Information

Could being exposed to excess UV in the arctic lead to a human eye color change? If so, what is the mechanism?


The CBS News article Expedition Antarctica: A father and son's journey to save the planet says (in part):

Thirty-two years ago, Robert Swan made history as the first person to walk to both poles. Even as a young man, these grueling expeditions took a harsh toll on his body. Passing directly beneath the hole in the ozone layer, Swan's face became badly burned and his eyes even changed color. But the Arctic explorer now says that all of that physical duress pales in comparison to the agony of watching his son go through the same experience 32 years later. (emphasis added)

Skin color change can happen after exposure to UV light. From Wikipedia:

Melanin is a natural pigment produced by cells called melanocytes in a process called melanogenesis.

Question: Can the human eye really change color due to excess UV light from the Sun, in this case through a polar "hole" in the ozone layer? If so, what is the mechanism?

above: "This winter, Barney and Robert Swan became the first explorers to ever trek to the South Pole surviving exclusively off of renewable energy." Robert (the elder) is on the right. From here. Credit: SHELL-Technical Partners


A photobiological approach to biophilic design in extreme climates

The biophilic design approach has potential benefits in extreme cold climates, especially for Nordic occupants.

Lighting design should be developed to deal with the challenging state of living and working in northern latitudes.

Non-image-forming effects of light have become the missing link between human needs and lighting design standards.

Adaptive envelopes should be developed to optimize biophilic quality and fulfil the photobiological needs of Nordic people.


Abstract

Ions, including anions and heavy metals, are extremely toxic and easily accumulate in the human body, threatening the health of humans and even causing human death at low concentrations. It is therefore necessary to detect these toxic ions in low concentrations in water. Fluorescent sensing is a good method for detecting these ions, but some conventional dyes often exhibit an aggregation caused quench (ACQ) effect in their solid state, limiting their large-scale application. Fluorescent probes based on aggregation-induced emission (AIE) properties have received significant attention due to their high fluorescence quantum yields in their nano aggragated states, easy fabrication, use of moderate conditions, and selevtive recognization of organic/inorganic compounds in water with obvious changes in fluorescence. We surmarize the recent advances of AIE-based sensors for low concentration toxic ion detection in water. The detection probes can be divided into three categories: chemical reaction types, chemical interaction types and physical interaction types. Chemical reaction types utilize nucleophilic addition and coordination reaction, while chemical interaction types rely on hydrogen bonding and anion-π interactions. The physical interaction types are composed of electrostatic attractions. We finally comment on the challenges and outlook of AIE-active sensors.


Which Biomolecules Can Host an Electronically Excited State?

A colored object is an excited object. It reflects the wavelength responsible for that color and absorbs the others, with the absorbed photons exciting pigments in that tree or painting as long as daylight remains. But these are short-lived singlet states that dissipate as heat. For triplet states, the ideal host for a dioxetane loses an electron easily, providing a site for O2 attack, and also has an electron-deficient site to which the –O–OH can cyclize. Molecular rings containing delocalized electrons (aromatic molecules) are candidates and several are important in biochemistry, including melanin, indoles, and flavins.

Melanin has many unusual properties. It is an effective protective pigment because of its broad and peakless light absorption spectrum ranging from UV to infrared. But it also absorbs sound, hosts persistent radicals, scavenges free radicals, and binds large amounts of Ca ++ and metal ions when exposed to UV, it ionizes easily, generates O2 •− and 1 O2*, and can rapidly dissipate energy by proton transfer [24�]. Melanin′s structure is uncertain, but it appears to be a stack of planar aromatic oligomers. Its monomers are quinones, aromatic rings containing a pair of carbonyls that readily interconvert with an –OH form to ‘transduce’ between 1-electron and 2-electron transfer reactions, facilitate charge transfer, and form charge-transfer complexes that bind drugs which are facile electron donors [28, 29]. These properties may be the reason melanin is found throughout the body – ion buffering and radical scavenging have been proposed – but they also augment the electron transfer and excitation reactions that underlie chemiexcitation. Yet melanin may be the tip of the iceberg, with other families of molecules also able to host chemiexcited states.

Melanin and its eumelanin monomers are members of the broader class of indoles, a merger of two electron-rich rings that lose electrons easily and undergo n→π* transitions. The indole family includes tryptophan, the hormone melatonin, and the neurotransmitter serotonin, each of which can form a dioxetane [21, 30]. A ring of four pyrroles constitutes the porphyrin of heme, the iron-containing compound found in hemoglobin and a cofactor in many enzymes where it transfers electrons. Melanin’s catechol ring may also form dioxetanes [31] and it is similar to the catecholamine neurotransmitters such as dopamine and noradrenaline. Polymers of oxidized serotonin, dopamine, or related neurotransmitters, bound to protein and lipid, constitute neuromelanin [32].

A separate class of electron-exchanging molecules are flavins. These three-ring compounds contain two nitrogens that can accept hydrogen, allowing it to also conduct 1- or 2-electron reactions. These are also frequently cofactors in enzymes.

Non-aromatic dioxetane hosts also exist, including chains of conjugated double bonds such as polyunsaturated lipids [33]. Carbonyls and imine compounds (C=N) can also do this an example is a sugar that acquires a =N by reacting with an amino acid (the "Maillard reaction") [34, 35].

