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The Origin Of Species By Natural Selection Essay
The Origin Of Species By Natural Selection Essay
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First, that the distribution of life on earth can't be predicted based on abiotic factors. Among the examples given is that between the Old and New World, there exist very similar habitats that contain very different suites of animals. Conversely, there can be strikingly similar animals that exist under various environments. Since the theory that life was created at several geographic points on earth also says that each species was created in their best habitat, both these examples give evidence against such a theory.
Secondly, that isolation contributes to the suite of taxa present in an area. Darwin assigns the strength of a barrier effect based on the presence of stopping places. A long distance ocean barrier without stopping places would have the strongest isolation effect, as on many islands. Other barriers with an isolating effect are mountain ranges, deserts, and large rivers. This applies to marine life as well; for example, the Isthmus of Panama serves as a thin but impassable barrier between seas. Without an isolating effect, there is generally a gradient of clearly related species as one travels along a continuous habitat (whether terrestrial or marine). Fossils give historical support for this observation. When discussing the lack of barriers and the relatednes...
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...m a different angle than earlier sections. Namely, that some organisms which are basal to a taxon have had ample time to experience those rare dispersal events mentioned earlier; as well as being relatively slow to change compared to more recently derived species. In most cases, this combination should allow them to be widely found. This tendency makes sense only when taken from the single radiation point theory, with colonization occurring from the most likely source with subsequent modification.
Overall, Darwin presents compelling evidence for distribution of species from a single radiation point using knowledge of geologic history from the time, extrapolations from his theory of descent by modification, observations from himself as well as Gould, Wallace and others, and contributions from other disciplines--largely ecology, but also paleontology and glaciology.
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text: Camping near the Ocean..So many memories bounded to that place..The Beast is RoaRing..Comment what do u like in this pic..;)At the beach, life doesn't move hour to hour but mood to moment. We live by the Vamsidhar Reddy-The sailor manI love this pic..The redness had seeped from the day and night was arranging herself around us. CExperiencing one of the best sunsets in India ..while studying the behaviour of G Prashanth Reddy-says sunset is free bhai..dont miss it....:dVote which one do u prefer in Rain..Breezer or Chai?Hum saath saath hai.. While heading towards Karnataka..Thoughts......The mind of friends are like railway track. they never meet.. but has to go togePleasant evening @Vagator beach..Scenic view from the top of Tungabhadra DamThe scenic surrounds with nostalgia for heavenly bliss and eternal calmness.For GoaHotelsMapCandolim beachHotelsMapFort AguadaHotelsMapShantadurga Temple Kavlem Ponda GoaHotelsMapVagator BeachHotelsMapAnjunaHotelsMapChapora FortHotelsMapDona PaulaHotelsMapAlwar HomeHotelsMapTungabhadra DamHotelsMapCandolimHotelsMapTungabhadra Dam HospetHotelsMap

subset: commoncrawl


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For the finale premiere series Hamlet's Lunacy will draw parallels between Shakespeare's Hamlet and the present-day conflicts. Hamlet's Lunacy involves a journey through time and space inviting the audience to confront and reflect on the ethics of action. As Hamlet discovers in Shakespeare's dramaturgy, to do nothing is to take position. What to do in a world of fake news where bearings on'reality'are slipping fast? do you take arms against a sea of troubles and blow them to the moon? To do or not to do?
Hamlet's Lunacy explores the living history of Hamlet by conveying historical and scientific data in ways that are visually compelling. Through the play of Hamlet it looks at how technological advances and scientific developments lead to new ways of interpreting the world and perceiving ourselves.
Eric Joris and Mesut Arslan push the boundaries of what can be visually represented to forge new ways of seeing and inhabiting data.
The audience is divided in 4 groups that rotate.


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This book is listed in:
- Historical ( 1,036 )
- Fiction ( 17,656 )
- Paranormal ( 768 )
- LGBT Fiction ( 5,075 )
- Romance ( 6,506 )
- Ghost & Horror ( 576 )
Stranger at the Door
Book Description
South Carolina lawyer Calvin Amos is confident he can gain Thomas Basinger his freedom on appeal. Thom was convicted of a murder during an armed robbery gone bad. But Basinger's case proves more difficult than Cal anticipated, and the battle he assumed he'd win turns into a devastating failure. Remorseful over the personal defeat, after Basinger is executed, Cal throws himself out of his office window.
Bizarrely, the fall doesn't kill him. Even stranger, Thom Basinger rings Cal's doorbell looking for a job. Both men are drawn to each other. Before long, the two forge a unique, heartfelt connection that transcends the boundaries of life and death.
Calvin Amos always imagined himself in possession of some great love or other. He didn't know he had to die to find it.
- Hardcover: 87 pages |
- Publisher: Dreamspinner Press |
- Publication date: May 25, 2015 |
- Language: English |
- Format: Ebook


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Mar 29, 2018
Point of Sale (POS) for the business automation
- 5Comments
- Gaurav Rai
POS Systems are best to be used in retail environment. Techbit Solutions has recently started developing POS Systems for retail, restaurants, pharmaceuticals, health industries and super markets with support of different hardware include touch screen, Thermal printers, Label printers, bar code scanners, cash drawers and normal LPT Printers. Systems also include loyalty programs, marketing and other features to promote the business. It's also having support of Mobile/iPad to operate from any hand held devices. In technology, we are using Microsoft Windows Presentation Foundation (WPF), Microsoft Windows Communication Foundation, XAML, C#, SqlLite version to get installed easily on different operating systems.
POS systems are developed on the basis of client/server architecture where there remains one common server software that interacts with all the terminals to be used by different operators accompanied with POS hardware. All transactions are stored on the server and with the help of port forwarding, mobile apps installed on iPad/Tablets are able to communication with POS system. Main features of POS system:
· Hardware Integrations (Touch Screen, Label and Thermal Printers, Bar code scanner, Pole device, Cash Drawers and Payment Processing)
· Inventory Management
· Order Management
· Stock Adjustment
· Waste Management
· Accounting
· Automatic Backup and Restoring
POS system works for:
· Retail and Supermarket
· Healthcare/Pharmacy
· Hotels and Restaurants
· Ticketing Systems
New comment
Prashant Patel
8/22/2018 | https://www.softwaresuggest.com/us/retail-pos-system
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Lead category for all firearms disciplines.
3GUN events held monthly at LC & SA.
IDPA events held monthly at LC & SA.
NRA Rimfire Qualification Program. Previously known as the NRA Light Rifle Qualification Program.
The general membership meeting that is held on the first Wednesday of each month.
LC & SA Committee events.
Club events that do not fall into one of the other categories.
All training classes held at LCSA.
Use this category when a facility at the club is closed for use by the general membership.
Members must:
Members not adhering to the above are subject to suspension of membership privileges up to and including expulsion from the club.
No firearm will be handled or touched while people are down range, or when the range is declared SAFE.
LC & SA Firearm Range Rule
Continue to execute all the express provisions of our national Constitution, and the Union will endure forever--it being impossible to destroy it, except by some action not provide for in the instrument itself.
Abraham Lincoln First Inaugural Address
Date: March 4, 1861


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I've never had any experience and even though I dont plan on doing this anytime soon, I want to know just in case. How do you guys confess to a girl? Do you have a speech like in those dramas? Or do you just say something simple like, "you know, I really like you"?
Either way can work. It's a lot easier to just tell them you like them, but if you can dig up the courage for a long speech go for it! The girl who I like -- I've wanted to tell her I like her for a while but I couldn't find the right moment. Recently though, the timing felt right and I just told her "I like you." She may or may not have gotten that I really like her, but I was finally able to say it at least.
You don't. You imply it.
Ignore you see in TV or movies. It's called fiction for a reason.
Well, whatever you do, don't give her a dog biscuit and tell her to fetch. It usually isn't taken kindly.
Then again...
Seriously, don't give her a note. If you can't muster up the guts to talk to her and get the lay of the land, you have no shot with her anyway. Don't go on for months.
The advice we give you would probably be more efficient if we know if you're confessing to a girl online or in person.
Lots of people seem to think you should never tell a girl you like her, but I don't think you should think that can't work, if that's what you want to do. Personally it's just not my style. In my most recent close-distance relationship, I just asked her if she wanted to be my girlfriend and she said yes. Actually, my words were, "Would you like to be...intertwined?" It was pitiful! But that should show you that it doesn't matter how you go about doing it if the girls wants to date you. If she wants to, she wants to. If she doesn't, she doesn't. The way you go about asking probably won't make or break the deal, based on my experience at least. The most important thing is to get to know her and see if you two connect well.
It it's a long distance relationship over the internet, you fail. Period.
Maybe non-anonymous is better.
I don't mean to flame, but seriously, online relationships are such a hassle. I've been in one, and the only good thing I can say about the whole ordeal is that atleast the sex life doesn't get into a lull. Every time you meet the tension is there.
>Ignore you see in TV or movies. It's called fiction for a reason.
