text:
Nanoparticles Cure Blood Disorder, Provide Site-Specific Gene Editing
TOPICS:GeneticsHealthMedicineNanoparticlesNanoscienceYale University
By William Weir, Yale University June 27, 2018
Image of nanoparticles accumulating in the liver of a fetal mouse.
With the combined efforts of three Yale laboratories, researchers conducted the first demonstration of site-specific gene editing in a fetus, correcting a mutation that causes a severe form of anemia.
The technique, described in a paper published June 26 in Nature Communications, involves an intravenous injection of nanoparticles carrying a combination of donor DNA and synthetic molecules known as peptide nucleic acids (PNAs). The PNAs, which mimic DNA, bind to the target gene and form a triple helix — an aberration that triggers the cells' repair mechanisms. As part of this process, the healthy donor DNA — paired with the PNA in a nanoparticle — is used to fix the mutation.
For the study, this gene-editing package was injected into the fetuses of mice. At four months after birth, the mice had been cured of thalassemia, an inherited defect in oxygen-carrying red blood cells.
"The treated mice had normal blood counts, their spleens returned to normal size, and they lived a normal life span — whereas, the untreated ones died much earlier," said Peter M. Glazer, M.D., professor of therapeutic radiology and of genetics, who developed the technique of combining the PNA and DNA to repair gene mutations. "So we have a long-term survival benefit, which is pretty dramatic."
Distribution of nanoparticles in a litter of fetal mice after intravenous nanoparticle treatment. The intense green, yellow, and red areas show higher concentrations. The highest accumulation of nanoparticles in each mouse is in the fetal liver.
Using nanoparticles for delivery is crucial, said the researchers. When injected intravenously without nanoparticles, PNAs are cleared from circulation within about 30 minutes. When delivered by a nanoparticle and taken up by a cell, though, they remain much longer. Mark Saltzman, Yale's Goizueta Foundation Professor of Biomedical Engineering, Chemical and Environmental Engineering, and professor of physiology, made the nanoparticles with a degradable polymer and designed them small enough — 200 to 300 nanometers — to readily accumulate in the liver of the fetus, where the stem cells are located before migrating to the bone marrow.
In a previous study, the researchers yielded promising results when they conducted a similar procedure on adult mice. By editing the gene in the fetus for the new study, though, the researchers greatly minimized the amount of damage caused by the disease.
"People who have thalassemia, they get sicker and sicker as they go on because they don't have normal red blood cell function, and it gets harder to treat," Saltzman said. "Here, we're correcting the gene very early in development, so you see more benefits because they don't get sick."
One advantage of this technique, said the researchers, is that it can performed in a living animal, while other gene-editing procedures have mostly been limited to cells in a petri dish. Unlike technologies such as CRISPR — often referred to as a "genetic scissors" — the Yale researchers' technique is a chemical process, so repair of the targeted gene is more exact and results in fewer off-target effects.
Two challenges the researchers faced were the small size of their target and making sure the therapy would work after only one injection, as multiple injections to a fetus greatly increase risk of harm. For this, David H. Stitelman, M.D., an assistant professor of pediatric surgery, brought his expertise in accessing fetal stem cells.
"You have to catch these cells while they are in a state of massive proliferation, so this is literally a once-in-a-lifetime opportunity," Stitelman said.
The study's first author, Adele Ricciardi, an M.D./Ph.D. student, said the team is now looking at how their technique can treat other inherited single-gene disorders, such as cystic fibrosis and sickle cell.
"If a baby could be born with a lower burden of disease — or no disease whatsoever — that would have a profound impact on that child's life as well as the family," Ricciardi said.
Additional study authors include Raman Bahal, James S. Farrelly, Elias Quijano, Anthony H. Bianchi, Valerie L. Luks, Rachael Putman, Francesc Lopez-Giraldez, Suleyman Coskun, Eric Song, Yanfeng Liu, Wei-Che Hsieh, and Danith H. Ly.
Publication: Adele S. Ricciardi, et al., "In utero nanoparticle delivery for site-specific genome editing," Nature Communications, volume 9, Article number: 2481 (2018)
