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Bruges Revisited
The Rt Hon. Baroness Thatcher LG, OM, FRS
Foreword by Martin Holmes
It is impossible to overstate the importance of Margaret Thatcher's Bruges Speech of September 20th 1988. Its effect was dramatic on the debate over Britain's future relations with the fast accelerating process of European integration.
The Prime Minister's speech was one of vision, clarity and foreboding. She outlined a positive vision of a wider, decentralised and democratic Europe. She attacked the Europe of Delors and in the process reinvented Euroscepticism as an intellectually powerful and popular movement across the political spectrum.
With chilling accuracy she predicted the stark choice facing Britain with which we have wrestled since. Should Britain be part of a centralised, unaccountable federal Europe or should we use our influence to help create a Europe of independent, freely trading, cooperating nation states?
Margaret Thatcher opted for the latter choice and her vision was supported by the British people. They have never wanted to become part of a European Superstate and did not vote "Yes" to the Common Market in 1975 in order to join one.
Despite the claims of its critics the Bruges speech was a positive vision drawing strength from Europe's political and historical diversity. In her vision of a Europe stretching across the continent, Margaret Thatcher pointed to the countries of Eastern Europe which, as communism crumbled, were looking west for an example of liberty, democracy, private enterprise and free trade. How could Western Europe provide them with any model or inspiration when it was so rapidly sliding towards very much the kind of undemocratic, bureaucratic superstate that they were looking to escape from?
In fact the collapse of communism in Eastern Europe had occurred despite not because of EC integration. Its inspiration derived from the winning combination of free market economics and representative liberal democracy which Margaret Thatcher and Ronald Reagan personified. It was the AngloSaxon model which proved to be the inspiration not the "Social model" of EC consensus politics. Moreover, the myth that Britain's antifederalists were backwardlooking, nationalistic, even xenophobic "little Englanders" was dispelled by the speech. It attacked the EC from an internationalist perspective, stressed that the EC should not be protectionist and emphasised the wider responsibility to the Third World and to completing the Uruguay Round of GATT.
Of course Margaret Thatcher combatively attacked the Europe envisaged by Jacques Delors, the President of the European Commission. In a speech to the European Parliament before the Bruges speech Delors had predicted that 80% of decisions would be taken at European level in ten years time. His was an inward-looking Europe of state-sponsored corporatism where decisions were taken at supranational level and sovereignty transferred to Brussels. Unelected Commissioners, Delors hoped, would enforce unitary policies across Western Europe and in the process create a uniform European superpower to rival the United States. Lip service was paid to democracy through the machinations of the European Parliament which, in reality, was a tame tabby cat without teeth or claws.
Margaret Thatcher's Europe was a Europe which included the countries of the East, which left power in the hands of sovereign national parliaments and which retained its strength through its diversity. She looked forward and outwards to the new internationalist world while also showing respect for Europe's history and traditions. Her vision was internationalist; the federalist vision was supranationalist.
The speech had a major effect on informed opinion and helped fire those who wanted to forge a different kind of Europe. Academics, politicians, economists, journalists and other opinion formers were convinced by its logic and consequently felt free to express their own disquiet with the bureaucratic juggernaut that the European Community had become.
In February 1989 the Bruges Group was set up to campaign vigorously for the goals outlined in the Bruges speech thus becoming the first Eurosceptical organisation of the modern era. This reinvention of Euroscepticism enabled the Bruges Group to attract considerable interest and publicity in the following decade.
In a speech to the Bruges Group, Enoch Powell defined the men of Bruges as "the people who had hoped, and hope still to see their country again an independent selfgoverning nation." He further declared that "nothing will ever be the same since 20 September 1988. It remains a fact, a historic fact, made more historic by having come from one of the most astute politicians this country has known in the years since the war, somebody apt at intuitively appraising the mood of the people of this country."
Ten years on "Europe" is the most contentious domestic political issue. It now transcends party politics so that cross party coalitions have emerged. Both the major parties have been split over the issue. The initial cautious reaction to the speech has been replaced by a positive yearning for its vision of a future Europe. The archfederalist Sir Roy Denman revealed the devastating effect the speech brought upon the British Establishment when he admitted on "The Poisoned Chalice" (a BBC documentary on the history of Britain's relationship with Europe) that the speech had made Euroscepticism respectable and had unleashed a torrent of opposition against the federal process.
Such has been that torrent that Conrad Black (the proprietor of the Daily Telegraph) recently stated in a speech to the Centre for Policy Studies, "Since the European debate revived in earnest in the late 1980s, I have noticed a persistent trend. Intellectually, Eurosceptics have won the argument easily to the point where even the present Government, with its apparent Europrediliction and massive majority, feels obliged to move with the utmost caution."
The Bruges Speech and the activities of the Bruges Group have destroyed the notion of the inevitability of federalist ideas. Our present position is one of intellectual strength even though Britain's democratic and constitutional future is still at stake. This is the challenge which the contemporary men of Bruges will not shirk. Margaret Thatcher's seminal Bruges speech remains our inspiration.
Britain & Europe
The text of the speech delivered in Bruges by The Rt. Hon. Mrs Margaret Thatcher, FRS, on 20th September 1988
First, may I thank you for giving me the opportunity to return to Bruges - and in very different circumstances from my last visit shortly after the Zeebrugge ferry disaster, when Belgian courage and the devotion of your doctors and nurses saved so many British lives.
Second, may I say what a pleasure it is to speak at the College of Europe under the distinguished leadership of its Rector, Professor Lukaszewski. The College plays a vital and increasingly important part in the life of the European Community.
Third, may I also thank you for inviting me to deliver my address in this magnificent hall. What better place to speak of Europe's future than in a building which so gloriously recalls the greatness that Europe had already achieved over 600 years ago?
Your city of Bruges has many other historical associations for us in Britain. Geoffrey Chaucer was a frequent visitor here. And the first book to be printed in the English language was produced here in Bruges by William Caxton.
Mr Chairman, you have invited me to speak on the subject of Britain and Europe. Perhaps I should congratulate you on your courage. If you believe some of the things said and written about my views on Europe, it must seem rather like inviting Genghis Khan to speak on the virtues of peaceful coexistence!
I want to start by disposing of some myths about my country, Britain, and its relationship with Europe. And to do that I must say something about the identity of Europe itself.
Europe is not the creation of the Treaty of Rome. Nor is the European idea the property of any group or institution. We British are as much heirs to the legacy of European culture as any other nation. Our links to the rest of Europe, the continent of Europe, have been the dominant factor in our history. For three hundred years we were part of the Roman Empire and our maps still trace the straight lines of the roads the Romans built. Our ancestors - Celts, Saxons and Danes - came from the continent.
Our nation was - in that favourite Community word "restructured" under Norman and Angevin rule in the eleventh and twelfth centuries.
This year we celebrate the three hundredth anniversary of the Glorious Revolution in which the British crown passed to Prince William of Orange and Queen Mary. Visit the great Churches and Cathedrals of Britain, read our literature and listen to our language: all bear witness to the cultural riches which we have drawn from Europe - and other Europeans from us.
We in Britain are rightly proud of the way in which, since Magna Carta in 1215, we have pioneered and developed representative institutions to stand as bastions of freedom. And proud too of the way in which for centuries Britain was a home for people from the rest of Europe who sought sanctuary from tyranny.
But we know that without the European legacy of political ideas we could not have achieved as much as we did. From classical and mediaeval thought we have borrowed that concept of the rule of law which marks out a civilised society from barbarism. And on that idea of Christendom - for long synonymous with Europe - with its recognition of the unique and spiritual nature of the individual, we still base our belief in personal liberty and other human rights.
Too often the history of Europe is described as a series of interminable wars and quarrels. Yet from our perspective today surely what strikes us most is our common experience. For instance, the story of how Europeans explored and colonised and - yes, without apology -civilised much of the world is an extraordinary tale of talent, skill and courage.
We British have in a special way contributed to Europe. Over the centuries we have fought to prevent Europe from falling under the dominance of a single power. We have fought and we have died for her freedom. Only miles from here in Belgium lie the bodies of 120,000 British soldiers who died in the First World War. Had it not been for that willingness to fight and to die, Europe would have been united long before now-but not in liberty, not in justice. It was British support to resistance movements throughout the last War that helped to keep alive the flame of liberty in so many countries until the day of liberation.
Tomorrow, King Baudouin will attend a service in Brussels to commemorate the many brave Belgians who gave their lives in service with the Royal Air Force - a sacrifice which we shall never forget.
It was from our island fortress that the liberation of Europe itself was mounted. And still today we stand together. Nearly 70,000 British servicemen are stationed on the mainland of Europe.All these things alone are proof of our commitment to Europe's future.