IAWTC. Like I'm saying in that other thread, the entire concept of "confessing" like in movies or whatever is asinine. Big speeches aren't necessary; just say a few words to let her know how important she is to you, and all the rest can go unsaid.
>>8 I agree with you. I have been in a long distance relationship and it was such a hassle, and the long distance was pretty much the cause of our break-up. I said to myself, "I am never getting into an online relationship again!" but I am falling for a girl all over again (I have better judgement nowadays, so it isn't just puppy love or desperation out of loneliness or anything like that). So, while I don't think you should go out of your way to look for girls on the internet instead of real life, don't totally avoid the internet. If you meet a girl online and eventually fall for her, don't shun it just because it's online. If you really don't think you could find a girl you like more anywhere else, I say go for it. Long distance relationships are a hassle, but they can be worth it as long as it could eventually become short distance.
Here's a word of advice.
Personally I think it is the stupidest thing you can ever do in your entire life.
Don't confess, period. If you can't strike it up without such banalities, pack it up and go home.
BTW, I've fallen for a girl in real life.
First of all...don't be so quick to give up your freedoms for some stupid girl.
Second, you don't confess shit to a girl. You just do whatever. Women want Men. They want to be taken, not begged over.
>>"They want to be taken, not begged over."
This ties very neatly into the whole tired "women fall for jerks" argument. Women don't fall for jerks. Women just find high self-esteem attractive. Surely a guy who is more confident in his abilities is more fun to be around than some whining kid?
>>14 is one of the bitter dorks that ruin discussion boards like these. Don't worry, be happy, brother.
>>14 seems very biased against relationships, so I wouldn't take his advice to heart.
So it's a RL relationship huh? I would say what you should do first is try to get her out just with you, or with some friends if that's all you can get. If you already know eachother well, ask her if she wants to go to the movies or something. I personally don't see a problem with confessing and saying you like her. It really depends on the type of people you are, I guess. All the girls I've liked didn't find it strange that I told them I liked them, and told me they liked me too. If you're nerdy type of people, chances are she won't expect you to be really cool and smooth about getting with her.
> I'm sure you can get into a relationship with her without confessing, too. Ask her out sometime.
Is a confession of sorts appropriate on a first date? Obviously it's not the first topic of conversation, but could an 'I really like you and value our time together' kind of thing finish a date and possibly be a bridge to a second meeting?
>Obviously it's not the first topic of conversation, but could an 'I really like you and value our time together' kind of thing finish a date and possibly be a bridge to a second meeting?
Saying it that way sounds just a little too much, especially if the date was only a couple hours long or so. Go for something that's a little more short-term sounding, like "I had a good time today/tonight. Can we hang out again (Friday)?"
How do you flirt? It's one of the things I never understood or learned.. Please help. OTZ
>>20 I wish I could help, but every time I think of someone "flirting" with a girl, the only thing I can imagine is an obnoxious kind of flirting. The only thing I can think of is physical contact, like sitting close to her, casual stuff like that.
If you have a crush on someone, and have nothing to talk about with her but don't have the balls to just ask her out, it's not going anywhere. (Or maybe I'm just bitter.)
Try making friends.
I can ask her out (I've asked her before but we haven't had a plan work yet) and I have friends (guys and girls) but I have no idea how to flirt.
I have had a guy confess his love for me in a speech once. His words were very powerful...and even shocking to me, because nobody had ever used the words he did to describe me before. He of course waited until it was too late and treated me like a burden the entire time we knew each other.
TRU DAT. The last bad relationship I had started out with the guy asking me out over the internet, so in retrospect, I should have seen what a whiny coward he was from the way he started the relationship.
I am >>14 and I will have my detractors know this:
If anything, it is people like me who SAVE boards like this and keep things in perspective. People with your love and doves attitudes are the same people who set themselves up for failure.
>>26 what you don't understand is that not all women are simply "women," and people have different kinds of relationships and different ways of forming them than you do. It's fine if you go about it the way you're saying, but it's wrong to totally pass off strategies more on the confession side. I have had three relationships (real ones with real women) in my life, and they all started by me telling the girl I liked her or wanted to be with her (after getting to know them for a month or two, and in one case a year or two), and her returning my feelings. I have never been turned down or thought of as a creep. Maybe I'm just lucky, but at the very least I am proof that it's more than possible to get a girlfriend without changing your personality to be a suave and aggressive.
as much as I wish that were possible, more and more 26 seems right
Well I have dated three girls this far in life and have been liked by at least three others, and I am not a very manly man. Though I'm not hopeless, needy, and desperate either. I think >>26 is right in that respect -- it would be difficult to find a girl that wants to be with a guy like that. But if you find a girl that likes you for who you are, I really can't imagine she'd think of you as any less of a man because you were shy about telling her how much you like her.
>People with your love and doves attitudes are the same people who set themselves up for failure.
Of course. You set yourself up for failure every time you ask a girl "Hey, wanna go grab a cup of coffee with me?" How the hell do you intend to find a relationship if you don't set yourself up for for failure?
God.....you just hate it when someone sets you straight.
Set me straight? rofl.
There's lots of points in your post I'd like to address, but frankly I think my time could be spent on better pursuits. Suffice it to say that you'll find things much faster if you're actually looking for them, and I'll leave it up to the readers of this thread to decide which of us is having a better time in life.
>>31 There are as many wrong ways to live a life of romance as there is to live a life of ~fun dating~. I once contemplated just dating for fun after a big breakup, but I decided against it. I don't need sex so badly that I can't wait for the right girl to come along. I feel people who just date for fun and sex are very shallow and lead an unfulfilling life. I don't care what your reasons are -- that's what I think of it. Maybe it's unreasonable to think that? If it is, it's not nearly as unreasonable as thinking serious relationships are phoney when you've never even been in one. Or maybe you have, and it turned out bad, causing you to have this attitude towards them? I don't know, nor do I care. In my eyes, you are very wrong about love. I've been in serious relationships. I know the happiness that comes out of them as well as the heart-wrenching sadness. And you know what? It's very worth it.
Maturity helps. Confessing is needless provided you're both mature enough. This probably doesn't fit your situation.
I think the best way to go about it is to just reflect it in your behavior. Show your interested by flirting, being friendly, and being yourself. Going overboard however will make you a creep so don't be any different then you are normally.
I prefer being in love with anime characters, it's just so much more fulfilling than any real relationship could ever be
yeah it's awesome, especially the two-way communication and the sex
A confession should be stating the obvious.
Fun dating....
No it's just not taking everything so seriously. God some of you are almost suicidally set on this love and romance kick.
>>39 What is wrong with you? Most people here aren't hell-bent on winning a girl over. I don't know why you can only group people in two categories: People that haaaaaaave to be in a relationship, and people like you? Just because someone wants to confess to a girl, it doesn't mean they spend their entire life thinking about love and romance and can't do anything else until they have a serious relationship with a girl. You're obviously irrationally biased against serious relationships for whatever reason, so I hope nobody has taken your advice.
>>40 I hope people DO take my advice because the second you "confess your love" you are going to send some girl into a real creep out zone. That takes people by surprise. Especially if they don't feel the same way about you that you do about them.
Ideally, a confession shouldn't be needed. If you like each other it will come naturally. If you have to confess it usually means it's one sided and not mutual.
>>41 You're still going on about "confessing" like the situation you're describing is the only possible situtation there could ever be in the world of "confessing to girls." I have "confessed" four times and never sent the girl into a "creep out" zone. Like I said, there are right ways and wrong ways to do it. Saying there is no right way to confess is ignorant since I am LIVING PROOF that it's entirely false.
>>42 Though it's true a confession isn't necessary to begin a relationship, that doesn't mean it's ideal. Along with the feelings not being mutual, it could also mean one or both sides are shy in nature; don't have experience with relationships; aren't sure if the other likes him/her; etc. There's simply too much to consider in any given situation to say a confession is -never- needed.
Wow...a lot of views here to consider. However, I still have a question. How do I flirt? I sorta missed out on that life lesson.
>>45 it somewhat depends on the type of person you are and lifestyle you lead. What I means is, a nerdy person can't really flirt the same way a really outgoing "jock" would flirt. The gist of it is to make physical contact, maybe some flirtacious comments/jokes. Just try to feel for a moment to make an advance. This is probably no help to you, but I don't know what else to say lol
When I flirt I usually say "nice tits".
For some reason it works well for me, lesser people might get kicked in the balls, maced, or shot though.
eye contact, smiling, making jokes, dropping subtle hints, touching, etc.
It helps to be picky about women.
I usually make sure they believe in Valhalla and Odin before going any further than nice tits.
Okay... what exactly is the meaning of "flirting" ? Can somebody define?
I want to know how that meaning applies to singles and to the ones in relationships.
I'm not sure that you can call flirting "flirting" if you're ina relationship with the girl. Flirting is basically doing things to make the girl know you're interested in her.
>>51 not really
flirt: playful behavior intended to arouse sexual interest
is what google giving me.
