text:
package com.cubicb.ssm.perks;

import com.cubicb.ssm.chat.ChatUtils;
import com.cubicb.ssm.events.CustomDamageEvent;
import com.cubicb.ssm.events.UpdateEvent;
import com.cubicb.ssm.events.UpdateType;
import com.cubicb.ssm.util.MathUtil;
import com.cubicb.ssm.util.VelocityUtil;
import me.libraryaddict.disguise.DisguiseAPI;
import me.libraryaddict.disguise.disguisetypes.DisguiseType;
import me.libraryaddict.disguise.disguisetypes.MobDisguise;
import me.libraryaddict.disguise.disguisetypes.watchers.CreeperWatcher;
import org.bukkit.Sound;
import org.bukkit.entity.Entity;
import org.bukkit.entity.LivingEntity;
import org.bukkit.entity.Player;
import org.bukkit.event.EventHandler;
import org.bukkit.event.block.Action;
import org.bukkit.event.entity.EntityDamageEvent;
import org.bukkit.event.entity.PlayerDeathEvent;
import org.bukkit.event.player.PlayerInteractEvent;
import org.bukkit.util.Vector;
import org.inventivetalent.particle.ParticleEffect;

import java.util.HashMap;
import java.util.Iterator;

public class PerkExplosiveLeap extends Perk {

    private HashMap<Player, Long> active = new HashMap<Player, Long>();

    public PerkExplosiveLeap() {
        super("Explode", new String[]
                {
                        "Explosive Leap",
                });
    }

    @EventHandler
    public void Activate(PlayerInteractEvent e) {

        if (e.getAction() != Action.RIGHT_CLICK_AIR && e.getAction() != Action.RIGHT_CLICK_BLOCK)
            return;

        if (!e.getPlayer().getItemInHand().getType().toString().contains("_SPADE"))
            return;

        Player player = e.getPlayer();

        if (!kit.hasKit(player))
            return;

        if  (manager.getCooldown().setCooldown(player, this, "_SPADE", 8.0, true)) return;

        active.put(player, System.currentTimeMillis());

        Ignite(player, true);

    }

    @EventHandler
    public void Update(UpdateEvent event) {

        if (event.getType() != UpdateType.TICK)
            return;

        Iterator<Player> chargeIterator = active.keySet().iterator();

        while (chargeIterator.hasNext()) {
            Player player = chargeIterator.next();

            double elapsed = (System.currentTimeMillis() - active.get(player)) / 1000d;

            //Idle in Air
            player.setVelocity(new Vector(0, 0, 0));

            //Sound
            player.getWorld().playSound(player.getLocation(), Sound.CREEPER_HISS, (float) (0.5 + elapsed), (float) (0.5 + elapsed));
            player.setExp(Math.min(0.99f, (float) (elapsed / 1.5)));

            //Not Detonated
            if (elapsed < 1.5)
                continue;

            //Unpower
            Ignite(player, false);

            //Effect
            ParticleEffect.EXPLOSION_HUGE.send(manager.getGame().getPlayers(false), player.getLocation(), 0,
                    0, 0, 0, 1, 128);
            player.getWorld().playSound(player.getLocation(), Sound.EXPLODE, 2f, 1f);

            //Damage
            for (Entity ent : player.getWorld().getEntities()) {
                if (!(ent instanceof LivingEntity))
                    continue;

                if (ent.equals(player))
                    continue;

                double dist = MathUtil.offset(player.getLocation(), ent.getLocation());

                double maxRange = 8;
                double damage = 20;

                if (dist > maxRange)
                    continue;

                if (ent instanceof Player)
                    if (!manager.getGame().isAlive((Player) ent))
                        continue;

                LivingEntity livingEnt = (LivingEntity) ent;

                double scale = 0.1 + 0.9 * ((maxRange - dist) / maxRange);

                //Damage Event
                manager.getDamageManager().NewDamageEvent(livingEnt, player, null,
                        EntityDamageEvent.DamageCause.CUSTOM, damage * scale, true, true, false,
                        getName());
            }

            //Velocity
            VelocityUtil.velocity(player, 1.8, 0.2, 1.4, true);

            //Inform
            manager.getGame().message(player, "Skill", "You used " + getName() + ".", ChatUtils.MessageType.BROADCAST);

            chargeIterator.remove();
        }
    }

    private void Ignite(Player player, Boolean ignite) {

        if (DisguiseAPI.getDisguise(player).getType() == null) return;
        if (DisguiseAPI.getDisguise(player).getType() != DisguiseType.CREEPER) return;

        MobDisguise disguise = (MobDisguise) DisguiseAPI.getDisguise(player);
        CreeperWatcher creeper = (CreeperWatcher) disguise.getWatcher();

        creeper.setIgnited(ignite);

    }

    @EventHandler
    public void Knockback(CustomDamageEvent e) {
        if (e.getReason() == null || !e.getReason().contains(getName()))
            return;

        e.addKnockback(getName(), 2.5);
    }

    @EventHandler
    public void Death(PlayerDeathEvent e) {

        if (!kit.hasKit(e.getEntity()))
            return;

        active.remove(e.getEntity());

        //ignite(e.getEntity(), false);
    }

}


text:
- Humour
- Sam Heughan
In pictures: 10 things you need to know about Glasgow's Duke of Wellington statue and his cone
AS the Duke was given a golden cone to celebrate Scotland's medal haul at the Commonwealth Games, we tell you 10 things you didn't know about the statue.
The Duke of Wellington
GLASGOW'S Duke of Wellington statue has been given a Commonwealth Games makeover and the city hasn't stopped talking about it.
The monument to Arthur Wellesley, the 1st Duke of Wellington, had its trademark orange and white cone replaced with a golden one by our sister paper the Daily Record, to pay homage to Team Scotland's record breaking medal haul at the Games.
It has become a popular attraction over the years with many tourists snapping pictures of the statue, which sits in Glasgow's Royal Exchange Square.
Here, we pay tribute to the Category A-listed monument by revealing 10 things you didn't know about the Duke of Wellington and his cone:
1: In 2011, the Lonely Planet guide included the monument to Arthur Wellesley, 1st Duke of Wellington in its list of the "top 10 most bizarre monuments on Earth", along with the Washington National Cathedral, USA, and the Rocky Balboa statue in Žitište, Serbia.
Tourists and Glaswegians were mystified when the iconic traffic cone had vanished from the Duke of Wellington's head before the Games
2: Scottish artists and designers have paid homage to the iconic sight, such as Bonnie Bling - which you can buy at our Scotland Now shop.
Bonnie Bling's Wellington Statue necklace
3: Author Muriel Gray has confessed to once putting the cone on his head when she was 19, steaming, and out with a bunch of students.
Muriel Gray
4: It was given a golden hat (cone) by our sister paper the Daily Record to celebrate Scotland's record breaking 39 medal success at the 2014 Commonwealth Games. Watch the video below:
The Live Event you are trying to watch is either unavailable or has not started Please refresh this page in your browser to reload this live event video
5: The Duke of Wellington statue was at the centre of controversy last year as Glasgow City Council's plans to double the height of the monument's plinth as part of a £65,000 restoration project in November 2013. The plans received a furious backlash from the public and were ultimately shelved.
Duke of Wellington Statue in Royal Exchange Square with it's landmark cone
6: It is a right of passage and began as a student dare in the city
Pranksters replace the iconic traffic cone on the Duke of Wellingtons head
7: The Wellington Statue even has its own Wikipedia page - http://en.wikipedia.org/wiki/Wellington_Statue,_Glasgow
The Duke of Wellington's Wikipedia page
8: Placing the cone on top of the Duke requires collaboration - you definitely need a leg up to do it, or ladder as the boys from Scottish wrestling promotion ICW did.
Stars of Scottish wrestling promotion ICW place a cone on the Wellington Statue
9: We may have shown you images of people climbing the statue to position the cone, but there is actually a method of magic behind the Duke's hat. On rare occasions - particularly on a cold day - the Duke's horse springs to life by bowing its head and flicking its tail. It then stoops down towards the pavement, picks up a traffic cone with its mouth and flicks it overhead, perfectly landing on top of the Duke. If you don't believe us, then watch the video above for proof...
10: Despite the controversy with Glasgow City Council last year, the cone was a vital part of the Commonwealth Games opening ceremony as an emblem of Glasgow's quirky sense of humour.
The Duke of Wellington Statue and traffic cone was celebrated during the Commonwealth Games opening ceremony
Glasgow 2014: Team Scotland welcome world to the city as Commonwealth Games begin with stunning show
Glasgow's famous Duke of Wellington statue has its iconic traffic cone removed
Most Recent in Lifestyle
What people who hate Christmas are secretly thinking during the festive season
Best April Fool's Day pranks and jokes to play on your friends or your boyfriend and kids at home - if you dare
Best April Fools' Day pranks and jokes to play on your friends or your boyfriend and family at home - if you dare
You know you've got a Scottish maw when ...
'Keep my lipstick in yer sporran': 28 reasons you know you're a Scottish woman

redpajama_set_name: RedPajamaCommonCrawl


The REV Test Small hatchbacks Ford Fiesta vs Seat Ibiza vs Vauxhall CorsaThe item s5 a13 bosch agm car battery 12v 95ah type 019 s5a13 is in sale since Friday, January 18, 2019. S5 A13 Bosch AGM Car Battery 12V 95Ah Type 019 S5A13. This item can be shipped to United Kingdom.


text:
est un film d'horreur américain réalisé par Rich Ragsdale, sorti en 2005.

Synopsis

En Californie, Maria a des cauchemars terribles avec la vision du suicide de sa sœur commis il y a un an.
Sa colocataire Chris l'invite à voyager avec elle et ses amies Tanya et Rose en vacances à la maison de son oncle en Arizona, pour se détendre.
Lorsque les filles arrivent à la maison, elles se rendent dès le premier soir à une boîte de nuit.

