text:
Q: Is if possible to use c# to access excel files? Hi simple question I want to go into a folder look for the excel files. Then go into each excel file and change red font coloring to black using c#. Is this Possible?
namespace Excel_font_color_change
{
    public partial class Form1 : Form
    {
        public Form1()
        {

            InitializeComponent();
        }

        private void button1_Click(object sender, EventArgs e)
        {
            List<string> HtmlPathList = new List<string>();
            string folderToSearch;

            FolderBrowserDialog fbd = new FolderBrowserDialog();
            fbd.ShowNewFolderButton = true;//allow user to create new folders through this dialog
            fbd.RootFolder = Environment.SpecialFolder.MyDocuments;//defaults to my computer
            System.Windows.Forms.DialogResult dr = fbd.ShowDialog();//make sure user clicks ok
            if (dr == DialogResult.OK)
            {
                folderToSearch = fbd.SelectedPath;//gets folder path
                try
                {
                    var allFiles = from files in Directory.EnumerateFiles(folderToSearch, "*.xls*", SearchOption.AllDirectories)
                                   select Path.GetFullPath(files);//gets all files with htm & htm + something for extensions
                    foreach (string filepath in allFiles)
                    {
                        HtmlPathList.Add(filepath);//adds each filepath found to the list
                    }
                }
                catch (UnauthorizedAccessException UAEx) { Console.WriteLine(UAEx.Message); }//error handling
                catch (PathTooLongException PathEx) { Console.WriteLine(PathEx.Message); }//error handling
                Console.WriteLine("1");
            }
        }

        private void button2_Click(object sender, EventArgs e)
        {

        }
    }

This is what I have so far, I want the second button to take the file path that are in  HtmlPathList and edit the font colour to black if it is red. I am looking thru How to read data of an Excel file using C#? right now.

A: Check out this library. It works for xlsx only though.
http://www.microsoft.com/en-us/download/details.aspx?id=5124
If you want to read old xls files you can use Interop assemblies.
http://www.microsoft.com/en-us/download/details.aspx?id=3508

A: This solution requires a reference to the Excel Interop Assemblies (Excel must be installed on the machine that is executing the utility as the Interop Assemblies are executing excel in the background):
    using Microsoft.Office.Interop.Excel;

    /// <summary>
    /// sets a cell range's font color
    /// </summary>
    /// <param name="filename"></param>
    /// <param name="startCell"></param>
    /// <param name="endCell"></param>
    /// <param name="color"></param>
    public void setCellRangeFontColor(string filename, string startCell, string endCell, string color)
    {
        Microsoft.Office.Interop.Excel.Application xlApp = new Microsoft.Office.Interop.Excel.Application();

        if (xlApp == null)
        {
            MessageBox.Show("EXCEL could not be started. Check that your office installation and project references are correct.");
            return;
        }
        //xlApp.Visible = true;

        //Workbook wb = xlApp.Workbooks.Add(XlWBATemplate.xlWBATWorksheet);
        Workbook wb = xlApp.Workbooks.Open(filename,
                Type.Missing, Type.Missing, Type.Missing, Type.Missing,
                Type.Missing, Type.Missing, Type.Missing, Type.Missing,
                Type.Missing, Type.Missing, Type.Missing, Type.Missing,
                Type.Missing, Type.Missing);
        Worksheet ws = (Worksheet)wb.Worksheets[1];

        if (ws == null)
        {
            MessageBox.Show("Worksheet could not be created. Check that your office installation and project references are correct.");
        }

        ws.get_Range(startCell, endCell).Font.Color = System.Drawing.ColorTranslator.ToOle(Color.FromName(color));

        wb.Close(true, Type.Missing, Type.Missing);

        //wb.Save();
        xlApp.Quit();

        releaseObject(ws);
        releaseObject(wb);
        releaseObject(xlApp);
    }

    public static void releaseObject(object obj)
    {
        try
        {
            System.Runtime.InteropServices.Marshal.ReleaseComObject(obj);
            obj = null;
        }
        catch (Exception ex)
        {
            obj = null;
            //MessageBox.Show("Exception Occured while releasing object " + ex.ToString());
        }
        finally
        {
            GC.Collect();
        }
    }

redpajama_set_name: RedPajamaStackExchange


text:
Alestorm - Curse Of The Crystal Coconut
'We're just hear to have fun, get drunk and make loads of money!' Alestorm boisterously proclaim on their opening track, 'Treasure Chest Party Quest'. Their new record Curse Of The Crystal Coconut is another truly excellent offering. The band has positioned themselves as the ultimate festival act. The group who you NEED to see because even after a decade of doing it they are finding ways to make their festival appearances even more exciting, fun and action packed. This new collection of songs will only elevate the band.
Alestorm has long been to ridiculous for most, and this record changes none of that. With tracks like 'Zombies Ate My Pirate Ship' the band are just as silly as ever. Beyond that though there are still the standard pirate metal tracks here, oftentimes paired with some of the more bizarre elements of the bands discography. As with their last offering, No Grave But The Sea the band certainly leans into the more bro-y aspect of festival culture here, tongue in cheek as always. Even the surprisingly introspective 'Call Of The Waves' starts with a look inwards before descending into an anthem about conquering the oceans.
In other words - Alestorm continue to be the kings of feel good pirate metal. Guest appearances from members of Finntroll, Rumahoy and Patty Gurdy of Patty Gurdy's Circle provide breadth to the record, and remind us that through it all Alestorm are looking to grow as musicians and embrace more unique collaborations. This is a fun record that is going to remain fun, over the top and more than a little bit ridiculous. Alestorm have always been a blast to listen too and now more than ever they seem ready to take on the world.
https://www.facebook.com/alestormband/
Labels: Pirate Metal
Sharon Wayne June 20, 2020 at 10:27 AM
For more details about Dr Emu visit his Website: http://emutemple.website2.me/

redpajama_set_name: RedPajamaCommonCrawl


Attention Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder (onset before age 12) with a persistent pattern of inattention and/or hyperactivity-impulsivity that interferes with functioning or development. ADHD usually persists into adulthood as well and needs long-term management. Inattention is manifested in several ways such as failing to pay close attention to details, difficulty focusing on tasks or daily activities, reluctant to engage in tasks that require sustained mental effort, or difficulty in planning and organization. Hyperactivity refers to excessive motor activity when it is not appropriate: tapping, fidgeting, talking excessively. Impulsivity may manifest as social intrusiveness, difficulty in turn taking, hasty actions and decisions that can have harmful consequences. These features do not occur due to defiance or lack of comprehension and are present in more than one setting (home, school, work). All these features are related to executive functioning which can loosely be defined as the ability to direct behavior to attain goals and solve problems. Executive functions are then used for self-regulation. Most theories of ADHD suggest a lack of sustained motivation to carry out tasks or follow rules necessary for living especially in a larger social context. Thus due to neurological differences, people with ADHD find it more difficult to perform tasks that require a longer period of effort and without immediate and tangible rewards. It is important to note that the difficulty is with motivation and not intellect or ability. Possible deficits in academic or working capacity come about as a result of inattention as secondary outcomes but can be managed and worked around.
Dividing tasks into smaller, manageable portions with rewards for each: As mentioned before, ADHD comes with a difficulty in sustained effort and motivational deficits. Thus breaking up a task into daily activities that are rewarded more often is helpful. Ex: a month-long project can be broken into daily tasks which are assimilated and rewarded weekly or bi-weekly as per the motivational needs of the individual.
Externalizing the internal self-regulatory information: For people with ADHD, management of behavior is problematic as the internal dialogue/processes used by people to control behavior are not effective enough to sustain behavior. Thus charting out a daily routine or putting up rules to be followed in engaging ways can help fill the gap in internal motivation. The child/adult can be made to repeatedly verbalize the rules as well. Picture exchange communication system (PECS) can be a useful device. It helps visually represent objects or tasks that the child has to follow through the day making up externally for the shortage of internal regulation.
It is of utmost importance that the modifications being made in controlled environments should be made applicable in natural settings as well: Working within the playroom or therapist's office without applying the learning to the child's natural environment will not lead to any actual functional improvement. Thus the parents/caretakers need to be on the same page as the therapist/teachers so that the same set of behaviors is being replicated across different settings.
Resource pool of effort (willpower) is the cognitive energy available with the individual to apply to a particular task: ADHD makes this resource less available especially over time. Therefore, timely breaks, experiencing positive emotions, periodic small rewards, consuming a glucose-rich beverage between strenuous tasks help rapidly replenish the resource pool. Over time, regular physical exercise and routine practice of tasks involving self-regulation can increase the capacity of the resource pool.
Further, as the parent/primary caregiver, it is important to manage one's own emotions and frustrations. Not only does that impact the child's self-esteem, but children also mirror the emotions and actions of the authority figures. Support groups with other parents, family therapy, individual counseling for the parent are also useful. Even as adults, people with ADHD can have difficulties in relationships and would need partners who are aware about and sensitive to the particular struggles with the condition. Therapy and support groups can be useful for partners and close friends/relatives as well.
Barkley, R. A. (2012). Executive Functioning and Self-Regulation: Extended Phenotype, Synthesis, and Clinical Implications. New York: Guilford Publications. Projected publication date, early 2012.