If it's a definition you want, go look it up in a dictionary or google. I would always recommend practicality...so go hang out in a uni / college bar or regular bar to see what people get up to.
So flirting is basically stuff like compliments?
not so much compliments...but those would be incorporated when talking to the person you like.
Ultimamtely, through the discussion, will get sense if they are "in" to you or not...which culminates in YOU asking HE/SHE out...
Being practical...agreed thumbs up


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Dating does not set you up well. It puts an ungodly unreal quantity of stress on each parties. It glosses up for the hope of romantic gestures that always tend to be stale, robotic, and rehearsed. I imagine in allowing like to be natural hat we should not be forcing our lives into little compartments to direct romance. Romance can occur asiandate at any time and infrequently does unexpectedly. Love will come by itself time. I do assume you need to put together for it, however attempting to take the bull by the horns only frustrates the bull; you must let it come to you and allow itself to be gentle at your side.
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There is no feminism in Russia or Ukraine. Sure, up to date Slavic women need to have equal rights but they don't go out of their technique to prove that they are just like men, in the best way Western girls typically do. They do not wish to refuse good clothes and cosmetics; they imagine asian date that a girl should look womanly. Russian girls still have traditional views on how a man ought to behave: when it comes to dating culture, they want their males to be real gentlemen with them. Every Russian lady likes when a man holds the door and lets her go first, when he helps her take away her coat, when he stands up when sees her approaching him, and when he brings flowers on a date and pays for dinner.
It is easy to say thank you" in the beginning of the connection, but additional down the street, we start forgetting those two treasured words. Even worse, we begin taking things without any consideration. So bear in asiandate.com mind to say thank you" for all the nice issues she has given you, stated about you, or has executed for you. It might not sound like a lot, however for her, she'll see it as a really considerate notice.


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I have a beloved wife
It's such a wonderful thing to be invited to a wedding. Friends are vulnerable, brave and so articulate about the way they feel. It makes me weep, every time. I am useless!
I definitely love my closest friends, but I don't often shout that out in front of 150 people and then make a speech about how great they are. Hearts are out. It's pretty mega.
I am of course excited about the lifetime of happiness that awaits my newly-wed-friends-to-be…but I am also excited about having an excuse to wear some of my favourite dresses. I'm not sure I can justify buying any new ones. This blue one from Solace London in the photo is a favourite but I'll have to choose between that and the orange version of it I also own (lol).
However, dresses aside. For anyone getting married in the next few months, I found a poem about marriage which to me evokes the familiarity and love symptomatic of the best kind of long-term partnership. First read over two years ago but the sentiment stays with me today. It's just the most beautiful collection of words.
Makes me pretty excited about watching one of my best friends get married to the most wonderful of men in a few weeks time. Beloved as they already are to each other.
I have a beloved wife,
Familiar as the skirt
Of a well-worn robe,
And so this distant journeying
Fills my heart with grief.


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Space 4 Art has launched a Kickstarter campaign to raise $8,000 by May 21 to pay artists who exhibit in the space and to make gallery improvements. In an email, May-ling Martinez, one of the studio artists at Space 4 Art who sits on the gallery committee, said the venue has been holding exciting, relevant shows without much of a budget for the last two years.---
"We want to keep working, expand and [we] would love to be able to compensate the artists participating with a stipend," she wrote. "We have been doing a lot with very little, imagining what we are capable to do with more."
Space 4 Art had submitted its application for official nonprofit status, says co-founder, board member and studio artist Chris Warr.
"While they wait for final approval," he said, "they need to raise quick money to pay the artists already on this year's roster."
"We really want to improve our programming and start to pay artists immediately," Warr said.***
Last Wednesday, San Diego Mayor Jerry Sanders and arts and culture leaders announced what most people who read CityBeat should already know: Funding the arts is a good investment. Sanders announced the release of the 2011 Arts and Culture Economic and Community Impact Report, issued annually by the city's Commission for Arts and Culture and the San Diego Regional Arts and Culture Coalition. According to the report, funding from the Commission for Arts and Culture supported 68 local arts organizations, generated approximately $170 million for San Diego's economy in the last fiscal year and raised about $202 million in revenue. Organizations funded through the city's Organizational Support Program also served about 612,000 people and 5,270 schools and community groups, the report said.
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Colin Cloud to give Edinburgh a sneak preview of Vegas show
AMERICA'S Got Talent star Colin Cloud has been packing them in to his last full Fringe run this year so successfully, that he has decided to give fans of his forensic mind-reading, an extra special treat - a sneak preview of his Las Vegas show.
Wednesday, 21st August 2019, 1:03 pm
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This will be the one and only chance to come and experience a 'best of' from Cloud as he brings together his favourite material from his previous Fringe shows.
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Tickets are strictly limited and sure to fly out the door, make sure you get yours now.
www.thestand.co.uk/shows/893-colin-cloud-does-not-exist/# £10


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Nice and spacious room. Breakfast is very good. Lots of selections
Elite Hotel Esplanade
- Free WiFi
- Breakfast included
- Pet Friendly
- Air Conditioning
What's nearby
- Lilla Torg
- 1 min walk
- Stortorget
- 2 min walk
- Malmo Town Hall (Radhuset)
- 2 min walk
- Malmo (MMX-Sturup)
- 31 min drive
Choose your room
Book online or call:1-800-238-0767
Your dates need to occur after 2019-10-20. Try updating your dates to see prices for your trip.
About this area
Located in Malmo's Centrum neighborhood, Elite Hotel Esplanade is on the Strip and near a train station. Notable landmarks in the area include Lilla Torg and St Petri Kyrka. Aq-va-kul and Ribersborgs Kallbadhus are also worth visiting. Our guests appreciate the hotel's location for the sightseeing.
What's nearby
- Lilla Torg - 1 min walk
- Stortorget - 2 min walk
- Malmo Town Hall (Radhuset) - 2 min walk
- St Petri Kyrka - 5 min walk
- Malmo Concert and Congress Hall - 8 min walk
Getting around
- Malmö Central Station - 5 min walk
- Malmo (MMX-Sturup) - 31 min drive
- Quan – Restaurant with a bar offering Asian cuisine. Serves breakfast, lunch, and dinner on select days.
About this property
Elite Hotel Esplanade
Along with a restaurant, this smoke-free hotel has a 24-hour health club and a bar/lounge. Full breakfast is free. Other amenities include self parking, a business center, and conference space. All 128 rooms boast deep soaking tubs and offer free WiFi and LCD TVs. Other amenities available to guests include minibars, room service, and coffee makers.
Property amenities
- Available in all rooms: Free WiFi
Parking and transportation
- Self parking: SEK 255 per day
- Limited parking spaces
- Parking height restrictions apply
Food and drink
- Free full breakfast available 6:30 AM–10:00 AM on weekdays and 7:30 AM–11 AM on weekends
- 1 restaurant
- 1 bar
- Room service available
Things to do
- 24-hour health club
Family friendly
- Dry cleaning service
- Elevator
- Free newspapers in lobby
- Front-desk safe
Guest services
- 24-hour front desk
- Daily housekeeping
- Dry cleaning service
- Luggage storage
- Multilingual staff
Languages spoken
- Danish
- English
- German
- Spanish
- Swedish
- Thai
Business services
- Business center
- Computer station
- Meeting rooms
- Conference space (11119 square feet)
- If you have requests for specific accessibility needs, please note them in the special requests field on the booking page after selecting your room.
- Accessible bathroom
- In-room accessibility
- Smoke-free property
Room amenities
- Air conditioning
- Bathtub or shower
- Deep soaking bathtub
- Free toiletries
- Hair dryer
- Pay movies
- Satellite channels
Food and drink
- Coffee/tea maker
- Minibar
- Connecting rooms available
- Desk
- Iron/ironing board
- Safe
Nearby things to do
Where to eat
- Quan – Restaurant with a bar offering Asian cuisine. Serves breakfast, lunch, and dinner on select days.
Great location and comfort level
Beautifully position just off the main square in the old town, and a convenient 5 min walk from the station (with luggage) you find the Elite Hotel Esplanade. The room is large and well appointed. The TV has a range of streaming services for staying in touch with English shows. The bathroom is a very decent size and the water pressure good. Wifi throughout the hotel is strong. The staff are friendly. The beds are comfy. My room looked over the internal roof area so wasn't very pleasant. Other rooms may have a street view. Might be worth asking on check in. You can definitely walk from the station. No need for a taxi. The last little stretch (100 or so metres) is over cobble stones but manageable - I had 40 kgs / two bags in tow.
Upon our arrival after 3:00 pm, our room was not ready for check in. We were compensated with free parking for the inconvenience. Hotel is conveniently located next to the beautiful Lilla Torg square. Our room was clean and spacious. Breakfast was included but could use more variety. Overall a nice property in a beautiful area of Malmo that allows for easy access and enjoyment of the city.


