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The Barcelona Series is a series of fifty black and white lithographs made by Joan Miró and published in 1944. They are currently in the permanent collection of the Miró Foundation in Barcelona.

Description
This print series can be considered a forerunner to Miró's 1941 oil series Constellations. These black and white lithographs depict deformed images of animal and human figures. The pictures were a reaction to the Spanish Civil War, which was being waged at the time they were created. Even prior to the war, Miró had painted figures which expressed the pain of the forthcoming conflict in his Wild Paintings, such as in Man and Woman in Front of a Pile of Excrement. Here he used the printing skills he had been experimenting with since the 1930s to create a series that can be interpreted as either 50 individual pieces of art or as only one.

Miró includes distorted ogres who are impotent. The ogres could represent Franco and his generals, but are known also to be based on the fictitious dictator, Ubu Roi, who was created by Alfred Jarry in 1898.

The printing of these lithographs during the war required 350 sheets of paper. It is thought that the limited availability of paper led to the print run being limited to a total of just seven sets. After the publication of these prints Miró went to Paris in 1947, again taking a leading place in an exhibition of Surrealist Art, confirming his important position within that movement.

Provenance
The images were created between 1939 and 1944 by the artist. They were printed at Miralles, a small printer in Barcelona, in 1944, after Miró returned from his self-imposed exile in France. Only five sets were created of the series, together with two artist's proof sets. Today only the location of two of these series is known. One set is in the Joan Miró Foundation and a second set is owned by the descendants of Joan Prats. Because of the censorship in Spain under General Franco following the civil war, it was impossible to exhibit these pictures. Miró at the time was in internal exile in Mallorca.