We see that cells contain a surprisingly large collection of molecules whose electrons can be excited, even if excitation is not the molecule’s normal function.


Life in the laboratory box

The idea that laboratory mice have been selected over a century for traits associated with both husbandry, such as fast maturation and ease of handling, and with those of specific scientific interest, such as predisposition to the diseases for which they are used as models, is perhaps expected. However, strains differ considerably in their ‘wildness’ and aggression (Wahlsten et al., 2003). Some commonly used strains, such as SPRET/EiJ, are notoriously difficult to handle. The AKR strain, which shows a high incidence of leukemia, has a very high degree of intra-strain aggression (Simon, 1979). AKR was derived from a pet shop stock in the 1920s and SPRET/EiJ from wild captured Mus spretus stock from Spain in the late 1970s. It is unclear whether aggression was co-selected during the active selection for the desired strain characteristics in the research laboratory environment, or whether it was retained in these and other strains. However, it is quite evident that rearing in a laboratory environment does not automatically result in selection for docile mice.

An example of laboratory selection from wild-type variation is that of the progressive retinal degeneration phenotype associated with the rd1 allele (Pde6b rd1 ), first discovered in CBA mice and then as independent spontaneous mutations in C57BL/6 and C3H mice (Farber et al., 1994). These mice are used as a model for human retinal degenerative diseases such as autosomal recessive retinitis pigmentosa (OMIM:180072). Retinal degeneration mutations are found in many mouse strains, but it is unclear whether these have been selected by the laboratory environment itself or whether the environment is simply permissive for their spread through laboratory strains. It would seem likely that mice carrying these mutations would not have survived in the wild. However, they have been found in some recent wild-derived inbred strains, implying that the mutations may be present in some wild populations (Chang et al., 2002). Retinal degeneration mutations are similarly relatively common in the human population, with 1 in 2000-3000 individuals having some form of genetic retinal degenerative disease (Veleri et al., 2015).


Conclusion

We believe that a fundamental failure to understand the genetic basis for the ethnic variability in susceptibility to obesity in the developed world is a contributory factor in the modern obesity pandemic in these countries. The obesity pandemic has coincided with not only an increase in poor eating habits but also mass immigration of various ethnicities in these countries. Whereas the thrifty and drifty genotype hypotheses make the assumption that the selection pressures faced by the ancestors of all inhabitants of developed countries today were the same, we have argued that this is not entirely accurate. The descendants of early humans who remained in Africa and those who migrated to equally tropical or subtropical environments such as black Americans and Pacific Islanders maintained heat adaption genes. The descendants of those who migrated to colder regions such as Europe and Siberia such as Caucasians and Chinese acquired genes for cold adaptation. A group of early Siberians who migrated to the Americas and settled in subtropical regions in North and Central America lost their cold adaptive genes and reacquired genes for heat adaptation. We postulate that positive selection for cold adaptation in their ancestors equips Caucasians and East Asians such as Chinese, Japanese, and Koreans with efficient BAT and UCP1 function, an advantageous by-product of which is a higher metabolic rate and resistance to obesity. The opposite is true for Africans and South Asians whose ancestors had no need to evolve efficient BAT and UCP1 function, resulting in an increased propensity for obesity in these populations when combined with a sedentary and hypercaloric western lifestyle. Figure 1 is a diagrammatic representation of the impact of historical human migration on selection of genes for heat and cold adaptation and consequent obesity prevalence in industrialized countries today. In summary, we suggest that the modern obesity pandemic in the developed world is largely due to differential climatic exposure of the ancestors of present day people in these countries as a result of historical human migration that began when modern humans left Africa 40 000 to 60 000 years ago. This new perspective has crucial implications for combating obesity in industrialized countries.

Map of historic human migration out of Africa 70 000 years ago (70k). By 60 000 years ago (60k), humans had reached Central Asia from where a population headed northeast into Siberia and Northeast Asia, acquiring genes for cold adaptation, which also confer higher resting metabolic rates (RMRs) and thus resistance to obesity (Obes). A second group of migrants from Central Asia headed north and west into Europe, also acquiring genes for cold adaptation, displacing the resident Neanderthals. A third group migrated south, through Southeast Asia and into Australia, and maintained genes for heat adaptation. Their descendants, the Aborigines, still inhabit Australia and have low resting metabolic rates and an increased propensity for obesity and type 2 diabetes (T2D). A group of Northeast Asians crossed the Bering Strait 20 000 years ago (20k) into Alaska. Some of their descendants still inhabit the Canadian Arctic and are highly resistant to cold and have exceptionally high resting metabolic rates. Some Mongoloids migrated south along the Pacific coast of North America toward Mexico where they encountered hotter climates and reacquired genes for heat adaptation, discarding those for cold. Their descendants, the Pima Indians, have some of the highest rates of obesity and cardiovascular disease (CVD) in the world. Their evolutionary cousins, the Yaghan people of the Tierra del Fuego whose ancestors continued the southern migration toward the subantarctic South American Cone, probably reevolved BAT capability and have high resting metabolic rates.

