment groups: daily application of a sun protection factor 15-plus sunscreen to the head, neck, arms, and hands, and beta-carotene supplementation (30 mg per day); sunscreen plus placebo tablets; beta-carotene only; or placebo only. The endpoints after 4.5 years of follow-up were the incidence of basal-cell and squamous-cell carcinomas both in terms of people treated for newly diagnosed disease and in terms of the numbers of tumors that occurred. The 1383 participants underwent full skin examination and 250 of them developed 758 new skin cancers during the follow-up period. There were no significant differences in the incidence of first new skin cancers between groups randomly assigned daily sunscreen and no daily sunscreen. Similarly, there was no significant difference between the beta-carotene and placebo groups in incidence of either cancer. In terms of the number of tumors, there was no effect on incidence of basal-cell carcinoma by sunscreen use or by beta-carotene but the incidence of squamous-cell carcinoma was significantly lower in the sunscreen group than in the no daily sunscreen group (1115 vs 1832 per 100,000). The authors concluded that there was no harmful effect of daily use of sunscreen in this medium-term study. Cutaneous squamous-cell carcinoma, but not basal-cell carcinoma seems to be amenable to prevention through the routine use of sunscreen by adults for 4.5 years. There was no beneficial or harmful effect on the rates of either type of skin cancer, as a result of beta-carotene supplementation (Green et al. 1999).
There are numerous risk factors for the development of malignant melanomas including genetic and environmental aspects. The most important genetic risk factor is a mutation in the CDKN2A gene, which is a tumor suppressor-gene that regulates the cell cycle. In addition, the familial dysplastic nevus syndrome shows a marked risk for the development of malignant melanoma. Patients with xeroderma pigmentosum have an inability to repair UV-induced DNA defects. This constellation leads to early development of epitheliomas and malignant melanomas. Constitutional risk factors are fair-red hair and blue eyes with a high tendency for sunburns. The most important environmental factor is UV-exposition. Sunburns before the age of 15 and the total 10 cumulative UV-dosage are high impact risk factors. The most important preventive measures are to check the whole skin at a regular base in a patient with the familal dysplastic nevus syndrome, and in addition all such persons should wear a hat, trousers, shirt and glasses. Furthermore direct sun exposure should be avoided during noon time. (Itin P.H., 1999).
In general, prevention of sunburn should be the most important goal, but sunburn often cannot be avoided. Avoiding sun between the period of peak solar radiation from 10 AM to 3 PM and wearing protective clothing including hats is a major preventive method. Sunscreens have assumed a major component of primary prevention programs based on their convenience of use. Sunscreens work by absorbing, reflecting or scattering the sun""s rays on the skin and are labeled with sun protection factor (SPF) numbers. If one sunburns in 10 minutes, a SPF 15 formula will protect the skin for 15 times longer, or 150 minutes. These products protect predominantly in the UVB range for which there is a SPF grading, as well as having some activity in the UVA range. Regular use of sunscreens with an adequate sun protection factor (SPF) applied 30 minutes before exposure to sun can help protect skin. Chemical barriers are used in most sunscreens. PABA (para-amino benzoic acid) PABA esters and their derivatives such as octyl dimethyl PABA diffuse into the stratum corneum and bind to protect skin from UVR. However, PABA agents may stain clothing or cause contact dermatitis, and are not recommended for use on children less than 6 months of age. Other chemical blocking agents include cinnamates, salicylates, anthranilates and benzophenones or various combinations. However, all of these chemicals photodecompose into unknown compounds and the long-range safety effects have not been studied. Physical barriers such as zinc oxide, talc, and titanium dioxide provide excellent protection but are often not used because they are less appealing cosmetically. Oral canthaxanthin tablets have also been marketed as a form of xe2x80x98sunless tanningxe2x80x99 and protection against UVR (Marks R. 1999). Aspirin, ibuprofen, acetaminophen and other non-steroidal anti-inflammatory drugs (NSAID""s) have anti-prostaglandin effects and are useful to relieve pain and inflammation when given early. Systemic steroids may shorten the course and reduce pain of sunburn when given early and in relatively high doses. Topical steroids show minimal, if any benefit.