Relevant Exhibitions

1984 - Casa Elizalde . - Joan Miró Barcelona series

References

Sources

1944 paintings
Paintings by Joan Miró
Paintings in Barcelona


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Saturday, August 28, 2021 11:45 AM
7 tips for surviving Stranded Deep
Stranded Deep released on consoles last year after having spend half a decade in early access on Steam. I downloaded it for my PS4 when it was offered as the free monthly game, and had a lot of trouble getting into it. I was very frustrated with how little the game bothers to explain itself, and how much trial-end-error I had to put up with just to learn the basics. However, I did stick with it, and started to warm up to it after several restarts and some time spent on the wiki.
I imagine I'm not the only one checking out this game on consoles, especially since it was free for PSPlus users earlier this summer, so I thought I'd share 7 tips that I wish I'd known when I had started out. Hopefully, I can spare other players a lot of the trial-and-error and frustration that I had to endure, so that you can get to enjoying the game a lot quicker and more fully. I also want to point out that I'm playing the game on a PS4, and I understand that the PC version of the game is a little bit different. The tips that I offer here should also be relevant to PC players, but they are geared towards console players. That being said, here are 7 tips for surviving Stranded Deep:
Tip #1: Have the wiki open!
Aside from some load screen tips and the brief tutorial, there are no in-game explanations of how anything works or what anything does. The crafting menu does not explain what the item being crafted does or how it is intended to be used, nor does it give any indication as to where the requisite materials can be found or harvested from. Because of this, I recommend keeping the wiki open on a phone, tablet, or laptop next to you while you're playing. Pause the game frequently and read what things do before you attempt to craft them. Otherwise, you might find yourself wasting valuable materials crafting things that you don't really need yet, and then not having those materials available for crafting things that you do need later.
For example, in my first attempt, I crafted a "container shelf", expecting that I could use it to store empty coconut flasks and other supplies for use later. Nope, these shelves are only used to store the wooden crates that you'll find in shipwrecks. Everything I attempted to set on the shelf would just fall or roll off. It was a waste of perfectly good planks, and even after I had tried crafting a raft, I wasn't even able to pick up the shelf and move it onto the raft, and attempting to break it down did not return enough of the components to allow me to craft a more useful replacement on the raft.
This container shelf didn't work how I expected, and was a waste of materials.
The lack of explanations also left me wondering how to obtain some basic crafting components. I actually got stuck in the tutorial trying to figure out how to craft lashing. I thought it would come from palm tree leaves, so I tried cutting off the fronds of adult palm trees. That didn't work, so I was left wandering around the starting island for several minutes before caving and looking at a wiki. For the record, lashing is crafted from fibrous leaves, which come from yucca and the baby palms that sprout out of the ground. I passed right by the baby palms, expecting that they would provide the same useless fronds as the adult palms, and I didn't even see the yucca at first because there were only 2 on the island, and one was hidden up against a boulder.
Later in the game, I found myself wondering if there is a functional difference between hunting weapons. Does an axe, spear, or bow and arrow do any more damage than the other?
I also wondered if there is a functional difference between the components used to craft a raft. Does it matter whether I craft the raft out of buoys, tires, or wood? Will one go faster or be more stable or durable than the other? What about the floor? Does it matter if the floor is made of planks or scrap metal? Will the scrap metal be heavier and slower? Will it turn my raft into a heat box that will cook me out in the open sun? Or are the different components just there to add some false variety to the game and which to use is entirely up to what's available and the player's personal preferences? As far as I can tell, it's just personal preference.
Tip # 2: Time passes while in crafting menus
It's also important to know that time passes while you're in the crafting menu. Don't stand around staring at the crafting menu too long, as your hunger, thirst, and SPF meters will continually drain while you're doing so. If you're trying to figure out what to do next, just pause the game and start browsing the wiki. Or you could save at a shelter, then browse the crafting menus to your heart's content, and re-load the save if you ended up wasting away an entire in-game afternoon not producing anything.
Yucca and baby palms respawn periodically.
Tip #3: Some resources are renewable
If you're feeling like your resources are strained after a few days of being stranded, you may be relieved to hear that yucca and baby palms (which provide fibrous leaves) will continually respawn every few days. Additionally, animals will also periodically respawn. This not only includes the small crabs, sardines, and seagulls (which all seem to respawn daily), but it also includes the larger, predatory animals like the giant crabs, hogs, and, of course, sharks (which seem to respawn if you leave an island for several days and return).
The fact that fibrous leaves and animals continually respawn, and since these are the raw materials for water and food, means that you don't have to worry about ever running out of water and food. It also means that anything you can craft with these components are also technically unlimited. That includes lashing, leather, and cloth.
Everything else, however, does appear to be limited and does not respawn. Don't bother checking to see if that potato, aloe or pipi plant has respawned; they won't! If you want a renewable supply of crops like potatoes, quawawa, aloe, or pipi, you'll have to craft a farming plot, plant one copy of the respective plant in the farming plot, and then be sure to water it regularly. If you do that, you'll periodically be able to harvest the plant for an additional supply of food, sunblock, or poison antidote.
Water stills and campfires can be re-filled
with renewable fibrous leaves.
Tip #4: Use Fibrous Leaves for fuel
Speaking of Fibrous leaves, did you know that you can use these to refill campfires and water stills? I sure as heck didn't! It's a good idea to use fibrous leaves as fuel whenever possible because (as mentioned earlier) the yucca and baby palms that they are harvested from do regularly respawn. Using fibrous leaves as fuel will make your camp much more sustainable long-term at relatively little extra cost or effort.
If you're always refilling your campfire with sticks, and refilling your water still with adult palm fronds, you will eventually run out. The trees that these are harvested from do not respawn, and you'll quickly run low on your camp's island if you keep chopping them down for firewood and water, and then not have it available for crafting other things later. The wood in particular is useful for so many other crafting projects that it's a good idea to conserve it as much as possible.
You can also carry a lot more fibrous leaves than sticks or palm fronds, which means you can easily harvest a bunch from other islands and bring them back to your camp with you.
Tip #5: Pick your base camp location wisely
It's tempting to set up a permanent base camp on the first little island that you wind up on -- the one used for the tutorial. While this island will typically provide all the basics that you'll need for survival: respawning yucca and baby palms, some tidepools for catching crabs, and probably some seagulls for you to snare; it might not be the ideal place for you to establish permanent base camp. You might want to explore to find a larger island that contains some giant crabs and/or hogs, as these will provide better sources of food (and the hogs in particular will provide a supply of hides that can be crafted into leather). A larger island will also likely have more potential fibrous leaves, and more trees for collecting coconuts, sticks, palm fronds, and so forth, when you start getting to the point that you're crafting rafts or a beach bungalo. it will also likely have more room for farming plots and hopefully some flat beach for putting together a large raft.
If you do chose to set up your main base camp on an island with hostile wildlife, just try not to set up too close to where they spawn and live. You don't want to return to base after a long expedition of foraging and scavenging, with your food, thirst, and maybe even health levels low, only to get run down and killed by a giant crab or hog as soon as you step off the raft. Nor do you want to wake up from sleeping at your shelter to have a giant crab or hog just waiting to charge you. If you're going to use a tide pool for catching crabs and fish, or for crafting your raft, you should also look out for the poisonous anemone and avoid settling near them. I've forgotten where they are every now and then and accidentally stepped on one while trying to pull my raft out to sea more than once.
Lastly, you can consider setting up a permanent base camp on an island adjacent to a frequently-visited (but potentially dangerous) island. This will spare you from having to make frequently lengthy trips across the ocean. This might not be practical for all map configurations, so a more central base camp might be your best bet.
Tip # 6: Start building a custom raft as soon as possible
The starting inflatable liferaft is very useful in the early stages of the game, but you shouldn't rely on it. It's kind of a trap. It's slow, provides no protection from the sun, has limited storage, and is easily tipped by sharks.
Build a multi-tile raft sooner rather than later so you can safely explore more islands.
I thus recommend that once you have a sustainable camp set up with a steady supply of water and food, that you start stockpiling supplies for crafting a raft. If you see buoys, barrels, or tires in a shipwreck, collect them and bring them back to camp so that you can turn them into a raft base. If you find corrugated scrap, bring that back to camp to be crafted into a raft floor. You can combine multiple bases together to make a bigger raft, and should try to make a raft that is at least a few tiles. This will be more stable, and will be harder (or impossible) for sharks to flip.
You can't paddle the custom rafts, so you'll also need a sail and a rudder in order for the raft to be usable. I also recommend crafting a canopy over the segment of the raft that the rudder is attached to. This will reduce your exposure to afternoon sun as you pilot the raft between islands. If you have space left on your raft, start populating it with container shelves and fill those container shelves with any wooden crates that you find in your explorations. This will allow you to haul large quantities of supplies from island to island.
Tip #7: Save frequently, and keep a backup
Once you have a sustainable camp set up which you are happy with, I recommend making a backup of your save game on external USB drive or on cloud storage. This way, if you screw up, or get lost at sea, or get crippled, you have the option to go back to a safe save game and try again, without having to restart the entire game and go through the tutorial and basic camp setup again.
Then, once you have a viable custom raft, I recommend making another backup of your save, for the same reasons.
Stranded Deep also has ways that small mistakes can compound and cascade into more severe mistakes later on, long after you've overwritten your local save game. Consuming too many resources, letting crops die, and other mistakes can be mistakes that are hard or impossible to recover from, and you might not find out that you've committed those mistakes until in-game days (and several saves) after it's too late.
Backup a save to the cloud or external storage after you have a sustainable base camp established.