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Back to Journals » OncoTargets and Therapy » Volume 11
Inhibition of XIAP increases carboplatin sensitivity in ovarian cancer
Authors Zhang Y, Huang F, Luo Q, Wu X, Liu Z, Chen H, Huang Y
Received 13 April 2018
Accepted for publication 2 October 2018
Published 5 December 2018 Volume 2018:11 Pages 8751—8759
DOI https://doi.org/10.2147/OTT.S171053
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Andrew Yee
Peer reviewer comments 3
Editor who approved publication: Prof. Dr. Geoffrey Pietersz
Yiping Zhang,1,2 Furong Huang,3 Qingyu Luo,3 Xiaowei Wu,3 Zhihua Liu,3 Hongyan Chen,3 Yinghui Huang1
1Cancer Institute, College of Life Science and Bioengineering, Beijing University of Technology, Beijing, China; 2China National Center for Biotechnology Development, Beijing, China; 3The State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Purpose: Carboplatin is a first-line treatment for ovarian cancer. However, most patients develop resistance and undergo disease recurrence. This study aims to explore the relationship between the expression of X-linked inhibitor of apoptosis protein (XIAP) and carboplatin sensitivity in ovarian cancer.
Patients and methods: We examined the expression of XIAP in ovarian cancer by immunochemistry. Next, we investigated the role of XIAP in regulating carboplatin sensitivity in ovarian cancer ES2 and 3AO cells through Cell Counting Kit-8 cell viability assay and fluorescein isothiocyanate-Annexin V/propidium iodide apoptosis assay. Expression of apoptotic effectors was measured by Western blot.
Results: The immunochemistry results showed that high XIAP expression levels inversely correlated with carboplatin response (P=0.03) and progression-free survival (P=0.0068) in patients with ovarian cancer. Knockdown of XIAP repressed the cell viabilities in the carboplatin-treated cells and increased carboplatin-induced caspase activation. In summary, our data show that XIAP mediates carboplatin sensitivity of ovarian cancer.
Conclusion: In summary, our data show that XIAP mediates carboplatin sensitivity of ovarian cancer and XIAP may be a novel target for the treatment of carboplatin-resistant ovarian cancer.
Keywords: XIAP, carboplatin, chemosensitivity, ovarian cancer
Ovarian cancer is the most lethal type of malignant tumors of the female reproductive system, and the patient's 5-year survival rate is relatively low and has the highest mortality rate. Platinum compounds have been proved to be the most effective drugs for the treatment of ovarian carcinoma. Carboplatin has long been established as a first-line drug for the treatment of ovarian carcinoma,1 but the resistance of patients to platinum compounds is a major challenge in the treatment of ovarian cancer.2 So far, there is no very effective solution to this problem.3,4 Therefore, it is important to identify markers for predicting response to carboplatin, which may allow for the development of therapeutic strategies for overcoming chemoresistance.
Inhibitor of apoptosis protein (IAP) family has been reported to promote tumor formation and metastasis.5,6 X-linked inhibitor of apoptosis protein (XIAP) is a member of the IAP family. XIAP not only exerts an anti-apoptotic function but also inhibits autophagy via XIAP-Mdm2-p53 signaling.7 In addition, XIAP has been involved in regulating innate immune responses by mediating NOD signaling through interaction with RIP2.8 Also, XIAP confers resistance to some chemotherapeutic drugs in various types of cancer including ovarian cancer.9–14 For example, phenoxodiol, Piceatannol, and HtrA1 enhance cisplatin sensitivity in ovarian cancer via the degradation of XIAP.9–11 However, there have been no studies that investigated the role of XIAP in conferring carboplatin sensitivity in ovarian cancer.
In the present study, we examined the expression of XIAP in clinical ovarian cancer samples (151 cases) and analyzed the relationships between XIAP expression and clinicopathological features of ovarian cancer. Furthermore, we investigated the functional role of XIAP on carboplatin sensitivity at the cellular and molecular level.
Materials and methods
Tissue specimens
Tissue samples were collected from 151 patients with ovarian serous adenocarcinoma during their initial treatment at the Chinese Academy of Medical Sciences Cancer Hospital (Beijing, China). All cancer tissues were diagnosed as primary ovarian cancer by histopathology. Patients received platinum-based adjuvant chemotherapy treatment after the first cytoreductive surgery and signed informed consent forms for sample collection to participate in this research. This study was approved by the Institutional Review Board of the Chinese Academy of Medical Sciences Cancer Institute.
An ovarian cancer tissue microarray including primary ovarian tumors was constructed with each case represented twice. For immunohistochemistry (IHC) staining, the slides were deparaffinized, rehydrated, immersed in 3% hydrogen peroxide solution for 10 minutes, heated in a microwave in citrate buffer (pH 6.0) for 10 minutes, and cooled at room temperature. The slides were blocked by 10% normal goat serum at 37°C for 30 minutes and then incubated with rabbit polyclonal antibody against XIAP at a dilution of 1:500 overnight at 4°C. IHC was performed using the PV-9000 Polymer Detection System for Immuno-Histological Staining kit (Beijing Golden Bridge Biotechnology Company). 3,3′-Diaminobenzidine was used to visualize the reaction, followed by counterstaining with hematoxylin. Visual analysis was performed using ImageScope software (Aperio Technologies). The percentage of staining was automatically assessed by ImageScope software, and the expression score was determined by multiplying the percentage of staining by the staining intensity. Based on the median IHC score, tumors with scores were classified into the high-expression group (marked 1) and the low-expression group (recorded as 0). The location and scoring of the tumor were completed with two professional clinicopathologists.
Cell lines and cell culture
Ovarian carcinoma cell lines (ES2, SKOV3, 3AO) and 293 T cells were preserved in our laboratory. The ovarian cancer cell lines were cultured with RPMI-1640 medium containing 10% FBS, 100 U/mL penicillin, and 100 mg/mL streptomycin. 293 T cells were maintained with DMEM supplemented with 10% FBS, 100 U/mL penicillin, and 100 mg/mL streptomycin. All cells were cultured at 37°C in a humidified atmosphere containing 5% CO2.
The immunohistochemistry antibody for XIAP (PRS3331) and the specific antibody for β-actin (A5316) were purchased from Sigma-Aldrich Co (St Louis, MO, USA). The antibody against caspase 3 (9662S) and caspase 9 (9502S) were from Cell Signaling Technology. Specific antibodies against PARP (Sc-7150) and XIAP (Sc-55551) were purchased from Santa Cruz Biotechnology Inc. (Dallas, TX, USA).
Packaging of virus and transfection
The shGFP or shXIAP lentiviral and packaging vectors were transfected into 293 T cells according to manufacturer's instructions. The shRNA sequences were as follows: shXIAP-4: ACACGTACTTGTGCGAATTAT; shXIAP-6: GACTCTACTACACAGGTATTG; shGFP: GAGAAGCGCGATCACAT. Viral supernatants were collected after 48 hours and filtered through a 0.45 μm filter. ES2 or 3AO cells were seeded in six-well plate (2×105/well) and infected with shGFP, shXIAP-4, and shXIAP-6 lentiviral particles, and then the cells were selected with puromycin (2 μg/mL). The knockdown efficiency of XIAP was confirmed by quantitative real-time PCR and Western blot.
IC50 value determination
Ovarian cancer cells were seeded in 96-well plate (1×104/well) and treated with carboplatin concentrations ranging from 40 μg/mg to 360 μg/mg for 24 hours. The cell viability was measured by Cell Counting Kit-8 (CCK-8) assay. Half-maximal inhibitory concentration (IC50) value of ovarian cancer cells was calculated by GraphPad Prism 6 software.
Quantitative real-time PCR
Total RNAs were extracted by TRIzol reagent (Thermo Fisher Scientific, Waltham, MA, USA). One microgram of total RNAs was reverse-transcribed to cDNA by using Quantscript RT Kit (Tiangn, Beijing, China). The expression of XIAP and GAPDH was analyzed by quantitative real-time PCR (RT-qPCR) with Power SYBR Green PCR Master Mix (Thermo Fisher Scientific). Primer sequences of XIAP and GAPDH were as follows: XIAP forward: 5′-GGACCCTCCCCTTGGAC-3′ and reverse: 5′-TGATGTCTGCAGGTACACAAGTT-3′; GAPDH forward: 5′-GGTGAAGGTCGGAGTCAACG-3′ and reverse 5′-TGGGTGGAATCATATTGGAACA-3′.
Western blotting
Cells were lysed with lysis buffer on ice and centrifuged at 12,000 rpm at 4°C for 20 minutes to collect the supernatant. Protein was quantified using bicinchoninic acid protein assay reagent. Protein samples were separated by SDS-PAGE and transferred to polyvinylidene difluoride membranes. Then, the membranes were blocked with 5% milk for 1 hour and subsequently incubated with primary antibodies at 4°C overnight, washed with TBST (Tris-buffered saline containing 0.05% Tween-20) for three times, followed by incubation with secondary antibodies. The membranes were washed with TBST for three times. Images were exposed by LAS-4000 imaging system (Fujifilm, Valhalla, NY, USA).