Algae and Astaxanthin:
Although natural sources of astaxanthin are numerous, nearly all are found in very low concentrations. Astaxanthin is quite common in nature, especially in the marine environment and is probably best known for providing the pinkish-red hue to the flesh of salmon and trout, as well as shrimp, lobsters and crayfish. These animals obtain astaxanthin in their diet from zooplankton, insects or crustaceans that have accumulated astaxanthin from phytoplankton.
The green algae Haematococcuspluvialis provides the most concentrated natural source of astaxanthin known, from 10,000-40,000 ppm (mg/kg) astaxanthin in addition to other important carotenoids such as beta-carotene, lutein and canthaxanthin. Whereas, the flesh of wild Atlantic salmon contain approximately 5 ppm of astaxanthin, Coho salmon about 14 ppm astaxanthin and sockeye salmon average 40 ppm (Turujman, 1997). Other sources of astaxanthin include processed crustacean wastes from krill, shrimp, crab and crawfish, the fermentative yeast Phaffia rhodozyma and chemically synthesized astaxanthin. Haematococcus pluvialis, also referred to as Haematococcus lacustris or Sphaerella lacustris, is a ubiquitous green alga of the order Volvocales, family Haematococcaceae. It is now known that the alga occurs in nature worldwide, where environmental conditions for its growth are favorable and most often found in cooler pools of fresh water such as garden birdbaths.
Under nutrient-rich conditions, Haematococcus is motile and utilizes the available nitrate, phosphate, and other nutrients to grow and reproduce. However, when nutrients become limiting or the pool begins to dry the alga form a protective cell wall and encyst. High concentrations of astaxanthin are produced, and the cells undergo a dormant stage until the next influx of water and nutrients. Cells can remain viable in this encysted stage with its protective astaxanthin for many years. Red cysts are significantly more resistant to strong light and oxygen radicals than green cells, suggesting significant protective roles for astaxanthin (Kobayashi et al., 1992a).
Astaxanthin, is biosynthesized through the isoprenoid pathway, which initiates at acetyl-Co-A and proceeds through phytoene, lycopene, beta-carotene, and canthaxanthin before the last oxidative steps to astaxanthin. Fatty acids are esterified onto the 3xe2x80x2 hydroxyl group(s) of astaxanthin after biosynthesis of the carotenoid, and allow it to have more solubility and stability in the cellular environment. The carotenoid fraction of green vegetative cells consists of mostly lutein (75-80%) and beta-carotene (10-20%). Whereas in red cysts, the predominate carotenoid is astaxanthin (Renstrom et al., 1981). Free astaxanthin and its mono- and diesters from Haematococcus have optically pure (3S,3xe2x80x2S)-chirality (Grung et al., 1992 and Renstrom et al., 1981).
Advanced technology has been developed to grow Haematococcus and harnesses the unique properties of the algae to produce very high concentrations of natural astaxanthin. Lots are generally standardized to contain 1.5% (15,000 ppm) astaxanthin, other beneficial carotenoids such as beta-carotene, canthaxanthin, and lutein are also present in lesser amounts. The astaxanthin is predominately in the esterified form, which provides the highest stability. Most importantly, the production process includes a technique which xe2x80x98cracksxe2x80x99 greater than 95% of the cells to enable maximum bioavailability, resulting in a fine dark red powder.