The European Community is one manifestation of that European identity. But it is not the only one. We must never forget that East of the Iron Curtain peoples who once enjoyed a full share of European culture, freedom and identity have been cut off from their roots. We shall always look on Warsaw, Prague and Budapest as great European cities.
Nor should we forget that European values have helped to make the United States of America into the valiant defender of freedom which she has become.
Europe's Future
This is no arid chronicle of obscure facts from the dustfilled libraries of history. It is the record of nearly two thousand years of British involvement in Europe, cooperation with Europe and contribution to Europe, a contribution which today is as valid and as strong as ever. Yes, we have looked also to wider horizons - as have others - and thank goodness for that, because Europe never would have prospered and never will prosper as a narrowminded, inwardlooking club.
The European Community belongs to all its members. It must reflect the traditions and aspirations of all its members.
And let me be quite clear. Britain does not dream of some cosy, isolated existence on the fringes of the European Community. Our destiny is in Europe, as part of the Community. That is not to say that our future lies only in Europe. But nor does that of France or Spain or indeed any other member.
The Community is not an end in itself. Nor is it an institutional device to be constantly modified according to the dictates of some abstract intellectual concept. Nor must it be ossified by endless regulation.
The European Community is the practical means by which Europe can ensure the future prosperity and security of its people in a world in which there are many other powerful nations and groups of nations.
We Europeans cannot afford to waste our energies on internal disputes or arcane institutional debates. They are no substitutes for effective action.
Europe has to be ready both to contribute in full measure to its own security and to compete commercially and industrially, in a world in which success goes to the countries which encourage individual initiative and enterprise, rather than to those which attempt to diminish them.
This evening I want to set out some guiding principles for the future which I believe will ensure that Europe does succeed, not just in economic and defence terms but also in the quality of life and the influence of its peoples.
Willing Co-operation Between Sovereign States
My first guiding principle is this: willing and active cooperation between independent sovereign states is the best way to build a successful European Community.
To try to suppress nationhood and concentrate power at the centre of a European conglomerate would be highly damaging and would jeopardise the objectives we seek to achieve.
Europe will be stronger precisely because it has France as France, Spain as Spain, Britain as Britain, each with its own customs, traditions and identity. It would be folly to try to fit them into some sort of identikit European personality.
Some of the founding fathers of the Community thought that the United States of America might be its model.
But the whole history of America is quite different from Europe. People went there to get away from the intolerance and constraints of life in Europe. They sought liberty and opportunity; and their strong sense of purpose has over two centuries, helped create a new unity and pride in being American - just as our pride lies in being British or Belgian or Dutch or German.
I am the first to say that on many great issues the countries of Europe should try to speak with a single voice. I want to see us work more closely on the things we can do better together than alone. Europe is stronger when we do so, whether it be in trade, in defence, or in our relations with the rest of the world.
But working more closely together does not require power to be centralised in Brussels or decisions to be taken by an appointed bureaucracy.
Indeed, it is ironic that just when those countries such as the Soviet Union, which have tried to run everything from the centre, are learning that success depends on dispersing power and decisions away from the centre, some in the Community seem to want to move in the opposite direction.
We have not successfully rolled back the frontiers of the state in Britain, only to see them reimposed at a European level, with a European superstate exercising a new dominance from Brussels.
Certainly we want to see Europe more united and with a greater sense of common purpose. But it must be in a way which preserves the different traditions, Parliamentary powers and sense of national pride in one's own country; for these have been the source of Europe's vitality through the centuries.
Encouraging Change
My second guiding principle is this: Community policies must tackle present problems in a practical way, however difficult that may be. If we cannot reform those Community policies which are patently wrong or ineffective and which are rightly causing public disquiet, then we shall not get the public's support for the Community's future development.
That is why the achievements of the European Council in Brussels last February are so important.
It wasn't right that half the total Community Budget was being spent on storing and disposing of surplus food. Now those stocks are being sharply reduced.
It was absolutely right to decide that agriculture's share of the budget should be cut in order to free resources for other policies, such as helping the less well off regions and training for jobs.
It was right too to introduce tighter budgetary discipline to enforce these decisions and to bring total EC spending under better control.
Those who complained that the Community was spending so much time on financial detail missed the point. You cannot build on unsound foundations, financial or otherwise; and it was the fundamental reforms agreed last winter which paved the way for the remarkable progress which we have since made on the Single Market.
But we cannot rest on what we have achieved to date. For example, the task of reforming the Common Agricultural Policy is far from complete. Certainly, Europe needs a stable and efficient farming industry.
But the CAP has become unwieldy, inefficient and grossly expensive. Production of unwanted surpluses safeguards neither the income nor the future of farmers themselves.
We must continue to pursue policies which relate supply more closely to market requirements, and which will reduce overproduction and limit costs.
Of course, we must protect the villages and rural areas which are such an important part of our national life-but not by the instrument of agricultural prices.
Tackling these problems requires political courage. The Community will only damage itself in the eyes of its own people and the outside world, if that courage is lacking.
Europe Open to Enterprise
My third guiding principle is the need for Community policies which encourage enterprise. If Europe is to flourish and create the jobs of the future, enterprise is the key.
The basic framework is there: the Treaty of Rome itself was intended as a Charter for Economic Liberty. But that is not how it has always been read still less applied.
The lesson of the economic history of Europe in the 1970s and 1980s is that central planning and detailed control don't work, and that personal endeavour and initiative do. That a State-controlled economy is a recipe for low growth; and that free enterprise within a framework of law brings better results.
The aim of a Europe open to enterprise is the moving force behind the creation of the Single European Market by 1992. By getting rid of barriers, by making it possible for companies to operate on a Europewide scale, we can best compete with the United States, Japan and the other new economic powers emerging in Asia and elsewhere.
And that means action to free markets, action to widen choice, action to reduce government intervention.
Our aim should not be more and more detailed regulation from the centre: it should be to deregulate and to remove the constraints on trade.
Britain has been in the lead in opening its markets to others.
The City of London has long welcomed financial institutions from all over the world, which is why it is the biggest and most successful financial centre in Europe.
We have opened our market for telecommunications equipment, introduced competition into the market for services and even into the network itself - steps which others in Europe are only now beginning to face.
In air transport, we have taken the lead in liberalisation and seen the benefits in cheaper fares and wider choice.
Our coastal shipping trade is open to the merchant navies of Europe. I wish I could say the same of many other Community members.
Regarding monetary matters, let me say this. The key issue is not whether there should be a European Central Bank. The immediate and practical requirements are:
to implement the Community's commitment to free movement of capital - in Britain we have it; and to the abolition throughout the Community of the exchange controls - in Britain we abolished them in 1979;
to establish a genuinely free market in financial services, in banking, insurance, investment;
to make greater use of the ecu. Britain is this autumn issuing ecudenominated Treasury bills, and hopes to see other Community governments increasingly do the same.
These are the real requirements because they are what Community business and industry need, if they are to compete effectively in the wider world. And they are what the European consumer wants, for they will widen his choice and lower his costs.
It is to such basic practical steps that the Community's attention should be devoted.
When those have been achieved, and sustained over a period of time, we shall be in a better position to judge the next moves.
It is the same with the frontiers between our countries. Of course we must make it easier for goods to pass through frontiers. Of course we must make it easier for our people to travel throughout the Community. But it is a matter of plain commonsense that we cannot totally abolish frontier controls if we are also to protect our citizens from crime and stop the movement of drugs, of terrorists, and of illegal immigrants.
That was underlined graphically only three weeks ago, when one brave German customs officer, doing his duty on the frontier between Holland and Germany struck a major blow against the terrorists of the IRA.
And before I leave the subject of the Single Market, may I say that we certainly do not need new regulations which raise the cost of employment and make Europe's labour market less flexible and less competitive with overseas suppliers.
If we are to have a European Company Statute, it should contain the minimum regulations. And certainly we in Britain would fight attempts to introduce collectivism and corporatism at the European level - although what people wish to do in their own countries is a matter for them.
Europe Open to the World
My fourth guiding principle is that Europe should not be protectionist. The expansion of the world economy requires us to continue the process of removing barriers to trade and to do so in the multilateral negotiations in the GATT.
It would be a betrayal if, while breaking down constraints on trade within Europe, the Community were to erect greater external protection. We must ensure that our approach to world trade is consistent with the liberalisation we preach at home.
We have a responsibility to give a lead on this, a responsibility which is particularly directed towards the less developed countries. They need not only aid; more than anything they need improved trading opportunities if they are to gain the dignity of growing economic strength and independence.