Cell proliferation assay
Cells were seeded in 96-well plate (1×104/well) and treated with vehicle control or carboplatin (80 μg/mL or 200 μg/mL). Cell proliferation was detected at 0, 24, and 48 hours using CCK-8 reagents (Wbsbio, Beijing, China) according to the manufacturer's instructions.
Flow cytometry analysis of apoptosis
Cells were seeded in a six-well plate (2×105/well) and treated with carboplatin (200 μg/mL or 400 μg/mL) for 24 hours. Then, cells were harvested for analysis of apoptosis using Annexin V-propidium iodide apoptosis detection kit (BD Biosciences, Franklin Lakes, NJ, USA) according to the instructions. The cell apoptotic rate was detected by BD LSR II flow cytometry (BD Biosciences).
Statistical analysis
SPSS 21.0 and GraphPad Prism 6 were used for statistical analysis. Pearson's chi-squared test was used to detect the relationship between XIAP level and clinical parameters. Kaplan–Meier survival analysis was used to calculate the relationship between various factors and patient's short progression-free survival (PFS). Data were presented as mean values with SD. P-value <0.05 was considered to be statistically significant.
High expression of XIAP was associated with poor prognosis and chemotherapy resistance in ovarian cancer
It has been reported that XIAP is associated with cisplatin sensitivity in ovarian cancer;9–11 we therefore investigated the relationship between XIAP expression and carboplatin sensitivity in ovarian cancer. Immunohistochemistry was performed on primary ovarian cancer specimens derived from 151 patients. Using the median expression value of XIAP as a cutoff point, the cohort was divided into XIAP high-expression group and XIAP low-expression group. Statistical analysis demonstrated that higher expression of XIAP was associated with lower probability of carboplatin sensitivity (Figure 1A), and that XIAP expression was also associated with primary CA125 levels (Table 1).
Further analysis showed that higher expression of XIAP was closely related to the patient's short PFS (Figure 1B and Table 2).
Therefore, we concluded that XIAP expression in ovarian cancer is associated with sensitivity to carboplatin in patients, thus affecting the prognosis of patients.
Establishment of stable XIAP knockdown cell lines
To further validate the relationship between XIAP and carboplatin sensitivity at the cellular level, we first tested the expression levels of XIAP in three ovarian cancer cells, ES2, 3AO, and SKOV3, at both protein and mRNA levels. The expression of XIAP was very high in these cells (Figure 2A). We then generated ES2 and 3AO cell lines with stable XIAP silencing by lentivirus-mediated RNA interference using two independent shRNA sequences (shXIAP-4 and shXIAP-6), and shGFP was used as control. The knockdown efficiency of XIAP was detected by RT-qPCR and Western blot. The results showed that XIAP expression was effectively suppressed (Figure 2B and C).
Knockdown of XIAP retards cell proliferation
To evaluate the cytotoxicity of carboplatin, we first evaluated the viabilities of ES2 and 3AO cells in a gradient carboplatin and determined the IC50 values of carboplatin in these cells (Figure 3A). Next, we investigated the inhibitory effect of carboplatin and assessed the role of XIAP in regulating carboplatin sensitivity. Based on the IC50 value, we treated stable XIAP knockdown ES2 and 3AO cells and their corresponding control cells with two concentrations of carboplatin (80 μg/mL or 200 μg/mL), and then cell proliferation was detected by CCK-8 reagents. As expected, suppression of XIAP not only significantly retarded ES2 and 3AO proliferation but also sensitized cells to carboplatin-induced cell proliferation inhibition (Figure 3B and C).
Knockdown of XIAP promotes carboplatin-induced cell apoptosis
To investigate the effect of XIAP on carboplatin-induced apoptosis in ovarian cancer cells, we treated ES2 and 3AO cells with stable knockdown of XIAP and their corresponding control cells with different concentrations of carboplatin (200 μg/mL or 400 μg/mL). Flow cytometry was used to determine cell apoptosis. Silencing of XIAP alone can significantly induce cell apoptosis in both cells. Moreover, suppression of XIAP further increased carboplatin-induced cell apoptosis (Figure 4A and B). Subsequently, the expression of apoptosis-related proteins (PARP, caspase 3, and caspase 9) was measured by Western blot. The results showed that attenuation of XIAP promoted carboplatin-induced cell apoptosis by increasing the cleavage of caspase 3, caspase 9, and PARP in ES2 and 3AO cells (Figure 5A and B). Taken together, these results suggest that XIAP is an important regulator of carboplatin sensitivity in ovarian cancer.
Carboplatin is most commonly used as the front-line chemotherapeutic agent in ovarian carcinoma. However, carboplatin resistance is the major clinical obstacle for the treatment of ovarian cancer and the underlying mechanisms remain poorly understood. Therefore, investigating the mechanism of carboplatin resistance is undoubtedly important and is the basis for exploring novel strategies. In the current study, we first revealed that the expression of XIAP in ovarian cancer tissues was associated with carboplatin resistance and short PFS. We further provide strong evidence that XIAP suppression increased carboplatin chemosensitivity in ovarian cancer cells.
With recent progress in drug resistance, it has become clear that loss of control on cell death and apoptosis may confer chemoresistance.15,16 XIAP, a member of the IAP family, prevents apoptosis induced by both extrinsic and intrinsic pathways through direct inhibition of effector caspases (caspases 3, 6, 7, and 9).17 It has been well-documented that XIAP plays a crucial role in tumor maintenance and resistance to chemotherapy treatments in many kinds of tumors.13,18–20 Cells that lack XIAP are sensitized to apoptosis. High expression of XIAP has also been found in ovarian cancer cells and implicated as determinant of the chemosensitivity of ovarian cancer.21–24 Increasing evidence has focused on XIAP suppression to develop new strategies for cancer prevention and treatment.25 Consistent with previous studies, we demonstrated the role of XIAP in the protection of ovarian cancer cells induced by carboplatin. We also confirmed that XIAP inhibited carboplatin-induced apoptosis via suppression of caspases 3 and 9. In future studies, in vivo experimental evidence needs to be further provided to confirm the functional role of XIAP in mediating carboplatin sensitivity. Mechanistic investigations have demonstrated that a number of signaling pathways are involved in the regulation of XIAP expression, including p53, NF-KB, c-Jun/AP-1, PI3K, and USP11-dependent signaling pathways.5,20,26–28 The precise molecular biological mechanism as to how XIAP regulates apoptosis of ovarian cancer cell must also be addressed in the future.
Our data clearly demonstrate that XIAP suppression enhances chemosensitivity of carboplatin and that XIAP can act as a predictor of carboplatin sensitivity. Thus, XIAP-targeted regulation may markedly contribute to the identification of biomarkers of chemotherapy and present a promising therapeutic strategy to improve chemotherapeutic efficacy in ovarian cancer.
This work was supported by National Natural Science Foundation of China (81472452), Chinese Academy of Medical Sciences Initiative for Innovative Medicine (2017-I2M-3–004), and Beijing Science and Technology Commission Project (K2015311201501).
Author contributions
Yiping Zhang, Zhihua Liu, Hongyan Chen and Yinghui Huang conceived the study, interpreted the results and wrote the manuscript. Yiping Zhang performed immunohistochemistry and analysis. Yiping Zhang, Furong Huang, Qingyu Luo and Xiaowei Wu performed laboratory experiments and statistical analyses. All authors contributed to data analysis, drafting and revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.
The authors report no conflicts of interest in this work.
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Agarwal R, Kaye SB. Ovarian cancer: strategies for overcoming resistance to chemotherapy. Nat Rev Cancer. 2003;3(7):502–516.
Stone RL, Sood AK, Coleman RL. Collateral damage: toxic effects of targeted antiangiogenic therapies in ovarian cancer. Lancet Oncol. 2010;11(5):465–475.
Bookman MA, Gilks CB, Kohn EC, et al. Better therapeutic trials in ovarian cancer. J Natl Cancer Inst. 2014;106(4):dju029.
Gyrd-Hansen M, Darding M, Miasari M, et al. IAPs contain an evolutionarily conserved ubiquitin-binding domain that regulates NF-kappaB as well as cell survival and oncogenesis. Nat Cell Biol. 2008;10(11):1309–1317.
Mehrotra S, Languino LR, Raskett CM, Mercurio AM, Dohi T, Altieri DC. IAP regulation of metastasis. Cancer Cell. 2010;17(1):53–64.
Huang X, Wu Z, Mei Y, Wu M. XIAP inhibits autophagy via XIAP-Mdm2-p53 signalling. Embo J. 2013;32(16):2204–2216.
Krieg A, Correa RG, Garrison JB, et al. XIAP mediates NOD signaling via interaction with RIP2. Proc Natl Acad Sci U S A. 2009;106(34):14524–14529.
He X, Khurana A, Maguire JL, Chien J, Shridhar V. HtrA1 sensitizes ovarian cancer cells to cisplatin-induced cytotoxicity by targeting XIAP for degradation. Int J Cancer. 2012;130(5):1029–1035.