Tis the season of gift giving and from homeware to hardware, Breed and Company has options to meet every shopper's needs.
Let's start with some great handbag and travelware brands like Jon Hart and Spartina.
And don't even get me started on the kitchen... there's the Kitchen Aid mixer and all things Cuisinart, Le Creuset for your dutch oven needs, my recently acquired best friend, Nespresso, and my even more recent best friend Breville for their fabulous tea maker.
Breed is also popular for wedding registries because of their great China collections with brands such as Lenox, Herend, and Waterford. And don't forget your Lismore crystal.
And a personal favorite of mine - collections of classic Blue and White or Woodland Spode.
onto the hardware side of things, where to begin? There's your all-in Craftsmen Tool kit, or everything a la carte - wrenches, screwdrivers, hammers, et al. Of course, don't forget your power tools, too. Locks, keys, paint, and so on.
For outdoors, there's your hose, your reel, and even a bird camera!
It's also the place to get your Texas Tervis tumbler fix.
And speaking of Texas, look no further for your BBQ outfitting. Breed has Weber grills galore, along with your tool set, grill brush, grill basket, and on.
And speaking of BBQ, you can never have too many Yetis on demand.
And for grooming, there are plenty of Jack Black products to meet your needs.
So swing by Breed & Co. It's great for gifts any time of year.


text:
Q: How to do an Ajax form field on Flask Admin I'm building a Flask-Admin app that uses a REST API as its backend database, which I've implemented as my own BaseModelView. I've got it working with a custom model, and implemented all the functions to edit and save the model.
However I have one field, User, which needs to search another REST API endpoint for a User ID based on name/email, and as the list of users is expected to become quite large I want that field to be an AJAX lookup as I've seen in the SQLAlchemy example looking up a foreign key via Select2/Ajax.
As I need my own Ajax lookup, from following the docs and reading through the code, I'm struggling to find a working example of how to implement it myself and was wondering if anyone can direct me.
I've tried implementing an AjaxSelectField and using the form_ajax_refs property of BaseModelView to override the User field of the form (created in the scaffold_form method) without success.
Does anyone have an example of how I can put a custom Select2 Ajax lookup field, that looks up data from a REST API, on my model form so I can search for a User ID to assign to the model when I create/edit a model?

A: Figured it out finally, you have to add 2 things to your BaseModelView to do this:
In your BaseModelView class - Add an AjaxSelectField to your form with a custom model form:
def scaffold_form(self):
  class AccountForm(Form):
    owner =  AjaxSelectField(UserAjaxModelLoader('owner'),
                                     label='Owner', blank_text="Select User...")
  return AccountForm

Then add a reference to your form_ajax_refs field:
form_ajax_refs = {
    'owner': UserAjaxModelLoader('owner')
}

Finally the implementation of the UserAjaxModelLoader class which provides the AJAX endpoint and strings it all together:
from flask_admin.model.ajax import AjaxModelLoader, DEFAULT_PAGE_SIZE

class UserAjaxModelLoader(AjaxModelLoader):

    def __init__(self, name, **options):
        super(UserAjaxModelLoader, self).__init__(name, options)

    def format(self, model):
        if model:
            return (model.uid, model.email)

        return None

    def get_one(self, pk):
        return auth.get_user(pk)

    def get_list(self, query, offset=0, limit=DEFAULT_PAGE_SIZE):

        # Put your code to search REST API for users here

        return users


C500 is VJOYCAR first released 3rd generation hud, no need paste the film on the car windshield glass, no need buy extra car phone holder, it can project the digitals on its own holder… very clearly, no double image. Won't affect the sight-view of car, the best car safety gadget!
New Innovation! The 3rd General Smart Speed Display!
1st generation hud: Project the speed on the film. Double image, not very clear.
2st generation hud: Project the speed on hud holder glass. No need to paste the film, but it has double image still.
3rd generation hud: Display the speed on the hud holder glass directly. Not projection. No Double Image!


text:
Four Business and Industry Leaders Elected to Alliance to Save Energy's Board of Directors
Release Date: Tuesday, December 29, 2015
Washington, D.C., December 29, 2015 – The Alliance to Save Energy (Alliance) Board of Directors has elected four individuals who will help support the Alliance's mission of achieving a more energy-efficient future. We are confident that with their added expertise and support, the Alliance will soar to new heights in the year ahead. The newly elected Directors, who represent top business, utility and industry entities, include:
· Jeff Hohn, VP & General Manager, Renewable Energy Division, 3M
· Randy Leslie, VP of Marketing, Distribution & Product Support, Building Efficiencies Group, Johnson Controls, Inc.
· Terence Sobolewski, SVP, CCO, Customer Organization, National Grid
· Tom Kuhn, President, Edison Electric Institute
Alliance President Kateri Callahan, elated to welcome the newest additions to the board, said, "It is the diversity of voices and perspectives that has continually set the Alliance's board apart. We look forward with great anticipation to these four new stellar voices joining the team, and are confident that our mission to advance energy efficiency will be strengthened by their contributions."
Honorary chair Senator Jeanne Shaheen (D-N.H.) said, "The combined experience of the Alliance's new board members will surely help us move towards common sense, bipartisan energy policies that will in turn create jobs, lower pollution, and save consumers and taxpayers money."
Jane Palmieri, Dow Chemical Company's business president for Building & Construction and Alliance board co-chair said, "I am eager to work closely with Jeff, Randy, Terence and Tom in 2016 and beyond. I am certain that their leadership will bring a great deal of added value to the Alliance, and that their contributions will be invaluable as we continue to advance energy efficiency policy throughout the coming year."
Jeff Hohn, vice president and general manager of the Renewable Energy Division at 3M, brings vast leadership experience with global technology companies in the electronics, solar, display (LED and OLED) and data storage industries. Hohn said, "Working with the Alliance presents a great opportunity to encourage enhanced energy efficiency including strategies within the manufacturing sector. I am privileged to join this capable board to advance our shared goal of pushing forward energy efficiency."
Randy Leslie, vice president of Marketing, Distribution & Product Support in the Building Efficiencies Group at Johnson Controls, Inc. brings broad experience in strategic marketing, engineering services, learning and development, commercial operations and government and partnership relationships. Leslie said, "Johnson Controls continues to explore strategies that expand our energy efficiency initiatives in order to benefit the consumer, and to contribute positively to the environment. I am looking forward to working closely with my colleagues on the board to advance the cause of energy efficiency."
Terence Sobolewski, chief customer officer of National Grid U.S., is responsible for the company's strategy on customer engagement and development, sales of gas conversion and energy efficiency programs, gas and electric procurement and supply, and customer analytics. Sobolewski said, "As one of the largest investor-owned energy companies in the world, we see incredible opportunity in the inextricable link between energy efficiency, demand-side management programs, and customer engagement. Looking ahead to what we hope will be a productive year for energy efficiency, I am grateful to have the opportunity to join a board that brings so much value to the clean energy discussion."
Tom Kuhn, president of Edison Electric Institute, has rejoined the board after recent term limitation. Kuhn brings a wealth of energy knowledge gained during his more than thirty years in the industry. Kuhn said, "Throughout my years in the energy sector, I have seen time and time again that energy efficiency is a key to saving money for consumers and for businesses. I am eager for the opportunity to renew collaboration with the Alliance's diverse board and to help our country continue to reap the benefits of energy efficiency."
The Alliance to Save Energy is a leading voice in the effort to build a healthier, cleaner, and stronger economy.
Rep. Peter Welch
(D-Vt.)


text:
Sarah Poewe (Ciudad del Cabo, Sudáfrica, 3 de marzo de 1983) es una nadadora alemana de origen sudafricano especializada en pruebas de corta distancia, donde consiguió ser medallista de bronce olímpica en 2004 en los 4 x 100 metros estilos.

Carrera deportiva

En los Juegos Olímpicos de Atenas 2004 ganó la medalla de bronce en los relevos de 4 x 100 metros estilos, con un tiempo de 4:00.72 segundos que fue récord de Europa, tras Australia (oro) y Estados Unidos (plata).

Referencias

Enlaces externos

Nadadores de Alemania
Medallistas olímpicos de natación
Nacidos en Ciudad del Cabo

redpajama_set_name: RedPajamaWikipedia


text:
Роторно-лопастной двигатель Иванова (Вигриянова) — роторно-лопастной двигатель внутреннего сгорания. Особенность двигателя — применение вращающегося сложносоставного ротора, размещённого внутри цилиндра и состоящего из четырёх лопастей.

История разработки
Роторно-лопастная схема двигателя была предложена ещё в 1910 году. Предлагалось только придумать к ней механизм, позволяющий двигаться лопастям по определённой закономерности. В шестидесятых годах прошлого века немецкая фирма Клёкнер-Хумбольд-Дойц () провела исследование этого двигателя с механизмом Кауэрца (). Результаты были отрицательными. Одним из отрицательных факторов была работа самого механизма преобразования движения лопастей.

В 1973 году была разработана идея нового механизма преобразования движения лопастей. Идея пришла одновременно О. М. Иванову (Томск) и группе людей из Бердска (Новосибирская область) независимо друг от друга. М. С. Вигриянов к этому не имел ни малейшего отношения. Информацию о возможности изготовления роторно-лопастного двигателя он получил лишь в 1978 году, когда Иванов по приезде в Бердск изготовил первый макет этого двигателя.

Бердская группа не стала дальше работать над двигателем по причине внутренних разногласий. Иванов же создал группу из трёх человек: О. М. Иванов — автор идеи, М. С. Вигриянов — инженер-патентовед, В. А. Перемитин — слесарь.

На бердском опытно-механическом заводе (БОМЗ) был изготовлен рабочий образец, который не удалось запустить по простейшим причинам, которые стали понятны позже. За время работы с образцом стали видны некоторые недостатки этого механизма. Иванов предложил новый механизм преобразования движения, который можно было легко изготовить на доступном оборудовании. Двигатель с этим механизмом был изготовлен в Институте теплофизики СО РАН. Из бракованных деталей был собран макет, демонстрируемый Вигрияновым на фотографиях.