Europe and Defence
My last guiding principle concerns the most fundamental issue, the European countries' role in defence. Europe must continue to maintain a sure defence through NATO. There can be no question of relaxing our efforts even though it means taking difficult decisions and meeting heavy costs.
It is to NATO that we owe the peace that has been maintained over 40 years. The fact is things are going our way: the democratic model of a free enterprise society has proved itself superior; freedom is on the offensive, a peaceful offensive, the world over for the first time in my lifetime. We must strive to maintain the United States' commitment to Europe's defence. That means recognising the burden on their resources of the world role they undertake, and their point that their Allies should play a full part in the defence of freedom, particularly as Europe grows wealthier. Increasingly they will look to Europe to play a part in outofarea defence, as we have recently done in the Gulf.
NATO and the WEU have long recognised where the problems with Europe's defences lie, and have pointed out the solutions. The time has come when we must give substance to our declarations about a strong defence effort with better value for money.
It is not an institutional problem. It is not a problem of drafting. It is something at once simpler and more profound: it is a question of political will and political courage, of convincing people in all our countries that we cannot rely for ever on others for our defence, but that each member of the Alliance must shoulder a fair share of the burden.
We must keep up public support for nuclear deterrence, remembering that obsolete weapons do not deter; hence the need for modernisation.
We must meet the requirements for effective conventional defence in Europe against Soviet forces which are constantly being modernised.
We should develop the WEU, not as an alternative to NATO. but as a means of strengthening Europe's contribution to the common defence of the West.
Above all, at a time of change and uncertainty in the Soviet Union and Eastern Europe, we must preserve Europe's unity and resolve, so that whatever may happen our defence is sure. At the same time, we must negotiate on arms control and keep the door wide open to cooperation on all the other issues covered by the Helsinki Accords.
But let us never forget that our way of life, our vision, and all that we hope to achieve is secured not by the rightness of our cause but by the strength of our defence. On this we must never falter, never fail.
The British Approach
I believe it is not enough just to talk in general terms about a European vision or ideal. If we believe in it, we must chart the way ahead and identify the next steps. That is what I tried to do this evening.
This approach does not require new documents: they are all there, the North Atlantic Treaty, the Revised Brussels Treaty, and the Treaty of Rome, texts written by farsighted men, a remarkable Belgian - Paul Henri Spaak - among them.
However far we may want to go, the truth is that we can only get there one step at a time.
What we need now is to take decisions on the next steps forward rather than let ourselves be distracted by Utopian goals.
Utopia never comes, because we know we should not like it if it did.
Let Europe be a family of nations, understanding each other better appreciating each other more, doing more together but relishing our national identity no less than our common European endeavour.
Let us have a Europe which plays its full part in the wider world, which looks outward not inward, and which preserves that Atlantic Community - that Europe on both sides of the Atlantic - which is our noblest inheritance and our greatest strength.
May I thank you for the privilege of delivering this lecture in this great hall to this great College.


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What Is Image Segmentation?
3 things you need to know
Image segmentation is a commonly used technique in digital image processing and analysis to partition an image into multiple parts or regions, often based on the characteristics of the pixels in the image. Image segmentation could involve separating foreground from background, or clustering regions of pixels based on similarities in color or shape. For example, a common application of image segmentation in medical imaging is to detect and label pixels in an image or voxels of a 3D volume that represent a tumor in a patient's brain or other organs.
Several algorithms and techniques for image segmentation have been developed over the years using domain-specific knowledge to effectively solve segmentation problems in that specific application area. These applications include medical imaging, automated driving, video surveillance, and machine vision.
Medical Imaging
During medical diagnosis for cancer, pathologists stain body tissue with hematoxylin and eosin (H&E) to distinguish between tissue types. They then use an image segmentation technique called clustering to identify those tissue types in their images. Clustering is a method to separate groups of objects in a scene. The K-means clustering algorithm finds separations such that objects within each cluster are as close to each other as possible, and as far from other objects in other clusters as possible.
Autonomous Driving
When designing perception for autonomous vehicles, such as self-driving cars, semantic segmentation is popularly used to help the system identify and locate vehicles and other objects on the road.
Image segmentation involves converting an image into a collection of regions of pixels that are represented by a mask or a labeled image. By dividing an image into segments, you can process only the important segments of the image instead of processing the entire image.
A common technique is to look for abrupt discontinuities in pixel values, which typically indicate edges that define a region.
Another common approach is to detect similarities in the regions of an image. Some techniques that follow this approach are region growing, clustering, and thresholding.
A variety of other approaches to perform image segmentation have been developed over the years using domain-specific knowledge to effectively solve segmentation problems in specific application areas.
With MATLAB®, you can:
- Use apps to interactively explore different segmentation techniques
- Simplify image analysis workflows using built-in image segmentation algorithms
- Perform deep learning for image segmentation
Using Apps to Interactively Threshold Images
Image Segmenter App
Using the interactive Image Segmenter app, you can iteratively try several methods to segment an image before achieving the desired result. For example, you can use the app to segment and further refine the results of an MRI image of a knee with different methods.
Color Thresholder App
This Color Thresholder app lets you apply thresholding to color images by manipulating the color of the images interactively, based on different color spaces. For example, you can use the Color Thresholder app to create a binary mask using point cloud controls for a color image.
Using a Variety of Image Segmentation Techniques
With functions in MATLAB and Image Processing Toolbox™, you can experiment and build expertise on the different image segmentation techniques, including thresholding, clustering, graph-based segmentation, and region growing.
Using Otsu's method, imbinarize
performs thresholding on a 2D or 3D grayscale image to create a binary image. To produce a binary image from an RGB color image, use rgb2gray
to first convert it to a grayscale image.
This technique lets you create a segmented labeled image using a specific clustering algorithm. Using K-means clustering–based segmentation, imsegkmeans
segments an image into K number of clusters.
Graph-Based Segmentation
Graph-based segmentation techniques like lazy-snapping enable you to segment an image into foreground and background regions. MATLAB lets you perform this segmentation on your image either programmatically (lazysnapping
) or interactively using the Image Segmenter app.
Region Growing
Region growing is a simple region-based (also classified as a pixel-based) image segmentation method. A popularly used algorithm is activecontour
, which examines neighboring pixels of initial seed points and determines iteratively whether the pixel neighbors should be added to the region. You can also perform this segmentation on images using the Image Segmenter app.
Deep Learning for Image Segmentation
Using convolutional neural networks (CNNs), a deep learning technique called semantic segmentation lets you associate every pixel of an image with a class label. Applications for semantic segmentation include autonomous driving, industrial inspection, medical imaging, and satellite image analysis.
Using MATLAB, you can design and train semantic segmentation networks with a collection of images and their corresponding labeled images, and then use the trained network to label new images. To label the training images, you can use the Image Labeler, Video Labeler, or Ground Truth Labeler apps.

subset: commoncrawl


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Global capital flows to further diversify, while investors to remain cautious and selective in 2020
The fundamentals of Asia Pacific's commercial real estate market will again serve as a major draw for investors in 2020
"The fundamentals of Asia Pacific's commercial real estate market will again serve as a major draw for investors in 2020. Despite macroeconomic challenges and the highly unpredictable nature of the Covid-19 outbreak, longer-term investor sentiment remains extremely positive. We foresee investor strategies becoming more selective and further diversification into the logistics, living and datacentre sectors. The continued low interest rate environment and supportive central bank policy will also offset some of the macro headwinds and provide further confidence to investors' cross-border strategies," says Stuart Crow, CEO, Capital Markets, Asia Pacific, JLL.
"Investors will remain highly selective in their capital allocations in Asia Pacific. A shortage of supply will likely prompt investors to rethink medium-term strategies and look more closely at alternative asset classes across the region. While there may be some moderation in overall transaction volumes, we expect moderation to be influenced by broader considerations including geopolitics, supply shortages, and allocation repositioning," says Regina Lim, Executive Director, Asia Pacific Capital Markets Research, JLL.
Key takeaways:
New flow records: 2019 stands as the most active year for global real estate investment on paper as measured by transaction volume. Investment in global commercial real estate increased by 10 per cent in Q4 2019, rising to US$245 billion, bringing full-year activity to US$800 billion, up 4 per cent.
Cross-border world: Global cross-border transaction volumes spiked in Q4 2019, reaching US$107 billion, representing the second-highest level on record behind Q4 2017. In total, 2019 full-year cross-border activity reached US$349 billion, a new high for the current cycle. Inter-regional flows increased significantly in 2019, with US$254 billion moving from one region to another, well above the long-run average of US$177 billion.
Industrial draw: The industrial sector registered its most active ever year on record. Global investment rose by 24 per cent to US$166 billion, and the industrial appeal is motivating investors to look outside of their home markets for assets as cross-border investment in the sector grew to a new high of US$53.6 billion.