Farrand L, Byun S, Kim JY, et al. Piceatannol enhances cisplatin sensitivity in ovarian cancer via modulation of p53, X-linked inhibitor of apoptosis protein (XIAP), and mitochondrial fission. J Biol Chem. 2013;288(33):23740–23750.
Miyamoto M, Takano M, Aoyama T, et al. Phenoxodiol Increases Cisplatin Sensitivity in Ovarian Clear Cancer Cells Through XIAP Down-regulation and Autophagy Inhibition. Anticancer Res. 2018;38(1):301–306.
Zhang X, Huang L, Zhao Y, Tan W. Downregulation of miR-130a contributes to cisplatin resistance in ovarian cancer cells by targeting X-linked inhibitor of apoptosis (XIAP) directly. Acta Biochim Biophys Sin (Shangai). 2013;45(12):995–1001.
Lin YF, Lai TC, Chang CK, et al. Targeting the XIAP/caspase-7 complex selectively kills caspase-3-deficient malignancies. J Clin Invest. 2013;123(9):3861–3875.
Zhao WJ, Deng BY, Wang XM, Miao Y, Wang JN. XIAP associated factor 1 (XAF1) represses expression of X-linked inhibitor of apoptosis protein (XIAP) and regulates invasion, cell cycle, apoptosis, and cisplatin sensitivity of ovarian carcinoma cells. Asian Pac J Cancer Prev. 2015;16(6):2453–2458.
Fernandez-Capetillo O, Chen HT, Celeste A, et al. DNA damage-induced G2-M checkpoint activation by histone H2AX and 53BP1. Nat Cell Biol. 2002;4(12):993–997.
Arts HJ, Van Der Zee AG, De Jong S, De Vries EG. Options for modulation of drug resistance in ovarian cancer. Int J Gynecol Cancer. 2000;10(S1):47–52.
Gyrd-Hansen M, Meier P. IAPs: from caspase inhibitors to modulators of NF-kappaB, inflammation and cancer. Nat Rev Cancer. 2010;10(8):561–574.
Gu L, Zhu N, Zhang H, Durden DL, Feng Y, Zhou M. Regulation of XIAP translation and induction by MDM2 following irradiation. Cancer Cell. 2009;15(5):363–375.
Tosello V, Bordin F, Yu J, et al. Calcineurin and GSK-3 inhibition sensitizes T-cell acute lymphoblastic leukemia cells to apoptosis through X-linked inhibitor of apoptosis protein degradation. Leukemia. 2016;30(4):812–822.
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International Holiday: rated 4.8/5 (based on 66614 reviews) | Packages starting from ₹2,700/-
With about 200 nations in the world, there are a plethora of places to explore and a great many things to do abroad with best international tour packages from India. If France is famed as one of the most romantic travel destinations, then Cambodia and Jordan are known to offer a perfect retreat for people who love to unveil the history of a new place. While, places like South Africa, Thailand, and South Africa are meant to satiate the hunger of every adventure junkie. So, if one is planning a tour to an international destination, they can book a package with TravelTriangle for a suitable time, and get on an excursion that they can cherish for life.
To visit any of the international destination in the world, you need to know the best time to enjoy a vacation. While there are seven continents and 195 countries in the world, there are even more climatic changes a particular destination experiences. Therefore, we suggest you consider the peak time to visit your favorite destination. You may also enjoy a budget-vacation during the off season. To visit the countries of Europe, the months of May, September and October can be considered as the ideal time to visit at least most of the destinations here. During this time, crowds are lesser and the rates for accommodation is cheaper. While there are several packages offering a wonderful international tour experience, our curated list of packages offer you even more. Take a look below at our best-selling destinations for family and friends.
Best-selling International Tour Packages In 2019
|International Holiday Tour Packages
|France and Switzerland Tour Package
|7 Night/8 Days
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|Luxurious Dubai Tour Package With Atlantis
|5 Night/6 Days
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|Best Of Thailand Holiday Package
|7 Night/8 Days
|View Details
|5 Country Europe Tour Package
|15 Night/16 Days
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|Lovely Vietnam And Cambodia Tour Package
|7 Night/8 Days
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|Spain Holiday Package
|8 Night/9 Days
|View Details
|Alluring Paris Tour Package
|3 Night/4 Days
|View Details
Our world tour packages are equipped with fun-filled experiences, and that too at an affordable cost, which make them the first choice of every traveler. Whether you want to book a package for a single person or your entire family, you can easily customize the package according to your travel needs. Along with several facilities, you will also be offered hassle-free transfers and a seasoned guide to help you during your international tour. These packages offer you the best experience of sightseeing at all the important places listed in the itinerary along with several things to do during your international trip.
Best Experiences for an International Trip
From tropical beaches in Southeast Asia to Christmas markets in Europe, and from island hopping in Bali to adventures in the Alps, book your holidays with TravelTriangle to make your getaway memorable. Here are some of the most fascinating places to plan a trip with your friends and family.
1. Thailand:
Best Time to Visit - You will find a pleasant, inviting weather in Thailand from the month of November to March.
Ideal Duration of Stay - A 5 nights and 6 days trip to Thailand might be the ideal duration to stay and cover the major tourist attractions.
Land Package for International Trip - The tour package generally starts from an affordable price of INR 12,349/-. Stunning beaches, Buddhist temples, floating markets, and legendary nightlife; what more can one ask for on a holiday in Thailand. The islands of Koh Samui and Phi Phi group offer ultimate watersports like diving and glass bottom boat rides for travellers of all ages. On the other hand, the bustling streets of Bangkok and iconic temples like Wat Arun and Wat Saket keep history lovers and occasional travellers busy.
2. Dubai:
Best Time to Visit - The city beckons thousands of tourists throughout the year because of its conducive climate. However, the best time to visit is between October and March.
Ideal Duration of Stay - Keep some good time in hand to explore the many attractions of Dubai. A stay of 5 days and 4 nights is usually recommended. Land Package for International Trip - Fares usually start from INR 22,999/-. It may vary according to customizations. Between the Dhow Cruise on the Dubai Creek and desert safari on the Arabian Desert, this ultra-modern city in the UAE is an ultimate family holiday destination. While kids can make a splash at Dubai Aquarium and Wild Wadi Water Park, adults can enjoy a visit to Dubai Fort and Museum, and the Dubai Mall. To put the icing on the cake, travellers can enjoy views of the city from Burj Khalifa, the tallest building in the world. Another highlights in Dubai include dune bashing, camel rides, and musical fountains.
3. Europe:
Best Time to Visit - Europe boasts a suitable climate all round the year. Ideally, April to October are the best months to visit the major countries. Ideal Duration of Stay - Depending upon the countries you wish to cover, you may spend 12 to 15 days here.
Land Package for International Trip - Our budget fares start with the price of INR 18,000/-. Between the vineyards of Tuscany and the canals of Amsterdam, Europe is a mesmerizing place. Tourists can enjoy gondola rides in Venice, skiing in the Alps, the nightlife of Budapest, a live opera performance in Vienna, Thames River cruise in London, and a 360-degree view of Paris from the Eiffel Tower. Switzerland, France, Italy, Germany, and Spain are top tourist places to explore on a holiday in Europe.
4. Sri Lanka:
Best Time to Visit - Sri Lanka experiences a pleasant climate with sunny skies all year round. The best months to visit are December to March and April to September.
Ideal Duration of Stay - To cover the West coast, South coast and ancient cities of Sri Lanka. You need 5-6 days in hand.
Land Package for International Trip - The prices for Sri Lanka tour starts from IN 15.486/- Sri Lanka was once a hidden gem but it is now becoming one of the most visited countries across the globe due to its richness in culture and history. It is a country blessed with natural beauty, aesthetic beaches, woods, intricate temples, monasteries, museums, and rich culture and history.
5. Bali:
Best Time to Visit - Bali is a year round destination. Still, July to September are usually the peak months for honeymoon in Bali.
Ideal Duration of Stay - An ideal time period of 5 days and 4 nights may be sufficient to cover the major tourist attractions of Bali.
Land Package for International Trip - Our basic Bali package tour starts from INR 17,000/-. Bali is yet another striking place to visit for a fun and relaxing holiday. One can undergo spa and rejuvenating sessions here to soothe the mind, body, and soul. number of adventure activities to enjoy, surfing being the best among all.
6. Hong Kong:
Best Time to Visit - The weather of Hong Kong remains pleasant during December to February. You may also visit the place during May-August also.
Ideal Duration of Stay - You may easily spend 6-7 days exploring the major places of Hong Kong.
Land Package for International Trip - The Hong Kong tour packages start from INR 14,999/-. Our Hong Kong tour packages are very children friendly where you can enjoy the most with your kids and family. The very famous Disneyland will make your children go wow and will give them some peaceful and a time to cherish.
7. Singapore:
Best Time to Visit - The months between February and April are considered the best time to visit Singapore. The weather remains pleasant during these months.