Разработкой интересовались в России и за рубежом: немцы, американцы, бразильцы. Предполагалось просто проверить на работоспособность данную схему, и если бы мотор проработал всего лишь пять минут, авторов схемы это вполне удовлетворило бы. Испытания показали, что в принципе мотор работоспособен, но требует больших доработок. Иванов предложил применить пластинчатые уплотнения вместо канальных в версии Вигриянова и выполнить их из графита. Нерешённой осталась схема уплотнений и смазки торцов валов.

Больше этот двигатель не изготавливался. Директор Института теплофизики СО РАН академик Владимир Накоряков создал акционерное общество для производства данного двигателя. Интересы Иванова в данном деле не присутствовали. Без автора мотор дальше дорабатывать было некому. Авторство Вигриянова в некоторой степени ставится под сомнение, так как по сути никаких кардинальных изменений в конструкции двигателя с его стороны не было, тем более не мог продолжить разработку.

Последняя волна интереса к РЛД была связана с озвученным публично намерением российского олигарха Прохорова, тогда - кандидата в президенты РФ, оснастить им свой Ё-мобиль, однако все изготовленные экземпляры данного транспортного средства оснащались "временно, до доведения до серийного образца РЛД", обычными ДВС.

Конструкция

На паре соосных валов установлены по две лопасти, разделяющие цилиндр на четыре рабочие камеры. Каждая камера за один оборот совершает четыре рабочих такта (набор рабочей смеси, сжатие, рабочий ход и выброс отработанных газов). Таким образом, в рамках данной конструкции возможно реализовать любой четырёхтактный цикл.

Преимущества и недостатки

Преимущества двигателя Иванова (Вигриянова) (роторного двигателя с неравномерным однонаправленным (пульсирующе-вращательным) движением главного рабочего элемента) характерны для любого роторного двигателя:

 отсутствие специального механизма газораспределения,
 высокая удельная мощность.

Недостатки этого типа роторных двигателей связаны с принципом организации рабочего процесса и в конструктивной схеме двигателя, которая подразумевает снятие мощности с двух разных валов (каждый соединён со своим «коромыслом» с лопастями), движущихся неравномерно — то мгновенно и полностью затормаживаясь(!), то резко ускоряясь, поочередными импульсами (при этом как бы то догоняя, то останавливая друг друга). Снятие мощности с таких «пульсирующих» валов крайне затруднительно. Чрезвычайно затруднительной оказывается синхронизация их движения друг относительно друга. Согласование выполняется крайне сложным и громоздким механизмом синхронизации и схемой движения-вращения с двух валов. На фотографии этот механизм виден на задней части корпуса — его диаметр и ширина больше, чем сам диск рабочей камеры, где происходят рабочие циклы. Именно эта неравномерность вращения двух рабочих валов, импульсный характер их вращения и определяют все трудности создания работоспособных типов этого подкласса роторных двигателей. В созданных прототипах двигателей огромные инерционные нагрузки быстро разрушали механизмы синхронизации валов и связанных с ними лопастей. По этой причине реально работающих моделей этого типа двигателя до сих пор не создано.

К недостаткам можно отнести также высокую тепловую напряженность роторов, особенно их лопастей. Для мощных РЛДВС обязательна эффективная принудительная система охлаждения роторов.

В работе двигатель Иванова (Вигриянова) равнозначен восьмицилиндровому четырёхтактному поршневому двигателю, поскольку за один оборот реализует четыре рабочих цикла.

Отношение М. Вигриянова к перспективам развития РЛДВС

В 2002 году в СМИ появилась статья о том, что проблема механизма преобразования попеременного движения лопастей в постоянное движение вала якобы была решена:
упоминается, что решение достигнуто с помощью некого "дифференциального механизма". Однако, в приведённой статье какие-либо строгие подтверждения этого факта отсутствуют, но при этом указано, что изготовить двигатель не удалось, по словам автора, из-за отсутствия финансов.

См. также
 Роторный двигатель
 Роторно-поршневой двигатель

Примечания

Двигатель внутреннего сгорания


US Open Tennis Championship 2015 is into its last rounds and we decided to take a look at at history of US Open and see who has won most US Open titles in both men's and ladies single events. US Open dates back to 1881 when it was played as yearly US national event with only US tennis players taking part in the competition and Richar Sears won the first 7 events from 1881 to 1887. William Larned also manage to win 7 titles in early 1900s before the event went global. But we are only going to take a look at modern era starting from 1968 when the competition was rebranded as "US Open Tennis Championship" and also given a grand slam status.
US Open Tennis Men's Singles Championship (Modern Era): Since 1968 when the Championship was given proper grand slam status, 3 players have won the US Open title 5 times with american duo Jimmy Connors and Pete Sampras plus Swiss player Roger Federer.
While american John McEnroe won the title 4 times in mens singles event since 1968 and Czecho-Slovakian player Ivan Lendl has won the US Open singles event 3 times. From current crop Rafael Nadal has two titles and Djokovic and Murray has both won once.
Women's Singles US Open Championship – (Modern Era): As far as women's singles titles are concerned, since 1968 the start of "Open Era" two american players Chris Evert and Sarena Williams has won most titles with 6 each to their name.
Sarena Williams has a great chance of winning her record breaking 7th title this year which will get her within 1 title short of Norway's Molla Bjurstedt Mallory who won 8 us open titles in amature era.