Map of historic human migration out of Africa 70 000 years ago (70k). By 60 000 years ago (60k), humans had reached Central Asia from where a population headed northeast into Siberia and Northeast Asia, acquiring genes for cold adaptation, which also confer higher resting metabolic rates (RMRs) and thus resistance to obesity (Obes). A second group of migrants from Central Asia headed north and west into Europe, also acquiring genes for cold adaptation, displacing the resident Neanderthals. A third group migrated south, through Southeast Asia and into Australia, and maintained genes for heat adaptation. Their descendants, the Aborigines, still inhabit Australia and have low resting metabolic rates and an increased propensity for obesity and type 2 diabetes (T2D). A group of Northeast Asians crossed the Bering Strait 20 000 years ago (20k) into Alaska. Some of their descendants still inhabit the Canadian Arctic and are highly resistant to cold and have exceptionally high resting metabolic rates. Some Mongoloids migrated south along the Pacific coast of North America toward Mexico where they encountered hotter climates and reacquired genes for heat adaptation, discarding those for cold. Their descendants, the Pima Indians, have some of the highest rates of obesity and cardiovascular disease (CVD) in the world. Their evolutionary cousins, the Yaghan people of the Tierra del Fuego whose ancestors continued the southern migration toward the subantarctic South American Cone, probably reevolved BAT capability and have high resting metabolic rates.


Effects of Nuclear Earth-Penetrator and Other Weapons (2005)

EFFECTS ON HUMANS

The health effects of nuclear explosions are due primarily to air blast, thermal radiation, initial nuclear radiation, and residual nuclear radiation or fallout.

Blast. Nuclear explosions produce air-blast effects similar to those produced by conventional explosives. The shock wave can directly injure humans by rupturing eardrums or lungs or by hurling people at high speed, but most casualties occur because of collapsing structures and flying debris.

Thermal radiation. Unlike conventional explosions, a single nuclear explosion can generate an intense pulse of thermal radiation that can start fires and burn skin over large areas. In some cases, the fires ignited by the explosion can coalesce into a firestorm, preventing the escape of survivors. Though difficult to predict accurately, it is expected that thermal effects from a nuclear explosion would be the cause of significant casualties.

Initial radiation. Nuclear detonations release large amounts of neutron and gamma radiation. Relative to other effects, initial radiation is an important cause of casualties only for low-yield explosions (less than 10 kilotons).

Fallout. When a nuclear detonation occurs close to the ground surface, soil mixes with the highly radioactive fission products from the weapon. The debris is carried by the wind and falls back to Earth over a period of minutes to hours.

The first three of these effects are &ldquoprompt&rdquo effects, because the harm is inflicted immediately after the detonation. By contrast, the radiation dose from fallout is delivered over an extended period, as described in Chapter 5. Most of the dose from fallout is due to external exposure to gamma radiation from radionuclides deposited on the ground, and this is the only exposure pathway considered by the computer models that the Defense Threat Reduction Agency (DTRA) and Lawrence Livermore National Laboratory (LLNL) used to estimate health effects for this study. Below is a discussion of the possible

contribution of other exposure pathways, such as inhalation of contaminated air and consumption of contaminated water and food, to the total radiation dose received by humans.

Radiation has both acute and latent health effects. Acute effects include radiation sickness or death resulting from high doses of radiation (greater than 1 sievert [Sv], or 100 rems) delivered over a few days. The principal latent effect is cancer. Estimates of latent cancer fatalities are based largely on results of the long-term follow-up of the survivors of the atomic bombings in Japan. The results of these studies have been interpreted by the International Commission on Radiological Protection (ICRP) 1 in terms of a lifetime risk coefficient of 0.05 per sievert (5 × 10 &minus4 per rem), with no threshold. 2 For the present study, acute radiation effects were estimated by both DTRA and LLNL latent cancer deaths were estimated only by LLNL.

The computer models used by DTRA and LLNL were developed primarily to estimate effects on military personnel rather than for civilian populations. Thus, there is no consideration of the presumed greater sensitivity to radiation of the very young and the elderly. Also, there is no consideration of the sensitivity of the fetus. From the experience in Japan, it is known that substantial effects on the fetus can occur, and these effects depend on the age (stage of organogenesis) of the fetus. 3 One such effect is mental retardation. The transfer of radio nuclides to the fetus resulting from their intake by the mother is another pathway of concern. Radiation dose coefficients for this pathway have been published by the ICRP. 4

Another long-term health effect that is not considered here is the induction of eye cataracts. This effect has been noted in the Japanese studies and also in a study of the Chernobyl cleanup workers. 5

Compared to the fatalities from prompt, acute fallout and latent cancer fatalities, the absolute number of effects on the fetus is small and is captured within the bounds of the uncertainty. The number of eye cataracts, based on the experience of the Chernobyl workers, is not small. The occurrence of eye cataracts in the now aging Japanese population is several tens of percent among those more heavily exposed.

Finally, there has been a recently confirmed finding that the Japanese survivors are experiencing a statistically significant increase in the occurrence of a number of noncancer diseases, 6 including hypertension, myocardial infarction, thyroid disease, cataracts, chronic liver disease and cirrhosis, and, in females, uterine myoma. There has been a negative response in the occurrence of glaucoma. A nominal risk coefficient for the seven categories of disease is about 0.9 Sv &minus1 (0.009 rem &minus1 ). The largest fraction of the risk is due to thyroid disease.