Gene Editing Tool Provides New Approaches to Prevent Disease
Yale Develops New Gene Editing Strategy to Correct Mutations
Scientists Demonstrate Efficient Method for Converting Fat Cells to Liver Cells
MIT Researchers Reverse a Rare Liver Disorder in Mice
Small Nanoparticles Provide Dramatic Improvements in Polymer Materials
Researchers Use CRISPR-Carrying Nanoparticles To Edit Genomes
Study Shows Nanoparticles in Consumer Products Can Damage DNA
Bearing a Male Child Can Alter a Woman's Brain
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The New Zealand Orienteering Championships 2016 event programme available. The champs will be in the Nelson Tasman region, upper South Island on 25 to 28 March 2016. Entries close on Friday 4th March 2016.
Make sure you have Katoa Po on your calendar for 12th -13th March 2016! This year the classic weekend event is on a brand new map, which is located up behind Reporoa dairy factory – so we are out of the Taupo gullies.
Entries close 15th January for the Orienteering Waitangi 2016 Sprints weekend to be held in Wellington.
6 sprint events over 3 days – including a WRE. All events within an hour from Wellington and accessible by public transport.
Event 4 on Sunday afternoon will be an IOF World Ranking Event (WRE).
The Orienteering NZ High Performance Plan for the 5 year period 2015-2019 has been published and is available online now.
The benefits of getting ONZ's committee convenors together around a table were realised at a workshop held in Wellington during mid November. Whilst providing each convenor with the chance to highlight the goals and progress made by their respective committee, it also raised opportunities for interaction on common issues.
Nelson Orienteering Club is calling for expressions of interest in the position of Controller for the Long Distance event at the 2016 NZ Orienteering Champs on Easter Sunday.
On-line entries now open for this event, 3 races over two days. In the sprint race at Arataki on Saturday afternoon, all elite class runners will be using SPORTident Air! This is a first for any major event in New Zealand!
The Wellington Orienteering Champs – Hawkes Bay – 17-18 October 2015 Day 1: AM Middle Maraetotara Day 1: PM Sprint Arataki Day 2: AM Long Fire Station See www.hborienteering.com for more details coming soon.
The Oceania Orienteering Championships will be run in the Auckland region over Easter (14-17 April 2017), the weekend prior to the start of the World Masters Orienteering Championships (WMOC) being held as part of the World Masters Games from 21-30 April in Auckland. The NZ Orienteering Nationals will be hosted by Hawkes Bay Orienteering Club and will take place at Labour Weekend 2017.
The Auckland World Masters Games 2017 Orienteering information flier has been published.
Download it now from the Orienteeering NZ World Masters Games 2017 page.
Dunedin Orienteering Club welcomes you to NASEBY, for the 2015 South Island Orienteering Championships, which will be held over Labour Weekend 24 – 26 October 2015.
WMOC 2016 will take place from 5-14 August 2016 in Tallinn, Estonia. Don't miss out on the opportunity to take part in one of the biggest orienteering events and discover this beautiful country. Register now for this amazing journey in Estonia.
The May edition of the Orienteering NZ e-newsletter Compass Point. Queen's Birthday Weekend is almost here and looks full of promise. The event has a Pinestars v Bushrangers Senior and Under 23 Test event as well as hosting the trials for the NZ Secondary Schools Teams to compete in the Southern Cross Challenge in Ballarat in late September.
Full Event Details and Start Times for the New Zealand Orienteering Championships 2015 (Nationals) have been published by host club Counties Manukau Orienteering Club.
The next entry deadline for the World Masters Orienteering Championships 2015 to be organized in Gothenburg, Sweden is approaching: it is still possible to enter with the 70 EUR accreditation fee until 31 March!
Experience terrain similar to World Masters Games and Oceania Orienteering 2017! The jafa 2015 Queen's Bday Orienteering, 30 May – 1 June 2015, Auckland New Zealand website is live and entries open.
Canterbury Champs scheduled for the 9th-10th May 2015 have been postponed to the weekend of 15th/16th August 2015.
Two teams have completed the GODZone Adventure race orienteering section based on the Waikaia orienteering map. Good navigation is an essential part of the adventure race. Find out more on the event website.