There's also plenty of cheap or undeserved deaths and injuries in Stranded Deep. For instance, I couldn't figure out how to get down from this crow's nest on this shipwreck because the game didn't give me a prompt to climb down the ladder. So I had to just let myself fall and mash the button to grab on before I hit the ground. But if I didn't pull it off, I'd fall and break a leg.
Once you learn the game a bit better, and know how everything works, then you can start over on a different map and try an ironman mode or enable permadeath for the extra challenge. But when you're learning, it's a good idea to save yourself some time and energy in case things go way south. Don't make learning the game worse for yourself than it needs to be.
Hope these tips helps you to survive
Well, there it is, 7 hopefully useful tips for surviving Stranded Deep. Its indie nature means there's not a whole lot of tip or strategies about this game, so hopefully this fills a particular niche and will be valuable to a lot of people.
If you enjoyed this content, and would like to see more like it, I do have a Patreon campaign, and I hope you'll make a contribution and become a supporter.
I hope these tips help you survive Stranded Deep.
98e841f1-6d81-4aa2-be97-02fa4da70423|0|.0
Tags:Stranded Deep, wiki, raft, save scum
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Lifespan extension and elevated hsp gene expression in Drosophila caused by histone deacetylase inhibitors
Yanmei Zhao, Hui Sun, Jun Lu, Xiaoxue Li, Xia Chen, Dan Tao, Weifeng Huang, Baiqu Huang
Yanmei Zhao
Hui Sun
Jun Lu
Xiaoxue Li
Xia Chen
Dan Tao
Weifeng Huang
Baiqu Huang
The heat shock proteins (Hsps) play a positive role in lifespan determination, and histone acetylation has been shown to be involved in transcription of hsp genes in Drosophila. To further determine if hsp22 and hsp70 expression is correlated with lifespan, and if histone acetylation participates in this process, RNA levels for hsp22 and hsp70 were analyzed throughout the lifespan in the long-lived and short-lived iso-female lines. The results showed that hsp22 and hsp70 RNA levels were higher in long-lived line than in short-lived line and that the long-lived flies responded more rapidly to heat but were more tolerant to high temperature. Moreover, we investigated the influences of histone acetylation modification on longevity and on hsp gene expression by using histone deacetylase (HDAC) inhibitors TSA and BuA. The results demonstrated that both inhibitors were able to extend the lifespan and promote hsp22 and hsp70 expression. However, the optimal concentrations of these inhibitors, and probably the mechanisms of their actions, vary with the genetic background. In addition, we showed that HDAC inhibitors caused the hyperacetylation of core histone H3, implicating the involvement of chromatin modulation in hsp gene transcription. These data suggested a close correlation among histone acetylation, hsp gene expression and longevity in D. melanogaster.
hsp gene
The lifespan of an organism is influenced by both genetic and environmental factors. To date, our understanding of the mechanisms of aging is limited because of the biological complexities of the process. There has been evidence to support the hypothesis that aging is associated with the accumulation of abnormal and/or malfolded proteins and oxidatively damaged proteins in many organisms, including nematodes, flies and mammals (Gershon and Gershon, 1970; Stadtman, 1992). The heat shock proteins (Hsps) are induced in response to protein damage caused by heat and other stresses (Parsell and Lindquist, 1993). Induction of hsp genes during Drosophila aging might have a beneficial effect on the lifespan of flies (Wheeler et al., 1995; King and Tower, 1999). Mild heat stress of Drosophila transgenic for extra copies of the hsp70 gene produced increased expression of the gene and extended the lifespan (Tatar et al., 1997; Tatar, 1999). Heat-induced expression of hsp70 may reduce age-related mortality rates (Minois et al., 2001) and hsp22 and hsp23 genes were upregulated in selected lines for increased longevity (Kurapati et al., 2000), implicating the role of Hsp proteins in longevity determination. Molecular chaperones must be playing important roles in maintaining cellular functions during aging, through promoting protein renaturation and preventing proteins from aggregating and denaturing (Hartl, 1996; Marin et al., 1993).
Expression of hsp genes represents a special model of gene regulation involving basal and inducible expression. The acetylation/deacetylation modifications of N-terminal tails of core histones play critical roles in activation/repression of many eukaryotic genes, including hsp genes. In vitro, histone acetylation has been shown to be involved in hsp gene activation (Nightingale et al., 1998; Reid et al., 2000). Li et al. (1998) demonstrated that in Xenopus oocytes, p300 participated in the inducible transcription of the hsp70 gene both as a coactivator and an acetyltransferase. During Xenopus development, the presence of histone deacetylase (HDAC) inhibitors enhanced the heat shock-induced accumulation of both hsp70 and hsp30 mRNA in post-midblastula transition (MBT) staged embryos and resulted in the expression of hsp30 immediately after MBT rather than at the late neurula/early tailbud stage under normal conditions (Ovakim and Heikkila, 2003). In a previous study, we showed that HDAC inhibitors trichostatin A (TSA) and sodium butyrate (BuA) were able to affect the chromatin structure at the site where the hsp70 gene is located along the polytene chromosome and significantly enhanced both the basal and the inducible expression of hsp70 gene in Drosophila (Chen et al., 2002).
Histone acetylation has also been shown to be involved in lifespan determination. In Saccharomyces cerevisiae, sir2 and rpd3, which encode two important histone deacetylases, were found to be involved in the regulation of lifespan, and deletion of sir2 shortened the lifespan (Kaeberlein et al., 1999), while the rpd3 knockout increased lifespan (Kim et al., 1999). Additional copies of sir2 in Caenorhabditis elegans also increased the lifespan of the worm (Tissenbaum and Guarente, 2001). The lifespan extension was achieved by feeding the HDAC inhibitor phenylbutyrate (Kang et al., 2002), or by a hypomorphic mutation of rpd3 (Rogina et al., 2002) in Drosophila. These results indicate that histone acetylation is associated with lifespan. But the molecular mechanisms of HDAC-dependent changes in aging and lifespan remain unclear.
The aim of this study was to investigate the roles of histone hyperacetylation in expression of hsp genes during aging and longevity determination in Drosophila. Our results show that the increase in acetylation level of histone H3 enhances the basal and inducible expression of hsp22 and hsp70 during aging, and extends both mean and maximum lifespan, to variable extents, in different lines of Drosophila. This strongly implicates a correlation among histone acetylation, hsp gene expression and longevity determination.
Drosophila stocks and culture
Wild-type strain of Drosophila melanogaster, Canton-S, was used. Flies were raised on standard cornmeal/yeast/agar medium under a 12 h:12 h light:dark cycle.
Isofemale lines screening and lifespan determination
Eggs from a single female fly were collected and used for the screening of iso-female lines, and ten iso-female lines were established and the lifespan was measured. The long-lived and short-lived lines were then screened from these lines. To obtain flies of defined age, newly eclosed flies were collected and maintained at 25°C at a density of 50 per vial and were transferred to fresh vials every 3 days toprevent growth of bacteria or mold, and 200 flies for each line were cultured. The number of dead flies was counted every day.
HDAC inhibitor treatment and heat shock induction
The HDAC inhibitors trichostain A (TSA; Sigma, MI, USA) and sodium butyrate (BuA; Sigma) were used at final concentrations of 10 μmol l-1 and 10 mmol l-1, respectively. The third instars larvae were divided into equal aliquots for different treatments. Part of the larvae were cultured for 5 h in physiological brine (130 mmol l-1 NaCl, 4.7 mmol l-1 KCl and 1.9 mmol l-1 CaCl2) and then allowed to develop directly into flies. For the repeated mild heat shock (RMHS), the flies were induced at 32°C for 1 h every 3 days. Some of the larvae were heat shocked (HS) at 37°C for 30 min before they were allowed to develop into flies. For HDAC inhibitor treatment, the larvae were cultured in physiological brine with TSA or BuA and then allowed to develop into flies either without additional inhibitor feeding (o.TSA and o.BuA) or were continuously cultured on medium containing inhibitors (c.TSA and c.BuA). The remaining flies were treated with both HDAC inhibitors and RMHS (TSA-RMHS and BuA-RMHS).
Real-time quantitative PCR analysis of hsp mRNAs
The flies were cultured and treated as described above until 6 and 30 days old, or induced at 37°C for 2, 5, 10, 20 and 40 min. Total RNA was extracted from flies using the RNA extraction kit supplied by Promega. The reverse transcription (RT) reaction was performed by using a RT system (Promega) following the manufacturer's protocol. Quantification of mRNA was performed using an ABI PRISM® 7700 sequence Detection System (PE Applied Biosystems, Weiterstadt, USA) and SYBR® Green (PE Applied Biosystems) as a double-stranded DNA-specific fluorescent dye. Rp49 (ribosomal protein 49) was used as a housekeeping gene for standardizing hsp mRNA expression.
Amplification mix (50 μl) contained 4 μl cDNA solution, 10× SYBR® Green buffer, 0.24 mmol l-1 MgCl2, dNTP (0.2 mmol l-1 dATP, dCTP, dGTP, 0.4 mmol l-1 dUTP), 1.25 U AmpliTaq Gold DNA polymerase, 0.5 U Amp Erase UNG and 200 nmol l-1 DNA primers. Amplification primers for hsp22 were 5′-ctttcacgccttcttcc-3′ and 5′-gcggttttgtcttttgg-3′; for hsp70 were 5′-agccgtgccaggtttg-3′ and 5′-cgttcgccctcataca-3′; and for rp49 were 5′-agcacttcatccgccacc-3′ and 5′-atctcgccgcagtaaacg-3′. Samples were incubated for 2 min at 50°C to inhibit carryover of contamination. Thermal cycling conditions consisted of an initial denaturation step at 95°C for 10 min, followed by 40 cycles of 15 s at 95°C and 1 min at 60°C. All PCR reactions were run in duplicate.
The Ct (threshold cycle) was defined as the number of cycles required for the fluorescence signal to exceed the detection threshold. Data were analyzed by using the 2-ΔΔCt method, which is a convenient way to analyze the relative changes in gene expression (Livak and Schmittgen, 2001). Quantitative results are given as means ± s.e.m.
Western blot analysis
Flies were cultured and treated as described above. Nuclear protein was extracted as described by Giancotti et al. (1984), or whole flies were homogenized directly into lysis buffer [50 mmol l-1 Tris-HCl pH 8.8, 300 mmol l-1 NaCl, 1% NP-40, 1 mmol l-1 EDTA, 1 mmol l-1 dithiothreitol (DTT), 1 mmol l-1 phenylmethylsulfonyl fluoride (PMSF)] to obtain total proteins. Following 15% SDS-polyacrylamide gel electrophoresis (PAGE), protein was transferred to nitrocellulose membranes, then the membranes were incubated with antibodies to acetylated histones H3 and H4 (Upstate Biotechnology, Lake Placid, NY, USA), to Hsp22 (produced in rabbit), and to actin (Santa Cruz, CA, USA), respectively. Actin was used as a housekeeping gene product for normalizing the loading materials.
Screening of the long- and short-lived lines
Longevity is dependent on both genetic and environmental factors. Under the same environmental conditions, diversity of longevity occurs among the different individuals. We established 10 iso-female lines of Drosophila melanogaster, and the number of dead flies was counted every day. From these lines, we selected the long-lived line iso2 and the short-lived line iso4. The maximum and mean lifespan of the long-lived iso2 line were 73 days and 45.53 days, respectively (Fig. 1). In comparison, the maximum and mean lifespan of the short-lived iso4 line were 62 days and 38.47 days, respectively (Fig. 1).
Survival curves of adult Drosophila. iso2: the long-lived iso-female line, maximum lifespan 73 days, mean lifespan 45.53 days; iso4: the short-lived iso-female line, maximum lifespan 62 days, mean lifespan 38.47 days. The differences were significant (P<0.01). Values shown are the means ± s.e.m. of four parallel experiments.
Basal expression of hsp genes during aging in long- and short-lived lines