Thermal Radiation from Underground Bursts

Thermal radiation may make fire a collateral effect of the use of surface burst, airburst, or shallow-penetrating nuclear weapons. The potential for fire damage depends on the nature of the burst and the surroundings. If there is a fireball, fires will be a direct result of the absorption of thermal radiation. Fires can also result as an indirect effect of the destruction caused by a blast wave, which can, for example, upset stoves and furnaces, rupture gas lines, and so on. A shallow-penetrating nuclear weapon of, say, 100 to 300 kilotons at a 3 to 5 meter depth of burst will generate a substantial fireball that will not fade as fast as the air blast.

Detonation of a nuclear weapon in a forested area virtually guarantees fire damage at ranges greater than the range of air-blast damage. If the burst is in a city environment where buildings are closely spaced, say less than 10 to 15 meters, fires will spread from burning buildings to adjacent ones. In Germany and Japan in World War II, safe separation distance ranged from about 30 to 50 feet (for a 50 percent probability of spread), but for modern urban areas this distance could be larger. This type of damage is less likely to occur in suburban areas where buildings are more widely separated.

Once started, fire spread continues until the fire runs out of fuel or until the distance to the next source of fuel is too great. Thus, fire caused directly by thermal ignitions, fire caused indirectly by disruptive blast waves, and spread of fire are all potential, but uncertain, effects.

Illustrative Example: Washington, D.C.

The area over which casualties would occur as a result of the various weapon effects outlined above depends primarily on the explosive yield of the weapon and the height or depth of the burst. The areas affected by initial nuclear radiation and fallout also depend on the design of the weapon (in particular, the fraction of the yield that is derived from fission reactions), and, in the case of fallout, on weather conditions during and after the explosion (notably wind speed and direction, atmospheric stability, precipitation, and so on), terrain, and geology in the area of the explosion. The following calculations assume that the entire population is static and in the open.

As an illustrative example, 7 Figure 6.1 shows the area over which an individual in the open would face a 10, 50, and 90 percent chance of death or serious injury 8 from the prompt effects of a 10-kiloton earth-penetrator weapon (EPW) detonated at a depth of 3 meters and from the prompt effects of a 250 kiloton surface burst. (As discussed in Chapter 5, both of these weapons would produce a ground shock of about 1 kilobar at a depth of 70 meters.) These contours, which were produced by the DTRA using the Hazard Prediction and Assessment Capability (HPAC) code, are shown on a map of Washington, D.C., for scale. Figure 6.2 is similar, but also includes the probability of death or serious injury from acute exposure to external gamma radiation from fallout, for illustrative weather conditions, assuming hypothetically that 50 percent of the weapon yield is derived from fission and that a static population is in the open.

Figure 6.3 compares the numbers of casualties (deaths and serious injuries) due to prompt and acute effects of fallout from the use of both weapons. Under these conditions and assumptions, the 10 kiloton EPW is estimated to result in about 100,000 casualties, compared with 800,000 casualties for the

FIGURE 6.1 Illustrative example: The area over which an individual in the open would face a 10, 50, and 90 percent chance of death or serious injury from the prompt effects of a 10 kiloton earth-penetrator weapon (EPW left) and a 250 kiloton surface burst (right) detonated at 7:00 p.m. on July 14, 2004, in Washington, D.C. SOURCE: Estimates prepared for the committee by the Defense Threat Reduction Agency.

FIGURE 6.2 Illustrative example: The area over which an individual in the open would face a 10, 50, and 90 percent chance of death or serious injury from the prompt effects of fallout from a 10 kiloton earth-penetrator weapon (EPW left) and a 250 kiloton surface burst (right) detonated at 7:00 p.m. on July 14, 2004, in Washington, D.C. SOURCE: Estimates prepared for the committee by the Defense Threat Reduction Agency.

FIGURE 6.3 Illustrative example: Comparison of the number of casualties (deaths and serious injuries) from prompt and acute effects of fallout from a 10 kiloton earth-penetrator weapon (EPW) and a 250 kiloton surface burst detonated at 7:00 p.m. on July 14, 2004, in Washington, D.C. SOURCE: Estimates prepared for the committee by the Defense Threat Reduction Agency.

250 kiloton surface burst. Thus, in this example the use of an EPW would reduce casualties by about a factor of eight compared with a surface burst with equal destructive capacity against a buried target. Fallout is responsible for about 75 percent of the casualties from the 10 kiloton explosion compared with about 60 percent of the casualties from the 250 kiloton explosion.

The hazard to people entering the area after the explosion in these scenarios would be due largely to external gamma radiation from fallout. This hazard decreases rapidly with time: the dose rate after 1 week is 10 times less than the dose rate 1 day after the explosion, and after 2 months it is reduced by an additional factor of 10. Figures 6.4 and 6.5 illustrate this decay for the cases described above (the 10 kiloton EPW and the 250 kiloton surface burst), respectively, showing the areas exceeding a dose rate of 0.01, 0.1, 1, and 10 millisieverts per hour (1, 10, 100, and 1,000 millirems per hour) at 1 day, 1 week, 1 month, and 6 months after the explosion.