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text:
package org.apache.camel.spring.issues;

import org.junit.Test;

import org.apache.camel.spring.SpringTestSupport;
import org.springframework.context.support.AbstractXmlApplicationContext;
import org.springframework.context.support.ClassPathXmlApplicationContext;

/**
 *
 */
public class SpringInstanceFactoryBeanIssueTest extends SpringTestSupport {

    @Override
    protected AbstractXmlApplicationContext createApplicationContext() {
        return new ClassPathXmlApplicationContext("org/apache/camel/spring/issues/SpringInstanceFactoryBeanIssueTest.xml");
    }

    @Test
    public void testBean() throws Exception {
        getMockEndpoint("mock:result").expectedBodiesReceived("Hello World");

        template.sendBody("direct:start", "World");

        assertMockEndpointsSatisfied();
    }
}

redpajama_set_name: RedPajamaGithub


Description: Even after being cast into the dark place between worlds, LOKI continued to plot the downfall of Earth and Asgard. Patient years spent exploring the dark nowhere have finally led him back to the world of light, where his diabolical plans threaten all of creation.
This detailed LOKI figure puts you right into the heart of the battle for the future of the planet. This fierce villain figure bears his signature weapon – including snap-out blades! He's ready for anything and your Cosmic Spear LOKI figure will take your battles to the next level!
Figure comes with weapon accessories. May come in bilingual text packaging.


text:
Busan: 'Winter' is Coming to Market With Distribution Workshop
Variety by Patrick Frater
"Somewhere Winter," a Chinese-language romantic drama, has joined the sales slate of Distribution Workshop in time for the Busan International Film Festival's Asian Film Market.
The film is directed by David Wang Weiming ("Sex Appeal") and stars Ma Sichun ("Soul Mate," "The Left Ear") and Wallace Huo ("Our Time Will Come").
The movie tells a love story about two generations and three cities. Destiny brings the lovers together and then tears them apart. With all ups and downs over the years, only the song "It's About in Winter" remains the same. The story is based on the eponymous novel by Rao Xueman ("The Left Ear",) which was in turn inspired by famous singer Chyi Chin's popular 1987 song "It's About in Winter."
Production is by Jimmy Huang ("Life of Pi," "Cape No.7"). Production companies and investors include: Beijing Dino Films, Jiangsu Xue Man She Film Production, and Tencent Pictures (Hong Kong). Cinematopgraphy is by ace Mark Lee Ping Bing ("The Assassin," "In the Mood for Love").

redpajama_set_name: RedPajamaCommonCrawl


Over the last few months I haven't really been myself. It's no secret that I don't really do well with the mental health side of life. Well the last few months have been tough, well that last month.....well that's included countless night crying myself to sleep, crying into charlie after three attempts to take my own life, constant cutting and just the feeling like all I do is cause pain and upset for everyone. For every single moment of that Charlie has been there, hes been the one worrying what I'll do and I'm sorry for that.
It's time to try everything again. I'm back on the kalms, I now keep a rescue remedy spray in my work pencil case, I have to constantly be trying to do things to perk me up because stuff got to real again. I have everything I could want. I have the man of my dreams, a supportive family, me and Charlie are planning our dream holiday for next march and I know that no matter what ,well he is by my side through all of it. He may not understand it all but he's there for me.
This weekend we spent hours in a park, he took me to our little ice cream spot. Just a place for me and him. We spent our time being silly and just enjoying life. Sunday after the day from hell in work, I got home and just fell asleep. I was mentally and physically drained. I woke up to an arm draped around me stroking my hand. Charlie came round and just cuddle me until I woke up. We had the most perfect evening, diner with my parents and then went to see dead pool. The evening just got a bit worse and I snapped. My brain went into meltdown and I just sobbed. We went back to mine and charlie snuggled me into his chest and just sobbed. I cried and cried and cried and I got the best little pep talk. We put my little star projector on and just laid in silence while I tried to get my head straight.
I feel awful that still after having someone in my life who is a there for me to wipe away the tears, to always be there even if we argue, well I feel bad that I am still not fixed. I thought it would all go away. The truth is that I will never be 100%. There is a part of me that will always be slightly darker than I want it to be. I will always have the days where everything just crumbles, I just need to learn to accept help and anyone that is not on board with who I am, well they need to just leave me to it.
Charlie won't ever read this but in the rare chance he does, just thank you. Thank you for wiping away the tears when I'm crying my heart out. Thank you for dealing with the tiny insecurities that just blow up sometimes. Thank you for proving to me everyday that you were the best decision I could have ever made. At one point I thought I have to pick and every day I'm glad I chose you. Thank you for just loving me for who I am and never failing to love me. Thank you for just letting me act me, for not letting my weirdness freak you out. Thanks for being on team me all the time and reminding me every day why I love you.
I guess life has just got to a point where I know I have been trying to play catch up with people that are at very different points in their lives. I let everyone else's opinions of my relationship take it's toll on me and I think its just got too much. I need to just live life without worrying about the future. Charlies right, when I said to him "I don't know where I'm going, I don't have a clear future" he said to me "yes you do, you re looking at your future ". He's right. My future might not be clear if I will ever get a house, have kids or get a decent job. But he is right that my future is with him.
To anyone reading this feeling like there's no way to make it all better. There is. There is always a way to make it better. My way of coping now is just thinking of the little things, I'm reading a lot of self help books. I'm taking kalms to try and make me relax a little more. This isn't an easy fix. Like sometimes feels like it wont stop. My head feels like the darkest clouds are hazing my view of everything good. This isn't something I can just get over. It's a part of me and I think I'm just scared to admit that to people. Charlie is the only one of his family that know. They don't know what I do when I feel like I can't escape. They don't know that Charlie has to deal with a woman that's mind and heart are two opposite people, that he has to deal with me feeling like I need to end it all. He copes with all that and I just wish they understood that I cant help who I am.
I don't really know what the point of this was. I guess I just needed to put it all out there. I'm tired of going to work and acting like I can cope, smiling like I am the happiest woman on the planet, laughing like I haven't a care in the world. I'm facing the truth of who I am. No matter how much I try to fix myself, the damage is done but I think I'm finally ready to actually help myself.