text:
Genetic analysis using whole-exome sequencing in pediatric chronic kidney disease: a single center's experience
Whole-exome sequencing in pediatric CKD
doi : https://doi.org/10.3339/ckd.22.025
Hyeonju Lee1 , Jeesu Min1 , Yo Han Ahn1,2,3 , Hee Gyung Kang1,2,3
1Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Republic of Korea
2Department of Pediatrics, Seoul National University College of Medicine, Seoul, Republic of Korea
3Kidney Research Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea
Correspondence to Hee Gyung Kang Department of Pediatrics, Seoul National University Children's Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea E-mail: kanghg@snu.ac.kr
Received 2022 April 1; Revised 2022 April 26; Accepted 2022 May 30.
Chronic kidney disease (CKD) has various underlying causes in children. Identification of the underlying causes of CKD is important. Genetic causes comprise a significant proportion of pediatric CKD cases.
In this study, we performed whole-exome sequencing (WES) to identify genetic causes of pediatric CKD. From January to June 2021, WES was performed using samples from pediatric patients with CKD of unclear etiology.
Genetic causes were investigated using WES in 37 patients (17 males) with pediatric CKD stages 1 (n=5), 2 (n=7), 3 (n=2), 4 (n=2), and 5 (n=21). The underlying diseases were focal segmental glomerulosclerosis (n=9), congenital anomalies of the kidney and urinary tract including reflux nephropathy (n=8), other glomerulopathies (n=7), unknown etiology (n=6), and others (n=7). WES identified genetic causes of CKD in 12 of the 37 patients (32.4%). Genetic defects were discovered in the COL4A4 (n=2), WT1 (n=2), ACTN4, CEP290, COL4A3, CUBN, GATA3, LAMA5, NUP107, and PAX2 genes. WT1 defects were found in patients whose pathologic diagnosis was membranoproliferative glomerulonephritis, and identification of CUBN defects led to discontinuation of immunosuppressive agents. Genetic diagnosis confirmed the clinical diagnosis of hypoparathyroidism, sensorineural deafness, and renal disease; Alport syndrome; and Joubert syndrome in three of the patients with CKD of unknown etiology (COL4A4 [n=2], CUBN [n=1]). Extrarenal symptoms were considered phenotypic presentations of WT1, PAX2, and CEP290 defects.
WES provided a genetic diagnosis that confirmed the clinical diagnosis in a significant proportion (32.4%) of patients with pediatric CKD.
Keywords: Genetics; Pediatrics; Renal insufficiency, chronic; Whole exome sequencing
Chronic kidney disease (CKD) is a global health problem with increasing incidence and prevalence [1]. Children with CKD face mortality, lifelong morbidity, and a low quality of life [2-5]. Advancements in medical care have substantially improved the survival rate of children with CKD [1]. Identifying the underlying cause of this disease is essential because the progression, treatment, and prognosis may differ according to etiology. However, traditional diagnostic approaches, such as kidney biopsy, could be unrevealing or contraindicated when the kidneys are already failing [6]. Therefore, new diagnostic methods are required to identify the etiology of CKD.
CKD is a complex genetically heterogeneous disease with both genomic and environmental causes. The heritability of CKD is relatively high (30%–75%) [7], and at least 15% to 20% of early onset CKD (before the age of 25 years) is caused by genetic variation. Nearly all children who progress to end-stage kidney disease (ESKD) have an inherited form of CKD [8,9]. In addition, approximately 17% of patients with ESKD do not have a primary renal disease diagnosis and are therefore labeled as patients with CKD of unknown etiology.
The diagnostic accuracy provided by genetic testing [6] could enable the establishment of treatment guidelines and aid in the accurate prediction of patient prognosis. Genetic diagnosis is crucial for identifying high-risk groups and for appropriate family planning. The prevalence of CKD caused by genetic defects is approximately 10% in unselected adults [9] and 20% to 30% in children with nephropathy [7,10]. These findings indicate that the clinical application of genetic testing could transform diagnostic pathways by providing a timely and accurate genetic diagnosis [11].
Sanger sequencing of the causative genes is typically performed to obtain a genetic diagnosis when CKD is suspected. However, the number of known causative genes for CKD is increasing, as is the number of CKD cases. Therefore, traditional Sanger sequencing is not cost-effective in most cases, making targeted exome sequencing or whole-exome sequencing (WES) the preferred approaches for genetic diagnosis [12-15]. WES can screen most genes associated with diseases and can therefore be applied across diverse categories of renal disorders. In addition, it can potentially identify novel etiological genes associated with nephropathy. Therefore, WES is emerging as the preferred diagnostic tool for hereditary disorders [12-17]. It has provided a genetic diagnosis in up to 11.5%, 26%, and 32.7% of patients with congenital kidney anomalies, steroid-resistant nephrotic syndrome, and ESKD, respectively [18,19].
In this study, we present the preliminary results of utilizing WES to identify the genetic causes of pediatric CKD in Republic of Korea.
1. Study design and participants
We prospectively recruited 37 pediatric patients with CKD whose underlying etiology was uncertain or suspected to be monogenic. The male to female ratio of the patients was 20:17. All study participants were recruited from Seoul National University Children's Hospital, Seoul, Republic of Korea. Buccal mucosal samples were collected and analyzed from January to June 2021. Details of DNA extraction and analysis of WES data have been previously described [20]. The identified variants were classified based on the American College of Medical Genetics and Genomics standards for the interpretation of sequence variants [21].
2. Statistical analysis
The diagnostic yield was calculated based on the variants classified as "pathogenic" or "likely pathogenic." All statistical analyses were conducted using Microsoft Excel (Microsoft Corp., Redmond, WA, USA) and SPSS statistical software version 20 (IBM Corp, Armonk, NY, USA).
1. Cohort characteristics
A total of 37 patients with CKD were recruited for this study. The underlying causes of CKD among the study participants were focal segmental glomerulosclerosis, congenital anomalies of the kidney and urinary tract (CAKUT) including reflux nephropathy, ischemic disease, Fanconi syndrome, Bartter syndrome, and CKD of unknown etiology (Table 1). One patient had a family history of CKD. The median ages at the time of CKD diagnosis and recruitment were 6 and 13 years, respectively. The distributions of the CKD stages and clinical diagnoses are described in Tables 1 and 2.
Clinical category characteristic and diagnostic yield of genetic diagnose across clinical diagnostic categories
Patient clinical characteristics of having whole-exome sequencing
2. Genetic findings and diagnostic yield
Diagnostic variants were detected in 12 of the 37 patients (32.4%), encompassing seven distinct monogenic disorders. The detected genes were COL4A4 (n=2), WT1 (n=2), ACTN4 (n=1), CEP290 (n=1), COL4A3 (n=1), CUBN (n=1), GATA3 (n=1), LAMA5 (n=1), NUP107 (n=1), and PAX2 (n=1). An additional three patients had variants of uncertain significance. The diagnostic yield (Table 1) was the highest among patients with CKD of unknown etiology (n=6, 50%). In contrast, diagnostic variants were not detected in some (n=7) of the clinically diagnosed CKD cases, including Alport syndrome, CAKUT, and renal hypoplasia with diabetes mellitus.
3. Clinical implications of genetic diagnoses in the study
Table 3 summarizes the clinical characteristics and genetic results of the patients with diagnostic variants. In six cases including three patients with CKD of unknown etiology, WES clarified the clinical diagnosis or reclassified the disease, which considerably affected clinical decision making. In five cases, WES confirmed the clinical diagnosis of hypoparathyroidism, sensorineural deafness, and renal disease; Alport syndrome; and Joubert syndrome.
Diagnostic variants identified in whole-exome sequencing
Genetic diagnoses have direct consequences for medical management. The diagnosis of Alport syndrome enabled genetic counseling and screening for auditory and ophthalmological problems. Detection of WT1 defects in patients with pathological diagnoses of membranoproliferative glomerulonephritis led to more careful monitoring of malignancy. In accordance with Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, identification of CUBN defects in a patient with persistent isolated proteinuria resulted in discontinuation of immunosuppressive agents [22]. Patients with extrarenal symptoms were examined to obtain a genetic diagnosis of WT1 (sex reversal), PAX2 (retinopathy), and CEP290 (Joubert syndrome) defects.
In this study, we used WES to identify the genetic causes of pediatric CKD in Republic of Korea. The diagnostic yield of this approach was 32.4%, encompassing 10 genes, one copy number variation, and one microdeletion. This is similar to previous studies reporting detection rates of causal mutations. Mutations were detected in approximately 20% and 30% of patients who presented with CKD [7] and ESKD [10], respectively. These causal mutations were detected in patients diagnosed before the age of 25 years. Furthermore, children with kidney failure had a detection rate of approximately 40% [6]. With rapid technological advances, we expect that regular re-analysis, re-interpretation, and reclassification of variants will increase these detection rates [23,24].
The primary diagnosis in patients with ESKD is often inaccurate [25], resulting in its characterization as a CKD of unknown origin. In adults, WES provided a genetic diagnosis in 22 out of 92 patients (24%) with CKD of unknown etiology [26], whereas our study established a diagnostic yield of 50%. This shows that WES is effective in determining the genetic causes of CKD of unknown etiology. However, it is important to note that the number of patients in our study was small.
Establishing a precise genetic diagnosis can allow for the preemptive screening of extrarenal manifestations. Patients clinically diagnosed with isolated CAKUT can have mutations in genes that cause syndromic diseases [27]. In other cases, extrarenal manifestations could be detected later in life. Moreover, subtle phenotypes may be initially overlooked and only identified through a genetic diagnosis. In these cases of reverse phenotyping, identification of a genetic mutation can lead to preemptive screening for extrarenal manifestations, leading to early provision of treatment where possible. In our study, extrarenal symptoms were identified to obtain a genetic diagnosis of WT1, PAX2, and CEP290 defects.
Recent KDIGO guidelines recommend discontinuing immunosuppressive agents if a monogenic cause is discovered in a patient with focal segmental glomerulosclerosis. Furthermore, concerns regarding kidney donations by living donors may be alleviated because of the reduced risk of recurrence [28]. In addition, genetic diagnosis aids in choosing potential donors among living relatives. For example, if Alport syndrome is diagnosed in a male patient, his mother needs to be tested for the presence of pathogenic variants before considering donating a kidney to her son. This is of clinical importance because we genetically identified Alport syndrome in patients with a clinical diagnosis of focal segmental glomerulosclerosis. This finding is an indication of variable phenotypic expressions caused by mutations in Col4A genes, such as hematuria or proteinuria, and is consistent with recent studies [29-31].
The limitations of our study include a relatively short study period and small sample size, in addition to its single-center design. Another limitation is that only one patient had a family history of CKD. In addition, some compound heterozygous variants were not investigated for phasing. The significance of variants of uncertain significance was not investigated further because it was beyond the scope of this study. The inherent shortcomings of WES include the possibility of missing mutations in introns, copy number variations, trinucleotide repeat expansions, methylation abnormalities, and mutations in exons with low coverage [23].
In conclusion, WES provided a genetic diagnosis in a considerable proportion of patients with pediatric CKD in Republic of Korea, which may confirm clinical diagnoses, provide guidelines for patient management, and aid in genetic counseling. Our study provides more evidence supporting WES as a new diagnostic method for identifying CKD etiology in children.
Ethical statements
This study was approved by the Institutional Review Board of Seoul National University Hospital (No. 2011-048-1171). All patients were enrolled after informed consent was obtained from them and their caregivers.
This study was supported by a National Research Foundation of Korea grant funded by the Korean government (MSIT, No. 2020R1A2C1100974).
Conceptualization: YHA, HGK
Data curation: JM, YHA
Formal analysis: HL
Funding acquisition: HGK
Investigation: YHA
Methodology: JM
Project administration: HGK
Visualization: YHA
Writing-original draft: HL
Writing-review & editing: HGK
All authors read and approved the final manuscript.
1. Becherucci F, Roperto RM, Materassi M, Romagnani P. Chronic kidney disease in children. Clin Kidney J 2016;9:583–91.
2. Kaspar CD, Bholah R, Bunchman TE. A review of pediatric chronic kidney disease. Blood Purif 2016;41:211–7.
3. Moreira JM, Bouissou Morais Soares CM, Teixeira AL, Simoes E Silva AC, Kummer AM. Anxiety, depression, resilience and quality of life in children and adolescents with pre-dialysis chronic kidney disease. Pediatr Nephrol 2015;30:2153–62.
4. Al-Uzri A, Matheson M, Gipson DS, Mendley SR, Hooper SR, Yadin O, et al. The impact of short stature on health-related quality of life in children with chronic kidney disease. J Pediatr 2013;163:736–41.
5. Gerson A, Hwang W, Fiorenza J, Barth K, Kaskel F, Weiss L, et al. Anemia and health-related quality of life in adolescents with chronic kidney disease. Am J Kidney Dis 2004;44:1017–23.
6. Chen J, Lin F, Zhai Y, Wang C, Wu B, Ma D, et al. Diagnostic and clinical utility of genetic testing in children with kidney failure. Pediatr Nephrol 2021;36:3653–62.
7. Vivante A, Hildebrandt F. Exploring the genetic basis of early-onset chronic kidney disease. Nat Rev Nephrol 2016;12:133–46.
8. Devuyst O, Knoers NV, Remuzzi G, Schaefer F, ; Board of the Working Group for Inherited Kidney Diseases of the European Renal Association and European Dialysis and Transplant Association. Rare inherited kidney diseases: challenges, opportunities, and perspectives. Lancet 2014;383:1844–59.
9. Groopman EE, Rasouly HM, Gharavi AG. Genomic medicine for kidney disease. Nat Rev Nephrol 2018;14:83–104.
10. Mann N, Braun DA, Amann K, Tan W, Shril S, Connaughton DM, et al. Whole-exome sequencing enables a precision medicine approach for kidney transplant recipients. J Am Soc Nephrol 2019;30:201–15.
11. Rabbani B, Mahdieh N, Hosomichi K, Nakaoka H, Inoue I. Next-generation sequencing: impact of exome sequencing in characterizing Mendelian disorders. J Hum Genet 2012;57:621–32.
12. Lee H, Deignan JL, Dorrani N, Strom SP, Kantarci S, Quintero-Rivera F, et al. Clinical exome sequencing for genetic identification of rare Mendelian disorders. JAMA 2014;312:1880–7.
13. Yang Y, Muzny DM, Reid JG, Bainbridge MN, Willis A, Ward PA, et al. Clinical whole-exome sequencing for the diagnosis of mendelian disorders. N Engl J Med 2013;369:1502–11.
14. Dixon-Salazar TJ, Silhavy JL, Udpa N, Schroth J, Bielas S, Schaffer AE, et al. Exome sequencing can improve diagnosis and alter patient management. Sci Transl Med 2012;4:138ra78.
15. Bamshad MJ, Ng SB, Bigham AW, Tabor HK, Emond MJ, Nickerson DA, et al. Exome sequencing as a tool for Mendelian disease gene discovery. Nat Rev Genet 2011;12:745–55.
16. Goldstein DB, Allen A, Keebler J, Margulies EH, Petrou S, Petrovski S, et al. Sequencing studies in human genetics: design and interpretation. Nat Rev Genet 2013;14:460–70.
17. Katsanis SH, Katsanis N. Molecular genetic testing and the future of clinical genomics. Nat Rev Genet 2013;14:415–26.
18. Bierzynska A, McCarthy HJ, Soderquest K, Sen ES, Colby E, Ding WY, et al. Genomic and clinical profiling of a national nephrotic syndrome cohort advocates a precision medicine approach to disease management. Kidney Int 2017;91:937–47.
19. Bekheirnia MR, Bekheirnia N, Bainbridge MN, Gu S, Coban Akdemir ZH, Gambin T, et al. Whole-exome sequencing in the molecular diagnosis of individuals with congenital anomalies of the kidney and urinary tract and identification of a new causative gene. Genet Med 2017;19:412–20.
20. Seo GH, Kim T, Choi IH, Park JY, Lee J, Kim S, et al. Diagnostic yield and clinical utility of whole exome sequencing using an automated variant prioritization system, EVIDENCE. Clin Genet 2020;98:562–70.
21. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015;17:405–24.
22. Boger CA, Chen MH, Tin A, Olden M, Kottgen A, de Boer IH, et al. CUBN is a gene locus for albuminuria. J Am Soc Nephrol 2011;22:555–70.
23. Manickam K, McClain MR, Demmer LA, Biswas S, Kearney HM, Malinowski J, et al. Exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability: an evidence-based clinical guideline of the American College of Medical Genetics and Genomics (ACMG). Genet Med 2021;23:2029–37.
24. Deignan JL, Chung WK, Kearney HM, Monaghan KG, Rehder CW, Chao EC, et al. Points to consider in the reevaluation and reanalysis of genomic test results: a statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med 2019;21:1267–70.
25. Hoekstra T, Hemmelder MH, van Ittersum FJ. RENINE annual report 2015 Utrecht: Nederlandse Federatie voor Nefrologie; 2017.
26. Lata S, Marasa M, Li Y, Fasel DA, Groopman E, Jobanputra V, et al. Whole-exome sequencing in adults with chronic kidney disease: a pilot study. Ann Intern Med 2018;168:100–9.
27. van der Ven AT, Connaughton DM, Ityel H, Mann N, Nakayama M, Chen J, et al. Whole-exome sequencing identifies causative mutations in families with congenital anomalies of the kidney and urinary tract. J Am Soc Nephrol 2018;29:2348–61.
28. Baum MA, Ho M, Stablein D, Alexander SR, ; North American Pediatric Renal Transplant Cooperative Study. Outcome of renal transplantation in adolescents with focal segmental glomerulosclerosis. Pediatr Transplant 2002;6:488–92.
29. Malone AF, Phelan PJ, Hall G, Cetincelik U, Homstad A, Alonso AS, et al. Rare hereditary COL4A3/COL4A4 variants may be mistaken for familial focal segmental glomerulosclerosis. Kidney Int 2014;86:1253–9.
30. Deltas C, Savva I, Voskarides K, Papazachariou L, Pierides A. Carriers of autosomal recessive Alport syndrome with thin basement membrane nephropathy presenting as focal segmental glomerulosclerosis in later life. Nephron 2015;130:271–80.
31. Gast C, Pengelly RJ, Lyon M, Bunyan DJ, Seaby EG, Graham N, et al. Collagen (COL4A) mutations are the most frequent mutations underlying adult focal segmental glomerulosclerosis. Nephrol Dial Transplant 2016;31:961–70.
Clinical category
No. of patients (%)
Male sex
Sequencing performed
No. of diagnostic variant present (%)
Singleton genetic diagnoses
FSGS 9 (24.3) 3 9 3 (33.3) 0
CAKUT including reflux nephropathy 8 (21.6) 4 8 2 (25.0) 1
Other glomerulopathy 7 (18.9) 2 7 3 (42.8) 1
Unknown etiology 6 (16.2) 4 6 3 (50.0) 2
Others 7 (18.9) 4 7 1 (14.3) 1
FSGS, focal segmental glomerulosclerosis; CAKUT, congenital anomalies of kidney and urinary tract.
Total (n=37)
Age at diagnosis of CKD (yr) 6.00 (3.00–10.25)
Sex, male:female 20:17
CKD stage
Stage 1 5 (13.5)
Stage 3 2 (5.4)
Stage 5 21 (56.8)
Kidney transplantation state 18
On dialysis (HD or PD) 4
Values are presented as median (interquartile range) or number (%).
CKD, chronic kidney disease; HD, hemodialysis; PD, peritoneal dialysis.
Patient no.
Age (yr)
Genetic diagnosis
Nucleotide change
Clinical implications of genetic information
1 14 F KT Infantile NS, Bx: FGSG LAMA5 c.6883C>T: p.Gln2295Ter
2 9 F KT Bx: membranoproliferative glomerulonephritis genital anomaly (-) WT1 c.1447+4C>T
3 18 M 1 Continuous microscopic HU, PU, Bx: GBM disease Alport syndrome 2q36.3 deletion including COL4A4 Family counselling
(2:227773537-227890526x1)
4 14 F 1 Gross hematuria, proteinuria, brother: MELAS Alport syndrome COL4A3 c.1216C>T p.Arg406Ter, Family counselling
c.40_63del p.Leu14_Leu21del
5 17 F KT ESKD, Bx: FSGS ACTN4 c.718A>G: p.Met240Val
6 12 M KT ESKD, Bx: membranous glomerulonephritis WT1 c.1259A>G: p.His420Arg
genital anomaly (-)
7 18 F KT ESKD, Bx: FSGS NUP107 c.2492A>C p.Asp831Ala
8 23 F 4 Azotemia, duplicated kidney, sensory neural hearing loss HDR syndrome CNV including GATA3 Family counselling
9 6 F PD Dandy-walker syndrome, developmental delay Joubert syndrome CEP290 c.6012-2T>A
10 12 F 2 PU, azotemia, Bx: GBM disease Alport syndrome COL4A4 c.3161G>T p.Gly1054Val Family counselling
11 5 F 4 Azotemia, PU, hydronephrosis, CAKUT ocular anomaly (-) PAX2 c.76dup p.Val26GlyfsTer28
12 1 M 1 PU CUBN c.4855+2C>G Discontinuation of immunosuppressive agents
CKD, chronic kidney disease; F, female; M, male; KT, kidney transplantation; NS, nephrotic syndrome; Bx, biopsy; FSGS, focal segmental glomerulosclerosis; HU, hematuria; PU, proteinuria; GBM, glomerular basement membrane; MELAS, mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode syndrome; ESKD, end-stage kidney disease; FSGS, focal segmental glomerulosclerosis; HDR syndrome, hypoparathyroidism, sensorineural deafness and renal disease syndrome; CNV, copy number variant; PD, peritoneal dialysis; CAKUT, congenital anomalies of the kidney and urinary tract.