REIT performance: Globally, REITs have outperformed other global asset classes over the past decade. Since 2010, global REITs have produced an annualized total return of 11 per cent, compared to single-digit annualized returns for global equities and fixed income over the same timeframe — expected listings in Singapore and India in 2020 to diversify the REIT base regionally.
Asia Pacific moderates and matures: In Q4, Asia Pacific's record-breaking streak ultimately ended as a fourth-quarter slowdown while investment flows moderated 4 per cent relative to the same period in 2018. On the flip side, the robust start to the year means delivered an increase to full-year volumes of 6 per cent, to US$169 billion. The rise in activity centered on core markets, such as China, Japan, Singapore, and South Korea, where domestic and foreign investors alike remain active. Meanwhile, political uncertainty continues to impact Hong Kong, where investment is down by 53 per cent.
Global investment moderation to continue: Expect global investment in commercial real estate to moderate slightly, by 0-5 per cent, to roughly US$780 billion. While investors remain keen to access the sector, continued caution and selectivity, as well as limited availability of assets, stand to impact transaction volumes.
Conspicuous Headwinds: Continued political and macroeconomic uncertainty will influence investment volumes in 2020. While there are some hints that global growth may pick up slightly, pockets of concern remain from rising geopolitical tensions in Asia, and the emergence of the coronavirus will undoubtedly influence the rapid growth of corporate credit. Nevertheless, central bank policy remains accommodative, and the low-interest-rate environment will carry over into 2020.
For more information, download JLL's Global Capital Flows 2019 report here.
About JLL
JLL (NYSE: JLL) is a leading professional services firm that specializes in real estate and investment management. JLL shapes the future of real estate for a better world by using the most advanced technology to create rewarding opportunities, amazing spaces and sustainable real estate solutions for our clients, our people and our communities. JLL is a Fortune 500 company with annual revenue of $18.0 billion, operations in over 80 countries and a global workforce of more than 93,000 as of December 31, 2019. JLL is the brand name, and a registered trademark, of Jones Lang LaSalle Incorporated. For further information, visit jll.com.


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I have been feeling a little guilty ever since I put up this post, Naturally Resourceful: Getting Scrappy with Vegetables! I mentioned in that post that I was too time-crunched to have a compost heap even though it would be great for my plants and the environment.
Nothing has changed schedule-wise for me since then. However, my passion for gardening is now completely unhinged. (It gets me through the day, people!) I found I was spending an enormous amount of money on compost which is so riduculous considering I was, guiltily, throwing away things all the time that can be composted. So, I decided to save money, myself from guilt and, hopefully a little of the environment by starting a compost bin.
I decided to use this garbage pail because it has a lid and I want to keep creatures out of my bin. I burned holes in the sides:
And the lid:
With a hot glue gun. I do not endorse this method because melting plastic never seems like a great idea. However, my cordless drill wasn't charged (as usual) and I really wanted to get it done. I waited until I could no longer smell melted plastic and then gave the can a good swabbing before I started to add compost ingredients.
There are so many good resources for what to put in compost and even more importantly, what not to, like Jeff Yeager's Rotten Luv, I am not going to go into too much detail. Basically, you want a 2:1 ratio of brown matter to green matter. I used newspaper shreds for brown matter. (I figured The NY Times was appropriate for a compost heap named Miles) and for the green matter, I put in coffee grounds, eggshells (No, I didn't eat the eggs!), plant stems, veggie and fruit peels.
I layered the ingredients and gave it a stir. And that's it. I'll keep adding the ingredients in that 2:1 ratio, and keep stirring it up. Mostly, I can just let nature turn it into Black Gold for me. There are more significant holes in the bottom of the can. I placed it directly on dirt in the hopes that some worms will find their way in and take up residence, further enriching Miles with their castings.
Why did I name my compost heap? Jeff Yeager named his Gomer. I thought it was funny. So, I decided mine needed to be named too. So, Miles the Pile was born yesterday May 27, 2017. I am looking forward to seeing him and my garden grow!
Many blessings,


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Exploring Protein-DNA Binding Sites from Paired-End ChIP-Seq Data
This example shows how to perform a genome-wide analysis of a transcription factor in the Arabidopsis Thaliana (Thale Cress) model organism.
For enhanced performance, it is recommended that you run this example on a 64-bit platform, because the memory footprint is close to 2 Gb. On a 32-bit platform, if you receive "Out of memory"
errors when running this example, try increasing the virtual memory (or swap space) of your operating system or try setting the 3GB
switch (32-bit Windows® XP only). For details, see Resolve "Out of Memory" Errors.
ChIP-Seq is a technology that is used to identify transcription factors that interact with specific DNA sites. First chromatin immunoprecipitation enriches DNA-protein complexes using an antibody that binds to a particular protein of interest. Then, all the resulting fragments are processed using high-throughput sequencing. Sequencing fragments are mapped back to the reference genome. By inspecting over-represented regions it is possible to mark the genomic location of DNA-protein interactions.
In this example, short reads are produced by the paired-end Illumina® platform. Each fragment is reconstructed from two short reads successfully mapped, with this the exact length of the fragment can be computed. Using paired-end information from sequence reads maximizes the accuracy of predicting DNA-protein binding sites.
Data Set
This example explores the paired-end ChIP-Seq data generated by Wang et.al. [1] using the Illumina® platform. The data set has been courteously submitted to the Gene Expression Omnibus repository with accession number GSM424618. The unmapped paired-end reads can be obtained from the NCBI FTP site.
This example assumes that you:
(1) downloaded the data containing the unmapped short read and converted it to FASTQ formatted files using the NCBI SRA Toolkit.
(2) produced a SAM formatted file by mapping the short reads to the Thale Cress reference genome, using a mapper such as BWA [2], Bowtie, or SSAHA2 (which is the mapper used by authors of [1]), and,
(3) ordered the SAM formatted file by reference name first, then by genomic position.
For the published version of this example, 8,655,859 paired-end short reads are mapped using the BWA mapper [2]. BWA produced a SAM formatted file (aratha.sam
) with 17,311,718 records (8,655,859 x 2). Repetitive hits were randomly chosen, and only one hit is reported, but with lower mapping quality. The SAM file was ordered and converted to a BAM formatted file using SAMtools [3] before being loaded into MATLAB.
The last part of the example also assumes that you downloaded the reference genome for the Thale Cress model organism (which includes five chromosomes). Uncomment the following lines of code to download the reference from the NCBI repository:
% getgenbank('NC_003070','FileFormat','fasta','tofile','ach1.fasta'); % getgenbank('NC_003071','FileFormat','fasta','tofile','ach2.fasta'); % getgenbank('NC_003074','FileFormat','fasta','tofile','ach3.fasta'); % getgenbank('NC_003075','FileFormat','fasta','tofile','ach4.fasta'); % getgenbank('NC_003076','FileFormat','fasta','tofile','ach5.fasta');
Creating a MATLAB® Interface to a BAM Formatted File
To create local alignments and look at the coverage we need to construct a BioMap
. BioMap
has an interface that provides direct access to the mapped short reads stored in the BAM formatted file, thus minimizing the amount of data that is actually loaded to the workspace. Create a BioMap
to access all the short reads mapped in the BAM formatted file.
bm = BioMap('aratha.bam')
bm = BioMap with properties: SequenceDictionary: {5x1 cell} Reference: [14637324x1 File indexed property] Signature: [14637324x1 File indexed property] Start: [14637324x1 File indexed property] MappingQuality: [14637324x1 File indexed property] Flag: [14637324x1 File indexed property] MatePosition: [14637324x1 File indexed property] Quality: [14637324x1 File indexed property] Sequence: [14637324x1 File indexed property] Header: [14637324x1 File indexed property] NSeqs: 14637324 Name: ''
Use the getSummary
method to obtain a list of the existing references and the actual number of short read mapped to each one.