Dried Haematococcus algae, Phaffia yeast powder, or synthetic astaxanthin can be formulated into various food grade oils such as safflower, canola, tocopherols or rice bran and manufactured into gelcaps for convenient ingestion. Alternatively, dried Haematococcus algae, Phaffia yeast powder, or synthetic astaxanthin can be stabilized by various commercial processes and added directly to foods or beverages. Prior Research:
Ultraviolet radiation has long been known to cause epidermis photoaging and skin cancer. SKH 1 hairless mice sensitive to UV light are often used to understand the effects of artioxidants and light-induced polyamines. Polyamines are central to normal growth and activation of polyamine metabolism (putrescine in particular) is implicated in tumor promotion. In one study, female SKH1 hairless mice were weaned at eight weeks and fed six different diets containing 5-ppm beta-carotene, 10-ppm astaxanthin or retinol. After 4 months, one half of each group was exposed to ultraviolet light, sacrificed, and then putrescine, spermidine and spermine concentrations were measured in the epidermis. After irradiation, astaxanthin alone or in combination with retinol was remarkably effective in preventing increases of free putrescine after damage was induced. The putrescine of the control group increased 4.1-fold whereas the groups fed astaxanthin increased only 1.5-fold. Astaxanthin also had a stronger inhibitory effect on putrescine accumulation than dietary retinol. Additionally, spermidine and spermine concentrations were significantly lower in those groups fed astaxanthin. Taken together, the results indicate that astaxanthin exerts a specific action on transglutaminase enzymes to consume these polyamines in response to skin irradiation (Savoure, 1995).
In rat kidney fibroblasts, addition of astaxanthin exhibits superior protection against UVA light-induced oxidative stress compared to lutein and beta-carotene. Cell cultures were grown in differing concentrations of carotenoid-supplemented media and exposed to UVA light for four hours. Subsequently, various parameters were assayed. Catalase (CAT) and superoxide dismutase (SOD) were significantly decreased following the UV insult exposure compared to control cultures, whereas thiobarbituric acid reactive substances (TBARS) were significantly increased. Beta-carotene at a level of 1000 nM and lutein at 100 nM were necessary to protect against UV-induced loss of CAT, whereas it only required 5 nM of astaxanthin. Similarly, levels of 500 nM beta-carotene, 1000 nM of lutein and only 5 nM of astaxanthin were required to protect against loss of SOD activity compared to control cultures. Increases in thiobarbituric acid reactive substances (TBARS) were also measured as indices of oxidative stress. Supplementation of beta-carotene at 100 nM, lutein at 1000 nM and astaxanthin at only 1 nM prevented the UVA-induced increase in TBARS. The authors suggest that carotenoids other than beta-carotene, and particular astaxanthin, may be important biological antioxidants (O""Connor, 1998).
In one contradictory study, SKH hairless mice fed either beta-carotene, lycopene or astaxanthin as sole carotenoid sources tended to have higher probability of epidermal tumors. The authors state that it would be prudent to consume foods with mixed carcotenoids in addition to vitamins E and C, since they are thought to complete the antioxidant cascade (Black, 1998).
Researchers have developed a variety of methods to measure the antioxidant capacity of carotenoids. Some of these assays are conducted in test tubes (in vitro) to better control conditions or within cells themselves (in vivo). Typically, a chemical that generates free radicals or peroxides is mixed with a substrate such as a fatty acid that can become readily oxidized. When the reaction rate is determined, carotenoids or other antioxidants can then be added to determine how it quenches, or slows the peroxidation rate of the fatty acid. Numerous studies exist demonstrating the potent radical scavenging and singlet oxygen quenching properties of astaxanthin (Haila, 1997;Woodall, 1997;Nakagawa, 1997;Oshima, 1993; Tinkler, 1994). It has been demonstrated that astaxanthin is significantly more effective in neutralizing free radicals than beta-carotene and protects against peroxidation of unsaturated fatty acid methyl esters better than canthaxanthin, beta-carotene or zeaxanthin (Terao, 1989; Jorgensen, 1993).