Fiche technique
 Titre :  /
 Réalisation : Rich Ragsdale
 Scénario : Ryan R. Johnson
 Musique :
 Producteur :
 Production : Pretty Dangerous Films
 Distribution :
 Pays d'origine :
 Langue d'origine : anglais américain
 Lieux de tournage : Arizona, États-Unis
 Genre : Horreur
 Durée : 90 minutes
 Sortie :
  :
  (sortie DVD)
  (sortie télé)
  :
  (Fearless Tales Genre Festival)
  (Nashville Film Festival)
  (sortie DVD)
  :  (sortie DVD)
  :  (sortie DVD)
  :  (sortie DVD)
  :  (sortie DVD)

Distribution
 Andrew Bryniarski : El Charro
 Danny Trejo : El Charro (voix)
 Drew Mia : Maria (créditée comme Andrew Mia)
 Heidi Androl : Christina
 Kathryn Taylor : Tanya
 KellyDawn Malloy : Rosemary
 Philip Boyd : James
 Matthew Prater : le Roi (crédité comme Matt Prater)
 Tabitha Stevens : Elvira
 Liliana Signorelli : Homeless Woman
 Lyndsay Martin : Brittany
 Michela Fruet : la messagère
 Victoria Vanegas : la sœur de Maria
 Lemmy Kilmister : le prêtre (crédité comme Lemmy Kilmeister)
 James Intveld : l'Archange Michael

Autour du film
Bien que ce soit un film d'horreur, le film contient une scène érotique saphique entre Tabitha Stevens et KellyDawn Malloy.

Notes et références

Liens externes

  The Curse of El Charro sur The Encyclopedia of Lesbian Movie Scenes

Film américain sorti en 2005
Film d'horreur américain
Lesbianisme au cinéma
LGBT au cinéma aux États-Unis

redpajama_set_name: RedPajamaWikipedia


text:
Levels of Intervention Lessons Learned from Past Interventions Crisis Intervention ProgramsThink First Assisting Angry Youth to Become Better Problem Solvers
Join our mailing list and receive updates about our activities.
Implementing Effective Interventions
Interventions in schools can be conducted at three different levels. The school-wide or universal level applies to all students. Targeted interventions are implemented for high-risk students. Focused interventions are necessary for students who require more intensive wrap-around services. The links in this section provide examples of how to conduct such interventions. Most importantly, this section highlights the lessons that educators should learn from previous efforts of others to intervene.
Click on the links below to learn more.
Levels of intervention
Lessons learned from past interventions
Crisis intervention programs
How to defuse an angry student and turn him/her into a problem-solver
Assisting Angry Youth to Become Better Problem Solvers
This web site has been produced by The Melissa Institute for Violence Prevention and Treatment to provide research-based school violence prevention procedures for educators. The web site has been made possible with the generous support of the Robert and Renee Belfer Foundation and other supporters.
The Melissa Institute for Violence Prevention and Treatment to provide research-based school violence prevention procedures for educators


Home Farm House is a lovingly restored 19th century building set in the beautiful countryside of the north east Lake District just a few minutes' drive north of the shores of Ullswater. It was once a working farm but now has been converted into a charming holiday retreat. With an eye to detail and quality, the owner has created a highly desirable and luxurious holiday home that is now available for you to enjoy and to form the basis of many happy and fond holiday memories.
This traditional Lakeland farmhouse has been carefully reconfigured to create a beautiful holiday getaway offering space to relax, socialise with friends or enjoy quality family time together. The old traditional features of this house blend seamlessly with a high quality modern finish whilst retaining so much of the original character.
A beautiful sitting room with welcoming log burning stove is complemented by a cosy snug, the ideal spot to escape to with a good book. Forming the heart of the home is the quality kitchen with its large farmhouse table. Carefully designed to incorporate a bedroom and shower room on the ground floor and two further bedrooms, one with an ensuite, and a beautiful family bathroom on the first floor, Home Farm offers great flexibility to suit all the family.
The popular Lakeland market town of Keswick is just a ten minute drive from the house with a great array of cafes, bars and restaurants and of course the popular, award winning, twice weekly market and great local shops. Five minutes' drive south and you can be strolling on the shores of Ullswater, enjoying a trip on one of the traditional steamers or enjoying the spectacle of the famous Aira Force Waterfall. For those wanting to head to the high fells the challenging and awe-inspiring Blencathra, Helvellyn and Skiddaw are all within easy reach of Home Farm.
Standing at a junction of two peaceful country lanes Home Farm House appears as one would expect of a quintessentially Lakeland farmhouse. The garden wraps around the house and privacy is afforded by the hedge row to the front and parking for three cars is available to the side of the cottage.
The front door opens to a hall way leading to the kitchen and with a handy boot room off to the side, ideal for all your outdoor gear. The quality fitted kitchen includes an electric hob and oven, dishwasher, microwave, Nespresso coffee machine and a great farmhouse dining table ideal for everything from a hearty Lakeland breakfast to a social family dinner. To the side a utility room accommodates the fridge/freezer and washing machine.
An inner hallway connects the remainder of the ground floor rooms; the welcoming sitting room with comfortable sofas, relaxing log burning stove and sun porch, the cosy snug – the ideal spot to escape to with a good book or the weekend papers. The first of the house's three bedrooms is located on the ground floor, a pretty super king (that can be also made up as a twin room if you prefer – please specify when booking) and complemented by a luxurious family bathroom with walk in shower, basin and WC.
On the first floor there are two further sumptuous kingsize bedrooms including one with a high quality ensuite shower room with walk in shower, basin and WC. The final bathroom incorporates a beautiful feature bath, walk in shower, basin and WC.
Back downstairs and to the rear of the property there is a lovely patio with outdoor furniture looking across the garden to the rolling countryside beyond. The garden includes: a sizeable lawn, ideal for family games; mature shrubs and bushes and, an area (next to the woods) set aside by the owner, to encourage wildlife.
Back downstairs there is a further bathroom with walk in shower, basin and WC. The accommodation is completed with a utility area with fridge/freezer, washing machine and the drier is located in the boot room.


text:
import {inc, dec} from './actions';

window.onload = function() {
  let number = document.getElementById('number');
  let incBtn = document.getElementById('inc');
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  incBtn.addEventListener('click', function() {
    number.innerHTML = inc(+number.innerHTML);
  }, false);

  decBtn.addEventListener('click', function() {
    number.innerHTML = dec(+number.innerHTML);
  }, false);
};

redpajama_set_name: RedPajamaGithub


text:
GadgetsTablets
Samsung offers ultra-fast memory for smartphones and tablets
benking 01/05/2013
Samsung has announced memory DRAM New to PC טאבלט And smartphones, which will enable the development of handsets Performence And reduced energy consumption
Tablet PCs and smartphones today include impressive technical data and random access memory (RAM) In high volume, although the South Korean company Samsung wants to take matters into their own hands and bring the mobile gadgets to the edge of their performance capability. In fact,Has released The company on its website, announced סמסונג Officially on memory L Which will be manufactured in the 20 nanometer process and will bring its devices to the top of the performance tables.
The company says the new memory chips have capabilities Performence Equal to memory DRAM Standard on desktop computers. The new memory is able to transmit information at maximum speed of 2,133 Megabytes per second (Mbps), When it comes to performance almost as high as 3 compared to memoryL Which transfers information at a speed of 800Mbps.
For example, they say in Samsung that the new memory capability can transfer three quality movies Full-HD (Whose volume is more than 17 gigabytes) within one second. "Our new memory will enable the world's leading manufacturers to bring mobile devices with higher performance than ever before," said Zhen Yang-yun, סמסונג. The company believes that due to the continued growth of tablet and smartphone screens, memory More effective is definitely a necessary commodity.
MemoryL The new סמסונג Will be available at higher volumes when it is faster than identical memories produced in the process of 30 nm - because it is produced in such a way that it can provide Performence Are tens of percent higher. At the same time, the energy consumption it needs will develop significantly - which may indicate that the devices may become even more subtle and light.
Is the-Galaxy The new Note will be the first to include the memory The LPDDR3?
Samsung is expected to continue later this year declare On its 3 (probably in September), as more and more information surfaced around the Web that it would be the first device to include the "DRAM The new volume is generated in the 20 nanometer process. In addition, it is possible that the 11 Information about him They have also emerged recently, and will also offer the quickest memory.
DDR3 RAM Samsung Galaxy memory Unlocked סמסונג
The smartphone that brings an ornament back to its old age
LG also agrees: Micro-LED is the future of TVs
The ultimate smart sports watch - with a Google operating system
Rising Level: Advanced wireless headphones with 1More noise filtering
Sony is surprising: futuristic electric car and sports as you have not seen on screen
The home machine that dreams of beating the bartenders
Soon at home: a smart assistant in the mirror
Also with the official importer: the advanced Xiaomi Mi Note 10 Pro is available in Israel
Roy Commented:
And maybe Apple will stop their annoyance and start buying components from Samsung again…
AvielA Commented:
Anyone make up numbers?
If such a chip can transmit 2Gbps, more than 60 chips working together are needed to reach 17GB per second.
Theory and reality are different things.


Greta Gerwig's film Lady Bird is a masterpiece. Gerwig (Frances Ha, Mistress America) provides us an insight into life and a part of ourselves few films endeavor let alone accomplish.
Lady Bird stars Saoirse Ronan (Atonement – AAN, Hanna, The Grand Budapest Hotel, Brooklyn – AAN) as a high-school senior experiencing all that comes with this time of life. Instead of being a programmatic re-tread of Hollywood story-line(s) and character(s) presented in out sized and or and overly simplistic form, Lady Bird feels real from start-to-finish. Ronan – as almost always – is perfect in the role.
Better than any film in recent memory, Lady Bird shows us youth, age, inexperience, experience, warmth, cold, sincerity, insincerity, happiness, sadness, the ability to communicate feelings, and the lack thereof, the lack of appreciation and (ultimately) appreciation.
Laurie Metcalf (Mom's voice in Toy Story movies, The Big Bang Theory, Roseanne) and Tracy Letts (U.S. Marshals, The Big Short, Elvis & Nixon) are Lady Bird's parents. Lucas Hedges (Manchester By the Sea – AAN, Moonrise Kingdom), Beanie Feldstein (Orange is the New Black), Timothée Chalamet (Interstellar) and Odeya Rush (Goosebumps) are Lady's Birds circle of friends. Each of these six characters have roles that are rich and well developed. The actors prove to be more than capable in the role. Some with a level of true brilliance.
If you have not seen Atonement (AAN Best Film 2007) do so. All five films nominated in 2007 (Atonement, No Country for Old Men, Michael Clayton, Juno, There Will Be Blood) were worthy of the statue. Atonement, Michael Clayton and No Country for Old Men are in the Lubeck film library and watched repeatedly.
Gerwig is a strong actor. She is great at appearing to be completely self-centered with a total lack of self awareness. However her writing and directing skills may win the day.
The personality of Hedges character in Lady Bird is a 180 degree turn from that in Manchester By the Sea – a performance for which he was nominated for an Academy Award. He is so convincing in both – uncanny.