BioMap summary: Name: '' Container_Type: 'Data is file indexed.' Total_Number_of_Sequences: 14637324 Number_of_References_in_Dictionary: 5 Number_of_Sequences Genomic_Range Chr1 3151847 1 30427671 Chr2 3080417 1000 19698292 Chr3 3062917 94 23459782 Chr4 2218868 1029 18585050 Chr5 3123275 11 26975502
The remainder of this example focuses on the analysis of one of the five chromosomes, Chr1
. Create a new BioMap
to access the short reads mapped to the first chromosome by subsetting the first one.
bm1 = getSubset(bm,'SelectReference','Chr1')
bm1 = BioMap with properties: SequenceDictionary: 'Chr1' Reference: [3151847x1 File indexed property] Signature: [3151847x1 File indexed property] Start: [3151847x1 File indexed property] MappingQuality: [3151847x1 File indexed property] Flag: [3151847x1 File indexed property] MatePosition: [3151847x1 File indexed property] Quality: [3151847x1 File indexed property] Sequence: [3151847x1 File indexed property] Header: [3151847x1 File indexed property] NSeqs: 3151847 Name: ''
By accessing the Start and Stop positions of the mapped short read you can obtain the genomic range.
x1 = min(getStart(bm1)) x2 = max(getStop(bm1))
x1 = uint32 1 x2 = uint32 30427671
Exploring the Coverage at Different Resolutions
To explore the coverage for the whole range of the chromosome, a binning algorithm is required. The getBaseCoverage
method produces a coverage signal based on effective alignments. It also allows you to specify a bin width to control the size (or resolution) of the output signal. However internal computations are still performed at the base pair (bp) resolution. This means that despite setting a large bin size, narrow peaks in the coverage signal can still be observed. Once the coverage signal is plotted you can program the figure's data cursor to display the genomic position when using the tooltip. You can zoom and pan the figure to determine the position and height of the ChIP-Seq peaks.
[cov,bin] = getBaseCoverage(bm1,x1,x2,'binWidth',1000,'binType','max'); figure plot(bin,cov) axis([x1,x2,0,100]) % sets the axis limits fixGenomicPositionLabels % formats tick labels and adds datacursors xlabel('Base position') ylabel('Depth') title('Coverage in Chromosome 1')
It is also possible to explore the coverage signal at the bp resolution (also referred to as the pile-up profile). Explore one of the large peaks observed in the data at position 4598837.
p1 = 4598837-1000; p2 = 4598837+1000; figure plot(p1:p2,getBaseCoverage(bm1,p1,p2)) xlim([p1,p2]) % sets the x-axis limits fixGenomicPositionLabels % formats tick labels and adds datacursors xlabel('Base position') ylabel('Depth') title('Coverage in Chromosome 1')
Identifying and Filtering Regions with Artifacts
Observe the large peak with coverage depth of 800+ between positions 4599029 and 4599145. Investigate how these reads are aligning to the reference chromosome. You can retrieve a subset of these reads enough to satisfy a coverage depth of 25, since this is sufficient to understand what is happening in this region. Use getIndex
to obtain indices to this subset. Then use getCompactAlignment
to display the corresponding multiple alignment of the short-reads.
i = getIndex(bm1,4599029,4599145,'depth',25); bmx = getSubset(bm1,i,'inmemory',false) getCompactAlignment(bmx,4599029,4599145)
bmx = BioMap with properties: SequenceDictionary: 'Chr1' Reference: [62x1 File indexed property] Signature: [62x1 File indexed property] Start: [62x1 File indexed property] MappingQuality: [62x1 File indexed property] Flag: [62x1 File indexed property] MatePosition: [62x1 File indexed property] Quality: [62x1 File indexed property] Sequence: [62x1 File indexed property] Header: [62x1 File indexed property] NSeqs: 62 Name: '' ans = 35×117 char array 'AGTT AATCAAATAGAAAGCCCCGAGGGCGCCATATCCTAGGCGC AAACTATGTGATTGAATAAATCCTCCTCTATCTGTTGCGG GAGGACTCCTTCTCCTTCCCCTTTTGG' 'AGTGC TCAAATAGAAAGCCCCGAGGGCGCCATATTCTAGGAGCCC GAATAAATCCTCCTCTATCTGTTGCGGGTCGAGGACTCCT CTCCTGCCCCTTTTGG' 'AGTTCAA CCCGAGGGCGCCATATTCTAGGAGCCCAAACTATGTGATT TATCTGTTGCGGGTCGAGGACTCCTTCTCCTTCCCCTTCT ' 'AGTTCAATCAAATAGAAAGC TTCTAGGAGCCCAAACTATGTGATTGAATAAATCCTCCTC AGGACTCCTTCTCCTTCCCCTTTTGG' 'AGTT AAGGAGCCCAAAATATGTGATTGAATAAATCCACCTCTAT GGACTCCTTCTCCTTCCCCTTTTGG' 'AGTACAATCAAATAGAAAGCCCCGAGGGCGCCATA TAGGAGCCCAAACTATGTGATTGAATAAATCCTCCTCTAT CCTTCACCTTCCCCTTTTGG' 'CGTACAATCAAATAGAAAGCCCCGAGGGCGCCATATTC GGAGCCCAAACTATGTGATTGAATAAATCCTCCTCTATCT TTCCCCTTTTGG' 'CGTACAATCAAATAGAAAGCCCCGAGGGCGCCATATTC GGAGCCCAAACTATGTGATTGAATAAATCCTCCTCTATCT ' 'CGTACAATCAAATAGAAAGCCCCGAGGGCGCCATATTC GGAGCCCAAGCTATGTGATTGAATAAATCCTCCTCTATCT ' 'CGTACAATCAAATAGAAAGCCCCGAGGGCGCCATATTC GGAGCCCAAACTATGTGATTGAATAAATCCTCCTCTATCT ' 'AGTTCAATCAAATAGAAAGCCCCGAGGGCGCCATATTCTA GAGCCCAAACTATGTGATTGAATAAATCCTCCTCTATCTG ' 'GATACAATCAAATAGAAAGCCCCGAGGGCGCCATATTCTA GAGCCCAAACTATGTGATTGAATAAATCTTCCTCTATCTG ' 'GATACAATCAAATAGAAAGCCCCGAGGGCGCCATATTCTA GAGCCCAAACTATGTGATTGAATAAATCCTCCTCTATCTG ' 'GATACAATCAAATAGAAAGCCCCGAGGGCGCCATATTCTA GAGCCCAAACTATGTGATTGAATAAATCCTCCTCTATCTG ' 'GATACAATCAAATAGAAAGCCCCGAGGGCGCCATATTCTA GAGCCCAAATTATGTGATTGAATAAATCCTCCTCTATCTG ' ' ATACAATCAAATAGAAAGCCCCGAGGGCGCCATATTCTAG CCCAAACTATGTGATTGAATAAATCCTCCTCTATCTGTTG ' ' ATACAATCAAATAGAAAGCCCCGAGGGCGCCATATTCTAG CACAAACTATGTGATTGAATAAATCCTCCTCTATCTGTTG ' ' ATACAATCAAATAGAAAGCCCCGAGGGCGCCATATTCTAG CCAAACTATGTGATTGAATAAATCCTCCTCTATCTGTTGC ' ' ATACAATCAAATAGAAAGCCCCGAGGGCGCCATATTCTAG ' ' ATACAATCAAATAGAAAGCCCCGAGGGCGCCATATTCTCG ' ' ATACAATCAAATAGAAAGCCCCGGGGGCGCCATATTCTAG ' ' ATTGAGTCAAATAGAAAGCCCCGAGGGCGCCATATTCTAG ' ' ATACAATCAAATAGAAAGCCCCGAGGGCGCCATATTCTAG ' ' ATACAATCAAATAGAAAGCCCCGAGGGCGCCATATTCTAG ' ' ATACAATCAAATAGAAAGCCCCGAGGGCGCCATATTCTAG ' ' CAATCAAATAGAAAGCCCCGAGGGCGCCATATTCTAGGAG ' ' CAATCAAATAGAAAGCCCCGAGGGCGCCATATTCTAGGAG ' ' TAGGAGCCCAAACTATGTGATTGAATAAATCCTCCTCTAT ' ' TAGGAGCCCAAACTATGCCATTGAATAAATCCTCCGCTAT ' ' GGAGCCCAAGCTATGTGATTGAATAAATCCTCCTCTATCT ' ' GAGCCCAAACTATGTGATTGAATAAATCCTCCTCTATCTG ' ' GAGCCCAAACTATGTGATTGAATAAATCCTCCTCTATCTG ' ' GAGCCCAAACTATGTGATTGAATAAATCCTCCTCTATCTG ' ' GAGCCCAAACTATGTGATTGAATAAATCCTCCTCTATCTG ' ' GAGCCCAAACTATGTGATTGAATAAATCCTCCTCTATCTG '
In addition to visually confirming the alignment, you can also explore the mapping quality for all the short reads in this region, as this may hint to a potential problem. In this case, less than one percent of the short reads have a Phred quality of 60, indicating that the mapper most likely found multiple hits within the reference genome, hence assigning a lower mapping quality.
figure i = getIndex(bm1,4599029,4599145); hist(double(getMappingQuality(bm1,i))) title('Mapping Quality of the reads between 4599029 and 4599145') xlabel('Phred Quality Score') ylabel('Number of Reads')
Most of the large peaks in this data set occur due to satellite repeat regions or due to its closeness to the centromere [4], and show characteristics similar to the example just explored. You may explore other regions with large peaks using the same procedure.