The unique structure of astaxanthin scavenges lipid radicals and effectively breaks peroxide chain reactions (Terao, 1989). Di Mascio utilized a chemiluminescent technique to express the superior singlet oxygen quenching ability of astaxanthin compared to other carotenoids. He also concluded that the effectiveness and potency of astaxanthin was even better expressed at the lower oxygen concentrations found in tissues, as opposed to higher oxygen concentrations normally used with in vitro conditions (Di Mascio, 1989). Many antioxidant studies are conducted under conditions of low vitamin E (tocopherol) or vitamin A to better assess the actual effects of the added carotenoids. In vitamin E-deficient rats, astaxanthin protects the mitochondria from damage caused by lipid peroxidation.
The antioxidant activity of astaxanthin is much greater than vitamin E (Kurashige, 1990). A number of studies have shown that astaxanthin has an activity 80-550 times greater than alpha-tocopherol, also known as vitamin E (Di Mascio, 1989; Ranby and Rabek 1978; Shimidzu, 1996). One prominent researcher has proposed astaxanthin as the xe2x80x98super vitamin Exe2x80x99 (Miki, 1991). Although researchers use different assay systems, the antioxidant activity of astaxanthin has been shown to be approximately 10 times stronger than the antioxidant activity of other carotenoids such as zeaxanthin, lutein, beta-carotene and canthaxanthin (Miki, 1991).
Enzymatic and non-enzymatic antioxidant systems play a vital role in protecting tissues from excessive oxidative damage. Depletion of each of the antioxidant systems increases the vulnerability of various tissues and cellular components to reactive oxygen species (Ji, 1995). There is consistent evidence from human and animal studies that strenuous physical exercise may induce a state wherein the antioxidant defenses of several tissues are overwhelmed by excess reactive oxygen (Sen, 1995). For example, physical exercise causes oxidative stress that leads to the formation of reactive oxygen and nitrogen species (Poulsen, 1998; Caillaud, 1999). This may lead to DNA and muscle tissue damage.
Free radicals generated by oxidative stress have also been shown to change immune function and lead to an inflammatory response (Niess, 1999). Many components of the immune system exhibit adverse change after prolonged, intense exertion. A period of impaired immunity may last from 3 to 72 hours depending on the immune measure (Nieman, 1999). Prolonged stress as a result of excessive exercise can lead to a decline in certain aspects of immune system function such as natural killer cell cytotoxicity or secretory-IgA (Kelly, 1999)
Many researchers recommend the consumption of antioxidant compounds to counteract the oxidative damage that occurs free radical accumulation. Human studies have shown that dietary supplementation with antioxidant vitamins such as vitamin E and C have a favorable effect on lipid peroxidation after stress (Derkkers, 1996; Goldfarb, 1993; Kanter, 1998). Beta-carotene and antioxidant coenzyme Q10 have been suggested as dietary supplements to minimize the oxidative damage during stress (Witt, 1992). Selenium dietary supplements have also been shown to reduce free radical formation during exertion in rats (Konda, 1998).
Epidemiological studies have demonstrated a correlation between increased carotenoid intake and the reduced incidence of coronary heart disease and certain cancers, macular degeneration, and increased resistance to viral, bacterial, fungal and parasitic infections (Seddon, 1994; Zhang, 1999, Rao, 1999; Rumi, 1999; Batieha, 1993). Studies indicate that the mechanism for this protective attribute is partly due to the direct enhancement of the immune response by carotenoids. Anticarcinogenic effects of carotenoids are likely attributable to its antioxidant effect, insofar as oxygen radicals are related to the process of cancer initiation and propagation.
Singlet oxygen is also cytotoxic to the immune system by virtue of its ability to catalyze production of free radicals. This action can facilitate degradation of macrophage 25 cell membranes resulting in dysfunction and reduced efficiency of phagocytosis Bendich, 1991). Carotenoids have been shown to enhance both the non-specific and specific immune system and protect cell membranes and cellular DNA from mutation (Bendich A. 1989). Carotenoids have a significant stimulatory effect on the immune system, as seen by the proliferative response of spleen cells and thymocytes during antibody response of mice. Astaxanthin enhances the release of interleukin-1 alpha and tumor necrosis factor alpha in mice to a greater degree than canthaxanthin and beta-carotene. The conclusion of one study was that astaxanthin had the best cytokine-inducing activity and may provide an immunomodulating role (Okai, 1996).