A real-time quantitative PCR procedure was used to analyze the RNA expression of hsp genes in long- and short-lived lines during aging. It is clear from Fig. 2 that the hsp22 (Fig. 2A) and hsp70 (Fig. 2B) basal expression declined with aging and this decline was more distinct in the long-lived line than in the short-lived line (Fig. 2). On the other hand, hsp22 and hsp70 mRNA levels were higher in the long-lived line relative to the short-lived line in young flies (Fig. 2), but became less distinct in old flies (Fig. 2). No prominent differences were seen in the expression of other hsp genes, such as hsp26, during aging and between long- and short-lived lines (data not shown).
Difference in basal expression of hsp22 (A) and hsp70 (B) genes during aging between long- and short-lived lines. Total RNA was isolated from flies, which were cultured and treated as described in the Materials and methods until 6 days and 30 days. Quantitative real-time PCR was performed to determine the mRNA expression levels of hsp genes (N=3). Values are means ± s.e.m.
Differences in response to heat induction and in the level of expression of hsp between long- and short-lived lines
The hsp RNA expression after 37°C heat induction for different periods of time was also examined by real-time quantitative PCR. As shown in Fig. 3, differences in the response to heat induction and in the level of expression of hsp22 (Fig. 3A) and hsp70 (Fig. 3B) gene products in fly strains with different lifespan were observed. The long-lived line was more sensitive to heat shock than the short-lived line. Heat shock for 2 min caused rapid increase in the expression of hsp22 and hsp70 in long-lived line (Fig. 3, iso2), but in the short-lived line, a detectable change in hsp22 and hsp70 expression did not occur until 5 min of heat shock (Fig. 3, iso4). Also, hsp22 expression increased by approximate 130-fold in short-lived flies at 40 min of induction, while only an approximate 80-fold increase was detected in long-lived flies at the same time (Fig. 3A). It can also be seen from Fig. 3B that the intensity of hsp70 gene did not change significantly upon heat treatment.
Difference in response to heat induction and in the level of expression of hsp22 (A) and hsp70 (B) genes between long- and short-lived lines. The flies were heat induced at 37°C for 2, 5, 10, 20 and 40 min before RNA was extracted for reverse transcription. Quantitative PCR was performed to determine the inducible mRNA expression levels of hsp genes (N=3). Values are means ± s.e.m. **P<0.01 versus control; †130-fold increase compared to the control; ‡80-fold increase compared to the control.
Difference in stress resistance between long- and short-lived lines
The experimental results described above revealed a correlation between hsp gene expression and longevity in flies. We then investigated the tolerance of flies to persistent high temperature, and we found that the long-lived flies had a greater resistance to high temperature stress. Within 30 min of the treatment at 37°C rapid death occurred in the short-lived line, whereas in long-lived flies, the rapid death occurred after 60 min of the heat treatment (Fig. 4).
The death curves of adult flies maintained under high temperature. One hundred flies 6 days after eclosion were kept at 37°C and the number of dead flies was counted at each of the indicated time points for long-lived (iso2) and short-lived (iso4) lines. Values shown are the means ± s.e.m. of four parallel experiments.
Influence of heat shock and HDAC inhibitors on the lifespan of flies
To test the action of HDAC inhibitors (TSA and BuA) and heat shock in flies with different longevity, we cultured and treated flies as described in Materials and methods, and the lifespan was measured. The repeated mild heat shock (RMHS) resulted in an extension of both the mean and maximum lifespan of the flies (Fig. 5A,E), but the degrees of extension were different between the long- and short-lived lines. The maximum lifespan increased only slightly, by 5.6%, in long-lived flies, and moderately, by 11.5%, in short-lived flies; the mean lifespan increased moderately, by 10.3%, in long-lived flies and considerably, by 25.8%, in short-lived flies compared with the control. It can be seen from Fig. 5B,F that the HDAC inhibitor TSA strikingly influenced the lifespan in both long- and short-lived lines, but with variable degrees. For the long-lived flies, one-off TSA treatment (o.TSA) had no obvious effect on both mean and maximum lifespan, while continuous TSA treatment (c.TSA) only increased mean lifespan by 15.6% (Fig. 5B). For short-lived flies, o.TSA resulted in an extension of mean lifespan by 5%, and c.TSA significantly increased mean lifespan by 24.4% and maximum lifespan by 16.4% (Fig. 5F). Data in Fig. 5C,G demonstrated that BuA treatment only affected the lifespan of the short-lived line, as one-off BuA treatment (o.BuA) increased the mean lifespan by 25.8% and the maximum lifespan by 11.5%. When BuA was added continuously throughout their lifetime (c.BuA), the life extension effect became less obvious (Fig. 5G). When the flies were fed with HDAC inhibitor and RMHS was applied every 3 days, we found no significant differences among RMHS, TSA-RMHS and BuA-RMHS treatments, and a similar extension to that of the controls was seen (Fig. 5D,H).
Survival curves of adult Drosophila maintained at 25°C. (A) Influence of heat shock on lifespan in the long-lived line. RMHS extended mean lifespan by 11.5% and maximum lifespan by 5.6%. (B) Influence of the HDAC inhibitor TSA on lifespan in the long-lived line. Only c.TSA extended mean lifespan by 15.6%. (C) Influence of HDAC inhibitor BuA on lifespan in long-lived line. BuA treatment had no obvious effect on both mean and maximum lifespan. (D) Influence of heat shock and the HDAC inhibitors TSA or BuA on lifespan in the long-lived line. There was no significant differences among RMHS, TSA-RMHS and BuA-RMHS treatments. (E) Influence of heat shock on lifespan in short-lived line. RMHS extended mean lifespan by 25.8% and maximum lifespan by 11.5%, respectively. (F) Influence of the HDAC inhibitor TSA on lifespan in the short-lived line. o.TSA slightly increased mean lifespan by 5%, and c.TSA increased mean lifespan by 24.4% and maximum lifespan by 16.4%. (G) Influence of the HDAC inhibitor BuA on lifespan in the short-lived line. Only o.BuA increased mean lifespan by 25.8% and maximum lifespan by 11.5%, respectively. (H) Influence of heat shock and HDAC inhibitor TSA or BuA on lifespan in short-lived line. No significant differences existed among RMHS, TSA-RMHS and BuA-RMHS treatments. Values shown are the means ± s.e.m. of four parallel experiments. con, control without any treatment; HS, 37°C one-off heat shock induced for 30 minutes only in larvae; RMHS, 32°C repeated mild heat shock for 1 h every 3 days until death; o.TSA, 10 μmol l-1 TSA one-off treatment for 5 h only in larvae; c.TSA, continuous 10 μmol l-1 TSA treatment until death; o.BuA, 10 mmol l-1 BuA one-off treatment for 5 h only in larvae; c.BuA, continuous 10 mmol l-1 BuA treatment until death.
Hyperacetylation of histone H3 following HDAC inhibitor treatment and heat shock induction
In order to test if changes in histone acetylation are involved in HDAC inhibitor-mediated lifespan extension and hsp gene induction, we examined the acetylation levels of core histones (H3 and H4) after HDAC inhibitor treatment and heat shock using antibodies against acetylated H3 and H4. As shown in Fig. 6, acetylated lysine of histone H3 were detected. The photodensitometric analysis of the bands revealed that both TSA and BuA caused an increase in the acetylation level of H3 in long-lived (Fig. 6A) and short-lived (Fig. 6B) lines. More specifically, o.TSA and o.BuA treatments moderately increased the acetyl-H3 level (P<0.05) (Fig. 6C, o.BuA and o.TSA). c.TSA treatments brought about a significant increase (P<0.01) (Fig. 6C, c.TSA), whereas c.BuA treatment moderately increased the acetyl-H3 level in long-lived flies (P<0.05), and significantly increased it in the short-lived line (P<0.01) (Fig. 6C, c.BuA). Moreover, RMHS also increased acetyl-H3 (P<0.01) (Fig. 6C, RMHS). When a combined treatment of both HDAC inhibitors and heat shock was applied, there was an additive effect (P<0.01) (Fig. 6C, TSARMHS and BuARMHS). However, no changes were detected in the acetylated lysine of histone H4 under the same treatments (data not shown).
Hyperacetylation of histone H3 following HDAC inhibitor treatment and heat shock induction. (A,B) Western blots of the acetylated histone H3 (AcH3) in long-lived and in short-lived flies, respectively. The results of photodensitometric analysis of A and B are shown in C. The upper bands are the internal reference actin, and the lower bands are acetylated histone H3. Values shown are the mean ± s.d. of three independent experiments. *Significant (P<0.05); **highly significant (P<0.01). Abbreviations as in Fig. 5.
Influence of histone H3 hyperacetylation on hsp gene expression during aging
Next, we wanted to know whether the hyperacetylation of histone H3 influences hsp expression during aging. The hsp mRNA levels were assayed by quantitative real-time PCR, and it was found that after c.TSA and o.BuA treatments, hsp22 and hsp70 basal expression increased moderately in young flies (6-day old) of the long-lived line (P<0.05) (Fig. 7A,C, iso2), while it increased considerably in young flies (6-day old) of the short-lived line (P<0.01) (Fig. 7A,C, iso4). With the aging of the flies, the degree of increase in these gene products declined gradually. In 30-day old short-lived flies, only the basal transcription of hsp22 increased moderately compared with control (P<0.05) (Fig. 7B, iso4). For the inducible expression of hsp genes, only TSA treatment gave rise to the noticeable effect (Fig. 7E-H). In both long- and short-lived young flies, TSA-RMHS treatment caused a higher expression of hsp22 and hsp70 than RMHS (Fig. 7E,G). Similarly, the increase in inducible hsp expression declined gradually during aging (Fig. 7E-H). Until 30 days after eclosion, TSA-RMHS treatment only increased hsp22 expression in the short-lived line (Fig. 7F, iso4), while no increase in hsp70 expression was detected (Fig. 7H). In addition, to determine whether changes in mRNA levels actually reflect changes in the relative levels of proteins, we assayed Hsp22 protein content in young flies after HDAC inhibitor treatment and heat shock. Total protein was isolated from 6-day-old flies and Hsp22 protein was detected by western blot (Fig. 8). Consistent with changes in the hsp22 mRNA level, Hsp22 protein expression was up-regulated by the HDAC inhibitors (Fig. 8, c.TSA and o.BuA). Similarly, continuous TSA treatment (c.TSA) and one-off BuA treatment (o.BuA) strikingly increased Hsp22 protein basal expression and only TSA treatment produced a rise in inducible expression of Hsp22 (Fig. 8, TSA-RMHS). Additionally, it is noticeable that the HDAC inhibitor-induced up-regulation of Hsp expression was more prominent in the short-lived line than in the long-lived line (Fig. 8, iso2 and iso4).
Influence of HDAC inhibitor-induced histone H3 hyperacetylation on hsp mRNA expression during aging. (A,B) hsp22 mRNA basal expression in young flies (6-day old; A) and old flies (30-day old; B) after HDAC inhibitor treatment. (C,D) hsp70 mRNA basal expression in young flies (6-day old; C) and old flies (30-day old; D) after HDAC inhibitor treatment. (E,F) hsp22 mRNA inducible expression in young flies (6-day old; E) and old flies (30-day old; F) after HDAC inhibitor treatment. (G,H) hsp70 mRNA inducible expression in young flies (6-day old; G) and old flies (30-day old; H) after HDAC inhibitor treatment. Experiments were performed in triplicate. Bars represent means ± s.e.m. For basal expression (A-D), *P<0.05 and **P<0.01, versus untreated control. For inducible expression (E-H), *P<0.05 and **P<0.01, versus RMHS. Abbreviations as in Fig. 5.
Influence of HDAC inhibitor-induced histone H3 hyperacetylation on Hsp22 protein level. Western blot analysis of Hsp22 in long-lived (iso2) and short-lived flies (iso4). The upper bands are actin used as the internal reference and the lower bands are Hsp22 protein. Experiments were performed in triplicate. The abbreviations as in Fig. 5.