text:
In the Blink of Bird's Eye, a Model for Quantum Navigation
Lisa Grossman
European robins may maintain quantum entanglement in their eyes a full 20 microseconds longer than the best laboratory systems, say physicists investigating how birds may use quantum effects to "see" Earth's magnetic field. Quantum entanglement is a state where electrons are spatially separated, but able to affect one another. It's been proposed that birds' eyes […]
European robins may maintain quantum entanglement in their eyes a full 20 microseconds longer than the best laboratory systems, say physicists investigating how birds may use quantum effects to "see" Earth's magnetic field.
Quantum entanglement is a state where electrons are spatially separated, but able to affect one another. It's been proposed that birds' eyes contain entanglement-based compasses.
Conclusive proof doesn't yet exist, but multiple lines of evidence suggest it. Findings like this one underscore just how sophisticated those compasses may be.
"How can a living system have evolved to protect a quantum state as well -- no, better -- than we can do in the lab with these exotic molecules?" asked quantum physicist Simon Benjamin of Oxford University and the National University of Singapore, a co-author of the new study. "That really is an amazing thing."
Many animals -- including not only birds, but some mammals, fish, reptiles, even crustaceans and insects -- navigate by sensing the direction of Earth's magnetic field. Physicist Klaus Schulten of the University of Illinois at Urbana-Champaign proposed in the late 1970s that bird navigation relied on some geomagnetically sensitive, as-yet-unknown biochemical reaction taking place in their eyes.
Research since then has revealed the existence of special optical cells containing a protein called cryptochrome. When a photon enters the eye, it hits cryptochrome, giving a boost of energy to electrons that exist in a state of quantum entanglement.
One of the electrons migrates a few nanometers away, where it feels a slightly different magnetic field than its partner. Depending on how the magnetic field alters the electron's spin, different chemical reactions are produced. In theory, the products of many such reactions across a bird's eye could create a picture of Earth's magnetic field as a varying pattern of light and dark.
>'N@C60 is quite a sexy, interesting, promising molecule.'
However, these quantum states are notoriously fragile. Even in laboratory systems, atoms are cooled to near–absolute-zero temperatures to maintain entanglement for more than a few thousandths of a second. Biological systems would seem too warm and too wet to hold quantum states for long, yet that's exactly what they appear to do.
Researchers led by University of California, Irvine physicist Thorsten Ritz (.pdf) showed in 2004 that, although robins had no trouble pointing their beaks toward Africa under the influence of Earth's magnetic field alone, adding a second, shifting field destroyed their inner compasses. That second field was so weak -- less than one-third of 1 percent of Earth's field -- that it could only have influenced a quantum-sensitive system.
"It shouldn't be the case that the birds would even know that this had happened," Benjamin said. "If someone changed the brightness of the scene that you're seeing by a-third of 1 percent, you would struggle to know that it even happened. It certainly wouldn't muck up your vision.
In a new paper in Physical Review Letters, Benjamin and colleagues built a mathematical model of Ritz's experiment, including the Earth's magnetic field, the slight secondary field, and the quantum systems that might make up the birds' magnetic sense.
They calculated that, in order to be sensitive to such weak fields, entangled states in the birds' eyes must last for at least 100 microseconds, or 0.0001 seconds.
To put this in perspective, Benjamin introduced an exotic molecule called N@C60, a geometric cage of carbon with a nitrogen atom inside. This molecule is one of the best-known laboratory systems for maintaining entanglement. "The cage acts to shield the atom, which is storing the information, from the rest of the world," Benjamin said. "It's considered to be quite a sexy, interesting, promising molecule."
But at room temperature, even N@C60 only holds entanglement for 80 microseconds, or four-fifths of what birds appear to be doing.
"I think this is a very nice paper that attacks the problem from an interesting angle," said Schulten, who was not involved in the work. "They use a hugely simplified model, but they make an interesting point. Entanglement could stay protected for tens of microseconds longer than we thought before."
"The bird, however it works, whatever it's got in there, it's somehow doing better than our specially designed, very beautiful molecule," Benjamin said. "That's just staggering."
Images: 1) The European robin. Courtesy Ernst Vikne/Flickr. 2) Schematic drawing of N@C60. Courtesy Simon Benjamin.
Reverse-Engineering the Quantum Compass of Birds
Bats Use Sun to Calibrate Geomagnetic Compass
Birds Use Light, Not Magnetic Field, to Migrate
Leafy Green Coherence: Quantum Physics Fuels Photosynthesis
Lisa is a Wired Science contributor based loosely in Seattle, Washington.
Topicsanimalsbirdsphysicsquantum
How to Measure Ripples in Spacetime
Using the giant Virgo interferometer in Tuscany, researchers are recording gravitational waves created by interstellar cataclysms as they wash through our planet.
Benjamin Skuse
Why This Universe? Maybe It's Not Special—Just Probable
Two physicists find that our universe has a higher entropy—and is therefore more likely—than alternative possible universes.
Charlie Wood
Astronomers May Have Just Spotted the Universe's First Galaxies
NASA's new JWST space telescope has revealed some cosmic surprises, including galaxies that might have assembled earlier than previously thought.
Ramin Skibba
Today's devices can be thrown off by the slightest environmental interference. Algorithmiq is developing ways to counteract this and harness quantum's power.
Amit Katwala
How Your Brain Distinguishes Memories From Perceptions
The neural representations of a perceived image and the memory of it are almost the same. New research shows how and why they are different.
Yasemin Saplakoglu
Why Do You Get Sick in the Winter? Blame Your Nose
A new study shows that as temperatures drop, nasal cells release fewer of the tiny protectors that bind and neutralize invading germs.
Why the Search for Life in Space Starts With Ancient Earth
Need to estimate, from trillions of miles away, how likely another world is to host life? There's a flowchart for that.
When Did the Anthropocene Actually Begin?
Scientists want to pinpoint the technology that marked when humanity became a "geological superpower." On the short list: the H-bomb and the modern chicken.
Damian Carrington