To prevent these problematic regions, two techniques are used. First, given that the provided data set uses paired-end sequencing, by removing the reads that are not aligned in a proper pair reduces the number of potential aligner errors or ambiguities. You can achieve this by exploring the flag
field of the SAM formatted file, in which the second less significant bit is used to indicate if the short read is mapped in a proper pair.
i = find(bitget(getFlag(bm1),2)); bm1_filtered = getSubset(bm1,i)
bm1_filtered = BioMap with properties: SequenceDictionary: 'Chr1' Reference: [3040724x1 File indexed property] Signature: [3040724x1 File indexed property] Start: [3040724x1 File indexed property] MappingQuality: [3040724x1 File indexed property] Flag: [3040724x1 File indexed property] MatePosition: [3040724x1 File indexed property] Quality: [3040724x1 File indexed property] Sequence: [3040724x1 File indexed property] Header: [3040724x1 File indexed property] NSeqs: 3040724 Name: ''
Second, consider only uniquely mapped reads. You can detect reads that are equally mapped to different regions of the reference sequence by looking at the mapping quality, because BWA assigns a lower mapping quality (less than 60) to this type of short read.
i = find(getMappingQuality(bm1_filtered)==60); bm1_filtered = getSubset(bm1_filtered,i)
bm1_filtered = BioMap with properties: SequenceDictionary: 'Chr1' Reference: [2313252x1 File indexed property] Signature: [2313252x1 File indexed property] Start: [2313252x1 File indexed property] MappingQuality: [2313252x1 File indexed property] Flag: [2313252x1 File indexed property] MatePosition: [2313252x1 File indexed property] Quality: [2313252x1 File indexed property] Sequence: [2313252x1 File indexed property] Header: [2313252x1 File indexed property] NSeqs: 2313252 Name: ''
Visualize again the filtered data set using both, a coarse resolution with 1000 bp bins for the whole chromosome, and a fine resolution for a small region of 20,000 bp. Most of the large peaks due to artifacts have been removed.
[cov,bin] = getBaseCoverage(bm1_filtered,x1,x2,'binWidth',1000,'binType','max'); figure plot(bin,cov) axis([x1,x2,0,100]) % sets the axis limits fixGenomicPositionLabels % formats tick labels and adds datacursors xlabel('Base Position') ylabel('Depth') title('Coverage in Chromosome 1 after Filtering') p1 = 24275801-10000; p2 = 24275801+10000; figure plot(p1:p2,getBaseCoverage(bm1_filtered,p1,p2)) xlim([p1,p2]) % sets the x-axis limits fixGenomicPositionLabels % formats tick labels and adds datacursors xlabel('Base Position') ylabel('Depth') title('Coverage in Chromosome 1 after Filtering')
Recovering Sequencing Fragments from the Paired-End Reads
In Wang's paper [1] it is hypothesized that paired-end sequencing data has the potential to increase the accuracy of the identification of chromosome binding sites of DNA associated proteins because the fragment length can be derived accurately, while when using single-end sequencing it is necessary to resort to a statistical approximation of the fragment length, and use it indistinctly for all putative binding sites.
Use the paired-end reads to reconstruct the sequencing fragments. First, get the indices for the forward and the reverse reads in each pair. This information is captured in the fifth bit of the flag
field, according to the SAM file format.
fow_idx = find(~bitget(getFlag(bm1_filtered),5)); rev_idx = find(bitget(getFlag(bm1_filtered),5));
SAM-formatted files use the same header strings to identify pair mates. By pairing the header strings you can determine how the short reads in BioMap
are paired. To pair the header strings, simply order them in ascending order and use the sorting indices (hf
and hr
) to link the unsorted header strings.
[~,hf] = sort(getHeader(bm1_filtered,fow_idx)); [~,hr] = sort(getHeader(bm1_filtered,rev_idx)); mate_idx = zeros(numel(fow_idx),1); mate_idx(hf) = rev_idx(hr);
Use the resulting fow_idx
and mate_idx
variables to retrieve pair mates. For example, retrieve the paired-end reads for the first 10 fragments.
for j = 1:10 disp(getInfo(bm1_filtered, fow_idx(j))) disp(getInfo(bm1_filtered, mate_idx(j))) end
SRR054715.sra.6849385 163 20 60 40M AACCCTAAACCTCTGAATCCTTAATCCCTAAATCCCTAAA BBBBBBBBBBCBCB?2?BBBBB@7;BBC?7=7?BCC4*)3 SRR054715.sra.6849385 83 229 60 40M CCTATTTCTTGTGGTTTTCTTTCCTTCACTTAGCTATGGA 06BBBB=BBBBBBBBBBBBBBA6@@@9<*9BBA@>BBBBB SRR054715.sra.6992346 99 20 60 40M AACCCTAAACCTCTGAATCCTTAATCCCTAAATCCCTAAA =B?BCB=2;BBBBB=B8BBCCBBBBBBBC66BBB=BC8BB SRR054715.sra.6992346 147 239 60 40M GTGGTTTTCTTTCCTTCACTTAGCTATGGATGGTTTATCT BBCBB6B?B0B8B<'.BBBBBBBB=BBBBB6BBBBB;*6@ SRR054715.sra.8438570 163 47 60 40M CTAAATCCCTAAATCTTTAAATCCTACATCCATGAATCCC BC=BBBBCBB?==BBB;BB;?BBB8BCB??B-BB<*<B;B SRR054715.sra.8438570 83 274 60 40M TATCTTCATTTGTTATATTGGATACAAGCTTTGCTACGAT BBBBB=;BBBBBBBBB;6?=BBBBBBBB<*9BBB;8BBB? SRR054715.sra.1676744 163 67 60 40M ATCCTACATCCATGAATCCCTAAATACCTAATCCCCTAAA BBCB>4?+<BB6BB66BBC?77BBCBC@4ABB-BBBCCBB SRR054715.sra.1676744 83 283 60 40M TTGTTATATTGGATACAAGCTTTGCTACGATCTACATTTG CCB6BBB93<BBBB>>@B?<<?BBBBBBBBBBBBBBBBBB SRR054715.sra.6820328 163 73 60 40M CATCCATGAATCCCTAAATACCTAATTCCCTAAACCCGAA BB=08?BB?BCBBB=8BBB8?CCB-B;BBB?;;?BB8B;8 SRR054715.sra.6820328 83 267 60 40M GTTGGTGTATCTTCATTTGTTATATTGGATACGAGCTTTG BBBBB646;BB8@44BB=BBBB?C8BBBB=B6.9B8CCCB SRR054715.sra.1559757 163 103 60 40M TAAACCCGAAACCGGTTTCTCTGGTTGAAACTCATTGTGT BBBBBCBBBBBBBBBBBCBBBB?BBBB<;?*?BBBBB7,* SRR054715.sra.1559757 83 311 60 40M GATCTACATTTGGGAATGTGAGTCTCTTATTGTAACCTTA <?BBBBB?7=BBBBBBBBBBBBBB@;@>@BBBBBBBBBBB SRR054715.sra.5658991 163 103 60 40M CAAACCCGAAACCGGTTTCTCTGGTTGAAACTCATTGTGT 7?BBBBBB;=BBBB?8B;B-;BCB-B<49<6B8-BB?+?B SRR054715.sra.5658991 83 311 60 40M GATCTACATTTGGGAATGTGAGTCTCTTATTGTAACCTTA 3,<-BBCBBBBBB?=BBBBA<ABBBBBBBBB?79BBB?BB SRR054715.sra.4625439 163 143 60 40M ATATAATGATAATTTTAGCGTTTTTATGCAATTGCTTATT BBBBB@,*<8BBB++2B6B;+6B8B;8+9BB0,'9B=.=B SRR054715.sra.4625439 83 347 60 40M CTTAGTGTTGGTTTATCTCAAGAATCTTATTAATTGTTTG +BB8B0BBB?BBBB-BBBB22?BBB-BB6BB-BBBBBB?B SRR054715.sra.1007474 163 210 60 40M ATTTGAGGTCAATACAAATCCTATTTCTTGTGGTTTGCTT BBBBBBBB;.>BB6B6',BBBCBB-08BBBBB;CB9630< SRR054715.sra.1007474 83 408 60 40M TATTGTCATTCTTACTCCTTTGTGGAAATGTTTGTTCTAT BBB@AABBBCCCBBBBBBB=BBBCB8BBBBB=B6BCBB77 SRR054715.sra.7345693 99 213 60 40M TGAGGTCAATACAAATCCTATTTCTTGTGGTTTTCTTTCT B>;>BBB9,<6?@@BBBBBBBBBBBBBB7<9BBBBBB6*' SRR054715.sra.7345693 147 393 60 40M TTATTTTTGGACATTTATTGTCATTCTTACTCCTTTGGGG BB-?+?C@>9BBBBBB6.<BBB-BBB94;A4442+49';B
Use the paired-end indices to construct a new BioMap
with the minimal information needed to represent the sequencing fragments. First, calculate the insert sizes.