In one series of immune system challenges, astaxanthin enhanced T-helper cell antibody production even when suboptimal amounts of antigen were present. Furthermore, astaxanthin, but not other carotenoids (canthaxanthin, beta-carotene, lutein, lycopene), increased the number of antibody-secreting cells from primed spleen cells (Jyonouchi, 1996). Using human blood, it was shown that astaxanthin enhances the production of IgM, IgA and IgG antibodies in response to T-dependent stimuli (Jyonouchi, 1995a and 1995b). Another study indicates a significant immunomodulating action of astaxanthin for humoral immune responses to T-dependent antigens and the authors suggest that carotenoid supplementation may be beneficial in restoring humoral immune responses in older animals. Furthermore, it was speculated that dietary carotenoids could reduce the chance of developing autoimmunity and malignancies by enhancing T-helper functions and promoting specific antibody responses (Jyonouchi, 1994).
Monocytes are a particular type of white blood cell which contain surface proteins that distinguish cancer cells from normal healthy ones. When these MHC II proteins identify cancer cells they signal the immune system to attack them. Monocytes do not identify cancer cells if the monocytes don""t have enough MHC II proteins. It was demonstrated that supplementation with a carotenoid in the diet increases the number of MHC II proteins on monocytes. In turn, subjects had increased production of tumor necrosis factor alpha (TNF-a) which helps kills cancerous and virus-infected cells (Hughs, 1997).
Supplementation with carotenoids increases the number of circulating lymphocytes (T-helper cells), enhances T and B lymphocyte proliferation, improves rejection of foreign tissue, increases killer cell destruction of tumor cells and neutrophil killing of Candida fingi, and inhibits loss of macrophage receptors (Bendich, 1990). Mice fed carotenoids had significantly reduced tumor growth when the primary lesion was excised and then re-challenged with the same tumor (Tomita, 1987). Virus-induced tumors such as murine sarcoma are slowed by carotenoids, as well as adenocarcinoma, squamous cell carcinoma, fibrosarcoma, and chemically induced tumors (Bendich, 1990). These studies present strong evidence that orally administered astaxanthin and other carotenoids can directly affect the immune responses to foreign antigens and cancerous tumors.
In summary, with respect to the prevention ultimately of skin cancers, prevention of sunburn should be the most important goal. Avoiding sun during the period of peak solar radiation from 10 AM to 3 PM and wearing protective clothing including hats offers the best protection against sunburn. Regular use of sunscreens with an adequate sun protection factor (SPF) applied 30 minutes before exposure to sun can also help protect skin. Despite all of the precautions available, people are still exposed to excessive UVR each year and many sunburns result. Thus, in addition to those methods currently known, there remains a need for additional effective sunburn protection and prevention. The easiest form of sunburn prevention would be an oral form of sunburn prevention.
Astaxanthin is a potent antioxidant, over 500 times more powerful than Vitamin E and 10 times stronger than other carotenoids such as zeaxanthin, lutein, canthaxanthin and beta-carotene. Astaxanthin has also been shown to enhance and modulate the immune system. These effects in combination or separately are able to retard and prevent sunburns, and possibly some resulting skin cancers, when astaxanthin is ingested, injected, or delivered by a cream in a therapeutically effective dose.
Thus one aspect of the invention is to produce an inexpensive means to retard and prevent sunburns and possibly sunburn related cancers.
Another aspect of the invention is to provide a means to retard and prevent sunburns that is ingestible.
A further aspect of the invention is to provide a means to retard and prevent sunburns in a cream formulation for topical application.
Yet another aspect of the invention is to provide a means to retard and prevent sunburns that is injectable.