To put the dose rates referred to above in perspective, a person who remained indefinitely in an area where the dose rate was 1 millirem per hour at the time of that person&rsquos entry into the area would receive a total dose of less than 50 millisieverts (5 rems), which is the annual dose limit for U.S. nuclear workers. 9 Thus, military personnel could enter the unshaded areas shown in Figures 6.4 and 6.5 at the times indicated with minimal risk. Depending on the risk that is judged acceptable by commanders,

FIGURE 6.4 Illustrative example: Areas within which the dose rate from external gamma radiation exceeds 1, 10, 100, and 1,000 millirems per hour at 1 day, 1 week, 1 month, and 6 months after the detonation of a 10 kiloton earth-penetrator weapon at 7:00 p.m. on July 14, 2004, in Washington, D.C. SOURCE: Estimates prepared for the committee by the Defense Threat Reduction Agency.

FIGURE 6.5 Illustrative example: Areas within which the dose rate from external gamma radiation exceeds 1,10, 100, and 1,000 millirems per hour at 1 day, 1 week, 1 month, and 6 months after the detonation of a 250 kiloton surface burst at 7:00 p.m. on July 14, 2004, in Washington, D.C. SOURCE: Estimates prepared for the committee by the Defense Threat Reduction Agency.

soldiers could enter shaded areas for various periods of time. For example, a soldier entering the 10 millisieverts per hour (1,000 millirems per hour) contour 1 day after the explosion would accumulate a total dose of about 0.25 sievert (25 rems) over the next 2 days and 0.50 sievert (50 rems) over the next 2 weeks. U.S. regulatory guidelines allow doses of up to 0.25 sievert (25 rems) in lifesaving emergency situations, and the U.S. National Council on Radiation Protection and Measurements (NCRP) recommends that doses up to 0.50 sievert (50 rems) be allowed in such situations provided that individuals are aware of the risks. 10 Two reports from the Institute of Medicine address the U.S. Army guidance for situations in which troops might receive as much as 0.70 sievert (70 rems ). 11 Doses of 0.25 to 0.70 sievert (25 to 70 rems) are unlikely to cause serious acute effects, but they may ultimately cause death due to cancer in 1 to 3 percent of those exposed (in addition to the roughly 20 percent lifetime risk of dying of cancer from other causes).

Other Targets and Weapons Yields 12

The estimates shown in Figures 6.1 through 6.5 apply only to a particular set of assumptions about target location, weather, and weapons used to attack the target. The number of civilian casualties that would result from an attack depends on many variables, including the following: the distribution of the population around the point of detonation and the degree of sheltering that they have against blast, thermal, and radiation effects weapon yield and design height or depth of burst and weather conditions during and after the explosion. As shown below, the estimated number of casualties ranges over four orders of magnitude&mdashfrom hundreds to over a million&mdashdepending on the combination of assumptions used.

To explore in a parametric way the range of possibilities, the committee selected three notional targets:

Target A: an underground command-and-control facility in a densely populated area 3 kilometers from the center of a city with a population of about 3 million

Target B: an underground chemical warfare facility 60 kilometers from the nearest city and 13 kilometers from a small town and

Target C: a large, underground nuclear weapons storage facility 20 kilometers from a small town.

In each case, the committee asked DTRA to estimate the mean number of casualties (deaths and serious injuries from prompt effects, and acute effects of fallout from external gamma radiation) resulting from attacks with earth-penetrating weapons with yields ranging from 1 kiloton to 1 megaton, for populations completely in the open and completely indoors. The means are averages over annual wind patterns, but they ignore precipitation. DTRA also estimated the mean number of casualties resulting from surface bursts with yields from 25 kilotons to 7.5 megatons. For selected cases, the committee asked the Lawrence Livermore National Laboratory to estimate the number of deaths from prompt effects and fallout, and to quantify the variability in acute and latent deaths from fallout owing to wind patterns.

For Figures 6.6 and 6.7 the calculations assume that the entire population is static and in the open. Figure 6.6 shows the estimated mean number of casualties resulting from attacks on Targets A, B, and C with surface-burst weapons and earth-penetrator weapons of a range of yields from 1 kt to 10 kt, with the EPW detonated at a depth of 3 meters, assuming a static population in the open. Note that for a given yield there is little or no difference between the effects of surface bursts and the EPWs. 13 The curves for Target A are relatively flat (a factor-of-10 increase in yield produces a factor-of-2 increase in casualties) because the population is clustered around the target. The curves for Targets B and C are steeper (a

FIGURE 6.6 Estimated mean number of casualties (deaths and serious injuries) from attacks on notional targets A, B, and C using earth-penetrator weapons at 3 meters&rsquo depth of burst and surface bursts, assuming a static population in the open. SOURCE: Estimates prepared for the committee by the Defense Threat Reduction Agency.

FIGURE 6.7 Estimated mean number of casualties from prompt effects and acute radiation sickness and death from fallout resulting from attacks on notional targets A, B, and C using earth-penetrator weapons (EPWs) at 3 meters&rsquo depth of burst, assuming the entire population is in the open. SOURCE: Estimates prepared for the committee by the Defense Threat Reduction Agency.

factor-of-10 increase in yield produces a factor-of-6 to -10 increase in casualties), largely because the effects from higher-yield explosions can reach more-distant population centers.