text:
November 11, 1998 Press Contact: Steve Koppes
Huge fish-eating dinosaur emerges from the Sahara
An enormous predatory dinosaur with a skull like a crocodile's and foot-long thumb claws has been discovered in the Sahara by an international team led by Paul Sereno of the University of Chicago.
Measuring 36 feet in length and 12 feet high at the hip, the specimen is the most complete known of a peculiar group of fish-eating predators called spinosaurs, animals that grew to the size of Tyrannosaurus rex. In a paper in the Nov. 13 issue of Science, Sereno and his colleagues name the new species Suchomimus tenerensis, meaning "crocodile mimic from Tènèrè," a remote and forbidding, dune-covered region of the Sahara in the Republic of Niger in West Africa.
Sereno, and his 15-member expedition spent more than two months in the fall of 1997 scouring the desert in temperatures that climbed to 120 degrees. They unearthed 25 tons of bone and rock that included the remains of Suchomimus.
Team member David Varricchio spotted the huge, sickle-shaped thumb claw. "It was lying on the surface of the desert, completely exposed by wind and sand, and would have been visible like that for centuries to anyone who walked by," Sereno said. The claw led the team to 400 pieces of the skeleton, buried just inches under the desert plain.
Sereno said that the discovery reveals new information about the peculiar anatomy of spinosaurs, which he called "a dinosaur trying hard to be a crocodile." Its four-foot-long skull has an extremely long and narrow snout with large teeth near its end, as in specialized fish-eating crocodiles. The jaws were studded with more than 100 conical teeth that functioned like hooks rather than slicing blades.
The foot-long thumb claws and powerfully built forelimbs were used to snare fish and other prey as the dinosaur waded in rivers; the thin, bony sail along its back, which reached a height of two feet over the hips, may have been brightly colored for display.
Suchomimus lived in Africa about 100 million years ago in what was then a forested region dissected by broad rivers and home to other dinosaurs, huge crocodiles, turtles, pterosaurs and many kinds of fish. It would not have been a friendly place, Sereno said. "If you weren't grabbed by a spinosaur, you'd likely run into a 50-foot crocodile."
Suchomimus was the largest and most common predator of its day, judging from the numerous bones Sereno's team recovered. Its closest cousin is Baryonyx from Europe rather than the tall, sail-backed north African spinosaurid Spinosaurus. This far-reaching link suggests that, on at least one occasion, spinosaurs crossed the broad Tethyan seaway that separated northern and southern land masses at that time.
Spinosaur fossils were first discovered in Niger's Tènèrè Desert some 50 years ago and were collected in earnest 25 years ago by French paleontologists. The region's fossil-rich rock provides the best opportunity to unearth clues to plants and animals that thrived in Africa 100 million years ago, as the continent was drifting into geographic isolation.
The expedition and laboratory work on the fossils was supported by the National Geographic Society, the David and Lucile Packard Foundation, the Pritzker Foundation and the Women's Board of the University of Chicago.
NOTE: Suchomimus tenerensis will be on display at the National Geographic Society's Explorers Hall museum, 17th and M streets N.W., Washington, Nov. 13 through 29. It will be moved to Chicago Children's Museum, beginning Dec. 10.
http://dinosaur.uchicago.edu/
http://www-news.uchicago.edu/releases/98/981111.suchomimus.shtml