Another aspect of the invention is to use the unique antioxidant and immune modulation properties of astaxanthin to retard and prevent sunburns, or related cancers.
A still further aspect of the invention is to provide a therapeutically effective dose of astaxanthin in the range of about 1-100 mg per day to retard and prevent sunburns.

Method for retarding and preventing sunburn by UV light


An adhesive packaging tape comprising a backing and an adhesive composition, wherein the adhesive composition is coated onto the backing as a butadiene/acrylate dispersion having a butadiene content of more than 50% in a blend with resin dispersion and is then dried.

The invention relates to the development of pressure sensitive adhesive tapes based on butadiene/acrylate latices having a high butadiene content and resin dispersions.
In the patent literature there exists a large number of applications on the production of adhesive packaging tapes.
The time honored adhesive composition systems for adhesive packaging tapes are based essentially on natural rubber, styrene block copolymers and polyacrylates.
The natural rubber systems are commonly used as solutions in an aliphatic solvent mixture. Water based natural rubber compositions based on centrifuge latex are likewise known. For the required adhesive properties it is vital to add resins, fillers and aging inhibitors. Crosslinking takes place either chemically by way of added crosslinking agents or physically by way, for example, of electron beam curing.
Synthetic rubbers based on styrene block copolymers have also been described in the past as adhesive compositions for adhesive packaging tapes. These are 100% systems, which, after blending with resins and further coagents, may be applied in the melt state in the absence of solvents or water.
The use of polyacrylates as adhesive compositions for adhesive packaging tapes is likewise known. Besides solutions of polyacrylates, there have also been descriptions in the past of polyacrylate dispersions, which, after compounding with resin dispersions and further coagents, meet the requirements of an adhesive packaging tape composition. Acrylate dispersions exhibit relatively poor tack to cartons, especially when the substrate originates from papers which have been recycled a number of times, which is increasingly the case with packaging cartons. By adding resin dispersions this deficiency can be eliminated. Since natural resin dispersions based on rosin derivatives often have an undesirable influence on the cohesion of acrylate compositions, there is a tendency to use the more cohesive hydrocarbon resin dispersions, which are offered by a variety of resin producers.
Backing materials commonly used for adhesive packaging tapes are monoaxially or biaxially oriented polyolefins, PVC types or papers.
In the pressure sensitive adhesives field, butadiene/styrene latices have been used for many years to impregnate and stabilize backing materials. These backing materials include, primarily, papers, wovens, and nonwovens. Because of the application, the impregnation or coating must in no case be tacky. The butadiene/styrene copolymers used for this application must therefore contain a relatively high fraction of hardening monomers, but on the other hand must include sufficient softening monomer that the copolymer overall remains elastic. Butadiene/styrene latices with a butadiene content of about 25-50% fulfill this requirement very effectively. Depending on the butadiene content, films of these copolymers have an elasticity ranging from moderate to good and are not tacky. Such monomers have been available on the raw materials market for many years now (Butofan(copyright) grades from BASF, various grades from Dow and Synthomer). Because of their preparation, such latices and dispersions include emulsifier systems in order to bring about compatibility between the organic phase and the aqueous phase.
In the past, butadiene/styrene copolymers have also been used as base polymers for label compositions. In the labels segment, cohesion is frequently of secondary importance, so that, following compounding with customary tackifiers, weakly adhering systems exhibit properties which are sufficient in many cases.
As a framework polymer for adhesive packaging tape compositions, butadiene/styrene based copolymers with little or no tack are often poorly suited, since they can be made tacky only with considerable quantities of tackifier resins, which in turn is associated with a substantial loss of cohesion. This rules out their use as adhesive compositions for adhesive packaging tapes.
Butadiene/styrene copolymers or butadiene/methyl methacrylate copolymers having a high butadiene content, on the other hand, are of great interest as framework polymers for adhesive packaging tapes.