J = getStop(bm1_filtered, fow_idx); K = getStart(bm1_filtered, mate_idx); L = K - J - 1;
Obtain the new signature (or CIGAR string) for each fragment by using the short read original signatures separated by the appropriate number of skip CIGAR symbols (N
n = numel(L); cigars = cell(n,1); for i = 1:n cigars{i} = sprintf('%dN' ,L(i)); end cigars = strcat( getSignature(bm1_filtered, fow_idx),... cigars,... getSignature(bm1_filtered, mate_idx));
Reconstruct the sequences for the fragments by concatenating the respective sequences of the paired-end short reads.
seqs = strcat( getSequence(bm1_filtered, fow_idx),...
getSequence(bm1_filtered, mate_idx));
Calculate and plot the fragment size distribution.
J = getStart(bm1_filtered,fow_idx); K = getStop(bm1_filtered,mate_idx); L = K - J + 1; figure hist(double(L),100) title(sprintf('Fragment Size Distribution\n %d Paired-end Fragments Mapped to Chromosome 1',n)) xlabel('Fragment Size') ylabel('Count')
Construct a new BioMap
to represent the sequencing fragments. With this, you will be able explore the coverage signals as well as local alignments of the fragments.
bm1_fragments = BioMap('Sequence',seqs,'Signature',cigars,'Start',J)
bm1_fragments = BioMap with properties: SequenceDictionary: {0×1 cell} Reference: {0×1 cell} Signature: {1156626×1 cell} Start: [1156626×1 uint32] MappingQuality: [0×1 uint8] Flag: [0×1 uint16] MatePosition: [0×1 uint32] Quality: {0×1 cell} Sequence: {1156626×1 cell} Header: {0×1 cell} NSeqs: 1156626 Name: ''
Exploring the Coverage Using Fragment Alignments
Compare the coverage signal obtained by using the reconstructed fragments with the coverage signal obtained by using individual paired-end reads. Notice that enriched binding sites, represented by peaks, can be better discriminated from the background signal.
cov_reads = getBaseCoverage(bm1_filtered,x1,x2,'binWidth',1000,'binType','max'); [cov_fragments,bin] = getBaseCoverage(bm1_fragments,x1,x2,'binWidth',1000,'binType','max'); figure plot(bin,cov_reads,bin,cov_fragments) xlim([x1,x2]) % sets the x-axis limits fixGenomicPositionLabels % formats tick labels and adds datacursors xlabel('Base position') ylabel('Depth') title('Coverage Comparison') legend('Short Reads','Fragments')
Perform the same comparison at the bp resolution. In this dataset, Wang et.al. [1] investigated a basic helix-loop-helix (bHLH) transcription factor. bHLH proteins typically bind to a consensus sequence called an E-box (with a CANNTG
motif). Use fastaread
to load the reference chromosome, search for the E-box motif in the 3' and 5' directions, and then overlay the motif positions on the coverage signals. This example works over the region 1-200,000, however the figure limits are narrowed to a 3000 bp region in order to better depict the details.
p1 = 1; p2 = 200000; cov_reads = getBaseCoverage(bm1_filtered,p1,p2); [cov_fragments,bin] = getBaseCoverage(bm1_fragments,p1,p2); chr1 = fastaread('ach1.fasta'); mp1 = regexp(chr1.Sequence(p1:p2),'CA..TG')+3+p1; mp2 = regexp(chr1.Sequence(p1:p2),'GT..AC')+3+p1; motifs = [mp1 mp2]; figure plot(bin,cov_reads,bin,cov_fragments) hold on plot([1;1;1]*motifs,[0;max(ylim);NaN],'r') xlim([111000 114000]) % sets the x-axis limits fixGenomicPositionLabels % formats tick labels and adds datacursors xlabel('Base position') ylabel('Depth') title('Coverage Comparison') legend('Short Reads','Fragments','E-box motif')
Observe that it is not possible to associate each peak in the coverage signals with an E-box motif. This is because the length of the sequencing fragments is comparable to the average motif distance, blurring peaks that are close. Plot the distribution of the distances between the E-box motif sites.
motif_sep = diff(sort(motifs)); figure hist(motif_sep(motif_sep<500),50) title('Distance (bp) between adjacent E-box motifs') xlabel('Distance (bp)') ylabel('Counts')
Finding Significant Peaks in the Coverage Signal
Use the function mspeaks
to perform peak detection with Wavelets denoising on the coverage signal of the fragment alignments. Filter putative ChIP peaks using a height filter to remove peaks that are not enriched by the binding process under consideration.
putative_peaks = mspeaks(bin,cov_fragments,'noiseestimator',20,... 'heightfilter',10,'showplot',true); hold on legend('off') plot([1;1;1]*motifs(motifs>p1 & motifs<p2),[0;max(ylim);NaN],'r') xlim([111000 114000]) % sets the x-axis limits fixGenomicPositionLabels % formats tick labels and adds datacursors legend('Coverage from Fragments','Wavelet Denoised Coverage','Putative ChIP peaks','E-box Motifs') xlabel('Base position') ylabel('Depth') title('ChIP-Seq Peak Detection')
Use the knnsearch
function to find the closest motif to each one of the putative peaks. As expected, most of the enriched ChIP peaks are close to an E-box motif [1]. This reinforces the importance of performing peak detection at the finest resolution possible (bp resolution) when the expected density of binding sites is high, as it is in the case of the E-box motif. This example also illustrates that for this type of analysis, paired-end sequencing should be considered over single-end sequencing [1].
h = knnsearch(motifs',putative_peaks(:,1)); distance = putative_peaks(:,1)-motifs(h(:))'; figure hist(distance(abs(distance)<200),50) title('Distance to Closest E-box Motif for Each Detected Peak') xlabel('Distance (bp)') ylabel('Counts')
[1] Wang, Congmao, Jie Xu, Dasheng Zhang, Zoe A Wilson, and Dabing Zhang. "An Effective Approach for Identification of in Vivo Protein-DNA Binding Sites from Paired-End ChIP-Seq Data." BMC Bioinformatics 11, no. 1 (2010): 81.
[2] Li, H., and R. Durbin. "Fast and Accurate Short Read Alignment with Burrows-Wheeler Transform." Bioinformatics 25, no. 14 (July 15, 2009): 1754–60.
[3] Li, H., B. Handsaker, A. Wysoker, T. Fennell, J. Ruan, N. Homer, G. Marth, G. Abecasis, R. Durbin, and 1000 Genome Project Data Processing Subgroup. "The Sequence Alignment/Map Format and SAMtools." Bioinformatics 25, no. 16 (August 15, 2009): 2078–79.
[4] Jothi, R., S. Cuddapah, A. Barski, K. Cui, and K. Zhao. "Genome-Wide Identification of in Vivo Protein-DNA Binding Sites from ChIP-Seq Data." Nucleic Acids Research 36, no. 16 (August 1, 2008): 5221–31.
[5] Hoffman, Brad G, and Steven J M Jones. "Genome-Wide Identification of DNA–Protein Interactions Using Chromatin Immunoprecipitation Coupled with Flow Cell Sequencing." Journal of Endocrinology 201, no. 1 (April 2009): 1–13.
[6] Ramsey, Stephen A., Theo A. Knijnenburg, Kathleen A. Kennedy, Daniel E. Zak, Mark Gilchrist, Elizabeth S. Gold, Carrie D. Johnson, et al. "Genome-Wide Histone Acetylation Data Improve Prediction of Mammalian Transcription Factor Binding Sites." Bioinformatics 26, no. 17 (September 1, 2010): 2071–75.
See Also
| getBaseCoverage
| getgenbank
| getSummary


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This year's Sports Broadcast Summer Camp is now in session! Meet the production team who make the live broadcasts of the San Rafael Pacifics games possible.
Can't make it to a game? Don't panic! Marin TV will be broadcasting the San Rafael Pacifics LIVE to the Education Channel on Comcast 30 | AT&T 99 | http://cmcm.tv/liveedu.