text:
Thursday, 1 Sep 2016
By Paul Edmondson
In March 2010, The Shakespeare Birthplace Trust started to lift the turf on the site of Shakespeare's family home. It was the start of 'Dig for Shakespeare', a seasonal excavation that was always about three things: to find out as much as possible about New Place when Shakespeare lived there; to engage volunteers to work with the archaeologists; and to make the dig part of the general visitors' experience to the site. Archaeologists (now based at the Centre for Archaeology, Staffordshire University), augmented by around a hundred and twenty volunteers, were in quest of Shakespeare's lost home.
There were three main iterations of New Place. The first was the original house built by Hugh Clopton in the 1480s, and which Shakespeare purchased in 1597. Towards the turn of the eighteenth century, the New Place that Shakespeare had owned (which was still mainly Clopton's fifteenth-century house) was demolished and an entirely new house was built on the site (by the descendants of Hugh Clopton). That 'new' New Place was itself demolished in 1759.
Ours has led to the fullest – albeit fragmentary – picture of what Shakespeare's New Place was like in Shakespeare's time, its size and its layout. Not least, we discovered evidence for the large, late-medieval hall that stood in the courtyard, farthest from the main street. This was a main focal point for how people lived there, and suggests that Shakespeare had a taste for the old-fashioned, for the architecture of a former age. His house was as romantic as many of his plays. But it has long been suggested that Shakespeare, in the words of Lewis Theobald in 1733, 'repair'd and modell'd it to his own mind', which our dig was able to confirm. Fragments of a brick feature within the Hall suggest that Shakespeare had added an external chimney stack to it. Evidence also suggests that Shakespeare added a brand new street-frontage to the property, which included, as George Vertue noted in 1737, a long gallery.
The more we uncovered, considering our finds in relation to documentary evidence and comparative architecture, the more important New Place became to our understanding of Shakespeare's social status and career. In fact, what we have learnt about Shakespeare's lost home is now become an undeniable part of Shakespearian biography. He wouldn't have bought a house as grand as New Place and never spent any time there. It is likely that New Place became his writer's retreat, removed from the competing demands of London (where he was only ever an intermittent lodger). He could, when necessary, and like other of his townsfolk, commute to and from the capital, a journey of three, possibly two days on horseback.
To understand more about New Place – its archaeology, its size, its reputation, and to imagine what that meant to Shakespeare and his family – is no less than to revise how we write Shakespearian biography. Since we started to lift the turf in 2010, New Place will never be the same place again.
Finding Shakespeare's New Place; an archaeological biography by Paul Edmondson, Kevin Colls and William Mitchell is now published.
There is a one-day conference on Shakespeare's New Place at the Shakespeare Centre, Stratford-upon-Avon, on Saturday 17 September. To register and find out more, please email [email protected] or buy a ticket online, here. Attendance includes a copy of the book.
New Place has been entirely re-presented by The Shakespeare Birthplace Trust as part of the quatercentenary celebrations. You can find out more at www.shakespeare.org.uk


text:
Introducing Little Willie Farmer!
inTheir Musicon January 9, 2018
Little Willie Farmer was born in 1956 in the small town of Duck Hill, MS. He grew up on a farm where his father raised cows, chickens, cotton and corn. On Sundays, he had the choice between picking cotton and going to church. He usually chose church. His uncles and father would entertain each other with blues and gospel songs when their work was done. Little Willie picked up the guitar as a child and began to teach himself how to play. His mother and father had differing attitudes about what music he should be playing. His mother preferring that Willie stick to gospel and his father secretly encouraging the boy to play the blues whenever mother was out of earshot.
Little Willie Farmer getting his passport application filed in Mississippi
As Little Willie was getting better and better, his father offered him a piece of advice, "don't brag on yourself, if you're playing it right, others will brag on you." It was as much a lesson in humility as it was an advisory to his son to make sure news of his playing was slower to get back to his mother, who may have put a stop to it.
Little Willie began working in auto repair as a teenager and has operated his own shop for the past 44 years. On nights and weekends he travelled and performed in gospel quartet groups and at roadhouse music halls from Chicago, to Memphis, Clarkesdale and Montgomery.
In 2017, the Austrian blues label, Wolf, released Little Willie's first album "I'm Coming Back Home." On it, he alternates between acoustic and electric guitar, playing a style that closely resembles that of Lightnin' Hopkins.
When Music Maker reached out to Little Willie, he told us he was ready to hit the road and focus on his music. Music Maker assisted in getting Willie a passport and have been busy trying to get him to US festivals. Willie Farmer will play the Bullpen on Friday, January 19th.