Butadiene copolymers having a high butadiene content and containing a hard and thus cohesive segment as copolymerization partner are suitable as framework polymers for high performance pressure sensitive adhesive compositions, but exhibit only moderate tack on critical substrates. It is an object of the invention to provide adhesive compositions based on butadiene copolymers which do not have the aforementioned deficiencies and with which it is possible to make a pressure-sensitive adhesive tape which meets the requirements of an adhesive packaging tape.
This object has been achieved through the use of butadiene/acrylate dispersions having a high butadiene content which have been blended with suitable resin dispersions.
The group of the butadiene/acrylate copolymers comprises framework polymers of butadiene and a moderately hard comonomer such as butyl acrylate, for example. Butadiene/acrylate copolymers have markedly lower glass transition points than butadiene/styrene or butadiene/methyl methacrylate copolymers. At a butadiene content of about 75%, the glass transition point may be lowered by about 15xc2x0 C. to xe2x88x9270xc2x0 C. by passing from styrene to, for example, butyl acrylate as comonomer.
The compound formulations comprising framework polymer and resin dispersion may be admixed, if desired, with further coagents such as, for example, aging inhibitors or further emulsifiers, in order to improve the protection against aging, or to further adapt the unrolling properties to the application. After the adhesive composition has been coated onto a polymer or paper backing it is possible to obtain a pressure sensitive adhesive tape which entirely meets the requirements of an adhesive packaging tape in respect of tack, bond strength, cohesion, and unrolling properties.
Adhesive compositions:
The copolymerization of butadiene with acrylates such as butyl acrylate, for example, in an aqueous medium provides copolymers which are film forming and which have a glass transition point which is suitable for pressure sensitive adhering. Butadiene/acrylate dispersions are generally stabilized by incorporating small amounts of carboxyl-containing groups, which at the same time improves the adhesion to many substrates.
As adhesive compositions for the invention it is possible in particular to use carboxylated butadiene/acrylate copolymer dispersions having a butadiene fraction of 50-95%, preferably 60-85%, based on the overall butadiene and acrylate solids fraction, which in a mixture with resin dispersions exhibit outstanding suitability as adhesive compositions for adhesive packaging tapes. Carboxylated copolymers of this kind contain in particular below 10%, preferably below 5%, based on the monomer content, of carboxyl-containing comonomer, especially acrylic acid, in the copolymer.
Butadiene/acrylate dispersion types of the invention having a butadiene content  greater than 60% are available, for example, from Dow.
As the resin component it is possible to use not only dispersions of synthetic resins (e.g. hydrocarbon resins, terpene phenolic resins, etc.) but also natural resin dispersions (e.g., rosin derivatives, polyterpenes etc.).
Owing to their high cohesion, there is a distinct preference for hydrocarbon resin dispersions. The melting point of the base resins should be situated in the range 50-120xc2x0 C., preferably 60-100xc2x0 C. Based on the overall solids content in terms of butadiene/acrylate copolymer and resin, the resin fraction should be situated in the range 5-60%, preferably 10-40%. To tailor the adhesive properties it is also possible to use mixtures of different resins. To improve the aging behavior it is possible to add dispersions of customary aging inhibitors which are well known from the field of elastomers.
Furthermore, as and when required, it is possible to add further additives to modify the product properties, such as fillers, soft resins, oils or emulsifiers, for example, of the alkoxylated alkylphenol type. Using these additives it is possible to exert the desired influence over the unrolling properties.
The setting of the adhesion/cohesion balance may be done by chemical crosslinking, by way of the carboxyl groups present, by means of added crosslinking agents such as aluminum or titanium chelate, for example. In contrast to what is the case with many styrene block copolymers, radiation crosslinking is likewise possible owing to the sufficiently high molecular weight.
An overview of possible resin dispersions is given in Donatas Satas, Handbook of Pressure Sensitive Adhesive Technology, 2nd Edition Resin Dispersion by Anne Z. Casey, pp. 545-566.
Resin dispersions of the invention are obtainable, for example, through Hercules (NL).