Deputy Head of the Shchigrovsky urban district Aleksey Goncharov is detained for provocation.
Deputy Head of the Shchigrovsky District Public Utilities Department Aleksey Goncharov was detained for threatening to blow up a hospital, where doctors refused to receive his mother.
It is reported that Gocharov's 69-year-old came to a Shchigry hospital with a complaint of infection. Doctors could not urgently see the patient and advised her to come back in the evening. The woman reported this to her son, after which he called the police and threatened to blow up the hospital if the doctors did not see her.
As a result, siloviki wearing masks came to Goncharov's place. A criminal case was initiated against him. After being questioned, his mother was taken to the hospital to see a doctor.


text:
INSOLVENCY LAW
FINANCING AND BANKING LAW
PHARMACEUTICAL LAW
Family Office / Asset Protection
Boutiq
Assignment of Work to an Employee in a Frivolous Manner (Decision of the Supreme Court from 21 January 2015, file no. 21 Cdo 815/2013)
< Zpět na výpis
According to the Supreme Court, an employer cannot assign work to the employee if it aims to punish the employee for exercising the employee's rights in court; such work assignment is considered as frivolous.
This applies also in cases when the work assignment is in accordance with the employment contract and legal regulation. In the mentioned dispute the employer (high school teacher) demanded declaration of invalidity of the dismissal from employment. The employer dismissed the employee because of unexcused absences on certain lessons.
However, these lessons were assigned to the employee even though he had no corresponding qualifications. In fact, the employee was assigned with these new lessons after he had already been successful in supporting his claim against the employer with the court by invalidating another dismissal.
The Supreme Court ruled that even though the teaching of "new" lessons (mechanical engineering, mechanical components and the like) might fall under the scope of work agreed in the employment contract (high school teacher), it is necessary to consider other circumstances. Such noticeable change of work assignment as in this case (from the original teaching of English language) requires a review in order to determine if the employer's conduct in its entirety and logical consequence cannot be perceived as hidden punishing of the employee.
The Supreme Court concluded that assignment of work for which the employee has no corresponding qualification could represent such hidden punishing of the employee for exercising the employee's rights against the employer in the past.
© 2021 polverini strnad


text:
U.S., Russia agreement for ceasefire in Syria
Category: Expert's opinion, TopStories
Patrick Wintour,
The Guardian, Feb 21, 2016
Guardian headline:
'Provisional' Syria ceasefire plan called into question as bombs kill 120
By Patrick Wintour, The Guardian, Feb 21, 2016
A "provisional agreement" on a ceasefire in Syria has been reached between the US and Russia, the US secretary of state John Kerry said on Sunday, but serious doubts remain on whether it will come into force as the country reeled from a series of deadly car bombs in Syria's two biggest cities that left more than 120 dead.
In Homs, twin car bombs killed at least 57 people and wounded 100 on Sunday, and explosions hit parts of the capital, Damascus, killing a further 62 and wounding 180, according to the UK-based Syrian Observatory for Human Rights. The attacks on both cities were claimed by Islamic State.
Kerry said he had reached an agreement following phone talks with his Russian counterpart Sergei Lavrov, amid signs that Russia is putting some pressure on Syrian president Bashar al-Assad to comply. There are serious doubts over strength of the deal, which would need the agreement of Vladimir Putin and Barack Obama, who are expected to speak by phone later this week.
A previous UN-brokered ceasefire, agreed between the interested parties in Munich a fortnight ago, failed to come into force on Friday as expected, with Russia continuing its bombing campaign and the Syrian army moving to encircle Syria's second city of Homs.
"We have reached a provisional agreement in principle on the terms of a cessation of hostilities that could begin in the coming days," Kerry told a news conference in Amman with Jordanian foreign minister Nasser Judeh on Sunday. Kerry declined to go into the details of the agreement, saying it "is not yet done".
"The modalities for a cessation of hostilities are now being completed. In fact, we are closer to a ceasefire today than we have been," said Kerry, who was also to meet Jordan's King Abdullah. Despite the recent progress made by the Syrian army in northernSyria, Kerry said it was futile to think there was a military solution to the conflict.
Kerry indicated there were still issues to be resolved before the ceasefire could come into force and he did not expect any immediate change on the ground.
However, he reiterated the longtime US position that any political solution to the conflict would not work if Assad remains at the helm of the nation. "Make no mistake. The answer to the Syrian civil war will not be found in any military alliance with Assad," Kerry said. "Let me make that clear."
The Russian foreign ministry seemed to stop short of Kerry's announcement. The ministry said Lavrov and Kerry spoke on the phone Sunday for a second day in a row and discussed "the modality and conditions" for a ceasefire in Syria that would exclude groups that the UN Security Council considers terrorist organisations.
An aerial campaign by Moscow launched last autumn has driven the most significant gains by the Assad regime since the start of the war, having primarily targeted mainstream rebels bent on overthrowing him.
Fighting has intensified in Syria during recent weeks and the earlier deadline to cease military activities was not observed. The United States, Russia and other world powers agreed 12 February on a deal calling for the ceasing of hostilities within a week, the delivery of urgently needed aid to besieged areas of Syria and a return to peace talks in Geneva.
UN envoy Staffan De Mistura halted the latest Syria talks on 3 February, because of major differences between the two sides, exacerbated by increased aerial bombings and a wide military offensive by Syrian troops and their allies under the cover of Russian airstrikes. The humanitarian situation has worsened, with an estimated 13.5 million Syrians in need of aid, including six million children.
The need for a ceasefire has also become even more urgent due to signs that Turkey is threatening to invade northern Syria in a bid to contain the Syrian Kurds, and protect opposition forces. The US has been working with the Syrian Kurds, but Turkey, a key American ally, claims they have links with terrorist organisations inside Turkey. Ankara has been shelling Syrian Kurd positions from inside Turkey despite appeals from America to show restraint.
In an interview with El Pais on Saturday, Assad said he was ready for a ceasefire on the condition "terrorists" did not use a lull in fighting to their advantage and that countries backing insurgents stopped supporting them.
The Syrian opposition had earlier said it had agreed to the "possibility" of a temporary truce, provided there were guarantees Damascus's allies, including Russia, would cease fire, sieges were lifted and aid deliveries were allowed countrywide.
Russia has said it would exclude from the ceasefire operations against organisations "recognised as terrorist by the UN Security Council". This would in effect mean air operations against Isis and the al-Qaida-linked Nusra Front could continue, but there is a dispute about what other groups could be categorised as terrorist. The agreement of Iran would also be required.
Kerry did not suggest his ceasefire would lead to a quick change on the ground. He said: "I do not believe that in the next few days, during which time we try to bring this into effect, there is somehow going to be a tipping point with respect to what is happening on the ground … The opposition has made clear their determination to fight back," he said.
Meanwhile, at least 57 people were killed and 100 people wounded in a pro-government district of Homs, one of the deadliest attacks in the city in five years of civil war, the Syrian Observatory for Human Rights said. The districts hit – in the Zahra neighbourhood – are predominantly Alawite, the minority Muslim sect to which Assad belongs.
Four explosions hit the southern Damascus district of Sayeda Zeinab, where a revered Shia shrine is located, leaving 62 dead and 180 injured, according to the Observatory.
The attacks on Homs and Damascus targeted areas dominated by Muslim minorities reviled by the Sunni radicals of Isis.
A ceasefire and the resumption of aid deliveries has become a de facto precondition for substantive peace talks to start on a future government for Syria.
newcoldwar.org