In conclusion, this study clarifies the correlation between the elevated expression of hsp genes and the longevity in Drosophila melanogaster. The results revealed the higher hsp basal expression level, higher thermotolerance and higher response to heat shock, but lower hsp22 induction under continuous high temperature in long-lived than in short-lived flies. Drosophila lifespan could be extended by feeding the flies with HDAC inhibitors TSA and BuA, and/or repeated mild heat shock. The range of lifespan extension differed between long- and short-lived lines. HDAC inhibitor treatment promoted hsp basal expression, but with the time of aging, the extent of this increase declined gradually. Chromatin modulation may be involved in HDAC inhibitor-mediated hsp gene activation, since hyperacetylation was detected in core histone H3 upon TSA and BuA treatments. Thus, a close correlation among histone acetylation, hsp gene regulation and aging in D. melanogaster can be established.
Correlation between hsp gene expression and longevity
It has been shown that aging is associated with the accumulation of inactive enzymes, partially denatured and/or damaged proteins (Gershon and Gershon, 1970; Stadtman, 1992). Heat shock proteins are thought to reduce protein denaturation and aggregation, facilitate re-folding of partly denatured proteins, direct the entry of damaged proteins into proteolytic pathways and protect the organisms from additional stress (Wheeler et al., 1995; Parsell and Lindquist, 1993). Results presented in this report indicated that hsp22 and hsp70 genes were upregulated and more promptly induced in the long-lived iso-female line (Figs 2 and 3). Also, the thermotolerance was higher in the long-lived line (Fig. 4). Lin et al. (1998) demonstrated that the long-lived D. melanogaster mutant displayed resistance to starvation, high temperature and oxidative stress. A similar increased resistance to heat was observed in long-lived C. elegans lines (Lithgow et al., 1995). It is possible that higher expression of hsp genes may help maintaining cellular functions during aging and prolong the lifespan of the fly. Meanwhile, in long-lived flies, the higher response to heat shock perhaps results in the higher thermotolerance. On the other hand, both the basal expression and induction speed of hsp genes in short-lived flies were low. When the flies were kept in harsh conditions, such as high temperature, more Hsp22 was induced to repair the damage (Fig. 3A). This process presumably consumes more energy and therefore results in quicker death.
Previously, two patterns of hsp expression during aging were reported. With Oregon-R wild-type and W118 flies cultured at low density in culture bottles, hsp22 RNA levels were low or undetectable in young flies, but hsp22, hsp23, hsp70 were upregulated with age (King and Tower, 1999). In contrast, when the same Oregon-R flies were cultured at high density using population cage protocol, the starting level of hsp22 RNA in young flies was high, and the increase in hsp22 RNA during aging was minor or undetectable (Kurapati et al., 2000). In the experiments of this study, Canton-S wild-type flies were cultured using the high-density population cage protocol. In contrast to the previous observations, we found that hsp22 and hsp70 mRNA levels were relatively higher in young flies, and declined with age (Fig. 2). We presume that this may be partially due to the different strain used. Also, it is important to note that this difference was observed under conditions that were more stressful than the optimum.
Moreover, data in this study revealed that the response of hsp genes to heat induction varied in flies with different longevity. In the long-lived flies, hsp genes were more sensitive to heat than in the short-lived line. In addition, different hsp genes exhibited a variable response to heat, i.e. hsp22 was more responsive to heat than hsp70. This suggests that a more positive correlation may exit between hsp22 and longevity, while hsp70 may affect longevity to a lesser extent. In contrast, the expression of hsp26 did not differ significantly in expression between long- and short-lived flies (data not shown), implying that it may not be closely related to longevity. These results implicate the existence of a mechanism for preferential induction of hsp genes during aging.
Histone acetylation/deacetylation modifications and expression of hsp genes
The mechanisms of hsp gene induction by heat stress in Drosophila have been studied in some detail (Lis and Wu, 1993). Binding sites for the GAGA transcription factor and other cis-acting sequences at hsp promoters are required for generation of an accessible promoter structure in unstressed cells, which involves a transcriptionally engaged RNA polymerase paused ∼25 bp downstream of the start site for transcription (Gilmour and Lis, 1986; Lee et al., 1992; Rougvie and Lis, 1988). Upon heat shock, the heat shock factor (HSF) is converted into an active trimer from inactive monomers, and binds to the heat shock element (HSE), facilitating the transcription of hsp genes. However, the role of histone acetylation in transcription regulation of hsp genes is still obscure. In this study, we showed that the acetylation level of H3 was increased upon treatment with the HDAC inhibitors, TSA and BuA (Fig. 6). We also demonstrated that hsp genes were upregulated after HDAC inhibitor treatment (Fig. 7). Interestingly, we noticed that heat shock also increased the acetylation level of H3 (Fig. 6), further confirming the involvement of histone acetylation in hsp gene transcription in D. melanogaster. TSA and BuA are the two widely used HDAC inhibitors, but they may function through different mechanisms (Gibson, 2000; Finnin et al., 1999). TSA was originally identified as a fungal antibiotic with differentiation inducing properties, and it can strongly increase the acetylation level of histone H3 (Zhong et al., 2003). BuA is a simple chemical that can raise the acetylation level of H3 and H4 by suppressing HDAC activity via a noncompetitive mechanism (Gibson, 2000). TSA and BuA affected hsp gene expression differently in this study. TSA was able to induce the expression of hsp22 and hsp70 genes above their basal level, and it worked cooperatively with heat shock to raise the inducible transcription intensity of hsp22 and hsp70 genes (Fig. 7). BuA only promoted the basal expression of hsp genes (Fig. 7A,C). In addition, continuous TSA treatment (c.TSA) and one-off BuA treatment (o.BuA) increased hsp22 and hsp70 expression more in short-lived flies, and this result was consistent with the influences of these HDAC inhibitors on the longevity of the flies (Fig. 5F,G). Moreover, as aging proceeded, HDAC inhibitor treatments became less effective in promoting hsp gene expression. This may presumably be due to the increasingly inactive response and repair mechanisms in aged flies.
Histone acetylation/deacetylation modifications and the longevity
A balance of activation and repression of various genes regulates an optimal physiological and cellular environment for longevity. The acetylation/deacetylation modifications of histones play critical roles in activation/repression of many genes, and hence probably regulate the lifespan. In yeast and worms, the HDAC Sir2 and Rpd3 have been shown to be closely related to lifespan (Kaeberlein et al., 1999; Kim et al., 1999; Tissenbaum and Guarente, 2001), and feeding of the HDAC inhibitor phenylbutyrate (Kang et al., 2002) or a hypomorphic mutation of rpd3 (Rogina et al., 2002) in the Drosophila extended the lifespan. However, mutation in Drosophila sir2 (dsir2) gene did not shorten lifespan, as predicted from yeast and worms (Newman et al., 2002). It appears that the influence of histone acetylation on longevity is a complex process and may involve different pathways and mechanisms. We treated flies with a one-off and continuous feeding of HDAC inhibitors, heat shock, as well as combinations of both HDAC inhibitors and heat shock, in an attempt to elucidate the effects of HDAC inhibitor-mediated histone acetylation on longevity. The results showed that TSA strikingly extended the lifespan in different ways, as o.TSA treatment only increased the mean lifespan in the short-lived line, and c.TSA treatment extended the mean lifespan by 15.6% in the long-lived line; while in the short-lived line, it extended both the mean and maximum lifespan by 24.4% and 16.4%, respectively (Fig. 5B,F). Thus, a prolonged TSA action in vivo is probably necessary for longevity determination. However, BuA had less effect on lifespan. Only in the short-lived line did o.BuA treatment extend both the mean and maximum lifespan. When BuA was applied throughout the lifetime of the flies, its life-extension effect became insignificant (Fig. 5G). We presume that prolonged BuA feeding may be toxic, which reduced the survival rate. As a rule, both TSA and BuA were more effective in the short-lived line than in the long-lived line. It appears that different genetic background may determine the action as well as the type and optimal concentrations of the HDAC inhibitors. Furthermore, combined treatments of both inhibitors and heat shock (TSA-RMHS and BuA-RMHS) and heat shock alone (RMHS) had basically the same effect on life extension (Fig. 5D,H). We reason that the life extension by RMHS treatment may mask the influences of HDAC inhibitors. These results suggest that establishment of an altered cellular environment by HDAC inhibitors and heat shock changed the lifespan of flies, possibly through a pathway that involves the change in expression of certain genes resulting in inhibition of the accumulation of damaged proteins, and/or stimulation of repair mechanisms.
This work was supported by grants from The National Natural Science Foundation of China (30370316) and The Major State Basic Research Project of China (G1999053902).
↵* These authors contributed equally to the work
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Tanzanite History and Lore
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This 122.70-carat tanzanite is in the collection of the Smithsonian National Museum of Natural History. - Chip Clark, courtesy Smithsonian Institution
Tanzanite is relatively new to the colored stone galaxy. As the most common story of the tanzanite mining boom goes, in 1967 a Masai tribesman stumbled upon a cluster of highly transparent, intense violet-to-blue crystals weathering out of the earth in Merelani, an area of northern Tanzania. He alerted a local fortune hunter named Manuel d'Souza, who quickly registered four mining claims.
D'Souza hoped that he'd been shown a new sapphire deposit. Instead, the deposit contained one of the newest of the world's gems.
Although it's a newcomer to the gemstone industry, tanzanite has quickly become one of the most popular colored gemstones. - Courtesy Richard Krementz Gemstones
Within a short time, 90 more claims appeared in the same 20-square-mile area. No one was quite sure what the beautiful crystals were, but everyone wanted to lay claim to the profits they were certain to produce. The new gem would eventually be known as tanzanite, and it would, at times, rival the Big 3 in popularity.
Tiffany & Company recognized its potential as an international seller and made a deal to become its main distributor. Tiffany named the gem after the country it came from, and promoted it with a big publicity campaign in 1968. Almost overnight, tanzanite was popular with leading jewelry designers and other gem professionals, as well as with customers who had an eye for beautiful and unusual gems.
The instant popularity of this transparent blue-to-violet gem was tied to its vivid color, high clarity, and potential for large cut stones.
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Open Championship 2014 Royal Liverpool: Hole 14
Tiyah Hernandez-Pierrepont
Golf Monthly takes an in-depth look at the Royal Liverpool course ahead of the 2014 Open Championship.
Hole 14 – Par 4 – 454 yards
The 14th hole bears very strong similarities to the 12th hole however it is an exceptionally tough driving hole. The approach shot has to be hit over the side of a hill to a narrow green, with competitors attempting to avoid the cluster of three bunkers down the right hand side as well as the two on the left.
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Salomona solida är en insektsart som först beskrevs av Walker, F. 1869.  Salomona solida ingår i släktet Salomona och familjen vårtbitare.