Just a test post for the MMC blog
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On Thursday evening, Olga Gurina begged off work early, cooked a quick dinner for her teenage son and rushed to the Mikhailovsky monastery in her hometown of Kiev, where a field hospital had been set up to treat the wounded from that day's revolutionary violence. She found herself at the center of a citywide mobilization. That morning, police had openly used live ammunition against protesters for the first time since the uprising began in November. Dozens of people were killed. But instead of frightening the protesters away, it brought them out by the many thousands to help the revolt in whatever way they could.
Gurina, a middle-aged retail manager, offered the paramedic's training she remembered from her student years. The monastery's refectory had been turned into an operating room, with beds laid out beneath the gilded icons of Orthodox saints. In the entryway, a nurse in a surgical mask asked curtly about Gurina's qualifications and, apparently satisfied, told her to strip off her overcoat and get into scrubs. Until that point, Gurina had never taken part in street protests in Kiev or anywhere else. And why was today the day she joined? "Why?" she snapped back at a reporter. "Because they're killing us out there!" She may have wanted to say more, but a young woman who looked to be in her late teens was brought into the refectory screaming, a crude bandage covering the left side of her face. Gurina got to work.
A few blocks away, at the Hotel Ukraina, other volunteers had set up a makeshift clinic in the lobby and, in a nearby wing, a morgue for those who had died of their wounds. According to the medical corps of the Maidan, as Kiev's revolutionary encampment is known, between 70 and 100 people died in Thursday's violence, a staggering figure even by the standards of the Arab Spring revolts of the past few years. But this was not the Middle East. This was the biggest country in Eastern Europe, home to a large if fledgling middle class with aspirations of joining the European Union.
In late November, those aspirations first ignited the uprising against President Viktor Yanukovych when he decided to scrap an integration deal with the E.U. in favor of a closer alliance with Russia. But what began as a peaceful movement of students intent on a European future has morphed into an all-out insurrection against the state. With each successive attempt to scare away the protesters by force — first with police truncheons, then with tear gas and stun grenades, and finally with live bullets — the intensity and size of the revolt have grown. After Thursday's violence, much of the city center began to resemble a war zone. Young women on the square poured gasoline into empty beer bottles to make Molotov cocktails, hundreds of them. Young men in ski masks patrol the occupied city center armed not only with clubs but with rifles. And in other cities across Ukraine, the revolt continued to grow more violent. In the city of Lviv, an opposition stronghold in western Ukraine, an explosion caused a fire in the barracks of the Berkut riot troops, marking the latest in a series of attacks this week against the security services around the country.
The Mikhailovsky monastery, with its pastel blue chapels and gilded spires, has been a sanctuary for the revolutionaries from the beginning. When the first crackdown in late November saw riot troops beat dozens of students in the center of Kiev, many of them ran inside the Mikhailovsky cathedral and found haven inside its walls. By Thursday night, the monastery had become a logistical hub for the revolution. Hundreds of regular citizens, including elderly women and students in their teens, streamed through its gates all evening to provide assistance.
Some brought medicine, surgical equipment, warm clothing, a television, lamps, fire extinguishers, pots of soup and sandwiches. Others volunteered to stack and sort it all, to work the kitchen or treat the wounded. In the monastery yard, a young paramedic named Sasha laid a mannequin on a piece of cardboard and began teaching an open-air seminar on first aid, focusing on gunshot wounds and broken limbs. "Remember, your first priority is not to dull the victim's pain but to stanch the bleeding," he instructed. At least 50 people formed a circle around him and watched with rapt attention.
But amid the camaraderie of the gathering, there was also much anxiety and even paranoia. Smaller circles of people traded rumors of the military planning to use poisoned gas and of Russian death squads coming across the border in helicopters to help Yanukovych crush the revolt. Particular venom in these conversations was reserved for the Russian government, which the revolutionaries believe (with fairly good reason) to be goading Yanukovych into using force. So it was no surprise that my Moscow accent did not help me strike up conversations with the volunteers. Even after studying my American passport and press accreditation, the priests refused to give their names or answer questions. "We are only praying here," said one of them as he instructed volunteers on where to put deliveries of medicine. "The church is open to all."
It is, however, not open to any supporters of the President, for whom the role of the Mikhailovsky monastery has been a particularly bad omen. As one of the oldest religious institutions in Kiev, the birthplace of the Russian Orthodox Church, its solidarity with the revolutionaries has given the uprising not only moral weight but the air of a righteous crusade. Earlier in the day, the priests, some wearing bulletproof vests, had helped lay dead bodies along one of the monastery's walls so that people could come to identify them. As the bereft bent down to inspect the pale faces, the priests of the monastery stood silently in prayer.
In the refectory, the doctors sometimes found themselves unable to treat the wounded with their spare supplies (the clinic even lacked a defibrillator), and as morning turned to afternoon more corpses were brought out to the monastery yard. "Nearly all we've seen today are gunshot wounds," said one of the doctors, Alexander, declining to give his last name. But after receiving first aid, the victims often needed to be taken to hospitals, and some refused out of a fear of being arrested and taken from the state-run wards directly to prison. "Those were the hardest cases," Alexander added. "We did all we could." By nightfall, thankfully, the police had retreated from the Maidan, and there were no new victims coming to the refectory. So apart from changing bandages, Gurina and the other volunteers were then able to change the sheets on the dozen operating tables, getting them prepared for the clashes they feared would come by morning.


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Posts Tagged 'searching'
Most Popular Searches
September 4th, 2009by Gwyn Headley
Managing Director
When new members join fotoLibra they occasionally ask us questions (prodding us to see if we're mortal, I suppose). If they do ask, perhaps the most common is "What are people searching for?"
It's easily answered, and it's of no commercial use to them or us.
The answer is
1. Sex
2. Breasts
3. Tits
Need I go on?
A professional picture buyer doesn't do repeated searches anyway, so it's hard to analyse the information. Most of them simply tell us what they want and leave us to do the searching, which is why we keep rabbiting on to our members about the importance of key words.
When I saw a list of the most pirated ebooks this year I had a feeling I could guess what would be on it. I was not wrong.
These are the books that have been downloaded through BitTorrent between 100,000 and 250,000 times this year:
1. Kamasutra
2. Adobe Photoshop Secrets
3. The Complete Idiot's Guide to Amazing Sex
4. The Lost Notebooks of Leonardo da Vinci
5. Solar House – A Guide for the Solar Designer
6. Before Pornography – Erotic Writing In Early Modern England
7. Twilight – Complete Series
8. How To Get Anyone To Say YES – The Science Of Influence
10. Fix It – How To Do All Those Little Repair Jobs Around The Home
Depressing, but not as depressing as I'd feared.


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With our extensive range of 3D printers, 3D scanners and accessories, we have something to meet every one of your requirements, whether you're creating at home on a small scale or are looking for something that'll withstand regular, heavy-duty use such as in a school or manufacturing.
We stock 3D printers and 3D scanners from the world's leading suppliers including Ultimaker, MakerBot, CEL, 3D Systems, Zortrax and our high-quality own brand, RS PRO. Accessories include everything from printer filament to software.
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From the automotive industry to tooling and aerospace, there are many ways in which 3D printing and scanning can be used effectively. It's particularly good for design, as it enables designers to be able to see their ideas come to life, and make changes quickly and easily at a very low cost.


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All Care Guides
Ear Cleaning
Ear cleaning can help treat or prevent ear problems. Some pets are prone to ear problems and may need regular ear cleanings between veterinary visits. Ear cleaning can help remove dirt and wax that can prevent medications from reaching inflamed areas. It can also get rid of allergens and microbes that may contribute to inflammation or infection.
Read More Ear Hematoma
An ear hematoma is a pocket of blood that forms within the exterior portion of a pet's ear. Although both dogs and cats can have ear hematomas, the condition is more common in dogs.
Read More Ear Infections and Your Pet
Ear infections generally begin as inflammation of the skin inside the outer ear canal. Once the inflammation is present, discharge, redness, and other characteristics of an ear infection become established.
Read More Ear Mites in Dogs and Cats
Ear mites are small parasites that live on an animal's body, particularly in the ears of dogs and cats. Ear mites sustain themselves by eating skin cells, blood, and earwax. They deposit their waste (a dark, crusty debris) in the ear of the host animal. They also mate and produce eggs in the ear of the host. The mite's entire life cycle is only about 3 weeks, and the mite spends its whole life on the animal. Ear mites are contagious to some other animals (for example, cats, dogs, and ferrets), but they are not contagious to humans.
Read More Ehrlichia Testing in Dogs
Ehrlichiosis is a disease caused by bacteria of the Ehrlichia family. There are several species of Ehrlichia bacteria, and some of them can affect humans. Ehrlichiosis (whether it occurs in dogs or humans) is transmitted through the bite of a tick. The tick that most commonly spreads the disease is called the brown dog tick.
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