Unique Korean Haircut Style With Bangs For Medium Hair For Girls is free HD wallpaper. This wallpaper was upload at July 15, 2018 upload by darylfarahi in Hairstyle.
Unique Korean Haircut Style With Bangs For Medium Hair For Girls is high definition wallpaper and size this wallpaper is 778x1024. You can make Unique Korean Haircut Style With Bangs For Medium Hair For Girls For your Desktop Background, Tablet, Android or iPhone and another Smartphone device for free. To download and obtain the Unique Korean Haircut Style With Bangs For Medium Hair For Girls images by click the download button below to get multiple high-resversions.


text:
Lista siturilor arheologice din județul Alba - A conține toate siturile arheologice din județul Alba înscrise în Repertoriul Arheologic Național (RAN) și aflate în localități al căror nume începe cu litera A. RAN este administrat de Institutul Național al Patrimoniului și cuprinde date științifice, cartografice, topografice, imagini și planuri, precum și orice alte informații privitoare la zonele cu potențial arheologic, studiate sau nu, încă existente sau dispărute.

Puteți căuta un sit din localitățile care încep cu litera A folosind formularul de mai jos sau puteți naviga prin toate siturile din județ la Lista siturilor arheologice din județul Alba.

Note

Arheologice Județul Alba, Situri
Alba


text:
Posts tagged with "new music Fridays"
Quarterhead × Camylio – Is It Love
Revered DJ/production duo Quarterhead are back this year with yet another enthralling original production, "Is It Love". This time around, they've linked up with Camylio who provides a melodious vocal to the energetic endeavor.
The new track directly follows up Quarterhead and Max Giesinger's collaborative track "Nichts mehr zu sagen" from this February, in addition to Camylio's single "i tried" from earlier last month. Out now via Casablanca Records/Republic Records, "Is It Love" is available to listen to across all streaming platforms. LISTEN HERE.
The four-on-the-floor tune is replete with consistently pulsating bass, a propelling ambiance, and a high octane flair that's maintained with ease from start-to-finish. Throughout its entirety, it also features Camylio's textured vocal, which captivates the listener with each passing second. Rolling basslines and an infectious energy are paired alongside emotionally-charged lyricism, in turn creating a feelgood, club-ready anthem that also pulls at the heartstrings of the listener.
Placing a central focus on love and its intricacies, the track delves into the universal concept heavily, and serves as a prime accompaniment to Quarterhead's lively signature production sensibilities. A quintessential dance-pop crossover opus, it serves as a stellar new addition to the Universal Music Germany imprint and to both artist's flourishing back-catalogs.
"Writing a big anthemic club anthem with a happy sad feeling was on our agenda for a long time. When we jumped into the studio with Danish singer Daniel Schulz last fall, we knew it was time to give it a shot. The song is about the strongest feeling in the world: Love. And the way Camylio delivered his vocals was the perfect match to the melodies and lyrics." – Quarterhead
ABOUT QUARTERHEAD:
Quarterhead is a multiple gold and platinum awarded DJ/writer/producer duo consisting of multi-instrumentalists Josh Tapen and Janik Riegert from Germany. Their works include songs and productions with Cheat Codes, Ofenbach, Robin Schulz, ATB, HUGEL, Felix Jaehn, Ella Henderson, Lum!x, Alle Farben, KIDDO, Juan Magan, ILIRA, Benjamin Ingrosso, and many more.
After producing and singing on Lum!x's international hit "The Passenger" (which now sits at over 100 million streams on all platforms) in early 2020, the duo has been currently riding the wave of their own massive worldwide hit "Head Shoulders Knees & Toes." Since its release, it has accumulated over 500 million streams on all platforms, multiple platinum and gold awards in most European countries, a Spotify Global #50, a Shazam global top 30 ranking, and a #8 spot on the European radio charts. With over 52 weeks inside the German Top 50 radio charts HSKT now ranks it as one of the top radio songs of the early '20s.
The duo is also involved in Ofenbach's follow-up single "Hurricane" together with Ella Henderson, which now sits at over 100 million streams across all platforms plus multiple radio top 10s all across Europe. Their current lean towards a more credible house sound brings forth their songs "Love So Sweet", "Eyes On You" with DJ Superstar HUGEL, and "Juice," all of which were released via iconic club labels such as Defected Records or CR2.
ABOUT CAMYLIO:
Clad in a classic black shirt against a dark backdrop, Camylio leans into his microphone, presses down on the ivory of his keyboard, and sings with enough passion and power to stir the world to its feet. It's a scene meant for a stadium, but he's in his bedroom framed by a smartphone camera yet beamed out to an audience of millions on social media. Throughout 2021, he performed like this at a dizzying pace and quietly emerged as a phenomenon renowned for a Richter Scale-registering voice. For his 16th birthday, his parents allowed him to choose either "a car or a laptop." Thankfully, he chose the latter, spending countless hours poring over song credits and learning how to produce via YouTube and Twitch.
During November 2020, he launched his TikTok with one video daily. He filled an Amazon shopping cart with a $200 backdrop, ten black hoodies, ten black long-sleeve shirts, and five black short-sleeve shirts in order to maintain a consistent aesthetic. His cover of "Dusk Till Dawn" by Sia and ZAYN exploded with 7 million-plus views.
Eventually, he broke the internet as his take on SLANDER's "Love Is Gone" feat. Dylan Matthew generated north of 50 million views in under ten days. He caught the attention of Republic Records and signed to the label. After shaking the internet, the 20-year-old New York singer, songwriter, multi-instrumentalist, and producer properly introduces himself with his 2021 debut EP all the songs i used to love and latest single "i tried."
This entry was posted in Spirits and tagged 360, 360 Magazine, Camylio, camylio songs, camylio spotify, collaboration track, German artist, head shoulders knees and toes ofenbach, it it love, McKinley Franklin, music, new music, new music Fridays, ofenbach & quarterhead, ofenbach head houlders, ofenbach head shoulders knees & toes, ofenbach head shoulders knees and toes, Quarterhead, spotify, spotify and ig camylio, spotify camylio, Vaughn Lowery on 04/15/2022 by McKinley Franklin.
Winnetka Bowling League – pulp
Winnetka Bowling League debuted their hot fourth EP pulp via RCA Records on Friday February 4. The EP consists of new track fiimy (fuck it, i misss you) with Demi Lovato, as well as a few separate pre-released tracks. Listen and stream pulp HERE, and catch the full tracklist below.
Both Winnetka Bowling League and Demi Lovato came together when Demi got into touch with head singer Matthew Koma. He posted a short video of the track onto the popular platform of TikTok, where Demi was drawn to the song.
Matthew raves about the inspiration behind fiimy (fuck it, i misss you), saying ""fiimy" is about running into an ex for the first time since a break up and the rush of mixed feelings that ad target you. There's wondering if you even know that person anymore and there's reckoning with your own "did i fuck up a good thing". When Demi heard the lyrics, I think they reminded them of their own version of that experience…so it was really cool to hear them come with a verse framing how that story was told in their world. It takes dismissing a lot of pride to admit to yourself you miss someone."
Demi spoke on their collaboration on the track, stating, "Winnetka Bowling League has such a unique sound, and I am excited to be on this record with them. If these times taught us anything it's the power of human connection and missing someone, and I think this song speaks to that in a very honest and relevant way."
The new EP pulp was written and produced by Matthew, and comes after their accomplished 2020 EP Congratulations.
Matthew talks about pulp, asserting, "Writing songs feels nauseatingly self-important and talking about writing songs is worse than a writer's camp. But alas, I wrote most of the songs for the new EP in New York and felt panicked for 2 months that I was only capable of pure shit. I grew up in NY but I've spent the last 11 years in Los Angeles and sometimes the mentality here makes you forget about doing stuff you actually love. Being back in New York sort of sparked all these memories of being a kid recording terrible demos on ACID (the recording program, not the drug, unfortunately). And that headspace got me thinking about things and people I haven't thought about for a long time. Usually I'm arm wrestling myself to write something about my current circumstance that's relatable to more than my three friends who like quarantine as much as I do. But there was this shift in NY and I started writing about people and feelings I hadn't visited in a while. Time grants you kinder eyes and with songs like "barcelona" and "fiimy" I got to re-explore those relationships from a helicopter's view and see it a little differently. "pulp" was about this really odd memory that came back to me one day when I walked by Port Authority and smelled hot pretzels. It made sense to call the EP "pulp" because every song was born from some specific snapshot detail that wasn't at all the main juice (lol). I usually like my own music for 2-3 months after making it then I'm paralyzingly humiliated. I wrote this on 4/22/21 – use that information accordingly."
This spring we see Winnetka Bowling League heading out on a series of shows while backing CHVRCHES on their practically sold-out UK Screen Violence Tour. To access more information on the tour and to get your own tickets in Newcastle and Birmingham, visit HERE. See tour dates below.
About Matthew Koma and Winnetka Bowling League
Head artist in charge, Matthew Koma was raised in New Jersey and became a critically acclaimed performer, songwriter and producer who has worked for the likes of Britney Spears, Demi Lovato, Keith Urban, Shania Twain and Kelly Clarkson. The beginnings of Winnetka Bowling League came in 2018 when Matthew, his brother Kris Mazzarisi and Sam Beresford joined him to release their self-titled EP. They soon released two more Eps, Cloudy with a Chance of Sun in 2019 and Congratulations in 2020, all showcasing impeccable songwriting paired with memorable lyrics. V Magazine proclaimed, "Grammy-winning singer-songwriter Matthew Koma…[as] raw and honest, possessing a dry sense of humor that is reflected in both his songs and his mannerisms…[Winnetka Bowling League is] the perfect pairing of deep lyrical content and alternative rock melodies."
pulp EP track listing:
1. "pulp"
2. "fiimy (fuck it, i miss you)" with Demi Lovato
3. "barcelona" with Sasha Alex Sloan
4. "dandelion"
5. "emotionalporn"
CHVRCHES x Winnetka Bowling League tour dates
March 14th – Edinburgh UK – O2 Academy (SOLD OUT)
March 15th – Newcastle, UK – O2 City Hall
March 16th – London, UK – O2 Academy Brixton (SOLD OUT)
March 18th – Birmingham, UK – O2 Academy
March 19th – Manchester, UK – O2 Apollo (SOLD OUT)
This entry was posted in Uncategorized and tagged 360, 360 Magazine, artist, band, Britney Spears, Bruce Springsteen, CHVRCHES, cloudy with a chance of sun ep, collab, CONGRATULATIONS EP, critically acclaimed, Demi Lovato, ep, Feature, fiimy (fuck it, I miss you), Inspiration, Keith Urban, Kelly Clarkson, Kris Mazzarisi, MATTHEW KOMA, McKinley Franklin, mixed emotions, music collab, new ep, new music Fridays, New Song, Pentatonix, performer, producer, pulp, pulp ep, RAC, RCA records, relationships, Ryan tedder, Sam Beresford, Shania Twain, soldout tour, song, songwriter, songwriting, story, storytelling, the knocks, Tiesto, tiktok, tour, tracklist, tracks, UK Tour, v magazine, Vaughn Lowery, Winnetka Bowling League, writing songs on 02/05/2022 by 360 intern.