Underarter

Arten delas in i följande underarter:

 S. s. albipes
 S. s. solida

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solida

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Molly Ivins (August 30, 1944 – January 31, 2007) was an American newspaper columnist, liberal political commentator, humorist and author. From Americans Who Tell the Truth: "To honor a journalist as a truth teller is implicitly to comment on the scarcity of courage and candor in a profession ostensibly dedicated to writing and speaking the truth. Molly Ivins is singular in her profession not only for her willingness to speak truth to power but for her use of humor to lampoon the self-seeking, the corrupt and the incompetent in positions of public trust. Her wit and insight place her squarely in the tradition of America's great political humorists like Mark Twain."
Stand Up Against the Surge
AUSTIN - The purpose of this old-fashioned newspaper crusade to stop the war is not to make George W. Bush look like the dumbest president ever. People have done dumber things. What were they thinking when they bought into the Bay of Pigs fiasco? How dumb was the Egypt-Suez war? How massively stupid was the entire war in Vietnam? Even at that, the challenge with this misbegotten adventure is that WE simply cannot let it continue.
Stop This War, Now!
AUSTIN - The president of the United States does not have the sense God gave a duck—so it's up to us. You and me, Bubba. I don't know why Bush is just standing there like a frozen rabbit, but it's time we found out. The fact is we have to do something about it. This country is being torn apart by an evil and unnecessary war, and it has to be stopped now.
Thanks -- No, Seriously
It's time to give thanks, and I want to start off with a great, big thank you for the top American movement conservatives and all the fun we've had since Election Day. I know I promised not to gloat after this election was over, but I'm not talking unseemly gloating -- I'm talking about moments so brilliantly hilarious the only option is to put your head down on the desk and howl.
Campaign '06 -- Goodbye and Good Riddance
Right to the end, this insane conversation between reality and Not Reality. The president of the United States STILL says we are reducing terrorism by fighting in Iraq; STILL says we are creating democracy; STILL says we're preventing the spread of nuclear weapons and making Israel more secure; and, shoddiest of all, STILL not allowing that our fallen have died in vain.
Dear Leaders
AUSTIN, Texas - Nobody else seems to be asking the obvious question about Susan B. Ralston, former administrative assistant to Jack Abramoff and, until last week, assistant to Karl Rove. She got hired by Rove at $64,700 after the 2004 election and then received a raise to $122,000. Why? I've never gotten a 100 percent raise. Did you? Is this common?
Habeas Corpus, R.I.P. (1215 - 2006)
AUSTIN, Texas - Oh dear. I'm sure he didn't mean it. In Illinois' Sixth Congressional District, long represented by Henry Hyde, Republican candidate Peter Roskam accused his Democratic opponent, Tammy Duckworth, of planning to "cut and run" on Iraq.
A Tortured Debate
AUSTIN, Texas - Some country is about to have a Senate debate on a bill to legalize torture. How weird is that?
Remembering Ann Richards
AUSTIN, Texas—She was so generous with her responses to other people. If you told Ann Richards something really funny, she wouldn't just smile or laugh, she would stop and break up completely. She taught us all so much—she was a great campfire cook. Her wit was a constant delight. One night on the river on a canoe trip, while we all listened to the next rapid, which sounded like certain death, Ann drawled, "It sounds like every whore in El Paso just flushed her john."
Let the Truth-Telling Begin
Royal Masset, a Texas Republican political consultant who has been accused of being less than brilliant, recently had this to say about Karl Rove: "I think we actually like Karl a lot more now than we did when he was more active locally." He told the San Antonio Express-News he believed that Rove in Washington is remaining loyal to Bush while "fighting the good fight. He's fighting budgets. He's fighting wars. He's doing conservative kinds of things."
The Pols Who Cried Wolf
AUSTIN, Texas - We have nothing to fear but fear itself, especially since fear is now being fomented and manipulated for political purposes by a bunch of shameless hacks. Who is trying to make you afraid and why? This Karl Rove tactic is getting quite threadbare, in fact, and so much so that it is getting dangerously close to comedy.


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AJBH-EN
The Commissioner and the Deputies
How can you complain to the ombudsman?
Justitia Regnorum Fundamentum Award
Previous Ombudsmen
Events, Calendar
Handling Complaints
Lodge a complaint
Ongoing cases
Relevant legal provisions
Reports, statements, studies
Statistics and Human Rights Documents
How to get to the Office
Activities within the United Nations:
The Office of the Commissioner for Fundamental Rights is one of the UN's International Human Rights Institutions
As a result of the accreditation proceedings conducted by the UN's International Coordinating Committee of National Human Rights Institutions (ICC) in the spring of 2011, the Parliamentary Commissioner for Civil Rights, then since January 1, 2012, the Commissioner for Fundamental Rights has safeguarded fundamental rights in Hungary as a status B human rights institution.
In the summer of 2013, the Commissioner for Fundamental Rights requested the ICC Sub- Committee on Accreditation to conduct a re-accreditation procedure targeted at achieving status A, with a view to acknowledging the institution's full compliance with the so-called Paris Principles. At the Geneva meeting of the Sub- Committee on Accreditation of the International Coordinating Committee of National Human Rights Institutions held between October 27 and 31, 2014, the Commissioner for Fundamental Rights proposed that status A be awarded to the institution. This proposal was not objected to by the Member States. Thus, the Office of the Commissioner for Fundamental Rights may undertake an active role, in possession of full voting rights, in the meetings of the regional organizations and sub-committees of the Office of the UN High Commissioner for Human Rights (OHCHR) and those of GANHRI from the fall of 2014. Furthermore, the Office ensures the independent and professional supervision of the observance of fundamental rights in Hungary in compliance with the Paris Principles.
human rights consulting or consultancy based on proceedings launched ex officio or upon request by a mandatory of the Government, the National Assembly, or another government body,
preparation and publication of position papers, recommendations and reports on human rights issues,
preparation of recommendations to promote the ratification of international treaties,
participation in adapting the Hungarian human rights regulations to the international treaties and the subsequent promotion of the efficient application thereof,
active involvement in the compilation of human rights reports,
cooperation with the Hungarian and international human rights organizations,
conducting research and education in the field of human rights,
raising awareness to human rights issues (with special regard to discrimination) and to infringements.
On 12th January, 2012, Hungary has joined to the Optional Protocol to the UN Convention against Torture (OPCAT) adopted in 1984. The Convention requires the establishment of independent bodies both on national and international levels, which execute regular visits in the detention institutions for verifying conditions therein.
The UN Convention against Torture and other Cruel, Inhuman or Degrading Treatment or Punishment became part of the domestic legal system as a result of the adoption of Legislative Decree 3 of 1988.
The Parliament adopted Act CXLIII of 2011 on the Promulgation of the Optional Protocol to the Convention (hereinafter referred to as the "Protocol"), aimed at the practical implementation of the ban on torture and other cruel, inhuman or degrading treatment or punishment, on October 24, 2011. The Protocol established a system within which independent international and national bodies may regularly inspect those places where people deprived of their liberty stay.
The system is built on the Subcommittee on Prevention, comprising 25 independent experts and operating under the auspices of the UN, and on the National Preventive Mechanism operated by the State Parties.
The Committee on Prevention, just as the National Prevention Mechanism, may inspect on‑the‑spot the detention or imprisonment or the placement of a person in a public or private custodial setting which that person is not permitted to leave at will by order of any judicial, administrative or other authority. The competences of the Subcommittee on Prevention and the National Preventive Mechanism are identical.
As of January 1, 2015, the Commissioner for Fundamental Rights shall proceed as National Preventive Mechanism either personally or with the cooperation of his colleagues. The tasks related to the National Preventive Mechanism shall be performed by at least eleven staff members of the Office of the Commissioner for Fundamental Rights, all with an outstanding knowledge in the field of the treatment of persons deprived of their liberty or having at least five years of professional experience. Among the authorized public servant staff members, the number of the representatives of either sex may exceed that of the other by one at the most. Among them there shall be at least one person who has been proposed by the Deputy Commissioner for Fundamental Rights responsible for the protection of the rights of nationalities living in Hungary and at least two persons each with a degree in law, medicine and psychology respectively.
Our partner international organisations and networks
Roundtable of Institutions for a Sustainable Future
NEW LOCATION OF THE OFFICE AND THE CLIENT SERVICE OFFICE
2019 July 02.
Meeting of the Ombudsmen of the Visegrád (V4) Countries
2019 June 12.
Poster on the rights of psychiatric patients
2019 May 31.
Ombudsman's Office Attends Geneva Session of UN Commitee on the Elimination of Racial Discrimination
Delegation of the Office of the Commissioner for Fundamental Rigts at the Geneva Forum of the Economic Commission for Europe (March 21-22, 2019)
2019 April 11.
Commissioner for Fundamental Rights hosts the monitoring delegation of the organs of the Council of Europe
2019 March 21.
Commissioner for Fundamental Rights Welcomes Participants of Transzfeszt Cultural Festival in Letter (29–31 March 2019)
EQUINET Recommendation on combatting discrimination and hate speech in election campaigns
UN Sustainable Development Goals (SDGs)
2017 December 19.
European Network of Ombudspersons for Children (ENOC) Position Statement on "Intercountry Adoption"
2019 February 06.
AJBH-EN/
The Office/
International relations/
The Office of the Commissioner for Fundamental Rights
R70 Office building
H-1074 Budapest, Rákóczi út 70-72.
Tel: (+36) (1) 475-7100
Fax: (+36) (1) 269-1615
Email: hungarian.ombudsman@ajbh.hu
Parliamentary Commissioner
for Future Generations (Archive)
Parliamentary Commissioner for
the National and Ethnic Minority
Rights (Archive)


In Asia; In Africa; In Europe; china clay crushing unit cost. clay mining and processing costs kaolin clay . Analysis of Kaolin Mining 12 New Project Investment ..
Cost Of Feldspar Crushing Machine. Kaolin Clay Powder Crushing Granite Crusher Unit Grinding Mill China . Feldspar Crushing Units In Malaysia .
China Crusher Crushing, Cost effective first crushing stage used magnetite ore crusher. Clay crushing machine Clay crusher Two roller clay crusher machine.


text:
import { ExamplePageComponent } from './example-page/example-page.component';
import {NgModule} from '@angular/core';
import { RouterModule, Routes } from '@angular/router';
import { InputHelpComponent } from "./input-help/input-help.component";
const examplesRoutes : Routes = [
   {
    path: '',
    component: ExamplePageComponent,
    children: [
      {
        path: '',
        component: InputHelpComponent
      },
      {
        path: 'input',
        component: InputHelpComponent
      }
    ]
  }
];
@NgModule({
  imports: [RouterModule.forChild(examplesRoutes)],
  exports: [RouterModule]
})
export class ExamplesRoutingModule {}

redpajama_set_name: RedPajamaGithub


text:
Q: Python: the return of the function is just returning only the first line of the opened file VERSION "3"