Figure 6.7 shows the contributions of prompt effects and acute radiation sickness and death from fallout to the casualty estimates for EPWs. (The number of casualties is similar for surface bursts of the same yield.) Note that for yields of less than 300 kilotons, fallout is responsible for more casualties than are prompt effects. This is particularly true for Targets B and C, for which fallout is the only effect of low-yield explosions that can reach population centers.

It is always useful to compare model predictions against relevant experience. Fortunately, the relevant experience is very limited. In the case of the 15 kiloton device detonated over Hiroshima, an estimated 68,000 persons died and 76,000 persons were injured out of a total population of 250,000. For the 21 kiloton device detonated over Nagasaki, it is estimated that 38,000 persons died and 21,000 persons were injured out of a total population of 170,000. 14 These estimates are in rough agreement with the estimated 200,000 prompt-effects casualties shown in Figure 6.7 for Target A, taking into account differences in the size of the vulnerable populations. (The Hiroshima and Nagasaki weapons were detonated at a fallout-free height of about 500 meters and therefore produced no local fallout.)

As mentioned, the results shown in Figures 6.1 through 6.7 assume that the entire population is static and in the open. Assuming that the entire population remains indoors and is thereby shielded from radiation reduces mean total casualties by a factor of up to 4 for Target A, and by a factor of 2 to 8 for Targets B and C. Not accounted for are post attack movement or evacuation of the population, but it is unlikely that individuals could, by fleeing the area of an attack, reduce their exposure to fallout significantly more than by remaining indoors. Indeed, some people might greatly increase their exposure to fallout if they were to move through highly contaminated areas, as might occur if a major road out of the city were directly under the path of the cloud. Thus, in a population that has received no warning of an attack, the actual effects of sheltering and evacuation are likely to lie between the two extremes for a population that is assumed to be entirely indoors and one that is assumed to be entirely outdoors.

The use of an EPW instead of a surface-burst weapon generally will result in fewer casualties, because the yield of the EPW can be 15 to 25 times smaller than the yield of a surface-burst weapon for a given level of damage against a hard and deeply buried target (HDBT). Figure 6.8 shows the ratio of the mean number of casualties estimated for a surface burst to the mean number estimated for an EPW with a yield 25 times smaller, for Targets A, B, and C. For Target A, casualties are reduced by a factor of 7 at low yields appropriate for target depths of less than 100 meters and by a factor of 2 at high yields and deeper targets. For Target B, casualties are reduced by a factor of 10 to 30, and for Target C, by a factor of 15 to 60, depending on the yield and assumptions about shielding. In general, the reduction factor is larger for targets in rural or remote areas.

The DTRA results presented above do not include latent cancer deaths from fallout. The committee asked LLNL to estimate the mean number of latent cancer deaths for Targets A and B, for yields from 10 to 300 kilotons. 15 In the case of Target A, the inclusion of latent cancer deaths increased the total estimated number of fatalities by less than 20 percent. In the case of Target B, however, the inclusion of cancer deaths doubled the total number of fatalities. Including cancer deaths has little effect on the ratios shown in Figure 6.8.

The results given in Figures 6.6 through 6.8 are averages over annual wind patterns. Casualties from fallout can be substantially higher or lower, depending on the particular wind conditions during and immediately following the attack. Figures 6.9(a) and (b) show the variation in the number of deaths due to acute and latent effects from fallout from a 300 kiloton EPW on Targets A and B, respectively, as a function of wind direction. For Target A, estimated fatalities from fallout vary by more than an order of magnitude depending on wind direction, ranging from 90,000 to 800,000 for acute effects and from

FIGURE 6.8 Ratio of the estimated mean number of casualties from a surface burst to the mean number from an earth-penetrator weapon (EPW) with a yield 25 times smaller, for notional targets A, B, and C, assuming a static population entirely in the open or entirely indoors. SOURCE: Estimates prepared for the committee by the Defense Threat Reduction Agency.

30,000 to 200,000 for latent effects total fatalities, however, vary by less than a factor two, from 1 million to 2 million. For Target B estimated fatalities from fallout vary by more than two orders of magnitude depending on wind direction, from 3,000 to 1 million for acute fatalities, and ranging from 3,000 to 300,000 for latent fatalities total fatalities vary by a factor of 50, from about 15,000 to 800,000. Similarly large variations in fatalities are also possible if the target is just outside a major city. For example, if the detonation is moved 30 kilometers northwest of Target A (hereafter referred to as Target A), total fatalities vary from 50,000 to nearly 2 million, depending on whether the wind blows away from or toward the city center. Note that these estimates do not include the effects of precipitation, which would wash out and concentrate fallout in particular areas (which may or may not be populated). The committee expects that including the effects of precipitation would make the weather-related variability in the estimated number of casualties significantly greater than is suggested by this analysis. Of course, as mentioned frequently, Figure 6.9(a) and (b) are model runs and therefore are subject to the sources of uncertainty described in this report and emphasized in Chapter 8.