text:
Q: Selecting the best statistical analysis I'm going to begin an experiment about drying leaves. I want to learn about how some special kind of leaves are going to dry themselves in 2 different situation. A group of them will stay in a high density, and the another group I will spread out in a bigger area (for example, 1 m2 for the first, and 3 m2 for the second). Of course, I will repeat this experiment several times. In the end, I will get:

*

*Individual weight of the leaves (selecting samples) in the beginning

*Individual weight along 4 days

*Individual weight in the end

*Nutritional composition in the start and in the end

I am remembering my knowledge in stats and R, but I am still lost. My question is, which is the best comparison method to analyse this data? I want to know:

*

*How the humidity content change along the days

*To dry this kind of leaves, which drying area is better?

*Is it statistical significance between both method about losing water and nutrient content?

Kind regards!
Alex.

A: It is possible you are trying to cram too much into one design.
Here is a somewhat simplified version:
Consider three effects:

*

*Density (fixed effect $\delta$ at two levels High and Low)

*Leaves (random effect $L$ at $n$ levels)

*Times [fixed effect $\tau$, three levels (0, 4, Last), nested within Leaves].
These specifications to the model
$$Y_{ijk} = \mu + \delta_i + L_j + \tau(L)_{k(j)} + \{\delta*L\}_{ij}
+ e_{ijk},$$
where $e_{ijk} \stackrel{iid}{\sim} \mathsf{Norm}(0, \sigma).$
Lower-case Greek letters represent fixed effects, upper-case Latin
letters respresent random effects, parentheses indicate nesting;
$Y_{ijk}$ are measurements of weight and $e_{ijk}$ are normally
distributed random effects. [Parentheses are read as 'of ' not 'within'.]
The only interaction effect supported
is between Density and Leaf, a three-way interaction for density,
Leaf and time would be confounded with the error term, and there
cannot be an interaction between an effect $\tau$ and an effect $L$
within which it is nested.
[Many software packages have proprietary
notations for indicating fixed and nested effects; for example
Minitab declares random effects separately and indicates nesting
within the model by parentheses.]
You might do separate ANOVAs for humidity and nutritional content.
Alternatively, do a multivariate ANOVA [MANOVA] with weight, humidity, and
nutritional content as data dimensions.
This type of design is sometimes called 'partially hierarchical'
and sometimes called 'repeated measures'. But the terminology
'repeated measures' has been used in so many different ways in
different fields of study as to have become almost useless.
Whatever model you use, you must account for the fact that the
same leaves are measured at three times, but that the leaves
at High density are not the same as those at Low density.


Have an existing Angular 1 application and are wondering about upgrading to Angular 2? Well, read on and learn about our plans to support incremental upgrades.
We've focused across many scenarios to make your apps snappy. 3x to 5x faster on initial render and re-render scenarios.
Server-side rendering. Enables super-fast initial render and web-crawler support.
Web Workers. Move your app and most of Angular to a Web Worker thread to keep the UI smooth and responsive at all times.
Native mobile UI. We're enthusiastic about supporting the Web Platform in mobile apps. At the same time, some teams want to deliver fully native UIs on their iOS and Android mobile apps.
Compile as build step. Angular apps parse and compile their HTML templates. We're working to speed up initial rendering by moving the compile step into your build process.
Angular 2 offers dramatic advantages over Angular 1 in performance, simplicity, and flexibility. We're making it easy for you to take advantage of these benefits in your existing Angular 1 applications by letting you seamlessly mix in components and services from Angular 2 into a single app. By doing so, you'll be able to upgrade an application one service or component at a time over many small commits.
For example, you may have an app that looks something like the diagram below. To get your feet wet with Angular 2, you decide to upgrade the left nav to an Angular 2 component. Once you're more confident, you decide to take advantage of Angular 2's rendering speed for the scrolling area in your main content area.
To make all this possible, we're building a library named ng-upgrade. You'll include ng-upgrade and Angular 2 in your existing Angular 1 app, and you'll be able to mix and match at will.
You can find full details and pseudocode in the original upgrade design doc or read on for an overview of the details on how this works. In future posts, we'll walk through specific examples of upgrading Angular 1 code to Angular 2.
First, we need to solve for communication between parts of your application. In Angular, the most common pattern for calling another class or function is through dependency injection. Angular 1 has a single root injector, while Angular 2 has a hierarchical injector. Upgrading services one at a time implies that the two injectors need to be able to provide instances from each other.
The ng-upgrade library will automatically make all of the Angular 1 injectables available in Angular 2. This means that your Angular 1 application services can now be injected anywhere in Angular 2 components or services.
Exposing an Angular 2 service into an Angular 1 injector will also be supported, but will require that you to provide a simple mapping configuration.
The result is that services can be easily moved one at a time from Angular 1 to Angular 2 over independent commits and communicate in a mixed-environment.
In both versions of Angular, we define a component as a directive which has its own template. For incremental migration, you'll need to be able to migrate these components one at a time. This means that ng-upgrade needs to enable components from each framework to nest within each other.
To solve this, ng-upgrade will allow you to wrap Angular 1 components in a facade so that they can be used in an Angular 2 component. Conversely, you can wrap Angular 2 components to be used in Angular 1. This will fully work with transclusion in Angular 1 and its analog of content-projection in Angular 2.
In this nested-component world, each template is fully owned by either Angular 1 or Angular 2 and will fully follow its syntax and semantics. This is not an emulation mode which mostly looks like the other, but an actual execution in each framework, dependending on the type of component. This means that components which are upgraded to Angular 2 will get all of the benefits of Angular 2, and not just better syntax.
This also means that an Angular 1 component will always use Angular 1 Dependency Injection, even when used in an Angular 2 template, and an Angular 2 component will always use Angular 2 Dependency Injection, even when used in an Angular 1 template.
Mixing Angular 1 and Angular 2 components implies that Angular 1 scopes and Angular 2 components are interleaved. For this reason, ng-upgrade will make sure that the change detection (Scope digest in Angular 1 and Change Detectors in Angular 2) are interleaved in the same way to maintain a predictable evaluation order of expressions.
ng-upgrade takes this into account and bridges the scope digest from Angular 1 and change detection in Angular 2 in a way that creates a single cohesive digest cycle spanning both frameworks.
Here is an example of what an Angular 1 project upgrade to Angular 2 may look like.
c. (optionally) re-export the service into Angular 1 using ng-upgrade if it's still used by other parts of your Angular 1 code.
Note that each individual change can be checked in separately and the application continues working letting you continue to release updates as you wish.
I heard Angular 2 doesn't support 2-way bindings. How will I replace them?
Actually, Angular 2 supports two way data binding and ng-model, though with slightly different syntax.
When we set out to build Angular 2 we wanted to fix issues with the Angular digest cycle. To solve this we chose to create a unidirectional data-flow for change detection. At first it was not clear to us how the two way forms data-binding of ng-model in Angular 1 fits in, but we always knew that we had to make forms in Angular 2 as simple as forms in Angular 1.
After a few iterations we managed to fix what was broken with multiple digests and still retain the power and simplicity of ng-model in Angular 1.
Two way data-binding has a new syntax: [(property-name)]="expression" to make it explicit that the expression is bound in both directions. Because for most scenarios this is just a small syntactic change we expect easy migration.
What languages can I use with Angular 2?
ES6 provides much improved syntax and standards for common libraries like promises and modules. TypeScript gives you dramatically better code navigation, automated refactoring in IDEs, documentation, finding errors, and more.
Both ES6 and TypeScript are easy to adopt as they are supersets of today's ES5. This means that all your existing code is valid and you can add their features a little at a time.
What should I do with $watch in our codebase?
In order to gain speed and predictability, in Angular 2 you specify watch expressions declaratively in the HTML template or in annotations on your component directives. One additional benefit from this is that Angular 2 applications can be safely minified/obfuscated for smaller payload.
What can I do today to prepare myself for the migration?
Follow the best practices and build your application using components and services in Angular 1 as described in the AngularJS Style Guide.
Wasn't the original upgrade plan to use the new Component Router?
The upgrade plan that we announced at ng-conf 2015 was based on upgrading a whole view at a time and having the Component Router handle communication between the two versions of Angular.
The feedback we received was that while yes, this was incremental, it wasn't incremental enough. We went back and redesigned for the plan as described above.
Are there more details you can share?
Yes! In the Angular 1 to Angular 2 Upgrade Strategy design doc.
Mapping your Angular 1 knowledge to Angular 2.
A set of FAQs on details around Angular 2.
Detailed migration guide with working code samples.