Ideal Duration of Stay - Ideally, you must stay for at least 4-5 days to cover the best attractions of Singapore.
Land Package for International Trip - The basic fare for Singapore packages starts from INR 23,500/-. Singapore is also amongst the top-notch countries in the list of international holiday packages from Bangalore, Delhi, Mumbai, Kolkata and other cities of India. The country is very neat and clean with many sightseeing and fun options to enjoy with family. Gardens By The Bay, Sentosa Island, Universal Studios are some of the major charms of the country.
8. Mauritius:
Best Time to Visit - The best time to explore this rightly famed island is during the months of May to December. The weather is sunny, dry and cool.
Ideal Duration of Stay - A time period of 4-5 days is considered ideal to cover the major places in Mauritius.
Land Package for International Trip - The Mauritius tour package starts from INR 21,999/- Popular for its azure waters, sugar-white beaches and luxurious resorts, Mauritius attracts tourists from all over the world. Dive into the infinite, beautiful landscape of Mauritius for a lifetime of treasures. Also, do not forget to check out the cheapest international tour packages for a friendly budget fare.
9. Maldives:
Best Time to Visit - The best time to visit Maldives is generally between November and April as this season experience suitable weather. The high season lasts from December to March.
Ideal Duration of Stay - Plan you trip for 5 days and 4 nights to spend your vacation at Maldives.
Land Package for International Trip - The price fare to Maldives from India starts from INR 25,000/-. Fondly known as the Island Eden among travelers, Maldives is equipped with long stretches of sun kissed beaches and amazing underwater ecosystem. Discover the popular attractions of Maldives or indulge in some fun activities like snorkeling during your vacation. Make sure to book this trip through our foreign tour packages for a smooth journey.
10. Australia:
Best Time to Visit - The favorable months to spend your vacation in Australia are from September to November and from March to May.
Ideal Duration of Stay - A time duration of 10-12 days will be enough to stay in Australia.
Land Package for International Trip - Our trip packages to Australia from India starts at the price of INR 70,100/- Contemporary and wild, Australia has been a favorite vacation spot for Indian tourists. From hip cities to extraordinary wildlife, Australia is a universal destination for all kinds of travelers. Explore the majestic Australia through our international trip packages from India and get awestruck by its unending beauty!
11. New Zealand:
Best Time to Visit - Usually, New Zealand can be visited any time of the year, especially during the months of January to May.
Ideal Duration of Stay - Plan your vacation for some 5-7 odd days to cover the major tourist places.
Land Package for International Trip - Our package to New Zealand from India starts from INR 90,000/- Filled with deep, glacial fjords, New Zealand is the perfect destination for creating an epic vacation memory. Whether you like to ski or just take a walk in the beaches, New Zealand offers you with all you want! Get the first-hand travel experience of New Zealand by booking one of our budget international tour packages from India.
12. Seychelles:
Best Time to Visit - Although Seychelles can be visited any time of the year, still the best time can be during the months of March to November.
Ideal Duration of Stay - You can plan your vacation for a good 5-7 days in Seychelles.
Land Package for International Trip - The basic fare charges for Seychelles starts from INR 37,000/- Often termed as the African Haven for tourists, Seychelles is rich in turquoise water beaches and lush, green hills. Travelers can easily indulge in water activities like diving and snorkeling, or can simply engage in birdwatching. To avail the best of Seychelles during your vacation, reserve any of our foreign holiday packages from India at affordable rates.
Give Your Trips a Personal Touch
The most suitable time for an international holiday in cold regions is summertime, between May to August. The temperature usually ranges between 12 degrees Centigrade to 20 degrees Centigrade. However, if someone wishes to experience snow, they can visit cold destinations during peak winters, in December and January. International tourism packages can be customized according to the traveler's preferences in order to provide them with a comfortable tour, top-notch services, and delicious meals, all at the best possible prices.
These packages are aimed at providing a memorable and flawless vacation experience to the holidaymakers. Therefore, a full-fledged international tour itinerary is included in these packages which are specially crafted to cater to the needs of the travelers. From extensive sightseeing tours to thrilling outdoor activities, and luxurious and comfortable accommodations to hassle-free local and interstate transfers, these itineraries include all sorts of facilities that make a holiday even more enjoyable. Bearing in mind the interests and preferences of every kind of traveller, our international tour packages from India have been designed to let tourists savour the view of exotic landscapes, enjoying a sojourn along some breathtaking beaches, dive into the underwater world and experience adventure activities, or just cherish some blissful moments with their near and dear ones.
Enjoy a Sparkling Diwali with Amazing Tour Packages
Bestselling International Packages From Major Cities in India
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₹ 25,999/-₹ 28,888/-
Per Person on twin sharing
Hotel included in package:
- Kuta (4D)
- Ubud (3D)
The perfectly planned Bali honeymoon packages take you to some of the ....
Upto 4 Stars
₹ 49,000/-₹ 53,846/-
Per Person on twin sharing
Hotel included in package:
- Maldives (5D)
Planning a honeymoon trip to Maldives? TravelTriangle has got you covered with a variet....
Upto 5 Stars
₹ 49,500/-₹ 54,450/-
Per Person on twin sharing
Hotel included in package:
- Dubai (6D)
It's time to take that much-needed break with this customizable 5 night 6 days Du....
Upto 3 Stars
₹ 40,998/-₹ 44,235/-
Per Person on twin sharing
Hotel included in package:
- Hong Kong (4D)
- Macau (3D)
Book your dream vacation with our tailor-made 6 nights and 7 days Hong Kong and....
Upto 4 Stars
₹ 19,499/-₹ 21,428/-
Per Person on twin sharing
Hotel included in package:
- Maldives (5D)
Delight in a vacation like never before with this 4 nights, 5 days Maldives fam....
Upto 3 Stars
₹ 27,000/-₹ 29,670/-
Per Person on twin sharing
Hotel included in package:
- Dubai (6D)
Dubai is a city and emirate in the United Arab Emirates known for luxury shopping, ultr....
₹ 26,500/-₹ 28,191/-
Per Person on twin sharing
Hotel included in package:
- Dubai (7D)
Planning a family vacation and do not know what to do? Start with picking the destinati....
Upto 3 Stars
₹ 26,495/-₹ 29,115/-
Per Person on twin sharing
Hotel included in package:
- Mauritius (5D)
Mauritius is an island nation located off the southeast coast of the African continent ....
₹ 38,000/-₹ 42,222/-
Per Person on twin sharing
Hotel included in package:
- Paris (4D)
Expect nothing but the finest locations on an adorable vacation with your loved one whe....
₹ 54,999/-₹ 60,439/-
Per Person on twin sharing
Hotel included in package:
- Maldives (5D)
Are you planning your vacations to a place which you cannot decide? Then we are here to....
Upto 3 Stars
₹ 65,454/-₹ 71,404/-
Per Person on twin sharing
Hotel included in package:
- Athens (3D)
- Santorini (2D)
- Mykonos (2D)
White-washed bungalows, clear-blue skies, black-pebbled beaches, and pulsating nightlif....
Upto 3 Stars
₹ 27,999/-₹ 31,460/-
Per Person on twin sharing
Hotel included in package:
- Kuta (3D)
- Ubud (3D)
This 5 nights 6 days Bali tour package is perfect for those looking to....
Upto 3 Stars
₹ 66,000/-₹ 70,304/-
Per Person on twin sharing
Hotel included in package:
- Praslin (3D)
- Mahe (4D)
Seychelles is an archipelago of 115 islands, located to the east of the African mainlan....
Upto 3 Stars
₹ 18,079/-₹ 20,088/-
Per Person on twin sharing
Hotel included in package:
- Phuntsholing (1D)
- Paro (2D)
- Thimphu (2D)
Choose Bhutan for honeymoon as your romantic escapade and seek pleasur....
Upto 2 Stars
₹ 44,999/-₹ 50,561/-
Per Person on twin sharing
Hotel included in package:
- Singapore (5D)
An enchanting island city-state, Singapore tourism has reinvented itse....
Upto 4 Stars
₹ 18,400/-₹ 20,909/-
Per Person on twin sharing
Hotel included in package:
- Mauritius (5D)
Travel Triangle brings to you a luxurious 4 nights 5 days Mauritius family pack....
Upto 3 Stars
₹ 18,644/-₹ 20,716/-
Per Person on twin sharing
Hotel included in package:
- Thimphu (2D)
- Paro (3D)
For a wonderful holiday with your family in the Kingdom of Bhutan, book a 4 nights 5 da....
Upto 2 Stars
₹ 76,000/-₹ 83,516/-
Per Person on twin sharing
Hotel included in package:
- Hanoi (3D)
- Ho Chi Minh City (4D)
Honeymoon is always a special occasion. So, make it even more special by booking this
Upto 4 Stars
₹ 29,998/-₹ 32,998/-
Per Person on twin sharing
Hotel included in package:
- Hong Kong (5D)
With our customizable 4-nights and 5-days Hong Kong family tour package
Upto 3 Stars
₹ 47,999/-₹ 50,742/-
Per Person on twin sharing
Hotel included in package:
- Singapore (5D)
Singapore tour packages are wonderful bundles of lucrative vacationing experience for f....