Figures 6.10(a) and (b) use the information in Figures 6.9(a) and (b), together with the likelihood that the wind blows in each direction, to compute the probability of exceeding a given number of deaths due to acute and latent effects from fallout, as well as from all effects, for attacks with a 300 kiloton EPW on Targets A and B. In the case of Target A, for example, the 50 percent confidence interval for deaths due to acute effects of fallout (based solely on variability in wind direction) is 130,000 to 600,000 that is, there is a 75 percent chance of exceeding 130,000 deaths from acute effects of fallout, and a 25 percent chance of more than 600,000 deaths. The 50 percent confidence interval for total fatalities is considerably narrower: 1.1 million to 1.6 million. If the detonation is moved 30 kilometers northwest of Target A, the confidence intervals are much wider: 13,000 to 700,000 for deaths from acute

FIGURE 6.9(a) Variation in the estimated number of fatalities due to acute and latent effects from external gamma radiation from fallout from a 300 kiloton earth-penetrator weapon at 3 meters&rsquo depth of burst on notional target A as a function of wind direction, assuming that the population is in the open. SOURCE: Estimates prepared for the committee by the Lawrence Livermore National Laboratory.

FIGURE 6.9(b) Variation in the estimated number of fatalities due to acute and latent effects from external exposure to gamma-radiation fallout from a 300 kiloton earth-penetrator weapon at 3 meters&rsquo depth of burst on notional target B as a function of wind direction, assuming that the population is in the open. SOURCE: Estimates prepared for the committee by the Lawrence Livermore National Laboratory.


Structure

Alveoli are tiny balloon shaped structures and are the smallest passageway in the respiratory system. The alveoli are very thin, allowing the relatively easy passage of oxygen and carbon dioxide (CO2) between the alveoli and blood vessels called capillaries.

One cubic millimeter of lung tissue contains around 170 alveoli. While the total number can vary from one person to the next, there are literally millions within the human lungs spanning a surface area of roughly 70 square meters.

Cells of the Alveoli

The alveoli are made up of two different types of cells that have different functions:

  • Type I pneumocytes are the cells that are responsible for the exchange of oxygen and carbon dioxide.
  • Type II pneumocytes perform two important functions. They are responsible for repairing damage to the alveolar lining and also secrete surfactant.

There are also many immune cells known as alveolar macrophages in the alveoli. Macrophages are essentially the "garbage trucks" of the immune system, and phagocytize or "eat" debris they come across. They are responsible for cleaning up any particles that are not caught by the cilia or mucus in the upper respiratory tract, as well as dead cells and bacteria.


Introduction

Cataracts are a leading cause of blindness worldwide and are characterized by opacification of the ocular lens. The only available current treatment for cataract is the surgical removal of the lens and replacement with a synthetic one. Alternative treatments would be enormously valuable, particularly for third-world countries due to the relatively excessive cost of the surgery and limited access to trained surgeons. Development of alternative therapeutic options is significantly hindered by the fact that an in vitro model of cataractous aggregates that mimics the naturally forming aggregates is not available for testing drugs, understanding aggregation initiation, etc. Considering cataract as a protein aggregation disease and applying a strategy similar to that utilized with neurodegenerative disorders, it’s possible to elucidate the fibrillation mechanism in vitro and further utilize these fibrils as a platform for drug testing. In this regard, research focusing on in vitro cataractous fibril formation from the aggregation of a variety of crystallin proteins has been intensely investigated under various denaturing conditions: heat, denaturant chemicals, pH shifts and UV-radiation [1–4].

Ocular lens transparency is maintained by multiple factors, including the presence of a high concentration of crystallin proteins and the level of chaperone content within the lens tissue [5]. Lens epithelial cells surrounding the lens capsule maintain the transport to the lens and continue to differentiate into fiber cells with a decline with age. The decreased α-crystallin expressions in lens epithelial cells could be associated with cataractogenesis [6–8]. Moreover, due to the fact that the fiber cells within the adult lens have lost their ability to express new proteins [9], any damage to crystallin proteins within the lens accumulates over time, and this accumulation ultimately causes a loss in protein solubility, leading to the formation of cataractous fibrils [5].

A wide variety of protein modifications have been identified in cataractous tissues: deamination, oxidation, racemization, truncation, phosphorylation and backbone cleavage [10, 11]. These modifications arise by the natural pathways of ageing (oxidative stress) [12] and exposure to ultraviolet light [13]. Even though, various denaturing conditions have been shown to initiate crystallin aggregation in vitro, the sensitivity of different crystallin classes varies depending on the denaturant. For instance, α-crystallin is not affected by heat inactivation as much as it is affected by UV-photodamage [14]. Moreover it’s shown that α-crystallin can enhance its chaperone activity against photodamage after partially unfolding its quaternary structure by pre-incubation at higher temperatures up to 60 ° C [15]. On the other hand β-crystallins are more resistant to UV-induced aggregation than are γ-crystallins [16–18]. More importantly, the different denaturant sensitivities of crystallins designate the pathway of aggregation and in return result in aggregates with divergent structures. For instance, at microscopic scale, it is possible to observe the formation of granular structures under heat denaturation versus fibrillar assembly under acid-induction of γ-crystallin [4]. When compared to using acid to induce aggregates, UV-B induced aggregation results in covalent structure alterations such as cross-linking, polypeptide cleavage, and side chain damage in γ-crystallin [19]. In light of this, it can be said that all crystallin aggregates will structurally differ from each other depending on the denaturant conditions and therefore it will be impossible to suggest either a generalized pathway for aggregation or a common solution for their reverse aggregation.