The adhesive application rate is 10-120 g/m2, preferably 15-40 g/m2.
Backing materials:
Backing materials suitable for the invention are the backing materials customary for packaging applications. That is, essentially, films and papers whose properties and the production and/or aftertreatment process give them the requisite mechanical properties.
In the case of the films, those involved are substantially polyethylene, polypropylene, polyvinyl chloride, and other polymers and copolymers customary for the application, which may be used in either one or more layers. In the case of multilayer systems there may also be variation in the composition and thickness of the individual layers.
Monoaxially and biaxially oriented polypropylenes are frequently used for adhesive packaging tapes, strapping tapes and other adhesive tapes where a defined tensile strength is of not inconsiderable importance.
Monoaxially oriented polypropylenes exhibit particularly good tensile strength and little extension in the machine direction. Backing materials of this kind are frequently used for strapping applications.
In order to achieve uniform strength values in the machine and cross directions, the films must be oriented biaxially.
Both monoaxially and biaxially oriented polypropylenes and polyethylenes are particularly suitable as backing material for the invention. The stretch ratios are guided by the particular requirements.
Both blown film and flat film may be used.
The thicknesses of the films are between 10 and 250 xcexcm, preferably between 20 and 120 xcexcm.
In order to ensure sufficient adhesion of the adhesive composition to the backing material, the surface energy of the side to be coated must be situated within a defined range. This may be ensured either by way of an additional coating with a primer or by way of a surface treatment. Preference is given to a corona or flame pretreatment with which the desired surface energies may be achieved. The surface energies should be situated within a range of 25-50 mN/m, preferably 30-45 mN/m.
Suitable backing materials further include impregnated and highly sized papers with a defined crepe and having tensile strengths which satisfy the desired requirements. Depending on the desired application, it is possible to use not only papers having higher machine-direction than cross-direction extensibility but also papers having higher cross-direction than machine-direction extensibility, both in bleached form and in the environmentally friendly unbleached form.
All percentages are by weight.


A process and system for separating water from bio-oil by using a partial condenser. The process comprises partially condensing vapor conversion products from a biomass conversion reaction to produce a water-rich overhead stream and a water-depleted stream comprising condensed bio-oil. The partial condenser removes a substantial portion of the water from the bio-oil, while providing an effective and flexible process for producing bio-oil.

1. Field of the Invention
The present invention relates generally to the treatment of bio-oil. More specifically, the invention concerns processes and systems for removing water from bio-oil.
2. Description of the Related Art
With its low cost and wide availability, biomass has increasingly been emphasized as an ideal feedstock in alternative fuel research. Consequently, many different conversion processes have been developed that use biomass as a feedstock to produce useful biofuels and/or specialty chemicals. Existing biomass conversion processes include, for example, combustion, gasification, slow pyrolysis, fast pyrolysis, liquefaction, and enzymatic conversion. One of the useful products that may be derived from the aforementioned biomass conversion processes is a liquid product commonly referred to as "bio-oil." Bio-oil may be processed into transportation fuels, hydrocarbon chemicals, and/or specialty chemicals.
Despite recent advancements in biomass conversion processes, many of the existing biomass conversion processes produce bio-oils containing high amounts of water. These bio-oils with excess water are not readily miscible with hydrocarbons due to their high polarity and, thus, require extensive secondary upgrading in order to be utilized as transportation fuels, hydrocarbon chemicals, and/or specialty chemicals.
Bio-oils can be subjected to various separation methods in order to remove the excess water. Such separation methods may utilize distillation columns and/or total condensers to condense all the bio-oil and water for separation. However, many valuable water-soluble organic compounds are incidentally removed during these water removal processes, thus decreasing the bio-oil yield. A portion of these water-soluble organic compounds may be subsequently recovered from the removed water, but such processes have proven to be costly and energy inefficient.
Accordingly, there is a need for an improved process and system for removing water from bio-oil that maximizes energy efficiency.