text:
Il-8 production promoters and use thereof
An object of the present invention is to provide IL-8 production promoters derived from safe food materials and to provide immunostimulants or preventive or treating agents of infectious disease comprising the IL-8 production promoter. The present inventors have found that a composition comprising, as an active ingredient, at least one plant extract from peppermint, dokudami (houttuynia herb), or licorice promotes IL-8 production, and that a composition comprising, as an active ingredient, at least one compound selected from the group consisting of α-humulene, α-pinene, β-pinene, and L-menthol promotes IL-8 production. These IL-8 production promoters can be used in foods and drinks supplemented with immunostimulants or preventive or treating agents of infectious disease.
Satsu, Hideo (Tokyo, JP)
Mae, Tatsumasa (Hyogo, JP)
Tsukagawa, Misuzu (Hyogo, JP)
Kitahara, Mikio (Hyogo, JP)
Yokota, Shinichi (Hyogo, JP)
Shimizu, Makoto (Tokyo, JP)
424/757, 514/729, 514/763, 424/747
A61K36/185; A23L1/30; A61K31/015; A61K31/045; A61K36/00; A61K36/48; A61K36/484; A61K36/534; A61P31/00; A61P37/04; A61P43/00
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MELLER, MICHAEL V
BGL (CHICAGO, IL, US)
1. An interleukin-8 production promoter comprising as an active ingredient at least one kind selected from the group consisting of a peppermint extract and a dokudami (houttuynia herb) extract.
2. An interleukin-8 production promoter comprising a licorice extract as an active ingredient.
3. An interleukin-8 production promoter comprising as an active ingredient at least one compound selected from the group consisting of (α-humulene represented by formula (1): α-pinene represented by formula (2): β-pinene represented by formula (3): and L-menthol represented by formula (4): or a pharmaceutically acceptable salt thereof.
4. A composition for promoting interleukin production comprising an interleukin-8 production promoter according to any one of claims 1 to 3 as an active ingredient.
5. A composition for immunostimulation comprising an interleukin-8 production promoter according to any one of claims 1 to 3 as an active ingredient.
6. A composition for preventing or treating an infectious disease comprising an interleukin-8 production promoter according to any one of claims 1 to 3 as an active ingredient.
7. The composition according to any one of claim 4, wherein the composition is used for food and drink use.
8. A method for promoting interleukin production in mammal comprising administering an effective amount of at least one kind selected from the group consisting of a peppermint extract, a dokudami (houttuynia herb) extract, a licorice extract, a compound represented by formula (1), a compound represented by formula (2), a compound represented by formula (3), and a compound represented by formula (4) to mammal that need them.
9. A method for stimulating immunity in mammal comprising administering an effective amount of at least one kind selected from the group consisting of a peppermint extract, a dokudami (houttuynia herb) extract, a licorice extract, a compound represented by formula (1), a compound represented by formula (2), a compound represented by formula (3), and a compound represented by formula (4) to mammal that need them.
10. A method for preventing or treating an infectious disease in mammal comprising administering an effective amount of at least one kind selected from the group consisting of a peppermint extract, a dokudami (houttuynia herb) extract, a licorice extract, a compound represented by formula (1), a compound represented by formula (2), a compound represented by formula (3), and a compound represented by formula (4) to mammal that need them.
11. The composition according to claim 5, wherein the composition is used for food and drink use.
The present invention relates to interleukin-8 production promoters and to immunostimulants or preventive or treating agents of infectious disease comprising this interleukin-8 production promoter.
Intestinal tract directly comes into contact with various types of foods and so on taken orally, and therefore has both of two vital functions, the function of eliminating harmful substances and the function of absorbing useful components. While the physiological functions of foods are exhibited mainly by substance absorption in intestinal tract and by signal transduction or cytokine regulation brought about by the absorbed components via cells, intestinal immunity among those functions of the intestinal tract plays a key role as a front-line immune system in vivo. The intestinal tract has immunocompetent tissue (GALT: gut associated lymphoreticular tissue) that induces immune reactions against orally ingested antigens as well as intestinal epithelial cells that absorb useful components such as nutrients from foods. Food components act directly or indirectly on these cells and thereby perform immunoregulation, that is, immune promotion or suppression.
Intestinal epithelial cells are known to produce cytokines such as TGF-β, IL-1β, IL-10, and TNF-α, and chemokines such as IL-8, and lead to a increase in the chemokines by infection with a variety of pathogenic bacteria. The intestinal epithelial cells interact with immunocompetent cells through cytokines or chemokines. Among others, IL-8 is deeply implicated in host defense, immune systems, and inflammatory response. Interleukin-8 (hereinafter, abbreviated to IL-8), a neutrophil chemotactic/activating factor, was purified and cloned in 1987 from human peripheral blood mononuclear cells stimulated with LPS (Proc. Natl. Acad. Sci. USA, 84, 9233-9237, 1987).
IL-8 is produced by monocytes, macrophages, fibroblasts, vascular endothelial cells, mast cells, epidermal cells, and the like, and targets cells such as neutrophils, CD8+ T cells, natural killer cells, and monocytes. The known functions of IL-8 include: neutrophil chemotaxis; chemotactic activity for basophils and T-cells; the mobilization of neutrophils from the bone marrow to peripheral blood; neutrophil activation such as release of intracellular lysosomal enzyme, induction of leukotrien B4 (LTB4) production, and induction of active oxygen production, in neutrophils; enhancement of neutrophil adherence to vascular endothelial cells; neutrophil chemotactic activity for human umbilical vein endothelial cells (HUVEC) ; and involvement in vascularization (Cell Technology Suppl., Chemokine Handbook, Vol. 1, p. 32-34, Shujunsya, 2000).
Alternatively, it is known that neutrophils are leukocytes having a central role in host defense by virtue of their phagocytic abilities to engulf and kill invading bacteria (e.g., Escherichia coli, staphylococci, streptococci, and pneumococci), viruses, and fungi, and IL-8 promotes neutrophil activation and enhances abilities of neutrophils.
The action of aggressive immune enhancement through ingestion of foods imparts resistance to living bodies, leading to prevention or treatment of infectious disease. Moreover, cytokines and so on that are involved in immune enhancement provide for therapeutic effects on immune disease such as allergy and for antitumor effects. Although absorption and permeation of food components in intestinal tract have been reported previously, reports that have directly demonstrated the influence of food components on intestinal epithelial cells are few, which include the inhibition of IL-8 production by curcumin (J. Immunol., 163, 3474, 1999), and the promotion of IL-8 production by means of the oral administration of microbial cells such as lactic acid bacteria (Japanese Patent Laid-Open No. 2003-63991).
Alternatively, bacterial invasion to intestinal epithelial cells has been reported to increase IL-8production (J. Clin. Invest., 95, 55-65, 1995). Since IL-8 is closely related to host defense, immunity, and inflammatory response, the promotion of IL-8 production in intestinal epithelial cells can be useful particularly in aggressive immunostimulation and in the prevention or treatment of infectious disease.
It is an unknown fact that peppermint or extracts thereof, dokudami (houttuynia herb) or extracts thereof, and licorice or extracts thereof promote IL-8 production or are useful in immunostimulation or in the prevention or treatment of infectious disease, to which IL-8 contributes.
Moreover, it is also an unknown fact that (α-humulene, pinene, and L-menthol promote IL-8 production or are useful in immunostimulation or in the prevention or treatment of infectious disease, to which IL-8 contributes.
DISCLOSURE OF THE INVENTION
IL-8 production promoters derived from safe food materials are useful in stimulation of immune response and in prevention or treatment of infectious disease, for example as foods and drinks such as foods with health claims (foods for specified health uses, foods with nutrient function claims), health foods, and dietary supplements, or as pharmaceuticals or quasi drugs. However, it is difficult to continuously ingest chemokines such as IL-8 for the purpose of activating neutrophils to enhance their phagocytic abilities. Accordingly, an object of the present invention is to provide IL-8 production promoters derived from safe food materials and to provide immunostimulants or preventive or treating agents of infectious disease comprising this IL-8 production promoter.
The present inventors have conducted extensive studies for attaining the object and have consequently completed the present invention by finding that a composition comprising, as an active ingredient, at least one plant extract from peppermint, dokudami (houttuynia herb), or licorice promotes IL-8production, and that a composition comprising as an active ingredient at least one compound selected from the group consisting of α-humulene, α-pinene, β-pinene, and L-menthol promotes IL-8 production.
Namely, the present invention relates to an IL-8 production promoter comprising a peppermint extract and/or a dokudami (houttuynia herb) extract as an active ingredient.
The present invention also relates to an IL-8 production promoter comprising a licorice extract as an active ingredient.
Moreover, the present invention relates to an interleukin-8 production promoter comprising as an active ingredient at least one compound selected from the group consisting of α-humulene represented by formula (1):
α-pinene represented by formula (2):
β-pinene represented by formula (3):
and L-menthol represented by formula (4):
or a pharmaceutically acceptable salt thereof.
Hereinafter, the embodiments of the present invention will be described in detail.
In one aspect, IL-8 production promoters of the present invention comprise, as an active ingredient, at least one plant extract from peppermint, dokudami (houttuynia herb), or licorice. The IL-8 described herein refers to a leukocyte chemotactic factor with a molecular weight of approximately 8,000 that is produced by a variety of cells such as fibroblasts and endothelial cells.
Peppermint used in the present invention refers to an herb that belongs to genus Mentha of family Lamiacea (Mentha piperita L, and Mentha arvensis). Dokudami (houttuynia herb), also called "jyuyaku", used in the present invention refers to an above-ground part (e.g., leaves, stems, and flowers) of Houttuynia cordata Thunb. belonging to genus Houttuynia of family Saururaceae. Licorice used in the present invention refers to a rhizome of Glycyrrhiza uralensis Fish. belonging to genus Glycyrrhiza of family Leguminosae. All of these plants are foods or food materials and have sufficient history of use as foods, without problems associated with side effects and safety.
Each extract from peppermint, dokudami (houttuynia herb), and licorice used in the present invention can be obtained from the plants by solvent extraction or the like. A method for obtaining the extract is not limited to the solvent extraction, and other extraction procedures may be used, which include steam distillation and a supercritical extraction technique using carbon dioxide. Furthermore, the extract, unless containing impurities inadequate for foods and drinks or pharmaceutical drugs, can be used in the present invention, either directly in extracted solution form or as a crude or semi-purified extract.
The production method of the extract is preferably performed under room temperature and normal pressures using an extraction solvent. After extraction, the resulting product may be made into a liquid, paste, gel, or powder by means of concentration and drying or with use of fats and oils or the like. An extraction temperature is not particularly limited and is generally performed under a condition of −20 to 100° C., preferably 1 to 80° C., more preferably 20 to 60° C. Likewise, an extraction time is not particularly limited, and the extraction is generally performed with stirring or by leaving the starting material to stand for 0.1 to 1 month, preferably 0.5 hours to 7 days. Alternatively, the extraction may be performed under supercritical conditions using carbon dioxide or the like. The extract can optionally be purified by arbitrary procedures using active carbon treatment, ion-exchange resins, and so on.
When solvent extraction is performed, for example, an original, crushed or powder form of each of the plants can be dipped in a 1 to 20-fold volume of a solvent described below and stirred or left to stand, followed by filtration or centrifugation to obtain an extracted solution. Subsequently, the solvent can be removed from the obtained extracted solution by concentration to obtain the extract.
The solvent used in extraction is not particularly limited, and for example, a hydrophilic or hydrophobic solvent can be used. In this context, the hydrophilic solvent refers to a solvent with high polarity and includes water, lower alcohol such as ethanol and methanol, polyhydric alcohol such as propylene glycol, and ketones such as acetone. In this context, the hydrophobic solvent refers to a nonpolar solvent with low polarity and includes esters such as ethyl acetate, fats and oils such as rapeseed oil and olive oil, and hydrocarbons such as hexane. It is preferred that the solvent should be a safe substance available in production or processing of foods, food additives, pharmaceuticals, and so on. Examples of such a solvent include water, ethanol, acetone, glycerin, ethyl acetate, propylene glycol, hexane, and edible fats and oils. It is more preferable to use one or two or more solvents selected from the group consisting of water, ethanol, acetone, glycerin, ethyl acetate, propylene glycol, hexane, and edible fats and oils. The solvent such as ethanol, acetone, ethyl acetate, and hexane is more preferable from the viewpoint of extraction efficiency and ease of removing the solvent after extraction. It is even more preferable to use one or two or more solvents selected from the group consisting of ethanol, acetone, ethyl acetate, and hexane. Ethanol is most preferable from the viewpoint of safety of the residual solvent. The hydrophilic solvent may be used in the form of a hydrous solvent.
Among the extracts thus obtained, a peppermint extract obtained from peppermint herbs by steam distillation or solvent extraction is a kind of spice extract and is an existing additive applied to bitter agents and so on. Moreover, a dokudami (houttuynia herb) extract obtained from dokudami (houttuynia herb) leaves by ethanol extraction and purification is an existing additive applied to antioxidants. Furthermore, a licorice extract obtained from the licorice roots by ethanol extraction is an existing additive applied to antioxidants. In the present invention, these peppermint, dokudami (houttuynia herb), and licorice extracts accepted as food additives can also be used.
In one aspect, the present invention provides IL-8 production promoters comprising as an active ingredient at least one compound selected from the group consisting of peppermint component compounds, that is, α-humulene represented by formula (1) below, α-pinene represented by formula (2) below, β-pinene represented by formula (3) below, and L-menthol represented by formula (4) below, or a pharmaceutically acceptable salt thereof. The influence of the component compounds contained in peppermint on IL-8 secretion by Caco-2 cells was examined. As a result, α-humulene represented by formula (1) below, α-pinene represented by formula (2) below, β-pinene represented by formula (3) below, and L-menthol represented by formula (4) below were shown to have the effect of promoting IL-8 production.
A method for obtaining the α-humulene, α-pinene, β-pinene, and L-menthol represented by formulas (1) to (4) is not particularly limited. The obtained compounds can be used as single compounds or as mixtures of two or more of them in the IL-8 production promoters of the present invention. When these compounds are obtained from peppermint, the same extraction methods as above can be employed. After extraction, the resulting products can be subjected to additional procedures such as separation and purification, for example, filtration, distribution using solvents, concentration, distillation, steam distillation, chromatography, to obtain the compounds. It is preferred that extraction solvents, purification resin, tools, apparatuses, and so on, used in the procedures should be available for use in the production of foods or food additives. Types of plants from which α-humulene, α-pinene, β-pinene, and L-menthol are extracted are not particularly limited, and include cloves (Syzygium aromaticum) of the family Myrtaceae and hops (Humulus lupulus) and so on.
Salts of these compounds are also preferably available in the present invention. When the compounds have a basic moiety, the salts of the compounds can be formed by mixing solutions of the compounds with a solution of a pharmaceutically acceptable acid, for example, hydrochloric acid, sulfuric acid, methanesulfonic acid, fumaric acid, maleic acid, succinic acid, acetic acid, benzoic acid, oxalic acid, citric acid, tartaric acid, carbonic acid, orphosphoric acid. When the compounds have an acidic moiety, their pharmaceutically acceptable salts include salts formed with alkali metal salts such as sodium or potassium salts; alkaline earth metal salts such as calcium or magnesium salts; and salts formed with suitable organic ligands such as quaternary ammonium salts.
The IL-8 production promoters are capable of stimulating immunity in mammal or preventing or treating the infectious disease of mammal. The "immunostimulation" or "stimulating immunity" described herein refers to the activation of immunocytes such as leukocytes that are responsible for the immunological function of eliminating "not-self" such as invading foreign substances (such as bacteria and viruses) or cancer cells. The infectious disease described herein refers to food poisoning and disease caused by, for example, respiratory tract infection via droplets, vehicle-borne infection via water and foods, vector-borne infection via insects and animals, oral infection via foods and drinks, opportunistic infection with harmless indigenous bacteria or attenuated bacteria during the suppression of immunity. Examples of the infectious disease include respiratory infection disease, urinary tract infectious disease, and septicemia, and further include viral disease, bacterial disease, and AIDS.