Upto 3 Stars
FAQs for International
A) The best time to visit most of the European countries to enjoy good weather are : July and August are the best months to visit Northern countries like Iceland, Sweden, and Norway Mid-May to mid-September is the best time to visit the countries of continental Europe April/May or mid-September to late-October are the best months to visit Eastern and Mediterranean countries
A) Embark on a religious tour at one of these most religious destinations in the world :
- Shwedagon Pagoda, Myanmar
- Basilica of San Vitale, Italy
- Temple of Heaven, China
- Harmandir Sahib (Golden Temple), India
- Hassan II Mosque. Morocco
- Spanish Synagogue, Czech Republic
- Paro Taktsang, Bhutan
- Akshardham Temple, India
- Saint Basil's Cathedral, Russia
- Sheikh Zayed Grand Mosque, United Arab Emirates
- Wat Rong Khun, Thailand
A) A lot of countries boasts off its topography and areas where there is an abundance of flora and fauna. Such a list includes :
- Ireland
- Switzerland
- Netherlands
- Australia
- New Zealand
A) If budget is a constraint, then one can choose to travel to any one of these foreign destinations in the world :
- Thailand
- Vietnam
- South Africa
- Greece
- Prague
A) Some of the destinations in the world that offer the best tropical beachside holiday for tourists are :
- Bali
- Santorini
- Barcelona
- Maldives
- Mauritius
- Phuket
- India
A) To feel some adrenaline rush, travellers can trek the Inca Trail to Machu Picchu, enjoy walking safari in Zimbabwe, explore the lost city of Petra, paraglide over the Alps, and try surfing in Sri Lanka.
The Sahara Desert in Africa, the Thar Desert in India, and the deserts in Dubai and the rest of the Middle East are great places to enjoy the amazing sights and indulge in activities like sand duning, camel rides, and overnight cultural camps.
A) Out of all the multitude of places in the world, some of these places are the best ones to go for a historical tour :
- Stonehenge in the United Kingdom
- Angkor Wat in Cambodia
- Cairo in Egypt
- Athens in Greece
A) There is an abundance of experiences that one can enjoy in the world. A few of them are -
- Catching a bird's eye view of Paris from the top of the Eiffel Tower
- Interacting with the llamas at Machu Picchu
- Scuba diving at the Great Barrier Reef
- Marveling at the azure blues of the ocean at Bora Bora
- Absorbing art and culture at the Louvre Museum
- Hiking through Yosemite National Park
- Watching the Northern Lights at Iceland
A) There are many countries in the world that boast off amazing skiing opportunities. A few of them are Whistler Blackcomb in Canada, Courchevel in France, Zermatt in Switzerland, Aspen Snowmass in Colorado, and many more.
A) If one wants to hop on a solo trip, visit any of these places listed below :
- Rome
- New York
- Melbourne
- Amsterdam
- Chiang Mai
- Vietnam
- Thailand
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Travelers deal with only the top 10% reviewed agents who are selected after a 23 step rigorous assessment procedure by TravelTriangle.
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Travelers deal with only the top 10% reviewed agents who are selected after a 23 step rigorous assessment procedure by TravelTriangle.
Authentic Traveler Reviews for International
Read on to find out why our customers love us!
Trip to North EastTravel agent was always available to help. Cab driver was not good Snowfall at bumla and visit to war memorials
Trip to RajasthanRajasthan,This was a tour of Family and Friends with 17 people( 11 adults and 6 kids) for 10 Days and 9 Nights. We were little apprehensive of the Places, Travel and Accommodation due to group size. we could not judge what would be the best deal and who could provide the best service, but to our surprise, One stop Solution for all our requirements happen to be "SURAJ of UNIQUE TRIP MAKER". He took care of all our Trip requirements and could add Rooms everywhere with my last minute addition of the people. He has given us Good Bus, though not a great Driver. Suraj was very supportive throughout the trip and was very helpful with daily check-update of our trip status. He never shied away making the necessary changes, if required. Our Accomdations were at 1)Jaipur - Rajputana Haveli; 2) Bikaner- Jaswanth Bhavan; 3) Jaisalmer- Tokyo Palace; 4)Samdunes- Rojani Resort; 5)Jodhpur- Kuchaman Haveli; 6)Udaipur- Mukund Vilas; 7) Pushkar - Country Side Resort. I would rate all of them VERYGOOD with "JASWANTH BHAVAN @ Bikaner and ROJANI@Samdunes- OUTSTANDING" while "Kuchaman Haveli - BAD. It was my mistake of Choosing Kuchaman based on pics , though suraj insisted me to opt other one, wish we could have followed his instructions. This was a very organized trip and We, as a large group highly recommend "Unique Trip Maker" to plan vacation and we Rate 5 STARS for the service Suraj has provided. My first choice for our future Trips would be UTM- Suraj. Thanks TRAVEL TRIANGLE and UNIQUE TRIP MAKER for your OUTSTANDING service.
Trip to AndamanThe hotels were nice, could have been better if the resort in havelock and niel island were given wi fi i. Rooms as there was an issue with phone network,at least people will be in touch with there home, rest all was fine except some housekeeping minor issue.
Trip to BhutanGood service provided by button rentals and travels ... My agent preeri was available during the entire trip .... Overall a nice experience
Trip to MaldivesThé trip was amazing. Dealing with the ground staff Was really smooth and helpful. But the ASAP agents were really hard to get through. They were soft spoken till the booking, once the booking was done their behaviour towards us was very careless which was thé turn off point for us. We had to chase for each and every bit and we weren't getting any reply on calls and e-mails. Please try to improve your customer retaining policy by serving same services drom the booking tull thé trip ends. Snorkelling and scuba.
Trip to Sikkim - Gangtok - DarjeelingOver all experience was good..but i feel very disapoint by agent because they change my hotel without inform me..i have no obtion .by luckliy hotel was ok..not to much good not to much bad its ok ok. I suggest to the agent if you change hotel or something else so pls inform your client . Over all travel agent is okk okk.. Both drivers.. very helpful and co-operative and friendly nature
Trip to KeralaMy first visit to southern India and chauffeur at our disposal was horrible with no understanding of family needs. He will just have his way throughout trying to save parking fees, some kilometres, driving rash, abusing other commuters and so on. Travel agent was nice but not adhering to service standards and commitments. Trip could have been better if the chauffeur was slightly compassionate. Kerala is beautiful at every bit, corner. This is actually a traveller's heaven and dream destination. Best places are Munnar, Thekkady and Allepey. Cochin to be avoided.
Trip to DubaiStay and sight seeing experience was very nice. Cab drivers were very courteous and on time and seamless. However our experience with travel agent was not very pleasant. Had a lot of issues in booking and required a lot of follow up. Anyways our trip ended with satisfaction and good memories. Keep up the good work.
Trip to NainitalDriving was good but there was a problem in the attitude.He was just trying to escape from his duties and also misleading us. Behaviour was a problem and forced us to wrap up everyday by 5pm. We have hardly seen any places and also didnt get any knowledge from any place. Traveling was a pain cause there was no place to sit coz the luaggages had to be kept since there was no carrier on top. Since kausani was 200 km more he convinced us for Ranikhet to avoid extra driving. Behaviour was rude.As far as the experience goes, traveling with Mr. Sonu Joshi was pathetic and horrible..
Trip to MaldivesTravel Triangle is my one-stop destination hunter with best deals. Kashmir was my Honeymoon trip which went great. I'm sorry for the delay in sharing my review. Now, I'm here to share my anniversary trip. It's the "Heaven on Earth - Maldives". It's a great trip and awesome place. Richa From "Holidays 2 Cherish" was very polite and keen to help us in selecting the best destination for my anniversary trip. With her guidance, we've finalized "Adaaran Club Rannalhi". Everything was awesome including foods, location, ambiance and people, etc. Water Villa, Spa, Jet Ski-ride are highlights in the entire trip. I'm waiting for next international trip. Obviously, I'll prefer Travel Triangle only. I'll follow-up with "Richa" only for further trips. Thanks all for helping my first international trip as "Awesome and Remember-able journey in my life".
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In the Fall issue of watercolor magic there was a feature article titled Flatten Your Picture Plane by artist Goode. I tore itvout so I could reread it and also for inspiration. Her use of color blocks and is something I admire. I love her work. So studying and sketching from it may influence my own development. This is a painting she titled Sara in a Green Dress which she says is her first acrylic painting.
Tuesday, September 5, 2017
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Game description
Vote: Did you like this game? 108
This is a deserted cemetery. The history is very long. When it comes to the night, the blood will show on the gravestone. So, many bats will come here. They are monsters.Please kill them all.
Game controls:
mouse to shoot. Q to change the weapons. A to use guided missile. S to use bombs. Space bar to open/close aim point.
FightingShootingBloodKillingFirst Person ShooterVampireBats