NS_ :
NS_DESC_
CM_
BA_DEF_
BA_
VAL_
CAT_DEF_
CAT_
FILTER
BA_DEF_DEF_
EV_DATA_
ENVVAR_DATA_
SGTYPE_
SGTYPE_VAL_
BA_DEF_SGTYPE_
BA_SGTYPE_
SIG_TYPE_REF_
VAL_TABLE_
SIG_GROUP_

above is some text in a file, but after running it is just reading the first line even after using for loop what could be the reason as am new to this programming language please help me to get this?
def function(f):
lines = []
for Nrow,row in enumerate(f):
    lines = row.split(' ')
    return lines

with open('car.dbc', 'r') as f: #open the file
 contents = function(f)#put the lines to a variable (list).
 print(contents)

A: Aside from the whitespace in the question
lines = []
for Nrow,row in enumerate(f):
    lines = row.split(' ')
    return lines

will return on the first pass through the for loop.
You want to return when you have finished, appending (or extending) as you go:
lines = []
for Nrow,row in enumerate(f):
    lines.append(row.split(' '))
return lines

redpajama_set_name: RedPajamaStackExchange


Most of us have probably reached the toenail stage. One day you happen to get a glance of those bare feet and you're appalled. How do those toenails even fit in the shoe and how is she still able to walk??
So, you gently tell mom she needs to go in and have those nails professionally groomed by a doctor and thus starts the argument. For six months, I cajoled, begged, pleaded, threatened, reasoned with mom why those nails needed to be cut and she argued against me every time that she could do it herself, that she hated anyone touching her feet, and it was ridiculous to go to a doctor to have it done.
Every month I watched them get thicker, longer, more curled. I knew if she didn't go in, there would be worse consequences, like toenails growing into the skin, infections, and guess who would have to put the medication on the feet everyday!!!
I finally got a recommendation from a friend and made mom an appointment and I didn't tell her until the day before the appointment so that the arguing would be at a minimum. I told her she was going, I took her in, and then, just like that it was done.
That was bad enough but what was just as bad was the lack of support I got from friends and family. I even sent my brother pictures of moms toes and he said yeah, that's bad.
the whole six months about how stubborn mom was and they said, yeah, that's stubborn.
When it was finally done and I told my friends and brother, they said, well, that's good, now it's done.
Last night I felt so despondent that getting those stupid toenails cut took so much of my time and energy, and now it was simply done just because mom decided she would go.
This is the crux of our dilemma as caregivers. NOBODY GETS IT!!! We are so alone in our struggles and battles. After six months of frustration and anger trying to get this done, it's just over, and you have to just move on to the next battle.
The worse thing about caring for a parent is that, unless someone else is doing the same thing, they just have no idea what we go through and you end up feeling so alone in it.
Late last night at the end of that day, I went to this boomer site and found so many encouraging messages, that I actually was able to sleep and I woke up feeling better this morning.
The people on this forum are my best support group. I've been writing here for five years and this is the only place of true understanding that I've ever encountered in all that time. I can say anything and I'm never judged.
Thanks for taking the time to write your stories. You have no idea how much you may be helping someone else.
I get it. I SO get it. I'm so happy to have found this site - just yesterday. Venting to others who are in the same boat is such a relief - WOW! My mother finally passed away in February.
She had been in memory care for the 8 months prior to passing. She was mentally ill her entire life, which was pointed out to me by a very kind woman in a support group.
WILD that I never realized till the dementia set in, mom turned vicious and I went to the support group. I knew she was a piece of work. But not a clue that she was really ill. She was, however, one of the cleanest people I have ever known.
The beginning of the end of the last small shred of denial I may have harbored came the day I caught a glimpse of her toenails. I couldn't help myself - I thought of Howard Hughes and started laughing hysterically.
I had to leave the room and tell her I'd just been thinking of something funny at work. GOTT IM HIMMEL! She always ridiculed my aunt and me - and really any woman - for going for mani/pedis.
We were all a bunch of G0&&damm entitled idiots. I am NOT a princess. Not by a long shot. But I'd go every week if I could afford it. My mother COULD afford it and was going around like the Bride of Frankenstein.
Would she go to the salon with me? Would she let me take her to a podiatrist? Oh, certainly not! Yours truly got to cut those disgusting, filthy things. She paid me $50 AND dished out abuse the entire time.
I thought "great, my life has come to this. Sitting at the Queen's feet, trying to figure out if I should plant daisies or potatoes, listening to her big, foul, nasty mouth." But I did it a few more times.
I needed the money and she needed not to get an abscess and go lame. It's over now. But I never EVER thought I'd get the chance to vent my absolute disgust over THE TOENAILS to anyone. My dad is 95 and about to drive me around the bend. I vented here about him last night.
Came back today and saw the thread about TOENAILS and the home pedicures with The Wicked Witch all came flooding back. Wow. Caca. Urine. Long, filthy toenails. Abuse. Demands (the word "please" was the first to go). And the beat goes on. And on and on and on.
When my grandmother was being cared for in assisted living, her youngest daughter asked my mother (also a daughter) if she would go over and clip their mother's fingernails.
When my mom forgot to do this (and why should she have cut her nails, since granny was getting full care?) my sanctimonious aunt told me that rich granny had wanted to disinherit my mom for being the designated family blacksheep, years earlier.
The unjust moral of this lesson? Don't forget to do the bidding of a rich grandmother's daughter, or else you'll know what it is like to be considered a piece of dirt by your relatives. Bah!
Having one of those moments!
I couldn't help but laugh! I didn't mean to, but I was looking at my mom's feet today and she had the same response.
I am still tickled as I write this response. Not in joy of your discomfort, but finding a little glimpse in mine. You are so right, the struggle is real! I just started venting on this site and you're right it gives you a release in such a non-judgmental way!
I commend you for your efforts! Just to let you know, two years ago my mom and I used to go regularly and get our nails done together.
Now, I have to take her and let her get taken care of separately, while I manage her outbursts and give constant instructions of repeating what the technician is asking.
I take her to the same place each time and the young lady is very, very patient.
Yep. I get it all too well. I also understand why this site is like a lifeline to those of us caregivers who need a place to vent because, honestly, venting is the ONLY way we can cope day after day.
My mom's been with me for 3 years. She's 94. I'm 67. Except for arthritis (which makes it difficult for her to do most things) and the blessedly irritating hearing deficit, she's really not so hard to live with. Mostly it is the loss of privacy and the freedom to live my life as I've always assumed I could at this age. Naive, huh?
Last night was a really rough one for me ... firstly I have to tell you I've developed a serious lung/breathing issue.
I use a CPAP at night too and, until last night, I didn't realize how much I need it until the power went out at 10 pm and didn't get restored till 11 am this morn.
Suffice it to say I spent the entire night sitting very upright in a chair in my bedroom struggling to sleep, which I never achieved.
Besides needing my CPAP to work, I also needed my sister's dog - which I was babysitting for 5 days while she was on a vacay - to stop snoring, farting, and making generally other annoying sounds and smells.
I should've just put her in another room but my oxygen level was plummeting so I just stayed where I was and so did the dog.
Consequently I got no sympathy from her, not that I was looking for a pity party, but it just would've been nice for someone to acknowledge I'd had a rough night at least. Oh well. Onward and upward.
When the power came back on at 11 am, I told her I was going to bed so I could use my CPAP and get some rest. Not surprisingly, she asked "Why? Didn't you sleep last night? I did. I feel great!" I assured her I was happy for her, and reminded her, again, WHY I hadn't been able to sleep. I think I fell asleep on the way to my bed because I don't even remember laying down.
Until someone else has walked in your shoes its impossible for them to appreciate what you've had to deal with. But I did find an awesome article that helps me understand my resentment and cope a little bit more, so I'm going to insert a link to it here. Maybe some of you can relate to it, too.
"Why? You couldn't sleep last night??" Ugh.
Grrrrrrr!!! Don't I know it!
Once in a while a neighbor pitches in, and she's hinted that she'd like to be paid. While I appreciate her limited help (calling my mother once in a while and breaking down some empty Depends boxes), I don't see that as a paying job.
She says, "I know it is not easy! You are doing a great job!"
Thanks, but really, she *can't* know it isn't easy. She has toddlers and that's not harder than this.