In one aspect, the present invention provides compositions comprising the IL-8 production promoter as an active ingredient and supplemented with carriers, auxiliaries, food or drink materials, other pharmaceutically acceptable pharmaceutical materials, and so on known in the art. The extract of the present invention from at least one plant selected from the group consisting of peppermint, dokudami (houttuynia herb), and licorice promotes the IL-8 production of mammal including human beings. Moreover, the compositions for promoting IL-8 production of the present invention promote IL-8 production and as such, can be used as compositions for promoting immunostimulants or for prevention or treatment of infectious disease, to which IL-8 contributes.
The compositions provided by the present invention comprise, as an active ingredient, preferably 0.1 to 100% by weight, more preferably 1 to 100% by weight, of at least one kind selected from a group consisting of a peppermint extract, a dokudami (houttuynia herb) extract, a licorice extract, a compound represented by formula (1), a compound represented by formula (2), a compound represented by formula (3), a compound represented by formula (4), and pharmaceutically acceptable salts thereof. The compositions comprise even more preferably 10 to 100% by weight, still more preferably 20 to 100% by weight, most preferably 30 to 100% by weight, of the active ingredient.
A peppermint extract, a dokudami (houttuynia herb) extract, a licorice extract, α-humulene, α-pinene, β-pinene, and L-menthol used in the present invention can be evaluated for their effects of promoting IL-8 production by a method that adds or administers the extracts or compounds to an experimental system that produces IL-8. For example, in an in-vitro experimental system, human colon cancer-derived cell line HT-29 or Caco-2 cells secrete IL-8 into a medium and therefore, can be cultured in the medium supplemented with the extracts to evaluate the effects of promoting IL-8 production by quantifying the amount of IL-8 secreted in the medium. Alternatively, the effects of promoting IL-8 production can be evaluated in a similar experimental system using these cells stimulated with TNF-α in a manner that enhances the amount of IL-8 produced (Chowers, Y., et al., Gastroenterology, 120, 449-459, 2001; and Lahav, M., et al., Clin. Exp. Immunol., 127, 226-233, 2002). Specifically, tests are conducted as described in Examples below to assess significant components at a significant level: P<0.01 as having the effect of promoting IL-8 production.
The IL-8 production promoters, immunostimulants, and treatment or improvement agents of infectious disease of the present invention, and the compositions comprising any one of them as an active ingredient (hereinafter, referred to as the preventive or treating agents and compositions of the present invention) can be utilized for food and drink use and medicinal purposes. The forms are not limited, and the preventive or treating agents and compositions of the present invention can be used, for example as foods and drinks such as foods with health claims (foods for specified health uses, foods with nutrient function claims), health foods, and foods and drinks such as dietary supplements, or as easily available pharmaceutical drugs such as over-the-counter drugs, or as quasi drugs.
The preventive or treating agents and compositions of the present invention may contain components other than each extract from peppermint, dokudami (houttuynia herb), and licorice. Since each extract from peppermint, dokudami (houttuynia herb), and licorice conventionally applied to foods, or a compound contained in the extract serves as an active ingredient, the extracts or compounds of the present invention are highly safe for living bodies. Therefore, the IL-8 production promoters of the present invention can be contained in a wide range of products such as pharmaceutical drugs, functional foods, foods and drinks, and quasi drugs.
The content of the active ingredient in the preventive or treating agents and compositions of the present invention is not particularly specified and can be selected appropriately from within a range that exerts desired effects. When the preventive or treating agents and compositions of the present invention are administered to mammal, for example, human body, the dosage thereof is preferably 0.001 to 1000 mg/kg of body weight/day, more preferably 0.01 to 100 mg/kg of body weight/day, in terms of the amount of the active ingredient, in one dose or several doses.
When the preventive or treating agents and compositions of the present invention are used as foods and drinks, they can be ingested either directly or after they are made into preparations in easily taken forms such as capsules, tablets, or granules with use of additives such as carriers and auxiliaries known in the art. The content of the active ingredient (extract) in these preparations is preferably 0.01 to 100% by weight, more preferably 0.1 to 90% by weight. Types of intended foods and drinks are not particularly limited, unless they inhibit the effects of promoting IL-8 production exhibited by the extracts.
For example, the preventive or treating agents and compositions of the present invention are mixed with food and drink materials and can thereby be used in all kinds of foods and drinks including: confectionery such as chewing gums, chocolates, candies, jellies, biscuits, and crackers; frozen desserts such as ice creams and sherbets; drinks such as tea, soft drinks, energy drinks, and beauty drinks; noodles such as Japanese wheat noodles, Chinese noodles, spaghetti, and instant noodles; fish cake or processed marine products such as kamaboko (steamed fish paste), chikuwa (tubular fish cake), hanpen (fish minced and steamed); seasonings such as dressing, mayonnaise, and sauce; fats and oils such as margarine, butter, and cooking oil , and bread, hams, soup, retort pouch foods, and frozen foods.
When the preventive or treating agents and compositions of the present invention are ingested for food and drink use, the daily intake thereof in adult is preferably 0.001 to 1000 mg/kg of body weight, more preferably 0.01 to 100 mg/kg of body weight, in terms of the amount of the active ingredient.
When the preventive or treating agents and compositions of the present invention are processed into preparations for use as pharmaceutical drugs, the dosage forms are not particularly limited and can be tablets, capsules, injections, drops, powders, suppositories, granules, ointments, suspensions, emulsions, syrups, creams, or the like, selected depending on the purpose of administration, administration routes, and so on. These compositions can contain additives generally used in preparations such as binders, excipients, lubricants, disintegrants, stabilizers, emulsifiers, and buffers. Preferable examples of the binders include starch, trehalose, dextrin, and powders of gum arabic. Preferable examples of the excipients include white sugar, milk sugar, grape sugar, cornstarch, mannitol, crystalline cellulose, calcium phosphate, and calcium sulfate. Preferable examples of the lubricants include stearic acid, talc, wax, and polyethylene glycol. Preferable examples of the disintegrants include starch, carboxymethylcellulose, and cornstarch. Preferable examples of the stabilizers include fats and oils and propylene glycol. Preferable examples of the emulsifiers include anionic surfactants, nonionic surfactants, and polyvinyl alcohol. Preferable examples of the buffers include phosphate, carbonate, and citrate buffer solutions. The daily dosage of these preparations in adult is preferably 0.001 to 1000 mg/kg of body weight, more preferably 0.01 to 100 mg/kg of body weight, in terms of the amount of the extract, in one dose or several doses.
When the preventive or treating agents and compositions of the present invention are processed into preparations for use as quasi drugs, they are optionally supplemented with other additives and the like and can thereby be employed locally as, for example, ointments, liniments, aerosols, cream, soap, face washes, body washes, skin toners, lotions, and bath agents.
In one aspect, the present invention provides a method for promoting interleukin production in mammal, for stimulating immunity in mammal, or for preventing or treating an infectious disease of mammal, comprising administering an effective amount of at least one kind selected from the group consisting of a peppermint extract, a dokudami (houttuynia herb) extract, a licorice extract, a compound represented by formula (1), a compound represented by formula (2), a compound represented by formula (3), a compound represented by formula (4), and a pharmaceutically acceptable salt thereof to mammal that need them. The administration includes enteral administration (e.g., oral administration) and nonenteral administration (e.g., percutaneous administration). Oral administration is preferred. The mammal includes human beings.
FIG. 1 shows IL-8 concentrations in the culture supernatants of Caco-2 cells cultured with extracts;
FIG. 2 shows IL-8 concentrations in the culture supernatants of Caco-2 cells cultured with components;
FIG. 3 shows the cytotoxicity of the extracts; and
FIG. 4 shows the cytotoxicity of α-humulene.
Hereinafter, the present invention will be described more fully with reference to Examples. However, the scope of the present invention is not intended to be limited to these Examples.
Preparation of Peppermint Extract
In a glass container, 20 g of powder of a peppermint (Mentha piperita L.) herb (Kaneka Sun Spice Co., Ltd.) was dipped in 100 ml of ethanol and left with occasional stirring at room temperature for 1 week under shade conditions. The residual powder was removed by filtration using a filter paper (ADVANTEC No. 2) , and the solvent was removed from the resulting extracted solution by concentration under reduced pressure to obtain 1.30 g of peppermint extract.
Preparation of Dokudami (Houttuynia Herb) Extract
In a glass container, 20 g of powder of the above-ground part of dokudami (houttuynia herb) (Houttuynia cordata Thunb.) (Kaneka Sun Spice Co., Ltd.) was dipped in 100 ml of ethanol and left with occasional stirring at room temperature for 1 week under shade conditions. The residual powder was removed by filtration using a filter paper (ADVANTEC No. 2), and the solvent was removed from the resulting extracted solution by concentration under reduced pressure to obtain 1.11 g of a dokudami (houttuynia herb) extract.
Preparation of Licorice Extract
In a glass container, 20 g of powder of a licorice (Glycyrrhiza uralensis Fish.) rhizome (Kaneka Sun Spice Co., Ltd.) was dipped in 100 ml of ethanol and left with occasional stirring at room temperature for 1 week under shade conditions. The residual powder was removed by filtration using a filter paper (ADVANTEC No. 2), and the solvent was removed from the resulting extracted solution by concentration under reduced pressure to obtain 1.88 g of licorice extract.
Effect of Promoting IL-8 Production (1)
Caco-2 cells (human colon cancer-derived cell line; American Type Culture Collection, Rockville, Md., U.S.A.) were used as small-intestinal epithelial cell models to evaluate the influence of peppermint, dokudami (houttuynia herb), and licorice extracts on IL-8 production by the cells.
The Caco-2 cells were subcultured in 24-well plates. The resulting cells were cultured at 37° C. for 14 days under 5% CO2 conditions and thereby differentiated into small-intestinal epithelioid cells. Culture media used were DMEM media (SIGMA Corp.) containing 10% fetal calf serum, 1% non essential amino acid solution, 2% glutamine, 100 U/ml penicillin, and 100 μg/ml streptomycin. A peppermint extract obtained in Example 1, a dokudami (houttuynia herb) extract obtained in Example 2, and a licorice extract obtained in Example 3 were added at each final concentration of 100 μg/ml to the media, and the cells were cultured therein. After 6-hour culture, the media were replaced with additive-free media, followed by additional culture for 12 hours. The resulting culture supernatants were subjected to sandwich ELISA assay (Eckmann, L., et al., Gastroenterology, 105, 1689-1697, 1993) to quantify the amount of IL-8 in the culture supernatants. The relative IL-8 concentrations to a control are shown in FIG. 1.
As seen from FIG. 1, each of the peppermint, dokudami (houttuynia herb), and licorice extracts remarkably promoted IL-8 production by the Caco-2 cells, with a significant difference: P<0.01.
Caco-2 cells (human colon cancer-derived cell line; American Type Culture Collection, Rockville, Md., U.S.A.) were used as small-intestinal epithelial cell models to evaluate the influence of α-humulene, α-pinene, β-pinene and L-menthol on IL-8 production by the cells.
The Caco-2 cells were subcultured in 24-well plates. The resulting cells were cultured at 37° C. for 14 days under 5% Co2 conditions and thereby differentiated into small-intestinal epithelioid cells. Culture media used were DMEM media (SIGMA Corp.) containing 10% fetal calf serum, 1% non essential amino acid solution, 2% glutamine, 100 U/ml penicillin, and 100 μg/ml streptomycin. α-humulene (SIGMA Corp.), α-pinene (SIGMA Corp.), β-pinene (SIGMA Corp.), and L-menthol (SIGMA Corp.) were added at each final concentration of 100 μg/ml to the media, and the cells were cultured therein. After 6-hour culture, the media was replaced with additive-free media, followed by additional culture for 12 hours. The resulting culture supernatants were subjected to sandwich ELISA assay to quantify the amount of IL-8 in the culture supernatants. The relative IL-8 concentrations to a control are shown in FIG. 2.
As seen from FIG. 2, the α-humulene, α-pinene, β-pinene, and L-menthol remarkably promoted IL-8 production by the Caco-2 cells, with a significant difference: P<0.01.
Evaluation of Cytotoxicity by LDH (Lactate Dehydrogenase) Assay (1)
The cytotoxicity of peppermint, dokudami (houttuynia herb), licorice extracts was evaluated with Caco-2 cells. The Caco-2 cells differentiated into small-intestinal epithelioid cells in the same way as in Example 4 were cultured for 24 hours in media containing the peppermint, dokudami (houttuynia herb), and licorice extracts at each final concentration of 100 μg/ml. Subsequently, the media were removed, and the resulting cells were washed twice with PBS (phosphate buffered saline) (−) (Nissui Co., Ltd.). The cells were further supplemented with 700 μl of PBS (−) and left undisturbed at 37° C. for 2 hours. Then, the PBS (−) was collected, and the cells were dissolved in 500 μl of 0.1% Triton X-100 (Nacalai Tesque, Inc.). LDH-CytotoxicTestWako (Wako Pure Chemical Industries, Ltd.) was used to measure LDH concentrations in the collected PBS (−) and cell lysate. The principles of the assay are described in detail in Decker, T. and Lohmann-Matthes, M. L., J. Immunol. Methods, 115, 61-69 (1988). In summary, this assay is a method for quantifying cytotoxicity based on the activity of LDH released from dead cells by colormetrically determining formazan converted from a tetrazolium salt serving as a coloring reagent. The rate of free LDH (%) was calculated according to the equation below by using the LDH concentration in the collected PBS (−) as the amount of free LDH and the LDH concentration in the cell lysate as the amount of intracellular LDH.
Rate of free LDH(%)=(Amount of free LDH)/(Amount of free LDH+Amount of intracellular LDH)×100.
As seen from FIG. 3, each of the peppermint, dokudami (houttuynia herb), and licorice extracts did not differ from a control, and was therefore shown to produce no cytotoxicity. Furthermore, the effect of promoting IL-8 production exhibited by each of the peppermint, dokudami (houttuynia herb), and licorice extracts was shown to be independent of cytotoxicity.
The cytotoxicity of α-humulene was evaluated with Caco-2 cells. The Caco-2 cells differentiated into small-intestinal epithelioid cells in the same way as in Example 4 were cultured for 24 hours in a medium containing 100 μg/ml α-humulene. Subsequently, the medium was removed, and the resulting cells were washed twice with PBS (−) (Nissui Co., Ltd.). The cells were further supplemented with 700 μl of PBS (−) and left undisturbed at 37° C. for 2 hours. Then, the PBS (−) was collected, and the cells were dissolved in 500 μl of 0.1 Triton X-100 (Nacalai Tesque, Inc.). LDH-Cytotoxic Test Wako (Wako Pure Chemical Industries, Ltd.) was used to measure LDH concentrations in the collected PBS (−) and cell lysate. The rate of free LDH (6) was calculated according to the equation below by using the LDH concentration in the collected PBS (—) as the amount of free LDH and the LDH concentration in the cell lysate as the amount of intracellular LDH.
As seen from FIG. 4, the α-humulene did not differ from a control, and was therefore shown to produce no cytotoxicity. Furthermore, the effect of promoting IL-8 production exhibited by the α-humulene was shown to be independent of cytotoxicity.
Preparation of Capsule
A mixture was prepared in the proportion of 40 parts by weight of a peppermint extract obtained by the method described in Example 1, 30 parts by weight of sodium carboxymethylcellulose, 20 parts by weight of crystalline cellulose, and 10 parts by weight of vitamin C. The mixture was crushed and packed into a gelatin capsule to prepare a peppermint extract-containing capsule for food and drink use.
A dokudami (houttuynia herb) extract-containing capsule for food and drink use was prepared in the same way as in Example 8 except that the dokudami (houttuynia herb) extract described in Example 2 was used instead of a peppermint extract.
A licorice extract-containing capsule for food and drink use was prepared in the same way as in Example 8 except that the licorice extract described in Example 3 was used instead of a peppermint extract.
INDUSTRIAL APPLICABILITY
According to the present invention, IL-8 production promoters derived from safe food materials as well as immunostimulants or preventive or treating agents of infectious disease comprising this IL-8 production promoter can be obtained. These IL-8 production promoters and compositions are useful in the stimulation of immune response and in the prevention or treatment of infectious disease, and can be utilized as foods and drinks such as foods with health claims (foods for specified health uses, foods with nutrient function claims), health foods, and dietary supplements, or as pharmaceutical drugs or quasi drugs.
Previous Patent: Di-aryl substituted triazole modulators of metabotropic glutamate receptor-5
Next Patent: Process for preparation of labisia pumila extract