In order to build a platform to study the characterization and development of cataracts and to investigate alternative therapies for treating cataracts, it is crucial to have a system that forms cataractous fibrils under similar conditions as experienced in vivo. Among all applicable denaturant conditions, UV radiation may be the most relevant to disease initiation and progression. The effect of exposure to UV radiation in sunlight has already been associated with the formation of age-related cataracts [12, 20]. Also, it has been shown that UV induced aggregation of recombinant crystallins exhibit the same properties as proteins isolated from in vivo cataracts [21]. Within the UV spectrum, UVA (400–315 nm) lights that can penetrate deeper to the lens tissue are found to generate less damage to the ocular tissues compared to high-energy UVB (315–280 nm) lights, which are mostly absorbed by atmospheric ozone, upper eyelids and aqueous humor [22–27]. This effect can be associated with the presence of aromatic amino acid residues in crystallin proteins typically absorb in the wavelength range of UVB radiation [25, 28]. In general, photo-oxidation of proteins occurs due to the UV absorption by chromophore groups, which are tryptophan, tyrosine, phenylalanine, histidine and cysteine residues. Among them tryptophan residues are the most significant ones that absorb and filter most of the UV radiation within the range of 240–310 nm [29, 30]. However, long-term photo-oxidation results with their conversions -tryptophan to N-formylkynurenine and kynurenine, methionine to sulphoxide and cysteine to cysteine-, which introduces additional groups to the protein and therefore affect their hydrophobicity, stability and unfolding dynamics [31, 32]. Besides, the backbone cleavages (fragmentation of the protein) and cross-linking between altered histidine residues and lysine, cysteine or other histidine residues emanate. Collectively these alterations are found to result with high molecular weight, aggregated protein structures [33]. The effect of UV damage on lens tissue is prevented by the presence of UV filters. However, as a result of aging process, the concentration of UV filters in the lens decreases over time and the UV damage can be observed and lead to cataract formation [33].

So far, the aggregation profiles and aggregate structures of different crystallin classes have been studied under ultraviolet radiation and provide valuable information for individual proteins [34–37]. However lens tissue is composed of three different crystallin classes (namely α, β and γ-crystallins). Accordingly, aggregates formed within the lens are composed of various crystallin proteins. For this reason, we investigated the UV-B induced aggregation of recombinant α:β:γ crystallin mixtures in different ratios. Although it is evident that all three crystalline classes are found in in vivo aggregates, this situation is rarely studied in as systematic a manner as presented herein. Our results confirmed the development of amyloid-like fibrils, which were prone to protection by α-crystallin, as it should be in the natural eye. Thus, we believe, that mixture can serve as a platform for studying cataract formation and for testing the efficiency of drug candidates.


Antioxidants and antioxidant methods: an updated overview

Antioxidants had a growing interest owing to their protective roles in food and pharmaceutical products against oxidative deterioration and in the body and against oxidative stress-mediated pathological processes. Screening of antioxidant properties of plants and plant-derived compounds requires appropriate methods, which address the mechanism of antioxidant activity and focus on the kinetics of the reactions including the antioxidants. Many studies evaluating the antioxidant activity of various samples of research interest using different methods in food and human health have been conducted. These methods are classified, described, and discussed in this review. Methods based on inhibited autoxidation are the most suited for termination-enhancing antioxidants and for chain-breaking antioxidants, while different specific studies are needed for preventive antioxidants. For this purpose, the most common methods used in vitro determination of antioxidant capacity of food constituents were examined. Also, a selection of chemical testing methods was critically reviewed and highlighted. In addition, their advantages, disadvantages, limitations and usefulness were discussed and investigated for pure molecules and raw extracts. The effect and influence of the reaction medium on the performance of antioxidants are also addressed. Hence, this overview provides a basis and rationale for developing standardized antioxidant methods for the food, nutraceuticals, and dietary supplement industries. In addition, the most important advantages and shortcomings of each method were detected and highlighted. The chemical principles of these methods are outlined and critically discussed. The chemical principles of methods of 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulphonate) radical (ABTS ·+ ) scavenging, 1,1-diphenyl-2-picrylhydrazyl (DPPH·) radical scavenging, Fe 3+ –Fe 2+ transformation assay, ferric reducing antioxidant power (FRAP) assay, cupric ions (Cu 2+ ) reducing power assay (Cuprac), Folin–Ciocalteu reducing capacity (FCR assay), peroxyl radical (ROO·), superoxide radical anion (O2 ·− ), hydrogen peroxide (H2O2) scavenging assay, hydroxyl radical (OH·) scavenging assay, singlet oxygen ( 1 O2) quenching assay, nitric oxide radical (NO·) scavenging assay and chemiluminescence assay are outlined and critically discussed. Also, the general antioxidant aspects of main food components were discussed by a number of methods, which are currently used for the detection of antioxidant properties of food components. This review consists of two main sections. The first section is devoted to the main components in the food and pharmaceutical applications. The second general section comprises some definitions of the main antioxidant methods commonly used for the determination of the antioxidant activity of components. In addition, some chemical, mechanistic and kinetic basis, and technical details of the used methods are given.

This is a preview of subscription content, access via your institution.


Watch the video: ΑΝΝΑ ΒΙΣΣΗ ΑΓΑΠΗ ΥΠΕΡΒΟΛΙΚΗ (January 2022).