Instructional design is perceived as something separate from technical writing. Let's take a closer look at this field and see for ourselves whether a line should be really drawn between techcomm specialists and instructional designers.
We can clearly see that technical writers are no strangers to some instructional design tasks. We can even sum up technical writing in a pretty similar way - the means to explain to someone how something works, to teach users a product or a service.
However, instructional design is much more education-focused (while in case of technical writing we are mostly interested in the clarity of given information, instructional writing searches for ways to really teach people something) and, thus, approaches to similar tasks of providing a user with knowledge on how something works are quite different, too.
Instructional design is more creative. Ways of delivering information are chosen according to the audience and task. For example, a learning course can include animation, slides, written materials, or even be delivered in the form of an educational game. This brings us to the question of skills a successful instructional designer will most likely possess as compared to a documentation writer.
Any teacher should know learning methodologies in order to really teach somebody. There are certain specifics connected to learners' age, knowledge level, the content itself that will define future educational materials.
Learning methodologies include information on how content is absorbed by our brain, how much new data each educational chunk should contain and how to make sure this data will be fully processed and memorized.
We see instructional design leaning towards the pedagogical field, while help authoring is mostly just trying to be as clear and precise as possible.
Instructional designers are often faced with tasks that require a creative approach. In order to make learning more appealing, ideas need to be presented in some interesting manner. So, imagination should cooperate with learning methodologies here. And, to make all this happen, instructional design specialists require tools to work with imagery. They don't have to do all the work, of course, but, at the same time, instructional designers should be able to sketch and create mockups.
Technical writers do use different editors for videos, gifs, screenshots, but in a more pragmatic way. Help authoring hardly ever requires creativity.
This is kind of connected to learning methodologies, but this aspect certainly deserves special attention.
Instructional designers should understand how to assess users' knowledge, what tools to use for that. That's crucial for understanding how successful the educational content turned out to be, where excellent marks do not necessarily mean success, they can just mean that the topic is too easy. Correlation with what's expected matters more.
Technical writers have some assessment tools for user guides, as well. But these metrics don't test readers, they evaluate a doc team's performance, rate usefulness of help topics and content readability.
Instructional design and technical writing are different areas that are getting closer with time. Technical writers are now moving towards deeper analysis of user experience and further usage of this knowledge to create more reader-focused technical documentation. Earlier, the focus was placed on content more. Besides that, some forms of content coincide between the two occupations, like video tutorials or user guides. We think that it would be useful for tech writers to collaborate with instructional designers to learn tips and tricks that work well for educating users.


Individual auditions are Sunday the 24th June or Tuesday the 26th of June. Please book a time with the director.
This play has more than 50 scenes. No characters are named, given an age or gender. An ensemble will be cast by individual audition. Workshops will then be used to discover the actors' relationship to the text and the scenes will then be cast and go into rehearsal. It is a wonderful, intense, moving and funny play. Audio-visual will be used in performance.
All ages/genders/preferences from 16 to 90.
"The play asks us to consider how meaning is constructed and to participate in the process" – Jennifer Wilkinson.
Workshops and rehearsals will be most Sundays, Tuesdays and Thursdays from the 19 July to 2 October. Performances are 5 October to 20 October. All auditions, rehearsals and performances are in Emerald.
Please contact the director David Lawson-Smith on dlawsonsmith@bigpond.com to book an audition or with any questions.


Overlapping oblique survey is usually required to examine environmental impact such as river or coastal erosion or the spread of pollution. The images are taken to provide an overlapping continuous run along the area of interest. All imagery is provided with GPS data to allow easy and precise location of each image.


Education for Sustainable Development (ESD) requires knowledge and engaging in natural, social and economic plane. Each idea and well thought activating projects in a broad range of social foundations of sustainable development seem to be particularly valuable and very important here. Building a holistic view of environmental issues (with emphasis on social issues) will simplify finding solutions to problems under the new rules of the global population Human development. KOS programme activates to act younger and older people over 50 years of age. It combines youth and senior citizens as a source of knowledge and experience. The publication presents the program KOS: its purpose, beneficiaries, stages of implementation with the priorities and programme evaluation methods.


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↑ "Classification of Sudan in both North and Sub-Africa". Unstats.un.org. 20 September 2011. "The designation sub-Saharan Africa is commonly used to indicate all of Africa except northern Africa, with Sudan included in sub-Saharan Africa." This classification predates the secession of South Sudan from Sudan.
↑ "Political definition of "Major regions", according to the UN.". Retrieved 15 December 2010.
"UNESCO - Arab States". Portal.unesco.org.