This session reviews the most recent research on adolescent sexual behavior and well-being. Topics include the effectiveness of virginity pledges, STD prevalence, and the current rise in teenage pregnancy.
Session Objectives: Discuss the role of virginity pledges in adolescent pregnancy prevention. Describe the link between selected factors (i.e., youth assets, community factors, maternal hiv serostatus) and engaging in risky sexual behaviors as an adolescent. Explain factors contributing to the recent increase in the national rate of teenage births.


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Q: AWS <-> GCP S2S VPN with dynamic routing - filtering/priority adjustments I need to setup S2S VPN between AWS and GCP clouds. This needs to work in High Availability and use dynamic routing.
On AWS side I have a Transit Gateway with number of VPC networks attached to which I want to attach also the VPN (well, in fact on AWS that will be two VPN connections with 2 tunnels each). Important part is that one of the VPCs advertises route 0.0.0.0/0 and it has to stay the - this is the only exit to the public internet in this setup (other VPCs do not have own Internet Gateways and use this route instead). This route gets advertised to GCP...
Now, on GCP side all the routes received from AWS are registered with priority 100 while default GCP routes have priority=1000. This means that when I establish VPN entire public traffic from GCP starts flowing into AWS first (0.0.0.0/0 from AWS with prio 100 is considered better than default 0.0.0.0/0 through own GCP Internet Gateway with prio 1000). Besides the cost impact it also breaks some functionalities on GCP side (i.e. AppEngine Flex health checks can't get through firewall).
My question is: how can I avoid this?
I can think of number of solutions:

*

*Disable advertisement of public routes on AWS side somehow

*Increase priority of advertised routes on AWS side (increase MED value for each route)

*Increase all the priorities received from VPN on GCP side (like, "comes from VPN then add X to the MED value).

*FIlter some routes received from paired network on GCP side.

Any of these strategies would work for me but I have no idea how to do any of them. I have found filtering of advertised routes and custom MED value in GCP so that I could adjust what GCP advertises to AWS but I need exactly other way around...

A: You can adjust the priority of dynamic routes in the gcp side.
See https://cloud.google.com/network-connectivity/docs/router/how-to/updating-priority for more details

redpajama_set_name: RedPajamaStackExchange


Naval mines, perhaps more than any other maritime weapon, hold the potential to so substantially tip the cost of warfare as to make employment of forces practically unpalatable to a naval commander. Indeed, since the advent of modern warfare in the mid-1800s, mines have played a role in most major conflicts between nations. During the Civil War, naval mines cost Union forces more losses than Confederate guns. The mine barrage in the North Sea during World War I precluded German submarines from fully exploiting the battlefield. A quarter century later, the United States, Japan, Germany, and Italy employed naval mines against each other in World War II. Naval mines saw extensive use in Korea, Vietnam, and the Iran-Iraq War.


Increased pedestrian traffic on school days at a busy Solana Beach intersection led the city to help pay for two crossing guards there through the rest of the academic year.
The Solana Beach City Council voted 5-0 without discussion on Wednesday, April 10, to amend its agreement with the Solana Beach School District for sharing the cost of supplying crossing guards.
As a result of the change, the city will hire two guards to help ensure the safety of children and others walking across the street at Lomas Santa Fe Drive and Stevens Avenue.
Earl Warren Middle School and the Solana Beach Library are situated at the southwest corner, while Skyline Elementary School is northeast of the junction.
Under the agreement, the city pays 35 percent of the cost for crossing guards, while the district reimburses it for the remaining 65 percent. The city's cost for the two new guards is $2,534 of the $7,241 total.
The new hires will increase the crossing guard staff to eight at a total cost this year of $96,103, of which $33,636 will be paid by the city.
Other crossing guards are located on Lomas Santa Fe at the southbound Interstate 5 offramp, northbound I-5 onramp, and Santa Helena Drive, as well as at Santa Helena and Santa Victoria Drive near Solana Vista Elementary.
The agreement for the additional guards runs to June 30, the end of the fiscal year. City Manager Greg Wade said in his report to the council that the crossing-guard program will be reassessed after this school year to determine how it should be structured in the future.


FRANKIE Foster has opened up on his rugby player past as he heads into the Love Island villa.
Love Island has hit the villa residents with yet another twist as they've recruited 12 new Islanders.
Frankie Foster - a Business Management Student and Fitness Coach from Cheltenham - is just one of the six boys and six girls set to shake up the villa.
And ahead jetting off to Spain, the 22 year old bombshell revealed his claimed to fame.
So clearly Frankie — who has also done modelling in the past, too — is a rugby fanatic.
Over on his Instagram page, the new Islander has been posted snaps in his rugby kit since he was 2014 - making him just 18 at the time.
He previously played for the England Colleges and toured Belgium with the team in 2014.
Speaking of the tour, his former team mate Josh Williams told Love Rugby League: "I thoroughly enjoyed the tour as a whole, it was a group of great guys I was playing with and to get the win was fantastic," he said.
Judging by his Instagram page — the sportsman has 8,000 followers to date — Frankie took a step back due to an injury.
In March 2017, he posted a hospital snap in a gown, and followed up in April with some flash back of his rugby career.
It read: "3 weeks into 9 months out and already missing playing with the boys! #hottubclub #YTB #rugbyleague #shknee."
Of course he has kept up his fitness career since stepping back from professional sports.
He works as a fitness coach at a gym, and his profile reads: "It's great to see people not only reaching their fitness goals, but learning, enjoying themselves, and being excited to come back for more!"
Will he give personal trainer Adam Collard and gym owner Sam Bird a run for their money in the house?


(1)The problem, in this case, is hard to solve.
(2)Furthermore, several people telephoned the same night.
The average family income in our Kangming City increased from 8,000 yuan per year in 1998 to 20,000 yuan in 2008.In the meantime, the structure of the average family expenses has changed, too. These graphs show the change clearly.
Recently, we have made a survey of the people on physical training. Only 35 percent of the people surveyed have taken part in physical activities.
(1)Indeed, a dessert is always enjoyable.
(2)Above all, d山水画图片o not build an open fire in a forest.
(1)Yet there was still a chance that he would win.
(2)Except for one girl, all 视频下载,最易学会的"偷分"技巧:"换词大法"写英语作文!,非天夜翔the hikers returned.
(1)For instance, a telegram often costs more than a telephone call.
(2)Thus the trip finally began.
(1)In addition, the tour stops in Vancouver.
(2)Furthermore, the time for registration has been extended.
(1)First, you mail in an application. Second, you ask for an appointment. Third, you send them three personal references.
(2)Then you come to a traffic light and turn right.
(1)In the same way, we look for a good doctor.
(2)Similarly, the Thais enjoy spicy foods.
(1)In contrast, the red fluid does not lose its color.
(2)The husband wanted a boy, whereas the wife wanted a girl.


Take a break and align yourself!
As a yoga teacher, I obviously aim for all my students to go away from a class feeling better, more relaxed, stretched yet relaxed. However, it always warms my heart when someone tells me that they are practicing at home, and feeling the benefits of their practice in their daily lives. Taking our yoga off the mat and into every part of our day is an amazing way to improve our lives and boost our wellbeing, so I advocate taking 'minibreaks' of just 5 or 10 minutes whenever you can through the day, which will ultimately increase your productivity as well as making you feel amazing! During these brief pauses, you may like to take your awareness to your breath, to your surroundings, or, as in the practice below, to your posture….
So, how long have you sat at your desk without a break? It's so easy to get caught up in our work and stay in position for hours at a time, and only realise once we move how stiff and uncomfortable we have become!
So, if you're in need of a break, maybe change position as you read this and then try the visualisation to help improve your posture – and your energy, creativity and productivity as well!
So, if you're sitting (un)comfortably, let's begin!
Did you know that as your body stiffens up, you are blocking the free flow of energy around it? In yoga we think of the spine as housing the main energy centres of the body, whirling around and distributing energy all around the body (you can learn more about this in my upcoming workshop here). If you don't warm to that image, you can just think of the central nervous system and all the nerves emanating from the spinal cord to convey their messages to the body as a whole.
So, if we hunch ourselves up and restrict that flow, not only are we setting ourselves up for a variety of aches and pains – think backache, neck and shoulder tension and pain, headaches – we are also limiting ourselves in other ways. We might find that we keep pushing on to get through our workload, but that it's getting harder and harder to think straight. That our ideas are starting to dry up. That we are never ever going to finish and will have to work late into the evening…..aaaargh!
This is exactly the time to stop and have a break. It might seem counterintuitive, the idea that stopping will help us get things done more quickly, but I've found exactly that, time and time again. And our posture itself can sometimes be to blame.
So, right now, stop and think about how you are sitting. Are your feet flat on the floor, or do you have your legs crossed? What part of your body is making contact with the seat? (Yes, I know it's likely to be your bottom, but how is the weight distributed – central or to one side? Are you sitting on your tailbone or your sitting bones? Bet you can guess which ones you are meant to sit on!) How is your spine feeling? What about your shoulders? Your neck and your head?
Now, to adjust your position, place your feet flat on the floor and rest your weight on to your sitting bones (those two pointy bones in your buttocks – it can help to physically move the buttocks out of the way a bit with your hands!) Try to make the weight even between them as much as you can. If you can, adjust your seat height or use a cushion so that your hips are level with, or higher than, your knees, to ensure a good balance through the pelvis. Feel the spine lifting up from the pelvis, letting it lengthen, and then roll the shoulders back and down, letting the points of the shoulder blades slide down either side of the spine. Let your arms relax, maybe resting your hands gently in your lap, or letting them hang down by your sides. Now for your neck and head – let the neck lengthen and the head lift effortlessly…imagine your head is like a balloon, really light and free, and the spine is like the string – no tension at all. Now, just before you float away (you are meant to be working, after all!), think about the end of your string going down into a weight (like the weights you get on a helium balloon to hold them down). This weight corresponds to your points of contact with the seat and floor – your feet and sitting bones. Let your weight really drop down through them, letting gravity ease out your tensions and allowing your upper body to find more space.
Pause and observe your breath in this position for a while, letting any tension fall away with your outbreath.
And, when you feel better, and more refreshed, you can return to your work with a clearer head, and letting your energy flow freely – watch out, world!
In my last post, I wrote about the importance of being able to stay with our uncomfortable feelings, and to let them pass. In my yoga teaching and therapy practice, as well as in my own personal life, it is evident that we really struggle with our emotions, and may hold on to perceived hurts for long after the event which caused them. We may feed our sadness or our anger, dwelling on the events or circumstances of our lives to which we attribute the emotion, going over and over it in our minds. We can have a relatively small encounter which upsets us, and by repeatedly bringing it to mind, we can blow it out of all proportion; when it's a more significant event, we can hold on to the associated feelings for years. Once we dwell on and feed an emotion, it can become a part of us. It is no longer just an energy flowing uncomfortably – but ultimately harmlessly – through us. Instead, it crystallizes and becomes an attitude.
We all have these attitudes or outlooks, which can affect our whole lives and the way in which others perceive us. We all know people who we would describe as angry, sad, fearful or anxious – as well as those we would think of as basically happy, giving and forgiving types. We also flit in and out of these modes of being throughout our own lives. So what started as a brief, passing sensation can last much longer and colour our whole life.
But just because the attitude has begun to dominate our general mood, doesn't mean it has to be that way forever. The emotion may seem to have solidified, even to have become immovable, and yet it can still melt away once we become aware of it and begin to work with it. Even if anger has become such a basic part of our nature that we react irritably to minor events and explode when faced with bigger challenges; even if we are so fearful that we feel we cannot move forward in our lives. Things which seem permanent can change and dissipate over time.
Firstly, we need awareness. We must not close our eyes to the way we are. We must see the difference between the way we would like to be, and the way we truly are. Not judging, but seeing kindly, with compassion for the difficult parts of ourselves.
Secondly, we need to desire change, and to create the space to change. One way we create this space is through the breath; through meditation. Just sitting quietly – watching the breath, stilling the mind. Noticing the space between the inbreath and the outbreath. Calming the mind so that the endless chatter starts to ease away. An analogy often used is that of the sky – letting our thoughts be like clouds, just floating through our minds without holding on to them or spinning off in all directions. In this way, we slowly learn to stop fanning the flames of our emotions, and to be less reactive in our wider lives. Whilst we are learning – and this may be for the rest of our lives! – we must continue to be kindly observant of ourselves, to reflect on our progress and not only our inevitable failings. And whilst we are developing this kindness for ourselves, and learning not to identify with our difficult feelings – acknowledging, for example, that anger is a passing energy rather than turning ourselves into 'an angry person' – we could also think more kindly of the difficult people in our lives, allowing that they too can be other than the way we perceive them.