CHICAGO — Almost a year ago, Julie and Robert Carnithan lost everything they owned when fire gutted their Beverly home. They'd hoped to rebuild by next Christmas, but now they are worried whether they will have a home at all.
"I don't know what we are going to do. We're out of options so to speak," Julie said. "I really don't know where we go from here."
Contractors told them the entire house would need to be rebuilt from the ground up, but their insurance would only cover the depreciated value, coming up short of the money needed to rebuild. On top of that, they've been living in a rental while still paying their old mortgage. It was all adding up to be too much.
Word of their situation reached Ignite the Spirit, a charity supported by the Chicago Fire Department that swoops in to assist firefighters and their families in times of need. Julie's own cousin was Billy Grant, a firefighter who died in the line of duty in 2007.
"We do the fire and leave and the families are left with what's left, which is destruction and their lives are turned upside down. It's nice when we can come back and do something to help. That's what Ignite The Spirit is all about," president Rich Pinskey said.
Ignite the Spirit gave what they could to help the Carnithans. Friends and family also contributed to a GoFundMe campaign to help them get back on their feet. But they still won't be in a home by the holidays, so the guys who usually answer the call are putting out their own mayday.
Ignite the Spirit has helped more than 500 families like Julie over the years, but they rely entirely on the generosity of others to do that work.


text:
Home Opportunities
The Directors of Parkos: Peter Bosma and Arne Bos
"The better our people, the better our platform" an interview with Arne Bos of Parkos
by Thomas Ansell
in Opportunities
What does it mean to make it in the north? This is part of a series of portraits of local people, organisations, and companies working to further internationalise Groningen, Friesland, and Drenthe. This time we spoke to Arne Bos, Director at the fast-growing Internet Parking company Parkos.
Parkos has been officially up-and-running since 2014, and at one point in its history was situated in the offices under my apartment. It's a small space, and one which is a world away from the spacious, brightly-lit hive of activity that I enter at Parkos' new location. One thing that is particularly striking in the Parkos offices is the amount of languages being spoken, by a young and fashionable-looking staff.
Parkos came from a blog (started in 2007), which originally covered tips and tricks for saving on plane tickets and accommodation. But, after lots of readers reported terrible service and high costs for parking, an idea was born. Now, Parkos operates in eleven countries (including both the US and Australia), and includes seven of the largest ten airports in Europe on its rostrum.
Arne himself is, typically, modest about Parkos' ongoing success: "we began with two people, so we've grown a lot", he says as we wander through the serried ranks of Parkos staff: technicians, country managers, salespeople; marketing, communications, everything is in house. "We are, putting it simply, made up of our software and our staff", says Arne, "and so we have to make sure both work well and are well-looked after."
Being located in Groningen has some specific advantages, says Arne: "We're in a position now where we need skilled people with experience. We are on the hunt for a new country manager for France, for example, and if we were based in an enormous European city we would have enormous companies rivaling us for talent. So it's great to be somewhere that has a steady stream of people that we can work with."
Whilst at one point the company considered decentralising, and having a satellite office elsewhere in the Netherlands, its Directors decided to keep everything in one space to preserve the culture: "we think that the better our people, the better the platform", says Arne, "and we like all of our people to work together."
And this culture is indeed all-important: Arne notes that all of the leadership team are very happy to learn from their staff, especially if it is something to do with another culture. "One of our first expansions was into Germany, but what we didn't know is that lots of German consumers read the T's and C's: in the Netherlands most people ignore them! So, it was only with the help of a German person that we realised for our service to be trusted, it needed to have easily-accessible legal text."
Parkos' expansion has been led by its staff. Entering into the Italian market was only done with the help of an Italian member of staff: "when our Italian Country Manager first started working here, we had to be honest and say to her 'yes, this is great, but we are quite small at the moment and you'll have to start on 16-hours per week'. Now, the manager in question is full-time, and even has someone to help expand our Italian offering!"
Parkos is always on the look-out for more staff, and regularly posts jobs to Make it in the North. For this and many more opportunities in the North, just visit www.makeitinthenorth.nl
Tags: Airportairport parkingGroningeninternationalsjobsMake it in the NorthParkos
Housing Corporation WoonFriesland investing several million into Leeuwarder housing
First Emmen Make it in the North event very successful for both internationals and companies
Thomas Ansell
Breaking news: Isolated family in Drenthe farm appear to be members of the Unification movement


text:
package me.chanjar.weixin.mp.api.impl;

import lombok.RequiredArgsConstructor;
import me.chanjar.weixin.common.service.WxOcrService;
import me.chanjar.weixin.common.bean.ocr.*;
import me.chanjar.weixin.common.error.WxErrorException;
import me.chanjar.weixin.common.requestexecuter.ocr.OcrDiscernRequestExecutor;
import me.chanjar.weixin.mp.api.WxMpService;

import java.io.File;
import java.io.UnsupportedEncodingException;
import java.net.URLEncoder;
import java.nio.charset.StandardCharsets;

import static me.chanjar.weixin.mp.enums.WxMpApiUrl.Ocr.*;

/**
 * ocr 接口实现.
 *
 * @author Binary Wang
 * created on  2019-06-22
 */
@RequiredArgsConstructor
public class WxMpOcrServiceImpl implements WxOcrService {
  private final WxMpService mainService;

  @Override
  public WxOcrIdCardResult idCard(String imgUrl) throws WxErrorException {
    try {
      imgUrl = URLEncoder.encode(imgUrl, StandardCharsets.UTF_8.name());
    } catch (UnsupportedEncodingException e) {
      // ignore cannot happen
    }

    final String result = this.mainService.post(String.format(IDCARD.getUrl(this.mainService.getWxMpConfigStorage()),
      imgUrl), (String) null);
    return WxOcrIdCardResult.fromJson(result);
  }

  @Override
  public WxOcrIdCardResult idCard(File imgFile) throws WxErrorException {
    String result = this.mainService.execute(OcrDiscernRequestExecutor.create(this.mainService.getRequestHttp()),
      FILEIDCARD.getUrl(this.mainService.getWxMpConfigStorage()), imgFile);
    return WxOcrIdCardResult.fromJson(result);
  }

  @Override
  public WxOcrBankCardResult bankCard(String imgUrl) throws WxErrorException {
    try {
      imgUrl = URLEncoder.encode(imgUrl, StandardCharsets.UTF_8.name());
    } catch (UnsupportedEncodingException e) {
      // ignore cannot happen
    }

    final String result = this.mainService.post(String.format(BANK_CARD.getUrl(this.mainService.getWxMpConfigStorage()),
      imgUrl), (String) null);
    return WxOcrBankCardResult.fromJson(result);
  }

  @Override
  public WxOcrBankCardResult bankCard(File imgFile) throws WxErrorException {
    String result = this.mainService.execute(OcrDiscernRequestExecutor.create(this.mainService.getRequestHttp()),
      FILE_BANK_CARD.getUrl(this.mainService.getWxMpConfigStorage()), imgFile);
    return WxOcrBankCardResult.fromJson(result);
  }

  @Override
  public WxOcrDrivingResult driving(String imgUrl) throws WxErrorException {
    try {
      imgUrl = URLEncoder.encode(imgUrl, StandardCharsets.UTF_8.name());
    } catch (UnsupportedEncodingException e) {
      // ignore cannot happen
    }

    final String result = this.mainService.post(String.format(DRIVING.getUrl(this.mainService.getWxMpConfigStorage()),
      imgUrl), (String) null);
    return WxOcrDrivingResult.fromJson(result);
  }

  @Override
  public WxOcrDrivingResult driving(File imgFile) throws WxErrorException {
    String result = this.mainService.execute(OcrDiscernRequestExecutor.create(this.mainService.getRequestHttp()),
      FILE_DRIVING.getUrl(this.mainService.getWxMpConfigStorage()), imgFile);
    return WxOcrDrivingResult.fromJson(result);
  }

  @Override
  public WxOcrDrivingLicenseResult drivingLicense(String imgUrl) throws WxErrorException {
    try {
      imgUrl = URLEncoder.encode(imgUrl, StandardCharsets.UTF_8.name());
    } catch (UnsupportedEncodingException e) {
      // ignore cannot happen
    }

    final String result = this.mainService.post(String.format(DRIVING_LICENSE.getUrl(this.mainService.getWxMpConfigStorage()),
      imgUrl), (String) null);
    return WxOcrDrivingLicenseResult.fromJson(result);
  }

  @Override
  public WxOcrDrivingLicenseResult drivingLicense(File imgFile) throws WxErrorException {
    String result = this.mainService.execute(OcrDiscernRequestExecutor.create(this.mainService.getRequestHttp()),
      FILE_DRIVING_LICENSE.getUrl(this.mainService.getWxMpConfigStorage()), imgFile);
    return WxOcrDrivingLicenseResult.fromJson(result);
  }

  @Override
  public WxOcrBizLicenseResult bizLicense(String imgUrl) throws WxErrorException {
    try {
      imgUrl = URLEncoder.encode(imgUrl, StandardCharsets.UTF_8.name());
    } catch (UnsupportedEncodingException e) {
      // ignore cannot happen
    }

    final String result = this.mainService.post(String.format(BIZ_LICENSE.getUrl(this.mainService.getWxMpConfigStorage()),
      imgUrl), (String) null);
    return WxOcrBizLicenseResult.fromJson(result);
  }

  @Override
  public WxOcrBizLicenseResult bizLicense(File imgFile) throws WxErrorException {
    String result = this.mainService.execute(OcrDiscernRequestExecutor.create(this.mainService.getRequestHttp()),
      FILE_BIZ_LICENSE.getUrl(this.mainService.getWxMpConfigStorage()), imgFile);
    return WxOcrBizLicenseResult.fromJson(result);
  }

  @Override
  public WxOcrCommResult comm(String imgUrl) throws WxErrorException {
    try {
      imgUrl = URLEncoder.encode(imgUrl, StandardCharsets.UTF_8.name());
    } catch (UnsupportedEncodingException e) {
      // ignore cannot happen
    }

    final String result = this.mainService.post(String.format(COMM.getUrl(this.mainService.getWxMpConfigStorage()),
      imgUrl), (String) null);
    return WxOcrCommResult.fromJson(result);
  }

  @Override
  public WxOcrCommResult comm(File imgFile) throws WxErrorException {
    String result = this.mainService.execute(OcrDiscernRequestExecutor.create(this.mainService.getRequestHttp()),
      FILE_COMM.getUrl(this.mainService.getWxMpConfigStorage()), imgFile);
    return WxOcrCommResult.fromJson(result);
  }
}