Are you are an experienced Health Care Assistant (HCA) who likes variety and enjoys the challenges of working in a hospital environment?
We have a number of opportunities available for Health Care Assistants (HCA's) to work with us on a 'as and when needed' basis.
We care for patients 24 hours a day so flexibility with shifts would be an advantage. As an HCA in our casual pool you would be contacted and asked to work when departments need additional HCA support.
Working as an HCA your role will be to provide support to the ward nurses by assisting them with patient care and completing housekeeping and clerical tasks.
This is a great opportunity for those interested in working in a hospital environment as an HCA, as our casual pool HCA's are offered the first chance to apply for any permanent roles that become available.
Ideally you will be an experienced Health Care Assistant with NZQA Certificate in Health and Wellbeing Level 3 and have experience in working either in a health care environment.
However, training and development are a strong focus at Hutt Valley DHB, so we would love to hear from you if you have a desire to upskill.
For further information on this role, please email recruitment@huttvalleydhb.org.nz and indicate the vacancy number 8111372A-19 and job title in the subject line.


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The Orlando shooting wasn't organized terrorism. It was mass murder. There's a difference.
Here's the key distinction that everyone misses about the deadliest shooting in U.S. history
AP Photo/Phelan M. Ebenhack
byRyan Cooper
Dozens of people being systematically shot to death: It's as American as apple pie.
More so, in fact. Apples come from Asia and were first baked into pies centuries ago in Europe. But outside of failed states and active war zones, only America experiences these sort of mass shootings with such clockwork regularity. Our number was up yet again in Orlando, Florida, last weekend, when a man entered a gay nightclub and shot 102 people, killing 49 of them.
Conservative pundits and politicians jumped to their usual position and pinned the blame on Islam. It's little more than the usual anti-Muslim bigotry — but it also illustrates a key tactical distinction that is often overlooked at times like these. When confronted with an incident of political violence, it's critical to recognize whether it is organized or the result of a single unbalanced person — because it will call for a different response.
It is true that the killer was apparently Muslim, and in a 911 call before he was killed by police pledged allegiance to ISIS. If we call this terrorism then it was the worst such incident on American soil since 9/11.
However, another picture emerges from different details of his life. He had a young son, and wanted to be a police officer, even posing in NYPD shirts on his Myspace page. His ex-wife (they divorced in 2011), who described abuse at his hands, said in an interview that he was "mentally unstable and mentally ill," and not particularly religious. Others described a man with extreme anger problems and overt bigotry towards all manner of people.
Now, it would be equally unjust to pin the blame for the shooting on, say, New York cops. One of the more macabre parts of the post-mass shooting ritual is the breathless rooting through the culprit's biography for hints of the characteristics of one's political enemies. It's also a gross error to blame the mentally ill in general.
But when it comes to preventing this type of mass murder, these personal details are important in what they signal about the level of organization behind this attack. This was pretty clearly one person without any real institutional backing. Whatever the Islamic State's opportunistic claims of responsibility, it was one guy with weapons, ammunition, and body armor obtained legally.
Compare that to 9/11, where a highly organized team, trained in foreign camps and funded by a secret organization, exploited a security loophole in both airport checkpoints and the cultural expectation for how hijackings were supposed to work.
Considered so, it's obvious that two different kinds of attacks require a different response. After 9/11, federal authorities needed to upgrade airport security, passengers had to change how they thought about hijackings, and the government had to take some sort of action against al Qaeda. Some of those actions were completed before the end of the day, others were attempted but bungled, and others were a disastrous failure, but that a wise response would have included some of each of these things is indisputable.
A single person driven to commit an act of mass violence, even if he was radicalized by ISIS propaganda, presents a very different sort of problem. No use of force overseas can stop someone from developing radical views — Anwar al-Awlaki was killed by a drone strike almost five years ago, but it's impossible to scrub his videos from the internet. No change in security protocols can stop the formation of crowds.
For an example of the worst type of response, look no further than the presumptive Republican nominee for president, Donald Trump. He quickly blamed the incident on Islam, invoked it as support for his proposal to ban Muslims from entering the country, and said "we really have to increase the bombings." This wouldn't be an appropriate response after a classic terrorist attack — but it's especially inappropriate now.
What is actually needed is to make it more difficult to get the most lethal armaments and ammunition, access to quality mental health care for everyone, and quality police work to find people plotting an attack before it happens. The avoidance of collective punishment, state repression, or bigotry is of critical importance here, since the best intelligence always comes from people close to a potential plotter.
Or, if we wanted to play into ISIS's hands as much as possible, we'd elect Donald Trump.
Ryan Cooper
2 million words at The Week
The promise and peril of electric cars
The growth backlash
The Supreme Court is a bastion of unearned privilege
Biden calls classified files found at his home 'stray papers' from 1974
Old News?
Parents preparing to sue school district where 6-year-old shot teacher
virginia school shooting
Disney to cut 7,000 jobs, restructure company in cost-saving measure
Cuts at the Mouse House


Description: Radiating in a red raw silk choli, this set steals the show! The red choli comes with a gorgeous zardosi and sequins work that take the whole look a notch higher. the net lehenga with tassels on the side dori and the net dupatta subtle out the whole look. The dupatta is also bedecked with zardosi work and sequins.


Reminiscent of an old fashioned barber shop, with the leather chairs, barbicide, haircuts, aftershave, hair tonic and shaving foam give this bar it's soft but masculine scent. Jojoba and hemp oils with a touch of mango butter give this bar super nourishing and conditioning qualities. Clean and fresh, you'll be ready to hit the town!


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Institute for Global Environmental Strategies (IGES) -- Satoyama Development Mechanism 2016
The IGES, the United Nations University Institute for Advanced Studies on Sustainability, and Japan's Ministry of the Environment announce the latest round of sub-grants under the Satoyama Development Mechanism. The International Partnership for the Satoyama Initiative (IPSI) promotes the sustainable use of Socio-Ecological Production Landscapes and Seascapes. Grants are up to US$10 thousand for field projects; research; collaboration activities; and capacity building and outreach that link ecosystems and community systems on a sustainable basis. Applicants must be approved members of the IPSI at the date of submitting project proposals. The application deadline is 30 July 2016.
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Kyosho Mini-Z Calsonic Impul Z 2004 Fairlady Z (350Z) JGTC MR-02 RM ReadySet.
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Rodenbücher István (Szekszárd, 1984. február 22. –) magyar labdarúgó.

Pályafutása

2009-ben tagja volt az Összefogás Napja alkalmából megrendezett teremtornán győztes MTK csapatának.

Ferencvárosi TC
2010. június 2-án 3 éves szerződést írt alá a Ferencváros csapatához.

Lombard Pápa
2011. augusztus 26-án 3 évre írt alá a Lombard Pápa Termál FC csapatához.

Statisztika

Mérkőzései a válogatottban

Jegyzetek

Források
Profil a magyarfutball.hu-n
Profil az MTK hivatalos honlapján
Rodenbücher profilja az MLSZ honlapján
Rodenbücher István adatlapja a HLSZ.hu-n
Profil a footballdatabase.eu-n
Rodenbücher István adatlapja a national-football-teams.com-on
NS online játékosprofil
 Fradi-védőt igazoltak Véberék

Magyar labdarúgók
Labdarúgóhátvédek
Az MTK labdarúgói
A BFC Siófok labdarúgói
A Ferencváros labdarúgói
A Lombard Pápa labdarúgói
Szekszárdiak
1984-ben született személyek
A Vasas labdarúgói
A Paksi FC labdarúgói
Élő személyek
Magyar bajnok labdarúgók
A Szigetszentmiklósi TK labdarúgói